John S. Ebersole, Aatif M. Husain, Douglas R. Nordli Jr.-Current Practice of Clinical Electroencephalography-Wolters Kluwer (2014) PDF

Current Practice of Clinical
Electroencephalography
FOURTH EDITION
Current Practice of Clinical
FOURTH EDITION
EDI TO R S
Editor Associate Editor Associate Editor

John S. Ebersole, md Aatif M. Husain, md Douglas R. Nordli Jr., md
Professor Professor of Pediatrics and Neurology
Professor of Neurology and Director
Department of Neurology Northwestern University Medical School;
Adult Epilepsy Center and Clinical
Duke University Medical Center Lorna S. and James P. Langdon
Neurophysiology Laboratories Director, Neurodiagnostic Center Chair of Pediatric Epilepsy
Department of Neurology Veterans Affairs Medical Center Children’s Memorial Hospital
The University of Chicago Durham, North Carolina Chicago, Illinois
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Library of Congress Cataloging-in-Publication Data

Current practice of clinical electroencephalography / editors, John S. Ebersole, Douglas R. Nordli Jr.,
Aatif M. Husain—Fourth edition.
p.; cm.
Includes bibliographical references.
ISBN 978-1-4511-3195-6 (hardback)
I. Ebersole, John S., editor of compilation. II. Nordli, Douglas R., Jr., editor of compilation. III.
Husain, Aatif M., editor of compilation.
[DNLM: 1. Electroencephalography—methods. WL 150]
RC386.6.E43
616.8’047547—dc23
2014001992
Care has been taken to confirm the accuracy of the information presented and to describe gener-
ally accepted practices. However, the authors, editors, and publisher are not responsible for errors
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10 9 8 7 6 5 4
To our mentors, who taught us and gave us the opportunity to discover
new things on our own; to our colleagues, who supported us during
this endeavor; and to our wives, who lovingly tolerated the long process
of completing this volume.
CONTRIBUTORS
A.G. Christina Bergqvist, MD François Dubeau, MD Mohamad Z. Koubeissi, MD

Associate Professor Associate Professor Associate Professor
Department of Neurology and Pediatrics Department of Neurology and Neurosurgery Director, Epilepsy Center
Perelman School of Medicine at the University McGill University; Department of Neurology
of Pennsylvania; Head, EEG Laboratory and Epilepsy Monitoring Unit The George Washington School of Medicine
Director, Dietary Treatment Program of Epilepsy Montreal Neurological Hospital and Institute Washington, DC
Division of Neurology Montréal, Québec, Canada
The Children’s Hospital of Philadelphia Brian Litt, MD
Philadelphia, Pennsylvania John S. Ebersole, MD Professor
Professor of Neurology and Director Department of Neurology and Bioengineering
Robert R. Clancy, MD Adult Epilepsy Center and Clinical University of Pennsylvania;
Professor of Neurology and Pediatrics Neurophysiology Laboratories Director
Perelman School of Medicine Department of Neurology Penn Epilepsy Center
University of Pennsylvania; The University of Chicago Hospital of the University of Pennsylvania
Founder and Former director, Pediatric Regional Epilepsy Chicago, Illinois Philadelphia, Pennsylvania
Program The Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania Lawrence J. Hirsch, MD Douglas Maus, MD, PhD
Professor of Neurology Assistant Professor
Darryl C. De Vivo, MD Chief, Division of Epilepsy and EEG; Co-Director, Departments of Neurology and Bioengineering
Sidney Carter Professor of Neurology Yale Comprehensive Epilepsy Center University of Pennsylvania
Professor of Pediatrics Yale School of Medicine Epilepsy Division
Department of Neurology New Haven, Connecticut Hospital of the University of Pennsylvania
Attending Neurologist Philadelphia, Pennsylvania
Attending Pediatrician Aatif M. Husain, MD
New York Presbyterian Hospital Professor Douglas R. Nordli Jr., MD
Columbia University Department of Neurology Professor of Pediatrics and Neurology
New York, New York Duke University Medical Center Northwestern University Medical School;
Director, Neurodiagnostic Center Lorna S. and James P. Langdon
Dennis J. Dlugos, MD, MSCE Veterans Affairs Medical Center Chair of Pediatric Epilepsy
Associate Professor Durham, North Carolina Children’s Memorial Hospital
Department of Neurology and Pediatrics Chicago, Illinois
Perelman School of Medicine at the University of Pennsylvania; Philippe Kahane, MD, PhD
Director, Pediatric Regional Epilepsy Program Faculty of Medicine, Joseph Fourier University
Attending Neurologist Head, Epilepsy Unit, Neurology Department
Division of Child Neurology University Hospital of Grenoble
The Children’s Hospital of Philadelphia Grenoble, France
Philadelphia, Pennsylvania
vii
viii CONTRIBUTORS
Rodney A. Radtke, MD Joseph I. Sirven, MD William O. Tatum IV, DO

Professor of Neurology Professor of Neurology Professor of Neurology
Chief, Division of Epilepsy and Sleep Professor and Chairman Mayo Clinic College of Medicine
Department of Neurology Department of Neurology Mayo Clinic Florida
Duke University School of Medicine Mayo Clinic Arizona Jacksonville, Florida
Medical Director, Duke Hospital Neurodiagnostic Phoenix, Arizona
Laboratory
Andrew Trevelyan, MD, DPhil
Medical Director, Duke Hospital Sleep Laboratory Elson L. So, MD
Senior Lecturer in Network Neuroscience
Duke University Medical Center Director, Section of Electroencephalography
Institute of Neuroscience
Durham, North Carolina Department of Neurology
Newcastle University Medical School
Mayo Clinic
Newcastle upon Tyne, United Kingdom
Catherine A. Schevon, MD, PhD Rochester, Minnesota
Assistant Professor
Department of Neurology James Tao, MD, PhD Elizabeth Waterhouse, MD
College of Physicians and Surgeons Associate Professor Professor
Columbia University Director of Electroencephalography Laboratory Department of Neurology
New York, New York Department of Neurology Virginia Commonwealth University School
The University of Chicago of Medicine
Saurabh R. Sinha, MD, PhD Chicago, Illinois Richmond, Virginia
Associate Professor of Neurology
Vice-Chair for Education, Neurology
Duke University Medical Center
Director, Epilepsy Monitoring Unit
Duke University Hospital
Durham, North Carolina
PREFACE
This volume represents the fourth iteration of Current Practice of Clinical EEG. As such, we hope
it reflects the progressive changes and improvements in EEG and evoked potential recording and
interpretation that have occurred since the publishing of the third edition 10 years ago. The fourth
edition features two new associate editors, with expertise complementary to mine, and 12 new
chapter authors, who are expert in their own right. Our goal was to assemble a group of nation-
ally recognized authors who would produce a substantial, yet practical, compendium of EEG
know-how to serve as a reference for students, physicians-in-training, researchers, and practicing
electroencephalographers in the 21st century.
In addition to updating areas of clinical EEG that are well established, we wanted to emphasize
its neurophysiologic bases in order to promote a deeper understanding of EEG, rather than sim-
ply reemphasize a recognition of its patterns. We also expanded the discussion of rapidly evolving
areas in clinical neurophysiology, including intraoperative monitoring, ICU EEG, and advanced
digital methods of EEG and EP analysis. It is our hope that EEG interpretation will be appreci-
ated again as a science and not simply as a clinical art. As a field of endeavor, EEG is not stagnant,
nor has it reached the end of its evolution; rather, there is much remaining to learn and much to be
done to exploit to the fullest these electrical signals for the benefit of our patients.
John S. Ebersole, MD
ix
ACKNOWLEDGMENTS
A number of individuals contributed to this volume both directly and indirectly through the
software that they developed, which we used to create figures. These include Patrick Berg (Dipole
Simulator), Michael Scherg (BESA), Manfred Fuchs and Michael Wagner (Curry). We sincerely
thank them.
xi
CONTENTS
Contributors vii
Preface ix
Acknowledgments xi
Chapter 1 The Cellular Basis of EEG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Catherine A. Schevon and Andrew J. Trevelyan
Chapter 2 Cortical Generators and EEG Voltage Fields . . . . . . . . . . . . . . . . . . 28

John S. Ebersole
Chapter 3 Engineering Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

Douglas Maus and Brian Litt
Chapter 4 Recording Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78

Saurabh R. Sinha
Chapter 5 Normal Adult EEG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

William O. Tatum IV
Chapter 6 Normal Pediatric EEG: Neonates and Children . . . . . . . . . . . . . . . . 125

Robert R. Clancy, A.G. Christina Bergqvist,
Dennis J. Dlugos and Douglas R. Nordli Jr.
Chapter 7 Generalized Encephalopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
Elizabeth Waterhouse
Chapter 8 EEG in Focal Encephalopathies: Cerebrovascular Disease,

Neoplasms, and Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
Joseph I. Sirven
Chapter 9 Progressive Childhood Encephalopathy . . . . . . . . . . . . . . . . . . . . . 258

Douglas R. Nordli Jr. and Darryl C. De Vivo
xiii
xiv CONTENTS

Chapter 10 Pediatric Epilepsy Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283

Douglas R. Nordli Jr.
Chapter 11 EEG in Adult Epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315

Mohamad Z. Koubeissi and Elson L. So
Chapter 12 EEG Voltage Topography and Dipole Source Modeling

of Epileptiform Potentials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 338
John S. Ebersole
Chapter 13 Subdural Electrode Corticography . . . . . . . . . . . . . . . . . . . . . . . . . 367

James Tao and John S. Ebersole
Chapter 14 Intracerebral Depth Electrode Electroencephalography

(Stereoencephalography) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393
Philippe Kahane and François Dubeau
Chapter 15 Evoked Potentials Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442

Aatif M. Husain
Chapter 16 Neurophysiologic Intraoperative Monitoring . . . . . . . . . . . . . . . . . 488

Aatif M. Husain
Chapter 17 Continuous EEG Monitoring in the Intensive Care Unit . . . . . . . . . 543

Saurabh R. Sinha and Lawrence J. Hirsch
Chapter 18 Sleep Disorders: Laboratory Evaluation . . . . . . . . . . . . . . . . . . . . . 599

Rodney A. Radtke
Index 631
1 The Cellular Basis of EEG
CATHERINE A. SCHEVON • ANDREW J. TREVELYAN
Introduction The Relationship between Oscillations

Electrical Flow in the Brain and Cellular Activity
Action Potentials Hierarchical Phase-Amplitude Coupling
Synaptic Currents Cellular Basis of Epileptiform Activity
Active Conductances Neural Activity during Epileptiform Discharges
Gap-Junction Coupling Lessons from Microelectrode Arrays: Ictal
Nonneuronal Currents Discharges and the “Ictal Penumbra”
The Anatomical Organization of Cortical Currents Surround Inhibition
Hippocampal Anatomy EEG Markers of Ictal Territories: High-frequency
Oscillations
Basket Cells
Conclusion
Neocortical Anatomy and Thalamic Connections
Acknowledgments
Oscillations
References
The Structure of EEG
Introduction These qualitative properties of the signal include the structure and symme-
try of prominent spontaneous oscillations such as the posterior dominant
EEG remains, as it has been since Berger made his first recordings in the rhythm and sleep spindles, the relative mixture of frequencies and their spa-
1920s (1), a pivotal diagnostic clinical tool for assessing brain activity. Tra- tial organization, and the presence of paroxysmal waveforms such as epilep-
ditionally, EEG is interpreted by visual inspection of the signal traces, using tiform discharges.
a set of qualitative rules developed through collective clinical experience, to This empirical approach to EEG interpretation, in which certain features
define features of the EEG that are associated with particular brain states. of the EEG signal have become associated with particular brain states, has
1
served generations of neurologists and neurophysiologists well. Historically, great pace. Recent neuroengineering advances have resulted in clinical sensors
the reason this approach has been predominant is obvious: Berger and his capable of high spatiotemporal resolution recordings that augment standard
early followers quickly realized the significance of certain characteristic fea- EEG with information about neuronal firing. This makes available a broad
tures of EEG long before we had tools that could make sense of the signals. array of neurophysiological data types, ranging from oscillations synchro-
Over the ensuing decades, clinicians have learned to use these EEG features nized over large brain areas to unit firing in a single cortical macrocolumn,
as powerful indicators of focal or widespread cortical abnormalities. These which electroencephalographers should develop familiarity with, as the new
diagnostic associations have proved robust; they are standing the test of technologies find increased use in the clinical setting. There is also increas-
time well, and will be covered extensively in later chapters. ing use of sensors recording from below the dura or within the brain paren-
Is it enough then simply to understand EEG as a “black box,” and go chyma, which not only afford ever greater diagnostic possibilities but create
no further? We believe not. There are powerful arguments that we should new opportunities for the investigation of human cognitive function, a ven-
strive for deeper understanding, asking why these associations exist. One ture that requires close cooperation between neuroscientists and clinicians.
reason is that technology is advancing rapidly, allowing us to record and
manipulate brain signals in ways that will shed new light on the meaning Electrical flow in the brain
of old data sets. Another motivation is that in many ways, the EEG is an
impoverished signal, which prevents us from differentiating between various Changes in the extracellular field potential arise because ions flow in and
possible underlying activities. This leads to these different activities being out of cells at very focal sites, thereby creating ionic flow also in the ex-
pooled together, which then weakens what associations we can draw. An- tracellular space (Fig. 1.1). The driving force for the initial movement is
other important reason to explore the neural basis of these signals is that invariably the electrochemical gradients that exist across the cell membrane.
there are interpretative pitfalls. For instance, some uses of EEG, such as By far, the largest currents flow through ion channels; indeed a simple lipid
the localization of activity, are fraught with the problem of circular logic, if bilayer without channels is essentially impermeant to ions. There are also
independent measures of activity patterns are lacking. It is important to be small currents associated with electrogenic ion pumps—proteins that gener-
able to recognize these cases. ally are working to restore ion balances and thus are working against the
There is a tendency to rest on the simple intuition that the EEG signal is electrochemical gradient. Examples of these are the various ATP-dependent
merely a weighted average of everything that goes on beneath the electrode. pumps that restore Na+, K+, Ca2+, and H+ across various membranes.
In some ways, this is a truism, but the danger comes from confusing the These can ultimately shift the membrane potential by up to about 10 mV,
different levels of understanding the brain. The EEG derives from currents but in terms of rates of flow of ions, these currents are far smaller than
flowing in and out of cells, but the activity that most neuroscientists and neu- channel currents. It is possible that these pumps may contribute to extremely
rologists are ultimately interested in is neuronal firing behavior, because that slow frequency changes in the extracellular field, including so-called DC
is how information is thought to be processed. One of our aims in this chap- shifts, small step changes in the electric field that have been seen in certain
ter is to show that the ionic level and the firing levels do not always relate in a brain states including epileptic seizures—this remains an open question. It is
simple manner. Most importantly, we want to stress that these issues are not quite clear, however, that any rhythms higher than about 1 Hz are too fast to
merely of academic interest, but may seriously impact on clinical practice. be attributed to pumps, and that all such faster rhythms must therefore arise
In this chapter, we will describe findings in basic neuroscience that link from flow through ion channels. For the purpose of this chapter, therefore,
these EEG signal features to the sources of electrical activity in the brain. when referring to cell membrane currents, we will use the term conductance
Our goal is to provide electroencephalographers with an understanding of as a synonym for ion channel. Patch clamp studies can derive the unitary
the cellular activity that contributes to the electrical signals measured by conductance of a single ion channel, and so the total conductance is simply
EEG, the sources and structure of cortical oscillations, and the network be- the product of this unitary conductance and the number of channels that
haviors contributing to normal and pathologic EEG activity. are open. Since the total conductance is a nice intuitive term, reflecting the
We are at an exciting time in neuroscience, when new ways of recording, total number of channels open, it is used in preference to its reciprocal, the
analyzing, and even manipulating neuronal activity are being developed at resistance, when talking about membrane currents.
The Cellular Basis of EEG 3
Figure 1.1: Local circuits induced by transmembrane currents. A: Changes in intra-

cellular membrane potential (upper panel), and in the membrane conductance of
Na+ and K+ during an action potential. B: As the action potential propagates, the
highly focal changes in transmembrane conductance create large movements of
Na into, and K out of the cell. Currents moving into cells are referred to as current
sinks (i.e., relative to the extracellular space), and those moving out of cells and into
the extracellular space are called current sources. Charge redistribution away from
these sinks and sources can be measured by electrodes as fluxes in the electric field.
C: Schematic showing how the electric field drops with distance down a cable. A
steady state holding potential drops off with a space constant, l = (d·Rm/4·Ri)0.5. The
space constants for oscillating currents are shorter (the drop off is faster), because
the capacitance absorbs current proportional to the rate of change of the potential.
The dissipation of electric field in the extracellular space is likely to be similar, al-
though the complexities of the circuit are far greater than for intracellular currents,
and so we do not have analytical solutions for the extracellular space. D: Local elec-
trical circuits may also be created through synaptic conductances. E: Linear IV rela-
tionships follow Ohm’s law, where the gradient is the conductance (reciprocal of the
resistance), and (F) the intersection of the abscissa is called the reversal potential.
Persistent currents are also termed “passive conductances”—synaptic currents that
are Ohmic are not strictly speaking “passive” because they are gated currents, by
neurotransmitter binding. In contrast, other currents show large voltage-dependent
changes in conductance. These are referred to as “active conductances.” All gated
currents, including both neurotransmitter-gated and voltage-gated currents, can be
very rapidly activated, thereby generating large currents and rapid fluxes in the ex-
tracellular field.
Action Potentials juxtaposition of the firing neurons, and their positions relative to the record-
ing electrodes, influence the recorded signal. Consider, for instance, the case
The elucidation of the currents flowing during an action potential, by Alan when two closely apposed neurons are firing repeatedly at high frequency
Hodgkin and Andrew Huxley, was a seminal moment in the history of (>250 Hz) but 1 to 2 milliseconds out of phase with each other. Locally,
neuroscience (2–5) (Fig. 1.1). They described how, as a neuron is depolar- this induces small currents reverberating in the extracellular space between
ized from rest, there is a point at which voltage-dependent Na+ channels the cells, as Na+ ions go in and K+ ions come out of the cells. These rever-
are suddenly opened. There is then a surge in the inward current, creating berating extracellular currents may be recorded, but they are small and very
a positive feedback cycle, which is only terminated by the equally sudden local, and thus their visibility is very dependent on the exact positioning of
inactivation of the Na+ channels. Inactivation occurs very quickly, after the recording and reference electrode, and the impedance of the electrodes.
about a m illisecond, and coincides roughly with the slightly slower open- Now consider a larger cluster of neurons, say 10 cells firing at more typical
ing of voltage-dependent K+ channels. This combination of closing of Na+ rates for pyramidal cells, at 50 Hz, but again with some millisecond jitter. As
channels and opening of K+ channels rapidly brings the membrane poten- before, if the recording electrode is located within the cluster, then one may
tial back down to resting membrane potential (or even overshoots briefly). be able to discern the direction and amplitude of small, local extracellular
Restoration of the resting membrane potential results in shutting of the currents relating to particular cells (relative to the distant location of the ref-
voltage-dependent K+ channels. erence electrode), and this is the principle behind spike-sorting algorithms.
The density and kinetics of the ion channels (particularly the K+ chan- When the recording electrode is outside the cluster of neurons, the jitter in
nels) vary in different neuronal classes, allowing some cells to fire at far firing results in some destructive interference, and there may be little current
higher rates than others. Firing patterns are also influenced by other slower flow at the actual electrode. If, however, firing becomes more synchronous,
currents, which shape the tail end of action potentials, leading to after- then the currents become far more visible at that electrode. The visibility of
hyperpolarizations and after-depolarizations. The major currents underly- the currents, therefore, requires synchrony at the timescale of the transmem-
ing an action potential, though, last in the region of just 1 to 3 milliseconds. brane currents. We will return to this point shortly when considering the
Consequently, action potentials are very high-frequency signals, and this much longer duration synaptic currents.
affects how far they travel through electrical fields with significant ca- A second factor determining the visibility of currents is their amplitude.
pacitance (Fig. 1.1). Electrophysiologists refer to the “transfer function” Hodgkin and Huxley based their model on recordings of the squid giant
(6), which is the drop in electrical field going from point A to point B. axon, the largest axon in the natural world, but much subsequent work has
A steady holding potential at point A drops off rapidly when recorded shown that the essential features of the Hodgkin-Huxley model are also
at increasing distances. Most theoretical work on transfer functions has replicated in the far smaller neurons in mammalian brains. Regarding how
considered the flow of membrane potential changes intracellularly; for in- these currents appear in the EEG, however, in this instance, size matters.
stance, examining how a synaptic potential drops from the dendritic spine The essential details are exactly analogous to changes in concentration.
to where it is usually recorded at the soma. Extracellular transfer functions A drop of ink added to a thimbleful of water will cause a big change in
are considered to be analogous, except that the mathematical model is far color, but the color change might be imperceptible when a drop is added
more complex, with multiple parallel routes through the network and a to a bucketful. With neuronal membrane potential, we are dealing with
less clearly defined capacitive element, and an analytical solution, even if charging up membranes; so the structure of interest is a surface area, not a
it were possible, has not been worked out. Empirically though, it is clear volume, but the principle is exactly the same. For large structures, like a cell
that high-frequency voltages such as action potentials dissipate rapidly in body, or the squid giant axon, a large charge flow is needed to substantially
the extracellular space. In contrast, slower electrical fields, such as those change the membrane potential. Conversely, a large membrane potential
associated with synaptic currents, influence the electric field over a larger change implies a large transmembrane current. But for tiny structures, like
volume of the brain. most mammalian axons, the currents involved are, relatively, very small.
The very transient nature of action potential currents is also an impor- Furthermore, many mammalian axons are myelinated (although many lo-
tant issue when there are multiple neurons firing. The spatial and temporal cally connecting grey matter axons are not), and so still smaller currents
are involved per unit length of axon, because the current only flows at According to these equations, the driving force for any transmembrane
particular hotspots, the nodes of Ranvier. Consequently, as it propagates current is the difference between the reversal potential and the membrane
through the axonal tree, an action potential does not constitute a large potential. When a receptor opens on a dendritic spine, small ion movements
“sink” of current away from the extracellular space. Moreover, since action cause big changes in membrane potential (the ink and thimble analogy men-
potentials propagate rapidly down the axon, the current sink is distrib- tioned earlier), and so the membrane potential will shift rapidly toward the
uted over a spatially extensive area very quickly. In contrast, a rather more reversal potential of the receptor. As a result, the driving force drops sharply
visible current in the EEG arises from the postsynaptic consequence of in these small structures, and in turn, the current also drops quickly. In con-
axonal firing. trast, receptors on larger structures, such as the dendritic trunk or soma, do
not shift the membrane potential toward the reversal potential as easily; so
Synaptic Currents the driving force persists and the currents also remain high.
A second important feature of synaptic receptor currents is that, relative
Neurotransmitters released from axonal terminals and varicosities cause to action potential currents, they are long lasting; most last 5 to 20 milli-
postsynaptic receptors to open on dendritic spines, on the dendrites them- seconds, while others last hundreds of milliseconds. The best characterized
selves, and also on the soma and axon hillock. The same size argument as of these long-lasting synaptic currents are N-methyl-d-aspartate (NMDA)
outlined earlier, for axons, also applies for dendritic spines. In contrast, the plateau potentials (7). NMDA receptors require glutamate binding to
dendritic trunks may be relatively large (>5 μm diameter, compared to ap- open, but like Na+ channels are also voltage-gated, and can thus also pro-
proximately 1 μm or smaller for most axons and dendritic spines). Theoreti- duce regenerative currents. This is a kind of action potential, but unlike
cal calculations show that these size considerations impact on the currents our previous description of the Hodgkin-Huxley model, NMDA receptors
flowing through receptors at these different locations. The currents flowing are inactivated far more slowly than Na channels and thus induce a self-
are dictated by Ohm’s law sustaining depolarization. This “plateau potential” may also be boosted by
other voltage-dependent Ca2+ currents, because these too are inactivated
V = IR (1)
slowly, and hence also contribute to the self-sustaining depolarizing current
Turning this equation round, we get over tens of milliseconds. A further important feature of NMDA receptors
is their modulation by other extracellular ions and molecules. Mg2+ ions
V are critical for the voltage-dependency (8); in addition various amino acids,
I = (2) including glycine and serine, bind at extracellular sites and modulate the
R
NMDA opening properties (9). Thus, changes in the ionic and molecular
This may be rewritten more appropriately for transmembrane currents, in constitution of cerebrospinal fluid may influence the likelihood of such pla-
terms of the membrane driving forces and the conductance, g, which is the teau potentials occurring and also their duration.
reciprocal of resistance (g = 1/R). Thus, the current (note that the conven- The protracted nature of these postsynaptic currents means that they will
tion is to plot inward currents as negative) is expressed as summate strongly in the extracellular field, even when the initial, causative,
presynaptic action potentials are not absolutely synchronous. The time
I = g(Em − Erev) (3) scales of these currents are simply far longer than those of action potentials.
where Em is the membrane potential, and Erev is the reversal potential for the Furthermore, there is one obvious, and commonly occurring, situation when
ion in question, which is set by the concentrations inside and outside the cell, the postsynaptic currents are highly synchronized: when they arise from an
as given by the Nernst equation action potential in a single axon, releasing vesicles at multiple varicosities.
We shall return to this point later, in our discussion on basket cells.
[ion]out To summarize the section so far, postsynaptic currents are larger and lon-
Erev α In (4) ger lasting and have lower-frequency components than those underlying ac-
[ion]in tion potentials, and consequently are more visible in extracellular recordings.
Active Conductances
In addition to numerous synaptic receptors, the dendrites and somata have
many other conductances. The most relevant for EEG are so-called active,
or non-Ohmic, conductances. These change their conductivity with changes
in membrane voltage, unlike Ohmic conductances, which have a linear I-V
relationship. Hodgkin-Huxley channels and NMDA receptors are all exam-
ples of active conductances, but there are many others besides. Of particular
importance are the voltage-dependent Ca2+ channels, which in addition to
their role in gating neurotransmitter release at synaptic terminals, are also
found in the dendritic tree and soma where they underlie bursting behav-
ior in many neuronal classes, including certain classes of pyramidal cells in
cortex and hippocampus. In these pyramidal cells, there are great concentra-
tions of voltage-dependent Ca2+ channels at the tuft of the apical dendrite,
which may play a role in certain rhythmic activity and in distorting, and
especially boosting, synaptic inputs. Since these are concentrated within the
upper cortical layers, they are examples of highly localized current sinks. Figure 1.2: Entrainment of neuronal bursting induced by small fluctuations in
An important feature of these active conductances is that they can give the extracellular field (adapted from Fröhlich F, McCormick DA. Endogenous
rise to sudden and large changes in local transmembrane currents near their electric fields may guide neocortical network activity. Neuron 2010;67:129–143).
threshold voltage. However, synchronization of these currents in populations Spontaneous bursting activity in a brain slice was modulated by application of
of neurons, which is likely to be a prerequisite for such currents being visible small extracellular voltages of comparable size to those recorded in vivo. The
in EEG recordings, requires interactions between neurons. The most obvi- switch between up and down states is rapidly entrained to whatever extracellular
ous way this happens is through chemical or electrical synapses, although rhythm is being imposed, as shown by the close correlation between the period
of imposed field and the period of the entrained activity. Demonstrations like
recent work has provided experimental evidence also for so-called “ephaptic”
this provide a proof of principle that ephaptic effects are real, albeit very small.
interactions. Ephaptic interactions refer to how very small fluctuations in the
Indeed the intracellular effect is likely to be no larger than the summed activation
local field potential caused by one cell’s firing, passively entrain the a ctivity of less than about three to five excitatory synapses.
of other neurons (10–13) (Fig. 1.2). Several groups have now shown that elec-
trical fields, of comparable amplitude to those actually recorded in the brain
(2 to 4 mV/mm), can modulate firing patterns (13). Interestingly, the effect members of the same inhibitory neuronal classes. Thus, parvalbumin-
appears to be proportional to the rate of change of the field, so higher fre- expressing basket cells are connected through gap-junction syncytia, as
quency oscillations entrain more powerfully than lower frequencies, although are somatostatin positive neurons, but it appears that the two classes of
as we discussed earlier, lower frequencies propagate further in the brain. neuron do not connect with each other, and that the syncytia are thus
Thus, even though these local ephaptic interactions are tiny, the entrainment entirely separate. There are theoretical arguments and some experimental
may still grow to synchronize many neurons, in the same way that fireflies data also suggesting that pyramidal cells may be interconnected through
may coordinate their flashes, or theater audiences come to clap in synchrony. gap junctions located between axons, creating what is referred to as an
axonal plexus. It has been suggested that, in certain conditions, activity
Gap-Junction Coupling may spread and escalate through this plexus, building up eventually to a
full ictal event. This model of ictal initiation derives from a rather artifi-
Electrical synapses, through gap junctions, have been described in a number cial, in vitro epilepsy model in which all synaptic activity is prevented by
of cortical populations. The best evidence for such connections is between removing Ca2+ ions from the extracellular medium. In contrast to synaptic
function, gap-junction coupling appears enhanced in zero Ca2+ medium, there is continued debate regarding to what extent these data merely show
and sharp electrode recordings of neurons commonly show “spikelets,” the potential of glia, rather than what really happens in vivo. Our under-
which are presumed to be retrogradely propagating action potentials that standing of these phenomena continues to evolve, and will soon clarify what
invade the soma, but which fail to induce a full action potential there be- glia do in both physiological and pathologic brain states.
cause of the impedance mismatch going from the small axon to the large A more established function for glial syncytial networks is the redistribu-
soma. The trigger for the back-propagating action potential has been sug- tion of local inhomogeneities of extracellular ions. After intense bursts of
gested to be a gap-junction connection with another active axon. neuronal activity, extracellular K+ rises and Ca2+ drops markedly. Follow-
An important point to make is that gap-junction-mediated currents being an epileptic burst, extracellular K+ may easily exceed 10 mM. Steven
tween cells are likely to be virtually invisible to extracellular recordings. Kuffler, in the 1960s, suggested that glial networks may redistribute K+ ions
This is because gap-junction currents flow directly from one cell to the in these conditions. Recently, strong support for this has been provided by
next, without creating a local sink or source of current in the extracellular the demonstration that glucose imbalances in parts of cortical networks
compartment. They may be visible indirectly, however, by synchronizing cause increased coupling of glia, and thereby also enhanced the spread of
firing between cells (14,15). As such, gap-junction coupling may lead to a fluorescent glucose analog (17). If the same process occurs with charged
summation of transmembrane currents in such synchronized cells. Two ionic species such as K+ ions, then focal epileptic activity would trigger po-
other points are worth making. First, gap junctions may extend the elec- tentially a large current sink, with characteristically slow kinetics, and the
trotonic length of neurons: Quite simply, the cellular “unit” is extended current circuits would match the dimensions of the extent of changes in
into the adjacent cell, creating a syncytium, and so charge entry into one extracellular K+. This needs further research, but the theoretical argument
cell is then dissipated and eventually returned to the extracellular space suggests that such low-frequency currents, reflecting their slow kinetics, ap-
over a larger area. In this way, the effective circuit is increased in size, pear in the EEG as a change in very low-frequency (or DC) power, and
although in doing so, the “return” part of the circuit, away from the ini- may thus provide a useful marker of the location of intense epileptiform
tial current, carries a lower density current because it is distributed over a discharges.
larger surface area. The second is that while the conventional arrangement
is for hemichannels to be juxtaposed with hemichannels of adjacent cells, The anatomical organization
thus making a full gap junction, there are cases when the hemichannel of cortical currents
appears to exist in isolation. It is possible that such hemichannels may be
induced by epileptic activity (16), and cause further trauma to the partici- Hippocampal Anatomy
pating neurons, while also allowing currents that may be visible in EEG
recordings. The hippocampus in humans is tucked away from accessible sites for place-
ment of EEG electrodes, or even subdural electrodes. As such, activity in
Nonneuronal Currents the hippocampus is largely invisible in EEG or ECoG recordings, although
it can be recorded readily using depth electrodes. Hippocampal recordings
Finally, we come to currents flowing through glial networks. Glia are also both in vivo and in vitro have contributed hugely to our understanding of
highly connected through gap junctions, and this facilitates the spread of synaptic physiology and network oscillations. The usefulness of the hip-
waves of Ca2+ transients from cell to cell. The cytosolic Ca2+ surges come pocampus for these researches is that its anatomical organization is re-
primarily from intracellular stores, making them unlike those in neurons, markably laminar. Pyramidal somata are packed densely in the pyramidal
which primarily reflect transmembrane currents. As such, glial Ca2+ tran- layer, with dendritic trees that project almost perpendicular to that layer
sients are not likely to have a direct impact on EEG signals. They may do on both sides. The excitatory drive on to pyramidal cells is arranged per-
so indirectly though, by releasing neuroactive substances, which cause local pendicular to the dendritic trees, and parallel with the pyramidal cell layer.
neuronal discharges. There is good evidence from many laboratories sup- In short, one could not design a structure more suited to the study of as-
porting this view, although much of this derives from in vitro work, and sociative learning, allowing the simple independent stimulation of parallel
inputs onto a single cell by placing the stimulating electrodes at different at very high frequencies (>200 Hz). Furthermore, while current thinking is
depths along the somato-dendritic axis. Such stimuli, and indeed any bar- that all fast-spiking basket cells express parvalbumin, it is also the case that
rage of presynaptic inputs, induce a focal synaptic current with respect to other cell classes express parvalbumin too, and even that parvalbumin ex-
this same axis, and conversely, one may record current sinks along that axis pression may be altered by activity levels. Thus, all fast-spiking basket cells
and associate them with particular presynaptic inputs. Further, one may may be parvalbumin positive, but not all parvalbumin positive neurons are
progressively move a recording electrode along the somato-dendritic axis, fast-spiking basket cells. We make these points mainly to emphasize the fact
and record an inversion of the sign of the recorded field, and thus ascertain that interneuronal classification is a minefield for the unwary, and that many
the location on the dendrites of the transmembrane current. The direction specialists, quite rightly, get agitated when others are sloppy with their clas-
of the sign inversion may then indicate whether the transmembrane current sification. As ever, the devil is in the details, and we would encourage read-
represents a current sink (positive charge entering the cell, and thus “leav- ers to consult more specialist texts on this topic, of which there are many
ing” the extracellular space) or a source (negative charge entering the cell (19,20). We will limit ourselves here to some general, but important, points
[e.g., a hyperpolarizing GABAergic current] or positive charge leaving the that are particularly relevant to epilepsy and to the nature of EEG signals.
cell [late action potential K+ currents]). This approach to dissecting out the There are many notable features of these remarkable cells; the most im-
location of synaptic currents and neuronal firing is referred to as “current portant though regard their output. Basket cells project extremely densely
source density analysis” (18). on to the local pyramidal population. Indeed, each basket cell appears to
The arrangement of inhibitory circuitry in the hippocampus is similarly synapse on to every single pyramidal cell locally, and furthermore, makes on
ordered (19,20). Thus, anatomists have been able to classify many differ- average at least 10 synapses per connection. These synapses are all clustered
ent types of hippocampal interneuron, characterizing them according to densely around the proximal dendrites and the somata of the pyramidal
their stereotyped axonal and dendritic morphology and thus their drivers cells. The synapses show a high transmitter release probability, and the post-
and their outputs, the location of their somata, the expression of par- synaptic receptors have a high conductance. Thus a single action potential
ticular proteins (parvalbumin, somatostatin, VIP, calretinin, etc.), their in a basket cell may trigger a very large summed conductance in a very fo-
firing patterns, and many other cellular attributes. A major research goal cal region of cortex. We make a very important distinction here between
in recent years has been to characterize how these different interneuronal conductance and current, because as Ohm’s law states, the current depends
groups participate in different network oscillations, or even sculpt these on both the driving force and the resistance. Thus there may be a large con-
rhythms. ductance, but if the membrane potential is close to the GABAergic reversal
potential, the driving force is small. At rest, EGABA (typically about −60 mV)
Basket Cells lies close to the membrane potential, and under these conditions, the large
basket cell-induced, postsynaptic current is small.
Special mention needs to be made of one particular inhibitory cell class, In one very important situation, however, the driving force is large, and
that which targets the somata of pyramidal cells. The interneurons wrap therefore so is the GABAergic current. This occurs when there is concur-
their axons around the pyramidal somata, which thus appear like baskets rent glutamatergic drive and basket cell firing. The glutamatergic input drives
cupping the somata, hence the derivation of Cajal’s term, the basket cell the pyramidal cell to a more depolarized state, thus shifting the membrane
(his Golgi stains typically only labelled small number of cells, and so he saw potential away from the GABAergic reversal potential and creating a large
many examples when the presynaptic axonal basket was seen without the driving force. The inhibitory postsynaptic currents (IPSCs) are thus large,
contents of the basket, the pyramidal soma, being visible—it looks even and so constitute a powerful hyperpolarizing drive. They also have a second
more basket-like when the basket appears empty!). These cells also go by inhibitory action, which is referred to as shunting inhibition: They make the
other names, most commonly fast-spiking interneurons, and parvalbumin cell far more “leaky” and thus more current is required to depolarize them.
positive neurons, but these are not, strictly speaking, synonyms. It is clear, This is particularly relevant for pyramidal cells, which have a very striking
as the classification of cortical interneurons becomes more sophisticated, arrangement of synapses on their dendritic trees: All their excitatory inputs
that there are at least two populations of basket cells, only one of which fires are located on distal dendrites, with nothing on the most proximal dendrites
and soma, where instead, a huge density of inhibitory synapses is located. pyramidal cells are receiving essentially the same IPSCs, they are all inhib-
This distribution of synaptic input means that these proximal inhibitory syn- ited synchronously, but then all “bounce back” to fire in synchrony too.
apses can veto virtually any level of excitation. This is clearly predicted on Essentially, the same mechanism explains how a depolarizing agent such as
theoretical grounds, and has been shown experimentally for a comparable kainate, applied continuously to a cortical slice, sets up a gamma rhythm.
arrangement of synapses in crayfish (21), and more recently, in pyramidal In short, it creates a powerful depolarizing drive to most of the network,
cells themselves, in a simple model of epileptiform propagation (22). In this which is then overridden by firing of basket cells, but then the depolarizing
model, ictal discharges are induced by removing Mg2+ ions from the bathing influence kicks in again to create a pacemaker current. The exact rhythm
medium, thereby increasing excitation while preserving (at least initially) in- is essentially dictated by the rhythm of the basket cell firing, which is also
hibition. The cortical territories immediately ahead of the ictal wavefront are coordinated by gap-junction coupling as described earlier.
bombarded by excitatory barrages arising from the wavefront itself, but this is There is ongoing debate about whether this mechanism is the same for all
not necessarily translated into postsynaptic firing because of the power of the gamma rhythms. Gamma activity is considered to extend from about 30 to
inhibitory restraint on these neurons. Thus, there arises a kind of “ictal pen- 150 Hz, but this may be further subdivided into “low” and “high” gamma. It
umbra” around territories that have been recruited to a seizure, in which there is also relevant that in neocortical brain slices, certain pharmacological ma-
may be an extreme discrepancy between the level of synaptic currents (both nipulations may induce concurrent, but separate, gamma frequency rhythms
excitatory and inhibitory) and the level of neuronal firing. This is a very im- in the supragranular and infragranular layers (24). It remains to be resolved
portant scenario in human seizures as well, which we will return to later. what distinguishes the two rhythms in this model. It is notable, though, that
An important factor in the coordination of this restraining inhibitory the predominant laminar frequencies are the same as the firing rates of bas-
burst is that gap junctions interconnect these interneurons. Gap-junction ket cells in those same layers, suggesting that the two frequencies arise sim-
coupling has the effect of synchronizing firing in connected cells (14,15). ply because the different laminar basket cells vary in their sensitivity to the
Consequently, the high-frequency discharges of basket cells during these pharmacological agent, kainate. What this work does show, however, is that
bursts of activity may be synchronized with submillisecond precision across a single cortical column need not follow the same rhythm throughout the
an extended syncytium of cells. The pattern of inhibition during this re- cortical depth, and that the separation of rhythms may reflect the external
straint is of high frequency (100 to 300 Hz) and large amplitude IPSCs are drive. Gamma activity in vivo may show increased variations in the instan-
experienced by all pyramidal cells in a local area. Studies of these types taneous peak frequency, which is thought to reflect the fluctuations in the
of discharges in the magnesium washout model described earlier showed amplitude of the population IPSC: a large IPSC, perhaps unsurprisingly,
that these currents are highly visible in the local field potential. Although delays the rebound firing, and thus extends the period of the oscillation.
results from an in vitro model should be regarded only as proof of principle
rather than conclusive evidence of cause, this may be one of the mecha- Neocortical Anatomy and Thalamic Connections
nisms that can give rise to high-frequency oscillations in clinical recordings,
a potentially important epileptic biomarker. We will address this topic in Most of the same cell classes have been identified in neocortex, as have been
more detail in a later section. described in hippocampus. One difference is that in neocortex, pyramidal
In addition to a possible role in high-frequency oscillations, basket cells somata are distributed across almost the entire cortical depth, from layers 2
have a central role in gamma rhythm activity. Again, fundamental to this to 6. It is possible that this arrangement reduces the potential for ephaptic
rhythm is the power of basket cells in inhibiting pyramidal firing, which influences in neocortex, but the truth is we do not know why this evolution-
allows them to entrain pyramidal activity extremely well. This entrainment arily more recent cortical structure (“neo”-cortex) is arranged differently
has been shown compellingly by recording the initial desynchronized firing from archeocortex (hippocampus). A consequence is that the neocortical
of pyramidal cells from a baseline depolarizing state, and then imposing a anatomy is not as crystalline as in hippocampus, but it seems reasonable to
gamma frequency basket cell inhibition on the pyramidal cells (23). Each presume that the same basic principles elucidated using hippocampal prepa-
volley of IPSCs shut the pyramids down transiently, but this is followed by rations will also apply in neocortex. Because the somato-dendritic axes of
a narrow window between IPSCs when the pyramid can fire. Since all local the dominant cell type (pyramidal cells constitute about 80% to 85% of the
total neuronal population) are not all aligned, though, neocortical current acronym, HCN stands for “hyperpolarization-activated, cyclic-nucleotide
sinks and sources may not be so cleanly recorded as in hippocampal tissue. modulated”, which already tells us much about these conductances) (27).
An important feature of neocortical circuits is the pattern of recurrent These channels carry maximal current at relatively hyperpolarized levels
connections with thalamus. Thalamic nuclei not only provide the major ex- (about −80 mV), dropping down to almost nothing when cells are depo-
ternal drive to cortical circuits, but also receive back from cortex a large larized to about −30 mV. The key effect of this activation curve is that the
descending input, primarily from layer 6 pyramidal cells. This corticofugal currents act to resist changes from a moderately hyperpolarized state. Take
pathway sends collateral branches also to the reticular nucleus, a group of the situation where a cell is stable at rest at −65 mV. At this membrane po-
inhibitory neurons that then project on to the same set of thalamic neurons tential, there will be a subpopulation of these channels opened, which are
as the direct cortical pathway targets. Cortical discharges therefore not only providing a tonic depolarizing current that will be contributing to the steady
create a direct excitation of thalamic neurons, but also cause a disynaptic state at that membrane potential. If the cell experiences a hyperpolarizing
inhibition mediated through the reticular nucleus. drive though, some of these HCN channels will close, thus reducing the
A further key feature of this thalamocortical circuit is that both tha- depolarizing drive, and the membrane potential heads back toward −65 mV.
lamic and reticular neurons have a peculiar arrangement of low-threshold Remarkably, exactly the same effect happens if a hyperpolarizing drive
activated Ca2+ channels. The two nuclei express slightly different forms of is given, because this will cause HCN channels to open, thus providing a
voltage-gated Ca2+ channel: Both nuclei express the Cav33.3 isoform, but the stronger depolarizing current, and again causing the membrane potential
reticular nucleus also expresses Cav2.3, which is activated at higher threshold to head back toward −65 mV. The currents have quite slow kinetics how-
than those found in thalamocortical neurons, and this may be relevant to ever, opening or closing over a time course of about 10 to 15 m illiseconds.
the subtle distinction between pathologic and physiologic thalamocortical Thus, if these cells are given a sharp inhibitory synaptic drive, arising for
bursting (25), which we will discuss shortly. The presence of these channels instance in the reticular nucleus and mediated by both GABAA and GABAB
means that thalamic neurons discharge in two different ways. If they are receptors, the HCN channels will then create a pacemaker current from
activated from a relatively hyperpolarized state (below about −65 mV), then this inhibitory trough. If the inhibition is sufficient to de-inactivate the
the depolarization opens both Na+ and Ca2+ channels. The latter inactivate low-threshold voltage-gated Ca2+ channels (i.e., membrane repolarization
far slower than Na+ channels, and consequently, cause secondary firing; in following closure and inactivation of the Ca2+ channel changes its confor-
other words, the combined activation of both Na+ and Ca2+ channels causes mation to a closed, but activatable, state), the Ih pacemaker current can then
a burst of action potentials. This is the dominant pattern in sleep and also reactivate these channels, and the neurons fire a burst of action potentials.
underlies the spike and wave pattern of idiopathic generalized epilepsies. In This reactivates the reticular nucleus, which reinhibits the thalamus, and we
the waking state, thalamic neurons at rest are in a more depolarized state, at have the potential for a self-perpetuating rhythm.
about −60 mV, and in this state, the Ca2+ channels are already inactivated. This pattern of bursting provoked by voltage-gated Ca2+ channel acti-
A further, transient depolarization then only activates Na+ currents, and vation, the latency of synaptic delays between the reticular and thalamic
the cells fire just a single action potential. This slightly paradoxical state of nuclei, and the slope of the Ih-driven pacemaker drive a rhythmic 7 to 14 Hz
affairs, whereby neurons burst more intensely if driven from a more hyper- oscillation in the cortex, referred to as sleep spindles (28). These occur every
polarized state, is thought to underlie two different patterns of information 3 to 10 seconds in the early stages of sleep, and are most prominent in the
transfer in the thalamus. Bursts of activity may provide some kind of wake- frontal and midline regions. A related mechanism is responsible for the spike
up call, but the normal waking mode, in which thalamic neurons only fire and wave discharges (SWDs) that are a hallmark of idiopathic generalized
single action potentials may more faithfully transfer sensory information to epilepsy syndromes. These differ from spindles in several respects. They are
the cortex. slower (3 to 6 Hz), larger in amplitude, have a prominent spike component
There are three other notable membrane currents in thalamic neurons, preceding the slow wave, are recorded throughout the cortical mantle, but
which may influence the likelihood of rhythmic bursting (26,27): Ih, GABAB may be either frontally or posteriorly predominant. The most notable dif-
and tonic GABAA currents. Ih is the hyperpolarization-activated, nonspecific ference, though, is that unlike sleep spindles, SWDs may also occur during
cation current (Erev = −30 mV), encoded by HCN1 and HCN2 genes (the wakefulness, when they may be clinically manifest as absence seizures.
Sleep spindles and SWDs also appear to differ in the relative involvement (“blocking”) with eye opening were described by Berger in 1929 (1). Sim-
of the reticular and thalamic neurons. In vivo recordings in cats (29) and ilarly, the mu rhythm, with components in the alpha and beta frequency
the GAERS rats (“Generalized Absence Epilepsy Rats of Strasbourg”) (30) bands, is related to sensorimotor processing in the frontal and parietal lobes
suggest that the dominant bursting in SWDs occurs in the reticular nucleus (38). As we have discussed, spindles and rhythmic slow waves are distinctive
neurons, possibly secondary to some initial event in cortex (31). The burst of features of the sleep states, whereas during wakefulness, polymorphic and
reticular firing creates a flurry of inhibitory synaptic potentials in thalamic rhythmic, local or diffuse slow waves are commonly associated with cerebral
neurons, which consequently fire only single spikes or are silent, unlike their dysfunction. There are also many highly characteristic patterns associated
behavior during sleep spindles (29,32). The failure of the burst of inhibitory with particular seizure phenotypes, and we could list many other examples.
postsynaptic potentials to deinactivate the Ca2+ channels in the thalamic While these long-recognized clinical associations are reason enough to study
neurons in these recordings has been attributed to a pathologically high level oscillations, it is increasingly clear that the very nature of brain function is
of tonic inhibitory currents (these “tonic” currents pass through GABAA tied to oscillations (39,40). We will not understand the brain until we under-
channels that are persistently open—this may happen because there remain stand how and why groups of neurons behave this way.
low levels of GABA in the CSF, and certain receptor subtypes, notably those Interest in brain oscillations has grown immensely in recent years, moti-
that include δ-subunits, do not inactivate), which act to clamp the membrane vated largely by two pieces of research that suggested particular functional
potential above the level needed for deinactivation of the voltage-gated Ca2+ significance to oscillations. The first was a series of recordings made by John
channels (33). Intense cortical pyramidal and interneuron firing is also ob- O’Keefe and Colleagues using extracellular electrodes implanted into the
served during the spike component of the pathologic discharges, which is entorhinal cortex of rats that were trained to run along simple mazes and
not present in spindles (34). The two rhythms may be linked by the phenom- tracks (41). They could isolate the activity of single cells (“unit” recordings,
enon of augmenting potentials in thalamocortical circuits; stimulation any- detected and sorted from the high-pass filtered signal as we described ear-
where in the circuit at 10 Hz leads to incremental potentials, and ultimately lier), and also the local field potential (low-frequency bandpass recordings),
to spike and wave discharges very similar to those in absence seizures (35). all done with the same electrode. They found that as the rat moved along a
Thus, both these rhythms involve burst firing in the thalamic and reticular simple track, cells consistently fired when the rat was at certain points along
nucleus, but differ in the relative involvement of the two nuclei and cortex. the track. That is to say, individual cells represented particular places along
The rhythms may be influenced by neuromodulation (36), such as choliner- the track, and these cells were duly termed “place cells.” The other notable
gic projections from the brainstem and basal forebrain, which act by mod- finding was that the firing showed a very special relationship with the local
ulating the various active conductances, and in particular Ih (26). In both field potential, which had a predominant theta rhythm (5 to 8 Hz): As the
cases however, it is easy to see how the intensity of these rhythms, cycling rat moved through the place field for a particular neuron, the cell fired at a
between the thalamus and the reticular nucleus, may disrupt the flow of sen- fractionally earlier time point during each oscillation of the theta rhythm.
sory information through this relay, during both sleep and absence seizures. Another way of putting this is that the cell’s firing was at a very slightly higher
We have provided just a brief outline of these fascinating thalamic behaviors, frequency than the field oscillation. Its firing appeared to “progress” forward
which is covered in far greater detail in more specialist monographs (35,37). as the animal moved forward, and this gave rise to the term “phase progres-
sion” for this phenomenon. Thus the position of the rat was represented not
Oscillations only by activity of particular neurons, but also by the rhythm of their firing.
The second study was of recordings in cat visual cortex made by Singer
One of the most important tasks performed by electroencephalographers and Colleagues, of the responses of groups of neurons to presentations of
interpreting clinical EEG studies is the identification of visually prominent bars of light (42). What Singer and his team did was identify neurons whose
rhythmic patterns, or oscillations. These oscillations often provide clinically receptive fields were aligned, such that they could be stimulated by flashes
useful markers of both normal and pathologic activity. The first oscilla- of light, either independently with two short bars or together, by a single ex-
tion noted in human EEG was the 8 to 12 Hz posterior dominant (alpha) tended long bar of light. They found that both approaches increased the fir-
rhythm. The presence of this rhythm during wakefulness and its attenuation ing of the pair of neurons, but when they were activated together by a single
B
Comp
1.5 Hz
7 Hz
40 Hz
0 1 2 3
time (s)
Figure 1.3: Structure and interaction of brain oscillations. A: Amplitude spectrum of EEG recorded from a
lateral frontal subdural grid electrode during wakefulness, with frequency ranges shown as color-coded bars.
Note the near linear decrease in amplitude with frequency shown on a natural logarithm scale. B: Schematic
of hierarchical, phase-amplitude coupling in EEG. The top trace illustrates the typical observation: Oscillations
recorded in the brain are normally complex mixtures of components at different frequencies. The traces below
illustrate the individual oscillatory components in the delta, theta and gamma band that comprise the com-
posite waveform. Gamma oscillatory amplitude varies with the phase of the underlying theta oscillation, and
theta oscillatory amplitude varies with the phase of the underlying delta oscillation. C: Hierarchical coupling
in human microelectrode data recorded from lateral temporal neocortex during an auditory task (Besle and
Schevon, unpublished). A modulation index (56) was computed for phases between 0.1 and 20 Hz, and for
both amplitudes between 1 and 250 Hz and the amplitude of multiunit activity (MUA, above), filtered 500 to 5
kHz and rectified. Significant phase-amplitude coupling was found between delta phase and MUA (A), gamma
(B), and theta (C) amplitudes, and between alpha phase and both MUA (D) and high gamma amplitude (E)
color version is available online.
long bar of light, that is to say they were responding to the same object, their optogenetic techniques, we may now have the tools to test Singer’s remark-
firing became synchronized at gamma frequencies. The implication was that able hypothesis.
gamma synchronization was how the brain represents “unity”—that activity
in these disparate neurons were reflecting one and the same stimulus. This The Structure of EEG
has proved to be a very influential observation, triggering many subsequent
studies, but is limited in that it is just a correlation; what we need now is Cerebral signals recorded as EEG contain superimposed oscillations in a
to be able to modulate these rhythms, either to create or destroy the bind- wide range of frequencies (Fig. 1.3). In humans, recorded oscillations range
ing oscillation, so that we can really demonstrate causality between gamma from 0.05 to 600 Hz, divided into fixed frequency bands. At the high end
rhythms and the so-called “binding problem.” With the development of of the spectrum, above approximately 150 to 200 Hz, oscillations begin to
overlap with multiunit activity, or the extracellular signatures of action po- excellent tool for detecting brain rhythms with fine temporal resolution, but
tentials, rather than synaptic currents. Signal amplitude is much higher in its usefulness for locating the source of these rhythms is often limited. We
the lowest frequency bands, and decreases with frequency in a steep “1/f” will revisit this point later on, in the context of seizure recordings.
curve. This inverse relationship of signal amplitude to frequency is char- In previous sections, we described the electrical currents induced by firing
acteristic of many biological signals. A similar inverse relationship also ex- neurons, and gave examples of EEG rhythms that are generated by bursting
ists between the spatial extent of oscillations and frequency; as alluded to cells in the thalamus. We now shift our focus to the EEG oscillations them-
earlier, higher frequency oscillations are restricted to small cortical volumes, selves. Earlier, we discussed several mechanisms by which neuronal firing
while low frequencies are more broadly distributed (39). can be synchronized and regulated to generate rhythmic extracellular field
EEG recorded from the scalp is typically limited to frequencies under potentials, such as shunting inhibition from basket cells onto perisomatic
about 30 Hz, due to attenuation of the recorded signals by the skull and in- pyramidal neurons. Conversely, slow oscillations themselves may influence
tervening layers of tissue (43), as well as interference from extracerebral elec- the firing probability of a neuron through their effect on endogenous electri-
trical sources such as muscle activity. Higher frequencies are preferentially cal fields, as described previously in the discussion of ephaptic interactions.
screened out due to the smaller amplitude of the high-frequency signals, and The best described of these slow oscillations at the cellular and network
due to their limited spatial extent, which causes signal to be lost due to the levels are transitions from a relatively hyperpolarized membrane potential
effects of averaging across the listening sphere of scalp electrodes (44). For generally below −70 mV, when there is little firing activity, to a more depo-
example, interictal epileptiform discharges are rarely detected in scalp EEG larized state around −60 mV and far higher rates of firing. These two states
if they encompass less than 6 cm2 of cortex (45). It is not surprising, there- are conventionally referred to as “down” and “up” states, respectively. Such
fore, that EEG recorded from electrodes implanted onto the cortical surface activity is seen in many anesthetized states, and also during sleep, and be-
(e.g., subdurally) is far better than scalp electrodes at detecting gamma and cause many neurons switch in unison, the transitions between up and down
high gamma oscillations (up to 150 to 200 Hz). Frequencies above 200 Hz states are readily seen in EEG recordings as a delta rhythm (roughly 0.5
are dominated by action potentials, or the extracellular signatures of firing to 2 Hz). The synchrony appears far more global in the anesthetized state,
neurons. To detect action potentials, which are most prominent in neocorti- whereas during sleep, evidence suggests that the transitions propagate across
cal layers 3 to 5 about 1 mm below the cortical surface (46), we need to be yet the cortex as a wave, and are only synchronized locally, over a few square
more invasive. Action potentials can be recorded by tiny, high-impedance centimeters.
electrodes inserted into the brain parenchyma, such as microwires added to The transition from down to up state can be triggered by thalamic in-
the end of a clinical depth array (47,48), or the microelectrodes built into the puts. It is also likely to occur spontaneously within cortical networks, aris-
“Utah” array (9–1). Magnetoencephalography, which records from sensors ing from activity reverberating within the extensive recurrent connections.
on the scalp but uses magnetic signals that are less prone to attenuation by The greatly increased firing during the up state is modulated broadly in the
skull and scalp tissue (52), is therefore more sensitive to high frequencies gamma frequencies (20 to 80 Hz) (54), which is evident both in the statistics
than is scalp EEG, but is subject to a similar spatial averaging effect. of population firing and also in the pattern of synaptic currents recorded in
individual cells. This is an excellent example of higher frequency rhythms
The Relationship between Oscillations and Cellular Activity being nested within lower-frequency oscillations. Again, this rhythm is likely
to arise simply from the pattern of recurrent connections with their char-
In the 1930s, Bishop proposed that EEG is the direct result of rhythmic acteristic synaptic latencies and kinetics. What terminates these up states is
fluctuations in neuronal activity (53). Specifically, postsynaptic potentials, less clear, although obvious possibilities include a progressive synaptic de-
generated from neuronal ensembles firing in synchrony, induce extracellular pression, the kinetics of NMDA receptors and the consequent time course
potential fluctuations that summate to create waves that are the substrate of of NMDA plateau potentials, increasing levels of Ca2+, which in turn raise
EEG signals. These waves may appear at sites far removed from the location K+ conductance by opening Ca2+-gated K+ channels, and changes in other
of the presynaptic neurons, due to rapid and wide distribution of synaptic intrinsic neuronal conductances.
potentials down axonal pathways. This is a fundamental property that is The clearest examples of spontaneous EEG oscillations with up and down
important to keep in mind when interpreting clinical studies: EEG is an states are the physiological rhythms that occur during sleep, as we discussed
previously, and also pathologic slow waves. The delta rhythms of pathologic that would otherwise cause unwanted interference. High excitability peri-
focal or diffuse slow activity, as opposed to the slow waves that characterize ods, that is “up” states, are more likely to occur when an input stimulus is
stage 3 sleep, appear to be generated from the cerebral cortex, and their pres- expected, leading to improved accuracy and response time, while cortical
ence in the waking EEG is usually ascribed to underlying white matter abnor- response is reduced during “down” states (57,61).
mality or cortical deafferentation. Recordings from large deafferented cortical At the top of the oscillatory hierarchy, it appears that gamma activity,
slabs taken from cats revealed spontaneously synchronized slow rhythms, in especially high gamma (>80 Hz), provides a reliable index of colocated pop-
which neurons were hyperpolarized during positive peaks of the field poten- ulation firing (62,63) (Fig. 1.3). In addition to the work already described,
tial, and depolarized during negative peaks, at which time bursts of action there is evidence from related fields to support this view. Increases in in-
potentials were seen. The EPSPs (excitatory postsynaptic potential) propa- duced gamma power (>40 Hz) during motor and language tasks in patients
gated at speeds of 10 to 100 mm/second, to recruit nearby neurons (55). Thus, implanted with subdural grid electrodes has been found at sites positive for
rhythmic oscillations with up and down states may have either a thalamic or the same functions identified by electrocortical stimulation mapping (64,65).
cortical origin. Increased high gamma power is also positively correlated with high values
of fMRI (BOLD) signals (66), which are presumed to reflect task-related
Hierarchical Phase-Amplitude Coupling cortical activation. This tight relationship has proven to be advantageous for
applications such as creating control signals from EEG for a brain-computer
Oscillations recorded by EEG can be arranged in a nested structure, in interface (67), and it will also be relevant in the discussion of high-frequency
which the amplitude envelope of a higher frequency rhythm modulates (or oscillations in the next section.
is modulated by) the phase of a lower-frequency rhythm, as described ear-
lier for gamma activity nested within the delta-waves (Fig. 1.3). An example Cellular basis of epileptiform activity
of such cross-frequency coupling that is often seen in clinical recordings
is the so-called “sinusoidal alpha rhythm,” or a spontaneous modulation Neural Activity during Epileptiform Discharges
of the posterior dominant (alpha) rhythm amplitude that a ppears to vary
in a very slow (<1 Hz) rhythm. The amplitude envelope of high gamma The primary pathologic EEG findings in epilepsy are transient, high-
(80 to 150 Hz) activity has been shown to be maximal during the troughs amplitude deflections in the local field potential, typically on the order of
of theta or alpha oscillations at many recording sites in human intracra- hundreds of microvolts and seen over several square centimeters of cortex.
nial EEG (56). Thus, there are good experimental examples of gamma At the peak of the deflection, there is a burst of intense, hypersynchronous
having a phase-amplitude relationship with almost all lower-frequency multiunit activity, which is why epileptiform discharges appear “sharp.”
rhythms. Taking this concept one step further, a three-tiered hierarchy has Following this sharp peak, there is an after-going slow wave or amplitude
been described in recordings from macaque sensory cortices in which delta attenuation, with little or no multiunit activity. These may accompany a clin-
phase modulates theta amplitude, theta phase modulates gamma (30 to ical seizure, or occur during the quiescent interictal period between seizures.
50 Hz) amplitude, and gamma phase modulates stimulus-averaged multi- Interictal discharges most often occur as isolated events, while discharges
unit activity (57,58). that are part of an ongoing seizure generally appear in rhythmic trains. The
Entrainment of delta rhythms by external stimuli has also been demon- intracellular signature of both ictal and interictal discharges is thought to be
strated in human intracranial EEG. While these stimuli can be simple sen- the paroxysmal depolarizing shift (PDS), first described in the early 1960s
sory inputs (59), it is also possible to demonstrate entrainment following a in an in vitro penicillin (68) and in vivo freeze-induced lesion (68) seizure
nested theta and delta cadence, by stimuli as complex as spoken language. models. Since these early descriptions of the PDS, it has been demonstrated
Notably, experiments combining multiple stimuli, for example a “cocktail in many animal models of both acute and chronic seizures (for detailed re-
party” with two simultaneous conversation streams, showed that the en- view, see de Curtis and Avanzini, 2001 [69]). Indeed, the PDS appears to be
trainment follows the conversation to which the listener is paying attention a defining feature of seizures in these models.
(60), entrainment has been postulated to be an effective mechanism for fine- The most notable feature of the PDS is that the cell receives such a strong
tuning attention to follow behaviorally relevant stimuli, and ignore stimuli excitation that following each action potential, the cell remains in a relatively
A C
Surf. –
EEG
Depth –
EEG area 4
20 mV
0.5 mV
0.2 s
Intra - cell
20 mV
area 4
– 63 mV 20 ms
Intra - cell VL
0.5 s
–78 mV
Figure 1.4: Burst firing correlated with field oscillations in normal and pathologic condi-
B tions (panels A and B adapted from Timofeev I, Steriade M. Neocortical seizures: initia-
tion, development and cessation. Neuroscience 2004;123:299–336). A: Slow wave sleep in
anesthetized cat, with simultaneous intracellular recordings from a neuron in cortical area
4 and thalamocortical (TC) neuron in the ventrolateral (VL) nucleus, together with surface
and depth EEG from area 4. The depth-positive (upward) EEG waves are associated with
hyperpolarization of cortical and thalamic cells, whereas the depth-negativities are asso-
ciated with cortical depolarization and action potentials, followed by a rebound spike-
burst (expanded view, arrow) in the TC neuron. B: Paroxysmal depolarizing shifts during
a spontaneous neocortical seizure in anesthetized cat. EEG is shown in the top trace, with
fast ripples (80 to 300 Hz) in the second trace. The fast ripple correlates with intracellularly
20 mV
recorded spike bursts. C: Human in vivo microelectrode recording of interictal epileptiform

discharges (Schevon, Columbia Univ. unpublished). Fast activity can be seen over the nega-
tive EEG peaks (top), correlating with multiunit activity (300 to 3 kHz, middle), and detected
action potentials (bottom raster). Note the disorganized appearance of the firing bursts
accompanying the discharge peaks, compared to the spontaneous firing at other times.
The change in action potential shape, combined with likely distortion and/or contamination
of the signal from the filtering process, interferes with unit detection and greatly reduces
0.2 s its sensitivity.
depolarized state, and consequently, there is incomplete deinactivation of of firing, superimposed on the negative peak of the large depolarizing po-
the population of Na+ channels. With many Na+ channels not being “acti- tential, is characterized by a progressive change in the shape of the action
vatable,” subsequent action potentials are smaller, and also broader, reflect- potentials, and ultimately, somatic recordings often show a depolarizing
ing a lower K+ conductance too (Figs. 1.4 and 1.5). As a result, the burst blockade of firing. Theoretic studies show that even when the soma is in a
FIGURE 1.5: Gamma rhythms are dictated by fast-spiking interneurons. A: Cellular firing patterns during
gamma rhythms recorded in two different brain slice preparations. Panel Ai (adapted from Shu Y, Hasenstaub
A, McCormick DA. Turning on and off recurrent balanced cortical activity. Nature 2003;423:288–293) shows an
Up state in a ferret brain slice, induced and terminated by white matter stimulation. Panel Aii (adapted from
Ainsworth M, Lee S, Cunningham MO, et al. Dual gamma rhythm generators control interlaminar synchrony in
auditory cortex. J Neurosci 2011;31:17040–17051) shows persistent gamma rhythms induced in auditory cortex
by bathing the brain slice in kainate. Note the strong depolarizing drive reflected in the “pacemaker” voltages,
which follow each IPSC. B: Firing patterns recorded during gamma rhythms in vivo, in ferret prefrontal cortex
(adapted from Hasenstaub A, Shu Y, Haider B, et al. Inhibitory postsynaptic potentials carry synchronized
frequency information in active cortical networks. Neuron 2005;47:423–435). The fast-spiking interneurons fire
most cycles, in contrast to regular spiking cells (presumptive pyramidal cells), which fire only intermittently.
There is a marked dip in firing probability of the pyramidal cells shortly after the firing of the fast-spiking in-
terneurons, consistent with the model of gamma that has been derived primarily from brain slice models, and
which is schematized in (C). The schematic shows a pattern of large rhythmic IPSCs onto pyramidal cells, which
then have a narrow window of opportunity to fire between these IPSCs. If the frequency of IPSCs increases,
however, this window progressively shuts, and the network is suppressed locally. In this case, an extrinsic excit-
atory drive, such as arising from an adjacent cortical territory, may still provide a strong depolarization, thereby
shifting Em away from EGABA and creating a driving force for current through these large oscillatory inhibitory
conductances. We predict that this “relatively pure” inhibitory oscillation may have a very distinctive spatial
distribution reflecting an inhibitory surround mechanism, although this remains to be tested experimentally.
Bi. The fast-spiking interneurons. Bii. There is a marked dip.
depolarizing block, there may still be firing down the axon, away from the field potential deflection. Several different synchronization mechanisms
excitatory drive that is located on the dendrites. Thus an apparent somatic have been proposed, including the release of neuroactive substances from
depolarizing block should not be taken to mean that there is no axonal out- glia (5–7), short-range recurrent excitation, release of feedforward inhibition
put from these cells. This change in action potential shape distinguishes the (78), ephaptic interactions resulting from the effect of the large extracellular
pathologic PDS from the physiological “up” state, in which likewise there currents on membrane potential (79,80), electrical coupling between pyra-
is a sustained, and often rhythmically repeated, depolarization, with bursts midal cells via gap junctions (81,82), and low-calcium field bursts (10,83).
of action potentials superimposed, but the individual action potentials all Despite the universal association of the PDS with animal epileptic dis-
have the same shape. The primary difference, however, is probably simply charges and its clear extracellular signature, it has rarely been reported in
the intensity of the excitatory synaptic drive. The PDS then terminates with in vivo recordings of seizures from microelectrodes in humans (for obvious
a period of hyperpolarization and suppressed neural firing, resulting in at- reasons, these invariably are extracellular recordings). Recent results have
tenuation of local field potentials. This after-hyperpolarization may contrib- finally begun to shed light on the reasons for this apparent conundrum. The
ute to the periodicity of epileptiform discharges during seizures and other development of microelectrode arrays approved for use in humans has al-
situations, such as periodic discharges in acutely an injured brain. lowed us to link multiunit activity (action potentials from many neurons)
How PDSs are initiated remains unclear. At least part of the difficulty recorded over a small patch of cortex to standardly interpreted, clinically
discerning the mechanism is that there are many possible ways this might relevant EEG events—an unprecedented level of detail. It is now appar-
happen. It is appropriate to distinguish PDSs that occur during a full ic- ent that the extent of cortex that displays hypersynchronous burst firing is
tal event, or the afterdischarges during the clonic phase of a seizure or fol- often smaller than has hitherto been understood from conventional EEG
lowing electrical stimulation, from those that are interictal or at the very recordings. This is such an important point that is worth considering in
start of a seizure. The full ictal PDSs and afterdischarges are likely to arise more detail.
simply from the coordinated synaptic drive from other neurons. Computer
modeling work has suggested that the transition from sustained, tonic firing Lessons from Microelectrode Arrays:
to the clonic bursting behavior may arise from the interaction between fir- Ictal Discharges and the “Ictal Penumbra”
ing rates and synchrony, combined with slowed firing under strong synaptic
drive (70). Once the seizure is established, there are likely to be multiple Epileptiform events that correspond closely to the extracellular signature of
“re-entrant” loops (similar to the origin of certain pathologic heartbeats). the PDS have been detected in a small number of patients during seizures
Newly recruited territories, which are still at the tonic phase of firing, may (84) and interictal discharges (49,85) recorded with microelectrode arrays.
also act as a pacemaker for territories that have already entered the clonic The low-frequency signals recorded from the microelectrodes correspond
phase. This is the case in brain slices, when propagation is essentially one- very closely to those recorded from the overlying subdural grid electrodes.
dimensional, thereby allowing the visualization of activity propagating both Critically, though, the multielectrode arrays could also record action poten-
forward and backward from the moving ictal wavefront (71). tials, and so for the first time, we have a tool that allows a direct comparison
Regarding PDSs that arise de novo (interictal events, or those that initi- between local firing and the EEG over a spatially extended territory. These
ate a seizure), early theories focused on the concept of “epileptic neurons.” multielectrode recordings showed unequivocally that there can be a large
This concept developed from studies showing intrinsically generated syn- discrepancy between the low-frequency (EEG) signal, and the local level of
chronized bursting in multiple types of neuronal populations in neocortical neuronal firing (51), and that this is a routine occurrence at particular loca-
layers IV–V and the CA3 layer of hippocampus (72,73), and that such burst- tions during the extreme conditions of an electrographic seizure. In short, a
ing can entrain the occurrence of PDSs, albeit in a disinhibited brain slice, large EEG signal does not necessarily equate with local firing. This happens
which generated PDSs spontaneously (74). The intensity of the depolarizing where there are large synaptic currents that are not being translated into
drive, which underlies the PDS, however, suggests that its development re- postsynaptic firing.
quires synchronized neural activity in the local network, hence its associa- The large amplitude, rhythmic oscillations that are traditionally used to de-
tion with large population bursts and the characteristically high-amplitude, fine the onset and progression of a seizure were visible in all electrodes in the
multielectrode array, and also simultaneously over an extended region sam- A critical observation was that these rapid reverberations of low-frequency
pled by the overlying subdural grid. Volume conduction, or spread of cur- signals (<50 Hz) did not reflect the actual recruitment of neurons to the sei-
rent in a surrounding field by passive electrical properties of the extracellular zure. Thus, in contrast to the rapidly moving field potentials, a slow-moving
medium, has often been advocated as an explanation for the large field of (<1 mm/second) “ictal wavefront” was apparent in the multiunit firing re-
these discharges. However, the fractional delays and directional asymmetry corded with the multielectrode arrays (Fig. 1.6). The wavefront gradually in-
(49,86,87) instead indicate that they reflect the rapid axonal distribution of corporated the entire array over a 5- to 10-second period. Individual electrodes
postsynaptic currents. Similarly rapidly spreading field potential fluxes have showed an abrupt start of sustained, intense firing, approximately 30 times
also been demonstrated using current source density analysis in laminar mi- greater than seen during the interictal period. This tonic firing phase lasted
croelectrode recordings of animal (88) and human (89,90) epileptiform dis- about 1 to 2 seconds, before transitioning into a repeated bursting pattern that
charges, and in seizure recordings from cats using a dense subdural grid (91). was phase-locked to the dominant theta or alpha frequency rhythm (clonic
Figure 1.6: Microelectrode recordings of animal and human

seizures. A: Intracellular recording of an epileptiform event in
the 0 Mg2+ mouse model, showing the transitions between the
pre-recruitment state, with sporadic firing, the tonic phase with
sustained firing, and the post-recruitment, clonic phase with
burst firing. Note the decrease and variability in action poten-
tial amplitude in the latter two phases (Trevelyan, Newcastle univ.
unpublished). B: Clinical seizure recorded with a 4 × 4 mm mi-
croelectrode array, filtered into “uEEG” (gray) and MUA (black)
data streams. Two channels 3 mm apart are shown. The same
phase transitions seen in the mouse model are evident in MUA,
but have little effect on the predominant ictal rhythm that arises
from postrecruitment clonic bursting. Note the irregular pre-
recruitment firing in the bottom channel, and the post-recruit-
ment synchronization of burst firing and the ictal alpha-range
rhythm. C: Clinical seizure shown in its entirety, recorded from
a site that is never recruited. Note the irregular multiunit firing
and lack of correspondence with the low-frequency potentials. D:
Advance of the ictal wavefront during the clinical seizure shown in
panel B, as shown by a striking transient increase in multiunit fir-
ing rate. The recruited area, or “seizure focus” is to the left of the
ictal wavefront, and the pre-recruited area, or “ictal penumbra,”
is to the right. The progress of the wavefront, moving at a rate of
0.8 mm/second, is largely hidden when the view is restricted to 2
to 50 Hz amplitude (84).
phase). These recordings thus definitively show that the PDS and its context in during interictal discharges. Other researchers have confirmed and extended
laboratory seizure models is also a feature of human seizures; however, there these observations (3–5). Optical imaging of a 4-aminopyridine seizure model
are additional implications that are highly relevant to ictal EEG interpretation. in vivo in the rat (96) revealed a slowly expanding area of vasodilation sur-
Equally informative was the activity pattern at sites ahead of the ictal rounded by a narrow band of vasoconstriction, propagating at a speed similar
wavefront, or in areas that it never reached (Fig. 1.6). During the seizure, to that of the ictal wavefront observed in humans (Fig. 1.7).
activity outside the recruited territory was slightly raised above baseline The most detailed view of these inhibitory effects, though, comes from
(less than fivefold), although many electrodes were almost quiescent. Fur- studies of epileptiform propagation in brain slices (22,97). This simple
thermore, this low-level firing was not phase-locked to the low-frequency preparation allows a level of control and accessibility that is impossible to
rhythm: these neurons were clearly not dancing to the tune of the seizure. achieve in human recordings, and thus presents a far more detailed view of
Remarkably, this was true even in recording sites located within the seizure ictal events. Epileptiform activity was induced in these studies by remov-
onset zone, as it is standardly defined. Thus, there are relatively large corti- ing Mg2+ ions from the extracellular medium, thereby boosting excitatory
cal areas that display an extreme discrepancy between the large amplitude neurotransmission by reducing the voltage-dependent blockade of NMDA
EEG signals and the low level of firing locally. We suggest the term “ictal receptors, while preserving inhibition. During seizure-like events, a very
penumbra” for this region of cortex adjacent to the recruited territories (84). large excitatory drive extends forward, to sites well ahead of the ictal wave-
The penumbra may be fluid, shifting as the ictal wavefront progresses front (Fig. 1.8). This induces an even more powerful feedforward inhibition,
(Fig. 1.6). Interestingly, some territories in the penumbra, despite being mediated through local interneurons, which project onto local pyramidal
bombarded with ictal synaptic barrages throughout, were never actually re- cells. This disynaptic inhibition beats the monosynaptic excitation because
cruited to the seizure. Thus we can make a distinction between areas that are the interneurons are recruited very rapidly, and because their axons target
pre-recruitment and those that are never recruited, but both exist within the the somata of pyramidal cells, whereas the monosynaptic excitatory drive is
ictal penumbra. When repeated seizures were analyzed, the patterns of firing onto the more distal dendrites of the pyramids. Indeed, patch clamp stud-
during recruitment were highly stereotyped, whereas firing in the penumbra ies suggest that the threshold for firing an action potential may be exceeded
was very variable from seizure to seizure (84). In contrast, the EEG tends to 20-fold during this period of restraint (22). Moreover, the low level of firing
be stereotyped throughout the penumbra, indicating that this spatial wide- ahead of the wavefront is not well correlated in different neurons, in exactly
spread stereotypy at low frequencies is explained by the presynaptic neural the same pattern as was noted in the penumbra of human seizures. These
activity within the seizure focus, and not that in the penumbra. In summary, experiments therefore provide a cogent explanation of the ictal penumbra as
the recruited territories and the ictal penumbra show extreme differences a region in which neural firing is held off by feedforward inhibition from the
in the level of neuronal firing, but may appear very similar in the EEG. active focus—an intrinsic defense against seizures.
Indeed, the seizure onset zone, as it is usually defined, appears to include
both regions. EEG Markers of Ictal Territories:
High-frequency Oscillations
Surround Inhibition
One of the most active areas of investigation in epilepsy neurophysiology
Considerable support for this view of an ictal focus and penumbra comes from in recent years has been focused on potential biomarkers of epileptic brain
animal studies, suggesting that the penumbra region reflects surround inhibi- areas that can be identified from clinical EEG recordings. Historically, the
tory effects. The very first intracellular recordings of cortical neurons made in most commonly used method of validating these markers has been the
intact animals, by Powell and Mountcastle, showed that a focal activation of quality of seizure control post-surgery. This approach, however, is greatly
cortex induces large inhibitory currents in surrounding territories. A decade limited, as it is not possible to know whether the resection was larger than
later, in 1967, Prince and Wilder showed similar lateral inhibition during the minimum volume required to control seizures, or whether the length of
interictal bursts in rat hippocampus (92). They observed that pyramidal cells the follow-up period is adequate. Now, the new microelectrode technologies
adjacent to the focus were bombarded with inhibitory postsynaptic currents offer a more immediate means of assessing whether territories have been
Figure 1.7: High-frequency oscillations are associated with epileptic pathology. A: High-frequency oscilla-
tions recorded through a depth electrode close to the apparent epileptic focus in a human (98). B: Similar
oscillations can be recorded in brain slices in which synaptic neurotransmission is prevented by removing Ca2+
ions from the bathing medium. In this case, activity is presumed to spread through gap junctions, and support
for this comes from the observation that gap-junction blockers reversibly suppress the high-frequency oscilla-
tions (118). C: Intracellular recordings (bottom trace) in this model, often show evidence of “spikelets,” which
are like mini-action potentials. These are generally taken as evidence of gap-junction coupling, in which a full
action potential in one cell induces the spikelet in the coupled, recorded cell without triggering a full action
potential. D: The spread of activity in the non-synaptic (0 Ca2+) model has been explained in terms of ephaptic
interactions, which are likely to be extremely localized, and also by percolation of activity through axons in-
terconnected via gap junctions. E: The axonal location of the gap junctions in this model is predicated by the
need to explain very-fast-rising spikelets, which in this case are thought to be back-propagating axonal action
potentials which fail to induce a somatic action potential because of an impedance mismatch.
FIGURE 1.8: Activity patterns in the ictal penumbra, and fol-

lowing recruitment to an epileptiform event. This schematic
is based on imaging and electrophysiological recordings in
brain slice preparations in which epileptiform events are in-
duced by removing Mg2+ ions from the bathing medium.
The territories ahead of the ictal wavefront are characterized
by very low pyramidal firing despite cells receiving patho-
logically high levels of glutamatergic barrages projecting
forward from the wavefront. The restraint of these neurons
appears to be achieved through very intense feedforward
inhibition, because interneurons ahead of the wavefront
may fire at extremely high rates (>300 Hz).
recruited or are within the ictal penumbra, which we hope will resolve some frequency components higher than 200 Hz and may extend up to 600 Hz
outstanding issues in this field, exploring feasibility of various measures, or beyond.
and establishing their clinical utility. Ripples are present during hippocampal sharp-wave complexes, a normal
The “DC shift,” or transient fluctuation in very low-frequency (<0.5 Hz) feature that appears unrelated to epilepsy (103,108) and that are thought
power, is perhaps indicative of glial shunting of high extracellular K+ local to play a role in memory consolidation (109). Fast ripples, on the other
to seizure discharges (98,99), and has been recorded in clinical EEG (100). hand, appear to be pathologic in the hippocampus. They have been found
Another potential biomarker that has received a great deal of attention is almost exclusively in epileptogenic mesial temporal structures in patients
high-frequency oscillations, or transient increased signal amplitude above (103,110,111), and appear during epileptogenesis in a rat kainic acid model
80 Hz. These were first recorded from microwire bundles in mesial tem- (105). Similarly, increased fast ripples and signal amplitude above 200 Hz
poral structures in humans (1–3) and in animal models of seizures (4–7). during seizures appears to be a reliable localizing feature of EEG in both
Most high-frequency oscillations occur with epileptiform discharges, mesial temporal lobe epilepsy (112,113) and possibly also neocortical syn-
although they may sometimes be independent. Their typical duration is dromes. A limited clinical study in patients with neocortical lesional syn-
100 milliseconds or less. These may be subdivided into ripples, in which the dromes suggested that a resection confined to sites at which high-frequency
predominant frequencies are 80 to 200 Hz, and fast ripples, which contain oscillations were detected, resulted in rates of seizure freedom comparable
to that obtained with larger, traditionally defined, resection boundaries A hotly debated topic is to what extent these very high-frequency oscilla-
(114). Fast ripples recorded interictally from neocortex may be normal tions reflect the firing rates of individual cells. Fast ripples oscillate at fre-
findings, but may demonstrate broad spatial distribution when they are quencies well above the apparent maximal firing rate of most pyramidal
pathologic (115). This can explain their detection from surface electrodes cells. The maximal rate, though, is usually assessed in response to square
(114), although reduced frequencies may result from spatial averaging and pulse current injections, and it is possible that patterned inputs, including
the filtering effects of the electrode. Thus, caution must be exercised when strong transient inhibition, may allow faster repolarization and thus higher
using large, clinical electrodes to record high-frequency oscillations, as the firing rates briefly. Furthermore, there are other cell classes in neocortex
frequency ranges of these different types can blur together, and their gen- that can fire at close to these rates, including both fast-spiking interneurons
eration mechanisms and pathologic significance can be very different. (basket cells) and fast-rhythmic-bursting neurons, also termed “chattering”
The source of high-frequency oscillations remains controversial; implicit neurons (125). It is also relevant that these spiking properties may change
in this statement is that there are likely to be multiple sources. Hippocam- with experimental conditions (126,127). It is possible then that pro-epileptic
pal ripples (i.e., the fast components of sharp-wave complexes, generally at states are those that favor high-frequency burst firing.
<200 Hz) correlate with population spike bursts in normal and kainic acid Another possibility is that fast ripples emerge from lower-frequency pat-
treated rats (107,116,117), but neocortical ripples in epilepsy patients are of- terns due to locally desynchronized pyramidal cell populations, based on
ten seen without evidence of prominent neural firing in extracellular record- data from an in vitro model (128) and supported by in vivo data from a
ings (115). They may be generated by summated inhibitory postsynaptic kainic acid rat model (124) (Fig. 1.9). Analyses of these oscillations sug-
potentials (118), reflecting a feedforward inhibition by perisomatic interneu- gest that a sudden doubling of frequency can arise, possibly reflecting out-
rons that restrain pyramidal cell firing (97). This mechanism is thus likely of-phase firing. An intriguing possibility is that this may reflect another
to give a distinctive spatial pattern of high-frequency oscillations, reflecting well-documented pathologic mechanism in epileptic foci, that of increased
the delineation of active territories brought about by this intense inhibition. intracellular chloride. Increases in intracellular chloride cause a positive shift
A nonsynaptic mechanism has also been proposed based on neural network in the GABAergic reversal potential, thus compromising neuronal inhibi-
modeling (119,120) of the zero-Ca2+ brain slice model (121), reflecting axonal tion, which has been hypothesized to be the primary pathology in several
and somatic action potentials reverberating through a gap-junction coupled epilepsy syndromes, including postanoxic injury and pharmacoresistant
network (Fig. 1.7). The model is critically dependent on the degree of cou- temporal lobe epilepsy (129). This may be especially true for neonatal sei-
pling between neurons, and increased frequencies of oscillations up into the zures, which can display a paradoxical response to anticonvulsant drugs that
fast ripple range (>200 Hz) have been suggested to occur from pathologically act on GABAA receptors, due to different expression of chloride transport
high levels of coupling. This model can display escalating activity, leading ulti- channels compared to the adult brain. In tissue resected during epilepsy sur-
mately to seizure-like behavior, and thus cleverly combines the apparent asso- gery, some cells have abnormally low levels of the potassium-chloride co-
ciation of very high-frequency oscillations with ictogenesis. It is important to transporter, KCC2, the main mechanism for extruding chloride in cortical
realize, however, that the mechanism of escalating activity in this model is quite neurons; notably, these cells fire excessively during interictal events (130). In-
similar to that also proposed for ephaptic escalation, except that the ephaptic tense activation of GABAergic channels can overwhelm the chloride clear-
interactions are likely to be highly localized, whereas gap-junction coupling ance mechanism even without underlying deficits in KCC2 levels (131–133).
may be on distributed axonal processes and thus be over far larger distances. Also in simple in vitro models of epilepsy, chloride-sensitive dyes show a
Fast ripples, generally, appear to be a by-product of the burst of pyra- pronounced shift toward higher chloride in all neurons with each successive
midal cell firing at the negative peaks of epileptiform discharges, since the full ictal event (134).
duration of typical action potential waveforms matches the periodicity of The way these shifts in chloride translate to out-of-phase firing at high
signals in the 200 to 600 Hz range (107,115,122–124). The duration of ac- frequencies is secondary to the feedforward, high-frequency, GABAergic
tion potentials during a PDS may be increased by the inactivation of po- barrages. In experimental seizures in cats, if cells are artificially loaded with
tassium channels due to high levels of excitation, thus bringing the action chloride through the recording electrode, those cells are recruited dispropor-
potential waveforms into the fast ripple range (72). tionately early to the seizure, with intense bursting (135). This is consistent
Figure 1.9: High-frequency oscillations may reflect a pathologic response to the high-frequency discharge of fast-spiking interneurons. A: Fast-spiking interneurons can
display almost instantaneous transitions from complete quiescence to extremely high firing rates in certain conditions. These synaptically connected cells were recorded in
a brain slice, bathed in 0 Mg2+ artificial cerebrospinal fluid (Trevelyan, unpublished). In normal conditions, this inhibitory discharge creates a powerful restraint on local pyra-
midal activity, but in epileptic tissue, a similar burst of firing may give rise to out-of-phase firing (B) in populations of cells with different levels of intracellular chloride (125).
C: Artificially loading chloride into cells, via the recording electrode, causes them to fire very intensely at times when there is a large, high-frequency inhibitory synaptic drive
(135). Notably, the action potentials in these chloride-loaded cells appear to be at almost 180° phase shift from the firing of cells with low intracellular chloride.
23
with other descriptions of the feedforward inhibition ahead of the ictal Acknowledgments
wavefront. Chloride loading also occurs naturally though, as noted above.
AJT is currently a Senior Lecturer at Newcastle University. AJT currently
CONCLUSION holds a fellowship from Epilepsy Research UK. CAS is supported by NIH
NINDS K08 NS48871.
In order to make good use of EEG to identify and localize both normal
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2 Cortical Generators and EEG Voltage Fields
JOHN S. EBERSOLE
The Source of EEG Potentials Voltage Fields from Specific Cortical Regions
Factors Determining Scalp EEG Electrode Location and Nomenclature
Source Location Display of Voltage Fields in EEG Traces—Montages
Source Area Effect of Reference on EEG Fields
Source Orientation Conclusions
Amplitude References
Synchrony
EEG Source Characterization
Voltage Field Analysis
Propagation
The Source of EEG Potentials This chapter changes the spatial scale under review to the macroscopic level
of traditional scalp EEG. We jump to considering the combined electrical
Brain electrophysiology exists on numerous spatial scales, from single cells activity of more than 108 neurons in a cortical area of several square centi-
to columnar micropopulations to the cellular macropopulations that make meters. Accordingly, it is necessary to understand several biophysical con-
up cortical gyri and sulci. The physiology at each scale requires a differ- cepts in order to interpret traditional scalp EEG properly.
ent sensor to appreciate and characterize the activity of that generator— From its inception over 80 years ago, EEG has been displayed, and thus un-
microelectrodes for cellular events, mini electrodes to record from cortical fortunately thought of, as simply traces showing the voltage potential at scalp
columns and small cellular populations, traditional intracranial electrodes electrodes over time. It has likewise been a common misconception that each
to record from individual gyri, and finally scalp electrodes to record from electrode on the scalp records solely the activity of cortex immediately below it.
large cortical areas. The previous chapter discussed the electrophysiology Only recently, with the advent of digital EEG, has it become more widely ap-
of single neurons and small cellular populations, and how this activity is preciated that traditional EEG traces are a simplistic way to display large, time-
dependent on both intrinsic cellular properties and specific cortical circuitry. varying voltage fields across the surface of the scalp that are related to both
28
Cortical Generators and EEG Voltage Fields 29
local and distant generators. This chapter will review the relationships between
cortical sources of activity and the EEG voltage fields that these generators pro-
duce. If our goal is to be able to interpret the EEG in terms of the physiology of
particular brain areas, we must understand these relationships.
The principal generators of EEG fields that we measure on the surface of the
brain or at the scalp are graded synaptic potentials, namely, excitatory post-
synaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs),
of pyramidal neurons (1–5). At the synaptic site of an EPSP there is an ac-
tive current sink. Positive ions rush into the cell to depolarize the local mem-
brane. At the same time at a more distal portion of the cell, a passive current
source, consisting of current flow out of the cell, completes a closed-circuit
loop (Fig. 2.1). The opposite direction of current flow happens with IPSPs,
namely, a local active current source coupled with a distant passive current
sink. These currents, generated by synaptic activity, pass through the extracel-
lular as well as intracellular space and set up a potential field around the cell.
The current flow within the cell is called the primary current. The associated
current flow outside the cell to complete the loop is called the s econdary or
return current. For EEG generation, the extracellular secondary current is the
most important. For magnetoencephalogram (MEG) generation, the primary
intracellular current is most critical. Figure 2.1: Generation of extracellular voltage fields from graded synaptic activ-
Near a current sink, the extracellular space is relatively negative, while ity. A: EPSP at the apical dendrite is associated with a flow of positive ions into
near a current source, it is positive (Fig. 2.1). The current flow and associ- the cell (an active current sink) and an extracellular negative field. A passive cur-
ated field potential around individual cells are very small, and they would rent source at the level of the cell body and basal dendrites is associated with
not be recordable at the scalp except for the fact that the pyramidal cells an extracellular positive field. B: An EPSP on the proximal apical dendrite at the
form a palisade that is aligned perpendicular to the surface of the cortex. level of cortical layer IV is associated with an active current sink and an extracellu-
Because of this geometric arrangement, the voltage fields produced by indi- lar negative field. A passive current source at the distal apical dendrite in layers II,
vidual cells can summate to produce a potential large enough to be recorded III is associated with an extracellular positive field.
some distance from the generators if the activity is synchronous or at least
has some temporal overlap. Summation of potential fields due to synaptic on the location of the recording electrode. This juxtaposition of negative
currents can more readily occur than those due to sodium action potentials and positive charges is similar to that of a “dipole.” Pyramidal cells in the
because the former events are relatively long in duration (4), whereas the ac- cortex can be thought of as a large population of vertically oriented dipoles
tion potentials are brief and axons lack the palisade geometry. that together can form a “dipole layer,” that is, a curved sheet of cells whose
To a first approximation, EEG is generated by the large, vertically oriented fields add linearly to produce one resultant field that is now large enough to
pyramidal neurons located in cortical layers 3, 5, and 6. As an example, an be measurable at the scalp. Given this generator configuration, voltage fields
EPSP at an apical dendrite of a large pyramidal cell that extends through recorded on the surface of the head usually have a dipolar configuration,
several cortical laminae would produce an active current sink and a negative that is, two maxima: one negative and one positive. The amplitude and the
local field potential superficially in the cortex, whereas the passive current polarity of the potential recorded from the same cortical event depend, as
source at the cell body or basal dendrites would result in a positive field before, on the location of the electrode relative to the dipole source.
potential in the deeper cortical laminae (see Figs. 2.1A and 2.2A). The same The cortex is a multilaminar structure. Current sinks and sources can
synaptic event is thus viewed as potentials with opposite polarity depending arise in different locations, depending on the type of input into the cortex.
Figure 2.3: A: Surface-negative interictal spikes in temporal convexity cortex

(lightened) produce a negative field and potential recordable by electrodes
above the source. Deeper to this source, from underlying white matter and, in
Figure 2.2: Depolarization of specific cortical laminae determine the polarity of fact, from the contralateral scalp, a weak positive field can be recorded as a re-
voltage fields measured at the surface and depth. A: Depolarization of superficial sult of simple volume conduction. B: Surface-negative interictal spikes from the
laminae produces a surface-negative field and a deep-positive field. B: Depolariza- mesial cortex of the temporal tip (lightened) will produce a positive field and
tion of deep laminae results in surface positivity and a deep negativity. C: Repeti- potential recordable by electrodes above the source. Deeper to the source and
tive depolarizations and repolarizations brought about by recurrent interlaminar contralaterally on the scalp, a weak negative field will be recorded. The orienta-
circuits result in potentials of alternating polarity, such as the spike–wave. tion of the generator cortex relative to electrode determines which side of the
dipolar sheet that electrode will “see,” negative or positive.
Excitatory input into layer 4, a primary sensory-input-receiving lamina,
would produce a local depolarization and extracellular negativity that is Given a potential of surface-negative polarity, for example, there are basi-
associated with a passive source in superficial laminae and resultant cortically two possible sources for this in normal convexity cortex, namely, superfi-
cal surface positivity (see Figs. 2.1B and 2.2B). Thus, the early components cial laminar depolarization (an active sink) or deep laminar hyperpolarization
of normal sensory-evoked potentials, for example, are commonly surface- (a superficial passive sink). The opposite conditions are true for a positive po-
positive. Epileptic spikes, on the other hand, are commonly surface-negative tential. However, when there is infolded cortex from major fissures, certain elec-
due to depolarization of the superficial laminae (see Figs. 2.1A and 2.2A). trodes may “see” the underside of the active cortical layer (Fig. 2.3B). In these
Electrodes in deeper cortical layers, in the underlying white matter, or even on instances, positive potentials may be recorded instead of the usual negative po-
the scalp at the opposite side of the head, would record a positive potential tentials and vice versa. Thus, the exact cortical generator of a given potential
with this event (Fig. 2.3A). Subsequent repolarization and depolarization cy- field can be ambiguous. However, the shape and contours of the entire voltage
cles, due to recurrent excitation and inhibition among laminae, result in the field over the head do provide localizing information to reduce this ambiguity.
typical sequence of a negative spike, followed by a positive after-potential,
which is in turn followed by a negative wave (Fig. 2.2C). Spikes that originate Factors Determining Scalp EEG
in deeper cortical layers may show an initial surface positivity. This is partic-
ularly true for “generalized” spike–wave discharges. They commonly have an A number of factors determine whether the extracellular voltage field pro-
initial positive component before the negative spike (Fig. 2.2C). This is likely duced by a region of cortex can be recorded from scalp EEG electrodes.
due to thalamocortical activation of middle laminae. Propagation of activity These factors are both physical and functional. Physical factors include
from one layer to another also changes the laminar arrangement of extracel- source location, orientation, and area. Functional factors include potential
lular voltage. Horizontal laminar circuits also allow the activity to spread amplitude, frequency, and synchrony. A transient potential, such as an epi-
in area, and as it does, synchrony may lessen. Accordingly, each subsequent leptic spike, serves as a good example for appreciating these relationships
potential in a spike and wave complex is less sharp, as synchrony is lost. between source character and EEG fields.
Source Location sources, but this usually requires averaging hundreds to thousands of time-
locked signals, such as potentials evoked by sensory stimuli.
It is both logical and correct that the scalp EEG voltage field should be
related to the location of its cortical source. However, this relationship is Source Orientation
not straightforward. An unfortunately simplistic assumption in traditional
EEG interpretation is that the source of an EEG potential must necessarily Spatial summation of the voltage field generated by multiple cortical
underlie the electrode recording it, hence the practice of referring to epilep- sources is three-dimensional. If adjacent active cortical areas have the same
tic discharges by the name of the electrode recording the maximal potential. orientation, their voltage fields will combine and the resultant voltage field
This assumption is true only in limited cases. That a negative field maximum measured at the scalp will be the linear sum of the fields of both sources. If,
is recorded from a particular electrode does not necessarily mean that the however, adjacent active regions of cortex have a different orientation, the
spike source is beneath it, as will be discussed in detail later. voltage fields will summate in relation to the geometry of their respective
field vectors. If, for example, two cortical areas have an opposite orientation,
Source Area such as the two sides of a sulcus, cancellation will occur and no voltage field
from them will be evident at the scalp (Fig. 2.6, source 3).
The importance of source area in determining whether cortical activity will Source area is maximal for a given electrode (and the solid angle is greatest)
be recordable on scalp EEG has been appreciated for some time. Using a when the orientation of the active cortical region is face-on. This is usually
simulated cortical source beneath a piece of fresh cadaver skull, Cooper the case when the resultant voltage field is radial and the electrode is directly
et al. (6) determined that 6 cm2 of synchronously active area is probably above the source (Fig. 2.6, source 2). In this instance that electrode will record
necessary to produce a scalp-recordable field. Gloor (7,8) also discussed the the field maximum. As the orientation of a cortical source changes, such that
importance of source area in appreciating EEG fields at the scalp in his dis- its field becomes progressively less radial and more tangential to the skull,
sertation of the “solid angle” theory. In essence, only when a cortical region the electrode directly above it detects a voltage field of progressively less am-
subtends a large enough solid angle, from the perspective of a given electrode, plitude. Even if a source is directly below an electrode, but its orientation is
will that electrode “see” (i.e., record) the potential generated by it. Tao et al. such that the field it generates is perfectly tangential, the electrode records no
(9), in an investigation using simultaneous intracranial and scalp recordings, potential. This scalp location, though nearest to the active cortex, is on the
showed that for individual epileptic spikes, 10 cm2 was a more likely minimum zero isopotential line of the source’s scalp field (Fig. 2.6, sources 1 and 4).
source area for spontaneous spikes to be appreciated in scalp EEG (Figs. 2.4 To summarize the concepts illustrated in Fig. 2.6, cortical sources 2 and
and 2.5). Smaller sources do produce fields, but they cannot be differentiated 3 produce voltage fields with a net radial orientation, and correspondingly
from the ongoing background EEG. What was demonstrated in addition, they have a negative field maximum on the scalp directly above them. Sources
however, was that the area of sources for typical scalp interictal spikes is often 1 and 4 result in a tangential field. The zero isopotential line is located on
substantially larger, often encompassing 20 to 30 cm2 of gyral cortex. the scalp immediately above these sources, whereas negative and positive
Because of the attenuating properties of the intervening skull, spatial maxima are displaced on either side. In general, midline interhemispheric
summation of cortical activity is critical for producing a scalp-recordable and basal cortical sources tend to be tangential; lateral convexity cortical
voltage field. As commonly observed with implanted electrodes in epilepsy sources tend to be radial. Sources on one bank of a sulcus in the lateral
surgery candidates, most of the cortical activity recorded from subdural or cortex may be tangential; however, epileptiform sources that produce scalp-
depth electrodes is not evident in the scalp EEG (1,9). This is not necessar- recordable signals are commonly so large that both banks of the sulcus are
ily because the amplitude of the individual cortical potentials is too small, activated. These opposing fields would cancel, as depicted in source 3, which
but more often it is because the area of the cortical generator is not large leaves only the radial field from the sulcus bottom to predominate.
enough. Although not well appreciated, it is perhaps this factor, source area, Taken from the perspective of the entire head, a radial source will produce
and a closely related factor, source orientation, that are the two most impor- one field maximum directly above it, and the other field maximum of opposite
tant variables in determining whether or not cerebral potentials are scalp- polarity will be on the diametrically opposite side of the head (Figs. 2.3A and
recordable. True, EEG can in certain circumstances detect small and remote 2.6, source 2). For a superficial cortical source, the scalp maximum nearest
Figure 2.4: Simultaneous intracranial

(A) and scalp (B) EEG recording of a
spike with a cortical source area of ap-
proximately 10 cm2. Note barely visible
deflections in the left temporal scalp
EEG. Scalp voltage map (C) shows a
low-amplitude physiologic field. Ac-
tive intracranial electrodes are denoted
as black circles on a three-dimensional
reconstruction of the patient’s subdural
grid and strip implantation (D).
the source will be significantly greater in amplitude than that on the opposite the source, the farther apart are the maxima, and vice versa. The simplistic
side of the head. In the case of a spike, for example, the negative field maxi- assumption that the cortical generator underlies the voltage field maximum
mum above the source will be of greater amplitude than the positive maxi- is thus clearly not true for tangentially oriented sources. This is a very impor-
mum on the other side of the head (Fig. 2.6, source 2; see also Fig. 2.8C). For tant concept! False localization and even false lateralization commonly occur
cortical sources whose net orientation is progressively more tangential, the when cortical sources result in fields that are tangential to the skull.
nearest field maximum will be progressively displaced away from the region
directly above the source. Conversely, the field maximum of opposite polar- Amplitude
ity will move progressively closer. For a source that is tangential to the skull,
both maxima are displaced equally in opposite directions on either side of the Several functional factors also affect what can be recorded with scalp EEG.
source and the fields are of equal amplitude (Fig 2.6, source 1). The distance Amplitude of cortical activity is important, but it has a physiologic upper limit.
between the two maxima is dependent on the depth of the source. The deeper Normal background rhythms and evoked potentials may generate potentials
Figure 2.5: Simultaneous intracranial (A)

and scalp (B) EEG recording of a spike
with a cortical source area of approxi-
mately 25 cm2. Note prominent spike in
left temporal scalp EEG. Scalp voltage
map (C) shows classic anterior temporal
spike field. Active intracranial electrodes
are denoted as black circles on a three-
dimensional reconstruction of the pa-
tient’s subdural grid and strip implantation
(D). Note that nearly the entire lateral
temporal lobe is involved.
at the brain’s surface of several hundred microvolts, and pathological poten- activity may cancel itself despite its amplitude (Fig. 2.7). Within an active
tials, such as epileptic spikes, may be greater than a millivolt in amplitude. dipole layer, there are cells that are firing synchronously (i.e., their activity
is coherent) and cells that are asynchronously active. The potentials due to
Synchrony the individual coherent sources sum linearly by superposition to produce a
combined source. The potentials of the incoherent sources tend to cancel
Other functional factors may become equally or more important than one another. Given the 107 pyramidal cells in 1 cm2 of cortex, it is estimated
source amplitude in determining the eventual scalp voltage field. The syn- that if only 1% are coherent, their relative contribution to the scalp EEG
chrony of cortical activity is crucial. EEG is the measure of spatially and potential would be 30 times greater than the 99% of incoherent neurons
temporally averaged activity of a large population of neurons. EEG em- (10). Thus, not all the neurons in a cortical patch have to be synchronous.
phasizes the contribution of synchronous sources, whereas asynchronous However, those sources that are highly coherent produce the potentials that
Figure 2.6: Schematic of a brain cross section illustrating four rep-

resentative cortical EEG sources. Note that the alignment of the py-
ramidal cells (and thus the EEG voltage field) is orthogonal to the
orientation of the cortical surface. Minus (−) and plus (+) signs de-
pict the polarity of the epileptiform potentials generated by these
sources. Top and back views of the head show the scalp voltage field
generated by each source. Shading denotes field polarity “(speckled
= negative)”. A line across each back-view head defines the v oltage
field orientation. Sources 2 and 3 produce radial fields, and the neg-
ative voltage maximum is directly above them. A weak positive field
maximum is noted at the other end of the field vector. Fields from
opposing sulcal walls cancel each other in source 3, leaving the ra-
dial component from the sulcus bottom to dominate. Sources 1 and
4 produce tangential fields. No voltage is recorded directly above
them; instead, negative and positive voltage maxima are displaced
to either side.
are recordable at the scalp. When neuronal synchronization is limited to rel- EEG Source Characterization
atively small regions of cortex, their resultant voltage field may not be great
enough to be recognized. Regions of cortical synchronization commonly Voltage Field Analysis
become larger with certain pathological potentials, such as epileptic spikes
or seizures, making them more easily appreciated on scalp EEG. Given the previous discussion, it becomes obvious that one cannot use
Source synchrony also leads to waveform sharpness. The difference between a single voltage field maximum to identify the location or orientation of
a spike and a sharp wave is simply the synchrony of its component cortical gen- a cortical EEG generator. In all instances, excluding a purely radial source,
erators. The more synchronous the activity, the sharper will be the summated the EEG field maxima are displaced from a position directly above it. To
field. Another EEG phenomenon that is in large measure related to cortical characterize a cortical source, the location of both field maxima, negative
source synchrony is the changing character and amplitude of a focal seizure. Ic- and positive, and their relative strengths must be taken into consideration.
tal rhythms not only evolve, but sometimes they appear to disappear, only to re- Sometimes only one voltage maximum is evident from scalp electrodes. This
turn later. This is not because the cortical seizure activity has stopped, but rather is usually because the second maximum is located where electrodes may not
because the different component sources have lost synchrony momentarily. have been placed, such as the bottom half of the head. A radial field with
Figure 2.7: Left: Simultaneous intracranial and scalp EEG recording of a temporal lobe seizure. Although the
seizure rhythm from the hippocampus is synchronous (depth electrode contacts RPT4–8), seizure rhythms from
the temporal neocortex are relatively asynchronous (subdural strip electrode contacts RAT1–6 and RMT1–5).
Scalp EEG shows a poorly developed seizure rhythm despite the high-amplitude cerebral activity. Right: The
seizure rhythm from the temporal neocortex is relatively synchronous (subdural electrode contacts RAT1–6
and RMT1–4), but of less amplitude than that depicted in the left frame. Scalp EEG, however, shows a well-
developed seizure rhythm because of source synchrony.
one maximum at the vertex and the other at the base of the skull is such an electrodes. There are a variety of algorithms for this interpolation and even sev-
example. In order to maximize the likelihood of recording both voltage field eral approaches for estimation of voltage values in locations where there are no
maxima, electrodes in the “southern hemisphere” of the head are necessary. electrodes (11). These are typically based on an estimation of a spherical head
The voltage fields over the head are measured only from a limited number of and the recognition that scalp voltage fields are predominantly dipolar. Scalp
sensors (electrodes). In order to construct a topographic map of these fields, voltage maps can be drawn as either two-dimensional or three-dimensional
computer programs must interpolate (estimate) the voltage values between projections. Voltage gradients may be depicted as progressive shades of color
or as lines of equal potential (isopotential lines), similar to the isobars of a closer to the field maximum of greater amplitude. In the case of most epilep-
weather map. Frowned upon are the multicolored “brain maps” of the past. tiform potentials, the negative field maximum is larger, and thus the source
The relative location of the two voltage field maxima most easily and is closer to it (see Fig. 2.8). In the case of sources with tangentially oriented
accurately defines field and thus source orientation. A three-dimensional fields, the separation of the negative and positive maxima is dependent on
line drawn between the two maxima identifies the orientation of the field the depth of the source. A three-dimensional line connecting the maxima will
(Fig. 2.8). Accordingly, the net orientation of the cortical surface generating travel deeper through the head when the maxima are farther apart. The center
the field will be orthogonal to this line (see Fig. 2.6). As a first approxima- of the source again should lie along this line, proportionately closer to the
tion, the center of the cortical source should lie somewhere along this three- field maximum of greater amplitude. Thus, by simply inspecting the scalp
dimensional line. The amplitude and gradient of the field maxima determine voltage topography of any EEG potential, much can be learned about the
this location, that is, the depth of the source. The source is proportionately cortical source generating it.
Figure 2.8: EEG traces depicting a left

temporal spike are shown in a common
average reference montage. Three vertical
cursors define successive time points at
spike onset, at the F9 spike peak, and at the
F7 spike peak, respectively. Voltage maps
(columns A, B, C) illustrate the field topog-
raphy at these times. Shading denotes
field polarity “(speckled = negative)”. A
three-dimensional line is drawn through
negative and positive field maxima. These
lines define the orientation of the source
field. Note that the voltage field topogra-
phy changes over the course of the spike.
At time (A) the field orientation is tangen-
tial and vertical; at time (B) it is between
tangential and radial; at time (C) it is radial
and horizontal. The net orientation of the
generator cortex is orthogonal to the field
orientation line, and its location, depicted
by the black dot, lies along this line pro-
portionally nearer the field maximum of
greater amplitude. These successive volt-
age field maps suggest propagation of the
spike from the left temporal lobe base to
anterior inferolateral temporal cortex and
then to anterior lateral temporal cortex.
Propagation Also, given that cortical sources need to be quite sizeable, namely, greater
than 10 cm2, to produce a recognizable scalp potential, one seldom needs to
If cortical activation remains localized to one area, which undergoes the consider the contribution of small individual sulci when predicting a resul-
usual depolarization and repolarization sequence, the resultant voltage fields tant EEG field. Only deep sulci or fissures have the source area necessary to
on the scalp will rise and fall in amplitude and reverse in polarity, but the generate such a potential, and also only if the activity of one side is unop-
location of the maxima will not change, nor will the overall shape of the posed by that of the other side. Thus, we will examine the typical fields of
fields change. If, however, the activity propagates into adjacent cortical re- gyral and fissural cortex.
gions, the overall geometry of the source will change. A new location to Starting with the temporal lobe, one notes that the major surfaces for gen-
the overall center of activity and a new net orientation of the source cortex erating scalp EEG potentials are the lateral, basal, superior, and tip regions.
will exist. These changes will result in a different voltage field. Movement Focal activity in these areas produces EEG fields directly related to the loca-
of scalp field maxima or change in the shape of the fields over tens of mil- tion and more importantly to the orientation of the cortical generator surface
liseconds suggests propagation of source activity. This is particularly com- (Fig. 2.9). Lateral temporal cortex will produce radial fields, while the temporal
mon with epileptiform spikes or seizures (12). Such changes in voltage fields base, superior temporal plane, and temporal tip will produce tangential fields.
can provide important information concerning propagation direction and Tangential EEG fields, such as those produced by the latter three temporal
extent. For example, in Fig. 2.8 the voltage maps at three time points during sources, can confuse the inexperienced EEG reader because the negative field
the spike show progressive movement of the field maxima. At spike onset maximum is not above the source. Accordingly, phase reversals using bipolar
(Fig. 2.8A) the tangential and vertical field orientation is consistent with a montage chains would not localize the source. Note also that the negative field
source in temporal base cortex. At the time of the F9 spike peak (Fig. 2.8B), maximum for a temporal base source would be recorded only by subtemporal
the field orientation is oblique (between tangential and radial), which sug- electrodes, and not by standard International 10–20 electrode positions.
gests an inferolateral temporal cortex source. Finally, at the time of the later Convexity cortex of frontal, central, parietal, and occipital regions all pro-
F7 spike peak (Fig. 2.8C), the field orientation is horizontal and radial, which duce simple radial fields (Fig. 2.10). In these cases, the source is under the
is consistent with a lateral temporal cortex source. A simple way of under- negative field maximum. Note that the intensity or amplitude of the nega-
standing the relationship between voltage field orientation and its cortical tive field gradient provides additional information about its source. Sources
source is the knowledge that the net orientation of the cortical pyramidal cells closer to the overlying scalp produce steeper voltage gradients; sources that
generating the field is the same as the orientation of the field and that this are deeper or larger in area produce less steep gradients. Frontopolar and
is orthogonal to the net orientation of the surface of the cortical generator. temporal tip sources both yield EEG fields with a frontal negative field max-
imum; however, the field of the true frontal cortex source has a much steeper
Voltage Fields from Specific Cortical Regions field gradient (compare Figs. 2.9D and 2.10B).
Fields that are tangential in orientation are typical of midline perisagit-
Given the preceding understanding that the scalp voltage fields of EEG are tal sources from frontal to occipital cortex (Fig. 2.11A). These sources are
dependent on various physical and functional characteristics of their corti- often the most difficult to localize by traditional visual inspection of EEG
cal source, we can predict, and indeed model, the typical voltage fields of because the source does not underlie either field maxima, but rather it is
epileptiform discharges from specific cortical regions. As noted earlier, these between them. As noted previously, this can lead to false localization or
fields are likely not to show a simple relationship between the source loca- even false lateralization, given that the negative field maximum is over the
tion and the field maxima, except for those rare purely radial sources. In the contralateral hemisphere. Tangential fields are also seen with orbitofrontal
end, understanding and appreciating these typical fields will lead to the abil- and inferior frontal opercular cortex (Fig. 2.11B, C). Sources in deep sulci,
ity to localize EEG sources more scientifically and accurately. Furthermore, such as the central sulcus, also produce tangential fields.
analysis of voltage fields, by eye or with computational algorithms, is the It is essential for the sophisticated interpreter of EEG to realize that as the
basis of nearly all source modeling methods. There are no additional data, voltage field shifts from being purely radial to oblique (a mixture of radial
other than the distribution of voltage fields over time, that are used by these and tangential) to purely tangential, the location of source moves from be-
sophisticated programs, as will be further discussed in a later chapter. ing directly under the negative maximum to midway between the maxima.
Figure 2.9: EEG voltage fields from specific cortical

sources are predicted using a forward projection of a di-
pole model of that cortex. Black dot shows source loca-
tion, and the attached vector depicts field orientation.
Voltage fields are shown as isopotential lines of increas-
ing amplitude. Speckled areas have negative polarity. The
four most common EEG fields produced by the temporal
lobe are shown. A: Source activity in the lateral temporal
cortex results in a radial field. The source resides beneath
the negative field maximum. Source activity in the tem-
poral lobe base (B), tip (C), and superior temporal plane
(D) result in tangential fields. The source of each resides
between the field maxima and under neither.
Only the voltage gradients of the two maxima determine where, along the because most of the electrode locations are 10% or 20% of standard circum-
three-dimensional line between them, the source lies. ferential or coronal interauricular distances. However, interelectrode distances
in the standard 10–20 system average a rather large 4 to 6 cm, and the most
Electrode Location and Nomenclature inferior temporal chain of electrodes normally passes across the superior
aspect of the temporal lobe (Fig. 2.13). Enhanced spatial sampling can be
Spatial sampling of scalp voltage fields is obtained by means of multiple elec- achieved with a modified combinatorial 10–10 electrode system that uses sup-
trodes placed in standardized positions relative to head landmarks such as plementary intermediary locations (Fig. 2.12) (13). It is now appreciated that
the nasion, inion, and preauricular points. The International 10–20 electrode electrodes below the standard temporal chain are important in characterizing
positions are commonly used in practice (Fig. 2.12) (13). They are so named voltage fields from basal temporal, orbitofrontal, and occipital regions (12)

Voltage fields are shown as isopotential lines of increasing
amplitude. Speckled areas have negative polarity. Exam-
ple radial sources from convexity cortex are shown. Source
activity in lateral central cortex (A) and frontopolar cortex
(B) result in radial fields. The sources reside beneath the
negative field maxima in each.

Voltage fields are shown as isopotential lines of increasing
amplitude. Speckled areas have negative polarity. Exam-
ple tangential sources are shown. Source activity in mid-
line parasagittal cortex (A), orbitofrontal cortex (B), and
inferolateral frontal opercular cortex (C) result in tangential
fields. The sources of each field pattern are under neither
field maximum, but between them.
Figure 2.12: Left: Head sche-

matic illustrating standard In-
ternational 10–20 electrode
positions. Right: Modified com-
binatorial 10–10 electrode posi-
tions. Note the new electrode
designations—T3 becomes T7,
T5 becomes P7, T4 becomes T8,
and T6 becomes P8 in order to
achieve numerical consistency
among transverse rows of elec-
trodes. The 10–10 system has
not only intermediary positions
but also supplementary inferior
temporal electrodes.
EEG machines, wires from electrodes were physically connected to ampli-

fier inputs to produce a channel’s differential signal. In modern digital EEG
machines, signals from individual electrodes are combined mathematically
to create any desired voltage comparison for a channel. This process, called
reformatting, is a major advantage of digital recorders.
Early electroencephalographers noted that many clinically important
EEG potentials were negative in polarity (e.g., epileptiform spikes). EEG
machines and montages were accordingly developed to emphasize this po-
larity. By convention, and not by any rule of physics, if the potential of E1
is more negative than that of E2, this difference will be displayed as an up-
ward deflection in the EEG trace. Conversely, if E1 is more positive than E2,
the deflection will be downward. This convention, coupled with a chained
bipolar montage, produced the easily recognizable “phase reversal.” Obvi-
ously, these are relative, not absolute, comparisons. For example, if E1 has a
small positive potential and E2 has a large positive potential, the EEG trace
deflection is still upward because E1 is relatively more negative.
Montages are simply an array of these differential voltage measurements
that provide spatial as well as temporal and amplitude information. So-called
bipolar montages typically compare the potential at two nearby electrode
sites. These montages are usually arranged in longitudinal or transverse linear
linked chains (Fig. 2.14). It is important to remember that bipolar montages
Figure 2.13: International 10–20 electrodes plus a supplementary subtempo-
ral chain of electrodes superimposed on a three-dimensional head and brain
display the difference in potential between neighboring electrodes and not the
MRI reconstruction. Note that the standard temporal chain of electrodes passes absolute amplitude of the potential at these sites. Thus, two electrodes record-
across the superior aspect of the temporal lobe. Inferior temporal electrodes are ing a large potential of similar magnitude and polarity will yield a bipolar
better positioned to record from inferior temporal and frontal regions. montage channel displaying little or no deflection (Fig. 2.14B). For the same
reason, amplitude measures should not be made in a bipolar montage. To do
so quantifies voltage gradient between electrodes, not absolute amplitude.
(Fig. 2.13). Recording from subtemporal electrodes routinely makes sense, Given these deflection characteristics, a chain of linked bipolar derivations
given the fact that these areas are common locations for epileptogenic foci. that traverses a negative voltage field maximum will result in an “instrumen-
tal” phase reversal; that is, the trace deflections in adjacent channels will point
Display of Voltage Fields in EEG toward each other (Fig. 2.14A). If the negative maximum is broad, a middle
Traces—Montages bipolar pair will record nearly the same amplitude of negativity, and thus
that channel will display little or no deflection, whereas channels on either
The measurement of EEG potentials is always relative to a reference. Po- side have phase-reversing deflections (Fig. 2.14B). Conversely, a linked bipo-
larity and amplitude are thus dependent on this comparison. Differential lar chain traversing a positive voltage field maximum would yield a reversed
amplifiers magnify the difference in voltage potential between two measure- or phase away reversal. A waveform deflection that is upward in a bipolar
ments, whether from real or derived electrode locations. A particular EEG montage does not mean that the field is positive. Trace deflection depends on
channel can be thought of as the potential at electrode 1 minus the potential the relative polarity and magnitude of the inputs to the differential amplifier.
at electrode 2. Each EEG channel is thus designated as such, E1 − E2. E1 Bipolar montages have both advantages and weaknesses. Noncerebral ar-
is typically a single electrode; E2 may also be a single electrode or some tifacts are lessened by differential amplification because neighboring elec-
mathematical average of a number of electrodes. In traditional pen-written trodes “see” nearly the same extraneous signal. Bipolar montages emphasize
shallow voltage gradient of the contralateral positive field would yield mini-
mal voltage differences between adjacent electrodes, and thus only a barely
detectable phase away reversal would result.
If there is not a phase reversal in bipolar montage traces, field maxima
(e.g., a spike focus) cannot be localized. This situation can arise with a
tangential field (Fig. 2.15A). Neither the negative field maximum nor the
positive field maximum is defined; only the field gradient can be determined.
Even if a phase reversal is present, bipolar montages typically do not char-
acterize tangential fields well (Fig. 2.15B).
In traditional pen-written EEG, localization of a spike focus required that
similar spikes be identified in both longitudinal and transverse bipolar chains
to define the maximum in both anterior-posterior and left-right directions.
With modern referential digital recordings, only one spike need be recorded.
Reformatting allows the virtual creation of any desired montage to achieve
localization.
The other major category of montages is termed “referential.” In reality,
all montages and all EEG measurements are referential, but in practice this
term is used when the potential of a given electrode is compared to another
that is distant rather than neighboring. When all the electrodes or all those
of one hemisphere are compared with a single electrode, the term “common
FIGURE 2.14: A: Electrodes in a longitudinal bipolar montage cross a small reference” montage is applied. Typically the common reference is an ipsilat-
negative field maximum, resulting in a phase reversal between channels 2 and 3. eral ear, contralateral ear, or midline electrode, such as Cz. Conceptually,
B: Electrodes in the same bipolar montage cross a broader negative field maxi- the intent is to use as reference an electrode that is distant from or outside
mum, resulting in a phase reversal between channels 1 and 3, flanking channel the field of a scalp potential. As explained earlier, this is seldom achievable.
2, which has no deflection. Electrodes that derive channel 2 record a similar po- EEG deflections when using a referential montage obey EEG machine
tential, resulting in no difference in signal. C: Electrodes in a common average polarity conventions. However, because the reference electrode is relatively
reference montage cross a small negative field maximum, resulting in the largest distant, the amplitude of the deflection becomes more a measure of ab-
upward deflection in channel 3 and smaller deflections in the remaining chan- solute potential amplitude, particularly relative to neighboring electrodes.
nels. D: Electrodes in the same referential montage cross a broader negative
Negative field maxima are defined by the largest amplitude, upward EEG
field maximum. Equally large upward deflections are noted in channels 2 and 3
with lesser deflections in channels 1, 4, and 5. All electrodes in the chain record
deflections, and positive field maxima by the largest downward trace deflec-
a more negative field than the common average reference; therefore, all channel tions (Fig. 2.14C, D). Because EEG fields are typically dipolar, both upward
deflections are upward, depicting accurately the large negative field. and downward deflections are commonly observed in referential montages.
Sometimes these channels are situated spatially near one another to give the
appearance of a phase reversal. Some refer to this as a “true” phase reversal;
local or focal differences in potential and steep voltage gradients. Thus, they however, it is better to appreciate this as simply a reflection of negative and
are best for characterizing close, “near-field” sources. Conversely, broad positive field maxima that are common to all EEG potentials.
fields from distant, “far-field” sources may not be apparent, and potential Referential montages also have strengths and weaknesses. Both sharply
amplitudes cannot be easily determined. Reflecting on a typical voltage map defined fields from near-field sources and broad fields from extended or far-
of a lateral temporal spike, such as in Fig. 2.8C, one can appreciate that the field sources are appreciated. True amplitude of signals, rather than gra-
steep voltage gradient of the negative field would be nicely identified by a dients, can be identified. Tangential fields are just as well characterized as
bipolar montage that traversed it as a distinct phase reversal. However, the radial fields (Fig. 2.15C, D). On the other hand, extrinsic noise and artifacts
would now agree that varying the reference does not alter the contours or
gradients of the voltage fields, that is, the relative differences, or the infor-
mation concerning source character (14). What is altered is simply the dis-
play of the same data. In fact EEG source models, such as dipoles, which
use topographic voltage distributions as raw data for calculation, are
reference-independent.
The easiest way to appreciate the effect of the recording reference is to
think of EEG voltage topography as geographical topography, namely,
mountains of one polarity and valleys of another. The reference in this
model would be the level of a coexisting ocean that covers part of this land-
scape. Everything above sea level has an altitude of one polarity and every-
thing below sea level a depth of the opposite polarity. With a different sea
level, the altitudes and depths of particular points on the landscape will
change, but the shape of the mountains or the undersea valleys will not
change. Choose the highest mountaintop or the deepest ocean valley to be
the reference, and all points on the landscape will be of one polarity or the
other; yet the underlying structure will not have changed. The same is true
for changes in EEG recording reference (Fig. 2.16).
Any reference can be used and data interpreted properly if one is aware
of the effect of reference on the EEG display. There is no such thing as an
Figure 2.15: A: Electrodes in a longitudinal bipolar montage cross tangential
“inactive” reference because any point on the head or body carries some
voltage fields. No phase reversal is evident. Only an anterior more negative than electrical potential. Traditionally, reference electrodes were thought to be
posterior gradient can be determined. B: A phase reversal detects the negative “active” only when they were within the negative field of a spike. This was
field maximum, but the positive maximum goes undetected. C: Electrodes in a due in part to the misconception that outside of this negative field there
common average reference montage cross the same tangential voltage field. was no other activity related to the spike. Spikes were commonly thought to
Both negative and positive field maxima are recognized. D: Similarly, both nega- have only a negative field maximum, except for the “horizontal dipoles” of
tive and positive fields are characterized in the same referential montage. Bipolar benign rolandic epilepsy. In fact, all spikes have by electromagnetic necessity
montages poorly depict tangential fields. both negative and positive field maxima. Depending on source location and
orientation, both maxima may not be recorded in standard 10–20 montages,
can be greater. If the common reference records a large signal, all channels as discussed earlier. Because positive field maxima were not thought to be
using it are “contaminated.” If the electrodes in a given region record very present in most spikes, reference manipulations were often performed to
little signal, such as over a large infarct, channels using those electrodes will eliminate the appearance of positive potentials whenever they did occur.
display principally activity from the reference. In reality, there is no reference For example, common average reference derivations were often calculated
electrode site that is inactive. only after removing the electrodes recording the largest negative potentials.
If one did not, it was said, positive potentials might appear on the opposite
side of the head. These were thought to be reference artifacts rather than
Effect of Reference on EEG Fields the true opposite polarity field maximum that is produced by any dipolar
source. Deleting electrodes with the most negative potential from the aver-
There has been considerable debate about the effect of choice of reference age simply shifted the reference “sea level” in a positive direction so that the
on the appearance of EEG traces and on voltage field maps. Authorities true positive field would appear to have less amplitude (see Fig. 2.16).
Figure 2.16: Bottom: The magnitude and polarity of

a right temporal spike recorded in common average
reference from a midcoronal chain of electrodes are
graphed into a two-dimensional landscape. The volt-
age topography of this spike is illustrated in the figure
at the right. Isopotential lines are drawn at every 30 µV;
hatched area is negative. Top: EEG traces of this spike
are displayed using each electrode in the midcoronal
chain in succession as the common reference. Note that
changing reference only alters where the zero voltage
line is placed. The relative voltage differences among
electrodes remain unchanged. When T10, the negative
field maximum, is the reference, all EEG deflections are
positive (downward). When Cz, the positive field maxi-
mum, is the reference, all EEG deflections are negative
(upward). When T9 is the reference, the EEG deflections
are similar to those of the common average reference
because this electrode lies on the common average ref-
erence zero isopotential line.
As discussed earlier, however, maximal information about source char- Conclusions

acter can be obtained only by identifying both field maxima. A simple, yet
very effective, way to do this is to use a common average reference made Scalp EEG is a multidimensional signal and a carrier of abundant informa-
from all recording electrodes. If one uses the mean potential recorded from tion that is often not fully used. Limitations of traditional EEG are mostly
all electrodes as a zero reference level, then by necessity both negative and artificial and imposed, in part, by simplistic interpretation methods. Practitio-
positive fields will be accentuated and thus more easily identified. This type ners of modern EEG must go beyond two-dimensional thinking and pattern
of reference also makes physical sense. By the laws of physics, the net charge recognition to extract more from it. It is essential to appreciate the relation-
or net potential over the surface of the head from any source should be ships between the character of cortical generators and the EEG voltage fields
zero, that is, positivity balancing negativity. Using the mean of all recording they produce in order to move EEG interpretation beyond simple descrip-
electrodes is an approximation of this. Obviously the more electrodes used, tions of waveforms toward an analysis of brain source location and character.
particularly from undersampled regions of the head, the more such a refer-
ence will approximate the true zero potential. To the untrained eye, such a References
reference may initially cause confusion because fields of both polarities are
emphasized. Focal negative spikes from one hemisphere or lobe will be ac- 1. Eccles JC. Interpretation of action potentials evoked in the cerebral cortex. Electroen-
cephalogr Clin Neurophysiol 1951;3:449–464.
companied by positive potentials commonly from the opposite hemisphere. 2. Li CH, Jasper H. Microelectrode studies of the electrical activity of the cerebral cortex in
This distribution does not represent bilateral spike sources, but rather the the cat. J Physiol 1953;121:117–140.
normal dipolar field of any cerebral generator. The greater amplitude and 3. Purpura DP, Grundfest H. Nature of dendritic potentials and synaptic mechanisms in
cerebral cortex of cat. J Neurophysiol 1956;19:573–595.
steeper voltage gradient of the negative maximum identify the source as be- 4. Humphrey DR. Re-analysis of the antidromic cortical response, II: on the contribution
ing nearer to it, while its geometrical relationship to the positive maximum of cell discharge and PSPs to the evoked potential. Electroencephalogr Clin Neurophysiol
conveys the overall field orientation and thus the net orientation of the gen- 1968;25:421–442.
5. Creutzfeldt O, Houchin J. Neuronal basis of EEG waves. In: Creutzfeldt O, ed. Handbook
erating cortex, which is orthogonal to the field. of electroencephalography and clinical neurophysiology, Vol 2C. Amsterdam, the Nether-
Although the common average reference has many strengths, it is by no lands: Elsevier, 1974:5–55.
means perfect. This is particularly true when spatial sampling over the head 6. Cooper R, Winter AL, Crow HJ, et al. Comparison of subcortical, cortical and scalp
activity using chronically indwelling electrodes in man. Electroencephalogr Clin Neuro-
is limited. If one of the true field maxima is not recorded, as is the case when physiol 1965;18:217–228.
it is located at the bottom of the head where there are no electrodes, false 7. Gloor P. Neuronal generators and the problem of localization in electroencephalography:
maxima will be created by the requirement of having equal amounts of both application of volume conductor theory to electroencephalography. J Clin Neurophysiol
1985;2:327–354.
polarity evident in the sum of channels. For example, vertex sharp waves 8. Gloor P. Contributions of electroencephalography and electrocorticography to the neu-
will have positive maxima in the most inferior electrodes bilaterally (closest rosurgical treatment of the epilepsies. In: Purpura DP, Penry JK, Walter RD, eds. Ad-
to the head bottom), and eye blinks with a frontopolar positive maximum vances in neurology, Vol 8: neurosurgical management of the epilepsies. New York, NY:
Raven Press, 1975:59–105.
will have a compensatory negative maximum at the most distant occipital 9. Tao J, Ray A, Hawes-Ebersole S, et al. Intracranial substrates of scalp EEG interictal
electrodes. In the latter case, suborbital electrodes added to the array will spikes. Epilepsia 2005;46(5):669–676.
record the true negative field maximum of the eye blink and eliminate the 10. Nunez P, Srinivasan R. Electric fields and currents in biological tissue. In: Nunez P, Srini-
vasan R, eds. Electric fields of the brain: the neurophysics of EEG. New York, NY: Oxford
false occipital maximum. University Press, 1981:47–202.
There are a variety of other mathematically derived montages. Some at- 11. Perrin F, Pernier J, Bertrand O, et al. Spherical splines for scalp potential and current
tempt to emphasize local brain activity better than traditional montages. density mapping. Electroencephalogr Clin Neurophysiol 1989;72(2):184–187.
12. Ebersole JS. Defining epileptogenic foci: past, present, and future. J Clin Neurophysiol
Among these are the Laplacian and Hjorth source montages (10,14). The 1997;14:470–483.
trade-off with these montages is that information regarding far-field activity, 13. American EEG Society. Guidelines for standard electrode position nomenclature. J Clin
usually the positive field maximum, is lost. Thus, true field and source orien- Neurophysiol 1991;8:200–202.
14. Lehmann, D. Principles of spatial analysis. In: Gevins A, Reymond A, eds. Handbook of
tation is lost. As sources become more tangential, localization may become electroencephalography and clinical neurophysiology, Vol 1: methods of analysis of brain
compromised. These montages are infrequently used in clinical applications. electrical and magnetic signals. Amsterdam, the Netherlands: Elsevier, 1987:309–354.
3 Engineering Principles
DOUGLAS MAUS • BRIAN LITT
Electrical Basics New Electrodes

Fundamental Electrical Components Preamplifiers
Resistor Antialiasing Filter
Capacitor Digitizer
Inductor Digital Transfer/Storage
Voltage Sources Digital Processing
Element Combinations Finite Impulse Response Filtering
Circuits Infinite Impulse Response Filtering
Voltage Divider FIR versus IIR
Input Impedance Filtering Examples
Differential Amplification Display Considerations
Time-Varying Circuits Electrical Safety
Impedance and Alternating (Sinusoidal) Circuits Improper Grounding
Simple Filters Leakage Currents
Digitization Double-Grounding
Time Discretization Exacerbating Factors
Voltage Discretization (Signal Resolution) Regulations
Digitizer Electronics Conclusions
EEG-Specific Acquisition Acknowledgments
Electrodes References
Common Types of Electrodes Appendix
45
This chapter discusses the engineering principles important to the electrical TABLE 3.1 Electrical Terms and Symbols
equipment used in clinical electroencephalography (EEG). In particular, we
emphasize two major engineering aspects of EEG: (a) principles important to Term Units Symbol Comments
faithfully recording and representing cerebral electrical activity, and (b) iden- Charge Coulombs (C) Q 6 × 1018 electrons
tifying and minimizing electrical dangers to patients undergoing EEG.
Engineering technology in EEG has markedly advanced since the last Current Amperes (A) I I = dQ/dt
edition of this book, particularly with respect to broadband recording. Voltage Volts (V) V, E, EMF Joules/Coulomb
Clinician researchers are expanding the spatial and temporal scales of the
Energy (work) Joules (J) E (or W) kg × m2/s2
technology, with clear, early evidence that these changes may become im-
portant to clinical care. These forces are expanding EEG technology from Resistance Ohms (Ω) R V=I×R
the standard 0.1- to 70-Hz bandwith of pen and paper machines, which was Capacitance Farads (F) C I = C × dV/dt
initially directly ported to digital EEG, to sophisticated systems recording in
the kilo Hertz frequency range from electrodes spaced hundreds to tens of Inductance Henrys (H) L V = −L × dI/dt
microns apart in intracranial EEG. Using these systems requires a more so- Impedance Ohms (Ω) Z Complex (real and
phisticated knowledge of the effects of electrode size, impedance, and digital imaginary)
sampling technique on the accuracy of signal reproduction. Although many Reactance Ohms XC XC = 1/(2pÑ C)
of these issues are beyond the scope of this chapter, we want to convey our (capacitance)
enthusiasm for the exciting advances in EEG technology unfolding before Reactance Ohms XL XL = 2pÑ L
us, as clinicians begin to reach down into a world traditionally inhabited (inductance)
only by cellular neuroscientists. In this chapter, we briefly touch upon some
Power Watts (W) P P=I×V
of these topics and encourage the reader: hold onto your hat and follow the
EEG literature along with us as these exciting stories unfold.
Let’s not get too far ahead of ourselves though. This chapter is not focused
on the hottest new technology or research. Rather it aims to convey the en- polarity, or positive. The standard macroscopic unit of charge is the Cou-
gineering knowledge required to be a good, effective EEGer. Starting with lomb (C)—the total charge of 6.24 × 1018 electrons. Individual atoms have
the basics, we move to cover important concepts relevant to clinical practice, a balanced equal number of electrons and protons, and so are electrically
touching briefly at the end on exciting developments just around the corner. neutral. In biologic systems, sodium and other cations typically exist with
a missing electron, and so have a net positive charge. Importantly though,
Electrical Basics the mass of a positively charged sodium ion is many orders larger than a
single electron, so despite the identical magnitude of electrical forces, by
The electromagnetic force is the foundation of this chapter, and indeed the Newton’s Law, the acceleration imparted to a sodium ion would be much
most important basic force on the scale of biologic systems (Table 3.1). smaller.
Electric charge is dichotomized into positive and negative. Like charges re- The electric potential (as opposed to the raw forces that have both mag-
pel, and opposites attract, and the magnitude of force diminishes as the in- nitude and direction vectors) is an extremely useful simplifying concept.
verse square of the distance between the charges (Coulomb’s Law). Moving In physics, where conservation of energy is a supremely useful principle,
charges generate a magnetic field, and varying magnetic fields create electric electric potential is shorthand for potential energy, and is basically a topo-
currents in conductors (Faraday’s Law) (1). graphic map, analogous to maps of altitude of terrain, each point having a
Charge comes in single indivisible units—each electron has the same single height. In this analogy, the height of a point on the map represents its
amount of charge—one elementary unit, by tradition called negative. potential energy (the amount of energy required to carry it there), compared
Each proton has exactly the same magnitude of charge, but opposite in to the “ground,” which by definition has no potential energy. In electrical
Engineering Principles 47
engineering, where three-dimensional geometry can be further idealized

into simple circuits with lumped elements, the essential behavior is encapsu-
100 Ω
lated further into the electric potential (voltage, measured in Volts, V) and
simple equations relating voltage and current. In models of the brain, it
makes more sense to consider the physics of the three-dimensional spatial +
10 V
distribution of electric potentials across cells, nuclei and circuits, while in 0.1 A
the electronic EEG machine, the simplified scalar voltage is the more useful
representation, though the two methods treat the same concept of potential I=V/R
energy. This chapter will generally use the simplified voltage of electrical
engineering.
When electric potentials exist and differ in regions, charges exposed to the Figure 3.1: Simple circuit illustrating Ohm’s law. I = V/R = 10 V/100 Ω = 0.1 A,
corresponding electric forces may move. Current is this movement or flow where V is a 10 V battery, and R is a 100 Ω resistor.
of charge, and has the standard macroscopic unit of Amperes (A or amps),
where 1 A = 1 C per second. Current encapsulates both amount and speed, The equivalent of Ohm’s law with conductance is then:
just as the measured water flow (cubic feet per second) on a river does not
distinguish a wide, slow region from a narrow, fast section. I = V·G
Fundamental Electrical Components Capacitor

Resistor There are other circuit elements that can store charge. These elements are
capacitors, illustrated in Fig. 3.2. In general, the amount of charge stored in
Given a constant potential difference between two points, the amount of a capacitor (Q) is proportional to the voltage difference across it. The con-
current that flows can depend on a multitude of factors involving the instant of proportionality is the capacitance, and represented by C:
tervening material, but for huge number of conditions, a very good ap-
proximation is that the current flow is linearly proportional to the potential Q = C·V
difference. This is expressed in Ohm’s law: In static (constant) circuits, these elements do not pass current through them
V = I·R (they act as infinite resistance). In time-varying circuits (see later for more
where the resistance (R) is the proportionality constant between the voltage
difference (V) and the current (I). Resistance is measured in units of Ohms
(Ω), and 1 Ω = 1 V per A. A circuit element that follows this law is said to be Capacitor
“Ohmic,” and is a resistor, illustrated in Fig. 3.1. Where there are resistors Battery +Q Conductive plate
in circuits, and current flows through them, the drop in electric potential + insulator
energy across them is converted into thermal/heat energy. V (dielectric)
Another framework for discussing current and voltage is to use the con- −Q Conductive plate
cept of conductance. Conductance (G) is defined as the inverse of resistance,

and is expressed in Siemens (S).
1 Figure 3.2: Conceptual diagram of a charged capacitor. The charge, Q, is pro-
G
R portional to the applied voltage, V.
detail), these capacitors have a more subtle and important role. Though no Element Combinations
charge actually crosses the insulator between the plates of capacitors, in ef-
fect current flows through a capacitor, depending on the rate of change of Resistors
voltage across the capacitor: The effective total resistance of two or more resistors in series is the sum of
their individual resistances:
∂Q ∂V
C
∂t ∂t R R1 R2 ⋅⋅⋅ RN
∂V Using the fluid analogy mentioned earlier, two consecutive identical kinks in
I C
∂t a hose will resist flow through the hose twice as much as one.
The capacitance of a typical parallel-plate capacitor can be predicted For two resistors in parallel, the effective resistance is less than both of the
from the physics of its geometry, and is proportional to the cross-sectional individual resistance. The reciprocal of the effective resistance is the sum of
area of the plates divided by the distance between the plates. the reciprocals of the individual resistances:
1 1 1

Inductor R R1 R2
Inductors are formed from loops of current—typically wire twisted into spi- In this case, the fluid analogy is that two parallel branches in a hose with the
rals. From the principles of electromagnetism, when charges flow through same size kinks will allow twice as much water to flow as one hose of the
the loops in these coils, a magnetic field is generated. While capacitors con- same size with the same-sized kink.
vert electric energy into a stored electric field, inductors store electrical en- Note that in parallel, two equal resistors have an effective resistance that is
ergy into magnetic fields: half their individual resistance. See Fig. 3.3 for an illustration of series and
∂I parallel combinations of resistors.
V L Identical results can be obtained if one uses the concept of conductance
∂t
(G, the reciprocal of resistance). Conductances in parallel simply add:
Of the various ways of conceptualizing an inductor, one is that given a con-
stant voltage across an inductor (ideal, with no real resistance), the amount G = G1 + G2
of current that flows through the inductor will increase linearly over time.
(while conductances in series follow the reciprocal formula).
Another concept is that when there is a time-varying voltage across an in-
ductor that would generate a current through it, the inductor generates an
intrinsic voltage that opposes it, and which is proportional to the rate of
change of the current through it.
Series Parallel
Voltage Sources 50 Ω
In electrical circuit theory, generators of voltage are represented by ideal 100 Ω 200 Ω 200 Ω
voltage sources. These voltage sources are idealized, in that they are pre-
sumed to generate the same voltage no matter how much current is flow- 50 Ω
ing through the circuit. There are limitations in this idealization: most
voltage sources cannot deliver an infinite current across a short circuit Figure 3.3: Diagram of resistors, a combination in series on the left, and a com-
(a conducting wire with negligible resistance), nor should they for safety bination in parallel on the right. All three arrangements of resistors have the
reasons. same equivalent resistance, 100 Ω.
Capacitors
From the prototypical parallel-plate model of a capacitor, two capacitors in R2
parallel act as if their cross-sectional areas are added, so the effective capaci-
tance of two capacitors in parallel is +
V
C = C1 + C2
Capacitors in series follow the reciprocal formula: R1 V1
1 1 1

C C1 C2 Figure 3.4: A circuit illustrating the concept of a voltage divider. The voltage V1
will be proportional to R1 over the total resistance (R1 + R2).
Inductors
They follow the same pattern of formulas as resistors.
we are concerned with a voltage source and two resistors in series, and
Circuits we determine how the voltage is distributed across each of the individual
resistors.
Given a configuration of electrical components, the currents and voltages in
The total voltage must equal the total current times the effective resistance:
the circuit (2) can be determined from two essential laws, both due to Gustav
Kirchhoff. V = I·R
Kirchhoff’s voltage law states that the sum of voltages across a complete
The effective resistance is determined by summing the resistances of these
path of the circuit must be zero. Another way of phrasing this is that the
resistors in series:
sum of the drops in voltage across the elements in a circuit must be equal to
the input voltage. This is an expression of conservation of electrical poten- V = I·(R1 + R2)
tial energy. One example consequence is that elements in parallel have the
The current through one resistor must be the same as the current through
same voltage across them.
the other resistor (by Kirchhoff’s current law); so we simply call it I, and
∑V k 0 solve for it in terms of the voltage and resistances.
loop
V
Kirchhoff’s current law states that the net current flow in a node (junction I
R1 R2
point) in a circuit must be zero; that is, at steady state, there is conservation
of charge: the current into a node must be balanced by the current out of The voltage across resistor 1 follows Ohm’s law:
that node:
R1
∑I
node
k 0 V1 I R1 V
R1 R2
If the resistances are equal, then the voltage across either one is half the
Voltage Divider total voltage. If they differ significantly in resistance, there is more voltage
drop across the larger resistance. This circuit with appropriate choices of
Consider the application of these circuit laws in combination with Ohm’s R1 and R2 can be used to obtain a fixed fraction of the original voltage—to
law to a circuit known as the voltage divider, illustrated in Fig. 3.4. Here divide the voltage into the required fraction.
Input Impedance impedance of most clinical EEG equipment is >100 MΩ. For equipment
with higher electrode impedance, the input impedance of the measuring
The instrument to measure a voltage in part of a circuit—a voltmeter— equipment should be adjusted upward accordingly.
would ideally not disturb the circuit in any way. However, actual instruments
that measure voltage may perturb the system. A very simple model of a Differential Amplification
voltmeter to show the effect of the input resistance or impedance is shown
in Fig. 3.5. Measuring the EEG voltages, at some stage, requires amplifying the signals.
The voltage to be measured is modeled by an ideal source voltage, Vs, EEG voltages are measured at each electrode relative to some chosen refer-
in series with a resistance, Rout. An ideal voltmeter (in our case an EEG ence electrode. That is, the measured voltage is the difference in potential
machine) would draw no current, but actual voltmeters may draw a small between the electrode and the reference. To measure this voltage difference,
current, here modeled by a (shunt) resistor in parallel with the meter, with specific kinds of amplifiers are employed, called differential amplifiers, il-
resistance Rinput. The voltage that is measured by the voltmeter then depends lustrated in Fig. 3.6.
on the input resistance relative to the output resistance of the source: The ideal differential amplifier is insensitive to large offsets of the volt-
ages being compared, but actual differential amplifiers are imperfect. The
Rinput general formula for the actual output for a differential amplifier follows:
Vmeas Vs
Rinput Rout 1
Vout Ad (V − V ) Acm (V V )
2
when Rinput >> Rout ,Vmeas Vs
Here Ad is the differential gain, and Acm is the common-mode gain. A good
1 differential amplifier will have a large Ad and as small a Acm as possible.
when Rinput ∼ Rout ,Vmeas Vs
2 The standard metric for how well a differential amplifier ignores the aver-
In order that the measured voltage Vmeas most accurately reflects Vs, it is easy age (common-mode) voltage is the common-mode rejection ratio (CMRR),
to see that the input resistance of the voltmeter should be large compared typically expressed in the logarithmic decibel scale:
with the equivalent source resistance, Rout. The source resistance for clini-  A 
cal EEG depends on many factors—one significant factor is the electrode CMRR 20 log10  d 
resistance, which is typically on the order of 5 kΩ. In practice, the input  Acm 
V+
Rout Vout
Rinput V−
Vs
(Iso ground)
Figure 3.5: The model for a real voltage-measuring (voltmeter) device, illustrat-
ing the concept of input impedance, Rinput. The measured voltage will be propor- Figure 3.6: Simple concept of a differential amplifier. Ideally, the output voltage
tional to Rinput divided by the total resistance Rinput + Rout. The measured voltage is proportional to the difference between the input voltages. See text for formu-
will be most accurate when Rinput is very large compared to Rout. las of CMRR.
(The factor of 20 is because in engineering the convention is to consider the R

power ratio.)
For a differential amplifier that is quoted as having a CMRR of at least
80 dB, then the ratio of the differential gain to the common-mode gain is
+
4 orders of magnitude, or Ad/|Acm| > 10,000. V0 − C VC
There are several variations of differential amplifiers. A differential am-
plifier particularly designed to handle large common-mode voltage is some-
times termed an isolation amplifier. An instrumentation amplifier is one
that has input buffers to stabilize the input voltages. Figure 3.7: RC circuit. A resistor and capacitor in series, and examining the volt-
age across the capacitor.
Time-Varying Circuits
The units of resistance (Ohm) and capacitance (Farad) are related such that
Next consider the circuit in Fig. 3.7, with one resistor and one capacitor, and 1 Ohm·Farad equals 1 second. Using this fact, in equations such as these,
a voltage source that is zero, but then is abruptly stepped up to some voltage, the lumped value of the resistance times the capacitance is known as the
V0, at time t = 0. We use Kirchhoff’s voltage law and differential calculus to “time constant,” usually denoted by tau:
solve for the voltage across the capacitor and across the resistor as a func-
RC ≡ t
tion of time after the voltage is abruptly stepped.
The time evolution of these voltages is illustrated graphically in Fig. 3.8.
V0 I R VC 0 (Kirchoff's voltage law) After the voltage is stepped, the capacitor begins to charge—the voltage
across the capacitor starts at zero and climbs to eventually approach the
V0 VC same magnitude as the applied voltage. Initially, the voltage across the resis-
I (re-arranged) tor is large, but then falls. The current also jumps to an initially large value
R
∂VC
I C (capacitor definition)
∂t
Capacitor
∂VC V0 VC
I C (combining equations for current)
∂t R
Voltage
∂VC V0 VC

∂t RC 1/e
0.3679

t

VC V0  1 e RC
 (solution to differential equation)
 2
Resistor
1/e
t 0.1353

VR V0 e RC
t
V0 RC 0 Time 2 3 4 5
I e
R Figure 3.8: Time evolution of charging RC circuit.
and then falls, also, eventually approaching zero—this current provides resistance, while the imaginary part, which contains frequency information,
the charge that charges the capacitor. At all times, the sum of the voltage is called the reactance. The imaginary part of the impedance is a mathemati-
across the resistor and the voltage across the capacitor sum to equal the ap- cal way of describing any phase difference between the driving oscillation
plied voltage. After 1 time-constant, the voltage across the resistor (in ratio and the output response.
to its starting voltage) falls to e−1 = 1/e ≈ 0.368, after 2 time-constants to The impedance of a pure resistor is just its resistance.
1/e2 ≈ 0.135, and so on. After 5 time-constants, the values are for practical
ZR = R
purposes near enough to the steady-state values.
The impedance of a capacitor is
Impedance and Alternating (Sinusoidal) Circuits 1
ZC
jwC
Electrical equipment in which the sources alternate (alternating current,
AC) typically follow a sinusoidal pattern; see Fig. 3.9. Furthermore, any (In electrical engineering, the imaginary number is represented by j, since I
rhythmic pattern (like square stimulation waves, etc.) can be usefully treated and i are used for current. Angular frequency, w, is often used for simplicity
as a combination of sinusoids: the pattern can be broken down into its sinu- in place of conventional or temporal frequency, f, and these are related by
soidal components at different frequencies, then the effect on the individual w = 2p.)
frequency components may be considered, and the end result can be recon- The impedance of an inductor is
structed by combining the modified frequency components. This principle
ZL = jwL
is called superposition.
In electrical engineering of alternating sources, a generalization of the
resistance can be made, called the impedance. The impedance is technically Simple Filters
a complex quantity, with real and imaginary parts. The real part is the pure
Consider a (partial) circuit with just two elements—a resistor and capaci-
tor, arranged to alter an input voltage and generate an output voltage
across the capacitor, illustrated in Fig. 3.10. Consider this as a voltage di-
1
vider, but acting on sinusoidal varying frequencies. At very low frequencies
(less than 1/RC), the impedance of the capacitor is very large, much larger
than the resistor, so the voltage across the capacitor is nearly identical to
the input voltage. At very high frequencies, the impedance of the capacitor
falls to nearly zero, so the voltage across it also falls to nearly zero. This
Amplitude
circuit will then act to preserve (pass) low frequencies, but eliminate high
0
Vin C Vout
−1
Degrees 0 90 180 270 360
Radians 0 /2 3 /2 2
Cycles 0 1/4 1/2 3/4 1
Figure 3.9: The sine wave. Figure 3.10: RC circuit as a lowpass filter.
frequencies. The precise formulas for the frequency dependence of the filter 1.0
are as follows: 0.7071 −3 dB
ZC
Vout Vin
ZC ZR
1
Vout jω C
0.1 −20 dB
Vin 1
R
jω C
Vout 1
(complex)
Vin 1 jω RC
Vout 1
(magnitude)
Vin 1 (ω RC )2
0.01 −40 dB
Vout 1 1 10 100 1000 10000

Vin 1 (2 RC f )2 Frequency (Hz)
Vout 1 Figure 3.11: Plot of the transfer function of an RC filter with a cutoff frequency of
100 Hz, showing the ratio of the output voltage to the input voltage as a function
Vin  f 
2
of frequency. This filter passes low frequencies, and attenuates high frequencies.
1 
 fcutoff  Note the log–log axes, the convention for analog filters.
shall use the standard engineering terminology of referring to the band that
Here, the cutoff frequency has been defined as fcutoff = 1/(2pRC) = 1/(2p·t). is passed or allowed, so these are lowpass filters.
In this example, t = RC, and is known as the “time constant” of the filter. More complicated lowpass filters can be constructed that are “sharper”—
As an example, if the resistor and capacitor are chosen such that 2pRC is the attenuation as a function of frequency (or “roll-off ”) is steeper after the
0.01 seconds, which corresponds to a cutoff frequency of 100 Hz (=1/0.01 cutoff frequency. The complexity of these filters is described in terms of the
seconds), then the output voltage as a function of the input voltage will fol- “order” of the filter, roughly proportional to the number of elements with
low the plot in Fig. 3.11. (Note that this graph uses log-log axes, as is the reactance (capacitors or inductors) that would need to be placed in a circuit
convention for analog electrical filters.) to create the particular filter profile. Figure 3.12 compares the transfer func-
For low frequencies (below the high-frequency cutoff), the output voltage tion roll-off of first-, second-, and third-order lowpass filters. For higher-
is nearly the same as the input voltage—called the passband. At high fre- order filters, the cutoff frequency is still defined to be where the response
quencies (much above the cutoff), the output voltage is much lower than the falls by −3 dB, and is the same (100 Hz) for each in this figure. The roll-off
input voltage—called the stopband. At the cutoff, where f/fcutoff = 1, the out- above the cutoff is seen to be much steeper for the higher-order filters. On
put voltage is 1 / 2 ≈ 0.7071 of the input voltage, and this cutoff is where log-log graphs as the frequency increases, in theory the roll-off moves closer
the output voltage has a “shoulder,” beginning to rapidly fall with increasing to a straight vertical line. The slope of this line is often expressed in terms of
frequency. In engineering terminology, this filter is technically known as a attenuation per decade (frequency increasing by factor of 10) or per octave
lowpass filter (it passes or allows low frequencies). Because it “cuts out” (frequency increasing by factor of 2). The first-order filter has a roll-off at
high frequencies, sometimes it is termed a “high-cut” or “high-frequency” 20 dB per decade (or 6 dB per octave), the second order at 40 dB per decade
filter, which can become confusing. For the remainder of this chapter, we (12 dB per octave), and the third order at 60 dB per decade (18 dB per octave).
1.0
Passband Stopband Stopband Passband
0.7071 −3 dB
1st order
0.1 −20 dB Lowpass filter Highpass filter
2nd
Stop
3rd
Stop Pass Stop Pass Pass
0.01 −40 dB
1 10 100 1,000 10,000
Frequency (Hz)
Bandpass filter Notch filter
Figure 3.12: Plot of transfer functions for lowpass filters of first-, second-, and
third-order, all with cutoff frequency of 100 Hz. Note the steeper slope in the Frequency Frequency
stopband for increasing order. Figure 3.13: Diagram of the effects of the four basic types of filters: lowpass,
highpass, bandpass, and notch (or bandstop). These all are plotted as log-log
graphs, as is the convention for analog filters.
Different designs of higher-order filters include Butterworth (3),
hebyshev, and Elliptical. Some of the trade-offs in these designs include
C
the steepness of the roll-off versus the amount of ripple in the passband
or stopband. Also note that while higher-order analog filters may have versions of such filters were formerly very important in eliminating the
better stopband attenuation and narrower transition band, they require 60-Hz powerline noise. Figure 3.13 shows diagrams of the frequency effects
more circuit elements, greater expense to design, more exacting specifica- of these four basic types of filters. In modern digital EEG acquisition,
tions, and each element can add noise to the overall circuit. More is not highpass, bandpass, and notch filtering are typically handled by software
always better. digital postprocessing (see later).
Of analog filters, for EEG, the most important type is this lowpass filter,
for reasons that will become clear in the section on digitization. Analog Digitization
filters can also be designed that act to pass high frequencies and attenu-
ate low frequencies (highpass), and the concepts of lowpass and highpass In order to be captured, stored, and processed by computers, the electrical
filters can be combined to create bandpass filters, which pass frequency signals of the biologic systems need to be digitized—converted from analog
components in a defined band of frequencies bordered by the high and signals to digital representations. For time-varying signals, the digitization
low pass filters, but attenuate very low and very high frequencies. Finally, acts to quantize along two dimensions: time and magnitude. That is, sam-
analog filters can be designed to attenuate (“stop”) a very narrow range ples are extracted at discrete and regular time intervals and also converted
of frequencies. This filter is called a notch or a bandstop filter, and analog to discrete values of magnitude (4).
Time Discretization present in the signal to be digitized, a nefarious complication can occur,
known as aliasing. Figure 3.14 demonstrates the issue.
Digital machines operate with very precise clocks, changing states at very In this example, a sinusoidal signal at 11 Hz (dashed curve) is digitized at
regular intervals. Digitization takes samples at set intervals of time—regard- 16 samples per second. With this sampling rate, the Nyquist limit is just 8 Hz.
less of whether the magnitude is changing slowly or quickly, the sampling rate The actual digitized sample points are plotted as solid squares, and these are
is fixed. Since this sampling rate is fixed, care must be taken to judiciously what the computer actually records. It can be seen that the gray curve also
choose an appropriate sample rate. The choice of sampling rate places re- fits the sample points. This gray curve is a sinuisoid at 5 Hz. In this way, sig-
strictions on the information available in the digitized series. This constraint nals above the Nyquist frequency appear as aliases at frequencies below the
is known as the Nyquist limit. In essence, the frequencies that are detectable Nyquist frequency. The signals above the Nyquist frequency are said to have
in a digitized time series are those below half the sampling rate. For concrete- been “folded back,” like a paper folded over at the Nyquist limit, illustrated
ness, if the sampling rate is 400 samples per second, then components with in Fig. 3.15.
frequencies up to 200 Hz are captured. Signals with frequencies above 200 Hz In this way, random noise components with frequencies above the Nyquist
have not been captured in any way that is detectable or recoverable. limit can worsen the signal-to-noise ratio (SNR) of digitized signals, illus-
If signals above the Nyquist limit were simply lost, this would be a simple trated in Fig. 3.16, and may introduce spurious features in the EEG, which
limitation. However, if signals with frequencies above the Nyquist limit are are not really in the brain signals being recorded. These waveforms are an
artifact introduced by improper sampling.
+1
0
0.5 1
−1
seconds
0 Nyquist Sample
Figure 3.14: Example of aliasing. An analog 11-Hz sine wave (represented by
(8 Hz) rate
the dashed line), digitized at 16 samples per second, yields the sample points
represented by solid squares. A sine wave at 5 Hz (the light-grey line) matches Figure 3.15: Illustration of digital sampling aliasing, showing the mapping of
the same sample points exactly. Sine waves at frequencies above the Nyquist fre- frequencies above the Nyquist frequency to apparent frequencies below the Ny-
quency (here, 8 Hz) can always be equivalently matched by sine waves between quist frequency, as if the paper were “folded” at the Nyquist frequency—the
0 and the Nyquist frequency. source for the alternative description of aliasing as “folding.”
Spectrum
Original
0 Hz 256
Low−pass filtered
Filter
0 0
0 2.0 0 2.0
Noise folded
Digitize Digitize
128 Hz 128 Hz Figure 3.16: Illustration of the adverse effect of failure to filter out
frequency components above the Nyquist frequency before digitiz-
ing (data simulated). Top left: an analog tracing with a signal at 5 Hz
with “white” noise components up to 256 Hz (visible in the power
spectrum—inset top right). Bottom left: if this analog tracing is digi-
tized at a sampling rate of 128 Hz (Nyquist of 64 Hz), the noise above
0 0 64 Hz is folded, and adds to the noise below 64 Hz. The SNR is actually
worsened. Top right: if the analog tracing is lowpass filtered (with an
RC filter, for instance), the noise components above the Nyquist are
attenuated/removed. Bottom right: if the lowpass filtered analog
tracing is then digitized at a sampling rate of 128 Hz, the SNR is pre-
0 seconds 2.0 0 2.0 served, and the original signal remains easily visible.
In order to avoid this aliasing of noise above the Nyquist limit, digitizers and digital value 1 would represent 10 m V. There is no way to meaningfully
as a rule have an analog lowpass filter prior to the digitization step. This store the value 3 m V—this would be approximated to a digital value of 0,
lowpass filter (which can be similar to that described in the analog electrical while 7 m V would be rounded up and stored as 10 m V = digital 1. This con-
filter section) is called an antialiasing filter. figuration would then have what is known as a resolution of 10 m V, or 10 m V
per bit. The number of bits allocated to store each sample value is known as
Voltage Discretization (Signal Resolution) the bit-depth. There is a simple and fixed relationship between the maximum
voltage recordable (or the range), the bit-depth, and the resolution.
Digitization samples the voltage at a specific time and then converts the volt-
age into a digital value. The precision of this conversion is limited. For ex- Range
Resolution
ample, with an 8-bit digitizer, every sampled voltage is stored in 8 bits. With 2 bitdepth 1
8 bits, there are approximately 256 distinct possible values (28 = 256). This
would mean that the highest voltage could be stored as +127, while the most Figure 3.17 shows an illustrative example if a digitizer has a bit-depth of 5 bits,
negative voltage could be stored as −128 (when using two’s complement and the range was chosen to be 310 m V (minimum −160 to maximum +150 m V).
signed integer representation). Suppose +127 is chosen as the digital value For current commercial EEG equipment, a typical dynamic range is
to correspond to +1,270 m V. Then the digital value 0 would represent 0 m V, from +5 to −5 mV. Some early EEG digitizers had a bit-depth of 8, which
max +150 V time, and many are capable of being reconfigured—one can choose to digi-
tize 1 channel at an extremely fast sampling rate, or can choose to digitize
64 channels at a proportionately slower sampling rate. In general, the total
throughput (N channels × sampling rate) for a digitizer is limited. This is a
2N levels 32 levels
measure of the total capacity to digitize data for a given ADC device. For
further details on analog-to-digital conversion, the Amateur Radio Relay
League (5) handbooks are good guides.
Range 310 V
Resolution 10 V Ref+
Flash converter
R
−
min −160 V R +
Figure 3.17: Example of digitizer resolution. In this example, the bit-depth is 5,

−
giving 32 different digital values. If the maximum and minimum are chosen to be
+150 and −160 m V, then the range is 310 m V. The resolution is then 10 m V. R +
−
was nearly inadequate for EEG, giving resolutions of 4 m V. Modern EEG +
R
machines have a bit-depth of 16, which gives resolutions on the order of
5,000 2 (25,000)m V 10,000m V Vin 2N comparators Encoder N bits

16
5 5 0.153m V.
2 21 65535
Digitizer Electronics −
R +
There are several different electronic architectures for construction of
analog-to-digital converters (ADCs), which we shall cover only briefly
−
here, illustrated in Fig. 3.18. A standard design is the flash converter. This R +
architecture is rather easy to comprehend. A flash ADC uses N compara-
tors simultaneously to bracket the digital representation for a voltage. For −
a bit-depth of b, the number of comparators required is N = 2b. These flash R +
ADCs are quite fast, but because of the requirement for N high-quality
comparators, they are typically rather expensive. Two other common ar- A Ref−
chitectures for ADC are the successive approximation and the sigma-delta Figure 3.18: A–C: Three different kinds of ADCs.
architecture. These are less expensive than flash ADC, but are also typically A = Flash converter
somewhat slower. The successive approximation architecture basically uses B = Successive-Approximation Converter
one comparator, but N clock cycles to successively hone in on the voltage C = Sigma-Delta Converter
to be measured. In general, an ADC can operate on multiple channels at a (continued)
Successive-Approximation Converter sodium cations (Na+) and negatively charged chloride anions (Cl−). At elec-
trodes, these two different methods of carrying current must be converted.
Converted digits
Clock At the interface of the biologic system and the electrode, chemical reactions
Register occur, in which electrons are transferred. For example, for flow of negative
current from the biologic system to the electronic system, an electron could
DN−1 DN−2 D2 D1 D0 be transferred from a chloride anion to a platinum electrode. The chloride
anion would then become (briefly) a neutral chlorine radical, before partici-
pating in other chemical reactions.
DAC
The ease with which the charges are transferred from electrode to biologic
system and vice versa may be asymmetric: It may be much more chemically/
energetically easier for positive current to flow into the electrode than for it
Comparator to flow out of the electrode to the biologic system. In fact, this asymmetry
+ can be quantified by what is called the electrode potential. When the elec-
trode potential is large compared to the voltages of interest, the electrode
Vin S/H − interface is said to be polarizable. Electrodes where the asymmetry is small
B
are said to be nonpolarizable or reversible (6). The commonly used silver/
silver-chloride electrodes fall into the category of reversible electrodes. In
Sigma-Delta Converter this example, if the electrode becomes negative in potential, neutral AgCl
Integrator Comparator dissolves into Ag+ and Cl− and the Cl− passes into the biologic system.
Vin Silver/silver chloride electrodes may be fabricated by immersing silver wire
∑ in a solution of electrolyte containing chloride and placing a positive volt-
Digital Bitstream age across the electrode. Chloride ions migrate to the surface of the silver
filter
and impart a distinctive gray color. When a chloride-treated silver electrode
comes into contact with NaCl solution on the skin, currents of Cl− ions flow
freely between the electrode and the solution and prevent the electrode from
1-Bit becoming polarized. Polarization is avoided because the electrode and the
C DAC solution can communicate with ions (namely, Cl− ions from electrode and
Figure 3.18: (continued) electrolyte, respectively) that exhibit identical mobilities in solution. Silver
chloride electrodes are useful for recording DC and potentials of very low
frequency. Conversely, electrodes that are polarizable can be modeled as
EEG-specific acquisition having a capacitance, and act as highpass filters (attenuate low frequencies),
and are thus not well suited for DC or very low-frequency measurements.
Now armed with the basics of electricity and electrical engineering, we turn to Figure 3.19 shows this effect from several different metals used as electrodes.
the actual signal path of acquiring EEG recordings and the issues at each step. Large electrode resistances, greater than 5,000 Ω for skin electrodes or
15,000 Ω for needle electrodes, can result in noise artifacts in the EEG re-
Electrodes cording. This happens because strong electric fields present around the EEG
machine induce currents in the electrodes and cables. The currents are small
The charges that actually carry current in an electronic machine are simply but relatively fixed in magnitude, and flowing across the large electrode re-
electrons, flowing through metal conductors. In biologic systems, there are sistance generates large voltages. Because of a small area of contact with
no free electrons, but currents are carried by ions such as positively charged the subject, a needle electrode has high impedance and is more susceptible
by viscous gels, by mechanical restrictions (bands or rubber caps), or by

collodion. Collodion is a glue formulated from pyroxylin in ether, alcohol,
or camphor; it is liquid when applied, but it is able to dry to a strong adhe-
sive within minutes. It is suitable for patients who cannot keep still or who
need electrodes in place for more than a few hours. Ether is highly flam-
mable. Flames, excessive heat, or pure oxygen should not be near collodion
applications, and collodion should be used only in well-ventilated areas. It
must be remembered that collodion is not an adequate conductive medium:
Conductive gel must be injected into the cup electrodes and refreshed
periodically. A blunt needle is usually employed for this task. C
ollodion is
removed with acetone scrubs, and its application or removal always requires
a very well-ventilated room.
Common Types of Electrodes

Each of the commonly used electrodes has a simple design: a metal contact
surface, flexible and insulated wire, and a connecting pin to mate with the
headbox or jackbox of the EEG machine. Wires are usually color-coded for
Figure 3.19: Ability of various types of commonly used e
lectroencephalographic easy tracing during troubleshooting.
electrodes to reproduce a 10 mV, 10 mA square-wave input. (From Cooper R. Traditional scalp cup electrodes (Fig. 3.20A) are suitable for most routine
Electrodes. Am J EEG Technol 1963;3(4):91–101.) recordings and are usually of the reversible type. They are most often made
of chloride-treated silver cups 4 to 10 mm in diameter. Electrodes fabri-
to line (60 Hz) artifacts. In certain circumstances, the benefits of a needle cated from platinum, gold, or tin are sometimes used. Properly applied elec-
electrode may outweigh the drawback of high impedance. Electrode imped- trodes demonstrate resistances of a few hundred ohms. Resistances smaller
ances are tested after application by ohmmeters, sometimes integrated into than this usually indicate a short circuit in the electrode. According to the
clinical EEG stations. These devices pass a small current through the elec- international standards for the EEG, electrode resistances should be less
trode circuit and a remote reference (e.g., on the forehead or ear) attached to than 5,000 Ω and greater than 100 Ω. Positioning of scalp electrodes and
the patient. Voltage change is measured, and Ohm’s law is used to calculate methods for constructing montages of electrode pairs are considered else-
impedance. Impedance is frequency dependent, and the ohmmeter should where in this book.
therefore use frequencies in a range relevant to the EEG, such as 10 to 30 Hz. In recent years, prolonged EEG monitoring of patients in ICU settings
Before placing an electrode, the scalp must be prepared by being rubbed has brought new challenges and issues related to electrodes. These critically
vigorously with alcohol or with a skin preparation agent. This action re- ill patients may require frequent brain imaging, and so traditional metal cup
moves dirt and oil from the electrode site and lowers the impedance of the electrodes are disadvantageous because they cause artifact on X-ray-based
scalp-electrode junction. Obviously, excessive cleaning can be irritating to CT scans. Equally or more important, they are incompatible with MRI
the patient. Similarly, some patients are sensitive to paste containing salt because they cause artifact and may pose a hazard to patients from heat and
solutions or bentonite. Several varieties of electrode attachment media, in- electromagnetic induction effects. Recently, electrodes have been developed
cluding sodium chloride pastes or gels, conducting sponges, and other spe- that are MRI friendly (7). These electrodes are shaped like the metal cup
cialized electrolytes, are available to lower impedance at the electrode-tissue electrodes but the cup is formed from Teflon-coated plastic, which is then
interface. Scalp electrodes are usually cupped, with a hole at the peak, to plated with a thin layer of conductive silver. These have been shown to be
facilitate contact with electrode paste or gel. Electrodes may be held in place relatively safe with MRI, and cause less artifact on CTs.
(8) into the subdural space, ideally lying flat against the cortical surface.
The electrode contacts are typically circular disks with exposed surface of
roughly 2.3 to 5 mm in diameter.
Depth electrodes (see Fig. 3.20) are designed for introduction directly into
the substance of the brain by a neurosurgeon (also called “stereo EEG” in
some centers). Typically, depth electrodes consist of a plastic tube (diam-
eter approximately 1 mm) with a set of six or eight exposed metal cylinders
(the contacts), each about 2.3 mm in length, center spaced 5- or 10-mm
apart. These allow spatial sampling along the mesial and neocortical tem-
poral structures. Depth electrodes are usually implanted stereotactically
(according to a three-dimensional coordinate reference frame), although
some experienced neurosurgeons prefer to place the electrodes freehand or
with radiographic guidance, under sterile protocol. Orientation, targets, and
methods for implantation differ among institutions. Other chapters in this
text review various approaches. The amygdala, hippocampus, entorhinal or
orbitofrontal cortex, and supplementary motor areas of the frontal lobe are
popular targets for depth electrode placement.
Intracranial EEG recordings usually demonstrate excellent SNR, because
these electrodes have relatively low impedance, are relatively unaffected by
Figure 3.20: Photograph of commonly used electroencephalographic electrodes.
muscle and movement artifact, and bypass the high-resistance skull. Depth
A: Depth (intracranial) cylindrical electrode contacts on right, and guidewire ex-
tending from left, with multicontact connector. B: Scalp cup electrode set made of
EEG clearly increases the ability to detect and localize epileptiform activity
conductive plastic coated with silver/silver-chloride (“CT friendly”). C: Single scalp in selected patients (9), but it has disadvantages. First, not all brain sites can
cup electrode made of gold (with nontouch connector). D: Subdermal (scalp) be studied with this technique, and thus there is a possibility of sampling er-
stainless-steel needle electrode. E: Intracranial microelectrode array in plastic ror. Epileptiform activity originating in intracranial electrode only indicates
button. This particular array has 16 micro-contacts. These arrays can be used that the electrode is closer than the others to the epileptic network and not
alone, or inserted into a larger macro grid (Leuthardt Grid System). F: Intracranial necessarily that it is within the network (or “focus”). Second, the technique
subdural strip 1 × 6. G: Intracranial subdural grid 4 × 8, with four connectors of is invasive, with risks for hemorrhage, infection, reactive meningitis, edema,
eight contacts each. (Photo courtesy of Liberty Simmons, R.EEG.T.) and headache. Use of these electrodes should be restricted to experienced
centers.
Intracranial electrodes are typically subdivided into subdural and depth New Electrodes
electrodes. They are used to detect and localize brain activity not visible
with scalp EEG recording. Both typically use platinum or stainless steel, In recent years, a variety of new technologies for electrodes have been de-
since Chloride-treated silver can irritate brain tissue after direct contact for veloped for research purposes. The Utah Intracortical Electrode A rray
several days, and stainless steel and platinum are relatively inert and safe. (UIEA) (10) is one of the earlier types. This is a high-density array of
Intracranial electrodes may remain in place for days or weeks. microelectrodes. As shown in Fig. 3.21, it has a 10 by 10 array of needle
Subdural strips and grid electrodes (see Fig. 3.20) are flat rectangular ar- electrodes in a square with width 4.2 mm on a side, each electrode etched
rays of electrodes encased in plastic (silastic). These are placed by a neu- to project 1.2 mm, further etched to expose about 50 m m of conducting
rosurgeon via craniotomy (or craniectomy at some institutions, where the surface at the tips. The needles penetrate the pia mater into the upper layers
bone flap is stored away from the skull until implantation has concluded) of the cortex. This electrode array was developed for use in brain-computer
Figure 3.21: Utah Intracortical Electrode Array, UIEA. (Photo courtesy of Richard
A Normann, University of Utah.)
Figure 3.22: High-resolution, flexible, active electrode array with 360 ampli-
fied and multiplexed electrodes. Only 39 wires are needed to sample from all
interface (BCI) systems, with the intent to be able to isolate and measure of the 360 electrodes simultaneously. The electrode array is ultrathin and flex-
single units or small groups of multi-unit potentials. However, the penetrat- ible, allowing close contact with the brain and high-resolution recordings of sei-
ing electrode arrays are reported to cause gliosis and may lose function zures. (Photo courtesy of Travis Ross and Yun Soung Kim, University of Illinois at
after 6 to 12 months. Urbana-Champaign.)
Recently, another microelectrode array was developed that is nonpenetrat-
ing and flexible/foldable (11). Shown in Fig. 3.22, it is constructed on a plas-
tic (polyimide) base, with active electronics (multiplexing and amplification significant noise. For example, several clinical EEG vendors quote input im-
transistors) also on the array itself. It is hoped that these nonpenetrating pedances of more than 100 MΩ, and CMRR of more than 80 dB.
arrays will avoid the disadvantage of gliosis, as well as possibly permitting
even longer functioning. Microelectrode arrays such as these hold great in- Antialiasing Filter
terest for studying epileptic seizure evolution on the scale of multi-unit net-
works, and while these are being used in BCI research on human subjects Crucially, just before the digitizer step, an analog antialiasing filter must be
(12), use in clinical EEG is not yet mainstream. inserted. The filter should eliminate the frequency components above the
Nyquist. Typically, the cutoff frequency is chosen to be lower than the Ny-
Preamplifiers quist to ensure that adequate attenuation is achieved. The American Clinical
Neurophysiology Society (ACNS) 2006 guideline 8 (13) recommends that
The electrodes are typically next connected to amplifiers. These first ampli- digitization “should occur at a minimum sampling rate three times the high-
fiers should be well-designed: to have high input impedance, to be accu- frequency filter setting, e.g., 100 samples/s for 35-Hz high filter.” (This cor-
rate differential amplifiers (high CMRR), and to amplify without adding responds to an antialiasing filter cutoff at 66% of the Nyquist frequency.)
Digitizer filter would pass low frequencies and attenuate high-frequency compo-
nents. There are digital filtering techniques that are modeled after analog
Typical clinical EEG acquisition stations have a bit-depth of at least 16 bits, RC filters, but there are many digital techniques that have no such analog
and input ranges of ±5 mV, thus yielding resolution of 0.153 m V. counterparts.
The ACNS 2006 guideline recommends “at least 11 bits” and a resolution
of “0.5 m V.” Finite Impulse Response Filtering
EEG equipment vendors provide equipment with sampling rates of
512 samples per second on 64 or more channels. Some can reach sample Consider a simple operation on a sequence of digital samples: for each input
rates of 1,024 samples per second though often with reduced number of point x[n], replace it with the average of itself and the just prior sampled
channels, such as 32. Intracranial recordings with grids and strips can easily value x[n − 1], yielding the new output y[n]. This is called the “two-point
reach 128 electrodes or more. Some research equipment packages are able to moving average”:
1 1
sample at rates of up to 32 kHz on 128 channels simultaneously. y[ n ] x[ n ] x[ n − 1]
2 2
Digital Transfer/Storage If the sampled sequence is constant—unchanging—then the averaged
sequence is identical to the original. If, however, the original sampled sequence
The carefully acquired digitized samples are then transferred to digital is a sinusoid at the Nyquist frequency (e.g., +100, −100, +100, …), then the
computers and stored in a fixed format. Many vendors have proprietary new averaged sequence is uniformly zero. It should not be a surprise that this
formats, though the open published standard of EDF/EDF+ (14) is grow- averaging operation acts as to smooth the sequence, attenuating high fre-
ing in support. File sizes of EEG records can be easily calculated with the quencies, and is thus a lowpass filter. The two-point moving average is one of
knowledge of the bit-depth, number of channels, and sample rates. For ex- the simplest finite impulse response (FIR) filters. The general feature is that
ample, 40 minutes of 32 channels sampled at 512 Hz with a bit-depth of 16 an FIR filter acts only on current and prior samples in the original sequence.
will be 2 bytes × 512 samples per second × 32 channels × 40 minutes × Incorporating a greater number of past samples (higher order) can be used
60 seconds = 78,643,200 bytes, or about 80 MegaBytes (MB). Video record- to create a lowpass filter that has a sharper cutoff (see chapter appendix).
ing will typically require much more storage, even with modern video codecs
(coding/decoding) such as H.264. With higher-resolution devices and higher Infinite Impulse Response Filtering
sample rates, other data formats employing lossless compression on the fly
to a fraction of EDF, such as MEF (approximately 90% compression com- Next consider a filter in which each point is replaced by half of the current
pared to EDF) may be required (15). input plus half of the last output.
1 1
Digital Processing y[ n ] x[ n ] y[ n − 1]
2 2
The raw data of each digitized channel can then be recovered exactly, and This filter will also act to generate a smoother version of the input sequence.
displayed at any later time. It can also be algorithmically processed—for However, this filter differs from the two-point moving average in the way
instance to search for possible epileptiform discharges (“spikes”) (16) that it responds to sharp transients. For a single sample point that is an
or analyzed for trends in alpha power (17). Simple conventional display extreme outlier, the two-point moving average will only show the effect of
of EEG tracings on computer screens requires some rudimentary digital this outlier on two points in the output—the output point y[n] and the next
processing—digital filtering. (See the chapter appendix for a fuller discus- output point y[n + 1]. However, this filter will continue to have its output
sion of digital filtering.) reflect the transient since it has feedback —the last output is added into the
The aims of digital filtering are, like analog filtering, to attenuate certain current output. The transient (impulse) will form part of the response for
components in the signal based on the frequency—for example, lowpass infinite future points, and infinite impulse response (IIR).
FIR versus IIR 0.1 Hz

1
Both FIR and IIR filters can be designed for lowpass, highpass, bandpass, 1 Hz
and notch (bandstop) filters. There is no simple reason to claim that FIR or
IIR is better. In general, FIR filters require much higher order (more com- 10 Hz
putations) to achieve similar “sharpness,” but have the advantage of linear 0.707
phase alteration and consequently constant group delay (waveforms may be
delayed, but will have similar shape). IIR filters that are “sharp” can be con-
structed with lower order (and faster computation time), but have nonlinear
phase distortion and frequency-dependent group delay (i.e., they may alter
the phase and the shape of waveforms, with distortion roughly commensu-
rate with the order of the filter). Despite many claims that FIR filters with
linear phase are “better,” it can be pointed out that many experts routinely
use IIR filters. For instance, in the widely used Matlab suite, the important
digital signal processing function decimate() requires a lowpass filter, and
currently the default filter type is an IIR Chebyshev filter, and in the past
was an IIR Butterworth filter.
0
If the entire sequence to be filtered is available; phase distortion and 0 10 128
group delay can be eliminated from both FIR and IIR filters—through the Frequency (Hz)
technique of forward-backward filtering. In this method, forward (conven- Figure 3.23: Digital highpass filter transfer functions for different cutoff frequencies,
tional) filtering with an IIR or FIR results in the expected phase alteration with a sample rate of 256 Hz (Nyquist of 128 Hz). These are plotted as linear-linear
and group delay. These effects are then neatly reversed by then running the graphs, since these are for digital time-domain filters. Note there is some attenua-
same filter backward over the signal produced by forward filtering, yielding tion above the cutoff frequencies, and incomplete attenuation below the cutoffs.
zero-phase distortion and no group delay.
If it is desired to emulate a traditional analog filter, it is possible to con- revealed to not be ideal. The amplitude of components at the cutoff fre-
struct an IIR filter that fairly closely mimics the result (using the matched- quency is shown to be about 70% (30% reduced). That is, at the cutoff, there
Z-transform or impulse invariance techniques). See the chapter appendix for is still a significant amount of amplitude allowed, there is a still a slight
details. reduction at frequencies even above the cutoff, and frequencies below the
cutoff still have nonnegligible amplitude contribution. Figure 3.24 shows a
Filtering Examples practical example of the effect of highpass filters on the traditional calibra-
tion signal. Note the connection between the specified cutoff frequency, the
Most EEG reading software includes digital filters for highpass (the most time constant, and the length of time for the exponentials to decay toward
typical use is to flatten a wavering baseline), lowpass (to attenuate muscle the baseline. In particular, with the cutoff of 1 Hz, in three time-constants
artifact), and notch (tuned to eliminate 60 Hz or 50 Hz, depending on local (0.16 second × 3 approximately 0.5 second), the square wave nearly decays
powerline frequency). to the baseline, nicely fitting with the exponential decay curve in the ana-
As one example, consider the digital highpass filter. The cutoff frequency log section of this chapter. Finally, Fig. 3.25 shows the effect of highpass
can usually be selected by the software user. The effect of a highpass filter filters of different cutoffs on an actual EEG. With an inadequate highpass
on components as a function of frequency is shown in Fig. 3.23, for sev- filter (0.2 Hz), the baseline is seen to waver. With the cutoff set at 1 Hz, the
eral different cutoff frequencies: 0.1, 1, and 10 Hz. As can be seen, all three baseline is improved and the focal slowing of the left temporal region is
eliminate true zero frequency components (DC). However, these filters are quite apparent. However, at too high of a cutoff, the focal delta slowing is
calib (50 µV, 0.5 s)
0.01 Hz / 16 s
0.1 Hz / 1.6 s
0.3 Hz / 0.53 s
1 Hz / 0.16 s
3 Hz / 0.05 s
Figure 3.24: Effect of digital highpass filters of different cutoffs on the

traditional calibration signal. The cutoff frequency and the time constant
10 Hz / 0.016 s for each filter are indicated. Note closely: for the filter with time-constant
0.16 seconds, after three time-constants (0.5 sec), the signal has nearly
decayed to baseline.
misleadingly reduced. The wise electroencephalographer should always be Electrical Safety

careful about the settings of the digital filters.
EEG is an extremely safe procedure, but a small possibility of injury does
Display Considerations exist. It is imperative that the technologist and electroencephalographer un-
derstand how to minimize this risk. Current is the most important predic-
A final engineering consideration that impacts the clinical interpretation of tor of electrical injury. It can cause pain and burns if applied to the skin
the EEG centers on the specifications and limitations of the final display. (Table 3.2). Seizures can result from certain types of current applied di-
Traditionally, electroencephalographers have expected to be presented with rectly to the brain or to the scalp. Current can electroplate irritating met-
10 seconds of EEG in one “page” (30 cm). However, with modern digital als from intracranial electrodes into brain tissue. Current can even kill, by
sampling rates, there are more sample points than can be presented with cur- inducing ventricular fibrillation. Injury risk can be discussed in terms of
rent pixel resolutions. Consider: with a sampling rate of 512 Hz, 10 seconds three groups with different types of relationships to EEG equipment. The
of EEG contains over 5,120 individually sampled points. Current main- safest group comprises persons who are simply near and possibly touching
stream LCD displays have between 1,280 and 1,920 horizontal pixels. That an electrical device but not intentionally connected to it. The second group
is, there are at least 2 time points and up to 4 or 5 points per horizontal comprises people with electrodes attached to skin, in the absence of other
pixels. This leads to inability to present all the sample points at one time. medical instrumentation. The third group contains patients at higher risk,
Low-frequency activity is not much affected, but the problem becomes very such as neonates and patients with intravascular catheters or other medical
apparent for higher frequencies, as shown in Fig. 3.26. instrumentation.
Fp1 - F7 Fp1 - F7
F7 - T3 F7 - T3
T3 - T5 T3 - T5
T5 - O1 T5 - O1
Fp2 - F8 Fp2 - F8
F8 - T4 F8 - T4
T4 - T6 T4 - T6
T6 - O2 T6 - O2
Fp1 - F3 Fp1 - F3
F3 - C3 F3 - C3
C3 - P3 C3 - P3
P3 - O1 P3 - O1
Fp2 - F4 Fp2 - F4
F4 - C4 F4 - C4
C4 - P4 C4 - P4
P4 - O2 P4 - O2
Fz - Cz Fz - Cz
Cz - Pz Cz - Pz
LOC LOC
ROC ROC
EKG EKG
A B
Figure 3.25: Effect of digital highpass filters at different cutoffs on actual EEG with focal slowing.
A = highpass at 0.2 Hz, B = highpass at 1 Hz, C = highpass at 5 Hz.
There are several potential sources of dangerous currents that may flow and some current might flow through the patient even if the proper safety
through patients connected to EEG machines and cause them harm. These mechanisms were intact during a short circuit. If the machine ground con-
sources are described as follows. tact is not intact, substantial current (possibly life-threatening) may pass
through the patient.
Improper Grounding EEG machines should never be powered by an inadequately grounded
circuit: Three-prong to two-prong adapters must not be used. Machines
Improper grounding can result from a disruption of the ground circuit in- must always be protected with regulation fuses. Fuses must not be defeated:
side the EEG machine or from the use of a two-prong socket. The cylin- There is always a reason when a fuse stops working, and it is important to
drical contact (green wire) on the three-prong plug is the ground contact. discover that reason rather than subject the patient to an electrical hazard.
Should a short circuit occur in the machine and a current-bearing element Hospital-grade power outlets should be used whenever possible for EEG
make contact with the chassis of the machine, this current should immedi- machines (or for any other machines that are to be connected to patients).
ately be shunted to the ground contact, because this is the path of lowest These outlets are labeled with a green dot and indicate a higher standard
resistance. This would quickly blow a fuse or circuit breaker in the EEG ma- of safety and quality of construction than do other outlets (18). A sched-
chine, which would sense the abnormally high current flow through the now ule of preventive maintenance on the EEG machine and outlets should be
very low resistance of the short circuit. This would not happen immediately, enacted.
Fp1 - F7 a few microamperes. Nevertheless, if applied directly to the heart, 0.1 mA

F7 - T3 could cause ventricular fibrillation.
T3 - T5 Each wire carrying current to and through the EEG machine induces a
T5 - O1 magnetic field that, in turn, creates currents in other wires, including neutral
Fp2 - F8 and ground wires. These currents are usually shunted directly to the ground
F8 - T4 contact, but, again, they may be conducted through the patient should some
T4 - T6
ground malfunction (ground fault) occur. Stray inductances generally are of
T6 - O2
less magnitude than stray capacitances.
According to Hill and Dolan, cited in Cooper et al. (19), maximum leak-
Fp1 - F3
age currents allowed for the three groups defined earlier are 500 m A for those
F3 - C3
having casual contact with a medical device; 100 m A for those connected to
C3 - P3
electrical devices; and 10 m A for the group at high risk.
P3 - O1
Fp2 - F4
Double-Grounding
F4 - C4
C4 - P4 If a patient is connected to an EEG machine and to another electrical
P4 - O2 instrument, there is probably more than one ground connection. This cre-
Fz - Cz ates a situation referred to as double-grounding or a ground loop. Because
Cz - Pz no two ground connections are at identical potential, current may flow from
LOC one ground connection to the other through the patient. Figure 3.27 shows a
ROC simplified circuit diagram illustrating the problem. There are several poten-
EKG tial sources of ground-loop currents. Short circuits in the machine or other
C
circuit faults can deliver massive current to a ground loop. Less dangerous
Figure 3.25: (continued) but more common are currents in the ground circuit as a result of stray ca-
pacitance and stray inductance. Additional currents may be induced in the
Leakage Currents ground wires by nearby magnetic fields. In this case, the induced potentials
in question are small, but the resistances of the ground paths are also small.
Leakage currents arise from two main sources: stray capacitance and stray Large currents could flow from one ground circuit to another through the
inductance. Stray capacitance usually arises from wires connected to a wall patient.
socket or to the EEG machine power supply. Capacitance is a function of Double-grounding is of particular concern in areas where patients are
the construction of the power cords and of their length. Nearby wires in connected to multiple devices, such as intensive care units and operating
a power cord are insulated from each other and therefore can function as rooms. It is not unusual to observe patients connected to EEG machines,
a capacitor. AC current flows through the “hot” (black) wire in the cord electrocardiographic monitors, temperature monitors, electric blood pres-
and induces small capacitive currents in the neutral (white) and ground sure cuffs, ventilators, pulse oximeters, warming or cooling blankets, electric
(green) wires as they alternately charge and discharge with the AC cur- beds, arterial and venous catheters, intracranial pressure monitors, and a
rent. This leakage current is usually shunted directly to the ground contact; variety of other hardware. In such circumstances, the presence of a ground
however, if the ground connection is not properly made, this current may loop is virtually guaranteed. The solution is to connect all devices attached
flow through the patient. Extension cords should not be used with EEG to the patient to a common ground connection plugged into the same wall
machines, because they increase the capacitive current to a potentially dan- outlet. If necessary, a grounding bar can be used to “gang” together the vari-
gerous amount. Because wires are inefficient capacitors, capacitive currents ous ground connections. This provides only one low-resistance ground path
from an EEG machine are generally far less than 0.1 mA and may be only (not through the patient) for stray currents.
Figure 3.26: Diagram illustrating the issues related to digital sampling rates in excess
of visual display resolution. The upper half shows sine waves at escalating frequencies.
The lower half shows how these sine waves may be displayed on a computer monitor
with the indicated pixel sizes, where there are two digital time steps per horizontal
pixel. Note that the higher-frequency activity is blurred, and one is unable to deter-
mine the actual frequency of activity.
Table 3.2 Estimated Effects of 60-Hz Current on Skin/Externally of multiple ground connections, in addition to being a requirement for pa-
tient safety, improves recording quality.
15/20 A Common fuse or breaker opens circuit In high-risk circumstances, such as when patients have intravenous cath-
2A Cardiac standstill and internal organ damage eters, special equipment with “isolated grounds” should be employed. These
boxes use optical isolation or solid-state variable resistors to separate the
100 mA Ventricular fibrillation threshold
patient from any currents generated in the EEG machine (18).
20 mA Paralysis of respiratory muscles
16 mA Maximum current an average man can grasp and “let go” Exacerbating Factors
1 mA Barely perceptible
Predicting the consequences of an electric shock is difficult, because several
0.1 to 0.03 mA from internal/intracardiac catheters have been reported to cause ventricu-
factors influence the biological response. In the clinical setting, the most
lar fibrillation and death (see, e.g., Weinberg et al. [24].)
important factor is instrumentation. A transvenous pacemaker or a central
Adapted from National Institute for Occupational Safety and Health. Worker deaths by
electrocution: a summary of NIOSH surveillance and investigative findings. Cincinnati,
venous pressure catheter provides a low-resistance route for stray currents
OH: National Institute for Occupational Safety and Health, May 1998. to travel directly to the heart. Ventricular fibrillation can result from cur-
rents that would not even be perceived through intact skin. Skin wounds or
The EEG technologist must remember the principle of single-grounding excessive abrasion with cleaning paste may increase the risk for injury by a
when an accessory ground connection is necessary to eliminate 60-Hz inter- given current at those sites. Good general health may be a factor in resist-
ference. All ground connections should travel to one point. If the patient is ing effects of electric shock, but many hospitalized patients are ill. Table 3.3
already grounded by another device, it is not necessary (and is potentially summarizes important safety rules in EEG recording.
dangerous) to attach another ground connection to the patient. Avoidance
Regulations
Engineering principles for the construction of medical equipment can
+V +V
be found in other texts (20). Standards for the construction and de-
sign of electrical equipment have been published by the International
Electrotechnical Commission (IEC). In particular, IEC 60601 is a series
of technical standards for the safety and effectiveness of medical electri-
cal equipment. B esides the general requirements for all medical equip-
ment, specific standards for EEG equipment are published under IEC
60601-2-26 (“Particular safety of electroencephalographs equipment”).
Safe Unsafe! A short checklist of rules to follow to ensure electrical safety during EEG
Figure 3.27: Diagram of the potential problems from a “ground loop.” On the is shown in Table 3.3.
left, if a ground electrode is applied on a patient, and connected to the “ground”
of a device, but by poor design or malfunction, this device ground is inadver- Table 3.3 Safety Rules for Performing Electroencephalography (EEG)
tently at an electric potential different from actual earth ground, the patient is
still safe since there is no conductive path from patient to earth ground. On the Maintain machinery to avoid faulty circuits
right, if more than one device ground is connected to the patient, but any of
Always use a grounded (three-prong) plug to power
these device grounds have an electric potential, there is now the possibility that
current through the patient can complete the “loop.” If there are electrodes in- Properly fuse the EEG machine
side the patient (intracardiac electrodes), even a small potential difference may Use one ground connection to patient or ground to a common point
be enough to generate a current of 50 to 100 m A, which could cause ventricular
Use machines with isolated-ground in high-risk situations
fibrillation (microshock).
CONCLUSIONS The authors are greatly indebted to Robert Fisher, MD, PhD, for his
wonderful and witty input to this chapter in prior editions. The thoughts
Electrical engineering is a vast field, but having a basic understanding of expressed in this chapter reflect past experiences and continued learning with
the principles is important for all clinical electroencephalographers, so that many wonderful electroencephalographers throughout training and practice,
they may understand the factors required for faithful recording of cerebral such as Alan Krumholz, Peter Kaplan, Tom Henry, Chip Epstein, Jacqueline
activity, be able to detect and correct sources of artifact, and importantly, French, John Ebersole, Bob Webber, and others too many to be named.
supervise the proper and safe use of these electrical machines to avoid harm Finally, a large measure of gratitude is due Ernst Niedermeyer for pro-
to patients, technologists, and themselves. viding teaching and mentoring over the years about the importance of a
New developments are being made to acquire more detail both spatially meticulously recorded and judiciously interpreted EEG. His memory lives
(with smaller electrodes trying to pinpoint seizure onset) and in frequency on through his many students and their intellectual offspring who populate
(much higher sampling rates). These are exciting times to expand and ex- this exciting, thriving field.
plore the technology underlying EEG.
Acknowledgments
The authors greatly appreciate Liberty Simmons, R.EEG.T for providing
the photographs of common clinical electrodes, and constructive comments
on the text from the wisdom of a superlative technologist.
Appendix
There are many textbook references for digital filtering—one that covers In this instance, the current output is formed from one-quarter of the cur-
many concepts in great detail is Discrete-Time Signal Processing by Op- rent input plus three-quarters of the prior output.
penheim et al. (4). In general, any formula that includes any of the last M inputs or prior
In general, the framework for discrete or digital signal processing operates outputs can be written as
on an input sequence, x, denoted: M M
y[ n ] ∑ bk x[ n − k ] ∑ ak y[ n k ]
(x0, x1, x2, …) = x[n] k0 k1
Digital filtering is the mathematical conversion of the input x[n] into an-
This is, in general, called a linear constant coefficient difference (LCCD)
other new or output ordered sequence y[n] using some formula.
equation. The filter defined by this is said to be of order M. Our two-point
In the traditional digital filtering convention, the formula for conversion
moving average would be of order 1, and b0 = b1 = 1/2, and ak are zero
uses constant coefficients (the coefficients do not change throughout the
(nonexistent). In general, if only coefficients bk exist (no ak coefficients),
sequence). The formula can use the current input point and previous inputs,
then the filter is a finite impulse response (FIR) filter. If any coefficients
as well as previous outputs.
ak are nonzero, it is an infinite impulse response (IIR) filter. (Note that by
As the simplest example, consider the formula: y[n] = 2·x[n]. That is, the
necessity a0 is always 1, since it is the necessary coefficient of y[n] on the left
output is proportional to the input sequence but each value is doubled, akin
side of the equation.)
to amplifying the input.
The frequency response of such a filter is simple in form. The transfer
For the next simple example, consider
function shows the magnitude of the ratio of the output relative to the input
y [ n ] 1 x [ n ] 1 x [ n 1] amplitude as a function of frequency.
2 2
M
With this formula, the output is the average of the current input and the ∑b e k
k j 2p f
prior input. This will tend to produce a smoother version of the sequence. H( f ) k0
M
In digital filtering terms, the high-frequency components are attenuated, but ∑a e k
k j 2p f
the low-frequency components are preserved, so it is a lowpass filter. The ef- k0
fect of this filter as a function of the frequencies components of the original For example, for our two-point moving average:
input can be plotted as in Fig. 3.28.
1 1 j 2p f
Next consider a formula where the output depends on the current input H( f ) e
and prior outputs: 2 2
1 3 A computer plotting program can verify that this formula gives the graph
y[ n ] x[ n ] y[ n 1]
4 4 in Fig. 3.28.
71
1 filter. When an instantaneous step in voltage is applied to this filter, the volt-
Magnitude age across the resistor will follow:
t

τ
Vr e
We now try to emulate this with a digital process. Consider that, given the
0.5 voltage at some time t0, then the voltage at a later time t1 = t0 + tk is then
t1 tk t0
− − −
τ τ τ
Ve e e
In fact, for a digital time-step of tk, this holds no matter what initial time, t0.
This could be viewed analogously in the discrete time formalism as
0
0 Frequency 0.5  tk 
y[ n ]  e τ   y [n21]
 
This could be modeled as
0 0°
tk
−
Phase a1 e τ e− t ⋅2p fcut k
For instance, for a sampling rate of 256 samples per second, for a highpass
filter with a cutoff frequency of 1 Hz, we would calculate that
− /4 −45°
a1 e− t k ⋅2p fcut e− 2p /256 e−0.0245 0.97575
If one uses Matlab or Octave to generate a first-order highpass IIR (Butter-
worth form) filter (these use the convention of scaling frequency so that the
Nyquist frequency is 1.0, so the denominator is 128 instead of 256):
− /2 −90°
0 Frequency 0.5 [b, a] 5 butter (1,1.0 / 128.0,‘high’)
Figure 3.28: Graphs showing the effect of the two-point moving average digital b 5 0.9878820.98788
filter on the frequency components, in the magnitude of the contributions to a 5 1.0000020.97575
the output and the effect on the phase in the output, as a function of frequency
(frequency of 0.5 corresponds to the Nyquist frequency, for any chosen sampling We have thus demonstrated how the software arrives at the coefficient for a1.
rate). The two-point moving average preserves low frequencies and attenuates (The b coefficients are constructed for normalization reasons.) The transfer
high frequencies, and has a linear alteration of phase. function for this digital IIR highpass filter is shown in Fig. 3.29.
Now let us consider how to construct a lowpass filter from the analog
electrical RC model. If we choose a cutoff frequency of 32 Hz, with a sam-
pling rate of 256 samples per second, and use the technique of “impulse
IIR Filter Theory and Construction invariance”—effectively trying to mimic the impulse function that would be
seen in the analog electrical model—we obtain
For examples of how to construct IIR filters, let us now consider the simple
analog electrical filter composed of an RC circuit arranged as a highpass a1et k 2p f cut e0.7854 0.45594
1 1
0.707
0
0 Frequency 0.5
Figure 3.30: Solid line shows the transfer function for a digital first-order IIR
0 lowpass filter with a cutoff frequency of 32 Hz and a sampling rate of 256 samples
1 Frequency (Hz) 128
per second, which was constructed using the impulse invariance method. The
Figure 3.29: The transfer function for the first-order digital IIR highpass filter with dashed line shows the effective transfer function for an analog RC lowpass filter
coefficient a1 = −0.975755. with the same cutoff.
To normalize so that the transfer function is 1.0 at zero frequency (DC): FIR Filter Theory and Construction
b0 (1 a1 ) 0.54406 Now we return to FIR filters. Conceptually, the ideal lowpass filter is il-
lustrated in Fig. 3.31. The ideal filter is sometimes called the “brick-wall”
The transfer function for this lowpass filter is shown as the solid line, filter. The brick-wall is an idealization in the frequency domain. Digital fil-
with corresponding analog electrical RC filter transfer function as ters operate in the time domain. It is instructive to consider what the form
dashed line in Fig. 3.30. This can be seen to act as a lowpass filter, and of the ideal brick-wall filter would be in the time domain. The (Inverse)
while it fairly closely mimics the RC filter, both can be seen to pass sig- Fourier Transform of the frequency-domain brick wall becomes, in the time
nificant amounts of power at the Nyquist frequency. To completely at- domain, the sinc function:
tenuate frequencies at the Nyquist, another technique called the bilinear
transform (BLT) may be used for the construction of IIR filters. This sin(t )
sinc(t ) ≡
technique essentially warps the entire analog frequency range so that the t
digital Nyquist is equivalent to infinite analog frequency, and a lowpass The sinc function is illustrated in Fig. 3.32. Examining it closely, we see that it
filter can result in complete attenuation at the Nyquist frequency. De- extends infinitely in both time directions. This would imply that to create the
tails of the differences between the methods of impulse invariance (II), brick-wall filter, we would have to be able to apply this filter to future points in
matched-Z-transform (MZT), and BLT may be found in digital signal the sequence. This could not be done if we wished to filter in real-time, that is,
processing textbooks. apply the filter to the sequence point-by-point as it enters the digitizer buffer.
“Pass” (low frequencies) This would be known as an acausal filter. We also note that the sinc function
1
does not become absolutely zero at any specific point away from time 0. A true
brick-wall filter would require filtering all points of the sequence.
In order to implement the brick-wall filter with a finite and causal filter,
we truncate the sinc function and shift it back. Importantly, this shift causes
a group delay in the filter of half the order of the filter. As the order of
the filter grows large, this delay can become quite significant. Typically, the
order (M) of the filter is chosen to be even, leading to an odd number of
coefficients (M + 1). In Fig. 3.33, we show the effect of truncation, with an
“Cut” (high frequencies)

0
0 0.2 Frequency 0.5
Figure 3.31: The ideal lowpass filter, sometimes called a “brick-wall” filter. In the
perfect case, this filter perfectly passes all frequency components below the cut-
off (here chosen to be 20% of the sample rate or 40% of the Nyquist frequency),
and perfectly eliminates all frequency components above the cutoff.
0
–20 –12 −4 4 12 20
1
Time
0
0.1 0.2 0.3 0.4 Nyquist
−16 −12 −8 −4 0 4 8 12 16 Frequency
Figure 3.32: The sinc function, which is the (Inverse) Fourier Transform of the Figure 3.33: A truncated sinc function (FIR with order 32) and its transfer function
“brick-wall” filter. in the frequency domain. Note the ripple in both the passband and the stopband.
1 1
Hann
−20 −12 −4 4 12 20
Time
0
0 N-1
1
Figure 3.34: The Hann windowing function. By formula: 0.5 − 0.5 cos[2pn/(N − 1)]
order M = 32 filter with a cutoff frequency at 40% of the Nyquist. Note the
significant amount of ripple in both the passband and the stopband. For the
most part, the ripple (in frequency domain) is a consequence of the abrupt
truncation. Higher order can be used to reduce the ripple in the frequency
domain, but this is a trade-off (A) in computational time and (B) more pro-
longed ringing in the time domain when transients (impulses) are encoun-
0
tered. One technique for reducing the frequency-domain ripple is to apply 0.1 0.2 0.3 0.4 Nyquist
a window to the sinc function, where the window is nearly 1 in the middle, Frequency
and tails to 0 on either side. There have been many windowing functions
developed in engineering. One of the simplest windows in the Hann window Figure 3.35: The FIR filter with Hann windowing function. In the top panel, the
is shown in Fig. 3.34. Applying the Hann window to our truncated, order truncated sinc function of Fig. 3.33 has been multiplied by the Hann window
of Fig. 3.34. The corresponding transfer function for this windowed FIR filter is
32 filter is shown in Fig. 3.35. As you can see, the Hann window smoothing
shown in the bottom panel. Note the reduction in the ripple, but also the slower
has resulted in less ripple in both the passband and the stopband, at the cost roll-off in the transition band.
of a slower roll-off. There are a multitude of more complicated techniques
to determine the coefficients for FIR filters. Some are straightforward, while
other more complicated methods require algorithms to repeatedly adjust
coefficients until some criterion is reached. As one example, the method of Digital Filters in EEG
Parks-McClellan (21) iteratively adjusts the coefficients until the transfer
function meets certain criteria, such as maximum allowed ripple and transi- The actual details of the digital filters used in major commercial EEG ven-
tion bandwidth. Further details of FIR filter design may be found in digital dors’ software are not immediately apparent. Most contain highpass, low-
filtering textbooks. pass, and notch filters, and have settings to select the cutoff frequencies.
However, the cutoffs are typically only allowed to be in a preselected set of namely, highpass cutoff of 1.6 Hz and lowpass cutoff of 70 Hz, and sen-
frequencies—for example, 0.1, 0.5, 1.0, 1.6 Hz. The type of filter (IIR or sitivity of 7 m V per mm. All show that the square waves decay to baseline
FIR) is not typically named or described. With careful inspection of known due to the highpass filters eliminating zero frequency (DC). The decay is
and well-described signal sequences, some inferences can be made about the monotonically exponential in both Fig. 3.36A and B, and nearly identical.
most typical types of filters. Figure 3.36 shows screen captures of calibra- One of these is known to be an IIR filter of first-order, and it can be inferred
tion signals viewed with three different software viewers (A, B, and C). The that the other is as well. (An FIR filter to generate a similar monotonic expo-
calibration signal is a square-wave with 1 second per phase, and amplitude nential decay would require an extremely high order, which is impractical.)
of ±25 m V. For all of the viewers, the filters were selected to be the same, However, in Fig. 3.36C, the decay has an overshoot (below and beyond the
A
C
Figure 3.36: Screen captures of a calibration signal viewed with three differ-
ent software viewers, with the same ostensible filter settings (highpass cutoff of
1.6 Hz; lowpass cutoff of 70 Hz), illustrating that these viewers use different kinds
of digital filters. The calibration signal is a square wave of 1 second per phase,
±25 m V. The tracings show that after filtering, (A) and (B) are essentially identi-
cal (with (B) known to use a highpass first-order IIR filter), while in (C) the square
waves decay toward baseline similarly, but have overshoot, and thus likely use a
B second-order IIR filter for the highpass filter.
baseline), and from this it can be inferred that the highpass filter in this case 6. Cooper R. Electrodes. Am J EEG Technol 1963;3:91–101.
7. Mirsattari SM, Lee DH, Jones D, et al. MRI compatible EEG electrode system for routine use
is probably IIR of higher order (likely second-order). in the epilepsy monitoring unit and intensive care unit. Clin Neurophysiol 2004;115:2175–2180.
While most EEG viewing software hides the implementation details and 8. Wyler AR, Ojemann GA, Lettich E, et al. Subdural strip electrodes for localizing epilep-
has little documentation of the digital filter details, there is one major com- togenic foci. J Neurosurg 1984;60:1195–1200.
9. Spencer SS, Spencer DD, Williamson PD, et al. The localizing value of depth electroen-
mercial vendor that has settings to change the filter types. The permitted cephalography in 32 patients with refractory epilepsy. Ann Neurol 1982;12:248–253.
types are IIR filters, FIR of Chebyshev type, and the obscurely termed 10. Maynard EM, Nordhausen CT, Normann RA. The Utah Intracortical Electrode Array:
Walraven FIR. This filter is based on the publication of an algorithm (in a recording structure for potential brain-computer interfaces. Electroencephalogr Clin
Neurophysiol 1997;102:228–239.
FORTRAN source code) for an FIR filter in a computer society magazine 11. Viventi JA, Kim DH, Vigeland L, et al. Flexible, foldable, actively multiplexed, high-density
from the 1980s (22). This is, in turn, an implementation of a filter design electrode array for mapping brain activity in vivo. Nat Neurosci 2011;14(12):1599–1605.
technique published in 1974 by J. Kaiser, a Bell Labs researcher (23). In this 12. Donoghue J. Connecting cortex to machines: recent advances in brain interfaces. Nat
Neurosci 2002;5(Suppl):1085–1088.
algorithm, the user essentially selects a cutoff frequency and a maximum 13. American Clinical Neurophysiology Society Guideline 8: guidelines for recording clinical
permitted ripple, and the algorithm estimates the required order of the FIR EEG on digital media. J Clin Neurophysiol 2006;23(2):122–124.
filter, and some parameters of the window function. This is an example of 14. Kemp B, Olivan J. European Data Format ‘plus’ (EDF+), an EDF alike standard format
for the exchange of physiological data. Clin Neurophysiol 2003;114:1755–1761.
software permitting some additional control over the filter configuration, 15. Brinkmann BH, Bower MR, Stengel KA, et al. Large-scale electrophysiology: acqui-
with a few modifiable parameters, but not requiring extensive expertise in sition, compression, encryption, and storage of big data. J Neurosci Methods 2009;
the design of digital filters. 180:185–192.
16. Gotman J. Automatic detection of spikes and seizures. J Clin Neurophysiol 1999;
In summary, digital filters are a powerful tool in the processing and inter- 16(2):130–140.
pretation of EEG. While they may seem complex and mysterious at first, a 17. Claasen J, Hirsch LJ, Kreiter KT, et al. Quantitative continuous EEG for detecting
basic understanding of the principles enables the clinical electroencephalog- delayed cerebral ischemia in patients with poor-grade subarachnoid hemorrhage. Clin
Neurophysiol 2004;115:2699–2710.
rapher to anticipate the effects of digital filters (both for good and bad) in 18. Tyner F, Knott J, Mayer WJ. Fundamentals of EEG technology. New York, NY: Raven
the interpretation of digital EEG. Press, 1983.
19. Cooper R, Osselton JW, Shaw JC. EEG technology. London, England: Butterworth and
Co, 1969.
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Wiley, 1989.
1. Purcell E. Electricity and magnetism, 2nd ed. Cambridge, England: Cambridge Univer- 21. Parks SW, McClellan JH. Chebyshev approximation for nonrecursive digital filters with
sity Press, 2011. linear phase. IEEE Trans Circuit Theory 1972;19(2):189–194.
2. Horowitz P, Hill W. The art of electronics, 2nd ed. Cambridge, England: Cambridge Uni- 22. Walraven R. Digital filters. In: Proceedings of the DECUS (Digital Equipment Corpora-
versity Press, 1989. tion Users Society); 1984; fall issue.
3. Butterworth S. On the theory of filter amplifiers. Exp Wireless Wireless Eng 1930;7:536–541. 23. Kaiser JF. Nonrecursive digital filter design using the I0-sinh window function. In:
4. Oppenheim AV, Schafer RW, Buck JR. Discrete-time signal processing, 2nd ed. Upper Proceedings of the 1974 IEEE International Symposium on Circuits and Systems;
Saddle River, NJ: Prentice Hall, 1999. 1974:20–23.
5. American Radio Relay League. ARRL handbook for radio communications. Newington, 24. Weinberg DI, Artley JL, Whalen RE, et al. Electric shock hazards in cardiac catheteriza-
CT: American Radio Relay League, 2012. tion. Circ Res 1962;11:1004–1009.
4 Recording Techniques
SAURABH R. SINHA
Introduction Montages
Cerebral Generators of EEG Potentials Unpaired, Paired-Group, and Paired-Channel
Electrode Placement Montages
Recording Conventions and Sensitivity/Filter Settings Display Conventions
Issues Related to Digital Recording Referential and Bipolar Montages
Polarity Conventions Conclusion
Calibration and Sensitivity References
Filters
INTRODUCTION montage. Different types of montages and different arrangements of chan-

nel within a montage can help to highlight certain types of activity. In this
Electroencephalography (EEG) measures electrical fields generated by chapter, we will briefly discuss the generators of the EEG signal, how these
neuronal activity by recording the amplified potential differences between signals are recorded (electrodes, amplifier characteristics, and filters), and
electrodes placed on the scalp, directly on the cortex (e.g., with subdural how they are routinely displayed and analyzed (montages).
electrodes), or within the brain (e.g., with depth electrodes). EEG analysis
attempts to draw conclusions about the nature, location, and configuration CEREBRAL GENERATORS OF EEG POTENTIALS
of the generator of the EEG patterns; this helps to determine if the activity
is normal or abnormal and epileptiform or nonepileptiform. When conclu- EEG signals reflect neuronal activity at a macroscopic scale; they represent
sions about the EEG signal are combined with other information (patient the summated electrical activity generated by large groups of neurons (105 or
symptoms and signs, imaging results, etc.), diagnostic conclusions and man- more) (1). Due to the need for summation of the activity of a large population
agement decisions can be made. of neurons, the main source of EEG potentials are cortical neurons, which are
Scalp electrodes are traditionally placed according to the International arranged in layers in roughly the same orientation beneath the cortical surface.
10–20 system. Assessing the spatial distribution of the recorded electri- They are aligned with their long axis perpendicular to the cortical surface. They
cal field requires the orderly arrangement of multiple channels, termed a are activated by synapses located on their soma and dendrites. The postsynaptic
78
Recording Techniques 79
potentials produced in the cortical neurons are the major contributors to the
EEG signal. Although other types of neuronal and glial activity may contrib-
ute to the EEG, neuronal action potentials do not because their very brief du-
ration prevents significant summation across a population of neurons.
All generators of scalp-recorded electrical activity behave like a dipole, a
generator with a positive and a negative pole. For example, synaptic activity
at a point on a pyramidal cell produces an active ionic current as a result of
the opening of a pore in a neurotransmitter receptor or an ion channel. All
current flows in a closed loop; in the case of synaptic activation of neurons,
the current loop is completed by passive flow through the neuronal mem-
brane at a distant, relatively inactive site. Thus, synaptic input at one end
of a pyramidal cell causes current flow through the cell membrane whose
direction at the surface is opposite to its direction in the depth. This produces
polarization shifts (voltage changes) in the extracellular space in opposite di-
rections at the surface and in the depth. Thus, synaptic activity on a pyrami-
dal neuron produces an extracellular, radially oriented dipole. Because both
the type of postsynaptic potential (excitatory versus inhibitory) and its loca-
tion (somatic or proximal dendrites versus distal dendrites) impact the direc-
tion of the dipole, it is not possible to determine whether a given polarization
change results from excitatory or inhibitory synaptic activity (Fig. 4.1).
ELECTRODE PLACEMENT
A variety of systems have been used in the past to locate electrodes on the
scalp for EEG recording. The General Assembly of the International Fed-
eration of Clinical Neurophysiology (IFCN) recommended a specific sys-
tem of electrode placement for use in all laboratories (Fig. 4.2A) (2, 3). This
system is known as the International 10–20 system. Specific measurements
are made based on bony landmarks (nasion, inion, and preauricular point)
to determine the placement of electrodes. From these landmarks, specific Figure 4.1: The direction of the dipole generated by the activation of a pyra-
measurements are made and then 10% and 20% of a specified distance is midal neuron depends on both the type of activation (excitatory vs. inhibitory)
used as the interelectrode interval. This enables replication consistently over and its location on the neuron (distal dendrites vs. proximal dendrites or soma).
time, between technologists, and among different laboratories. Uniform in- A: An excitatory input in the distal apical dendrites causes active (solid line) in-
ward current flow there; passive current flow (dashed lines) completes the circuit
terelectrode distances and symmetric placement of electrodes over the left
with outward current closer to the soma. In the extracellular space, this generates
and right hemispheres are important for EEG interpretation, especially for
a relative negative potential in dendrites and a relative positive potential near
detecting asymmetry between the two hemispheres. the soma. A dipole that is surface negative is generated. B: An inhibitory input
The American Clinical Neurophysiology Society (ACNS) has recommended in the distal dendrites generates a surface positive dipole. C: An inhibitory input
using a minimum of 21 electrodes from the International 10–20 system. Each near the soma generates a surface negative dipole (the same as an excitatory
electrode is named by a letter/number combination. The letter designates input in the distal dendrites). D: An excitatory input near the soma generates a
the approximate anatomical location (“F” for frontal, “T” for temporal, surface positive dipole (the same as an inhibitory input in the distal dendrites).
Figure 4.2: A: Electrode nomenclature of

the 21 most commonly used electrodes from
the International 10–20 system. B: Electrode
nomenclature of the International 10–20 sys-
tem. Electrodes in black are those with differ-
ent names in the 10–10 system compared to the
10–20 system.
“Fp” for frontopolar, “C” for central, “P” for parietal, and “O” for occipi- the International 10–20 system (F7, F8, A1, and A2) for detecting interictal
tal). Odd-numbered electrodes are placed over the left side of the head and discharges (5, 6). T1 and T2 are placed 1 cm above the line connecting the
even-numbered electrodes are placed over the right. Although less consistent, external auditory meatus to the outer canthus at a point one-third of the
smaller numbers are closer to the midline (with “z,” indicating zero, being in distance from the former to the latter. Additional electrodes from the 10%
the midline) and larger numbers are more lateral. system, especially those near the midline, are often useful for assessing activ-
In 1991, the American Electroencephalographic Society (the forerunner ity near the midline, for example a medial frontal focus.
of the ACNS) added nomenclature guidelines for 75 electrode positions
along five anterior-posterior planes, lateral to the midline chain of 11 spe-
cific sites (Fig. 4.2B). In addition, there are eight coronal chains (four ante- RECORDING CONVENTIONS AND SENSITIVITY/
rior and four posterior to the chain of 13 electrode sites between the earlobe FILTER SETTINGS
electrodes along the midline through the Cz electrode). Several electrodes
are named differently in the International 10–20 system and the extended Issues Related to Digital Recording
nomenclature (the 10% system or International 10–10 system). Electrodes
T3 and T4 in the 10–20 system are referred to as T7 and T8 in the expanded Voltage measurement always requires a reference: The voltage at any point
system, and T5 and T6 are referred to as P7 and P8. For neonates, fewer can only be defined with respect to the voltage at another point, and there
electrodes are used and the precise number is somewhat variable from labo- is no absolute value for voltage. In an electronic circuit, the reference point
ratory to laboratory. The ACNS has suggested using at minimum Fp1, Fp2, is usually a fixed voltage referred to as the ground. In EEG, the voltages or
C3, Cz, C4, T3, T4, O1, O2, A1, and A2 (4). potentials on the scalp are measured with respect to another point, usually
In certain situations, additional electrodes can be applied to increase the on the scalp or at least on the body. The output of an EEG amplifier is the
yield of EEG recordings. These include sphenoidal and T1 and T2 elec- amplified difference between the voltages at the points connected to its two
trodes in patients with suspected temporal lobe epilepsy. In direct compari- inputs. For an analog EEG system, the two points are selected and physi-
sons, T1 and T2 electrodes have been found to be as effective as sphenoidal cally connected to the amplifier at the time of the recording and cannot be
electrodes and superior to nasopharyngeal electrodes and electrodes from changed once the data is acquired.
For digital EEG recording, all data are measured with respect to a com- than input 1. The polarity convention also specifies that the 10–20 electrode
mon reference electrode. The signal is then digitized via an analog-to-digital names, separated by a dash, designate electrodes connected to the two inputs
converter (ADC). Digitization refers to the discretization of the analog in- of a differential amplifier (“electrode 1” − “electrode 2”), with “electrode 1”
put signal (which is continuous) into specific voltage and time steps. The connected to input 1 and “electrode 2” connected to input 2.
sampling rate (in Hertz) of the ADC indicates the number of times per sec-
ond that data from each channel is sampled and recorded. By the Nyquist Calibration and Sensitivity
theorem, a sampling rate of N cannot faithfully record frequencies higher
than N/2. The resolution of the ADC indicates the number of discrete val- The gain of an amplifier specifies how much it amplifies the input voltage;
ues that it can produce over the allowed range of values of the analog input. for example, an amplifier with a gain of 100 will produce a 200-mV output
For example, an 8-bit ADC has 28 − 1 (=255) voltage intervals. Thus, if the when supplied with a 2-mV input. For EEG amplifiers, the gain is usually
input voltage range is −5 to +5 mV (=10 mV), the ADC voltage resolution expressed as sensitivity, which is expressed as microvolts per millimeter. This
is approximately 39 µV (10 mV/255). Fortunately, most ADCs in use today specifies the input voltage necessary to produce a given vertical deflection
have resolutions of 16 bits or even higher. on the screen or paper. For digital recordings, the actual gain of the EEG
After acquisition, for display and analysis, the data from two electrodes amplifiers is usually not adjusted; instead, the gain is usually preset to a
are mathematically combined into a “derivation.” For example, for two elec- level that amplifies the typical range of input voltages to make maximal use
trodes, E1 and E2, the data will be collected with respect to the common of the input range of the ADC. This serves to optimally use the full resolu-
reference electrode (REF, also called the system reference). These are labeled tion of the ADC. If the input voltage is significantly higher than expected,
as E1 − REF (the voltage at E1 with respect to the voltage at REF) and it will be amplified to values outside the range of the ADC and these values
E2 − REF. The derivation E1 − E2 can then be obtained by subtraction as will be clipped (i.e., set to the maximum or minimum value that the ADC
the common reference then cancels out: can handle). Changes to the sensitivity made by the technologist during ac-
quisition will only change how the digitized signal is processed for display;
E1 − E2 = (E1 − REF) − (E2 − REF)
the data being collected is unchanged. This is obviously also the case for
Thus, theoretically, the choice of the common reference electrode is i rrelevant adjustments to sensitivity during review of the data. In analog EEG sys-
as it mathematically cancels out. Practically speaking, REF is usually still an tems, adjustments made to the sensitivity actually modified the gain of the
electrode placed on the scalp to minimize large extracerebral potentials that amplifiers. In these systems, the technologist played a much more active role
could saturate the amplifiers. A common choice for system reference is an in selecting an appropriate sensitivity to collect and display data optimally.
extra electrode placed midway between Cz and Pz. Calibration of the equipment is an integral part of insuring faithful
Not only does digital recording permit post hoc recombination of electrodes reproduction of the recorded signal; this is especially critical in analog sys-
to obtain different derivations, it also allows for postprocessing of EEG sig- tems where the output device (pen on paper) is an integral part of the hard-
nal by digital filtering. Some minimal filter settings are necessary when re- ware and can impact calibration. Typically, a small voltage (approximately
cording the raw signal. At the lower end, this is necessary to avoid artifacts 50 µV) is used at a sensitivity of 7 to 10 µV per mm; this is usually applied
related to electrode polarization and drift. At the upper end, this is necessary as a train of square waves. The output signal produced in all channels is
to attenuate frequencies above the sampling capabilities of the ADC. assessed to make sure that an appropriate and equivalent deflection is pro-
duced. An additional biological calibration (usually by connecting Fp1–O2
Polarity Conventions to all amplifiers) is performed to ensure that all amplifiers respond equally
and correctly to a variety of frequencies and not just the square wave used
EEG signals are measured using a differential amplifier, which amplifies for calibration. A second calibration is also recommended at the end of
the difference between the voltages at its two inputs. These inputs are des- EEG recording, with all of the sensitivities and filter settings that were used
ignated input terminal 1 and input terminal 2, and have historically been during the recording. In digital systems, calibration is still important, but
referred to as “G1” and “G2.” By convention, an upward deflection occurs is much more reliable and stable. Calibration for digital systems may be
when input 1 is more negative than input 2 or when input 2 is more positive performed only once during a recording; amplifier gains and direct current
offsets can be corrected automatically by the software to yield the same side, artifacts related to movement and sweat, among others, are prominent
response characteristics across all channels. Calibration at different fre- at low frequencies. Muscle artifact and the significantly lower amplitudes of
quencies is a built-in function, and thus manual biological calibration is no high-frequency activity are limiting. For these reasons, scalp EEG record-
longer necessary (7). When EEG is performed to assess electrocerebral inac- ings have traditionally been limited to a band from 0.5 to 70 Hz or 100 Hz.
tivity, there is a requirement to calibrate with a 2- to 5-µV calibration signal. Analog and digital filters are used to select which frequencies are recorded and
displayed. For all EEG systems, analog filters are used to select the frequency
Filters range to be recorded. In the case of digital EEG systems, further filtering can
be performed using digital filters (software) applied to the digitized signal. The
Voltage changes related to neurophysiological activity occur over a broad high-frequency filter, also referred to as the low-pass filter, selectively attenuates
range of frequencies, from at least 0.01 Hz at the low end to several hun- higher frequencies. A commonly used high-frequency filter setting is 70 Hz. An
dred Hertz at the high end (8). Recordings covering this entire band of fre- ideal 70-Hz high-frequency filter would remove all activity with a frequency
quencies would best reproduce the biological activity. However, there are higher than 70 Hz with no effect on frequencies below 70 Hz. A real-world
biological and technical factors that make recording at extremely high and filter has minimal impact on frequencies far below 70 Hz and maximally at-
low frequencies difficult. On the technical side, recording at low frequencies tenuates frequencies well above 70 Hz. The transition between these two zones
are difficult due to electrode polarization and drift in amplifiers and other is referred to as the roll-off: the steeper the roll-off, the more closely it resembles
electronics. Recording of higher frequencies is technically difficult due to an ideal filter. Using a high-frequency filter setting of 35 Hz or even lower
the need for higher sampling rates and electronic/random noise; further- can significantly lower artifact related to muscle activity; however, it can also
more, for analog pen/paper system, the physical characteristics of the pen significantly alter the biological EEG signal and attenuate/blunt epileptiform
limited the maximum frequency that could be recorded. On the biological discharges and make apparent artifacts appear physiological (Fig. 4.3).
Figure 4.3: A: Ictal pattern for a left hemisphere

seizure displayed with LFF of 0.5 Hz, HFF of
100 Hz. Although the rhythmic theta activity over
the left hemisphere can be seen, it is marred by
muscle artifact. B: The same EEG shown with
HFF of 50 Hz. The muscle artifact is reduced and
the left hemisphere theta is much more appar-
ent. C: The same EEG with HFF of 15 Hz. The
muscle artifact is significantly reduced; however,
now the right hemisphere activity, mainly due to
muscle artifact, could be mistaken for cerebral
activity, especially over the temporal regions.
Figure 4.3: (continued)

Figure 4.4: A: EEG with prominent L temporal

irregular slowing shown with LFF of 0.5 Hz, and
HFF of 70 Hz. B: Same EEG shown with LFF of
5 Hz, which largely attenuates the left temporal
slowing.
The low-frequency filter, also referred to as the high-pass filter, selectively combinations. This is equivalent to filtering the signal across space. Just like
attenuates lower frequencies. Frequencies below the low-frequency filter setting high-frequency and low-frequency filters that have the potential to accentu-
are selectively attenuated and frequencies above are not. Low-frequency filters ate activity of interest but can also distort the signal, montages can high-
are sometimes described by their time constant (τ). For a square wave input, the light certain types of activity while distorting others. The type of montage
time constant is defined as the time it takes the voltage to decline by 63% from and the arrangement of electrodes within that montage impact what spatial
its peak. For a simple filter (consisting only of resistors and capacitors), a time information is well-preserved and what is lost. For example, a longitudinal
constant of 1 second corresponds to a low-frequency filter setting of 0.16 Hz: montage preserves information about spatial relationships best in the sagit-
1 tal plane, while a transverse montage preserves information about spatial
fcutoff relationships best in the coronal plane.
2pt
Montages may be classified as: (1) unpaired, electroanatomical paired-
Judicious use of low-frequency filter may allow better appreciation of group or paired-channel (referring to the relative arrangement of elec-
high-frequency activity in a record dominated by low-frequency physiologi- trodes within a montage), (2) referential, bipolar or laplacian (referring
cal activity or artifact; however, it may also lead to losing relevant informa-
tion, like focal slowing (Fig. 4.4).
Another issue related to filtering is that of phase advance and phase de-
lay. This refers to the fact that a filter not only affects the amplitude of a
waveform, it also shifts the position in time. For a periodic signal, this cor-
responds to a change in the phase of the signal. A phase advance indicates
that the peak of the signal is moved to an earlier time—this is the impact
of applying a low-frequency filter. A phase delay indicates that the peak of
the signal is delayed to a later time—this is the impact of applying a high-
frequency filter. For typical filter settings, the phase shifts are typical only a
few milliseconds. As long as the filters are applied uniformly to all channels,
the phase shifts will have little impact on EEG interpretation. However, this
can be a more significant issue if different filter settings are used for different
channels. It is also a bigger issue for evoked potentials, where a small shift in
latency can be significant (Fig. 4.5).
Montages
The EEG signal is generated by a complex, three-dimensional structure, the
cerebral cortex. Significant spatial information is lost by the act of recording
this signal using electrodes placed at a handful of locations on the scalp.
While adding more electrodes can increase the spatial information, it can-
not fully compensate for the lack of information from deeper points in the
brain. Spatial information is further degraded by the need to display how Figure 4.5: Example of phase shifting. The center panel shows a bipolar
the signal varies over time. Thus, spatial information is typically only con- temporal chain of electrodes with a left temporal sharp wave (near isoelectric at
veyed within the orderly arrangement of different electrode derivations, the F7–T3) with LFF of 0.5 Hz and HFF of 100 Hz. The dashed line marks the time of
montage. Voltages recorded from multiple scalp locations simultaneously the peak. Increasing the LFF to 5 Hz (top panel) shifts the peak earlier. On the
are displayed by combining the signal from different electrode pairs or other hand, decreasing the HFF to 15 Hz (bottom panel) shifts the peak later.
to derivations used), and (3) longitudinal, transverse or circular (refer- Referential Montages
ring to arrangement of channel along sagittal, coronal or axial planes, In a referential montage, the voltage at each electrode is displayed with
respectively). respect to a common electrode known as the reference. Note that this
reference is not the same as the system reference used for recording the EEG
Unpaired, Paired-Group, and Paired-Channel Montages signal (see earlier). Ideally, the common electrode is inactive with respect
to the activity of interest (i.e., does not contain any of this activity). This
In unpaired montages, channels are arranged in anatomical neighboring is not possible in real life, as the reference electrode is always active to
sequence: for example, sequentially from front to back or left to right. An some degree. So, the goal is to identify a relatively inactive electrode. Com-
example is a transverse, bipolar montage where electrodes are arranged in monly used reference electrodes include A1 and A2 (“ipsilateral ear” and,
coronal planes from anterior to posterior, with electrodes going from left to rarely, “contralateral ear”), A1 + A2 (“linked ear”), Cz, a balanced non-
right in each plane. In paired-group montages, electrodes from homologous cephalic reference such as the neck-chest region, and the average reference.
areas are placed adjacent to each other. For example, left and right temporal The average reference is derived electronically (analog) or mathematically
are placed together as are left and right parasagittal chains. Paired-group (digital) by averaging the voltage in all active scalp electrodes and using it
montages are always longitudinal as the brain does not have homologous as the reference (9). Sometimes electrodes containing a prominent artifact
regions in the coronal direction. A longitudinal bipolar montage is an (e.g., frontal electrodes with eye movement artifact) or prominent signal
example. In paired-channel montages, channels from homologous brain (e.g., electrodes with focal slowing) are excluded from the calculation of the
areas are paired. Typically, pairs of electrodes from the left and right are average reference; this avoids contamination of the reference electrode.
then subgrouped together in longitudinal lines, with unpaired midline elec- With appropriate selection of a reference (where the reference is signifi-
trodes placed separately. Paired-group and paired-channel montages allow cantly less active than the other electrodes), a referential montage clearly
for better detection of asymmetry between the two hemispheres. displays the polarity and field distribution of potential being measured.
Selection of the reference is crucial. If the selected reference has a signifi-
Display Conventions cant active contribution, it will distort the recorded activity. For example,
using an ipsilateral ear reference in a patient with temporal discharges may
In montages, electrodes are always arranged in anterior-to-posterior actually minimize the activity in nearby temporal electrodes. A major disad-
sequence. For longitudinal montages, the chains proceed from front to back; vantage of referential recordings is that no single reference choice is optimal
for transverse montages, chains are displayed in a front-to-back sequence. In for all situations; for example, a Cz reference may be ideal for looking at
the US and Canada, “left-over-right” convention is typically used. For lon- abnormal activity over the temporal regions but would be an extremely poor
gitudinal montages (unpaired or paired), the left-sided electrodes are placed choice for abnormal activity near the midline or any type of activity during
before the right-sided electrodes or electrode groups. For transverse mon- sleep (Fig. 4.6).
tage, each chain proceeds from left to right. A “right-over-left” convention
is used routinely in Europe and is recommended by the IFCN (3).
Bipolar Montages
Referential and Bipolar Montages In bipolar montages, both inputs are connected to active recording elec-
trodes and no single electrode is common to both inputs. Bipolar mon-
As mentioned previously, the main purpose of arranging EEG data as tages link sequential pairs of electrodes to form chains in the longitudinal
montages is to aid in localization of the recorded activity. Localization (sagittal), transverse (coronal), or circular (axial) directions. In these chains,
requires that multiple measurements of the voltage distribution be made. a single electrode becomes common to two adjacent channels; for example,
For longitudinal or transverse chains of electrodes, one is trying to identify A–B, B–C, C–D, and D–E. In such a chain, the site of maximal voltage
the electrode that registers the maximum voltage. Precise localization in two within a potential field becomes a phase reversal, that is, simultaneous de-
dimensions requires identifying the maximally involved electrode in both the flections in two channels sharing a common electrode with the maximal
sagittal and coronal planes. voltage will be in opposite directions. The direction of the phase reversal
Figure 4.6: A: A bifrontal discharge, likely a

vertex wave, shown on a longitudinal bipolar
montage. Phase reversals are seen at F3 and F4.
B: The same discharge shown on a transverse
bipolar montage, with phase reversals at Fz,
Cz. Fp1–Fp2 is nearly isoelectric. In combina-
tion with A, this discharge can be localized to
the midline at approximately the level of Fz.
C: The same discharge shown on an average
reference montage. Maximum amplitude is
seen at Fz, consistent with localization from the
bipolar montages. However, note the effect of
the large discharge contaminating the average
reference: a deflection in the opposite direction
at relatively inactive electrodes like O1 and O2.
D: The same discharge shown on a Cz reference
montage. Note how the use of an active elec-
trode as a reference leads to mislocalization:
the discharge appears to be a surface positive
discharge located near the back of the head
(maximal at O1 and O2).
Figure 4.6: (contiuned)

(deflections coming together for a surface negative peak and diverging for a CONCLUSION
surface positive peak) assists in determining polarity. If the voltage associ-
ated with a potential field is equal in two adjacent electrodes, they are equi- EEG is the most readily available and clinically relevant tool for ascertain-
potential. A channel involving these two electrodes will show cancellation ing cerebral activity, especially as it relates to seizures. Proper interpreta-
and no deflection will be seen in this channel. Localization by phase reversal tion and utilization requires an understanding of the biological basis of
is only possible if the bipolar montage fully encompasses the voltage peak. the EEG, including the inherent limitations in such a macroscopic mea-
If the peak occurs at the end of a chain, for example a spike located at O1, surement of complex neuronal activity. The technical aspects of recording,
no phase reversal will be seen. Adding an additional electrode, for example a displaying, and analyzing the EEG signal have been simplified over time.
suboccipital lead, may reveal a phase reversal and aid in localization. The use of digital recording systems that allow for reformatting and re-
Bipolar montages are ideally suited to highlighting activity that changes processing of the data and that are often engineered with capabilities well
rapidly in space, that is, has a fairly localized field. By subtracting the beyond older systems has allowed us to be less aware of potential techni-
potential in adjacent electrode, only those signals that are changing b etween cal issues. These issues were often just under the surface of older systems
the two locations will be accentuated. Another way of looking at it is that whose capabilities were sometimes just barely adequate for their purpose.
a bipolar montage provides the first spatial derivative of the EEG signal: However, even with today’s systems, under special circumstances (e.g., re-
signals that are changing rapidly in space are best seen. On the other hand, cording high-frequency oscillations), these technical issues can still impact
potentials that have a broad field, that is, those that are not changing rap- the EEG.
idly in space, will be relatively equipotential between adjacent electrodes
and will cancel out in a bipolar montage. A corollary to this is that the
REFERENCES
amplitude in a channel of a bipolar montage does not reflect the actual
amplitude but only how rapidly it is changing in space. Unlike a referential 1. Gloor P. Neuronal generators and the problem of localization in electroencephalography:
montage, a bipolar montage does not require an inactive electrode or care- application of volume conductor theory to electroencephalography. J Clin Neurophysiol
1985;2(4):327–354.
ful selection of a reference. However, the level of activity at individual elec- 2. Jasper HH. The ten-twenty electrode system of the International Federation.
trodes cannot be directly compared using a bipolar montage, only inferred Electroencephalogr Clin Neurophysiol 1958;10:371–373.
indirectly. 3. Jasper HH. The ten-twenty electrode system of the International Federation. In: In-
ternational Federation of Societies for Electroencephalography and Clinical Neurophysi-
ology: recommendations for the practice of clinical neurophysiology. Amsterdam, the
Selection of Montages Netherlands: Elsevier, 1983:3–10.
As discussed earlier, each type of montage has advantages and disadvan- 4. American Clinical Neurophysiology Society. Guideline two: minimum technical stan-
dards for pediatric electroencephalography. 2006 [cited November 11, 2013]. Available
tages. Optimal EEG recording combines both referential and bipolar mon- from http://www.acns.org/pdf/guidelines/Guideline-2.pdf.
tages. Comprehensive assessment of the potential field requires combining 5. Binnie CD, Marston D, Polkey CE, et al. Distribution of temporal spikes in relation to
these methods intelligently. With analog equipment, where data could not the sphenoidal electrode. Electroencephalogr Clin Neurophysiol 1989;73(5):403–409.
6. Sadler RM, Goodwin J. Multiple electrodes for detecting spikes in partial complex
be reformatted after collection, it was essential to record the data using a va- seizures. Can J Neurol Sci 1989;16(3):326–329.
riety of montages. The ACNS recommended that a standard record should 7. Wong PKH. Digital EEG in clinical practice. Philadelphia, PA: Lippincott-Raven,
include, at minimum, a longitudinal bipolar montage, a transverse bipolar 1996.
8. Vanhatalo S, Voipio J, Kaila K. Full-band EEG (FbEEG): an emerging standard in
montage, and a referential montage. The specific montages to be used are electroencephalography. Clin Neurophysiol 2005;116(1):1–8.
not specified; however, each laboratory should have a set of standard mon- 9. Goldman D. The clinical use of the “average” reference electrode in monopolar recording.
tages. The existence of such standards montages does not replace the active Electroencephalogr Clin Neurophysiol 1950;2(2):209–212.
role of a trained technologist who may select or set up special montages or
electrodes to highlight a particular activity.
5 Normal Adult EEG
WILLIAM O. TATUM IV
Introduction Activating Procedures

Parameters of Recording Sleep Architecture
Bandwidths in the Normal Adult EEG Benign Variants of Uncertain Significance
Alpha Variations of the Normal EEG
Mu Rhythm Misinterpreted Normal EEG
Beta Conclusion
Theta References
Delta
Introduction routinely used in the assessment of normal EEG, though three-dimensional

source localization is possible (2). To be believable as a source of electrical
EEG has made a unique and valuable contribution to our understanding activity that emanates from the brain, an appropriate polarity (Table 5.1)
of the brain’s electrical function. The utility of EEG lies in its applica- and accompanying electrophysiological field must exist (3). The correct in-
tion to a number of neurological conditions associated with altered brain terpretation involves synthesizing complex waveforms from different band-
function. To understand what constitutes an abnormal EEG, a solid foun- widths generated by a cerebral source to determine whether the combined
dation of what constitutes the normal boundaries is essential. EEG rep- result is normal. Because the routine interpretation of EEG as normal is
resents a three-dimensional cerebral source graphically represented in a most routinely a qualitative skill, the result is based upon one’s knowledge,
two-dimensional plane. Most of the human cortex lies deep beneath the training, and experience. No single parameter or collective group of fea-
scalp surface where EEG has limited capabilities in assessing subcortical tures present in the EEG can identify a tracing as normal. It is the overall
abnormalities. The origin of cerebral potentials is based upon the intrin- pattern of waveform organization and orderly progression over time that
sic electrophysiological properties of the nervous system (1). Scalp EEG is best represents the “brain waves” as normal. Recognizing common features
90
Normal Adult EEG 91
TABLE 5.1 Polarity with Respect to Electrode Pairs: Input Parameters of Recording
Terminal 1 (aka G1) and Input Terminal 2 (aka G2)
versus Surface Waveform Deflection (Arrows) Frequency, polarity, amplitude, morphology, duration, and distribution are
elements that govern the description and reflect the identity of individual
Electrode 1 Electrode 2 waveforms. Symmetry, reactivity, appearance, and synchrony constitute the
Negative ⇑ ⇓ temporal characteristics of all the waveforms. The absolute waveform metrics
Positive ⇓ ⇑ and their temporal relationship is relative to all other components in the EEG.
Analyzing the EEG requires a systematic approach. In the routine interpreta-
By convention, when G1 is relatively electronegative, the deflection is up. tion of scalp EEG, recordings are usually performed with standardized pa-
rameters. A visual display of 30 mm per second is utilized to reflect the “paper
of normal EEG, the infrequent variations seen with a normal record, and speed.” Amplifier sensitivity is initially recorded at 7 μV per mm, though are
the benign variants of uncertain significance that are considered normal adjusted based upon requirements of the individual. Lower amplitudes neces-
is an essential task to ensure appropriate interpretation. The changes that sitate a higher amplifier gain (i.e., higher sensitivity setting) that is often seen
normally occur in the EEG with advancing age are also important to rec- normally in younger patients. Filter settings are routinely set between 1 and 70
ognize. From the time of birth to old age, the appearance of waveforms Hz. Adjustment of the low-frequency filter (to a higher cutoff frequency) may
that are inappropriate for other ages may occur. Understanding the tem- be required if artifact is problematic such as with sweating. High-frequency
poral relationship (Table 5.2) that occurs with time is essential for an age- filter modification (to a lower cutoff frequency) may be necessary if myogenic
appropriate assessment of a normal EEG. Misinterpreting an EEG usually artifact is prominent, and a selective “notched” filter at 60 Hz may be required
occurs from the overinterpretation of a normal record as abnormal. This in cases where electrically hostile environments exist. Standard settings are
can result in the incorrect treatment of patients and potentially lead to seri- used in the examples throughout the text unless otherwise noted. The state
ous consequences (4). and age of the patient may be known to the electroencephalographer prior
to interpretation, though most typically initially interpret the EEG indepen-
dent of background information. This is to facilitate a final interpretation of
TABLE 5.2 Essential Features of the Normal EEG Involving
the EEG in the proper clinical context of recording. Physiologic functions
Waveform Measurements and Temporal
Characteristics such as eye opening and closure, visual scanning, and activating procedures
are components that are utilized in analyzing normal EEG. In adults, an in-
Waveform Metric (units) Temporal Characteristics terpretation should be performed without prior knowledge of the patient’s
Frequency <0.5 to >500 Hz history to prevent bias during interpretation. Recognizing an adult EEG that
(traditionally 1–70 Hz) has normal background organization with characteristic waveforms makes
Polarity (positive vs. negative) even the information about the age and state nonessential. The EEG of neo-
Amplitude (μV) Symmetry nates, infants, and children under 3 years of age, on the other hand, normally
Morphology (mono-/polymorphic, Reactivity (eye opening/closing,
has electrocerebral activity that varies substantially based upon age and state.
regularity, rhythmicity, special extremity movement, visual A purists’ approach to analysis of the adult EEG is to develop a working
features) scanning, activation techniques) impression without any information. Indicating the patient’s level of alert-
Duration (milliseconds) Appearance (rare, intermittent,
ness is important. An example would be to misinterpret a normal background
occasional, frequent, continuous) rhythm less than 8 Hz in drowsiness as abnormal.
Every routine EEG should include at least one montage that uses the lon-
Distribution (anterior-posterior, Synchrony
hemispheric, regional, focal) gitudinal bipolar, reference, and traverse bipolar montages. Newer modi-
fied electrode systems use electrode placement with more closely spaced
92 Normal Adult EEG
electrodes in a 10–10 system. High-density arrays and complex methods of observed during relaxed wakefulness and normally has a side to side dif-
signal analysis, such as independent component analysis and phase congru- ference of less than 1 Hz. The frequency of the alpha rhythm is coupled
ency, may increase the sensitivity of scalp EEG further to refine the location with cerebral blood flow and falls when blood flow is compromised. The
of the generators in normal and in abnormal EEG (5,6). Changes in mon- alpha rhythm has been evaluated in relationship to cognitive and mental
tage, sensitivity, and display speeds as well as post hoc filtering, spike and function (10,11). Reactivity and a posterior location distinguish the alpha
seizure software applications, quantitative EEG analysis, and artifact rejec- rhythm from an alpha frequency. In majority of people, the occipital re-
tion may clarify an EEG that is not otherwise interpretable (7). gion is the site of maximal activity for the alpha rhythm (Fig. 5.1). While
a posterior dominant rhythm first becomes apparent at 3 to 4 months of
Bandwidths in the Normal Adult EEG age, an alpha rhythm of 8 Hz is achieved in the majority by 3 years of age
and is 10 Hz by age 10. The frequency may transiently increase after eye
Normal EEG produces waveforms represented by a spectrum of frequencies closure for an instant to lie in the beta bandwidth. However, this rhythm
(Table 5.3). Routine interpretation of the routine scalp EEG typically involves is seen on eye closure and is reactive, independent of the beta frequency
bandwidths of frequencies that lie between 1 and 30 Hz. Alpha, beta, theta, and is known as alpha squeak. The alpha rhythm is best observed dur-
and delta frequencies comprise the major frequencies for analysis. Most ing periods of relaxed wakefulness and often during periods of relative
amplitudes range between 10 and 100 μV. Invasive EEG (iEEG) reveals a physical and mental inactivity. In normal EEG, a dominant alpha rhythm
similar spectrum of frequencies as those recorded at the scalp (8). “Ultra-fre- is present over the posterior aspect of the head and lies within the 8- to
quencies” may be observed below 1 Hz (infraslow activity) and above 30 Hz 13-Hz bandwidth. Measures of the alpha rhythm vary over time and are
(high-frequency oscillations), depending upon the technical limitations of the age-dependent, reflecting the changing physiology of brain function with
recording. Altered morphology, higher amplitudes (5- to 15-fold on iEEG), aging. Only 1% of a healthy young population has an alpha rhythm of
and shorter durations contrast the bandwidths noted with scalp EEG (9). 8 Hz. While an 8-Hz alpha rhythm is considered normal for an adult, this
broad interpretation should be liberally applied in adults greater than 65
Alpha years of age but more restrictive in younger patients. With advancing age,
the alpha rhythm frequency steadily declines, though should remain stable
The alpha rhythm is the starting point to assess the background activity with normal frequencies of 8 Hz even into late life. Therefore, even in those
when interpreting the EEG. The normal range for the alpha frequency greater than 80 years of age, an alpha rhythm of 7.5 Hz should be viewed
in the occipital region in adults is 8 to 13 Hz. The alpha rhythm is best critically as an abnormality.
Reactivity is a characteristic of the alpha rhythm. Attenuation of the al-
TABLE 5.3 Frequencies in the EEG and Their Bandwidths pha activity is seen in response to eye opening. With eye closure, there is a
return of higher voltage alpha frequencies in the occipital region denoting
Frequency Bandwidth (Hz) the reaction to visual input. This “block” is temporary and dependent upon
Ultraslow 0–0.3 a stimulus that may eliminate or attenuate the voltage of the alpha rhythm.
Delta <3.5 Reactivity may be seen with other forms of stimulation, including cognition,
Theta >3.5–<8 though the most powerful remains eye opening and closure. Complete unre-
Alpha 8–13 sponsiveness of the alpha rhythm is not expected in normal EEG.
Beta >13–30 In approximately one-fourth of normal adults, the alpha rhythm is poorly
Gamma >30–80
visualized or it may be only intermittently visualized. Amplitudes also vary
Ripples >80–250
between individuals, over the time of recording and lifetime. Low-amplitude
Fast ripples >250–500
Ultra-fast ripples 500–1,000 recordings may be present, and in less than 10% of patients, voltages of
less than 15 μV are seen. The alpha rhythm is distributed maximally in the
Normal Adult EEG 93
FIGURE 5.1: A 10-Hz alpha rhythm in an awake

45-year-old woman with spells dissipates when
the eyes are opened (gray box). A return of
alpha is noted demonstrating reactivity upon
eye closure (black arrow). Note the increase in
frequency immediately following eye closure
known as alpha squeak.
occipital regions, and shifts anteriorly during drowsiness. Asymmetries of The morphology of the alpha rhythms is typically sinusoidal, though
the alpha rhythm are best assessed at two posterior electrode sites (i.e., pa- at times may normally appear with a sharp surface negative component
rietal and occipital), with both bipolar and referential recordings to ensure especially in younger patients. It may show a waxing and waning “beat-
consistency. Higher amplitudes are usually noted over the right hemisphere ing” pattern due to varying amplitudes. These alpha “spindles” may be
between 20 and 60 μV in the majority of individuals from peak to peak. noted in some people, while in others, this pattern is absent. The spindle
Using the P4-O2 derivation, normal amplitudes of 15 to 45 μV are typi- pattern, however, is a continuous pattern unlike the proper use of the
cally encountered. Higher amplitudes are noted with slower alpha rhythms. term spindle that is associated with sleep. The cerebral field involved
Voltage asymmetries of greater than 50% should be regarded as abnormal. with the alpha rhythm involves the posterior quadrant of the head. When
When the left side is greater than the right by greater than 35%, it is more it extends into the central regions, it may be confused with mu. If the
likely to be associated with abnormality. temporal region is involved, it may be misinterpreted as an abnormal
94 Normal Adult EEG
epileptiform discharge (4). Some temporal alpha may be detected in the of the alpha rhythm during rising body temperatures. Cardiac pacemakers
presence of a breach rhythm and is believed to be independent of the have been shown to increase the a lpha frequency by more than 1 to 2 Hz,
posterior alpha and mu rhythms, and has therefore been referred to as probably due to increased cardiac output and improved cerebral blood flow
the “third rhythm” (12). (15). Drugs that are used even as prescribed may result in slowing of the
Unilateral failure of the alpha rhythm to attenuate reflects an ipsilateral alpha rhythm. In cancer patients exposed to hyperthermia of 41°C for treat-
abnormality involving the posterior head region (Bancaud’s phenomenon). ment purposes, slowing of the alpha rhythm is encountered with depression
Paradoxical alpha occurs when alertness results in the presence of alpha of the electrocerebral activity (16).
and drowsiness does not. Alpha harmonics are normal features of the alpha
where frequencies that are exactly two times the alpha (supraharmonics) or Mu Rhythm
one-half the frequency (subharmonics) are seen (Fig. 5.2). The mu (aka motor) rhythm is a normal, centrally located, reactive, alpha
No sex-dependent differences in the alpha rhythm is seen in the EEG (13). frequency. It has characteristics that are similar to the alpha rhythm but
The relationship of the menstrual cycle relative to EEG has been proposed, it is physiologically distinct. However, it has been referred to as the “so-
with acceleration of the alpha frequency and amount reduced in the premen- matosensory alpha rhythm” with a restricted central location approximat-
strual phase, with slowing of the alpha and amount increased during menses ing the pre- and postcentral gyrus to approximate the sensorimotor cortex
(14). A relationship to body temperature has been shown with acceleration in relaxed wakefulness. Mu is typically asymmetric and asynchronous with
FIGURE 5.2: The alpha rhythm noted in the occipital region in two-thirds of patients (black arrows) with
subharmonics below (A) during drowsiness that is half the frequency of the normal 10-Hz alpha rhythm. In
(B), an alpha rhythm is less than 13 Hz occasionally, not due to a supraharmonic in a 24-year-old after cardiac
transplantation.
Normal Adult EEG 95
interhemispheric shifting. It is well localized to the C3 and C4 electrode this frequency reflects the sensory cortical function, while 20-Hz reactive
locations, and is associated with a characteristic physiologic reactivity. The beta frequencies producing a notched appearance in the mu rhythm have
frequency of mu is 10 Hz and frequencies less than 8 Hz are probably ab- been suggested to have a greater correlation with motor function (20). Dur-
normal. The mu rhythm has been identified in the first year of life and is ing yoga, more than one element of the mu rhythm may coexist in the same
believed to reflect the early developmental necessity of evolving motor func- individual (14).
tion during early life. The reactivity of mu may mimic the central spread of Beyond the similar frequency that may slow with age, the distribution
the alpha rhythm. Though in contrast to the alpha rhythm that is eliminated of mu is typically asymmetric and asynchronous. It may appear in brief
by eye opening, the mu rhythm is eliminated by movement of a contralateral bursts and prolonged runs. It can be differentiated from alpha rhythm
limb (17). The reactivity of a mu rhythm highlights the impact of cognition despite the similarities by the asymmetry of the mu rhythm and the sym-
on EEG desynchronization on motor function (18). The reactivity of mu metry of an alpha rhythm. The amplitude of the mu rhythm is usually lower
has been shown in amputees attempting to initiate movement of an ampu- than the amplitude of the alpha rhythm. Morphological differences may
tated limb. Furthermore, just the thought of a movement has been enough be noted (Fig. 5.3). The morphology is arciform with a comb-like appear-
to create a bilateral blocking response. Light tactile stimulation to create a ance. The prevalence of mu has varied depending on the author, though
sensation and enhancement by photic stimulation has been demonstrated with computerized EEG, mu can be identified in most. When a lesion in the
to compound the idea of the sensory-motor function of mu rhythm to im- central region exists, this may diminish the presence of the corresponding
plicate both sensory and visual integration (14). Quantitative EEG (qEEG) mu rhythm or reduce its reactivity (21). When mu is strictly unilateral, an
has suggested that the mu is separate from the alpha rhythm and that the ipsilateral breach rhythm or rolandic cortical disturbance should be con-
rolandic beta is separate from a harmonic of the mu rhythm (19). The 10-Hz sidered. When it is persistent, unreactive, and associated with focal slowing,
frequency of the mu rhythm is most often encountered. It is believed that mu-like frequencies are abnormal.
FIGURE 5.3: Transverse bipolar montage demonstrating a mu rhythm

(gray arrows) as a “fragment” of the occipital alpha rhythm (black arrow).
Not the similar frequencies but different localization, reactivity with eye
closure, and mu assymmetry.
96 Normal Adult EEG
In epilepsy management, the mu rhythm has served as a reference point of greater than 50% suggest a cortical gray matter abnormality within the
for treatment using biofeedback (14). hemisphere having the lower amplitude. Lesser asymmetries may simply re-
flect normal skull thickness differences. Vertex beta should prompt a search
Beta for cortical dysfunction affecting the frontal region. Focal central beta has
been related to a mu rhythm demonstrating normal reactivity to motor or
Beta rhythms represent frequencies that are more than 13 Hz. They are also tactile stimuli. A skull defect may produce a breach rhythm that produces
referred to as “fast” frequencies. Beta is a frequency that is found in most focal beta activity (Fig. 5.4). Benzodiazepines, barbiturates, and chloral hy-
normal adult EEG. Beta activity normally increases during drowsiness, light drate are potent activators of generalized “fast activity.” Hypnotic agents
sleep, and with mental activation. Beta is a common frequency and is most usually occur within the 18- to 25-Hz bandwidth and may reach greater
often observed within the 18- to 25-Hz bandwidth in normal people with a than 50 μV occupying greater than 50% of the tracing. However, enhanced
voltage of less than 25 μV. Most frequencies higher than 80 Hz are beyond beta activity alone is without specificity to interpret an EEG record as ab-
the detection limits of scalp EEG, with beta represented by frequencies normal (14,22). Not unexpectedly, with the prevalence of sedatives and
greater than 13 Hz and less than 30 Hz. A frontal-central field is most often tranquilizer use (Fig. 5.5) in patients with psychiatric disorders, the beta
encountered and may even appear as a brief train that exceeds 30 Hz when frequencies may have a greater representation in this population, though
sleep is achieved. Rarely, a posterior dominant rhythm may appear to be it is of no clinical significance (23). Some frontal beta may appear close to
present that lies in the beta frequency bandwidth. With the faster beta fre- 30 Hz, especially during sleep. Even higher frequencies in the gamma range
quencies, voltages beyond 25 μV in amplitude are abnormal and amplitudes and above may occur with normal physiological functions that are involved
greater than 30 μV are unusual. Persistently reduced hemispheric voltages in cognition (24,25).
FIGURE 5.4: Left frontal breach rhythm (gray rectangle) with prominent
beta activity at F3 electrode derivation and admixed 5- to 6-Hz theta
seen at a focal region following a craniectomy for resection of a cavern-
ous vascular malformation.
Normal Adult EEG 97
FIGURE 5.5: AP longitudinal bipolar montage with diffuse 20- to 25-Hz

beta activity associated with alprazolam and oxycodone (gray arrow).
Note the photoelectric response (black arrow) with the infraorbital elec-
trode/eye movement monitor in association with the photic stimulation.
Theta between alpha and delta frequencies, with continuous focal theta suggest-
ing nonspecific abnormality (Fig. 5.6B). A long-standing recommendation
Theta frequency is composed of 4- to less than 8-Hz activity in the EEG. in considering abnormal theta has been to consider it abnormal in awake
Approximately one-third of normal young adults may show intermittent 6- patients if it is present in persistent focal bursts or runs. While this quantifi-
to 7-Hz theta rhythms during wakefulness (Fig. 5.6A). It appears as rhyth- cation seems helpful, its presence is more likely related to the state and age
mic activity that is maximal in the frontal or frontocentral head regions, of the patient, rather than reflecting a specific abnormality. In the elderly,
typically with amplitudes that are less than 15 μV, though varying amplitude intermittent bitemporal 4- to 5-Hz activity or even theta with a lateralized
and morphologies may be encountered. The presence of anterior predomi- predominance (usually left > right) may occur in about one-third of the
nant rhythmical theta may persist into to adolescence and young adulthood. asymptomatic normal seniors (14,27).
The appearance of frontal theta can be facilitated by heightened emotions,
concentration, and during mental activities such as problem solving (26). Delta
Theta activity is normally enhanced by hyperventilation (HV). It may also
occur in bursts during drowsiness and sleep transitioning. It is normally lim- Delta frequencies consist of activity that is less than 4 Hz. Delta may be con-
ited in the adult during the waking record. The appearance of theta in the sidered normal in young children less than 10 years of age as well as in nor-
EEG frequently occurs as a normal developmental feature, yet it may per- mal elderly individuals. In children, posterior slow waves of youth (PSWY) are
sist until 25 years of age (14). It was felt to be an intermediate bandwidth posterior delta frequencies that are prominent during childhood persisting
98 Normal Adult EEG
FIGURE 5.6: Bipolar montage demonstrating (A) normal 6- to 7-Hz theta prior to eye closure (black arrow) in
an awake 22-year-old during mental concentration and (B) right temporal continuous theta (gray arrow) in a
35-year-old with right temporal lobe epilepsy.
through young adulthood (Fig. 5.7A). Between ages 6 and 12 years, ar- associated with normal seniors and are found in greater than one-third of
rhythmic delta complexes may be intermixed with the alpha rhythm in the people greater than 60 years of age (27). Rare unsustained single complexes
occipital head regions. They typically have a duration of 200 to 400 milli- of left temporal delta in the elderly are considered normal findings incurred
seconds and are of moderate voltage (i.e., <120% of the background). They during the aging process (28). Still, the association between focal temporal
react like alpha, with elimination during eye opening and reappearance with slow waves and mild cognitive impairment with white matter hyperintensi-
eye closure. Rarely, there may be a superimposition of the alpha rhythm ties on brain magnetic resonance imaging (MRI) suggests a spectrum EEG
to “fuse” with PSWY, mimicking a sharp slow-wave complex (Fig. 5.7B). features on the normal-abnormal continuum associated with aging (29,30).
The similarity in distribution, frequency, morphology, and reactivity are Another delta frequency that may be seen in the healthy elderly is anterior
the clues to distinguishing PSWY amidst the alpha rhythm from an inter- dominant rhythmic delta that occurs during sleep onset. This normal find-
ictal epileptiform discharge (IED). In the older adults, single complexes of ing encountered during sleep onset resembles frontal intermittent rhythmic
delta may occur in the anterior temporal regions (Fig. 5.8). The contention delta activity (FIRDA) in morphology, though is not present as an abnor-
that these focal features are normal has been controversial. They have been mality during wakefulness (31).
Normal Adult EEG 99
FIGURE 5.7: AP longitudinal bipolar montage with (A) demonstrating reactivity (black arrow) in a 20-year-old
with PSWY. In (B), there is the appearance of the alpha rhythm coupled with PSWY (gray arrow) to produce the
false appearance of a sharp-and-slow-wave complex.
Activating Procedures it may produce EDs in patients with generalized seizure of genetic origin
in nearly 80%, especially for those with untreated absence epilepsy. Fo-
Activating procedures are a routine technique used in EEG. Activating cal slowing may be produced by HV in patients with localized cortical
procedures are designed to use various types of stimuli that could poten- dysfunction. HV is routinely performed for 3 to 5 minutes. The mecha-
tially elicit an abnormal electrographic or clinical response. Some normal nism associated with the response has been suggested to result from direct
responses are associated with characteristic patterns. Activating techniques vasoconstriction, creating a relative cerebral hypoxia (32). HV leads to
are commonly used to elicit slowing and epileptiform discharges (EDs). hypocarbia and vasoconstriction accompanied by reduced cerebral blood
HV and intermittent photic stimulation (IPS) have been employed as rou- flow, which is believed to form the physiologic basis for the EEG find-
tine procedures in almost all clinical EEG laboratories. Activation infre- ings. In youth, HV may show pronounced high-amplitude delta slowing,
quently activates EDs in patients with focal epilepsy (<10%). However, appearing either in bursts or continuous runs. HV normally produces a
100 Normal Adult EEG
FIGURE 5.8: Left temporal delta (arrows) and theta awake in a 91-year-
old nun admitted for evaluation of headache.
bilateral increase in theta and delta frequencies (aka build-up) on the fron- The effect of IPS normally produces a physiologic response consisting of
tally dominant and often high-amplitude EEG. The HV response often in- rhythmic activity in the occipital head regions. Photic “driving” occurs over
cludes the appearance of FIRDA in adults. When restricted to the period the range of flash frequencies when a time-locked response is coupled to
of HV, FIRDA is a normal finding (Fig. 5.9). A good effort, young age, the flash. Responses that are elicited consist of an entrained harmonic of
adequate posture to ensure fruitful respiration, and a lower blood sugar the flash frequency. Harmonics of the flash frequency are not uncommon.
produce the largest responses. A normal effect usually resolves within Individual waveforms consist of a flash visual-evoked potential (P100) that
2 minutes. When eye flutter artifact is intermixed with frontal myogenic is time-locked to the frequency of the photic stimulation. Short distances
potentials, confusion may result from superimposition of frequencies, from the lamp are used to deliver a series of brief flashes ranging from 1 to
falsely suggesting EDs (4). Contraindications include performing HV in 30 Hz. A distance of less than 30 cm from lamp to the head is used employ-
patients with severe cardiac or pulmonary disease, acute or recent stroke, ing a period of 10 seconds per flash frequency. A photic driving response is
significant large-vessel cerebrovascular disease, and sickle cell anemia or usually greatest when using frequencies that approximate the patient’s al-
trait. It should be used with caution during pregnancy to minimize the risk pha rhythm. A photoparoxysmal response (PPR) is an ED that occurs in
of premature labor. response to IPS. Typically, a PPR consists of generalized spike-and-wave
Normal Adult EEG 101
FIGURE 5.9: EEG demonstrating a robust “build-up” during HV per-

formed by an 18-year-old with migraine. Note the nearly continuous
frontally predominant rhythmic 3-Hz delta activity. This normal feature
during HV resolved in less than 2 minutes after the cessation of HV.
or polyspike-and-wave discharges with/without clinical signs. Responses are likely to activate paroxysmal discharges due to provocation by contrasting
typically bilateral, symmetrical, and synchronous, and are most commonly interfaces (33). Flickering red lights preferentially may produce photosensi-
generated between 15- and 18-Hz flashes. It may occur independently of tivity. In addition to the routine use of HV and IPS, sleep deprivation and
seizures and exist as an inherited trait expressed in the EEG. When the PPR pharmacological sedation may be used to activate the EEG. These tech-
outlasts the IPS, it may carry a higher association with epilepsy. Eye open- niques that facilitate sleep shorten the latency of sleep onset and lengthen
ing and closure is performed to enhance ED detection. A photomyoclonic the duration. Various protocols and hypnotic drugs are utilized. Individual-
response consists of a normal response that is composed of bi-frontally pre- ized stimuli, modalities, and techniques may also be used in an effort to help
dominant myogenic artifact on the EEG. The presence of a photomyoclonic activate or trigger abnormalities in an individual patient, especially those
response occurs due to regional perioccular and frontal muscle contraction with reflex epilepsy (34). Another result of using routine activating proce-
as a result of the IPS. The muscle “spikes” increase in amplitude as the fre- dures has been encountered in patients with spells where suggestion was
quency is increased. This may occur during states of high anxiety or sub- found to precipitate psychogenic nonepileptic attacks (35).
stance withdrawal. Low-range frequency high-amplitude driving responses
have been noted with neurological conditions such as ceroid lipofuscinosis Sleep Architecture
and mitochondrial disease. At mid- and higher-range frequencies, harmon-
ics of the primary frequency may be encountered (Fig. 5.10). The presence Sleep has a well-defined architecture in normal EEG that is relatively stable
of lambda waves may predict a robust driving response to IPS. Geometric throughout life (36). Sleep architecture has important clinical ramifications
patterns often provoke EDs. Closely spaced lines or flickering dots are more in recording EEG in patients with suspected epilepsy. Activation of IEDs
FIGURE 5.10: Photic driving with harmonics (rectangles) and suprahar-

monics (oval) of 8-Hz IPS. Note the effect is bilateral but asymmetric with
a higher amplitude in the right occipital derivations. The patient had
headache and no other findings in this normal EEG.
may occur, especially during drowsiness and light sleep (37). Most patients responses during sleep transitioning to wakefulness has resulted in over-
will obtain sleep in the EEG laboratory during a routine recording (38). interpreted “ictal” recordings, leading to treatment and, therefore, merits
Stage 1 or 2 (light sleep) is usually obtainable during the 20 to 30 minutes careful delineation from abnormalities seen with seizures (39).
of routine recording. Fortunately, these are the stages of sleep that are most Stage 1 sleep (N1 sleep) is the transitional phase of wakefulness to sleep
informative in patients with epilepsy. Sleep deprivation serves to induce and may be identified by fragmentation, attenuation, and slowing of the
sleep but also to enhance epileptiform and nonepileptiform abnormalities. alpha rhythm. Greater prominence of the beta activity, waning of the
Stage 3 sleep may occasionally be encountered during a routine 20-minute myogenic artifact, and slow rolling eye movements are seen. Early during
EEG, especially when sleep deprivation or sedation are utilized. Sleep with- stage 1, sleep is intermixed with 2- to 7-Hz frequencies (Fig. 5.12A). By late
out medication is preferable to sedated sleep, though when a sleep recording stage 1 sleep, sharp transients appear that are maximal at the vertex, known
is desired. Sedation may be utilized to increase the yield in patients with as vertex waves (V-waves). V-waves are stable waveforms that are typically
previous nondiagnostic studies (14). 200-milliseconds in duration, with a morphology that consists of diphasic
Stage W (wakefulness) is readily identifiable when a prominent alpha sharp transients with a maximal electronegativity at the vertex (Cz) elec-
rhythm is noted in the posterior head regions intermixed with myogenic and trode. V-waves may be seen though stage 3 sleep. They are bilateral, syn-
vertical eye blink artifact (Fig. 5.11). Artifact that is present during wake- chronous, and symmetrical, and may be evoked by auditory stimuli. Some
fulness can result in misinterpreted EEGs (3). Some normal physiologic vertex waves can appear “spiky” (Fig. 5.12B), especially in children, but they
FIGURE 5.11: Relaxed wakefulness with eyes

closed demonstrating reactivity and a normal
10.5-Hz alpha rhythm. Monitors (gray channels)
verify vertical eye blinks in seconds 1 and 4 de-
spite the absence of muscle artifact.
should normally never be consistently lateralized. Positive occipital sharp head regions waxing and waning in amplitude. A frontal representation of
transients of sleep (POSTS) are another feature signifying normal stage sleep spindles may be accompanied by slowing of the central frequencies to
1 sleep (Fig. 5.13). These are surface-positive, bisynchronous physiologi- 10 to 12 Hz. K-complexes are high-amplitude biphasic frontocentral wave-
cal sharp waves. Voltage asymmetries may occur over the occipital regions forms with an average duration of 0.5 seconds. It is typically composed of
manifest as single complexes or in repetitive bursts that may lead to the mis- an initial sharp transient followed by a high-amplitude slow wave that may
identification of these “occipital sharp waves” as pathological when, in fact, be though not necessarily associated with a sleep spindle. K-complexes are
they are normal physiologic sharp transients encountered during stage 1 and similar to V-waves and may be evoked potentials by a sudden auditory stim-
2 sleep. ulus. A persistent asymmetry of K-complexes similar to asymmetry seen
Stage 2 sleep (N2 sleep) is defined by the presence of sleep spindles (aka with V-waves is abnormal. The lesional hemisphere is ipsilateral to the side
sigma activity) and K-complexes. This stage has the same features as stage of the reduced sleep elements (Fig. 5.14).
1, with progressive slowing of the electrocerebral background frequencies Slow-wave sleep (N3 sleep, previously known as deep sleep or delta sleep)
and greater decline in myogenic artifact. Sleep spindles appear as transient is comprised of 1- to 2-Hz high-amplitude delta frequencies that accompany
sinusoidal 12- to 14-Hz “spindled” activity lasting 0.5 seconds in the central varying amounts of the background activity (Fig. 5.15). N3 sleep implies
FIGURE 5.12: Light sleep depicted in the EEG. State transition in (A) demonstrates frontal-central 6-Hz theta
initially (gray arrow) and then low-amplitude vertex waves later (black arrow) to signify stage 1 sleep. In (B) note
the “spiky” morphology and atypical location (rectangle) that resulted in misinterpretation of a normal vertex
wave as a pathological spike.
delta frequencies that occupy greater than 20% of the recording with volt- Benign Variants of Uncertain Significance
ages of greater than 75 μV (Fig. 5.16).
REM sleep (R sleep) is characterized by rapid eye movements, loss of Certain waveforms and patterns appear rhythmic and epileptiform with
muscle tone, and low-amplitude mixed-frequency EEG that is similar to features that mimic an abnormal EEG. Some unique patterns have been
stage 1 sleep. Saw-tooth waves are 2- to 5-Hz surface negative sharp tran- identified and though they appear “suspicious,” they are variant patterns
sients that often occur in series over the vertex head regions. However, it of uncertain significance (aka benign variants). Definitions of benign vari-
is the rapid eye movements that are characteristic of REM sleep with eye ants used by the Committee on Terminology of the International Federa-
movements that occur under 300 milliseconds (Fig. 5.17). Normally, non- tion of Societies for EEG and Clinical Neurophysiology (IFSECN) serve to
REM and REM cycle four to six times over a night. A predominance of delineate these patterns (40). They are considered benign because of their
non-REM appears in the first part of the night and REM in the last third appearance in patients without a diagnosis of seizures and epilepsy, as well
of the night. A routine EEG with REM sleep may reflect the effect of sleep as their appearance in normal individuals without neurological conditions
deprivation (Fig. 5.18) and may not necessarily imply a disorder of sleep- (41). These patterns are, therefore, important to recognize in order to pre-
onset REM, such as narcolepsy. vent erroneous identification as an abnormal finding.
FIGURE 5.13: Stage 2 sleep with POSTS that are identified by the polarity demonstrating “positive” sharp
transients that have a downward deflection in channel 1 (gray arrow) and upward deflection in channel 9 (black
arrow).
FIGURE 5.14: Stage 2 sleep demonstrating (A) symmetry of the sleep elements in an AP bipolar montage
with an apparent right voltage asymmetry of the sleep spindles (rectangles) that is not evident when viewed
in an ipsilateral ear reference montage (B). Note the frontal-central distribution.
Rhythmic midtemporal theta bursts of drowsiness (RMTD) refers to a is the sharply contoured morphology (Fig. 5.20) of RMTD that may mimic
pattern that consists of bursts or runs of 5- to 7-Hz theta waves that are EDs, leading to confusion. This pattern is seen during drowsiness and light
maximal in the mid-temporal regions (Fig. 5.19). In the past, it was referred sleep when EDs become prevalent. It rarely occurs during the fully awake
to as psychomotor variant. This was because of the similarity of the fea- state. It is a pattern that does not evolve spatially or temporally, though
tures on the EEG noted in patients with temporal lobe (“psychomotor”) may intermittently be detected in adjacent parietal or occipital electrode
seizures. The pattern is seen in 0.5% to 2.0% of selected normal adults. Sev- derivations. RMTD may be represented bilaterally or appear independently
eral forms of RMTD may occur, and these include a burst morphology that and asymmetrically over both hemispheres. It is seen in adolescents and
is composed of an arciform sharp, flat, or notched appearance. However, it young adults.
FIGURE 5.15: Stage 3 slow-wave sleep with prominent slow waves that
are intermixed with K-complexes (square), sleep spindles (black arrow),
and POSTS (gray arrow). (From Tatum WO, Husain AM, Benbadis SR,
et al. Normal adult EEG and patterns of uncertain significance. J Clin
Neurophysiol 2006;23(3):200.)
FIGURE 5.16: Slow-wave sleep (stage 4) with continuous high-amplitude

delta frequencies. Note the “mittens” in the anterior head leads (square)
from superimposition of normal frequencies and the brief artifact at the
start of second 6. Note the absence of POSTS and V-waves.
FIGURE 5.17: EEG demonstrating rapid eye movement during REM sleep that results in movement during a
behavior (second 8) in an 82-year-old with REM behavioral disorder. Note the rapid horizontal eye movement
artifact (arrows).
6-Hz Generalized spike-and-wave discharges (GSW) were previously (Fig. 5.21) (43). Linking homologous areas in a bipolar montage may
r eferred to as “phantom spike-and-wave.” They are brief 1-second bursts better define these discharges, more so than routine anterior-posterior
of 5- to 7 (usually 6)-Hz GSW discharges, with spike amplitudes that are longitudinal bipolar or referential recordings due to the low-amplitude
less than 25 μV and durations of less than 30 milliseconds (42). Two forms nature of the EDs (44). These discharges last for 1 to 2 seconds. Spikes
were initially described by Hughes; WHAM (wakefulness, high amplitude, are often of low amplitude and at times difficult to appreciate by visual
anterior, male) and FOLD (female, occipital, low amplitude, drowsy) analysis, hence the term “phantom spike-and-wave” discharges. When
FIGURE 5.18: Sleep-onset REM (second 6) following prolonged sleep

deprivation. Note the onset of REM sleep associated with saw-tooth
waves (black arrows) and lateral rectus “spikes” (beneath the gray star)
that occur with the rapid eye movement (ovals).
spikes are visible but consist of a low-amplitude discharge in drowsiness A burst of 6-Hz frequencies may appear independently (Fig. 5.22). Silver-
(i.e., FOLD), they usually represent a benign finding. When they are of man suggested that there is a spectrum of variant waveforms and develop-
high amplitude (i.e., WHAM), especially if they occur with a less than mental association overlapping 14- and 6-Hz positive bursts and 6-Hz GSW
6-Hz frequency, during wakefulness or persist into slow-wave sleep, there (45). Fourteen- and 6-Hz positive bursts are most common during adoles-
is a greater association with seizures. The overall occurrence in normal in- cence, although they may persist into adulthood, decreasing with advancing
dividuals and the appearance in those without specific conditions or dis- age. Use of a contralateral ear reference montage and greater interelectrode
ease states make 6-Hz GSW discharges a pattern of uncertain significance. distance is best to demonstrate this finding. The bursts are typically unilat-
Fourteen- and 6-Hz positive bursts, also referred to as ctenoids (due to the eral or may appear bilaterally asynchronous with a shifting predominance
resemblance of a comb), appear in the EEG as bursts of surface-positive preferentially affecting one hemisphere.
comb-like “spikes” that are maximally distributed over the posterior tem- Benign epileptiform transients of sleep (BETS: aka small sharp spikes
poral head regions. These bursts last for 0.5 to 1 second in duration. Most or benign sporadic sleep spikes of sleep) are low-voltage (<50 μV), brief-
often, the positive spikes occur at a frequency of 14 Hz (range, 13 to 17 Hz), duration (<50 milliseconds), simple waveforms with a monophasic or di-
though 6-Hz discharges (range, 5 to 7 Hz) may also be seen in longer bursts. phasic spike (Fig. 5.23). Each waveform consists of a rapidly ascending
FIGURE 5.19: A: Bilateral independent RMTD during light sleep demonstrating a rhythmic 7-Hz theta fre-
quency (open arrows) and in (B) a unilateral 5-Hz theta with a rounded morphology in the left temporal deriva-
tions (rectangle).
limb and steep descending limb, which are best seen in the anterior to mid- revealed a higher amplitude, but similar morphology and features to scalp
temporal derivations during non-REM sleep. They may appear with an recording (47).
after-going slow wave (usually of lower amplitude than the spike), but are Wicket spikes (wickets) are waveforms that are composed of bursts of
not associated with focal slowing and do not occur in runs. The most dis- monomorphic 6- to 11-Hz waveforms that may obtain high amplitudes up
tinguishing characteristic is that they disappear in slow-wave sleep. They to 200 μV. Wickets are suspected to represent normal fragmented tempo-
may appear unilaterally but are independent if they occur bilaterally. When ral alpha activity. Wickets are reported to be uncommon in patients with
they are noted bilaterally, they typically possess a field corresponding to seizures with a prevalence of their occurrence in less than 3% of adult trac-
an oblique or transverse dipole that results in opposite polarities within ings (48). They are the most commonly identified variant in the EEG of
the different hemispheres. Reports of source localization have been lim- adults over 30 years of age. While they are seen bilaterally over the tempo-
ited. BETS are most commonly seen in adults. This variant has uncertain ral regions during light sleep, independently or in bursts, no distortion of
significance; however, it has the appearance of an ED. A clear relationship the background, focal-slowing, or after-going slow wave is present. Instead,
to epilepsy or other neurological or psychiatric conditions has not been they appear as an arciform surface negative monomorphic waveform prefer-
established (46). Descriptions of BETS observed using depth electrodes entially located in the temporal regions. They appear as asynchronous and
FIGURE 5.20: Bursts of RMTDs are pictured in (A) with a bilateral sharply contoured appearance and with a
unilaterally sharply contoured morphology (squares) in (B). Note the montage and double-distance electrode
that accentuates the sharp appearance (under the arrow).
asymmetric waveforms often shifting between hemispheres and between Subclinical rhythmic electrographic discharge in adults (SREDA) is a rare
wakefulness and sleep. Wickets are most visible during light sleep but have pattern in the EEG that mimics an electrographic seizure. This is in contrast
been reported to occur into REM sleep (49). This variant is one of the most to the interictal patterns mimicked by the previously mentioned variants.
important variants to recognize, given their prevalence among the variants, Despite the similar morphology of the EEG to a seizure, no objective or
their occurrence in adulthood, and the morphology and location in the tem- subjective clinical signs exist during its appearance and no association with
poral regions (Fig. 5.24). They are therefore often and readily confused with epilepsy has yet been demonstrated. In contrast to most benign variants,
EDs, especially when they appear as isolated waveforms in the temporal re- SREDA is more likely to occur in individuals over 50 years of age. It may
gions (1). They may appear fortuitously in the EEG of patients with uncon- exist in two forms. In the most common form, SREDA may appear as a
trolled seizures undergoing a presurgical evaluation and even provide false bilateral episodic burst of rhythmic, sharply contoured 5- to 7-Hz theta fre-
“localizing” information. quencies maximal over the temporal-parietal regions. It is usually bilateral,
FIGURE 5.21: EEGs demonstrating two variations of 6-Hz spike-and-waves. In (A), the anterior pattern (aka
WHAM) and in (B) the posterior pattern (FOLD) are seen within the ovals.
though may be asymmetric. It may “evolve” from a single transient or series characteristic of seizures (51). Digital analysis suggests that SREDA is due
of sharp transients in either theta or delta bandwidth and increase to be- to a mixture of rapidly shifting, predominantly theta frequencies that pos-
come a continuous rhythmical theta pattern that mimics an electrographic sess poor temporal and spatial evolution (52).
seizure (Fig. 5.25). It may also exist in another form that may appear as
an abrupt monophasic series of repetitive sharp or slow waveforms that is Variations of the Normal EEG
present focally at the vertex and recurs in progressively shorter intervals un-
til a sustained burst is apparent to simulate the evolution of an epileptic Variations of normal physiologic activity may occur that deviates from the
seizure. SREDA occurs during the waking state. Rarely, both forms may patterns that are more commonly seen. Patterns may involve commonly
appear in the same person. Bursts of SREDA usually last between 40 and 80 occurring waveforms that appear epileptiform as well as nonepileptiform.
seconds; however, despite the ictal appearance, SREDA terminates abruptly Variations may be present that are atypical based on frequency, location,
or “fades” without postictal slowing and without impaired consciousness symmetry, or distribution. These patterns may at times appear “suspicious”
or overt clinical signs that accompany the discharge (50). Single photon because they are less often encountered. For example, an alpha squeak
emission computed tomography performed during SREDA has been unre- (Fig. 5.2A) or an alpha variant that possesses a notched appearance may
vealing and has not demonstrated regional cerebral hyperperfusion that is morphologically appear abnormal despite the similar frequency, location,
FIGURE 5.22: The 14- and 6-Hz positive bursts demonstrating both the 14-Hz component (A) noted by the
gray arrows and the 6-Hz component (B) identified by the black arrows using an average reference montage.
FIGURE 5.23: Benign epileptiform transients of sleep. The first 7 sec-

onds and following 4 seconds are taken from two different patients utiliz-
ing two different montages. Note the low-amplitude brief monophasic
spikes in the examples (arrows) with a rapid ascending limb and regional
temporal field in drowsiness and stage 1 sleep.
113
FIGURE 5.24: Bilateral wicket spikes in the left and right temporal deri-
vations during drowsiness (arrows).
and reactivity to characterize an alpha rhythm (Fig. 5.26). A skull defect clinical significance, and it may mimic nonspecific “slowing” if noted while
may produce a breach rhythm with focal, asymmetrical, higher amplitude awake. However, it is generally considered a normal pattern (54). Similar
beta activity that is more than three times the normal activity. The appear- frontal theta rhythms that occur upon arousal and parietal theta rhythms
ance is a focal higher amplitude waveform due to the absence of the in- have also been described as variations of normal. Variations in the intrinsic
tervening skull to attenuate the low-amplitude faster frequencies (Fig. 5.4). rhythms above typically mimic nonspecific slowing. When paroxysmal tran-
At times, the beta may even appear “spiky” to further create difficulties in sients occur in the normal EEG, these variants are most likely to lead to a
distinguishing a normal recording. Nevertheless, a breach rhythm is normal false diagnosis of epilepsy (55).
unless it is associated with focal slowing or EDs.
A normal midline theta rhythm that is sinusoidal or archiform, lies within Misinterpreted Normal EEG
the 4- to 7-Hz theta bandwidth, and is maximally expressed over the midline
vertex region reflects the Ciganek rhythm (22) (Fig. 5.27). Morphologically, These benign variants and normal variations may be challenging to inter-
the Ciganek rhythm may resemble a mu rhythm; however, it is not similarly pret. There are several variations of normal EEG that are worthy of men-
reactive and is slower in frequency occurring both in drowsiness and the tion due to the prevalence of their occurrence. The distribution of a common
alert state. It was initially believed to be a “projected rhythm” in patients frequency if it appears in atypical location, state of alertness, or when frag-
with temporal lobe epilepsy and may appear as flat, notched, or smoothly mented may create confusion (Fig. 5.28). Despite the morphological differ-
contoured (53). It has been seen with a variable frequency in a heterogeneous ences that may be encountered, the benign variants of uncertain significance
population, has been placed in the group of the benign variants of uncertain may mimic EDs or be “suspicious” if significant variations are seen. When
FIGURE 5.25: SREDA in a healthy 72-year-old evaluated for mild cognitive impairment. Note the onset in (A)
2 minutes after HV and the characteristic repetitive bilateral posterior potentials (B) that coalesce to diffuse
theta (C) and then gradually return to a baseline 10-Hz alpha rhythm without postictal slowing (D).
RMTD occurs in long runs, though it is monomorphic and does not possess runs to mimic a seizure (Fig. 5.30). Lambda waves (Fig. 5.31) are surface-
temporal and spatial characteristics that evolve like a seizure, fluctuation of positive sharp waves that occur in the theta bandwidth, which are elicited
a rhythmic pattern may attract the attention of even an experienced electro- by visual scanning. They appear bilaterally in the occipital region during
encephalographer (Fig. 5.29). Mu has been described as a rhythme en arceau wakefulness. These potentials have durations of 160 to 250 milliseconds and
due to the comb-like morphology that may appear very “spiky”; especially may at times be quite sharply contoured, asymmetrical, and with higher
in children and young adolescents appearing as brief bursts or in prolonged amplitudes than the resting posterior dominant rhythm. When they occur
FIGURE 5.26: Dual frequencies associated with IPS at 10 Hz with

supraharmonics recorded at 20 Hz. Note the polyspike-like appearance
(arrow) of superimposition of the frequencies and the concomitant right
central-temporal focal slowing during drowsiness (gray oval) outside the
duration of the photic flash.
FIGURE 5.27: Midline theta in a combined A–P bipolar longitudinal

(first and last 8 channels) and transverse (channels 10–17) montage. Note
the prominent theta frequency (rectangle) during the awake state. (From
Tatum WO. Normal EEG. In: Tatum WO, Husain AM, Benbadis S, et al,
eds. Handbook of EEG interpretation. New York, NY: Demos Medical
Publishing, LLC, 2008:1–50.)
FIGURE 5.28: Normal alpha in the posterior temporal location (arrow) during transition from the awake to
drowsy state. The higher amplitude and the sharp morphology in the left posterior temporal derivation due
to a breach rhythm.
FIGURE 5.29: The EEG below was obtained in a patient with PNEA
(Psychogenic Nonepileptic attacks). Left > right bilateral RMTD was
noted during prolonged video-EEG monitoring. The patient has
remained attack free following discontinuation of automatic external de-
fibrillators. Note the train of monomorphic 5.5-Hz theta during drowsi-
ness that demonstrates variable amplitude.
FIGURE 5.30: Left mu rhythm with an archiform morphology in the cen-

tral head regions. While the pattern might falsely be mistaken for an
ED, reactivity demonstrated by the thought of shaking the technologists
hand is present with disappearance of the mu rhythm (arrow).
FIGURE 5.31: Lambda waves (circle) associated with eye movements. Scanning eye elicits these waveforms
and a blank piece of paper in front of the eyes eliminates them. Note the same distribution as the alpha
rhythm.
FIGURE 5.32: Spike-driving (arrows) during IPS at 3 Hz. The location is

in the posterior head regions (bold black arrows), the sharp morphology,
and the surface-positive polarity evoked 100 milliseconds following the
flash (thin black arrows). Note the frontopolar discharge seen earlier than
the “spikes” in the electroretinogram (gray arrows).
asymmetrically, they may be confused with EDs and lead to misinterpreta- activity. To distinguish the ERG from the photoelectric effect, covering the
tion of the EEG. Best observed in young adults, they are most frequently electrodes with a cloth will demonstrate the persistence of the potentials.
found in children. Lambda waves are best elicited when the patient visu- Additionally, high rates of IPS will fatigue the retinal response.
ally scans a textured or complex picture with fast saccadic eye movements. Overlapping normal frequencies may also be deceiving. Superimposition
Placing a white sheet of paper in front of the individual will eliminate the of background frequencies may occur, resulting in complexity of different
visual input that is essential for their genesis. IPS may involve generation of waveforms that by virtue of the contrast between different frequencies, cre-
“spike-driving” at lower-range frequencies (Fig. 5.32). The pitfall includes ates the appearance of an epileptiform abnormality (Fig. 5.33). Resolving
overinterpretation of these “spikes” as pathological EDs that imply an as- the independent components that are superimposed, normal physiologic fre-
sociation with epilepsy. The electroretinogram (ERG) seen in the figure is a quencies may be difficult. When normal frequencies are superimposed on ab-
normal response of the retina to IPS. The amplitude is usually low voltage normal features in the EEG, this may be more difficult to discern (Fig. 5.34).
and appears in the anterior head regions. This electrophysiological poten- Following the principles that govern polarity and fields are key to avoid the
tial can be seen on the EEG and be confused with abnormal frontal sharp pitfalls of overinterpreting the EEG (37). The use of extracerebral monitors,
FIGURE 5.33: EEG demonstrating a hypnogogic burst of theta during

state transition from wakefulness to drowsiness. Note the appearance of
“spiky” waveforms (arrows) due to superimposition of normal beta and
theta and the intermixed myogenic artifact admixed within the burst.
FIGURE 5.34: A burst of wicket spikes (black square) stands out due
to morphology and distribution in the temporal region during sleep.
The patient was operated successfully for epilepsy 2 years prior to this
EEG performed before a trial of automatic external defibrillator taper.
A breach rhythm and focal delta was noted but no pathological ED
were seen and taper was successful. (With permission from Tatum WO,
Dworetzky BA, Schomer DL. Artifact and recording concepts in EEG.
J Clin Neurophysiol 2011;28(3):252–263.)
such as those placed around the eye, may be helpful in distinguishing slow Conclusion
ocular and fast myogenic sources from superimposing upon normal EEG to
mimic abnormality (56). Understanding the criteria to define normal rhythms is a prerequisite to
It is essential to avoid misinterpretation of EEG, which might carry im- understanding what constitutes an abnormal record. Learning to identify
plications that could lead to mistreatment (Table 5.4). EEG is neither spe- the patterns of normal includes features of the EEG that includes atypical
cific for the type of cerebral dysfunction nor does it imply that a normal variations and benign variants. These waveforms are crucial to interpreting
result carries definitive conclusion as to the reason the study was performed. normal “brain waves” correctly and to limit overinterpretation. Waveforms
When an abnormality is in question, a conservative interpretation is war- outside of the routine spectrum of normal frequencies comprise elements
ranted to minimize overinterpretation, which could result in an incorrect that are most subject to misinterpretation.
change in therapy (1,22,57). Avoiding a potential bias by interpreting the It is commonly said that a normal EEG does not exclude a clinical di-
EEG without knowledge of the reason for referral will maximize the objec- agnosis (Fig. 5.35). In much the same way, reports of an abnormal EEG
tive assessment of the EEG.
In the end, a good interpreter is only as good as the EEG report. Often-
TABLE 5.5 Warning Signs for an Overinterpreted EEG Report
times, the wording and style of the EEG report is a clue that overinterpreta-
tion may exist. A report that sounds confusing may have some warning signs Abnormal Report
(Table 5.5) that suggest the need for reinterpretation. Warning Signs Relevant EEG Features
Bias Check to see if the EEG interpreter is the
same person as the clinician
TABLE 5.4 Waveform Characteristics and the Approach
to Identifying Suspicious Features in the EEG Focal slowing Check the age of the patient to allow for
age-appropriate slowing or normal variant
Characteristic Suspicious Waveform(s) Single spike Doubt the significance of a single spike
Frequency Are there identical frequencies within the same without reproducibility
burst or epoch of time that are similar to normal Spikes Check to see if the location and state suggest
waveforms? a location where normal variant or artifacts
Polarity Does the polarity conform to a “believable” cere- occur (especially the parietal and posterior
bral field and reflect a valid electrophysiological temporal derivations)
generator? Sharp waves Check to see if the location is a common one
Amplitude Does the waveform “stand-out” from the back- where theta frequencies normally occur
ground and represent a finding that is >150% of around 200 milliseconds
the normal background? “Possible or suspicious” Check the description of the temporal and
Morphology Are there morphologies that overlap with the suspi- seizure spatial characteristics to ensure they
cious waveform in the same burst or epoch that correspond to a paroxysmal, evolving,
are normal? “believable” cerebral field
Duration Is the duration <20 or >200 milliseconds to sug- More than one or atypical Be suspicious if >1 or a variable field is
gest either an artifact (fast) or normal theta (slow) field in different present other than a bitemporal field
frequency? hemispheres (i.e., left parietal and right frontal)
Distribution Is the electrical field distributed in a way that is More than one mechanism Be suspicious when the report contains
compatible with patients that have a neurological in the report for EDs >1 mechanism, such as generalized and
abnormality? focal features (or epileptic and nonepileptic)
FIGURE 5.35. A: Normal EEG following a breakthrough seizure after amygdalohippocampectomy and sub-
sequent phase 2 and lateral neocorticectomy. Note the normal EEG (10–20 system of electrode placement)
despite the extensive resection of the left temporal lobe on the MRI in (B).
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Normal Pediatric EEG: Neonates
6 and Children
ROBERT R. CLANCY • A.G. CHRISTINA BERGQVIST • DENNIS J. DLUGOS •
DOUGLAS R. NORDLI Jr.
Introduction to the Pediatric Electroencephalogram Types and Significance of Abnormal Pediatric

Visual Analysis Electroencephalographic Backgrounds
State and Continuity Excessive Discontinuity
Organization and Principal Components Sharp Electroencephalographic Transients
Interhemispheric Symmetry and Synchrony Electrographic Neonatal Seizures
Special Features and Clinical Correlations
Abnormalities Sharp Waves and Spikes in the Older Infant
and Child
Overview of Electroencephalographic Ontogeny
Activity of Drowsiness, Arousal,
24 to 29 Weeks of Conceptional Age
and Sleep
Classification of the Neonatal
33 to 34 Weeks of Conceptional Age Electroencephalographic Background
35 to 36 Weeks of Conceptional Age and Its Implications
37 to 40 Weeks of Conceptional Age An Organized Approach to Visual Analysis
41 to 44 Weeks of Conceptional Age of the Electroencephalogram
45 to 46 Weeks of Conceptional Age Continuity and State Concordance
Early Infancy: 46 Weeks to 1 Year Gradient and Principal Components
Late Infancy: 1 to 2 Years Symmetry and Synchrony
Childhood: 2 to 10 Years Special Features
Adolescence Abnormalities
Composition of Electroencephalographic Final Words
Background Activity (Named Patterns) References
Neonatal
Infancy and Childhood
125
126 Normal Pediatric EEG: Neonates and Children
INTRODUCTION TO THE PEDIATRIC

ELECTROENCEPHALOGRAM
The previous chapter covered the normal adult EEG and introduced the
major necessary concepts to analyze EEG. Pediatric EEG interpretation
builds on these essential skills but requires one additional element: a thor-
ough knowledge of EEG ontogeny, or the orderly maturational changes in
pediatric EEG. Children are not small adults, and at first glance their EEGs
could not appear more distinct, but the same techniques used to systemati-
cally analyze the adult EEG can be applied to children once one appreciates
the organizational themes of pediatric EEG. Accordingly, this chapter will
not recapitulate elements from the prior chapter, but instead will focus on
the development of pediatric EEG from the premature to adolescence.
To make the discussion as practical as possible, the pediatric EEG will be
described in the same order in which it is typically analyzed, noting first the
continuity and then, in turn, the organization of the principal components,
the interhemispheric symmetry and synchrony of these components, and the
presence of various special features that often serve as signposts of matura-
tion. Finally, abnormalities are noted and described. The discussion will begin
with the most premature babies and will continue through to adolescence.
Before the visual analysis (VA) is discussed, there are a few technical mat-
ters that must be addressed. The international 10–20 system of electrode Figure 6.1a: Intrauterine MRI of fetus 30 weeks of estimated gestational age.
placement is modified for neonatal EEG recording because of neonates’ Notice the relatively simple convolutional markings of the frontal lobes in com-
small head size and the relative lack of EEG activity in the extreme frontopo- parison with the occipital cortices.
lar regions (Fig. 6.1a,b). The standard neonatal montage includes electrodes
Fp3 (halfway between Fp1 and F3), Fp4 (halfway between Fp2 and F4), C3, are considered premature if born before the 37th week. Term infants are born
C4, T3, T4, 01, 02, Fz, Cz, Pz, A1, and A2 (1). If the earlobes are too small, between the 37th and 42nd weeks of gestation, and postterm infants are born
mastoid leads (M1 and M2) may be substituted. Fp3 and Fp4 electrodes are after 42 weeks of gestation. In an arbitrary but practical manner, we stop
used because electrographic background activity and frontal physiological counting children’s ages in months sometime beyond the second or third year,
sharp waves are better visualized there than at the usual frontopolar loca- and convert to years, or fraction of years (e.g., 2.5-year-old child).
tions (Fp1 and Fp2) (2). Beyond 6 weeks of age or a head circumference of
40 cm, many laboratories will use the same complement of electrodes found
in adult tracings. At the same time, most EEGers in North America will VISUAL ANALYSIS
change the display to 30 mm per second, again resembling adult tracings.
The one piece of extraneous information that is needed to properly interpret State and Continuity
a pediatric EEG is the age of the patient (although in many circumstances the
skilled EEGer can develop a fairly accurate estimate). In neonates and young The VA begins with an assessment of the state of the child and the continu-
infants, the most relevant is the conceptional age. This is determined by add- ity of the background. For all pediatric EEG tracings, there should be a tight
ing the number of weeks since birth to the estimated gestational age (EGA). concordance between state and EEG background, and the tracing should be
The EGA is the age of the fetus since conception, calculated from the time of continuous in all states. The notable exception is the neonatal period where
the mother’s last menstrual period to the day of the infant’s birth. Newborns tracings are normally discontinuous in the premature. Indeed, an accurate
Normal Pediatric EEG: Neonates and Children 127
is uncommon. Occasional startles or arousals may briefly interrupt quiet

sleep. Since quiet sleep is most vulnerable to adverse medical or neurological
conditions, it is essential to try to capture quiet sleep for a thorough assess-
ment. In newborns and infants with mild encephalopathies, the awake and
active sleep recording may appear normal, but quiet sleep recordings reveal
previously unrecognized abnormalities.
Even in healthy newborns, much of sleep is indeterminate or transitional:
That is, even with a good-quality EEG and careful behavioral observation,
it is not possible to determine precisely whether the child is in active or quiet
sleep. This is clearly the case when the infant transits from one behavioral
state to another (transitional sleep), but it also applies when an exact des-
ignation of active or quiet sleep cannot be assigned. A large proportion of
total sleep time is indeterminate at term and increases in the setting of medi-
cal or neurological illness (Fig. 6.2).
The earliest vestiges of EEG activity are believed to arise after the 8th
week of gestation where the EEG tracing appears as a completely dis-
continuous recording in which brief periods of electric activity (“bursts”)
are interrupted by periods of quiescence (“interburst” intervals or IBIs).
With the development of central nervous system (CNS) maturity and the
increased influence of the deep grey structures that modulate cortical func-
tion, the duration of the burst (burst interval [BI]) increases, whereas the
length of the IBI decreases. EEG signals that regularly vary between the
high-amplitude “on” periods of the bursts and low-amplitude “off ” periods
of the IBI are called discontinuous EEGs. Those that display a relatively
Figure 6.1b: Modification of the international 10–20 system commonly used in steady amplitude are considered continuous.
neonates. A single montage includes anteroposterior, transverse, and midline The duration of the IBIs is a semiquantitative measurement of one
arrays. Fp3 and Fp4 replace the usual Fp1 and Fp2 electrode locations. aspect of the neonatal EEG. A typical, representative portion of the
discontinuous portion of the EEG is selected for review, and the dura-
assessment of the quantity and quality of the continuity of the background tion of the IBIs is measured and counted over a specific period of time:
in the various states is the single most important factor in neonatal EEG. for example, a 10-minute sample. In that representative portion of time,
Simple definitions of state suffice: in sleep, the eyes are closed, and in numerous measurements of the IBI are made, and the mean, median,
wakefulness, the eyes are open. In a well-developed newborn in active sleep, and longest IBI values can be measured. The prime determinant of
there are a variety of small and large body movements, sucking, and even measures of the IBI is the infant’s conceptional age. A typical median
crying behaviors that are punctuated by bursts of predominantly horizon- IBI at the conceptional age of 24 weeks is 10 seconds; this gradually
tal rapid eye movements—the REM phase of active sleep. Brief apneas are decreases at older conceptional ages to values around 2 to 4 seconds
relatively common, especially before term. Newborns often enter into active (Fig. 6.3) (2–12).
sleep from wakefulness. This pattern of sleep onset continues until about 3 Beyond 2 months of age, the EEG tracing should be continuous in all
to 4 months postterm, at which time quiet sleep precedes active sleep, just as states. The importance of this fact cannot be overstated. Any older infant
it will throughout adult life. with a discontinuous background is demonstrating signs of an encepha-
In a well-developed newborn and infant in quiet sleep, there are few head, lopathy, and this is one of the most powerful prognostic features in a wide
trunk, or limb movements. Respirations are regular, deep, and slow. Apnea variety of clinical settings, including epilepsy.
Figure 6.2: The percentage of total sleep time

occupied by indeterminate sleep is significantly
increased in sick newborns with abnormal electro-
encephalographic backgrounds. (Adapted from
Watanabe K, Miyazaki S, Hara K, et al. Behavioral
state cycles, background EEGs and prognosis of
newborns with perinatal hypoxia. Electroencepha-
logr Clin Neurophysiol 1980;49:618–625.)
Organization and Principal Components

Newborns do not have a consistent anterior to posterior voltage and
frequency gradient, but all older infants and children should. This d
evelops
by 3 months and from this point forward becomes the second most impor-
tant general feature of the pediatric EEG. In contrast to adults where low
voltage undifferentiated backgrounds may be seen as a normal variant,
this is virtually unheard of in infants and children. Awake children beyond
3 months should have a clear gradient. This is disrupted in drowsiness and
sleep; therefore, if the gradient is not present, one must wonder whether the
child is drowsy or encephalopathic.
The gradient is composed of three principal rhythmic components located
in the posterior, central, and frontal regions, corresponding to the alpha,
mu, and beta rhythms, respectively. While these more mature organized
rhythms are absent in the newborn, there are other named patterns that
are important to recognize. These named patterns are not truly precursors
Figure 6.3: Median IBI duration decreases with advancing conceptional age in to the more mature components and are not obligatory like the posterior
survivors of prematurity. The premature infants who died are characterized by IBIs dominant rhythm, but important signposts of maturation, nonetheless.
that are significantly longer in duration than the IBIs of survivors. (Adapted from Therefore, these components of neonatal EEG will be briefly mentioned in
Clancy R, Rosenberg H, Bernbaum J, et al. Survival outcome prediction in prema- the overview of the ontogeny and then in detail in the following section on
ture infants with IVH by cranial ultrasonography and EEG. Ann Neurol 1994;36:489.) principal components.
Interhemispheric Symmetry and Synchrony for age, but it is still possible to determine whether these same elements are sym-
metric. There are two facets of background symmetry to be judged: amplitude
Normal EEG activity arising from the two hemispheres or homologous brain and waveform composition (Figs. 6.4 and 6.5). Amplitude symmetry implies
regions should be essentially symmetrical at any age, including the newborn. It that, in a suitably large sample of cerebral electrical activity, the background
may be difficult for the reader unaccustomed to pediatric EEGs to accurately voltages between the hemispheres or specific regions are approximately equal.
judge whether the absolute quantity of various frequency elements is normal There is no universal agreement as to what amount of amplitude asymmetry
Figure 6.4: Asymmetry secondary to cerebral pathology in an infant 41 weeks of conceptional age with
Sturge-Weber syndrome affecting the right hemisphere. The right occipital region is slow and contains sharp
waves, in comparison with the normal-appearing left hemisphere.
Figure 6.5: Asymmetry secondary to scalp edema in an infant 41 weeks of conceptional age with tetralogy of
Fallot and seizures. The infant’s head was turned to the right, and marked right scalp edema was present. The
amplitude is decreased on the right side, but the background composition is similar to that of the left. The
asymmetry disappeared after the scalp edema resolved.
constitutes an electrographic abnormality. A useful interpretation guideline is Abnormalities

that an abnormality may be suspected if the amplitude difference between two
regions exceeds a 2:1 ratio (11,13–15). Likewise, guidelines for the complexity Many abnormalities such as slowing and attenuation have very similar sig-
of the waveforms are not well established, and therefore this is usually left to nificance in pediatric EEGs as in adult studies, but the clinical significance
the discretion of the reader to decide whether the frequency components are of certain abnormalities like sharp waves and spikes varies as a function of
relatively similar between two regions or hemispheres. age and location. This is most critical in the newborn, and therefore the spe-
Interhemispheric synchrony is another measure reflective of CNS matu- cial significance of sharply-contoured discharges will be reviewed in some
ration. In the neonates, interhemispheric synchrony is measured during the detail. Finally, neonatal seizures will be discussed—even though they are
discontinuous portions of the EEG. Asynchrony is defined as bursts of mor- never normal—as no review of neonatal EEG would be complete without
phologically similar EEG activity in homologous head regions separated by some discussion on this important topic.
more than 1.5 to 2.0 seconds (Fig. 6.6). Somewhat paradoxically, neonates
at a conceptional age of less than 30 weeks exhibit hypersynchrony, whereby
the majority of bursts arising within the two hemispheres appear at the same OVERVIEW OF ELECTROENCEPHALOGRAPHIC
time (Fig. 6.7). The physiological basis for interhemispheric hypersynchrony ONTOGENY
is unknown. After the conceptional age of 30 weeks, hypersynchrony gives
way to the appearance of asynchronous bursts of cerebral electrical activity The development of the fetal brain undergoes explosive changes with
between the two hemispheres. About 70% of bursts during quiet sleep are regard to its overall anatomic appearance, synaptic connectivity, time-
synchronized at the conceptional age of 31 to 32 weeks, increasing to 80% dependent genetic expression of neurotransmitter receptor subunits, and
at 33 to 34 weeks, 85% between 35 and 36 weeks, and 100% after 37 weeks their consequent functional abilities. In parallel with these anatomical and
(2,11,14,16). functional changes is an orderly, predictable pattern of neonatal EEG char-
In older infants, synchrony is largely judged by sleep architecture. Sleep acteristics that emerge simultaneously with advancing maturity of the fetal
spindles and vertex waves are normally asynchronous until 18 to 24 months, brain (Fig. 6.8). EEG maturation continues at a rapid pace during infancy,
at which point they are expressed simultaneously across the hemispheres slows during childhood, and nearly plateaus in adolescence, whereupon it
along with K complexes. settles into a form that remains relatively stable for the next seven to eight
decades. For practical reasons, the discussion of EEG ontogeny begins with
the infant at 24 weeks EGA, near the current boundary of fetal viability (7).
Special Features
It will proceed through infancy, into childhood, and finally adolescence.
A variety of special features are encountered in the pediatric EEG that are The general hope of this chapter is to provide a fluid discussion of pediatric
unique to this age or have a clinical significance that is different from that EEG interpretation from the premature to adolescence, with a consistent
seen in an adult. In neonatal, infant, and childhood EEGs, some of these method of reading that can be used throughout the age spectrum.
special features can be helpful signposts of maturation and will be discussed
in some more detail. The reader encountering these features for the first time 24 to 29 Weeks of Conceptional Age
is encouraged not to get lost in the details but to retain the general gestalt.
Overtime, it is critical to master the identification of these special features EEGs obtained from the very premature infant are, for the most part,
because these are the elements that are most likely to be confused with path- discontinuous recordings where low-voltage (<25 μV) quiet periods are
ological waveforms and may therefore lead to erroneous conclusions in the punctuated by brief epochs of moderate-amplitude activity. The latter are
interpretation. One example is the exuberance of rhythmic slowing normally composed of various recognizable, named patterns such as the delta brush,
seen in state transitions or during hyperventilation (HV) in the young. The monorhythmic occipital delta activity, and bursts of rhythmic occipital and
authors’ have seen these patterns misinterpreted as “paroxysmal discharges” temporal theta activity. The duration of the low-voltage IBIs varies with
when, in fact, they are completely normal for age. age, being longer in the youngest patient and decreasing in duration as the
Figure 6.6: Excessive asynchrony in an infant 46 weeks of conceptional age with nonketotic hyperglycinemia.
Bursts of right (large arrow) and left (small arrow) hemispheric activity are not synchronized.
Figure 6.7: Synchrony in a premature infant 27 weeks of conceptional age with dysmorphic facial features.
Cerebral activity is well synchronized between the hemispheres.
Figure 6.8: Overview of development of electroencephalographic background between 24 and 46 weeks of

conceptional age.
brain matures. The typical IBI averages about 6 to 12 seconds in physi- between the clinical and electrographic expressions of the biobehavioral
cally healthy infants at this age. Most of the EEG bursts are well synchro- state at this conceptional age.
nized, appearing simultaneously (within 1.5 to 2.0 seconds) between the left
and right cerebral hemispheres. Although infants clinically cycle through 30 to 32 Weeks of Conceptional Age
awake/asleep periods with eye opening (i.e., wakefulness) and eye closure
(i.e., sleep), there is qualitatively little difference in the appearance of the By this conceptional age, there first appears some differentiation of the EEG
EEG background. In other words, there is little concordance (agreement) pattern that distinguishes wakefulness (or REM/active sleep) from non-REM,
or quiet, sleep. There is some concordance between the appearance of the and electrographically, and the concordance between the appearance of
background EEG and the behavioral state. During wakefulness or active sleep, the EEG and the behavioral state is easier to recognize. Less of the EEG
the EEG begins to “fill in” some of the low-voltage IBIs that had previously is indeterminate—that is, lacking in the distinguishing characteristics that
remained monotonously invariant. The awake/active sleep EEG is relatively allow definitive classification into specific biobehavioral states. In the awake
more continuous, with longer-duration BIs. The actual composition of the and active sleep record, the background is more continuous, with further
bursts still largely resembles that at earlier gestational ages, dominated by the filling in of the gaps between the EEG bursts. The IBIs are fewer and briefer
synchronized, monorhythmic occipital delta activity, some of which are incor- than before. The monorhythmic occipital delta activity is fading, and most
porated into posterior delta brushes. The brief bursts of rhythmic theta activ- of the bursts of rhythmic theta activity appear in the temporal regions. Up
ity have migrated more from the occipital to the temporal areas. There are to this conceptional age, there are more delta brushes per minute in the
still many portions of the record that are discontinuous, even during wakeful- awake and active sleep portions of the recording than during quiet sleep.
ness and active sleep, but the IBIs are a little briefer, about 5 to 8 seconds on Trace discontinu continues to be the quiet sleep pattern, and the IBIs range
average. During well-developed quiet sleep, the record is persistently discon- from 5 to 8 seconds, but the synchrony of the bursts is, paradoxically, less
tinuous and is distinguishable from the awake/active sleep tracing. The term than at earlier conceptional ages. Only about 70% to 80% of the bursts in
trace discontinu (discontinuous tracing) is first applied to this early form of a the discontinuous portions of the study are synchronized, occurring within
healthy quiet sleep recording in which bursts of normal cerebral electric activ- 1.5 to 2.0 seconds between the two hemispheres.
ity are regularly interspersed with low-voltage (<25 μV) periods of quiescence.
The record may be marginally reactive to external stimulation: if the patient 35 to 36 Weeks of Conceptional Age
is provoked during quiet sleep, there is a visible change of the actual EEG
background (not just EMG or movement artifact from patient motion) with By this conceptional age, biobehavioral states are easily distinguished, and
the appearance of a more continuous background resulting from the arousal. the EEG shows definite and reproducible reactivity to external stimulation.
Trace discontinu is an important EEG maturational milestone, inasmuch In wakefulness and active sleep, the EEG is essentially continuous and is
as it is the first EEG pattern to emerge that differentiates wakefulness from composed of low- to moderate-amplitude, mixed-frequency activity. This
sleep in the premature infant. With the development of trace discontinu, there normal pattern that typifies the awake and active sleep record is commonly
is, for the first time, some concordance between the infant’s clinical state and called activité moyenne (“average activity”). There is little left of the high-
the EEG background. During quiet sleep, the trace discontinu pattern devel- amplitude monorhythmic occipital delta and only few remnants of the
ops; it consists of bursts of high-amplitude (≤200 μV) activity separated by rhythmic theta bursts. The signal is composed of admixed, coexisting fre-
periods of relative quiescence with amplitudes of less than 25 μV (Fig. 6.9). quencies ranging from delta to beta frequencies and a few delta brushes in
The bursts are composed of normal theta and delta activity, and the accept- the occipital, central, and temporal areas. The quiet sleep record remains
able range of the IBIs durations is determined by the conceptional age. discontinuous, but the amplitude of the IBI gradually increases as the dura-
By 32 to 34 weeks of conceptional age, the trace discontinu pattern is well tion further declines. At this point, the typical IBI duration is about 4 to
developed. Wakefulness and active, quiet, and indeterminate (transitional) 6 seconds, and its amplitude clearly exceeds 25 μV. The name of this normal
sleep EEG stages emerge with improved clinical concordance. Trace discon- immature, discontinuous quiet sleep pattern is trace alternant, indicating a
tinu remains the EEG pattern of quiet sleep until 36 weeks of conceptional pattern that alternates between high-amplitude BIs and low-amplitude IBIs.
age, when the IBI amplitude exceeds 25 μV, which defines the more mature Between 34 and 36 weeks of conceptional age, the trace discontinu pattern
pattern of quiet sleep, trace alternant. of normal quiet sleep begins to evolve into the more mature pattern of trace
alternant (Fig. 6.10) (5). In both trace discontinu and trace alternant, the
33 to 34 Weeks of Conceptional Age tracing is discontinuous. The fundamental distinction between trace discon-
tinu and trace alternant lies in the amplitude of the IBI. In trace discontinu,
By this conceptional age, there is further consolidation of the biobehavioral it is less than 25 μV, whereas in trace alternant, it is greater than 25 μV. The
states: active and quiet sleep are more clearly distinguishable both clinically bursts of cerebral activity in trace alternant consist of symmetrical delta
Figure 6.9: Trace discontinu in an infant 31 weeks of conceptional age with apnea. The tracing is discontinu-
ous. Bursts of activity are composed of normal patterns for age, and the amplitude of the IBI is less than 25 μV.
Figure 6.10: Trace alternant in an infant 37 weeks of conceptional age with hypotonia. The tracing is discon-
tinuous. Bursts of higher amplitude patterns, which are normal for age, alternate with lower amplitude activity.
The amplitude of the IBIs exceeds 25 μV.
activity, admixed with faster frequencies, with amplitudes of 50 to 300 μV. accounted for about 10% of total quiet sleep time at 36 weeks of concep-
The duration of the bursts varies considerably, but is typically more than tional age, 40% at 40 weeks, and 100% by 44 to 45 weeks (17) (Fig. 6.12).
2 seconds. The composition of the IBI of trace alternant resembles the This sets the stage for the EEG background that typifies quiet sleep for
EEG during wakefulness and active sleep and consists of mixed frequencies the rest of the life span. Trace alternant and CSWS comingle at this age.
with amplitudes of 25 to 50 μV. The duration of the IBI shortens as term Delta brushes remain more abundant in quiet sleep than in active sleep, and
approaches and normally does not exceed 2 to 4 seconds by 38 to 40 weeks the amplitude of background delta activity is highest posteriorly, an early
of conceptional age (2). Trace alternant itself begins to wane by 38 to 40 expression of a frequency-amplitude gradient (19).
weeks of conceptional age, although fragments may persist until 44 to 46
weeks of conceptional age. Trace alternant is gradually replaced by the more
mature pattern of continuous slow-wave sleep (CSWS) (6,17).
These bursts are typically more synchronized than at the prior concep- In healthy infants of this conceptional age, activité moyenne continues to
tional age; about 85% appear simultaneously between the two hemispheres. constitute the background during wakefulness/active sleep, whereas delta
Delta brushes are more abundant in quiet sleep than in active sleep, and brushes gradually disappear by 44 weeks. On occasion, the awake EEG dis-
much of the record can be assigned to definite sleep categories. plays broad biphasic lambda waves in the occipital regions bilaterally, coin-
cident with visual fixation. In quiet sleep, CSWS gradually replaces trace
37 to 40 Weeks of Conceptional Age alternant, except at the onset of quiet sleep. The bursts of activity in trace
alternant are well synchronized, but the IBI durations are quite brief, typi-
The waking EEG resembles the background of the onset of active sleep, cally less than 2 to 4 seconds, and their amplitudes exceed 50 μV. By the end
composed of low-amplitude (<25 μV), predominantly 4- to 7-Hz theta and of this epoch, all of the discontinuous portions of quiet sleep have been
low-amplitude delta activity (Fig. 6.11). There are two basic active sleep pat- “filled in,” and trace alternant is completely replaced by CSWS.
terns in neonates older than 36 weeks of conceptional age.
Neonates usually enter their sleep cycle in active sleep, and the dura-
tion of active sleep cycles varies between 10 and 45 minutes. As the infant 45 to 46 Weeks of Conceptional Age
enters active sleep the first time, the background is composed of moderate-
amplitude (25- to 50-μV) irregular theta and delta activity with relatively The distinguishing characteristic of this period is the first appearance of
few frontal transients (encoches frontales) (5). Subsequent cycles of active sleep spindles in CSWS (6,20) (Fig. 6.13). Once they arise, they appear
sleep have lower amplitude, more theta activity, and less delta activity, and with their usual frequency (about 12 to 14 Hz) and are typically centered
resemble the EEG of the awake state (activité moyenne). over the midline (Fz-Cz region), spreading to the neighboring left or right
In healthy full-term infants, there are clearly and easily recognizable peri- central regions (C3 or C4). In the course of the entire quiet sleep record,
ods of wakefulness/active sleep and quiet sleep. About 25% of total sleep there are about the same numbers of sleep spindles spreading into the left
time is occupied by indeterminate sleep (18). Once quiet sleep is established, and right central regions (i.e., they are symmetric), but they are not well
trace alternant first appears with typical IBIs of 2 to 4 seconds, and essen- synchronized.
tially all of the bursts arise synchronously. If the infant remains asleep for a
while, trace alternant gives way to a moderate- to high-amplitude, uninter- Early Infancy: 46 Weeks to 1 Year
rupted delta activity, the earliest expression of CSWS.
CSWS is the final major stage developed in the ontogeny of the EEG in The tracé alternant pattern gradually fades away over the next 4 to 6 weeks
quiet sleep. CSWS consists of nonstop delta and theta activity with ampli- as do frontal sharp transients and brushes. Active sleep continues to precede
tudes of 50 to 300 μV; it resembles stage-3 and -4 sleep seen in older patients. quiet sleep until about 3 months, at which time a quick transition will be
Discontinuity with BIs and IBIs is no longer present. The first fragments of made to non-REM sleep onset. EEGs after 46 weeks conceptional age and
CSWS emerge around 35 weeks of conceptional age. In one study, CSWS before 3 months of legal age are challenging to interpret because of the
Figure 6.11: Wakefulness in an infant 41 weeks of conceptional age evaluated for staring episodes. The trac-
ing consists of continuous, mixed-frequency activity of low to medium amplitude (activité moyenne). Muscle
activity (arrow) suggests wakefulness and helps to distinguish this pattern from that of active sleep.
Figure 6.12: Evolution of quiet sleep from imma-

ture trace alternant to CSWS in normal infants. At
32 weeks of conceptional age, all quiet sleep is dis-
continuous. By 46 weeks, all quiet sleep in CSWS.
(Adapted from Watanabe K, Iwase K, Hara K. Devel-
opment of slow-wave sleep in low-birthweight
infants. Dev Med Child Neurol 1974;16:23–31.)
inherent disorganization and lack of well-defined markers. By 3 months, an maintained. By 6 months, it matures to 4 Hz, and reaches 6 Hz by the first
anterior to posterior voltage and frequency gradient appears. Shortly there- year. Central theta rhythms are present by 6 months, and similar to the mu
after, occipital rhythmic activity responsive to eye opening will appear in rhythm seen in older children and adults have an arcuate morphology. Cen-
three-fourths of normal infants between 3 and 4 months of age. This domi- tral rhythmic theta activity may be strictly unilateral, bilateral, or shifting in
nant rhythm begins in a poorly sustained fashion and has a frequency of character. More anteriorly, there is low-voltage fast activity clearly visible
3.5 to 4. In young children, the alpha rhythm may totally block during eye throughout the wake tracing.
opening, so the true dominant rhythm will only be recorded with passive eye By 6 months, sleep spindles and vertex waves are both present in light
closure. Sometimes, spontaneous sustained eye closure will only occur just sleep. They are normally asynchronous at this age, but should be roughly
as the infant is about to go to sleep, and this may give a false impression of symmetrical when comparing one side with the next. They will be more pos-
a slowed dominant rhythm due to unrecognized drowsiness. Sleep spindles teriorly located compared with their final mature location, and during the
will be present, as early as 4 weeks. Vertex waves will often become apparent first year of life may occur in remarkably long monomorphic runs, some-
by 3 months and are certainly found by 6 months. times covering the entire 10-second page. Another interesting and common
From 3 months onward, the waking tracing becomes more complex and feature of sleep recoding are the so-called cone waves—large negative occip-
differentiated. This is perhaps most evident in the posterior head regions ital slow-wave transients that appear like an ice cream cone—and usually
where the dominant rhythm becomes increasingly well modulated and present in either side, seldom bisynchronously.
Figure 6.13: CSWS with sleep spindles in an infant 48 weeks of conceptional age with episodes of staring and
stiffening. Arrow indicates sleep spindles, arising asynchronously between the two hemispheres.
Conscious infants do not enjoy the experience of having strangers mea- technologist will recognize that the baby is drowsy, and make appropriate
sure their head and apply electrodes. As a result, it is very common for gentle attempts to alert the infant. Evidence of slow lateral eye movements
the routine tracing to begin with ample movement and sobbing artifact. may help to indicate drowsiness, in addition to fragmentation of the domi-
In addition to the myogenic potentials, this overbreathing will produce nant rhythm. Look for portions of the tracing where there is clear motion
a buildup of diffuse or posteriorly predominate rhythmic delta activity, and movement artifact indicating that the infant is more active, and spon-
which should not be interpreted as pathologic. Very experienced technolo- taneous eye opening and closing. If the previously noted slowing mark-
gists can sometimes apply electrodes with impunity, but in most circum- edly improves, it is most likely physiologic and related to unrecognized
stances, a brief period of crying is inevitable. Once the deed of connection drowsiness.
is done, the next task is to settle the infant as quickly as possible. Here Sleep architecture becomes more and more synchronized so that by 18
rhythmic patting artifact often becomes evident, or slower movement to 24 months sleep spindles and vertex waves are simultaneously distrib-
artifacts related to rocking. Sucking artifact is also common at this time. uted. K complexes are seen for the first time. Sleep architecture can become
In a short time, the exhausted infant will often begin to slumber, giving very sharply contoured and must be carefully differentiated from epilepti-
very valuable sleep recordings. After even a brief nap, the infant appears form activity. This is usually not difficult, and a few tips may be helpful:
refreshed, seems to be amnestic for the antecedent hookup event, tolerates most bona fide so-called generalized epileptiform discharges have a frontal
the electrodes very well, and awake tracings can be of remarkably good predominance in older children and a posterior predominance in very young
quality. Infants do not apparently hold a grudge, and as a consequence, children. Sleep architecture will be maximal at the vertex and in the fronto-
if one is patient, a very good sample of EEG can be obtained after gently central region. If in doubt, compare the topography of the patient’s sleep
waking the baby. architecture with the discharges of concern. Generalized spikes in children
It may be difficult to precisely gauge how much slowing should be seen with epilepsy are usually easily seen, and not solely admixed or fused with
in an infant’s EEG, and this is a matter of some experience, but certainly, sleep architecture. If the only discharges that appear “spikey” are in com-
the degree of slowing should be very symmetric between the two sides. It bination with the sleep architecture, beware. It is most likely that these are
is convenient to frequently compare the activity of homologous groups of simply sharply-contoured sleep features; if uncertainty remains, they could
electrodes, awake and asleep. be mentioned in the body of the report, but should not contribute in any
meaningful way to the clinical impression.
Late Infancy: 1 to 2 Years

Childhood: 2 to 10 Years
The second year of infancy remains very active from the EEG standpoint.
The posterior dominant rhythm matures so that it reaches 8 Hz by 2 years The EEG tracing already has all of the major components seen in adults
of age in most cases. Activity in the central region similarly increases in fre- by the second year of life. From this point forward, there is steady mat-
quency, and the low-voltage fast activity in the frontal derivations remains uration of the tracing, which can be highlighted by considering several
apparent. Overall, the tracing shows increasing complexity, and the anterior domains.
to posterior voltage/frequency gradient becomes more striking. Owing to The posterior dominant rhythm increases its frequency until it reaches a
the maturation of the background, it becomes easier to find admixed focal life maximum of approximately 10 Hz somewhere in late childhood or early
slow activity, since the predominate activity is no longer in the delta or slow adolescence. Throughout this period, it becomes progressively better sus-
theta frequency range. tained and modulated. Posterior slow waves of youth, which are sometimes
In this manner, it is important to recall that most infants show a marked admixed with the PDR in the immature, become progressively less obvious.
increase in slow-wave activity during drowsiness, which from time to time These can be distinguished from pathologic slowing by their attenuation
may appear asymmetrically, and sometimes dominates a good portion of with alerting maneuvers and eye opening. Slow alpha variants, a harmonic
the tracing. The critical thing is not to overinterpret this slowing. A skilled of the usual alpha, can still occur.
Adolescence punctuated by fleeting EEG transients (physiological or pathological sharp

waves) or electrographic seizures. The appearance and composition of the
By age 10 years, the EEG is very similar to that seen in adults with some background varies with state and conceptional age, but the predominant
exceptions. There will be a slight excess of theta activity compared with the frequencies that constitute the neonatal EEG are represented by theta and
adult and a more dramatic buildup of slow-wave activity with HV. In certain delta activity. There are, however, several specific components appearing
populations, photoparoxysmal responses are seen in up to 15% of normal in premature and full-term infants that warrant individual description and
adolescent girls, indicating that this can be an asymptomatic genetic trait with illustration.
drowsiness, frontal alpha rhythms are sometimes present. Stage II sleep con-
tinues to show very sharply-contoured waveforms. Sometimes, the very first Neonatal
few K complexes have a notched appearance and may resemble spike waves,
but in the authors’ experience, it is very rare for spike waves to appear only in Monorhythmic Occipital Delta Activity
this setting. Comparison of the morphology and topography with other sleep This activity represents a conspicuous, stereotyped run of monomorphic,
architecture later in the tracing can be very helpful. True generalized spike high-amplitude, surface polarity–positive, 0.5- to 1-Hz delta waves, often
waves have a different spatial distribution and configuration compared with appearing synchronously in the occipital scalp regions (Fig. 6.14). A run
vertex waves or K complexes. If the only suspicion for spike wave is found in of monorhythmic occipital delta activity can last from 2 to 60 seconds and
the first few complexes of sleep activity, it is best not to draw undue attention. appears relatively symmetrically and synchronized bilaterally. It is present
Beyond adolescence, of course, is adult life. What is noteworthy to a pediat the conceptional age of 23 to 24 weeks, peaks in abundance between 31
atric electroencephalographer is the incredible preservation of the funda- and 33 weeks, and then significantly fades by 35 weeks. Persistence of well-
mental EEG characteristics from this point forward, well up to senescence. developed monorhythmic delta activity after 35 weeks of conceptional age
There are few changes, and the EEG patterns are remarkably constant. Even is often considered evidence of electrographic “immaturity.” This pattern
healthy elderly people maintain their alpha rhythms. After the first two represents the dominant rhythmic activity in the posterior brain regions and
decades of explosive growth and dynamic changes, the EEG settles into a serves as the delta constituent of occipital delta brushes (see later discus-
very reliable and predictable constancy for many decades to come. The basic sion). This is also a sturdy rhythm in that it may persist in the presence
rhythms once established stay entrenched to serve the primary functions of of severe, acute encephalopathies, long after other specific patterns have
informational processing and execution of function. It is a remarkable phe- disappeared.
nomenon, and one that probably allows for more diagnostic precision or
detection of subtle pathology since the degree of normal variability is mark- Rhythmic Occipital Theta Activity
edly reduced. Once one is well trained in pediatric EEG, it is not difficult to
This specific pattern appears as brief (2- to 10-second) bursts of stereotyped,
interpret adult tracings, but the converse is not necessarily true because of
rhythmic, sinusoidal 4-Hz theta activity in the occipital regions (Fig. 6.15),
the aforementioned range of normal findings as a function of age. Skilled
sometimes spreading into the temporal regions. These bursts commonly
pediatric EEG interpretation takes substantial experience.
mingle or superimpose on coincident monorhythmic occipital delta activity.
They are present in the awake or sleeping infant and are apparent at the con-
ceptional age of 23 to 24 weeks. They peak in abundance by 30 weeks and
COMPOSITION OF ELECTROENCEPHALOGRAPHIC then fade from the occipital areas by 33 weeks; the rhythmic theta pattern
BACKGROUND ACTIVITY (NAMED PATTERNS) migrates anteriorly to the temporal areas at older ages.
EEG background refers to the presence of all the aggregated patterns, Rhythmic Temporal Theta Activity
waveforms, and frequencies that collectively constitute the ongoing cerebral This pattern is morphologically similar to that arising in the occipital
electric activity. As such, it represents an infrastructure or stage that may be regions. It peaks between the conceptional ages of 31 and 33 weeks. It
Figure 6.14: Monorhythmic occipital delta activity in an infant 31 weeks of conceptional age with apnea.
Occipital delta activity with delta brushes (arrow) is present. Note that the occipital delta transients are syn-
chronized between the two hemispheres.
Figure 6.15: Rhythmic occipital theta activity in an infant 30 weeks of conceptional age who underwent fetal
surgery for repair of myelomeningocele. Bilateral rhythmic occipital theta activity (arrow) is present, although
more on the right side than on the left.
appears as brief paroxysms simultaneously or independently in the tem- evolve in morphology or frequency. On occasion, an abortive or larval burst
poral areas (Fig. 6.16). However, over a long time period, these bursts are of this pattern gives rise to a “sharp wave,” but close examination shows that
equally represented bilaterally. They are occasionally “sharply” contoured, it is merely a morphological fragment of an abbreviated run of rhythmic
which raises the concern that they are a brief ictal discharge, but they do not temporal theta activity.
Figure 6.16: Rhythmic temporal theta activity in an infant 31 weeks of conceptional age with pneumonia.
Sharply-contoured rhythmic temporal theta activity (large arrow) is present. Also, note a run of low-amplitude,
positive left temporal sharp waves (small arrow), which are considered normal transients for age.
Centrotemporal Delta Activity appear semirhythmically, but they are not usually as regular and well modu-
This pattern is represented by the intermittent appearance of sustained lated as monorhythmic occipital delta activity. This pattern serves as the
trains of conspicuous, 0.5- to 2-Hz delta activity, often with a prominent delta wave foundation for rolandic and temporal brushes. It peaks by the
surface-positive polarity in the C3–C4 to T3–T4 areas (Fig. 6.17). They may conceptional age of 30 weeks and fades after 33 weeks.
Figure 6.17: Rhythmic centrotemporal delta activity in an infant 31 weeks of conceptional age with dysmor-
phic facial features. Arrows indicate left centrotemporal delta activity admixed with delta brushes.
Delta Brushes Infancy and Childhood

These patterns (also called “brushes,” “ripples of prematurity,” and
“spindle-like fast rhythms”) are often considered the premier electrographic The Alpha Rhythm
signature of the premature infant. The pattern is composed of a combina- The posterior dominant rhythm is well developed in children, and its pre-
tion of a specific delta frequency transient with a superimposed “buzz” of cursor can be seen in infants as early as 3 months. It is responsible for the
8- to 20-Hz activity (see Figs. 6.14 and 6.17). Brushes are symmetrically appearance of the frequency and voltage gradient and is one of the most
represented between the two hemispheres and homologous brain regions. important objective criteria we have for judging the integrity of the overall
They are not commonly displayed synchronously except when they arise in cerebral electrical activity. For all these reasons, we discuss it first.
concert with runs of monorhythmic occipital delta activity. They appear
in awake and sleeping infants, and so they should not be considered a type Frequency of the Posterior Dominant Rhythm
of precursor of the “spindle” of mature quiet sleep, which first appears
around the conceptional age of 46 weeks. Up to the conceptional age of The normal frequency of the posterior dominant rhythm as a function of
33 weeks, there are more brushes per minute in active sleep than in quiet age has been studied in different populations. The findings of one represen-
sleep. After the conceptional age of 34 weeks, brushes are more numerous in tative study are shown in Fig. 6.20. An occipital rhythmic activity responsive
quiet sleep. Brushes may appear in any scalp region but are scarce in the fron- to eye opening appears in approximately 75% of normal infants between
tal areas. In the youngest premature infants, brushes are mostly expressed in the 3rd and 4th months after (full-term) birth. Initially, this activity is not
the rolandic regions. At their peak expression (during the conceptional ages well sustained and has a frequency of approximately 3.5 to 4.5 Hz. The fre-
of 32 to 34 weeks), they arise mostly in the occipital, central, and temporal quency increases rapidly, reaching 5 to 6 Hz in approximately 70% of chil-
areas. By term, brushes may still persist in immature trace alternant but have dren by 12 months of age. At age 36 months, 82% of normal children born
largely vanished from the awake and active sleep portions of the recording. at full term show a mean occipital alpha rhythm frequency of 8 Hz (range,
By 1 month postterm, they are no longer in evidence. 7.5 to 9.5 Hz). By the age of 9 years, the mean alpha rhythm frequency is
9 Hz in 65% of controls; in the same percentage of persons, the mean is
10 Hz by the age of 15 (23,24).
Anterior Dysrhythmia Using a systematic history and neurological examination, normative EEG
This pattern appears as paroxysmal, brief bursts of frontally dominant, data were developed in Swedish schoolchildren ascertained in the late 1960s.
50- to 100-μV, semirhythmic delta activity (Fig. 6.18). Their morphological Remarkably, the average alpha rhythm between 1 and 2 years of age was
features may subtly evolve over a few seconds and acquire a sharp contour, 8.5 Hz. An equally meticulous study has not been fully replicated, perhaps
commonly admixing and blending with a related rhythm, encoche frontale due to the arduous nature of the work. As a result, carefully characterized
(Fig. 6.19). Runs of anterior dysrhythmia tend to arise symmetrically and normative data in heterogeneous populations, such as those found in North
synchronously between the frontal regions and may be present in all behav- America, are currently lacking. It is possible, therefore, that some of the
ior states. They are most conspicuous in the transition from active to quiet figures commonly used for normal tracings are inaccurate for the target
sleep, but scarce in the period of active sleep immediately after quiet sleep. population.
Despite the usual connotation of the “dys-” prefix, anterior dysrhythmia In infants and young children, the occipital alpha rhythm may totally
is a normal developmental electroencephalographic pattern. However, in block with the eyes open, and slower activity may be mistaken for the occipi-
the wake of definite encephalopathies such as hypoxia-ischemia or menin- tal alpha rhythm. For this reason, a portion of the awake EEG should be
gitis, its excessive presence may be considered a nonspecific electrographic recorded during passive eye closure. Infants and very young children usually
abnormality (9,21,22). Marked and persistent asymmetries of their number, do not close their eyes until they become drowsy and are ready to fall asleep;
morphology, or amplitude may also represent an electrographic abnormal- at that time, the occipital rhythm may slow before disappearing. Young chil-
ity. Its counterpart pattern, frontal sharp waves (encoches frontales) are dren do not appreciate having their eyes closed by strangers, so it is best to
described later. ask the parent to gently close the eyes or to play a game, like peek-a-boo.
Figure 6.18: Anterior dysrhythmia in an infant 40 weeks of conceptional age with pneumonia. Bilateral frontal
anterior dysrhythmia (arrow) is admixed with poorly formed encoches frontales.
Figure 6.19: Active sleep—in the same infant as in Fig. 6.11. The tracing also consists of continuous activity
of low to moderate amplitude (activité moyenne). REMs (arrow) and the lack of tonic muscle activity indicate
active sleep.
finding. For these reasons, many laboratories will not routinely list the volt-
age of the alpha rhythm in their pediatric reports.
Distribution and Symmetry

The occipital region is the site of maximal alpha rhythm voltage in 95% of
children (25). Likewise, in 95% of normal children, the alpha rhythm voltage
has an asymmetry between sides of up to 20%. In 98% of these children, the
lower voltage is on the left side, and there is no relationship to handedness.
In the 5% of children with asymmetries of more than 20%, none showed
a difference of more than 50%. Therefore, the same rule for adults should
be used in the assessment of asymmetries in children when the low voltage
appears on the right side, because the likelihood that the right side should be
the high-voltage side is 98:2 (23,24).
Alpha Variants
Figure 6.20: Curve showing the development of the occipital alpha rhythm In children, there may be harmonics of the alpha rhythm at a higher ampli-
between the ages of 4 months and 16 years. Some rhythmic 3- to 4-Hz activity tude rhythm and precisely half the frequency of the posterior dominant
is present in the electroencephalograms of awake infants aged 2 to 4 months, rhythm. This phenomenon was first described by Goodwin in 1947 (26).
but it is not reactive to eye opening. From the time rhythmic activity that is Posterior Slow Waves. Perhaps no EEG finding has been more misunder-
reactive to eye opening first appears, the frequency increases rapidly, reach- stood and misevaluated to the detriment of the patient than slow activity in
ing 5 to 6 Hz by 12 months and 8 Hz by 36 months. At that age, there is a the parieto-occipital and occipitotemporal regions. There are three simple
sharp inflection in the rate curve, and the frequency increases only 2 Hz over facts considering posterior slow waves in children. First, random, occipital
the next 6 years. (From Kellaway P, Noebels JL, eds. Problems and concepts slow activity may be present in normal children in a wide range of wave-
in developmental neurophysiology. Baltimore: The Johns Hopkins University forms, voltages, and wavelengths. Such waves are uncommon in children
Press, 1989.)
younger than 2 years, but they are maximally expressed (in amplitude and
incidence) in children aged 8 to 14 years (see Fig. 6.21B); they occur more
often in girls than in boys. They consist of moderate-voltage (defined as no
In contrast to adults, it is extremely unusual for a normal child not to have more than 120% of the alpha rhythm voltage) fused waves intermixed with
a posterior dominant rhythm, assuming there is an adequate portion of the the alpha rhythm (which is often superimposed on them). These waves have
recording with eyes closed. been called polyphasic waves (23,24) or posterior slow waves of youth (2). It
is common for the amplitude and incidence of posterior polyphasic waves
Voltage of the Posterior Dominant Rhythm in a child to diminish as the recording proceeds. The basis for this change
Petersén and Eeg-Olofsson (24), using the T5–O1 derivation, found that the is not clear; it may reflect a change in the anxiety or stress level of the child
average alpha rhythm voltage in children aged 3 to 15 years was 50 to 60 µV. (27–36). Second, in addition to random slow waves, occipital or “posterior”
There were no children with voltages less than 20 µV, and only 1.3% of rhythmic slow waves are seen in normal children (23,24). Episodic rhythmic,
the children had voltages of 20 to 30 µV, and all of those were older than 2.5- to 4.5-Hz, monomorphic and polymorphic low- to moderate-voltage
12 years. Approximately 9% of the children of this age group (predomi- waves (<100 μV) occur in the parieto-occipitotemporal region (usually max-
nantly those aged 6 to 9 years) showed alpha rhythm voltages of 100 µV imal at O1 and O2) in approximately 25% of normal awake children aged
or more. High voltage should never, in itself, be considered an abnormal 1 to 15 years. Such activity is most prominent in those 5 to 7 years of age.
A C
Figure 6.21: A: “Supernormal” EEG for age (10-year-old girl). Greater

amounts of slow “fused” (polyphasic) activity could appear in the occipital
leads, as in part B, or greater amounts on random 4- to 6-Hz moderate-voltage
activity could appear in the anterior leads and yet remain within the range
of normal for age. B: This EEG, from an asymptomatic boy aged 10 years,
2 months, shows greater amounts of “posterior slow waves of youth” than
in part A, but has slightly smaller amounts of anterior slow activity. C: Mod-
erately increased slow activity; random moderate-voltage, 4- to 6-Hz activity;
and some slower low-voltage fused forms in anterior derivations. Occipital
derivations show moderate amounts of polyphasic slow activity. The subject
B was 9 years, 8 months old.
Runs of this activity rarely last more than 3 seconds and are present only had random slow activity in an amount rated as normal for age. Approx-
2% of the time (23,24). HV generally causes this activity to become more imately 8% had lesser amounts of slow activity than this, and 4.3% had
continuous and higher in voltage. Third, except for this age-related finding, slightly greater amounts of nonrhythmic slow activity; in 0.5% of the series,
in the awake state there should be no rhythmic component in the occipital the random slow activity was MIL. This compares with the concept of the
regions that has a frequency slower than that of the normal range (for age) “ideal” EEG and the range of normal variation that was developed from
of the occipital alpha rhythm. The foregoing is a prelude to a plea: The cri- studies of asymptomatic but not highly selected children. Eeg-Olofsson and
teria for what is considered abnormal in children and indicative of disease Petersén found that the incidences of SIL and MIL were greatest in children
or disorder must be improved. between 6 and 11 years of age and were significantly higher in girls than in
Posterior Slow-Wave Transients Associated with Eye Movements. In some boys (9).
young children (aged 6 months to about 10 years), some eye blinks or eye Comparison of Eeg-Olofsson and Petersén’s prototypic EEG samples of
movements are associated with a single monophasic or diphasic slow tran- “normal,” “SIL,” and “MIL” slow activity with the authors’ own prototypes
sient that has a duration of 200 to 400 milliseconds and an amplitude of indicates that the highly selected healthy children in the Gothenburg series
early frequency-analysis study by Gibbs and Knott (37). This figure may (23,24) showed lesser amounts of random slow activity than did the authors’
be regarded as a fairly good approximation of the frequencies present and unselected asymptomatic children. If the criteria offered by the Gothenburg
their degree of expression in various regions at different ages. It does not, study of highly selected children are used as a basis of interpretation in rou-
however, provide information concerning the waveform of the activity, its tine clinical practice, considerable caution must be exercised in categorizing
voltage, or the manner of its occurrence (e.g., random, continuous runs), all an EEG of a given child as “outside” the range of normal variation; care
of which are critical elements of VA and are essential to clinical evaluation should be taken here because the “pathological” significance of an abnor-
of the EEG. mal EEG, which is too readily equated with brain “damage” (or, at best,
In evaluating the amount and duration of slow activity present in relation “dysfunction”), is often based on simplistic reasoning. The talent of the
to the age of the patient, it is helpful to use the concept of the “ideal” EEG clinical electroencephalographer is measured not so much by an ability to
for each age as a standard of comparison. “Ideal” is not used to convey make a VA of the tracing but by an ability to determine what the findings
perfection (particularly in a clinical sense), but is, instead, employed in the mean in a particular patient under particular circumstances in relation to a
platonic sense of “prototype.” The “ideal” is based on what 75% of asymp- particular clinical history. The characteristics of the EEG are determined
tomatic children of a given age show in terms of the slow activity present in by numerous influences, not the least of which may be the uniqueness of
the various derivations. Approximately 5% of normal children (same age) the laboratory environment. Factors that determine the characteristics of an
show less slow activity than the ideal, and their EEGs more closely approxi- individual’s EEG at any time are discussed in the final section of this chap-
mate the adult pattern (these are sometimes called “supernormal” EEGs) ter. It is beyond the scope of this chapter to attempt to convey the “ideal”
(23,24). Another 15% of normal children show slightly greater amounts of and the “range of normal variation” for each age. Figure 6.21 illustrates the
slow activity than the ideal, and 5% show moderately increased amounts concept for a single age level.
of slow activity. These general concepts have been adopted, modified,
and expanded by the authors’ colleagues and collaborators in Sweden and Mu Rhythm
underlie their categorizations of “slightly increased slow” and “moderately The mu rhythm 6 is a central rhythm of alpha activity frequency (usually 8
increased slow” (23,24). These benchmark papers of Eeg-Olofsson and to 10 Hz) (Fig. 6.22) in which the individual waves have an arch-like shape.
Petersén provide the essential data on which the kind of mental template It has been reported to be less common in children, with reported rates of
required for the evaluation of children’s EEGs can be developed. only 5% of normal children younger than 4 years, and 7% between 8 and 16
Eeg-Olofsson and Petersén (23,24) rated the amount of nonrhythmic years, but it is worth noting that these figures derive from EEG work in the
(random) slow activity in the EEGs of children in their normal series as 1960s when it was common to have half of the commonly used numbers of
“minute,” “normal,” “slightly increased (SIL),” and “moderately increased channels (23,24). As a result, good portions of these recordings were per-
(MIL)” for age. Of their highly selected healthy children, approximately 87% formed with just temporal lead coverage. In the authors’ experience, mu is
Figure 6.22: Episode of mu rhythm occurring during a

period when the eyes are open and the occipital alpha
rhythm is blocked. EEG of asymptomatic 25-year-old
woman. Mu-rhythm asymmetries of this degree are not
uncommon in normal subjects.
actually very commonly seen in pediatric tracings, with its precursor visible activity range may be distinguished: a common 18- to 25-Hz band, a less
in many tracings as early as 6 months. common 14- to 16-Hz band, and a rare 35- to 40-Hz band. In 97% to 98%
In infants whose occipital alpha rhythm is still less than 6 Hz, a well- of normal awake children, the voltage in the EEG is less than 20 µV; in 70%,
organized and fairly well-sustained 8- to 10-Hz activity may be present in it is 10 µV or less (recorded between closely spaced scalp electrodes) (24,25).
the central regions bilaterally. It lacks the characteristic waveform of the mu Beta activity with a voltage of 25 μV or more in the clinical EEG has been
rhythm but may be ontogenetically related to it. This activity was originally considered abnormal. Although such findings are statistically outside the range
described by Pampiglione in 1977 (38): of normal variation, little is known about the significance of beta activity. The
early literature documents a significantly higher percentage of “fast” EEGs in
In the rolandic area of each hemisphere and at the vertex some rhyth-
patients with epilepsy than in normal controls, but it has subsequently been
mic activity kept on appearing in most infants, at somewhat irregu-
shown that fast EEGs have no correlation with epilepsy in children (39–43).
lar intervals, in the form of 8–10 per sec waves of the order of 20–40
As in adults, many commonly used drugs (e.g., barbiturates, benzodiaz-
microvolts, with variable lateralization, often occurring independently
epines, chloral hydrate) and skull defects may increase the amplitude, and
over the right or the left side. … This activity would often diminish
thus apparently the amount, of beta activity (44,45). Because the incidence
or disappear altogether when the baby used his hands or played with
of beta rhythms with amplitudes much above 20 μV is statistically low in
toys, but it would increase when the baby was at rest with his arms and
normal persons, the presence of such activity suggests the possibility of
hands relaxed. … Distribution, frequency and behavior were similar to
drug ingestion. Although the 18- to 25-Hz band is the one most generally
those of the mu rhythm in older children and adults.
affected, some drugs also increase the 14- to 16-Hz activity.
Beta activity of 18 to 25 Hz usually increases in amplitude during drowsi-
Beta Activity ness, light sleep, and REM sleep, and it usually decreases during deep sleep.
Activities with frequencies higher than 13 Hz are commonly present in When a barbiturate or other beta-enhancing drug is administered to pro-
the EEGs of normal children. Three distinct frequency bands in the beta mote sleep during the EEG examination, the resultant fast activity increases
with the onset of light sleep, decreases markedly during deep sleep, and then activity in the routine EEG cannot be regarded as having pathological
remains prominent after the patient is aroused. This effect of sedation is significance. Approximately 35% of young, nondrowsy, asymptomatic
particularly pronounced in children. adults show some very-low-voltage (<15 μV) 6- to 7-Hz activity in the
Beta activity should have the same frequency on both sides. However, frontal or frontocentral region in the environment of a quiet, smoothly
even in normal persons, there may be a voltage asymmetry, with the activ- operating, clinical EEG laboratory. In 10%, the voltage is 15 to 25 μV,
ity being as much as 35% lower on one side. Such asymmetries may result and the activity tends to occur in rhythmic serials. The extent to which
from differences in skull thickness, as described earlier for the alpha rhythm. more sustained, higher voltage (>15 μV), 6- to 7-Hz rhythms reflect the
On the other hand, a consistently low voltage on one side (>35%), whether patient’s emotional state (27–34,36) or some other physiological condi-
focal, regional, or hemispheric, is often a useful diagnostic feature; it indi- tion cannot be assessed properly unless specific procedures are carried
cates cortical injury (e.g., acute contusion, acute ischemia, or the presence out. Hence, there is no clear-cut end point at which frontal theta activity
of a subdural or epidural fluid collection). Focal, regional, or hemispheric can be specified as abnormal. This problem is particularly important in
depression of beta activity may also occur transiently after a focal epileptic children, who are especially prone to increased theta activity in highly
seizure. Beta activity is generally the first to show diminished voltage in the emotional states and in whom frontal theta activity was once identified
presence of a cortical injury or subdural or epidural fluid collection; there- as an abnormality having a specific association with behavior disorders.
fore, its presence on the low-voltage side can be helpful in assessing the sig- Indeed, the presence of this “abnormality” in the EEG was originally
nificance of a voltage asymmetry of other background activity in the same thought to be “evidence of the organic nature of the behavior disorder
region (if the asymmetry is borderline in degree). In this regard, it must be present” (47). Clearly, enhanced theta activity in such children might
remembered that beta activity amplitude is particularly susceptible to the result from emotional upsets engendered by the behavior problem and
presence of subgaleal fluid, and special care should be taken by the technol- its consequences rather than from pathologically altered brain function.
ogist to note the presence of scalp swelling: its location, extent, and degree. The clinical interpretation of anterior theta rhythms in the EEGs of chil-
Beta activity in the 14- to 16-Hz band is usually most marked in the dren was overly influenced by a series of early reports, beginning with
frontocentral region, but may show maximum voltage elsewhere, even in that of Jasper et al. in 1938 (47), who stated that such activity was more
the occipital region. The location of the maximum potential field does not pronounced and more prevalent in children with behavior problems than
appear to have particular physiological or pathophysiological significance. in normal, age-matched controls. It is clear that Jasper et al. and sub-
Beta activity in this band, when present, is usually enhanced by HV and sequent investigators regarded this theta activity as evidence of funda-
indeed may become clearly evident only during this activity. It may be pres- mental brain pathology. Lindsley and Cutts (48), for example, reported
ent during sleep, but should be distinguished from sigma activity, which, by that although occasional brief runs of 5- to 8-Hz waves in the frontal
definition, occurs only in bursts. and central regions are not unusual in normal subjects, they should be
considered abnormal “if they are present as much as 10% of the time in
well-organized ‘runs’ or ‘bursts.’” This concept has been reiterated ever
Theta Activity
since (usually without critical reappraisal) as a criterion of abnormal-
Frontal and Frontocentral Theta Activity ity in children. However, the runs of 6-Hz activity shown in Fig. 6.23
In children, heightened emotional states enhance frontal rhythmic theta are comparable to those that Lindsley and Cutts described as abnormal.
activity in the 6- to 7-Hz range (27–34,36). Moreover, some normal per- The tracing in this figure is from the EEG of an asymptomatic 19-year-
sons show marked frontocentral rhythmic theta activity (with the eyes open) old man. Such rhythmic activity appears in approximately 15% to 20%
while performing certain tasks (46). It has not been established whether this of asymptomatic children and adolescents between the ages of 8 and
latter effect results from a change in affective state related to the task or is a 16 years; serial studies indicate that the occurrence of such rhythms is
concomitant of some other aspect of brain function. age-related, appearing in a given child at a certain age, increasing to a
Because the routine clinical EEG examination generally does not peak voltage at approximately the age of 8 years, and tending to diminish
encompass the evaluation of “affective state” or even of “vigilance” dur- and finally disappear thereafter (23,24). Thus, age and ontogenetic pro-
ing the recording, the presence of some 6- to 7-Hz random or rhythmic cesses are factors in the appearance of this type of anterior theta rhythm.
Figure 6.23: Monomorphic, rhythmic 6- to 7-Hz moderate-

voltage activity, occurring in fairly prolonged runs in the frontal
leads in an asymptomatic 19-year-old pilot. Theta activity of this
degree occurs in asymptomatic young adults, but usually not so
continuous or so pronounced at this age as in this subject.
Evidence also indicates that genetic factors may play a role (49). The rhythmic 4- to 7-Hz monomorphic waves often have a spindle shape, tend to
problem is: At what point do frontal 6- to 7-Hz rhythms—because of spread to the frontal and posterior regions, and tend to dominate the EEG.
high voltage, unusual persistence, or paroxysmal regulation—qualify as The rhythm occurs predominantly in children aged 2 to 6 years. It is a com-
evidence of abnormal function? mon feature in myoclonic-atonic epilepsy.
Monomorphic, rhythmic 6- to 7-Hz activity occurring in high-voltage
(>100 μV) paroxysmal bursts in the frontal or frontocentral region
(Fig. 6.24) is not typically seen in normal children (zero incidence in con- Midline Central Theta Activity
trols). The two extremes of rhythmic theta activity occurrence are shown in A midline central (Cz) theta rhythm has been described in children and
Figs. 6.23 and 6.24; however, all degrees of theta activity may be encoun- adults (55–57). As described by Westmoreland and Klass (57), it consists of
tered in pediatric practice. trains of rhythmic waves of sinusoidal or mu-like form having a consistent
Doose et al. (49–53) reported such rhythms as features indicating a suscep- frequency within the 4- to 7-Hz range. The rhythm, which is predominantly
tibility to epilepsy (54). They described the pattern as consisting of runs of 6 or 7 Hz, occurs episodically in trains that have a duration of 4 to 20 sec-
bilaterally synchronous, monomorphic 4- to 7-Hz rhythmic activity shown onds. It is present only in the awake state, is not related to drowsiness, and
most clearly by referential recording from the central regions. The runs of is a different rhythm from the bilateral rhythmic central theta activity that is
Figure 6.24: Monomorphic, rhythmic, high-voltage 6- to 7-Hz activity

in a 9-year-old boy. Rhythmic 6- to 7-Hz activity, similar to that seen in
Fig. 6.23, occurs commonly in this age group, but usually not so con-
tinuously as in this subject. This high-voltage, frontal theta activity is
outside the range of normal variation for any age.
a common finding in sleep. The rhythm has a high correlation with epilepsy as low voltage, excessive discontinuity, and poorly developed patterns and
but is not related to any particular type (56,57). It is, however, not specifi- rhythms. The major characteristics of each type of abnormality are consid-
cally related to epilepsy, inasmuch as about 25% of the persons who show ered separately.
this pattern have other disorders.
Excessive Discontinuity
A discontinuous EEG is an appropriate finding in the premature infant.
TYPES AND SIGNIFICANCE OF ABNORMAL PEDIATRIC With increasing conceptional age, the discontinuous EEG is confined to
ELECTROENCEPHALOGRAPHIC BACKGROUNDS behavioral quiet sleep, and by 44 to 46 weeks of conceptional age, even quiet
sleep is composed entirely of CSWS as the remnants of trace alternant dis-
Just as the characteristics of the normal pediatric EEG background may appear. Pediatric tracings beyond 46 weeks should not be discontinuous in
be described in terms of continuity, synchrony, composition, and voltage, any state. EEGs that have inappropriately long IBIs or an overrepresenta-
abnormal EEGs may also be judged from similar perspectives. Abnormal tion of discontinuous activity are excessively discontinuous for conceptional
EEGs commonly display multiple, overlapping pathological features such age (Fig. 6.25). Because trace discontinu and trace alternant are normal,
Figure 6.25: Excessive discontinuity for age in an infant 37 weeks of conceptional age with cervical teratoma.
The IBI is 11 seconds, which is excessive for an infant of this age.
age-specific EEG patterns in healthy infants, the terms are inappropriate to EEGs with burst-suppression patterns. The 5-year follow-up revealed that
apply to tracings that are abnormal and excessively discontinuous for con- 85% (35 of 41) had a very poor outcome, including eight deaths. In the
ceptional age recorded from encephalopathic or medically ill neonates. full-term infant, burst suppression is also a nonspecific pattern of a severe
When the EEG appears excessively discontinuous, it is important to scru- degree of encephalopathy that may be caused by numerous conditions,
tinize the composition of the bursts. If the burst activity is well preserved including asphyxia, stroke, encephalitis or meningitis, metabolic disorders,
and demonstrates a rich variety of the patterns and rhythms appropriate for inborn errors of metabolism (IEMs) such as nonketotic hyperglycinemia,
the conceptional age, the excessive discontinuity may have relatively little and cerebral dysgenesis. The rate of poor outcome for full-term infants with
significance. However, if the tracing is excessively discontinuous and if the burst suppression is also high, ranging from 85% to 100% in recent studies
bursts are poorly developed and lack normal background patterns, greater (59–63).
pathological significance can be presumed. In older infants and children,
any discontinuous EEG implies a marked degree of diffuse or multifocal Excessive Discontinuity for Age
cerebral dysfunction. Some critically ill, very young premature infants may not display all of the
As mentioned, the pediatric EEG should never be discontinuous beyond usual criteria for burst suppression. The presence of discontinuity per se
2 months of age. Discontinuity beyond this point is indicative of diffuse may be appropriate, even though the duration of the IBIs is usually quite
cerebral dysfunction, regardless of the clinical situation. In children with excessive. The bursts themselves may still preserve a few of the named
epilepsy, if seen in the context of slowed backgrounds with multifocal spikes, background premature patterns, especially delta brushes or monorhythmic
it often indicates a severe form of an epileptic encephalopathy. occipital delta activity. Although such tracings fall short of the criteria for
burst suppression, they also carry an ominous prognosis.
Burst-Suppression Pattern Less disturbed EEG backgrounds that also do not fulfill the criteria for
The most extreme degree of discontinuity is burst suppression (Fig. 6.26), burst suppression may nonetheless be judged abnormal by excessive discon-
characterized by an invariant, excessively discontinuous background with tinuity for conceptional age, determined by measuring the mean or median
prolonged IBIs of very low voltage (<5 µV) that are interrupted by brief duration of IBIs or the duration of the record’s longest IBI measurement.
(1- to 10-second) bursts of paroxysmal higher-voltage theta, delta, and other After 30 weeks of conceptional age, those with a median IBI duration of less
frequencies. These synchronous or asynchronous bursts may be admixed than 8 seconds fared better than those with longer IBIs (4). Hahn et al. (8)
with sharp waves. Differentiation among biobehavioral states is lost. Burst provided useful data concerning the values of the single longest acceptable
suppression should not be confused with the immature quiet sleep pat- IBI duration for different conceptional ages (Table 6.1). There are no uni-
terns of tracé discontinu and tracé alternant. Burst-suppression tracings are versally agreed-upon IBI duration criteria that define the exact boundaries
excessively discontinuous and invariant. The IBI duration may be exceed- of “mildly,” “moderately,” or “markedly” excessive discontinuity for con-
ingly long—30 minutes or more. The discontinuity is completely unreactive ceptional age. Previous studies (12,16,62,63) suggested that 30-second IBIs
to noxious stimulation, and no spontaneous cycling of state is apparent. were moderately prolonged for a conceptional age of less than 30 weeks or
Furthermore, in burst suppresion, the burst periods themselves are devoid 45 seconds for a conceptional age of 30 weeks or more. Typical IBIs exceed-
of the anticipated conceptional age-specific patterns (58). ing 60 seconds were markedly abnormal for any conceptional age. However,
It is important to be able to confidently recognize burst suppression these earlier criteria have not been revalidated for contemporary practice
because it is commonly seen in severe encephalopathies and has clear unfa- and are possibly outdated. Certainly, 30-second IBIs would be considered
vorable prognostic implications not only for premature and full-term infants, prolonged by today’s standards. Like burst suppression, excessive disconti-
but also children of any age. Only exceptional infants enjoy a normal out- nuity is an etiologically nonspecific EEG background abnormality.
come in the wake of burst suppression. However, confirmation of a persis-
tent burst-suppression pattern with serial EEGs is recommended before a Abnormal Voltage
definitive unfavorable prognosis is rendered. Tharp et al.’s (12) prospective The voltage or amplitude of a pediatric neonatal EEG regularly and predict-
study of 81 at-risk newborns of low birth weight (<1,200 g) included 41 ably varies with conceptional age and biobehavioral state. For example, the
Figure 6.26: Burst suppression in an infant 38 weeks of conceptional age with multiple contractures and dys-
morphic features. The burst of activity is clearly abnormal and contains obvious sharp waves and spikes. The
IBI is very low amplitude. This pattern persisted for the duration of the recording and did not react to noxious
stimulation.
TABLE 6.1 Longest Acceptable Single IBI Duration Values Isoelectric

for Conceptional Age When the neonatal or pediatric EEG is performed in accordance with the
Conceptional age (wk) 31–33 34–36 37–40 established technological criteria to determine electrocerebral silence (ECS)
<30
in cases of suspected brain death, the absence of any definite cerebral elec-
Maximal IBI (s) 30–35 20 10 6 trical activity greater than 2 μV constitutes an isoelectric tracing (Fig. 6.29).
Adapted from Hahn J, Monyer H, Tharp B. Interburst interval measurements in the EEGs The challenge is to distinguish the ubiquitous recording artifacts in the
of premature infants with normal neurological function. Electroencephalogr Clin Neuro- electronically hostile environment of the neonatal intensive care unit from
physiol 1989;73:410–414. genuine cerebral electrical activity. Unfortunately, different recording sensi-
tivity criteria have historically been used to define this pattern in neonates.
Reported amplitudes in isoelectric recordings have ranged from less than 2
voltages of the EEG bursts during quiet sleep in a premature infant are quite
to 10 μV, depending on the investigator. However, the absence of discernible
robust, whereas those during active sleep after quiet sleep are much lower in
background activity with the sensitivity set at 2 μV in a continuously nonre-
full-term infants. Several descriptions of background abnormalities caused
active record remains the formal criteria of the American Electroencepha-
by low voltage have been proposed. Other than the isoelectric recording, no
lographic Society (64).
single proposal has been universally accepted.
Persistent Low Voltage, with or without Lack of Differentiation Abnormal Asymmetry

The background in a persistently low-voltage record is attenuated and A persistent interhemispheric amplitude asymmetry of more than 50% is
usually composed of 5- to 15-μV activity during wakefulness and 10- to considered an electrographic abnormality (14,65,66). Persistent amplitude
25-μV activity during quiet sleep (59). Faster frequencies may be especially asymmetries may be broadly attributable to excessively high amplitudes in
“depressed” or of low voltage, but the EEG should otherwise have the nor- one area or excessively low amplitudes in another. In individual patients, it
mal states, patterns, and frequencies expected for conceptional age. This pat- may be difficult to decide which hemisphere is “abnormal” on the basis of
tern has been described in some full-term newborns and is prognostically amplitude criteria alone.
significant only if it persists into the 3rd week after term. Most causes of pediatric acute encephalopathy arise from diffuse patho-
Depressed and undifferentiated background describes the reduction of logical conditions such as global hypoxia-ischemia, metabolic abnormali-
rich, complex, faster “polyfrequency” background EEG patterns and does ties, or sepsis with meningitis, and EEGs recorded in these circumstances
not directly imply a depression of voltage, even though many records of this display symmetric abnormalities. Focal brain injury may be caused by local-
variety are, in fact, of very low amplitude (<10 μV) (Figs. 6.27 and 6.28). ized cerebral infarction (stroke), venous or dural sinus thrombosis, abscess,
These records may also be excessively discontinuous and do not change with restricted hemorrhage, contusion, or similar pathological processes. The
state or stimulation. Low-amplitude, poorly organized electrographic sei- EEG asymmetries in these circumstances often appear as a voltage reduc-
zures of the “depressed brain type” may be recorded. This is a nonspecific tion (from loss of signal generators), seizures arising from a limited number
pattern that may be present in many severe conditions, including asphyxia, of brain regions, depression of normal background patterns, focal slowing,
cerebral hemorrhage, overt dysgenesis, CNS infections, and IEMs. However, or sharp waves (see Fig. 6.4). On the other hand, when the electrographic
postictal states, hypothermia, high drug levels, and very abnormal acid-base asymmetry is purely a loss of voltage (see Fig. 6.5), with preservation of the
status may briefly cause similar EEG patterns and should therefore be ruled composition of the background, a technical problem (e.g., electrode spacing
out before a prognosis is made. or asymmetrical scalp edema) or possible subdural fluid collection could be
Persistent low-voltage EEGs are virtually never seen in normal children, responsible.
until adolescence, and even then, are very rare. If there is a concomitant lack The unfavorable prognostic significance of this abnormality has been
of the expected complexity diffusely, then the tracing should be recognized reported by several authors’ (3,4,52,55,67). In the setting of meningitis,
as consistent with diffuse cerebral dysfunction. Chequer et al. (21) reported that persistent EEG asymmetries correlated
Figure 6.27: Depressed and undifferentiated background in an infant 41 weeks of conceptional age with
birth trauma. The background shows little of the rich, polyfrequency activity expected in a healthy infant of
this age.
Figure 6.28: Extreme low voltage background in an infant 39 weeks of conceptional age with severe hypoxic-
ischemic encephalopathy. Cerebral activity is nearly absent, except for some minimal slow activity at Cz
(arrow).
Figure 6.29: Isoelectric or ECS in an infant 39 weeks of conceptional age with clinical brain death from severe
hypoxic-ischemic encephalopathy. No definite cerebral activity is seen at maximal recording sensitivity. Elec-
trocardiographic artifact is present.
well with specific localized injuries such as abscess or large vessel infarction. dysplasia and full-term infants affected with congestive heart failure from
Tharp et al. (62) noted that in nine patients with more than 50% amplitude a congenital heart defect. In these infants, the CNS may not mature at the
asymmetry persisting in all states, the prognosis was poor, including death appropriate rate. Such chronically ill infants experience an actual delay or
or definite neurological handicaps. In contrast, neonates with less than 50% arrest of physical brain development that can be reflected as “immaturity”
interhemispheric asymmetry with an otherwise normal EEG for concep- in serial EEG examinations (12,68).
tional age enjoyed a favorable prognosis, even if the abnormality persisted A neonatal EEG record is considered immature or dysmature (Fig. 6.30)
throughout the record. if it contains patterns that indicate that its current maturity is 2 or more
weeks younger than the stated conceptional age (66). Interpretative criteria
Abnormal Interhemispheric Asynchrony used to determine dysmaturity include the degree of discontinuity during
Synchrony is typically determined by analyzing 5 minutes of the discontinu- quiet sleep, the degree of interhemispheric asynchrony, the frequency and
ous portion of the EEG (12,59). Interhemispheric bursts separated by more location of delta brushes during active sleep and quiet sleep, the presence of
than 1.5 to 2 seconds of each other are considered asynchronous. The per- encoches frontales, and the number of temporal theta bursts. Rating an EEG
centage of EEG bursts that are synchronized approach 100% in the healthy as dysmature is relatively subjective, although normative scales have been
full-term infant. Gross asynchrony of the EEG is rarely encountered in suggested to aid with the diagnosis (8,69–71). The pathological correlate of
isolation; instead, it is usually accompanied by other obvious background a persistently immature EEG is actual CNS dysmaturity, visible as inappro-
abnormalities such as excessive discontinuity or burst suppression. Exces- priately delayed neuronal migration and maturation. Transient dysmaturity
sive asynchrony can be seen in a variety of acute causes of encephalopa- is not correlated with a poor prognosis, although persistent dysmaturity on
thy, such as hypoxic-ischemic encephalopathy (HIE) or meningitis, and in serial EEGs can be associated with an unfavorable outcome.
chronic conditions, such as cerebral dysgenesis. Neuropathological findings
in infants with an abnormally asynchronous EEG include periventricular Sharp Electroencephalographic Transients
leukomalacia, intraventricular hemorrhage, and any developmental abnor-
mality of the corpus callosum (65). Aicardi’s syndrome is confined to girls Sharp EEG transients (SETs) are defined as sharply-contoured waves of
and characterized by distinctive retinal colobomas, agenesis of the corpus brief duration that are clearly distinguishable from the ongoing background
callosum, occasional interhemispheric cysts, striking degree of interhemi- activity. In the neonatal EEG, the definitions of a sharp wave and a spike
spheric EEG asynchrony, and refractory, early-onset seizures that include are slightly different from those used in pediatric and adult EEG. SETs with
infantile spasms (2). durations between 100 and 500 milliseconds are called sharp waves, whereas
Usually, mention of interhemispheric synchrony in infants and older chil- those with durations of 100 milliseconds or less are spikes. The polarity of
dren pertains to sleep architecture. Vertex waves and sleep spindles are nor- sharp waves or spikes may be monophasic, biphasic, or polyphasic. SETs
mally asynchronous until approximately 18 months of age, at which time K may appear in any scalp location. Just as SETs in older persons may be
complexes also first appear. innocent (e.g., lambda waves or small sharp spikes) or pathological, a simi-
lar situation exists in the interpretation of neonatal EEGs. Interpretative
Abnormal Maturation criteria to assist in the discrimination between physiological and pathologi-
In the setting of acute encephalopathies such as HIE or trauma, the com- cal SETs have been proposed.
mon EEG background abnormalities of excessive discontinuity, depressed
background composition, and impaired reactivity are useful yardsticks for Neonatal Frontal Sharp Electroencephalographic Transients
measuring the impact of the disease on functional CNS integrity. How- Morphologically, physiological frontal sharp waves (encoches frontales) are
ever, infants exposed to subacute, prolonged illness may never experience a high-amplitude (>150 μV), broad, biphasic (negative-positive) transients
sudden, sentinel clinical event; rather, they are neurologically stressed over seen maximally in the frontal regions (Fp3 and Fp4). They generally appear
extended time frames. Examples of such infants are premature infants who symmetrically, bilaterally, and synchronously; however, when they first
require long-term mechanical ventilation because of bronchopulmonary appear at around 34 weeks of conceptional age, they may arise somewhat
Figure 6.30: Immature background for age in an infant 42 weeks of conceptional age with complex con-
genital heart disease. Rhythmic occipital delta activity (arrow) is not normally present in infants of this
conceptional age.
asynchronously. Encoches frontales may appear alone or may intermingle point they begin to disappear (5). Encoche frontales are normal, physiological,
with runs of slow 2- to 4-Hz waves (anterior dysrhythmia) (Fig. 6.31). Frontal age-dependent SETs that do not suggest a “lowered seizure threshold.”
sharp waves are most abundant during the transition from active sleep to early Several characteristics of pathological frontal sharp waves distinguish
quiet sleep and are scarce in the period of active sleep that immediately follows them from the innocent encoches frontales. A clearly excessive amount
arousal from quiet sleep. They persist until about 4 weeks after birth, at which of frontal slowing and encoches frontales in active sleep/wakefulness may
Figure 6.31: Encoches frontales in an infant 40 weeks of conceptional age with clinically suspected seizures.
Normal frontal sharp waves—encoches frontales—(arrow) are admixed with anterior dysrhythmia.
be seen in the context of resolving or mild HIE, meningitis, or metabolic Neonatal Temporal and Central Negative Sharp
encephalopathies. Frontal SETs that are atypical in morphology (e.g., true Electroencephalographic Transients
spikes) or are markedly asymmetrical may also be considered electrographic The initial and predominant deflection of negative SETs is surface polarity
abnormalities (Fig. 6.32). negative in standard bipolar derivations. They may be found in any scalp
Figure 6.32: Abnormal frontal sharp waves in an infant 41 weeks of conceptional age with head trauma. Fron-
tal sharp waves are excessively sharp and superimposed on a featureless background.
region, but are most frequent in the temporal and central regions. Negative EEGs from the seizure group, 16 (21%) had relatively normal backgrounds
centrotemporal SETs are best evaluated during the low-voltage, continuous and SETs that behaved similar to those of the comparison group. Most neo-
portions of the tracing, which correspond to wakefulness and active sleep. nates with EEG-confirmed seizures had interictal tracings characterized by
It is difficult to quantitatively evaluate sharp waves that may occur during abnormal backgrounds and excessive spikes or sharp waves that sometimes
the bursts of activity in immature quiet sleep, because many infants gener- recurred in brief runs and were distributed nonrandomly in the temporal
ate “spikey” or sharp-quality quiet sleep bursts. Few data describing SETs and central regions.
before the conceptional age of 33 to 34 weeks are available. This study has implications for interpreting EEG abnormalities in infants
The significance of abnormal negative sharp waves is controversial. Some with seizures that are suspected but not specifically confirmed by recording
authors’ consider them a nonspecific electrographic finding that may occur electrographic seizures. Neonates with abnormal backgrounds and abnor-
in a variety of pathological conditions without a clear relationship to clini- mal negative SETs are considered to display patterns of abnormalities simi-
cal or electrographic seizures (14,15). This situation has a counterpart in lar to those in infants with electrographically confirmed seizures. They may
adult EEGs in that sharp waves may be seen in uremia, hypoxia with isch- be considered to have EEG characteristics of a “lowered seizure threshold”
emia, and drug withdrawal without the presence of clinical or electrographic at that time. However, this constellation of interictal EEG findings is not
seizures, and may be interpreted as nonspecific electrographic abnormalities diagnostic of neonatal seizures. In contrast, neonates with abnormal back-
(72). However, there is also evidence in neonates that some characteristics grounds and normal negative SETs have nonspecific cerebral dysfunction.
of negative, centrotemporal SETs are epileptiform and are encountered But this does not exclude the possibility of neonatal seizures.
more commonly in infants with seizures. Clancy (73) examined the EEG Neonates with normal backgrounds and abnormal SETs are relatively
backgrounds and characteristics of SETs in 78 EEGs from 30 neonates uncommon. However, in the context of the “well neonate” with seizures who
with confirmed electrographic seizures and compared them with the EEG has a normal EEG background with abnormal SETs, the diagnostic pos-
characteristics of SETs recorded from 69 healthy neonates without seizures. sibilities should include conditions such as simple hypocalcemia, in which
Both the EEG background and specific features of negative SETs were excessive sharp waves tend to arise in the central or central vertex regions
contrasted in the seizure and comparison groups. In the seizure group, 41 (74), and mild subarachnoid hemorrhage, which may “irritate” the cortex.
(52.6%) of 78 tracings had EEG backgrounds classified as moderately or
severely abnormal, in comparison with 0 of 69 abnormal backgrounds in Neonatal Negative Sharp EEG Transients in Other Locations
the comparison group. Centrotemporal SETs were characterized in terms of Just as electrographic neonatal seizures can arise from any scalp regions,
abundance (number of SETs counted during a 10-minute continuous EEG abnormal negative spikes or sharp waves may arise from any or many areas.
epoch), morphology (spike versus sharp wave), repetitive behavior, and spa- Multifocal SETs may be recorded from some infants with diffuse encepha-
tial distribution (among locations C3, C4, T3, and T4). lopathies, including those involving the midline (Fz, Cz, or Pz) and occipital
In infants without seizures, centrotemporal SETs (Fig. 6.33A, B) occurred regions (Figs. 6.36 and 6.37). However, the significance of finding excessive
at a rate of less than one per minute (Fig. 6.34) and were evenly distributed SETs that are limited to the occipital and midline areas is unclear, inasmuch
between both hemispheres (T3 and C3 versus T4 and C4), both temporal as few studies have systematically examined them (75–77).
regions (T3 versus T4), and both central regions (C3 versus C4). SETs were
more abundant in the temporal areas than in the central areas (Fig. 6.34). Neonatal Positive Sharp Waves (Rolandic,
In this group, SETs consisted of sharp waves and only rare spikes; runs or Vertex, and Temporal)
bursts of SETs were not seen. In the seizure group, centrotemporal SETs Positive sharp waves may appear in the sick neonate as sharp EEG tran-
usually occurred more frequently than two per minute, were often spikes sients (duration less than 400 to 500 milliseconds) (1,78–90) with an initial
(rather than sharp waves), and often recurred in repetitive runs. In the sei- and predominant surface-positive polarity. They may arise from the rolan-
zure group, SETs were more often nonrandomly distributed: significantly dic regions (PRSs) (Fig. 6.38), the central vertex (positive vertex sharp wave
distributed to favor one location or hemisphere more than others (Fig. 6.35). [PVS]) (Fig. 6.39), and the temporal regions (positive temporal sharp waves
These distinctions between the groups, however, were not absolute. Of 78 [PTS]) (Fig. 6.40). These pathological waveforms are not indicative of a
A
Figure 6.33: A: Normal temporal sharp electrographic transients (SETs) in an infant 43 weeks of conceptional
age with pneumonia. Right and left temporal SETs (arrows) are present. In this tracing, SETs were infrequent
and were equally distributed between both temporal regions. B: Normal central SETs in an infant 39 weeks
of conceptional age with Pierre Robin syndrome. Arrow indicates a normal-appearing right central negative
sharp wave. Rare right and left temporal and central negative sharp waves were present in this record.
B
EEGs. However, PRSs were present in only one premature infant with-
out IVH. Clancy et al. concluded that PRSs have low sensitivity but high
specificity for destructive IVH. Among infants with larger hemorrhages
(grades 3 and 4), there was a higher incidence (69.2%) of PRSs than
among infants with lower-grade hemorrhages (31.8%). PRSs and PVSs
were most commonly observed between the 5th and the 8th postnatal day
of life and gradually disappeared by 3 or 4 weeks of age. It is difficult
to ascertain the prognostic significance of these patterns per se, because
they are often observed in the context of substantially abnormal EEG
backgrounds, which themselves forecast adverse outcomes. However, they
may be best considered electrographic signs of underlying structural brain
abnormalities.
PTSs (see Fig. 6.40) in full-term infants are maximally expressed in the
midtemporal regions (T3 and T4) (81,85). They have received less atten-
tion than PRSs and PVSs, but share similar morphological features and
also appear to be linked to structural brain lesions, including periven-
tricular leukomalacia, intracerebral hemorrhages, and infarctions. In the
study of Chung and Clancy (81), more than 1,000 neonatal EEGs were
reviewed for the presence of PTSs. Forty-six EEGs from 31 full-term
infants were found to have “excessive” PTSs, “excessive” being defined
as greater than one PTS per minute during the low-voltage, continuous
portions of the tracing. EEG backgrounds were normal in nine records
Figure 6.34: Normal abundance of sharp electroencephalographic transients and abnormal in the others. In 25 of the 31 infants, a neuroimaging study
by location and conceptual age. (Adapted from Clancy R. Interictal sharp EEG or an autopsy was performed; 16 (64%) of the 25 patients were found to
transients in neonatal seizures. J Child Neurol 1989;4:30–38.)
have focal or diffuse structural lesions, the most common of which were
infarction and hemorrhage. In patients with focal lesions, the side of the
lesion correlated with the laterality of the PTS. PTSs appeared within 2
to 3 days of the acute illness and disappeared within 4 to 5 weeks. Other
“lowered seizure threshold,” but rather are electrographic markers of paren- studies (78,86,90) have also found PTSs to be correlated with hypoxia-
chymal brain injuries, especially in the deep cerebral white matter, and can ischemia or structural brain pathological processes. Some authors’ how-
be seen in a variety of conditions, including periventricular leukomalacia, ever, have questioned the significance of isolated PTS in the absence of
intraventricular hemorrhage (IVH), hydrocephalus, meningitis, IEMs, and other EEG background abnormalities (15). There is agreement, however,
HIE. The usual locations of pathological positive sharp waves in the pre- that PTS are not specifically epileptiform and are not directly associated
mature infant are the midline vertex (Cz) and rolandic (C3 and C4) regions. with neonatal seizures.
PVSs and PRSs occur singly or in brief runs with moderate to high voltages Little is known about the significance of PTSs in the premature infant.
(50 to 250 μV) and sometimes are comingled with beta activity. PTSs of low to moderate amplitude have been noted in the EEGs of healthy
The clinical significance of identifying PRSs and PVSs in premature premature infants, with a frequency of 15% at 33 to 34 weeks of conceptional
infants has been investigated by several authors’. Clancy and Tharp (82) age, decreasing to 0.75% by 39 to 40 weeks of conceptional age (82). The
investigated 44 infants with IVH verified by computed tomography or morphological features and amplitudes of these benign PTSs differed from
autopsy. PRSs were present in 13 infants with IVH and in 22 of the 30 those of the pathological PTSs noted in full-term infants (see Fig. 6.40).
Figure 6.35: Abnormal temporal sharp SETs in an infant 38 weeks of conceptional age with persistent
pulmonary hypertension and seizures. Multiple right temporal sharp waves are present (arrow). In this record,
left temporal sharp waves are rare.
Figure 6.36: Abnormal vertex sharp SETs in an infant 43 weeks of conceptional age with seizures. Sharp waves
isolated to the central vertex are seen (arrow). If electrode Cz had been omitted from the montage, these SETs
would have been missed.
Figure 6.37: Multifocal negative sharp waves in an infant 37 weeks of conceptional age with HIE and seizures.
Abnormal sharp EEG transients are present at T3, C3, C4, and Cz.
Figure 6.38: Positive rolandic sharp waves in an infant 34 weeks of conceptional age with left-sided grade IV
intraventricular hemorrhage. Repetitive positive rolandic sharp waves are seen at C3 (arrow).
higher numbers of neonates with occult seizures (92,93). For example, Scher
et al. (94) found that 92 (2.3%) of 4,020 neonates admitted to an intensive
care nursery over a 4-year period had an electrographic neonatal seizure
(ENS), but clinical signs accompanied these seizures in only 28 (45%) of 62
preterm infants and 16 (53%) of 30 full-term infants.
The hallmark of an ENS is the sudden appearance of a repetitive dis-
charge event consisting of a definite beginning, middle, and end. ENS
evolve in frequency, morphological appearance, and amplitude (Fig. 6.41)
(1,67,93,95,96). An interpretative pitfall for the electroencephalographer is
to distinguish ENS from rhythmic extracerebral artifacts, which are typi-
cally monomorphic and do not evolve in frequency, morphological appear-
ance, or amplitude. The characteristics of ENS can be described in terms
similar to those used for pediatric and adult electrographic seizures: loca-
tion, duration, morphological appearance, and amplitude.
Location. The overwhelming majority of ENSs are focal in onset. Gen-
eralized, bilateral, synchronous spike and slow-wave discharges have only
rarely been described. An ENS may be recorded from any scalp region,
but the central and temporal regions are the most common sites of origin.
Repetitive ENSs originating from a single scalp region are termed unifo-
cal, whereas recurrent ENSs arising from multiple scalp regions are termed
Figure 6.39: PVS waves in an infant 29 weeks of conceptional age with right-
sided grade III intraventricular hemorrhage. PVS waves are seen at Cz (arrows). In
multifocal. Recurrent ENSs arising from a single scalp region should raise
this case, a recording montage that included Cz was necessary to record these the suspicion of a focal or lateralized structural lesion such as an infarction
abnormal transients. from an embolism (97), but not all unifocal ENSs are accompanied by local-
ized abnormalities on neuroimaging studies. Both unifocal and multifocal
ENSs may propagate to adjacent or distant scalp locations (see Fig. 6.41).
Simultaneous and independent ENSs may arise from multiple scalp regions
ELECTROGRAPHIC NEONATAL SEIZURES (Fig. 6.42).
AND CLINICAL CORRELATIONS Duration. A minimum ictal duration of 10 seconds is conventionally (and
perhaps arbitrarily) required for the designation of ENS in most studies.
It is a challenge for all involved in the care of neonates to distinguish The average duration of an ENS is brief. In one study of 487 ENSs (67),
epilepsy-based neonatal seizures from the wide array of nonepileptic par- 230 (47%) lasted less than 1 minute, and 90 (18%) lasted between 1 and
oxysmal behaviors that may occur in healthy or sick infants. The essential 2 minutes; the finding of a mean duration of 2.25 minutes in this study
role of video-EEG monitoring for accurate diagnosis of suspected neonatal was influenced by rare prolonged seizures that lasted up to 46 minutes. Dis-
seizures was established by Mizrahi and Kellaway (91), who analyzed video- charges lasting less than 10 seconds and showing typical evolution in fre-
EEGs from 349 neonates between the conceptional ages of 28 and 44 weeks, quency, morphological appearance, or amplitude have been termed brief
in whom there was a clinical suspicion of seizures. A total of 415 paroxysmal ictal rhythmic discharges (BIRDs) (98) and are of unclear significance.
clinical events were found in 71 patients, but only 119 (29%) of these events BIRDs (Fig. 6.43) clearly suggest a lower seizure threshold and may have the
in 23 patients had a close temporal association with an ictal EEG discharge; same significance as the longer-duration ENS. It is uncommon to encoun-
another 11 patients had occult seizures, which are electrographic seizures ter a single electrographic seizure in most routine ictal recordings. Instead,
without conspicuous clinical signs. Other studies have found significantly multiple ENSs are usually encountered (Fig. 6.44). The precise difference
Figure 6.40: PTS waves in an infant 40 weeks of conceptional age with HIE and seizures. Left- and right-sided
PTS waves (arrows) are present.
Figure 6.41: Ictal onset and propagation in an infant 40 weeks of conceptional age with HIE and seizures.
Ictal onset is seen over the left central region (large arrow), with subsequent propagation to the central vertex
region (small arrow). Eventually, ictal activity is also seen in the left temporal region.
Figure 6.42: Simultaneous, independent seizures in an infant 37 weeks of conceptional age with HIE and
seizures. Independent seizures are present simultaneously at C4 and O1.
Figure 6.43: BIRD in an infant 42 weeks of conceptional age with double-outlet right ventricle and a history
of cardiac arrest. A BIRD is present at Fp4 (arrow) and T4. The evolution in morphological appearance and
amplitude and the presence of a physiological field distinguishes this BIRD from artifact.
Figure 6.44: Continuous video-electroencepha-

lographic monitoring of an infant 40 weeks of con-
ceptional age with birth trauma revealed numerous
electrographic seizures each hour until the infant
was treated vigorously with thiopental. Many acutely
ill neonates experience multiple seizures.
between multiple ENSs and status epilepticus in the neonate is unknown. It Amplitude. Just as ENSs display evolution of waveform morphological
is difficult to apply the traditional definitions of status epilepticus (continu- appearance, they also typically evolve in amplitude. ENSs commonly first
ous seizure activity for 30 minutes or recurrent seizures without full recov- appear at relatively low amplitudes, which gradually increase as the seizure
ery of consciousness) to neonates. An alternative definition of neonatal evolves (Fig. 6.47).
status epilepticus used in some studies is (a) total seizure duration exceeding It is challenging to design a clinically useful approach for the use of EEG
30 minutes or (b) the sum of the duration of individual seizures exceeding in the high-risk neonate. One strategy is to limit the use of serial tracings to
50% of the tracing (60). According to these criteria, status epilepticus was tracings with clinically suspected seizures. This approach risks the underdi-
present in 22 (27%) of 81 neonates with EEG-proven seizures (60). agnosis of ENS, in view of the high frequency of occult seizures in this age
Morphological Appearance. ENSs are characterized by a rich variety of group. Another strategy, outlined by Laroia et al. (99), is to use the initial
ictal morphological appearances, both between patients and in a given EEG background to decide which high-risk infants would benefit from sub-
individual. All frequencies (delta, theta, alpha, and beta) are represented sequent prolonged monitoring. In the study validating that approach, 51
(Figs. 6.45 and 6.46). Ictal waveforms range from simple sinusoidal patterns infants with risk factors for seizures (such as HIE or meningitis) underwent
to complex, bizarre ictal patterns. Evolution of morphological appearance a 30- to 60-minute screening EEG, followed by continuous EEG monitoring
within an ENS is helpful in distinguishing ENS from artifact. for 18 to 24 hours. The EEG background of the initial tracing was classified
Figure 6.45: Delta frequency seizure in an infant 37 weeks of conceptional age with HIE and seizures. A delta
frequency seizure is seen to evolve from O1.
Figure 6.46: Theta frequency seizure in an infant 36 weeks of conceptional age who had recently suffered
cardiac arrest. After a burst of cerebral activity, an ictal discharge with a frequency of 5 Hz begins over the right
frontal region (arrow).
Figure 6.47: Amplitude evolution of an electrographic seizure in an infant 40 weeks of conceptional age with
respiratory syncytial virus pneumonia. A seizure is evolving in amplitude at T3 (arrow).
as normal, immature for age, mildly abnormal, moderately abnormal, or abnormal outcomes were found in 22 (85%) of 26 infants with normal EEG
severely abnormal. Only 1 (4.2%) of 24 infants with normal or immature backgrounds, in 5 (45%) of 11 infants with moderately abnormal back-
EEG backgrounds had subsequent ENSs. However, 22 (81%) of 27 infants grounds, and in 1 (2.7%) of 37 infants with severely abnormal backgrounds.
with abnormal EEG backgrounds had ENSs. Thus, a normal or immature In two other studies, researchers examined outcome after EEG-confirmed
initial EEG background predicted the absence of seizures in the subsequent neonatal seizures. Scher et al. (94) reported that 56 (61%) of 92 neonates
18 to 24 hours, with a sensitivity of 96% and a specificity of 81% (Table 6.2). with EEG-confirmed seizures survived. Normal outcome was documented
A developing strategy is the use of automated, computer-based ENS in 9 (25%) of 36 preterm infants and in 12 (60%) of 20 full-term infants.
detection algorithms. Such systems are highly sensitive when used to detect Legido et al. (109) monitored outcomes in 40 neonates with EEG-confirmed
seizures in older children and adults (100), but are more challenging to seizures. Twenty-seven (68%) survived, but outcome was unfavorable in 70%
design for use in neonates because of the different ictal waveform frequen- of those survivors. Factors associated with unfavorable outcome included
cies and characteristics. Brief, low-amplitude ENS are especially difficult to etiology (such as asphyxia, meningitis, or cerebral dysgenesis), moderately
detect. Nonetheless, computer-aided detection systems with sensitivities of or severely abnormal EEG background, and higher seizure frequency.
71% to 84% have been reported (101,102). Recommendations for review of
continuous neonatal recordings have been recently updated (103). Sharp Waves and Spikes in the Older Infant and Child
The impact of ENS per se on subsequent neurological outcome is diffi-
cult to determine. Outcome is heavily dependent on the underlying cause of Sharp waves and spikes are identified as epileptiform discharges somewhere
the seizures and the degree of background abnormality. Those with benign around 3 months of age. In infants and older children, the association of
neonatal seizures fare well (104,105), whereas infants whose seizures are interictal epileptiform discharges (IEDs) with epilepsy varies with location
provoked by acute illness face a much higher risk of permanent neurologi- and morphology of the IEDs. Pleomorphic IEDs and IEDs occurring over
cal handicap. In general, neonates with seizures superimposed on a normal the midline, frontal, and anterior temporal regions are highly correlated
EEG background have lower risks of adverse outcomes, whereas those with with clinical seizures: 75% to 95% of patients with these IEDs have epilepsy
ENS and a moderately or severely abnormal background have worse out- (110,111). In contrast, only about 40% of patients with central-midtemporal
comes (106). In their classic study of 137 full-term neonates with clinically spikes and 50% with occipital spikes have seizures (111). Regular generalized
diagnosed seizures, Rose and Lombroso (107) found that 67 (78%) of 85 spike-wave discharges may similarly be seen in asymptomatic individuals.
infants with normal backgrounds or a unifocal abnormality on initial EEG These stereotyped centro-temporal spikes and stereotyped occipital spikes
had normal outcomes, whereas only 4 (8%) of 52 patients with multifocal may all be transmitted as asymptomatic genetic traits in an autosomal dom-
abnormalities and low-amplitude or periodic backgrounds had normal out- inant fashion with variable penetrance. Blindness occurring in infancy may
comes. In a later study, Rowe et al. (108) examined outcome after clinically be associated with needle-like occipital spikes (112), and accounts for 15%
diagnosed seizures in 74 preterm and full-term infants. Normal or mildly of all occipital IEDs.
Hyperventilation Response
If effective HV is obtained in children, slow waves appear much more
TABLE 6.2 Association of EEG Background and ENSs abruptly and are more pronounced than in adults, and the slowing outlasts
the overbreathing for a longer time in children (113). The degree and abrupt-
Normal or immature Abnormal EEG
ness of the response seem to relate directly to age (113–116). Indeed, when
EEG background background
the blood Pco2 change produced by overbreathing is measured, there is a
No electrographic seizures 23 5
linear relationship between age and the effect produced (117,118). Practi-
Electrographic seizures 1 22 cally speaking, under routine laboratory conditions, in which respiratory
Adapted from Laroia N, Guillet R, Burchfiel J, et al. EEG background as predictor of effort and effect are not measured, the most pronounced responses to HV
electrographic seizures in high-risk neonates. Epilepsia 1998;39:545–551. usually occur in children 8 to 12 years of age (24,114,119) (Fig. 6.48).
Figure 6.48: Example of pronounced over-

ventilation response that may occur in chil-
dren 8 to 12 years of age. The subject was a
girl aged 9 years, 6 months, at the time of the
electroencephalographic study, with serum
glucose level of 110 mg per dL. She had no
history of seizures or evidence of CNS disease.
Note that initial posterior slowing, typically
seen in children, is quite marked after only
30 seconds of overventilation. Some frontal
delta activity continues 50 seconds after over-
ventilation stopped.
Practical experience has shown that in routine diagnostic EEG, inter- discussion is highlighted here: a photoparoxysmal response is more often
pretation must allow wide latitude for the degree of slowing and for the encountered in adolescents, and this may simply be a phenotypic marker of
abruptness and duration of the HV effect. Only the elicitation of abnormal a genetic susceptibility. One should be cautious about overinterpreting the
wave complexes (spike-and-slow-wave, sharp-and-slow-wave) or clear focal or clinical significance of a photoparoxysmal response in a teenager who has
lateralizing changes can be considered unequivocal evidence of abnormality. not had clear clinical seizures.
Even paroxysmal slow bursts are not acceptable evidence of abnormality,
because these may be elicited in normal children under certain circumstances
(23,24). Nonetheless, “susceptibility to HV” (120) and other characteriza- Activity of Drowsiness, Arousal, and Sleep
tions of pronounced overventilation responses have been used as diagnostic
measures in the evaluation of children (121). Monorhythmic Slow Activity
The blood glucose level is important in determining the degree of response Drowsiness is usually defined as a presleep state, or a prodromal or twi-
to HV (122–124). Most routine EEG studies of children do not control for light condition between being fully awake and being asleep. In infants and
this factor; however, even in adults, a low blood glucose level (<80 mg per young children, overt signs of drowsiness may not be evident, even though
100 mL) favors the appearance of slow waves, and a high level (>120 mg per the EEG shows changes indicating that the child is falling asleep. “Drowsi-
100 mL) tends to inhibit or prevent such an effect (124). ness” commonly conjures up a certain vision of a “heavy-lidded” appear-
ance and, on the contrary, infants may have their eyes wide open and may
Photic Stimulation be irritable and restless during a variable period before the onset of clinical
Photic stimulation and its age-dependent characteristics are discussed in and electrographic sleep. For that reason, the author and colleagues have
detail in the chapter on activation techniques. One aspect of this thorough used the less common term hypnagogic to refer to this state (125). A smooth
transition from the hypnagogic state to sleep may not occur, especially in the
strange environment of the EEG laboratory; instead, the child’s condition
may fluctuate between sleep, arousal, and transitional states. A steady state
of slow-wave sleep (stages II–IV) may not appear under ordinary conditions
in the EEG laboratory for intervals ranging from a few minutes to an hour
or more.
In order not to be misled by the sometimes dramatic changes in the EEG
that occur during the transition between wakefulness and sleep, the clinical
electroencephalographer must know the EEG patterns and their variations
that may occur during this state in children of various ages. The electro-
encephalographer can better understand and interpret what transpires if
the entire process of falling asleep is recorded. The irrational, if economi-
cal, practice of turning off the instrument while waiting for the child to fall
asleep may also result in loss of critical data: An important electrographic
event may occur only once or only during one stage of the sleep cycle. Fur-
thermore, the child sometimes drops precipitously into deep sleep, with a
consequent omission of the productive stages II and III of sleep.
The changes that take place in the transient stage between wakefulness
and sleep are best understood in view of the changes with increasing age
from birth onward: once a sustained, rhythmic, occipital activity appears at Figure 6.49: Age distribution and incidence of sustained monorhythmic slow-
approximately 3 months of age, the onset of the hypnagogic state is marked activity drowsiness in asymptomatic children.
by sustained, monorhythmic, slow generalized activity. When this activity
first appears, the frequency is 3 to 4 Hz, and it increases to 4 or 5 Hz in older
children. Approximately 30% of 3-month-old infants show this hypnagogic More commonly, as a shift toward sleep takes place, the occipital alpha
hypersynchrony; the degree of its expression and duration vary in a single rhythm becomes less persistent, and a central or frontocentral rhythm of 4
infant at different times and on different days. It may be seen in normal to 6 Hz develops; this rhythm may have a high voltage (200 μV). Examples
children up to the age of 12 or 13 years but is increasingly rare after the age of monorhythmic drowsy patterns in children of various ages are shown in
of 11 years, when it appears in only 10% of healthy children. Figure 6.49 Figs. 6.50 and 6.51.
shows the incidence of this drowsy pattern in the authors’ own series of
1,000 healthy children. The relation to age resembles that reported by Gibbs Paroxysmal Slow Activity
and Gibbs (126) in asymptomatic children and by Eeg-Olofsson et al. (127)
Gibbs and Gibbs (126) and Kellaway and Fox (125) were the first to describe
in highly selected normal subjects.
paroxysmal slow bursts during drowsiness in normal children. The latter
In some children, the occipital alpha rhythm may slow as drowsiness
authors’ described it as follows:
ensues (Fig. 6.50), and at a time when anterior derivations show the more
usual 4- to 5-Hz hypnagogic hypersynchrony, the occipital derivations may The onset of the hypnagogic phase is signaled by a general reduction
show some high-voltage, less regulated, slower (3 to 4 Hz) activity. The latter in the amplitude and rhythmicity of the activity of all areas. This rela-
effect occurs in not more than 3% of healthy children before the onset of tive ‘quiet’ may then be broken by paroxysmal bursts of high-voltage
sleep, but it occurs in approximately 6% after arousal. It commonly occurs sinusoidal waves which involve all leads but which are greater in am-
during a transient episode of arousal. In the authors’ series of healthy con- plitude in the precentral or central regions and generally more strongly
trols, all children with this pattern were younger than 4 years. expressed in the frontal than in the occipital regions.
Figure 6.50: A and B: Slowing of the occipital alpha rhythm as the

record shifts from the awake state (first two-thirds of part A) to the
drowsy state (last third of part A and all of part B) in an asymptomatic
girl aged 28 months. B
Figure 6.51: A: Almost continuous “hypnagogic hypersynchrony” in

an asymptomatic 6-month-old infant. B: Continuous “drowsy” pattern
B in an asymptomatic 12-month-old infant.
These paroxysmal bursts may reach extremely high voltages when

maximally expressed (in excess of 350 microvolts) and therefore con-
stitute a possible source of error both for the interpretation of sleep
where this is sought and for the interpretation of waking records
where the oscitant state may intervene without true sleep ensuing. . . . 
The appearance of such bursts in the period just preceding true sleep,
or at its onset, or at a time when the electrogram shows other evidence
of the hypnagogic state, is never considered an epileptiform manifesta-
tion unless accompanied by spike discharges in some form. Long ex-
perience has shown that if a patient with established petit mal epilepsy
shows abnormal paroxysmal activity during sleep, the spike compo-
nent is always strongly in evidence and the epileptiform serials persist
into fairly deep levels of sleep. A distinguishing characteristic then of
the pre-oscitant paroxysmal episodes is that they make a brief appear-
ance at the onset of sleep and do not persist into deeper stages.
The example of paroxysmal drowsy waves illustrated in the report of
Kellaway and Fox (125) is shown in Fig. 6.52. The paroxysmal activity in
this sample, which they considered representative for age (35 months), has a
frequency of 4.0 to 4.5 Hz, shows maximum voltage in the central regions,
and shows a spindle-like waxing and waning of amplitude typical of the
drowsy patterns seen in their series of asymptomatic children. Figure 6.52: Paroxysmal “hypnagogic hypersynchrony” in an asymptomatic girl
More complex waveforms, slower wave bursts, and a more frontal- aged 35 months. (From Kellaway P, Fox BJ. Electroencephalographic diagnosis
of cerebral pathology in infants during sleep, I: rationale, technique, and the
dominant distribution of the activity may also be seen in normal children.
characteristics of normal sleep in infants. J Pediatr 1952;41:262–287.)
The example of paroxysmal slow activity illustrated by Gibbs and Gibbs
(126) shows (a) some waves at the end of the bursts as slow as 2.5 to 3.0 Hz,
and (b) some complex waveforms with faster components superimposed waves of 100 to 300 μV, with a spike or spike-like component appearing
on, or intermixed with, the slow waves. Figures 6.53 and 6.54 show exam- briefly, early or late, in the burst. The pattern disappeared as soon as drowsi-
ples of activity of this type in drowsy asymptomatic children. It is difficult ness was replaced by deeper sleep. A wide diversity of patterns of paroxys-
to distinguish between such bursts and a pattern described by Gibbs and mal drowsy bursts, ranging from a common type with occasional notching
Gibbs (128), which they designated “pseudo petit mal.” They characterized of the slow waves to bursts with polyspike-like components, may occur in
the pattern as “paroxysmal diffuse 3–4 per second slow waves, with a poorly normal children (see Fig. 6.54).
developed spike in the positive trough between the slow waves, occurring Figure 6.55 illustrates the incidence of “paroxysmal hypnagogic hypersyn-
in drowsiness only.and most prominent in the parietal [central: C3–C4] chrony” in asymptomatic children of different ages. The hatched bars show
areas.” Gibbs and Gibbs saw this pattern only in children between the ages the incidence of what Brandt and Brandt called the “severe” type (i.e., slow
of 3 months and 9 years, and only in 0.1% of normal children aged 0 to bursts with sharp or “spike-like” components). The percentage approxi-
14 years. Eeg-Olofsson et al. (127), however, found similar activity during mates that found by Eeg-Olofsson et al. (127) in their highly selected normal
drowsiness in 7.9% of 599 highly selected normal children aged 1 to 16 years. children.
The highest incidence (12%) was in children aged 4 to 5 years. Gibbs and In routine clinical practice, if such bursts occur only during drowsiness
Gibbs described this “drowsy” pattern as consisting of bursts of 2- to 4- Hz or at the onset of sleep, they cannot be considered evidence of abnormal
Figure 6.53: Paroxysmal “hypnagogic hypersynchrony” in a 14-year-old girl, Figure 6.54: Complex wave configurations such as in O1 and O2, as well as low-
asymptomatic at the time of the electroencephalographic study and during the voltage, spike-like components seen in other derivations, are most common in
20 years after the tracing was made. There was no family history of seizures. Com- drowsy, asymptomatic children between the ages of 4 and 9 years. The subject
plex, paroxysmal slow bursts of this type, occurring only in drowsiness, are rare was an asymptomatic 7-year-old boy.
at this age (see Fig. 6.55).
function and certainly cannot support a clinical diagnosis of epilepsy. Even persist for prolonged periods. Transient arousals (Fig. 6.56) frequently elicit
bursts with a clearly defined spike component fitting Gibbs and Gibbs’s a paroxysmal type of slow pattern; thus, it is important for the technologist
(128) definition of “pseudo petit mal” have only a tenuous association (10%) to make note of such arousals and for the electroencephalographer to watch
with febrile convulsions. According to Gibbs and Gibbs, the incidence of for artifacts associated with such a change of state.
epileptic (other than febrile) convulsions is only 7% greater in children with Arousal from any level of sleep in infants and children is generally associ-
“pseudo petit mal” bursts than in children with normal EEGs, a difference ated with a paroxysmal change. This may be a single, high-voltage, sharp-
that is not statistically significant. wave transient similar to that in adults, or it may be a complex three-phase
From the ages of 3 months to 6 years, patterns of drowsiness may vary change, which, if unexpected or unrecognized as an arousal event, may be
from time to time in the same child. If sleep begins abruptly, little hypersyn- misinterpreted as abnormal.
chrony of any type may be seen. If there is a delay in the onset of true sleep, In general, the ages with pronounced arousal patterns coincide with those
continuous, rhythmic, high-voltage slow or paroxysmal slow activity may for hypersynchronous slow drowsy patterns.
Figure 6.55: Percentages of asymptomatic children of various ages who show par-
oxysmal slow bursts in drowsiness. Hatched areas show percentages having sharp or
spike-like components intermixed with slow waves, as in Figs. 6.53 and 6.54.
Activity of Arousal of desynchronization. Sometime between the 8th and 12th week, rudimentary
The electrographic arousal reaction is clearly defined before the age of diphasic slow-wave responses to applied stimuli may occur; also, at about this
2 months. During the first 8 weeks after birth, and especially during the first time, the first signs of a definite rhythmic hypersynchrony, similar to that of
6 weeks, the transition from sleep to waking is characterized only by a degree the drowsy state, appear in the immediate postarousal state. However, the slow
Figure 6.56: Transient arousal in an asymptomatic boy, aged 7 years.

Just before the beginning of the sample, the child had been asleep
(stage II). A brief period of desynchronization is followed by some
central and occipital alpha activity lasting 2.0 to 2.5 seconds and,
in turn, by a high-voltage, central-dominant, “drowsy” burst lasting
about 3 seconds; then sleep resumes.
component of the arousal reaction is rarely well defined before the age of 3 Postarousal Hypersynchrony
months. In children, the fast component of the arousal pattern is quickly followed by
The faster component of the arousal reaction usually does not appear what in adults would be called a “paradoxical arousal response.” Thus, as
before the age of 7 months. Initially rudimentary, it consists of a few mod- the child awakens, a high-voltage, monomorphic, quite slow rhythm (2.5 to
erately high-voltage sinusoidal waves of 4.0 to 4.5 Hz in the frontocentral 3.5 Hz) appears in the frontal regions (see Fig. 6.57C); and as further arousal
region, superimposed on a slower, irregular background activity. ensues, the rhythmic slow activity becomes less slow and moves posteriorly,
With increasing age, this fast component of arousal increases in frequency with the voltage and persistence of the rhythm progressively diminishing in
until it reaches the adult rate of 8 to 10 Hz. In children, it is maximal in the anterior derivations (see Fig. 6.57D). In infants and children in whom con-
central region (C3 to C4), and its field is such that its voltage is higher at F3 tinuous “monorhythmic slow” or “paroxysmal slow” activity occurs during
and F4 than at P3 and P4. Its appearance is transitory, and its duration is drowsiness, there may be similar episodes of postarousal hypersynchronous
usually no more than 4 to 5 seconds. Occasionally, runs of this activity may slow activity of similar frequency (125).
last as long as 30 seconds (125).
A
B
Figure 6.57: Response to stimulus, and phases of arousal response, in a normal child, aged 6 years. A: Handclap
elicits only a vertex transient, with no clinical or electroencephalographic evidence of arousal. Calling the child’s
name results in a full sequence of arousal, as follows: B: The first phase is the central-dominant fast component.
C: In the next phase, the central fast component is replaced by generalized slow activity, with rhythmic monomor-
phic delta activity in the frontal regions and slower, less rhythmic, activity in posterior derivations. D: The last phase
of the arousal pattern before the normal alpha rhythm reappears consists of posterior rhythmic and semirhythmic
delta activity. The child appears to be awake as soon as phase C (frontal delta activity) occurs. The calibration is the
same for all four tracings. Arousal in a child may be aborted at any of these phases, with a reversion to sleep. The
degree of arousal may alternate between phases two or more times before an awake state is sustained.
C D
The various components of arousal and awakening patterns in children over a wide area of the frontocentral region. These sharp waves are usu-
shown in Fig. 6.57 may be aborted at any point in the process. If an external ally diphasic, with an initial surface-negative deflection followed by a low-
stimulus triggers the arousal (if there is a sudden sound, if the child’s name is voltage, surface-positive phase. The sharp wave may be followed by a slow,
called, or if the child is touched), a diphasic sharp-wave transient appears in surface-negative wave and/or a sleep spindle.
the region of the vertex; if no arousal effect is produced, the background EEG From the time these waves first appear (at approximately 8 weeks postterm),
activity reverts immediately to its prestimulation character (as in Fig. 6.57A). they are bilaterally synchronous and essentially symmetrical on the two sides.
Presumably, a further degree of arousal is signaled by the appearance of the With persistent asymmetry of more than 20%, a lesion on the low side should
fast central component (as in Fig. 6.57B), and overt signs of arousal (e.g., be suspected. Some variable voltage difference between the two sides is not
movement or eye opening) do not occur until the hypersynchronous slow uncommon in young children, but if the low voltage always appears on the
activity appears (see Fig. 6.57C). Spontaneous arousal may occur without the same side, it should be regarded as significant. Unlike other sleep activity
appearance of the diphasic central (vertex) sharp-wave transient. (e.g., spindles), vertex transients are always bilaterally synchronous in normal
persons. A breakdown of this synchrony is usually a sign of increased intra-
Activity of Sleep
ventricular pressure (obstructive hydrocephalus). Asynchrony should be dis-
Vertex Sharp-Wave Transients tinguished from the situation not uncommonly seen in children in which the
The onset of stage II sleep is signaled by the appearance of bilaterally syn- vertex transients do not occur on both sides each time. In this situation, one
chronous sharp-wave transients in the central region (Fig. 6.58). Although or the other side may show more vertex transients (and spindles), but when-
maximal in voltage in the C3 and C4 electrode positions, when they are of ever they occur bilaterally, they are symmetrical on the two sides. Although
high voltage, as they sometimes are in young children, they may be evident this phenomenon—in which an occasional vertex transient (and spindle) may
Figure 6.58: Example of bilateral vertex transients in an

asymptomatic 12-year-old girl. Note the diphasic waveform
in central derivations.
be missing on one side—occurs in apparently healthy children, it is compara- often been applied to the spontaneous vertex transients of sleep. The electri-
tively rare (<3%) and may indeed be pathophysiologically significant. cal field of the slow component of the K complex at the scalp is essentially
The very high voltage that vertex transients may attain in children aged 2 to similar to that of the vertex transient, and the initial component may have a
4 years may come as a surprise to the electroencephalographer not accustomed similar waveform. It has, in fact, been suggested that vertex transients con-
to children’s records. The high-voltage and sharply peaked waveform must not stitute EEG responses to afferent stimuli arising from interoceptors.
lead to an incorrect interpretation of abnormality. Similarly, these vertex tran- Once stage II sleep has been reached, a single “click” stimulus will
sients in children, in contrast to the situation in adults, may occur in quick suc- elicit a sharp, diphasic wave in the central region bilaterally that is indis-
cession (every 1 to 2 seconds), and an “interference pattern” may result, giving tinguishable in waveform, amplitude, and field from the spontaneously
these waves a complex configuration that seems abnormal (Fig. 6.59). occurring vertex transient in the same individual. The spontaneous vertex
The voltage and, to some degree, the configuration of successive vertex transients may occur in relatively quick succession, as shown in Fig. 6.59,
transients in any series may fluctuate considerably, and in a given montage, and appear in quick succession (every 1 to 2 seconds) throughout stages
it may be difficult to distinguish the vertex transients (Fig. 6.60) from abnor- 2 to 4 of non-REM sleep; however, the central sharp-wave transients
mal sharp-wave discharges arising unilaterally or bilaterally from foci in this elicited by a stimulus show a relatively long refractory period and may
region (rolandic spikes). The problem can often be solved by mapping the disappear if the stimulus is repeated at short intervals over a period of
fields of the various sharp waves present. 30 seconds or more. This accommodation effect can be overcome simply
K Complexes and Vertex Transients. The term K complex was originally by changing to a novel stimulus: for example, by substituting the calling
used by Loomis et al. (129,130) to denote a series of waves that could be of the child’s name for one of the clicks (personal observations). The
detected in the EEG during sleep in response to an auditory stimulus (see duration of the refractory period in which a second stimulus (e.g., a click)
Fig. 6.61). As the word “complex” implies, the term was not meant to is not effective has not been measured precisely, but it is estimated to be
describe a single transient or sharp wave, although the term K complex has at least 5 seconds.
Figure 6.59: Vertex transients occurring in repetitive sequence

in an asymptomatic 11-year-old boy. Note the variable and often
sharp waveform. The higher-voltage transients cause blocking at
normal gain.
Figure 6.60: Characteristically “sharp” appearance of some vertex

transients in children is increased in this montage by the admixture of
electrocardiographic artifact and fast activity. The sample is from an
asymptomatic girl aged 9 years, 6 months with no evidence of CNS
disease.
Figure 6.61: Abortive-arousal response consisting of a slow-wave

transient, maximum in voltage in the frontal leads, followed by a train
of 9- to 14-Hz waves; the subject was a normal adult. Vertex transient
and low-voltage spindle (sigma) activity occur before the abortive-
arousal response. Such arousal patterns may occur spontaneously.
Spindles Sleep spindles are bilaterally asynchronous at the time of their first
appearance at 6 to 8 weeks postterm (125) (Fig. 6.62), and they become in-
creasingly more synchronous during the first year of life; thus by the 18th
month, most spindles are bilaterally synchronous. Before the age of 2 years,
asynchrony of sleep spindles cannot be considered evidence of abnormality.
The waveform and duration of sleep spindles in infants differ from those in
adults: The spindles may be 2 to 4 seconds in duration and lack the typical
fusiform amplitude modulation that gives the adult type of sleep spindle its
name. The individual waves of the spindle may be sharply peaked (reminis-
cent of the mu rhythm) in the surface-negative phase (125) (see Fig. 6.62).
Three types of spindles may be distinguished by their frequency charac-
teristics and potential field. The most common, and usually the only type
seen in adults, has a frequency of approximately 14 Hz, and the center of
the field coincides closely with the C3 and C4 electrode placements. The
spindles are characteristic of stages II and III sleep, but they are also the
distinguishing characteristic of “spindle coma” or “coma sleep” (131). Uni-
lateral slowing of spindle frequency may occur in the presence of lesions of
the ipsilateral hemisphere (132).
Spindles that have a fundamental frequency of approximately 10 to 12 Hz
and a more anterior locus of origin occur in 5% of normal children aged
3 to 12 years (Fig. 6.63). These “frontal” spindles, which are seldom more Figure 6.62: Typical infant sleep spindles. Note the asynchrony (attenuation)
than 3 seconds in duration, should be clearly differentiated from “continu- between the two sides, prolonged duration (>4 seconds), lack of fusiform ampli-
ous spindling” or “exaggerated” spindles, which are an abnormal finding tude modulation, and mu-like waveform.
Figure 6.63: A: Example of 12-Hz frontal-dominant

spindles in stage II sleep in an asymptomatic boy, aged
10 years, 10 months. These spindles are often high in volt-
age in comparison with 14-Hz central spindles and have a
larger potential field. B: Example of 10-Hz frontal-dominant
spindles in an asymptomatic 6-year-old boy. B
seen in children with certain types of cerebral palsy and mental retarda- seems to reach its maximum expression. After the age of 30 to 36 months,
tion. Frontal 10-Hz spindling that is almost continuous can result from pronounced fast activity during early sleep is less common, and in general,
drug action (e.g., morphine and halothane anesthesia), but the unremitting the amplitudes seen are not as great as in children aged 12 to 18 months.
character of the activity and the lack of reactivity to intense stimuli clearly Older children are much less likely to show fast activity during early sleep,
distinguish it from the frontal-dominant 10-Hz spindles of sleep (Fig. 6.64). and after the age of 7, it is relatively uncommon (125).
Fusiform bursts of 18- to 22-Hz activity in sleep should not be confused When sedation with a barbiturate or other fast activity–inducing drug
with sleep spindles (sigma activity). Most commonly, these bursts are effects is used to promote sleep, fast activity is increased in the awake and asleep
of medication, particularly the phenothiazines and barbiturates (Fig. 6.65), EEG. This fast activity has a frequency chiefly in the range of 18 to 22 Hz
but they are also associated with certain pathological conditions in the and a predominantly anterior distribution. When sedatives are administered
absence of drugs. at some point just before or during the recording, the fast activity induced
Fast Activity. Sometime between the 5th and 6th month, many infants begin displays maximum voltage during light sleep (stages 1 and 2) and is greatly
to show low-voltage fast activity during the early stages of sleep. This activ- diminished during deeper sleep. Upon arousal, the fast activity increases
ity occurs in all derivations but is most pronounced in the central or post- again and becomes much more pronounced than in the presleep record—
central region (see Fig. 6.66). The frequency averages approximately 28 Hz, unless there was an inordinate delay in the onset of sleep. Fast activity
but it varies as much as ±6 Hz in different subjects. When the fast activity induced by chronic medication, or by a drug administered a long time before
first occurs, its amplitude is very low (5 μV or less), but relatively high am- the recording, shows the same diminution during the deep sleep stages but is
plitudes (30 μV maximum) may be seen by the 12th to 18th month, when it equal during the presleep and postsleep awake tracings.
Figure 6.64: Almost continuous 10- to 12-Hz, moderately

high voltage, frontal-dominant activity showing a spindle-
like amplitude modulation in a woman aged 52 years who
was stuporous from a diazepam overdose.
Figure 6.65: Barbiturate “spindles” such as those in this

figure are sometimes confused with physiological sleep
spindles. Note the greater amplitude of paired frontal
derivation in comparison with homolateral frontal deriva-
tions; this is a common finding with barbiturate spindles
but is not characteristic of sleep spindles. The subject was
a boy aged 13 years, 4 months, with generalized seizures
and taking phenobarbital (150 mg per day). Fast activity
was not present before treatment. The sample is from
stage I sleep.
Figure 6.66: Posterior 20- to 22-Hz activity present almost

continuously but tending to show bursts of high voltage, in
an asymptomatic 18-month-old girl.
The voltage of both natural and induced fast activity should be essen- pattern occurs in persons aged 4 to 50 years and is most common and best
tially the same bilaterally. With a consistent difference of more than 30%, an expressed in those aged 15 to 35 years. The individual waves show a sharp,
abnormality on the low-voltage side should be suspected, except when the surface-positive peak, followed in some instances by a low-voltage, surface-
fast activity is confined to a circumscribed focal area, in which case it may negative peak. The initial deflection of each wave has a somewhat slower
be associated with a focal lesion in that region (133). (Beware, however, of time course than the ascending phase, and so the resultant waveform may
the pitfall mentioned elsewhere: the low-resistance pathway provided by a have a checkmark-like shape; some authors’ refer to them as occipital V
bone defect in the skull.) waves of sleep.
Fast activity of cortical origin is particularly susceptible to the effects of Positive occipital sharp transients of sleep (POSTs) (134) are always
ischemia, hypoxia, contusion, and the presence of subdural fluid. Thus, its bilaterally synchronous but are commonly asymmetrical on the two sides
depression or absence focally or unilaterally may be a useful sign on the (Fig. 6.68); voltage differences as great as 60% are seen in normal persons.
EEG, particularly in relation to other findings (e.g., the presence of a slow- This may lead to misinterpretation of POSTs as abnormal sharp-wave activ-
wave focus). ity in one or the other occipital region. In this regard, it is important to
remember that POSTs may occur at a time when the background activity
Positive Occipital Sharp Transients has an amorphous character that might be thought to represent drowsiness
Surface-positive sharp transients, occurring singly or, more commonly, or a slightly slow awake pattern (Fig. 6.69).
in runs of 4 to 5 Hz, are often seen in routine EEG sleep recordings The helpful distinguishing characteristics of POSTs are (a) their surface
(Fig. 6.67). These interesting waves are commonly seen in the EEG labora- positivity (abnormal surface-positive cerebral spikes are rare), (b) the fact
tory because they are prone to occur during daytime naps and particularly that they tend to occur in trains with a repetition rate of 4 to 5 Hz, and
if the patient has been partially aroused and quickly returns to sleep. The (c) their predominantly monophasic checkmark-like waveform.
Figure 6.67: Positive occipital sharp transients of sleep (POSTs) during

stage II sleep (note presence of 14-Hz spindles) in an asymptomatic
14-year-old boy.
Figure 6.68: Asymmetrical positive occipital sharp transients (POSTs) of sleep in
a healthy girl aged 11 years. Note considerable voltage difference between sides,
especially of the isolated sharp wave (POST) near the center of the sample. The facts
that the series shows a repetition rate of about 5 Hz at the right side of the sample
and that the sharp waves are positive at O2 provide clues to their identity. However,
although positive sharp waves or spikes rarely signify abnormal activity, electrodes
near the midline (e.g., O1 or O2) may reveal only the positive end of a dipole, presum-
ably because the negative end lies on the mesial surface of the hemisphere.
Figure 6.69: POSTs of sleep, occurring after drowsiness

but before spindle sleep, had been reached, in an asymp-
tomatic 17-year-old girl. Note the low-voltage, slightly slow
or “drowsy” appearance of the record. POSTs are often
seen during daytime naps that may occur during routine
studies in the typical electroencephalograph laboratory.
203
Figure 6.70: Cone-shaped, posterior slow transients

during light sleep in an asymptomatic 35-month-old boy.
Figure 6.71: Diphasic slow-wave transients in the occipi-

tal derivations in light sleep in the same subject as in
Fig. 6.69.
Occipital Slow Transients TABLE 6.3 Classification of Electroencephalographic

In children, the transition from light to deep sleep may be associated with the Background Activity
bilateral appearance of high-voltage slow transients in the occipital regions
1. Normal
(125). These waves vary from a cone-shaped configuration (Fig. 6.70) to a
2. Transient or persistent immaturity (dysmaturity)
diphasic slow transient (Fig. 6.71) reminiscent of a prolonged vertex transient.
At first, during light sleep, these transients occur every 3 to 6 seconds; with 3. Mildly abnormal
deepening sleep, they appear more frequently and seem to meld into the con- a. Mildly excessive discontinuity during the discontinuous portions of the
tinuous, occipital-dominant, random, very slow delta waves of stage IV sleep. tracing
b. Mildly excessive interhemispheric asynchrony for conceptional age
CLASSIFICATION OF THE NEONATAL c. Poor concordance between clinical and electrographic sleep states
d. Mild poverty of anticipated background rhythms for conceptional age
ELECTROENCEPHALOGRAPHIC BACKGROUND
(e.g., mild decrease in monorhythmic occipital delta activity, rhythmic
AND ITS IMPLICATIONS occipital or temporal theta activity, brushes)
e. Mild focal abnormalities (e.g., excessive sharp waves in temporal or
The EEG background correlates strongly with a child’s clinical neurologi-
central regions, focal voltage attenuation)
cal status, prognosis, and eventual neurological outcome. Several grading
systems of the neonatal EEG background have been suggested (82–90). 4. Moderately abnormal
Although there are minor differences among the grading scales, the main a. Moderately excessive discontinuity during the discontinuous portions
features are similar and broadly classify tracings as normal or mildly, mod- of the tracing
erately, or markedly abnormal according to criteria describing continuity, b. Moderately excessive interhemispheric asynchrony for conceptional
voltage, reactivity, and background composition (Table 6.3). Recent report- age
ing guidelines from the ACNS cover the subject of continuous neonatal c. Poverty of anticipated background rhythms for conceptional age
recordings in some detail (135). d. Definite focal abnormalities (e.g., persistent focal delta activity or focal
Most infants with markedly abnormal EEG backgrounds have an abnormal depression of expected background patterns such as brushes)
mental status (lethargy or coma) caused by the severe, diffuse acute encepha- e. Persistent low voltage (generalized reduction of voltage <25 μV for all
lopathy and face a very high risk of an unfavorable outcome such as death or states)
permanent neurological disability (85). Infants with an unexplained, grossly 5. Markedly abnormal
abnormal EEG background may harbor an unexpected cerebral dysgenesis
a. Markedly excessive discontinuity for age, despite the preservation of
such as holoprosencephaly. Infants with normal serial EEGs usually have
some age-appropriate background patterns
normal mental status, as assessed by examination, and were exposed to mild
or minimal diffuse pathological processes or to definite but restricted injuries. b. Burst-suppression pattern
For example, an infant with an acute embolic stroke usually has a normal c. Gross interhemispheric asynchrony
mental status and a well-preserved overall EEG, although focal abnormali- d. Extremely low voltage (<5 μV)
ties may be evident (97). Most infants with normal or mildly abnormal trac- e. Depressed and undifferentiated
ings have a favorable outcome. However, those with genetic disorders such as f. Isoelectric
Down’s syndrome who have not experienced any type of acute encephalopa-
thy also display nearly normal records, despite the realistic expectation for an Adapted from Clancy R, Tharp B. Positive rolandic sharp waves in the electroencephalo-
abnormal neurological outcome. Moderately abnormal EEGs fall between grams of premature neonates with intraventricular hemorrhage. Electroencephalogr Clin
Neurophysiol 1984;57:395–404.
these two extremes with regard to the coincident mental status, the cause or
causes of the encephalopathy, and the chances of an adverse outcome.
Watanabe et al. (18) assessed 173 full-term infants after HIE and found that
infants with mild background abnormalities that lessened over the first few
days of life had a good o utcome. Poorer outcome was noted if markedly
abnormal abnormalities persisted more than 4 days or if milder abnormali-
ties lasted many days.
What are the neuropathological correlates of the abnormal EEG? Few
investigators have attempted to address this important question by directly
associating the varieties and severities of EEG background patterns with
the results of postmortem brain examinations (13,63,65,136). Because
markedly abnormal EEGs empirically confer an adverse neurological out-
come, it is reasonable to attempt to understand its neuropathological basis.
In the largest study of its type, Aso et al. (13) analyzed 107 EEGs in 47
infants who later died during the neonatal period and on whom autopsy
was performed. Macroscopic and microscopic examinations were per-
formed in selected anatomical structures: the cerebral cortex, subcortical
white matter, corpus callosum, thalamus, hypothalamus, corpus striatum,
Figure 6.72: Kaplan-Meier survival curve shows significantly greater survival midbrain, pons, and medulla. Normal EEGs correlated with histologically
in premature infants with normal or mildly abnormal electroencephalographic normal brains, whereas progressively abnormal EEGs were associated with
backgrounds than in those with moderately or markedly abnormal tracings. more extensive and severe neuropathological processes. The degree of EEG
(Adapted from Clancy R, Rosenberg H, Bernbaum J, et al. Survival outcome pre- abnormality significantly correlated with the number of damaged brain
diction in premature infants with IVH by cranial ultrasonography and EEG. Ann regions counted at autopsy (Fig. 6.73). Some interesting electrographic-
Neurol 1994;36:489.) neuropathological associations were also revealed. Isoelectric EEGs were
correlated consistently with widespread encephalomalacia and, commonly,
with ischemic necrosis of the cortex, thalamus, corpus striatum, midbrain,
The prognostic value of serial EEGs in premature infants has been shown and pons. Burst-suppression patterns were also associated with multifocal
in many studies, including the study by Tharp et al. (63) of 81 infants lesions, including widespread neuronal necrosis but variably present IVH,
younger than 36 weeks of EGA. Markedly abnormal EEGs were associated periventricular leukomalacia, cerebral infarctions, and ponto-subicular
with a 96% incidence of death or adverse outcome. Worsening on serial necrosis. There was no single lesion present in all infants with burst sup-
EEGs was seen in 41% of the children with major neurological sequelae, pression. Interhemispheric amplitude asymmetries of more than 50% were
but only in 3% of patients with normal outcome and 15% of those with correlated with localized cerebral lesions, including infarctions and IVH.
minor sequelae. Tharp et al. (12) investigated infants weighing less than The hemisphere with more EEG attenuation was the worst affected patho-
1,200 g who were admitted to their neonatal intensive care unit and found logically. Excessive asynchrony was identified in 9 of 18 patients older than
that EEG was better than the clinical neurological examination at pre- 31 weeks of conceptional age. Their anatomical abnormalities were mild to
dicting poor outcome (72% versus 39%). Normal outcome was predicted moderate in severity but specifically involved the corpus callosum in only
with equal accuracy by the clinical examination and the EEG. In the study two. Conversely, no child with normal synchrony had a callosal lesion. PRSs
by Clancy et al. (4), of 101 premature infants with EEG and head ultra- were always associated with white matter lesions, but did not consistently
sound (HUS) examinations, survival rates were significantly better among correlate with any other type of neuropathology. PRSs were a highly specific
those with normal or mildly abnormal recordings (Fig. 6.72). The prog- but insensitive marker, inasmuch as the incidence of PRS was only 32% in
nostic value of serial EEG has also been investigated in full-term infants. those with proven white matter lesions.
thorough review of the background cannot be overstated, and it is some-

times given less emphasis than it should as attention is disproportionately
focused on interictal spikes.
Continuity and State Concordance

Continuity of the background is determined first. In very young premature
infants, the background is discontinuous, even when the infant is awake,
and it is necessary to count several representative IBIs in seconds to decide
whether the discontinuity is excessive. There is a range of counted values
with some unusually brief or long IBIs, but the typical IBIs should not
exceed the values found in Table 6.1. The tracing is considered excessively
discontinuous if the patient’s typical IBIs clearly exceed the norms for age.
By term, EEGs should be continuous in all stages, save portions of quiet
sleep. Somewhere between 6 weeks and 3 months, the tracing should be
continuous in all states. Continuity may be altered in patients outside the
neonatal period. This is especially true with patients with epileptogenic
encephalopathies and also with acute encephalopathies. In these situations,
continuity will be one of the most important clues to the type of epilepsy
and the prognosis.
Experienced readers will tie continuity to state, almost unconsciously, but
Figure 6.73: The correlation between the electroencephalographic background there are truly two steps that need to be taken. The first is to determine
and the number of neuropathological lesions. (Adapted from Aso K, Scher M, the state, and the second is to note the continuity. The state is not difficult
Barmada M. Neonatal electroencephalography and neuropathology. J Clin to determine. In neonatal tracings, one only has to look at the eye, EMG,
Neurophysiol 1989;6:103–123.) and respiratory channels, and it will often become immediately obvious. The
same applies for older children, though the evidence of eye movements and
muscle activity can be easily seen in the routine leads used for cerebral moni-
toring. Babies and children without eye blink and muscle/movement artifact
AN ORGANIZED APPROACH TO VISUAL ANALYSIS are usually asleep. Seldom does a normal child rest in quiet repose with his
OF THE ELECTROENCEPHALOGRAM or her eyes closed while the EEG is conducted. Babies and children who do
not move or blink their eyes are either asleep, deeply encephalopathic, or
The pediatric EEG can be approached in an orderly and similar fashion paralyzed. It is not difficult to distinguish these with even a modicum of
from the very premature to the oldest adolescent. It is good to have a sys- EEG knowledge.
tematic approach to the VA and the generation of the report to be certain It is sometimes stated that one needs to know the age and state of a patient
that all relevant information is extracted from the record. A great advantage in order to approach a pediatric EEG. Certainly, these can be helpful things
of the modern digital machines is that they allow the reader to jump quickly to know, but in fact, the experienced pediatric electroencephalographer does
to annotated portions of the study so that one may proceed somewhat sys- not require any information to begin the interpretation of the tracing. Once
tematically in the reading, reviewing various regions of interest before look- one is familiar with the normal ontogeny, it is possible to estimate age fairly
ing at the tracing continuously from start to finish. The importance of a easily, and the state of the patient is easily determined by even a cursory
examination of the record. The final interpretation requires the age and derivations. Thus, a slow occipital alpha rhythm usually denotes a more seri-
some clinical information to render a clinically useful impression. ous change than if its frequency were maintained. Conversely, preservation
of the occipital alpha rhythm despite marked slowing elsewhere is a favor-
Gradient and Principal Components able finding.
After the continuity of the record is judged, the composition of the tracing Symmetry and Synchrony
is evaluated. By 3 months, there should be an anterior to posterior volt-
age and frequency gradient with high amplitude, slower activity posteriorly, As mentioned earlier, symmetry is judged as an overall impression of the
and low amplitude, faster frequency activity anteriorly. In a child above amount, amplitude, and composition of background activity contrasted
3 months, this is the most important feature of the background. If a child is between homologous areas and both hemispheres. The easiest way to do
awake and does not have a background organized by such a gradient, then this is to visually focus on four channels at a time and to run your eyes across
there are only two possibilities: unrecognized drowsiness or an encepha- the screen comparing the activity from one side to the other. At the same
lopathy. The two can often be distinguished by alerting maneuvers and by time, note the synchrony of bursts in the neonate and sleep architecture in
watching the remainder of the study. Drowsiness should resolve, at least the older infant. Even major interhemispheric asymmetries that arise just
momentarily, with stimuli and alerting, and will ultimately yield to stage transiently have little significance. A persistent difference of at least 50%
II sleep. An encephalopathic background will not change appreciably with is usually necessary to declare a background abnormality on the basis of
these maneuvers and will often be more invariant. asymmetry alone. More often, significant asymmetries are detected in the
Next, note the principal patterns, rhythms, and frequencies that consti- company of other background abnormalities such as excessive discontinuity
tute the background. Are there specific, named, identifiable normal patterns or an abnormal profile of sharp EEG transients.
present? In the neonate, examples would include the monorhythmic occipi-
tal delta activity, bursts of rhythmic theta activity in the occipital or tem- Special Features
poral regions, delta brushes in the occipital or centrotemporal regions, and
runs of anterior dysrhythmia and encoches frontales. As discussed in this chapter, there are a number of special features peculiar
In infants, children, and adolescents, are other principal components pres- to pediatric EEGs. When one is confronted by an unexpected waveform, the
ent? The occipital posterior dominant rhythm is the next point for VA. The first question that should arise is whether it is of brain origin or artifact.
initial questions should be the following: Is an occipital rhythm present, and If it is determined to be of cortical origin, then consider whether it is a
are its characteristics appropriate for age? If there is little or no occipital recognized normal feature for age or an abnormality. A convenient way to
rhythm, is it because the patient’s eyes are open (reactivity) or because the approach this is to mentally describe the waveform. Note the type of wave-
patient is drowsy or asleep (state)? Or is it an abnormal finding? In addition form, its location, its morphology, and the state in which it occurs. In a sur-
to providing clues concerning the patient’s affective state (e.g., anxiety) or prising number of circumstances, this description will provide the answer,
level of arousal, the presence and character of the occipital alpha rhythm or at least help to direct one to the appropriate portions of a text or atlas.
are critical determinants in evaluating the significance of other activities
present. Thus, the presence of some low-voltage, 5- to 6-Hz rhythmic fronto- Abnormalities
central activity in an adolescent may, in the transient absence of an occipital
alpha rhythm, merely signify the patient’s drowsiness; in the total absence Finally, in the remainder of the review of the EEG, one is on the outlook for
of an occipital alpha rhythm, however, such activity may have pathological sporadic abnormalities, particularly intermittent slowing and epileptiform
significance. Similarly, the presence of the frontocentral theta activity would activity. It is very helpful to carefully examine the portions of light sleep for
be more ominous if the occipital alpha rhythm itself were slow (e.g., 7 Hz). epileptiform activity in the older infant or child. In neonates, it is likewise
It is important to remember that the occipital alpha rhythm may be pre- important to continue the study long enough to capture some quiet sleep
served in conditions that produce marked slowing of the activity in anterior because in some, electrographic abnormalities may be observed only during
this specific state. Other chapters in the text provide thorough discussions of 5. Dreyfus-Brisac C. Ontogenesis of sleep in human prematures after 32 weeks of concep-
tual age. Dev Psychobiol 1970;3:91–121.
the various abnormalities and their clinical significance. 6. Ellingson RJ, Peters JF. Development of EEG and daytime sleep patterns in normal full-
term infant during the first 3 months of life: longitudinal observations. Electroencepha-
FINAL WORDS logr Clin Neurophysiol 1980;49:112–124.
7. Goto K, Wakayama K, Sonoda H, et al. Sequential changes in electroencephalogram con-
tinuity in very premature infants. Electroencephalogr Clin Neurophysiol 1992;82:197–202.
Reading pediatric EEGs should be a pleasurable experience and never a 8. Hahn J, Monyer H, Tharp B. Interburst interval measurements in the EEGs of prema-
chore. The pleasure is a mixture of sensations and perceptions. A part of ture infants with normal neurological outcome. Electroencephalogr Clin Neurophysiol
it is the satisfaction in knowing that you are contributing, perhaps even in 1989;73:410–418.
9. Holmes H, Lombroso C. Prognostic value of background patterns in the neonatal EEG.
a small way, toward the health of a child. There is no more worthy work, J Clin Neurophysiol 1993;10:323–352.
and it is pleasing to know that your skills, honed by hours of training and 10. Hughes J, Fino J, Gagnon L. Periods of activity and quiescence in the premature EEG.
practice, are being put to good use. Then, there is the mental challenge of Neuropediatrics 1983;14:66–72.
11. Lombroso C. Neonatal EEG polygraphy in normal and abnormal newborns. In: Nieder-
decoding an abstract collection of waveforms and turning it into something meyer E, Lopes da Silva F, eds. Electroencephalography: basic principles, clinical applications
meaningful—not a commonly held ability—and worthy of the best transla- and related fields, 3rd ed. Baltimore, MD: Lippincott Williams & Wilkins, 1993:803–875.
tors. Finally, there is an indescribable aesthetic beauty in EEG. One won- 12. Tharp B, Scher M, Clancy R. Serial EEGs in normal and abnormal infants with birth
weights less than 1200 grams—a prospective study with long term follow-up. Neuropedi-
ders how something so seemingly random like a collection of firing neurons atrics 1989;20:64–72.
produces the most elaborate, intricate and intertwining patterns, as sophis- 13. Aso K, Abdab-Barmada M, Scher M. EEG and the neuropathology in premature neo-
ticated and elegant as a Bach fugue or Baroque architecture. Somehow, nates with intraventricular hemorrhage. J Clin Neurophysiol 1993;10:304–313.
14. Lombroso C. Neonatal polygraphy in full-term and preterm infants: a review of normal
these patterns allow children to process remarkable thoughts, store count- and abnormal findings. J Clin Neurophysiol 1985;2:105–155.
less memories, experience the full gamut of sensations, and call themselves 15. Lombroso C. Neonatal electroencephalography. In: Niedermeyer E, Lopes da Silva F,
to action. Even after tens of thousands of readings and countless hours of eds. Electroencephalography: basic principles, clinical applications and related fields, 3rd
ed. Baltimore, MD: Lippincott Williams & Wilkins, 1993:599–637.
observation, these impressions have not faded, and the wish is that they will 16. Tharp B. Electrophysiological brain maturation in premature infants: an historical per-
hold true for you as well. Happy reading! spective. J Clin Neurophysiol 1990;7:302–314.
17. Watanabe K, Iwase K, Hara K. Development of slow-wave sleep in low-birthweight in-
fants. Dev Med Child Neurol 1974;16:23–31.
Acknowledgments 18. Watanabe K, Miyazaki S, Hara K, et al. Behavioral state cycles, background EEGs and
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7 Generalized Encephalopathy
ELIZABETH WATERHOUSE
Introduction Fast Frequency Patterns

The Utility of EEG Monitoring Alpha Coma
EEG Description and Interpretation Beta Coma
Localization Spindle Coma
Reactivity Ictal Patterns
Slow Patterns Nonconvulsive Status Epilepticus
Generalized Slowing Low-voltage and Suppressed Patterns
Generalized Theta Activity Generalized Suppression
Generalized High-voltage Delta Activity Burst Suppression
Rhythmic Delta Activity Important Caveats in Using the EEG for Prognosis
Periodic Patterns Electrocerebral Inactivity
Generalized Periodic Discharges Conclusions
Triphasic Waves References
INTRODUCTION continuous EEGs over one or more days, our perspective has broadened, with
recognition of new challenges. The EEG is dynamic and complex, frequently
Over the past two decades, our understanding of encephalopathic EEG pat- demonstrating several patterns that wax and wane or change over time. It is also
terns has fundamentally changed. In the past, EEGs were recorded in discrete clear that electrographic seizures and status epilepticus (SE) are not uncommon,
20-minute studies that usually demonstrated a single dominant pattern—such and at times are challenging to distinguish from other encephalopathic patterns.
as generalized delta slowing, triphasic waves, generalized suppression, or gen- Study duration is not the only thing that has changed our perception of the
eralized periodic discharges (GPDs). With the ability to record prolonged EEG of encephalopathy. A significant number of EEGs in encephalopathic
213
hospitalized patients are now performed in an intensive care unit (ICU). TABLE 7.1 EEG Patterns Frequently Associated with Generalized
These patients frequently have several factors contributing to their clinical Encephalopathy
and electrographic encephalopathy. The underlying infectious, metabolic,
toxic, hypoxic, vascular, or postsurgical conditions for which they are hos- Generalized slowing (theta and/or delta activity, intermittent rhythmic delta
pitalized may cause generalized or focal abnormalities. Continuous intra- activity)
venous infusions of anesthetic medications and analgesics are widely used, Generalized fast activity (alpha and/or beta activity), sometimes with inter-
and cause generalized EEG changes. The increasing use of therapeutic mixed slower frequencies
hypothermia is another intervention that results in encephalopathic EEG Generalized ictal activity
patterns. In this complex setting, the relative contributions of the various Periodic discharges
potential etiologies may be difficult to determine.
Triphasic waves
Generalized suppression
THE UTILITY OF EEG MONITORING Burst suppression
Continuous EEG monitoring is a valuable tool in the assessment of coma,
as it can detect changes in cerebral function with subtle or absent clinical
manifestations. Vasospasm, hemorrhage, elevation of intracranial pres- EEG patterns are pathognomonic for a specific diagnosis, and accurate
sure, nonconvulsive seizures and SE are all treatable conditions that are interpretation of the encephalopathic EEG requires knowledge of its clini-
potentially detectable with EEG. Changes in EEG parameters, when appro- cal context. The potentially reversible effects of drugs, hypothermia, and
priately interpreted, can alter clinical management and influence outcome. some metabolic conditions are frequently associated with EEG findings
While some encephalopathic EEG findings are nonspecific with regard to that, in a different clinical setting, might portend a guarded or poor prog-
etiology, certain patterns such as triphasic waves may prompt an evaluation nosis. Ideally, the electroencephalographer should know the patient’s age,
for metabolic or toxic disorders. The appearance of a new or unexpected temperature, clinical state of consciousness, medications, and the clinical
lateralized EEG abnormality should raise concern for a structural lesion history in order to provide a useful EEG interpretation. Table 7.3 lists
or focal ischemia (1). EEG monitoring is frequently performed to identify some of the more common clinical correlations of encephalopathic EEG
seizures so that treatment can be initiated. EEG is also useful for deter- patterns.
mining trends (is the encephalopathy improving or worsening?), assessing
response to treatment with antiepileptic drugs (AEDs), monitoring depth of
Localization
sedation, and assessing prognosis.
EEG patterns correlate, to some extent, with anatomic localization. While
EEG DESCRIPTION AND INTERPRETATION decreased amplitude or frequency of the posterior dominant rhythm indi-
cates mild cortical dysfunction, subcortical white matter dysfunction is asso-
Just as the term encephalopathy encompasses a range of clinical states, so ciated with polymorphic delta activity or triphasic waves. Slowing of the
the EEG in encephalopathy demonstrates a variety of patterns (Table 7.1). It posterior dominant rhythm with intermixed arrhythmic delta activity indi-
can be challenging to translate a complex EEG pattern into words. Table 7.2 cates cortical and subcortical dysfunction. The EEG manifestation of brain-
lists parameters that are useful in describing generalized encephalopathic stem dysfunction is variable, and may consist of rhythmic or arrhythmic
patterns. Accurate description and interpretation of the key features of an delta slowing, diffuse spindle activity, or impaired patterns of arousal (2).
EEG rely on some or all of these parameters. Electrographic seizure activity is considered a cortical pattern, although
While the EEG remains an exquisitely sensitive tool for identifying rhythmic generalized spike-wave activity, as seen in absence seizures, is
encephalopathy and evaluating the degree of cerebral dysfunction, few influenced by thalamic oscillations and subcortical activity (3).
Generalized Encephalopathy 215
TABLE 7.2 Descriptive Parameters for Generalized TABLE 7.3 Common Clinical Correlations of Encephalopathic
Encephalopathic Patterns EEG Patterns
Parameter Examples of Descriptors EEG pattern Common Clinical Correlations
Distribution Generalized, bifrontally predominant, occipitally Generalized theta Metabolic disturbance, sedation, systemic infection,
predominant, midline predominant slowing dementia
Frequency Delta, theta, alpha, beta (specify in Hertz or pro- Intermittent Metabolic disturbance, midline or deep hemispheric
vide a range) rhythmic delta lesion, increased intracranial pressure
Amplitude Voltage ranges of the predominant frequencies, in activity
microvolts (or millivolts if appropriate) Continuous high- Diffuse subcortical white matter dysfunction, meta-
Occurrence Continuous, nearly continuous, discontinuous, voltage delta bolic encephalopathy, traumatic brain injury, sepsis,
periodic, intermittent, randomly occurring, wax- slowing diffuse encephalitis
ing and waning, fluctuating, evolving, stimulus- Prominent beta Medication effect (especially from benzodiazepines or
induced. If bursts are present, specify typical activity barbiturates), alcohol withdrawal
time interval, or range of time intervals, between Alpha coma Drug-induced coma, brainstem lesion, anoxic
bursts encephalopathy
Duration Time in seconds, minutes, or hours, that a pattern Triphasic waves Metabolic encephalopathy (hepatic dysfunction, renal
is present failure, hyponatremia), anoxia, sepsis, degenerative
Reactivity Change in voltage, frequency, periodicity, disorders, Creutzfeldt-Jakob disease
rhythmicity or other parameter, in response GPDs Severe metabolic disturbance, anoxic encephalopa-
to stimulation, OR specify absence of EEG thy, drug overdose, late SE, barbiturate withdrawal
change with stimulation. Identify the stimulus
given: passive eye opening, spontaneous eye Generalized ictal Coma, subtle signs of seizure activity (e.g., rhythmic
opening, auditory, tactile, or painful stimulation, activity eye movements, twitches of one or more limbs)
suctioning, etc. (see Table 7.4)
Waveform Triphasic wave, spike-and-wave, slow wave, poly- Burst suppression Anesthetic medications, anoxic encephalopathy,
morphic, monomorphic. When appropriate, hypothermia, drug intoxication
describe number of phases, sharpness, and/or Generalized Anesthetic medications, hypothermia, anoxic enceph-
polarity suppression alopathy, severe diffuse traumatic brain injury
Regulation Rhythmic, nonrhythmic, evolving. If evolution is Electrocerebral Deep anesthesia, hypothermia, brain death
present, describe changes in frequency, voltage, inactivity
or location over time
Symmetry Symmetric or asymmetric. Compare homologous
regions of left and right hemispheres with regard
to above parameters Reactivity
Synchrony Synchronous or asynchronous between the Reactivity indicates a reproducible cerebral response to an environmental stim-
hemispheres (refers to specific activities such
ulus. The change in EEG parameters varies widely between patients and base-
as bursts, sharp or slow wave discharges, or
spindles)
line EEG pattern. Frequency, amplitude, or both may increase or decrease in
response to stimulation. With mild encephalopathy, slow waves often attenuate
as an alerting response. A paradoxical arousal response occurs when higher- occurrence of this phenomenon is termed SIRPIDs (stimulus-induced rhyth-
voltage generalized delta activity occurs following stimulation (Fig. 7.1). In mic, periodic, or ictal discharges) (Fig. 7.2) (5). Concurrent video recording
general, any reactivity to stimulation indicates a less severe level of encepha- allows clinical correlation with these EEG changes, and helps to distinguish
lopathy than absence of reactivity (4). With worsening encephalopathy, the SIRPIDs from spontaneous electrographic seizures. For example, a recurrent
EEG becomes less reactive, and as it progresses into the delta frequency range, pattern that initially appears to be a generalized spontaneous ictal discharge
or becomes suppressed, there may be no response to stimulation. may, on video review, turn out to be recurrent SIRPIDS associated with
In critically ill encephalopathic individuals, an alerting stimulus may elicit an intermittent suctioning. SIRPIDs, and other patterns of EEG reactivity, may
EEG change with characteristics shared by ictal discharges. The reproducible or may not be associated with clinical manifestations of alerting.
Figure 7.1: EEG reactivity in an encephalopathic patient. The grey arrow at the top indicates when the
patient was stimulated. There is attenuation of voltage and of delta activity.
Figure 7.2: SIRPIDs in the setting of generalized suppression. GPDs occur when the patient is stimulated
during examination.
SLOW PATTERNS Two very common contributors to coma in the ICU—drugs and metabolic
problems—share mutual EEG features. Anesthetics, sedatives, and narcotic
Generalized Slowing analgesics frequently appear on the medication lists of comatose patients.
Some degree of metabolic abnormality is almost ubiquitous in ICU patients.
The earliest sign of mild encephalopathy on EEG is usually slowing of the EEG changes due to metabolic coma resemble patterns occurring with anes-
alpha rhythm. With further clinical impairment, slow wave activity becomes thesia, and not surprisingly, the EEG in both situations is abnormal and
intermixed, and eventually predominates. Generalized delta slowing occurs dynamic, modulating over time to reflect the degree of cerebral dysfunction.
as the encephalopathy progressively worsens. Patterns of burst suppression, The sequence of EEG patterns seen in response to anesthetic drugs pres-
generalized suppression, or GPDs usually correlate with deep coma. ents a paradigm for EEG progression in coma due to worsening metabolic
status (6). With light anesthesia, there is desynchronization, or fast activ- with septic encephalopathies and drug overdoses. Although other nonmeta-
ity. As anesthetic dose increases, voltage and rhythmicity increase. Higher bolic causes of encephalopathy, such as cerebral anoxia, may also mirror the
voltage, slower frequencies become intermixed with fast activity, and delta “anesthetic model” of EEG changes, with deterioration to a depressed EEG,
activity gradually becomes more prominent. As anesthesia deepens, burst neuronal death occurs in these cases and the EEG changes are irreversible.
suppression occurs, and the duration of suppression gradually lengthens.
With further escalation of the anesthetic dose, generalized suppression Generalized Theta Activity
persists without bursts, and ultimately the EEG becomes isoelectric.
With worsening metabolic abnormalities, the EEG evolves in a manner Generalized reactive theta slowing frequently occurs in the setting meta-
comparable to the EEG response to anesthetics. The reverse may also be bolic or drug-induced encephalopathy (Fig. 7.3). Indicators of wakefulness,
true. Just as the EEG returns to baseline when anesthetic drugs are tapered such as eye blink artifacts, or posterior dominant rhythm may be present.
and discontinued, even severe EEG abnormalities may resolve as metabolic Even when the patient is not awake, the EEG is often reactive, demonstrat-
parameters improve. Slowing and suppression are also potentially reversible ing either a change in frequency and/or voltage to stimulation. A reactive
Figure 7.3: Generalized theta slowing in a patient with metabolic encephalopathy.

pattern in a mildly encephalopathic individual has very different implica- With deepening coma, delta activity becomes nonreactive and slower. This
tions from nonreactive theta coma. Theta coma following anoxic injury pattern occurs in the setting of subcortical white matter lesions, or meta-
is usually grouped with alpha coma, as it has a similar prognosis, which bolic encephalopathy (8). A focal lesion of one hemisphere can cause gener-
depends on the etiology of the coma (7). While the majority of patients with alized but asymmetric delta activity, due to a secondary effect (from edema,
nonreactive theta coma die or remain vegetative, some do recover (6). or mass effect, for example) on the other hemisphere.
Generalized High-voltage Delta Activity Rhythmic Delta Activity

Generalized high-voltage delta slowing in the setting of coma is typically Intermittent rhythmic delta activity (IRDA) occurs in encephalopathic
polymorphic, with a frequency of 1 to 2 Hz. This pattern reflects a deeper patients, and consists of runs of high-voltage rhythmic 2- to 3-Hz activity
stage of coma than intermittent delta patterns or triphasic waves, and may recurring at irregular intervals, on a background of mild to moderate general-
demonstrate reactivity to stimulation with attenuation or accentuation. ized theta slowing (Fig. 7.4). Bursts are synchronous and most often bilateral,
Figure 7.4: FIRDA in a young patient with a pituitary tumor. There is generalized theta activity, with
intervals of 2-Hz generalized rhythmic delta activity.
although they may be asymmetric or unilateral. IRDA is characteristically The interval between complexes generally lasts one to several seconds (19)
frontally predominant in adults, and attenuates with eye opening or alerting. (Fig. 7.5). The waveform itself may be a sharp wave, spike, sharply contoured
The proposed standardized research nomenclature for IRDA that comprises slow wave, or more complex polyphasic discharge, but within a given EEG, it
1% to 10% of an EEG is “occasional brief 2 per second generalized rhythmic usually demonstrates a relatively consistent morphology and duration. The
delta activity,” and it may be further qualified as frontally predominant (9). waveform stands out from background activity, which is typically suppressed
or of low voltage. GPDs may have additional superimposed rhythmic activ-
Clinical Correlation ity of any frequency, and the pattern is then referred to as “GPDs-plus”
Rhythmic delta activity was first described by Cobb (10) in 1945. Using just (9). Periodic patterns may occur with a generalized, lateralized, or focal
two EEG channels, he documented rhythmic slow activity in patients with distribution.
tumors and acute head injuries. Subsequent early studies described frontal
intermittent rhythmic delta activity (FIRDA) in association with tumors Clinical Correlation
of the posterior fossa and third ventricle, deep midline lesions, and hydro- While focal periodic patterns signify an underlying focal lesion, such as a
cephalus (11–13). More recent retrospective studies report the occurrence stroke, tumor, or localized encephalitis, a generalized periodic pattern does
of FIRDA in patients with a wide range of encephalopathic conditions, in not imply a specific disease state. It commonly occurs in the setting of severe
those with focal structural lesions, and in the setting of diffuse brain injury acute or subacute encephalopathy from a variety of causes. Cerebral hypoxia
in combination with metabolic disturbances (14–16). Although FIRDA is or anoxia, anesthetic or sedative drugs, hypothermia, and nonconvulsive sta-
considered a projected rhythm from deep structures, its origin is unclear, tus epilepticus (NCSE) frequently cause GPDs. Other etiologies include dif-
and possible sources in the reticular activating system or the dorsomedial fuse encephalitis, sepsis, and severe metabolic encephalopathies (18). Periodic
nucleus of the thalamus have been hypothesized (12). patterns may appear during drug overdoses (barbiturates, baclofen, and
A prospective controlled study identified FIRDA in 6% of EEG record- other psychotropic substances) or in withdrawal states (20,21). Noncerebral
ings, and concluded that its occurrence should initiate a workup for toxic factors that can mimic periodic patterns include artifacts from ventilators,
or metabolic abnormalities, or for a structural lesion (17). Asymmetric palatal myoclonus, facial twitching, and electrocardiogram.
FIRDA, in particular, suggests underlying focal pathology. Although the Uncommon causes of periodic patterns include subacute sclerosing pan-
laterality of the lesion cannot be reliably identified, Accolla et al. found encephalitis (SSPE) and Creutzfeldt-Jakob disease (CJD). Distinctive peri-
higher-amplitude FIRDA on the side of the lesion in six of eight patients. odic patterns in the appropriate clinical setting may be diagnostic of these
Occasionally, FIRDA occurs during hyperventilation or during drowsiness rare entities (22). In SSPE, a long interval separates very high-voltage peri-
in normal subjects. While FIRDA is considered a nonepileptiform pattern, odic discharges or polyphasic bursts (19). The interburst intervals last 4 to
IRDA over nonfrontal brain regions has distinct clinical implications. Occip- 30 seconds, while the burst duration is 0.5 to 3 seconds. Early in the course
ital IRDA occurs primarily in children with absence epilepsy, while tempo- of SSPE, periodic discharges may be unilateral or bilateral. In ambulatory
ral intermittent delta activity is associated with temporal lobe epilepsy. patients, they typically occur every 5 to 7 seconds (23). The activity during
the interburst interval is not always suppressed, although it may appear to
PERIODIC PATTERNS be at the low sensitivity required to view the 200- to 1,500-μV complexes.
In one study, the EEG background remained normal when the interburst
Generalized Periodic Discharges interval exceeded 7 seconds, but became abnormal as the complexes became
more frequent (24). As the disease progresses, periodic discharges occur
A periodic pattern consists of “a stereotyped recurrence of paroxysmal more frequently, and are time-locked with mycolonic jerks. These discharges
complexes at relatively fixed intervals” (18). GPEDs (generalized periodic disappear late in the course of the disease.
epileptiform discharges) is not an entirely accurate acronym for all peri- A shorter interval between discharges typifies the periodic patterns of
odic patterns, because not all are definitively epileptiform. Thus the term CJD. These patients present with rapidly progressive dementia, and may
“generalized periodic discharges” is now considered to be more appropriate. have startle myoclonus. Generalized slowing characterizes the EEG of early
Figure 7.5: Generalized 1-Hz periodic discharges in a patient with anoxic encephalopathy following
cardiac arrest.
CJD. Within several months, periodic discharges appear. They are usu- background. This pattern is strongly, but not invariably, associated with a
ally generalized, but occasionally are unilateral or asymmetric, and occur poor outcome (26). The false-positive rate for poor outcome in these cases is
about once per second (19). The interburst interval varies between 0.5 and about 3%, which is considered insufficiently accurate for prediction of clini-
4 seconds. Myoclonus, when present, is not time-locked to the periodic dis- cal outcome. However, when GPDs are associated with myoclonic SE within
charges. One important caveat is that new variant CJD is not associated 24 hours of a primary circulatory arrest, the prognosis is invariably poor (26).
with periodic discharges, and despite severe cognitive disturbances, distinc- In myoclonic SE, myoclonic jerks are synchronized with periodic discharges
tive EEG patterns may be absent (25). or bursts. At times, it is difficult to determine whether EEG discharges origi-
nate in the brain, the muscles, or both. Administering a single dose of a
Prognosis neuromuscular blocking agent to an unconscious mechanically ventilated
The prognosis of a generalized periodic pattern depends on its etiol- patient with myoclonus helps to distinguish myoclonic artifact from cere-
ogy. Cardiac or respiratory arrests are common precursors to anoxic bral activity. The presence of neuromuscular blockade can also obscure the
encephalopathy and a generalized periodic EEG pattern on a suppressed recognition of myoclonic SE, by inhibiting its clinical manifestations.
Pathophysiology features. They are typically bifrontally predominant, with a frequency of

Neurophysiologists have not completely elucidated the mechanisms underly- 1.5 to 2.5 Hz, and an amplitude of 70 to 300 μV. On a bipolar montage, they
ing EEG periodicity. Early theories postulated that extensive white matter disappear as complex discharges that include three phases: (a) a negative sharp
ease caused deafferentation of the cortex. This theory was discounted when component, (b) a positive deflection of variable prominence, and (c) a nega-
Gloor described a series of patients who had periodic EEG discharges due tive deflection, leading into a slow wave. A fronto-occipital delay, or phase
to CJD or SSPE, and had grey matter pathology only, without involvement lag, in the second phase is often present on longitudinal bipolar montages.
of the white matter. He theorized that synchronous signals from subcortical Sometimes, a posterior-to-anterior phase lag occurs (Fig. 7.6). Triphasic
structures trigger periodic cortical discharges (8). The anatomic trigger is likely waves may occur intermittently in brief runs, or as a continuous pattern.
located in a brain structure that is not affected by the pathological process Clinical Correlation
(27). Others have suggested that EEG periodicity might depend on intrinsic
cellular characteristics such as the refractory period of neuronal membranes, Clinically, triphasic waves correlate closely with the severity of the encepha-
altered function of neurotransmitters, second messengers, or membrane lopathy. They are usually absent in alert or deeply comatose individuals, tend-
receptors, or viral or toxin-induced alteration in membrane structure. ing to occur in those whose mental status lies along the spectrum between
It is reasonable to draw the broad conclusion that periodicity likely arises these two extremes. They may increase or attenuate with stimulation. Foley et
from biochemical or anatomical disturbance in neuronal excitability, altering al. noted that “As the patient becomes less responsive, the bursts become lon-
cortical responsiveness to afferent input from distant structures (19). More ger in duration and more widespread in space … until the entire record con-
recent analytic methods support this statement. Using independent component sists of 2 per second activity” (29). Triphasic waves are not specific to hepatic
analysis and dipole source localization to study EEG discharges in six CJD coma, and have been described in a wide variety of clinical settings, includ-
patients, researchers found that basal ganglia and thalami, as well as frontal ing renal failure, hyponatremia and other metabolic derangements, hypothy-
cortices, are involved in generating periodic sharp-wave discharges in CJD (28). roidism, brainstem stroke, encephalitis, postanoxic encephalopathy, sepsis,
dementia and drug intoxications. When triphasic waves occur in the setting of
Triphasic Waves a rapidly progressive dementia, they suggest the possibility of CJD. Some elec-
trographic seizure discharges demonstrate a triphasic morphology, but these
The first description of what would later be called “triphasic waves” was a are continuous, rhythmic, and evolving, rather than intermittent or sporadic.
“blunt spike and a slow wave” pattern in patients with hepatic coma (29). The morphologic similarities between triphasic waves and spike-wave dis-
In addition to describing its bifrontal predominance and 2-Hz frequency, charges (SWDs) of NCSE frequently present a diagnostic dilemma. Benzo-
Foley et al. noted that “its component parts … may be either fused or diazepine administration does not reliably distinguish triphasic waves from
separate.” When fused, the initial steep rise of the slow wave corresponds NCSE, and may cause either to pattern attenuate (30). Several features help
with the ascending limb of the sharp wave, while the descending limb of to distinguish the two waveforms. Compared with triphasic waves, generalized
the sharp wave is absent, subsumed in the slow wave. In this variation, the NCSE discharges tend to have a higher frequency, averaging 2.4 versus 1.8 Hz,
complex has the appearance of a “squared off ” slow wave. In 1955, Bickford a shorter duration of phase one, extra spike components, and less severe gen-
and Butt originated the term triphasic waves, focusing on the prominent eralized background slowing (31). While a significant proportion (40%) of tri-
positive wave, which points downward on a bipolar montage. It is pre- phasic patterns demonstrate a prominent amplitude of phase 2, and an equal
ceded by a low-amplitude negative wave, and followed by a negative wave. proportion show phase lag, NCSE patterns tend to lack these characteristics.
More recently, a standardized descriptive terminology has been proposed. Painful or auditory stimulation may increase the occurrence of triphasic waves,
When 2-Hz triphasic waves comprise most of an EEG recording, they are but generally have no effect on epileptiform discharges (31). In one patient with
described as “continuous 2 per second GPDs,” and the qualifier “with interictal generalized SWDs, who developed hepatic triphasic waves, epileptic
triphasic morphology” can be added (9). spike-wave complexes were of briefer duration, and descended more steeply in
The contrasting early descriptions of triphasic waves reflect the vari- phase 2 than triphasic waves (32). In this patient, triphasic wave complex dura-
ability of the waveform between patients, and affirm the characteristic tion exceeded 0.3 seconds, with the slow-wave component maximal over the
Figure 7.6: Triphasic waves in a patient with hepatic encephalopathy. The grey diagonal line demonstrates
anterior-to-posterior phase lag. The numbers indicate the different components of the complex. 1 and 3 are
negative waves, and 2 is a positive wave.
223
fronto-central regions on a bipolar montage, while interictal epileptic SWDs medications, or metabolic encephalopathy. Alpha activity is usually 10 to
averaged 0.12 seconds in duration, and were more frontally predominant. 50 μV in amplitude, and may be generalized, or demonstrate an anterior or
posterior predominance. While alpha rhythm in an awake patient attenuates
FAST FREQUENCY PATTERNS with eye opening, the generalized alpha activity of alpha coma does not
react to passive eye opening, and may or may not react to noxious stimuli.
Alpha Coma The manifestation of reactivity, when present, is variable. Alpha frequencies
may increase or attenuate, or intermixed slower activities may increase or
A pattern of diffusely distributed invariant 8- to 13-Hz EEG activity in an decrease. Theta coma and alpha-theta coma patterns share the same etiolo-
unresponsive patient is termed alpha coma (Fig. 7.7). It occurs in the settings gies and outcomes as alpha coma, and are considered to be variants of the
of a postanoxic state, brainstem stroke, head trauma, infection, sedative alpha coma pattern (7,33,34).
Figure 7.7: Alpha coma, in a patient with anoxic encephalopathy, treated with propofol. There is a
generalized, frontally predominant 9-Hz alpha activity.
Pathophysiology In a comparison of 36 alpha coma cases with a control group matched

The pathophysiology of alpha coma is not completely understood, and by age and etiology (but not coma severity), outcomes were very simi-
likely varies according to etiology. It is clear, however, that an alpha pattern lar. Slightly more than a third of both groups awoke. Among those with
in the setting of coma is not a retained normal rhythm, but instead is newly cardiopulmonary arrest, 19% of both groups awoke (39). These findings
generated by pathologically altered neural pathways. The disruption of ana- suggest that the presence of alpha coma per se is not a helpful prognostic
tomic pathways at several locations may result in alpha coma. Brainstem indicator. Reactivity to painful stimulation, however, did predict survival,
lesions disrupt the ascending connections between the reticular activating with 8 of 15 patients with reactive alpha coma patterns due to various eti-
system and thalamocortical pathways, and functionally disconnect them ologies surviving, while only 3 of 19 patients with nonreactive alpha coma
from alpha-generating cortical neurons (35). Diffuse cerebral injury follow- patterns survived. The majority of survivors were significantly disabled.
ing hypoxia leads to laminar necrosis of cortical layers IV, V and VI, while The presence of brainstem reflexes in alpha coma did not reliably predict
deeper structures are relatively preserved. In this setting, neuronal circuits survival (39).
may be intact enough to generate alpha patterns, but insufficient to allow Based on these statistics, it is difficult to predict prognosis in an individual
wakefulness (35). Drug-induced alpha coma may arise from a direct effect patient with alpha coma following cardiac arrest. Sedative drugs should be
on alpha-generating cortical neurons, with or without a concurrent effect on excluded as a cause of this pattern, by discontinuing them, if possible. Some
afferent pathways. consider alpha coma a “transitional pattern” when it occurs soon after
a cardiac arrest (40). By the sixth day following the cardiac arrest, alpha
Clinical Correlation coma has usually evolved into a pattern that is easier to interpret. Survivors
develop continuous rhythms with electrographic reactivity to stimulation,
The first reports of EEG patterns resembling wakefulness in comatose while those who die without recovering awareness develop a nonreactive
patients were published in the 1950s (36). Early alpha coma descriptions burst-suppression pattern (7,39).
involved brainstem lesions, at or below the pontomesencephalic junction. When considering alpha frequency patterns in patients who appear coma-
At that time, ICUs were not widely available, and few people survived car- tose, it is important to identify those who may have a deafferentation syn-
diopulmonary arrest. Later case series documented that alpha coma also drome (locked-in syndrome). These patients are unable to move or speak
occurs in the setting of hypoxic or anoxic encephalopathy following cardiac due to a lesion of the ventral pons. Consciousness is retained because
or pulmonary arrest (35,37,38). the pontine tegmentum is not involved. In this circumstance, a normal-
Several EEG findings may assist in differentiating brainstem strokes from appearing EEG with reactive posterior alpha rhythm indicates wakefulness,
hypoxic encephalopathy. In the setting of brainstem stroke, alpha activity and a careful examination reveals appropriate clinical responses using eye
tends to be located more posteriorly. It demonstrates more variability and blinks. Psychogenic unresponsiveness is also associated with a normal pos-
reactivity, and persists over sequential recordings. Alpha coma in the set- terior alpha rhythm on EEG.
ting of anoxic encephalopathy is rarely reactive and may segue into other
encephalopathic EEG patterns on subsequent days (38). Sedative and anes-
Beta Coma
thetic drugs, widely administered to ICU patients, are another cause of alpha
coma, and when present, complicate the interpretation of this EEG pattern. Generalized fast activity in a comatose patient is usually attributable to
sedative medications, and may occur with drug overdoses, as well as with
Prognosis therapeutic use of sedative drugs in the ICU. Benzodiazepines, barbiturates,
The overall mortality of alpha coma is 76%, based on a study of 335 cases and propofol are commonly associated with beta coma. The fast activity in
reported in the literature (39). The etiology of alpha coma determines the this type of coma involves alpha and beta frequencies of up to 16 Hz, and is
prognosis, with the lowest mortality associated with drug-induced coma slower than the 20- to 25-Hz activity seen in awake, medicated patients (41).
(8%), and the highest mortality due to stroke (90%). The mortality of car- Fast activities are often intermixed with generalized delta activity. With
diopulmonary arrest patients with alpha coma is 88%. When the pattern is increasing doses or infusion rates of these medications, brief intervals of
associated with hypoxia but not cardiac arrest, the mortality is 61% (39). generalized suppression occur, and further dose escalation eventually leads
to a burst-suppression pattern, and ultimately generalized suppression and this pattern in patients with coma resulting from other structural lesions
electrocerebral inactivity. such as traumatic brain injury, brain hemorrhage, and paramedian midbrain
infarction, as well as nonfocal conditions such as hypoxia, and drug intoxica-
Spindle Coma tion, and metabolic derangements (43–46). In one study, spindle coma com-
prised about 6% of coma EEGs (45). Historically, the term has been applied
Spindle coma refers to sleep-like spindle patterns of 9 to 14 Hz in a comatose without consensus as to a precise definition. The literature includes reports
patient, despite noxious stimulation (Fig. 7.8). It was first described in the of a predominant spindle pattern, despite noxious stimulation, on a routine
setting of a hypothalamic midbrain tumor (42). Subsequent studies identified daytime EEG, as well as reports of spindles occurring briefly or cyclically
FIGURE 7.8: Spindle coma in a patient treated with propofol for partial seizures following renal
transplant. There is a generalized 13- to 15-Hz spindle activity.
at some time during a prolonged EEG. Other sleep patterns such as vertex Awake but confused or dazed patients may have focal or generalized ictal
sharp waves and K-complexes have been reported with spindle coma (47). activity. These patients often have a history of epilepsy. Absence SE corre-
sponds to a generalized, approximately 3-Hz spike-wave pattern. SE in the
Pathophysiology setting of juvenile myoclonic epilepsy may present with frequent bursts of
Spindle coma has been ascribed to dysfunction of the ascending reticular generalized polyspike-wave discharges and clinical myoclonic jerks, some-
activating system at the level of the midbrain, causing impaired arousal, times with preserved ability to respond in between jerks. Other causes of
with sparing of the pontine raphe nuclei and thalamocortical pathways that NCSE in awake but confused patients include focal lesions, benzodiazepine
mediate sleep patterns (43,44). In the settings of toxic, metabolic, hypoxic withdrawal, drug intoxication, metabolic derangement, systemic infection,
or infectious encephalopathies, with more widespread brain involvement, or early encephalitis (50,51).
the mechanism of spindle coma is less clear, but presumably also involves NCSE occurs in a significant proportion of ICU patients. The reported
impairment of activating reticulothalamocortical pathways. prevalence ranges from 8% to more than 30%, depending on the types of
patients studied and the duration of monitoring (52,53). Clinical risk fac-
Prognosis tors for NCSE in the ICU include coma, subtle ocular signs, such as nystag-
In general, the prognosis of spindle coma compares favorably with other mus, sustained or intermittent eye deviation, or hippus, and either a history
more malignant patterns of coma, but the outcome varies according to its of epilepsy or a remote risk factor for epilepsy (54,55). Convulsive seizures
cause, severity, age of the patient, and timing of the pattern in relation to are a risk factor for subsequent NCSE, which is associated with double the
coma onset. Reactivity of the spindle coma pattern to noxious stimula- mortality of convulsive SE alone (56,57). Critically ill children under the
tion is the strongest predictor of good outcome (48). A literature review age of 18 have a high risk of seizures on continuous EEG, ranging from
of 227 cases of spindle coma found a poor outcome (defined as death or 36% to 44% of those undergoing continuous EEG monitoring (55,58,59).
persistent vegetative state) in 23%, with mortality occurring in patients with Patients at risk for nonconvulsive seizures include those with encephalopa-
irreversible structural lesions, carbon monoxide poisoning, or intracerebral thy in the following settings: sepsis, anoxic injury, therapeutic hypother-
hemorrhage due to head trauma (48). All patients survived when spindle mia following cardiac arrest, stroke, lobar intracerebral hemorrhage, renal
coma was due to drugs, encephalopathy, or seizures, while the least favorable failure, history of organ transplantation, and following brain surgery or
prognoses were associated with strokes and brain tumors (73% poor out- traumatic brain injury. SE after cerebral anoxia is associated with a higher
come). Poor outcomes occurred in 15% of spindle coma patients with head risk of death (60).
trauma and one-third of those with hypoxia or cardiorespiratory arrest. Because seizures and NCSE are common, and are a risk factor for poor
outcome, continuous EEG monitoring, with video if possible, is recom-
ICTAL PATTERNS mended for many ICU patients. Clinical features associated with NCSE are
listed in Table 7.4. When one or more of the listed clinical signs is present,
Nonconvulsive Status Epilepticus there should be a high index of suspicion for the possibility of NCSE, and
EEG monitoring is indicated. When assessing possible NCSE, details of the
NCSE is increasingly recognized as a cause of encephalopathy. It is an epileptic patient’s medical conditions, level of awareness, concurrent medications, and
state of altered behavior or mental status and corresponding electroencepha- response to the administration of intravenous AEDs are essential to an accu-
lographic seizure activity, occurring either continuously or intermittently. If rate EEG interpretation. In addition to detecting and quantifying seizures,
intermittent, the patient’s mental status does not return to baseline in between continuous EEG monitoring is useful in detecting acute brain events, such
seizures. The duration of SE is a subject of debate. A 1993 definition of SE as ischemia due to vasospasm following subarachnoid hemorrhage, assess-
specified a duration of 30 minutes (49). Ictal activity lasting at least 10 minutes ing level of sedation, and assisting with prognostication. Concurrent video
is considered impending SE. Clinical presentations of NCSE range from the recording is helpful in identifying ICU artifacts, documenting presence or
ambulatory confused to coma in the setting of serious comorbidities. An EEG absence of clinical signs during seizures, and assessing stimulation and EEG
is required for diagnosis and to monitor response to treatment. response.
TABLE 7.4 Features Associated with NCSE and attaching an “ictal” or “nonictal” label may be misleading. When it is
unclear whether or not a pattern is definitively a seizure pattern, the most
Clinical signs accurate approach is to acknowledge that it lies along the interictal-ictal
continuum.
Coma or fluctuating mental status
Recent convulsive seizures
Topics of Controversy
Eye movement abnormalities
Nystagmus Although identifying features of NCSE have been proposed, areas of
Eye deviation uncertainty and debate remain (61–63). Periodic patterns that follow con-
Hippus vulsive SE have been recognized as a late stage of SE and may warrant
Subtle twitching of face or repetitive chewing treatment (64). However, some electroencephalographers maintain that
Posturing or twitching of limb(s) nonevolving periodic discharges in patients with an acute cerebral pro-
Paroxysmal autonomic changes cess, but no history of seizures, are an epiphenomenon of an injured brain,
Features of past medical history and do not treat them as NCSE (19,65). There is general agreement that
History of epilepsy nonconvulsive seizure activity must demonstrate evolution in frequency,
History of remote risk factors for epilepsy (traumatic brain injury, stroke) morphology, or spatial distribution (Figs. 7.9 and 7.10). Difficulties in
Acute clinical setting interpretation arise when rhythmic EEG patterns have slow frequencies and
insidious onset, evolution, and termination, as they frequently do in coma-
Recent convulsive seizure(s)
Acute supratentorial brain lesion tose patients, or encephalopathic patients with critical illnesses. Such evo-
Recent brain surgery lution may be so subtle that computer seizure-detection paradigms fail to
Recent organ transplantation identify it, and even the experienced electroencephalographer may suspect
Following cardiac arrest (with or without therapeutic hypothermia) it only after reviewing many hours of EEG and recognizing recurring or
Withdrawal of anesthetic or AEDs stereotyped sequences.
Encephalitis
Toxic or metabolic encephalopathy Proposed Criteria
Sepsis Published primary criteria for nonconvulsive seizures include the following
Initial EEG pattern criteria: (a) repetitive or continuous focal or generalized spikes, sharp waves,
Focal or generalized periodic discharges spike-and-wave or sharp-and-slow-wave discharges at greater than or equal
Burst suppression to 3 Hz; (b) repetitive or continuous generalized spikes, sharp waves, spike-
Brief ictal runs or seizures and-wave, or sharp-and-slow wave discharges at less than 3 Hz, with timely
response to an antiepileptic drug; or (c) sequential rhythmic, periodic, or
quasiperiodic waves at greater than or equal to 1 Hz and unequivocal evolu-
tion in frequency, morphology or location. In these proposed criteria, terms
have been strictly defined, in an effort to promote consistent application.
The Interictal-ictal Continuum Evolution of frequency is a gradual increase or decrease by at least 1 Hz.
The development of EEG criteria for NCSE has proven to be challenging. Evolution of amplitude only is not sufficient to diagnose NCSE, nor is
In ICU patients, especially those who are critically ill, have multiple comor- change in sharpness of the waveform, without other change in morphology.
bid conditions, or have fluctuating levels of pharmacologic sedation, the Evolution of location is specified as the gradual spread into or out of a region
EEG frequently demonstrates encephalopathic patterns that wax and wane involving at least two electrodes. AED response is defined as significant
in voltage, frequency, rhythmicity, or location. It is often difficult to say if improvement in the patient’s clinical state or the appearance of previously
or when the EEG activity is ictal, and when it is interictal. The attempt to absent normal EEG patterns, temporally coupled to the acute administra-
identify a single moment of transition becomes an arbitrary demarcation, tion of a rapidly acting AED. Resolution of epileptiform discharges leaving
FIGURE 7.9: Generalized nonconvulsive ictal activity, arising from a suppressed background. Note the evolu-
tion of frequency, voltage, and waveform. In this example, the discharges become faster, lower voltage, and
more regular as the seizure progresses.
diffuse slowing without clinical improvement, and without the appearance Unfortunately, the more common occurrence following a benzodiazepine
of previously absent normal EEG patterns, is not a sufficient response to dose is improvement in the EEG, without clinical change and without nor-
satisfy the criterion (61,62). malization of the EEG background—a nondiagnostic finding.
Figure 7.11 shows a proposed algorithm for the EEG diagnosis of NCSE There is reasonable consensus regarding a few patterns that do not consti-
based on these criteria (66). A key component in the diagnosis of equivo- tute NCSE. The benzodiazepine-induced attenuation of metabolic periodic
cal rhythmic or periodic EEG patterns is the administration of a bolus of patterns such as triphasic waves is not associated with clinical improvement,
rapidly acting short-acting benzodiazepine. A clear-cut clinical and electro- and does not indicate NCSE (30). Patients with epileptic encephalopathies
graphic benzodiazepine response is diagnostic of NCSE. Significant clini- such as Lennox Gastaut syndrome at baseline have very abnormal EEGs,
cal improvement alone also suggests the resolution of a seizure or NCSE. frequently including recurrent or periodic epileptiform discharges. These
Figure 7.10: The termination of a seizure, in a patient with NCSE. Discharges decelerate, and are
followed by suppression. Two channels are not recorded due to neurosurgical instrumentation.
patterns are not considered NCSE, but that concern should arise if there is of monitoring, in 5% of cases the first seizure is detected during day 2 of
a clinical change corresponding to a change in the EEG from baseline (63). monitoring, and in 7% the first seizure is not recorded until after 48 hours of
monitoring. Comatose patients are more likely than non-comatose patients
Duration of Monitoring to have their first seizure recorded after more than 24 hours of monitor-
A routine 20-minute EEG does not adequately evaluate for seizures in a ing (55). It is reasonable to monitor for at least 24 hours in a noncomatose
critically ill patient. A question that frequently arises with continuous EEG patient, and at least 48 hours in a comatose patient. Longer duration of
monitoring in the ICU is the appropriate duration of surveillance. While monitoring is appropriate if seizures or periodic discharges are recorded, or
continuous EEG detects the majority of seizures during the first 24 hours with sedative or AED withdrawal.
Clinical manifestations consistent Consider prolonged

Obtain EEG EEG normal? Yes
with NCSE >30 min EEG recording
No
No
Repetitive or rhythmic
generalized or focal spikes,
Frequency sharp waves, spike-and-wave, Prolonged
Yes Yes
>1 Hz? sharp-and slow-wave complexes, or EEG normal?
rhythmic waveforms lasting
>10 seconds?
No
Yes
No
Not NCSE
Significant Clinical
Frequency evolution in field, focal motor Trial of rapid-
No No No
>2.5 Hz? morphology, or symptoms? Onset IV AED
frequency? No
Clinical & EEG

EEG Response No response to
to IV AED? IV AED?
Yes Yes Yes
Yes Yes
NCSE NCSE NCSE NCSE Possible NCSE, monitor for

long-term clinical response
FIGURE 7.11: Algorithm for the electroencephalographic diagnosis of NCSE, proposed by Susan Herman,
MD. Reprinted from Herman ST. The electroencephalogram of nonconvulsive status epilepticus. In: Kaplan
PW, Drislane FW, eds. Nonconvulsive Status Epilepticus. New York, NY, Demos Medical Publishing, LLC,
2009, p. 43.
LOW-VOLTAGE AND SUPPRESSED PATTERNS bursts become briefer. A burst-suppression pattern is distinguishable from
GPDs, in that bursts last at least 0.5 seconds, cross the baseline at least three
Generalized Suppression times, and may occur at regular or irregular intervals. In contrast, periodic
discharges are briefer, lasting less than 0.5 seconds, and may consist of a
Generalized suppression refers to widespread persistent nonreactive low- mono- or biphasic waveform recurring at a regular interval.
voltage activity that is not completely isoelectric. Theta or delta frequencies
tend to predominate and the amplitude is less than 20 μV. A sensitivity of Clinical Correlation
2 or 3 μV per mm is needed to evaluate this low-voltage activity, and EKG The most common causes of a burst-suppression pattern are anoxic encepha-
artifact may be prominent. lopathy, anesthetic or CNS depressant drugs, and hypothermia. These etiolo-
gies often coexist in patients who are resuscitated after cardiac arrest, and
Clinical Correlation treated with therapeutic hypothermia and anesthetic drugs. It is difficult to
This pattern suggests diffuse cortical and subcortical damage, as can be seen distinguish whether the EEG findings are due to an underlying anoxic enceph-
in the setting of anoxic encephalopathy or severe traumatic brain injury (67). alopathy, medication effects, hypothermia, or a combination of these factors.
It can also occur in the settings of widespread neuronal dysfunction, such While the CNS effects of hypothermia and anesthetic drugs are potentially
as hypothermia, intoxication by drugs that depress the central nervous sys- reversible, the effects of cerebral anoxia frequently are not. In these cases, it
tem (CNS), or high doses of anesthesia. Suppression is potentially reversible is inappropriate to use the EEG to evaluate prognosis until the patient is nor-
when caused by hypothermia or drugs. In the case of cerebral anoxia, a sup- mothermic, and sedatives and anesthetic agents have been withdrawn.
pressed EEG portends a poor prognosis. Cerebral activity is coupled with In the setting of anoxic encephalopathy alone, three patterns are associ-
cerebral blood flow, and EEG changes occur within seconds of the onset ated with a generally, but not invariably poor prognosis: burst suppression,
of hypoperfusion. “Flattening” of the EEG occurs if hemispheric flow falls generalized suppression (20 μV or less), and epileptiform discharges on a flat
below 16 to 18 cm3 per 100 g of brain tissue per minute (68,69). The develop- background (26,70). With these patterns, the false-positive rate for poor out-
ment of cellular necrosis and infarction depends on the length of time that come is 3%—insufficient prognostic accuracy for life-and-death decision-
cerebral blood flow remains below a critical threshold. making (26).
A low-voltage pattern may occur in normal individuals. In these cases, It is important to recognize myoclonic SE, because when it occurs within
background activity is reactive and includes beta and alpha frequencies. 24 hours of a primary circulatory arrest, the prognosis for recovery is poor
Fragments of alpha rhythm may be present at rest or during hyperventi- (70). Postanoxic myoclonic SE occurs when there is sustained, repetitive,
lation, and during sleep, identifiable sleep patterns occur. While EEGs of spontaneous myoclonic twitching or jerking in a comatose patient. To the
patients with Huntington’s disease or hypothyroidism occasionally demon- observer, myoclonus may be obvious, or it may be very subtle, appreciable
strate a low-voltage background, the presence or absence of this finding is only with close examination of the face and limbs. It can be generalized,
not useful diagnostically for these conditions. focal, or multifocal. The EEG shows either a burst-suppression pattern,
or GPDs, with myoclonic twitches time-locked to the bursts or discharges.
Burst Suppression Myoclonic SE and other types of seizure activity occur in up to 35% of
postanoxic patients monitored with EEG, and are associated with a higher
A generalized burst-suppression pattern consists of brief intervals (bursts) risk of death (53,60,71).
of relatively high-voltage activity, with intervening periods of generalized
suppression (Fig. 7.12). Within the bursts, activity is of mixed frequency Important Caveats in Using the EEG for Prognosis
and variable waveform. Slow waves, sharp waves, and spikes may all occur
within a burst. The duration of bursts and of intervals of suppression var- Electroencephalographers should exercise caution when using the EEG to
ies, but generally suppression intervals last longer than the bursts of higher evaluate prognosis in a comatose patient following cardiac arrest. Stud-
voltage activity. With deepening coma, suppression intervals lengthen, and ies have not systematically analyzed the impact of confounding clinical
FIGURE 7.12: Burst suppression following cardiac arrest. There is a suppressed background with
intervals of higher voltage, mixed-frequency activity.
factors on the prognostic accuracy of EEG. Potential confounders include Electrocerebral Inactivity
current or prior use of sedatives, the presence of organ failure or car-
diac shock, and hypothermia. Each of these conditions may contribute Electrocerebral inactivity (ECI) or electrocerebral silence is defined as an
independently to a “malignant”-appearing EEG, and may diminish its absence of any EEG activity over 2 μV, when appropriate recording param-
prognostic accuracy. Neuromuscular blocking drugs, while helpful in eters are used. Guidelines advise recording from scalp electrode pairs 10 or
distinguishing muscle artifacts from cerebral discharges, also mask the more centimeters apart and interelectode impedances under 10,000 Ω, but
manifestations of myoclonus, and may delay or prevent the recognition over 100 Ω (72). ECI on an EEG does not make the diagnosis of brain death.
of myoclonic SE. This clinical diagnosis is made only after a detailed neurological exam and
full consideration of the clinical setting and supporting data. Hypothermia Apnea testing (all must be checked)
and drug intoxications are potentially reversible causes of ECI that must be
Patient is hemodynamically stable
excluded for a diagnosis of brain death.
Ventilator adjusted to provide normocarbia (Paco2 34–45 mm Hg)
Clinical Correlation Patient preoxygenated with 100% Fio2 for >10 min to Pao2 >200 mm Hg
Patient well-oxygenated with a PEEP of 5 cm of water
In the appropriate clinical setting, with irreversible coma of known cause Provide oxygen via a suction catheter to the level of the carina at 6 L/min
and a neurological examination indicating brain death, an EEG demon- or attach T-piece with CPAP at 10 cm H2O
strating ECI may be used to support or confirm that diagnosis (Table 7.5). Disconnect ventilator
Brainstem reflexes and respiratory drive must be absent, and the potential Spontaneous respirations absent
effects of sedative drugs, paralytic agents, severe metabolic derangement, Arterial blood gas drawn at 8–10 min, patient reconnected
hypotension and hypothermia must be ruled out. In 2010, the American to ventilator
Academy of Neurology published an update of its 1995 guideline on deter- PCO2 ≥60 mm Hg, or 20 mm Hg rise from normal baseline value
mining brain death in adults (70). This update found no published reports OR
of recovery of neurological function after a diagnosis of brain death using Apnea test aborted
Ancillary testing (only one needs to be performed; to be ordered only if
TABLE 7.5 Checklist for Determination of Brain Death clinical examination cannot be fully performed due to patient factors, or
if apnea testing inconclusive or aborted)
Prerequisites (all must be checked) Cerebral angiogram
Coma, irreversible and cause known HMPAO SPECTa
Neuroimaging explains coma Electroencephalogram (brain death protocol)
CNS depressant drug effect absent (if indicated toxicology screen; if bar- Transcranial Doppler
biturates given, serum level <10 μg/mL) a
HMPAO SPECT, Tc-hexamethylpropyleneamineoxime single-photon-emission com-
No evidence of residual paralytics (electrical stimulation if paralytics
puted tomography
used) Reproduced from Wijdicks EFM, Varelas PN, Gronseth GS, et al. Evidence-based guide-
Absence of severe acid-base, electrolyte, endocrine abnormality line update: determining brain death in adults. Report of the Quality Standards Subcom-
Normothermia or mild hypothermia (core temperature >36°C) mittee of the American Academy of Neurology. Neurology 2010;74:1911–1918.
Systolic blood pressure ≥100 mm Hg
No spontaneous respirations
Examination (all must be checked) the criteria reviewed in the 1995 American Academy of Neurology practice
parameter (73).
Pupils nonreactive to bright light
Corneal reflex absent
Technical Requirements
Oculocephalic reflex absent (tested only if C-spine integrity ensured)
Oculovestibular reflex absent The technical requirements for recording EEG in cases of suspected brain
No facial movement to noxious stimuli at supraorbital nerve, temporo- death are rigorous, in order to minimize the risk of a false-positive test.
mandibular joint In order to detect very low-voltage cerebral activity, if present, a sensi-
Gag reflex absent tivity setting of at least 2 μV per mm (preferably 1 or 1.5 μV per mm) is
Cough reflex absent to tracheal suctioning required. At this sensitivity, physiological and environmental artifacts are
Absence of motor response to noxious stimuli in all four limbs (spinally magnified. Concomitant recording of EKG and environmental “noise”
mediated reflexes are permissible) aids in the identification of these artifacts. Filter settings are optimized to
record a broad bandwidth of frequencies. The American Clinical Neurology
TABLE 7.6 Minimum Technical Standards for EEG Recording in Suspected Cerebral Death
1. A full set of scalp electrodes should be utilized.

2. Interelectrode impedances should be under 10,000 Ω but over 100 Ω.
3. The integrity of the entire recording system should be tested.
To verify that the electrode board is connected to the machine, and that the montage settings match the electrode placements, the technologist touches
each electrode of the montage gently with a cotton swab and document the electrode touched.
4. Interelectrode distances should be at least 10 cm.
Using the International 10–20 system, interelectrode distances on adults average 6–6.5 cm. Longer interelectrode distances allow a greater possibility of
recording cerebral potentials. With longitudinal or transverse bipolar montages, some double distance electrode linkages are recommended.
5. Sensitivity must be increased from 7 μV/mm to at least 2 μV/mm for at least 30 min of the recording, with inclusion of appropriate calibrations.
Recording with a sensitivity of 1.5 or 1 μV/mm allows a more confident assessment of the presence, or absence, of a 2 μV signal.
6. Filter settings should be appropriate for the assessment of electrocerebral silence.
The high-frequency filter should not be set below 30 Hz, and the low-frequency filter should not be set above 1 Hz. The 60-Hz notch filter may also be
used if needed.
7. Additional monitoring techniques should be employed when necessary.
Monitoring of EKG is essential. An additional noncephalic channel, recording from a pair of electrodes on the dorsum of the hand, 6–7 cm apart, is used to
monitor artifact emanating from the patient or the environment. It may be necessary to reduce or eliminate EMG contamination by using a neuromuscular
blocking agent, under the direction of an anesthesiologist. Ventilator artifact can be documented with specific notation on the record, or it may be
monitored by transducer. Definitive identification of respiratory artifact is achieved by briefly disconnecting the ventilator.
8. There should be no EEG reactivity to intense somatosensory, auditory, or visual stimuli.
9. Recordings should be made only by a qualified technologist.
10. A repeat EEG should be performed if there is doubt about electrocerebral inactivity.
Reproduced from American Clinical Neurophysiology Society. Guideline 3: minimum technical standards for EEG recording in suspected cerebral death. J Clin Neurophysiol
2006;23(2):97–104.
ociety Guidelines for Minimal Technical Standards for EEG Recording in

S activity, or low-voltage patterns. Each of these patterns is defined by, and
Suspected Cerebral Death are listed in Table 7.6 (72). described with, variable parameters that can direct us toward a diagnosis,
an understanding of severity and prognosis, and in many cases, a treat-
ment plan. Experienced electroencephalographers acknowledge the pitfalls
CONCLUSIONS that threaten accurate interpretation of encephalopathic patterns. Poten-
tial confounding factors include environmental artifacts that can mimic
EEG remains a highly sensitive test for evaluating encephalopathy, provid- physiological signals, the effects of sedative or anesthetic drugs, response to
ing a unique and immediate window into brain function. Although the pat- stimulation, hypothermia, and comorbid conditions. Despite these caveats,
terns of generalized encephalopathy vary, both between patients and in a prolonged continuous EEG recording allows a panoramic view of fluctua-
single patient over time, most encephalopathic patterns span one or more tions in cerebral function and provides opportunities for timely therapeu-
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EEG in Focal Encephalopathies:
8 Cerebrovascular Disease,
Neoplasms, and Infections
JOSEPH I. SIRVEN
Introduction Infections
Nonepileptiform Abnormalities Cerebrovascular Disease
Changes in Background Rhythms Role of the EEG in Stroke
Focal Slow-Wave Activity Focal Cortical Dysplasia
Epileptiform Abnormalities Conclusion
Periodic Lateralized Epileptiform Discharges References
Specific Pathologies
Brain Tumors
INTRODUCTION EEG, however, is complementary and has usefulness in these settings. EEG
provides physiologic function of the brain, information that is not readily
Before the introduction of modern imaging methods such as magnetic reso- available from imaging. Such information can be important in estimating
nance imaging (MRI) and computed tomography (CT), electroencephalogra- the extent of a functional impairment, recognizing a coexistent metabolic
phy (EEG) was routinely used to identify and localize intracranial pathology. or toxic encephalopathy, and indicating a lesion’s epileptic potential. Oc-
Over the ensuing decades, electroencephalographers refined these findings casionally, as in acute ischemia, EEG changes may proceed or outlast im-
and became somewhat adept at using them to localize superficial cerebral aging abnormalities. Combining imaging studies and EEG, therefore, will
lesions. However, for deep lesions, particularly those in the posterior fossa, often give a more complete neurophysiological picture than will either study
EEG can be limited, as the findings are typically nonspecific and diffuse. alone. In this chapter, we discuss the EEG associated with focal encepha-
In recent years, CT and MRI have replaced EEGs as diagnostic tests of lopathies. Etiologies commonly associated with focal encephalopathies
choice for detecting and localizing cerebral lesions. Both are superior to include cerebrovascular diseases, neoplasms, abscess, and other focal infec-
EEG for these indications and provide useful information about etiology. tions. Epileptiform and nonepileptiform abnormalities as it relates to these
238
EEG in Focal Encephalopathies: Cerebrovascular Disease, Neoplasms, and Infections 239
various lesions will be discussed. It is also important to understand that Thalamic Potential reduction of alpha activity None
many neurological conditions are often accompanied by several EEG find- hemorrhage/
ings (Table 8.1). No one finding is diagnostic of any given condition. stroke
Subarachnoid Polymorphic delta activity Occasional spike
TABLE 8.1 hemorrhage/ wave activity
Summary: EEG Findings in Focal Encephalopathies Arteriovenous Occasional false
Focal Nonepileptiform EEG abnormalities Epileptiform malformation lateralization
pathology abnormalities (AVM) of spike wave
activity
Brain tumors Focal enhancement of focal beta Rare spike waves
activity Rare periodic Focal cortical Localized slow-wave activity Focal epi-
Focal delta or theta activity lateralized dysplasia leptiform
Hyperventilation (HV) may epileptiform discharges
accentuate slowing discharges
Focal attenuation (PLEDs)
Brain abscess Background slowing PLEDs NONEPILEPTIFORM ABNORMALITIES
Frontal intermittent rhythmic delta Isolated focal
activity (FIRDA) spike waves Changes in Background Rhythms
Focal slowing
Herpes Diffuse slow waves Focal epilepti- Changes in the EEG produced by focal brain lesions may be categorized as
encephalitis Focal attenuation of background form activity either epileptiform or nonepileptiform. Epileptiform abnormalities include
Temporal PLEDs spikes, sharp waves, spike-and-wave or sharp- and slow-wave discharges,
Seizures and periodic discharges. Nonepileptiform abnormalities are of several types.
Subdural Slow posterior dominant rhythm PLEDs—rarely First, localized slow activity is the most prevalent abnormality associated
hematoma Diminished EEG amplitude with focal brain lesions; the slowing is further classified as arrhythmic or
Increased slow-wave activity rhythmic frontal intermittent delta activity. There can also be alterations in
Transient At time of event—focal slowing None
normally present cerebral rhythms such as frontal beta activity or the alpha
ischemic rhythm. Background activity can be attenuated locally. Finally, widespread
attack (TIA) or diffuse abnormalities that occur with focal lesions, especially those lo-
cated in the subfrontal cortex or thalamus where those that produce hydro-
Hemispheric Widespread arrhythmic delta over af- PLEDs over
stroke fected hemisphere affected cephalus could lead to nonspecific generalized changes.
Absence of ipsilateral alpha rhythm hemisphere Persistent asymmetry of beta activity indicates focal cortical dysfunction,
or lower amplitude which is often due to a cerebral lesion. The most common cause of focally en-
Diminished/suppressed electrical ac- hanced beta activity is the breach rhythm. This is usually the consequence of
tivity over the affected hemisphere intracranial surgeries requiring a craniotomy or burr hole (Figs. 8.1 and 8.2).
IRDA—intermittent rhythmic delta Less often, the breach rhythm results from a skull fracture. Skull defects en-
activity hance the voltage of frontal fast rhythms as much as threefold. This is most ev-
Vertebrobasilar EEG may be normal or nonreac- None ident at midcentral and temporal electrode sites because of their proximity to
stroke tive alpha activity if extensive underlying mu rhythms or temporal rhythmic activity in the alpha frequency
lesion of the upper pons or lower range. Although the enhanced beta activity is maximal nearest a burr hole
mesencephalon or craniotomy margin, there is typically a broad voltage distribution. Focally
240 EEG in Focal Encephalopathies: Cerebrovascular Disease, Neoplasms, and Infections
Figure 8.1: Breach Rhythm. EEG demonstrating a characteristic breach

rhythm over the left hemisphere. Note the increased beta activity over
the left hemisphere and higher-amplitude background rhythms.
enhanced beta activity is rare in other circumstances. It has been described cerebral spinal fluid results from a head injury, the underlying cortex is often
with brain abscess, stroke, arteriovenous malformation (AVM), tumors, and injured as well, invalidating this distinction.
focal cortical dysplasia. Localized attenuation of beta activity is much more Focal cerebral lesions can alter the alpha rhythm even when they do not
common in these conditions than enhancement. directly involve the occipital lobes and adjacent brain regions. Changes that
Asymmetrical beta activity should be considered abnormal if there is per- can result from focal lesions include (a) unilateral slowing of frequency
sistent voltage difference of 35% or more between homologous areas of the (1 Hz or more difference between the sides), (b) loss of reactivity, (c) loss of
two sides. Frontal beta activity tends to occur out of phase on the left and modulation, and (d) voltage attenuation. Unilateral attenuation or absence
right sides, and a voltage asymmetry can therefore be enhanced using bi- of alpha rhythm usually occurs with lesions of the occipital cortex and ante-
polar montages that connect homologous areas. Focal attenuation of beta rior ventral thalamus. Unilateral failure of the alpha rhythm to attenuation
activity is a reliable sign of cortical abnormality. with eye opening (Bancaud phenomenon) occurs with posterior subcortical
Focal attenuation of beta activity is seen in a number of conditions, in- lesions (Fig. 8.3). Voltage asymmetry, in itself, is only rarely an indication
cluding brain abscess, stroke, AVMs, and brain tumors. Green and Wilson of focal abnormality. In contrast, symmetries of frequency and reactivity
[1] concluded that beta activity seems to be diminished with vascular lesions are abnormal and reliably indicate the side of the lesion. Skull defects result
and enhanced by tumors. Barbiturates have also been used to bring out a in higher-voltage alpha rhythm, a difference that can be two to three times
beta asymmetry, because focal structural lesions often diminish the usual that of the normal side. Rarely, the alpha rhythm is higher on the side of the
enhancing effect of such drugs. Beta activity is also attenuated by subdural, brain tumor, but in such cases, the alpha rhythm is also usually less reactive
epidural, or subgaleal fluid collections. These selectively suppress higher- and poorly modulated.
frequency activity, much like a fast-frequency filter. Focal slowing usually Asymmetries and the response to intermittent photic stimulation may
accompanies parenchymal lesions, but not fluid collections, a point that is result from lesions on the side of lower voltage, but responses can also
sometimes helpful for interpretation. However, when extra-axial blood or be consistently lateralized in some normal individuals. Therefore, voltage
Figure 8.2: The EEG shows a typical Breach rhythm involving the left
hemisphere. Note the increased amplitude over the left hemisphere
along with increased beta rhythm. The patient has a history of a left tem-
poral lobectomy.
asymmetries in photic driving should not be interpreted as abnormal in the Focal Slow-Wave Activity
absence of corroborative findings such as focal slowing or localized attenu-
ation of background rhythms on the same side. Rarely, epileptogenic lesions Slow-wave activity is classified as arrhythmic or rhythmic, intermittent or
result in responses to photic stimulation that are of higher voltage on the continuous, focal or generalized. Focal polymorphic delta activity is slow-
side of the lesion. frequency activity, less than 4 Hz, that lacks sustained rhythmicity, char-
Normal sleep patterns, especially sleep spindles and vertex waves, can be acterized by constantly changing morphology, frequency, and voltage.
affected by cerebral lesions. In sleep stage N2, as well as established persis- Continuous focal polymorphic delta activity is highly correlated with a lo-
tent asymmetry of spindles indicate an abnormality on the side of lower calized structural lesion such as tumor, stroke, abscess, intraparenchymal
voltage. Lesions of the parietal lobe or thalamus can attenuate sleep spin- hematoma or contusion. Such delta activity usually persists during changes
dles. Thalamic lesions can also result in interhemispheric asynchrony of in physiologic states. The clinical correlation of intermittent polymorphic
spindles, affect regulation spindle frequency, or rarely lead to the appear- slow-wave activity is less well-defined as are those of delta waves, which at-
ance of spindle-like rhythms during the waking state. Skull defects enhance tenuate with eye opening or disappear with sleep. Voltage of focal polymor-
the scalp-recorded voltage of sleep spindles and vertex waves. phic delta activity is usually higher than ongoing background activity, but
Figure 8.3: Bancaud phenomenon. In this EEG, we see a persistence of

the alpha rhythm despite eye closure. The eye movement artifact con-
firms the phenomenon.
it can vary, depending, in large part, on the proximity of the lesion to the Bilateral synchronous delta or theta activity with an anterior pre-
cortical surface and recording electrodes. Typical voltage of focal polymor- dominance is often known as frontal intermittent rhythmic delta activity
phic delta activity is 100 to 150 µV in adults and up to 500 µV in children. (FIRDA). First described by Cobb (2), this activity need not necessarily
Focal polymorphic delta activity is often but not always maximal over be frontal nor does it have to possess exclusively delta frequency activity;
the lesion. This activity implies that a sufficient destruction of the cortex theta activity can also occur. IRDA (intermittent rhythmic delta activity)
in adjacent white matter (WM) has occurred. However, the voltage of the may be diffuse or lateralized with a sudden onset standing out from back-
delta activity is actually reduced over the area of maximal cerebral involve- ground EEG activity. In adults, the classic presentation is bifrontal where
ment by the lesion. It is particularly important to pay attention to areas of the acronym FIRDA applies, whereas in children, occipital predominance
relatively inactivity, flat or smooth polymorphic delta activity in which the is noted and the acronym is OIRDA (occipital intermittent rhythmic delta
voltage of both slow waves and faster frequencies are depressed. In these activity). When IRDA is predominant in the temporal lobe and coupled
cases, the voltage will be higher in the areas bordering the lesion. The local- with spike waves, the rhythm is known as temporal intermittent rhythmic
izing value of focal polymorphic delta activity is greatest when it is topo- delta activity (TIRDA).
graphically discrete and associated with depression of superimposed faster FIRDA must be differentiated from vertical eye blinks; simultaneous re-
background frequencies. Superficial lesions tend to produce more restricted cording of infraorbital and frontal scalp electrodes can easily distinguish
EEG changes, whereas deep lesions can result in hemispheric or even bilat- between the two patterns. FIRDA is in phase with recordings taken above
eral delta activity. Focal delta activity associated with lesions of the frontal and below the eye (Fig. 8.4). Other benign rhythms that need to be distin-
lobe typically spreads to homologous contralateral areas where it is typically guished from FIRDA include normal hyperventilation (HV) response, and
of lower voltage and has a smaller field than slowing ipsilateral to the lesion. hypnagogic hypersynchrony.
Lesions involving the posterior, frontal, and parietal lobes often produce IRDA is an abnormal yet nonspecific finding in adults. TIRDA is the
delta activity that is falsely localized to the temporal areas. only pattern correlated to epilepsy (Fig. 8.5). Anatomically, IRDA may
Figure 8.4: FIRDA detected with the use of eye leads. This EEG shows
FIRDA and how the use of eye leads can help to distinguish between
FIRDA versus eye movement artifact. Note how the delta activity is in
phase with the extra eye lead channels at the bottom of the montage.
arise from structural brain lesions, yet is more commonly associated with electroencephalographic changes are seen with a wide variety of conditions
diffuse encephalopathies. When associated with brain lesions, those abnor- affecting the central nervous system (CNS).
malities are anterior and hemispheric. Deep midline lesions, subcortical Although experimental, clinical, and brain imaging studies have demon-
abnormalities, and increased intracranial pressure may also cause FIRDA strated the strong correlation between localized anatomical pathology and
(Figs. 8.6 and 8.7). focal polymorphic delta activity, they also illustrate that delta activity can
Clinical and experimental data indicate that polymorphic delta activity occur in the absence of a demonstrable lesion. This is most likely to oc-
usually results from lesions affecting the cerebral WM. Involvement of the cur when the polymorphic slowing is intermittent and contains substantial
superficial cortex is not essential; indeed, lesions restricted to the cortical amounts of intermixed theta activity. In these cases, the underlying cerebral
mantle do not generally produce significant focal delta activity. Cerebral dysfunction is often reversible. Examples include migraine, trauma, enceph-
edema by itself does not make a substantial contribution to the production alitis, and postictal dysfunction. Focal arrhythmic theta activity can be seen
of delta waves. Brain tumors, abscesses, and areas of infarctions are electri- early in the course of benign or well-differentiated brain tumors and during
cally silent. The EEG changes produced by these lesions probably reflect resolution of acute lesions caused by stroke or head trauma.
alterations in cortical function caused (a) directly by anatomic disruption
of neurons in their local networks or locally impaired blood flow, cellular EPILEPTIFORM ABNORMALITIES
metabolism in the micro environment; and (b) indirectly by modification
of input to cortical neurons (3). EEG is generally not useful in distinguish- Seizures are a common final pathway for clinical presentation of several
ing among different types of brain lesions. This is largely because there are types of focal pathologies, so it should not be surprising that interictal epi-
only a limited number of ways the brain can react to injury; therefore, few leptiform discharges are frequently present in the EEGs of such patients.
Figure 8.5: TIRDA. The EEG displays TIRDA. As compared to FIRDA or

OIRDA, TIRDA is highly correlated to epilepsy.
Epileptiform activity is common in the EEGs of patients with well-differ- throughout most of the recording. Chatrian et al. introduced the term PLEDs
entiated glioma, traumatic injury, brain abscess, mesiotemporal sclerosis, in 1965 [4], although the phenomenon was first described in 1952 by E chlin (5).
and cortical dysplasia. In patients with benign or very slowly progressive PLEDs occur in all age groups, from infants to the aged. They are usually
tumors, focal epileptiform discharges sometimes antedate the appearance seen transiently in the setting of an acute destructive cerebral lesion and occur
of focal slow-wave activity by months or years. In general, however, patients early in the course of a patient illness. They can be seen less commonly with
with brain tumors usually have other EEG abnormalities such as focal slow- systemic diseases and a remote cerebral lesion. Rare chronic PLEDs persisting
ing, voltage attenuation, in addition to spikes or sharp waves. Epileptiform for a period of 3 months to more than 20 years have been reported in patients
discharges are less common with acute cerebral infarction or hemorrhage. with chronic brain lesions and associated partial seizure disorders. Bilateral
Although these typically occur ipsilateral to the infarct, they can be seen independently occurring PLEDs were recognized by Chatrian et al. in 1965
rarely contralateral to an acute stroke. A complete discussion of epilepti- and formally characterized in 1981. They are seen in the setting of multifocal
form abnormalities is provided in other chapters. or diffuse cerebral injuries such as anoxia and herald a less favorable prognosis
with higher mortality. Approximately 80% to 90% of patients with PLEDs
Periodic Lateralized Epileptiform Discharges experience clinical seizure activity, primarily focal motor seizures (6,7).
PLEDs are often described as sharp-wave discharges coupled with ad-
Periodic lateralized epileptiform discharges (PLEDs) are a relatively uncom- ditional small spikey morphological waves accompanying the larger sharp
mon electroencephalographic pattern characterized by lateralized or focal wave (Fig. 8.8). Slow waves often occur immediately after the sharp-wave
periodic or near periodic spike, spike-wave, or sharp-wave complexes present discharge, creating a complex pattern that distorts the local background
Figure 8.6: FIRDA. The EEGs here and in Fig. 8.7 show FIRDA from dif-
ferent causes. In this figure, FIRDA is secondary to a metabolic derange-
ment in a patient with a urinary tract infection and confusion.
activity. These waves may recur at a frequency of 3 to 12 Hz per minute. PLEDs plus denotes PLEDs associated with rhythmic d ischarges (Fig. 8.10)
By definition, PLEDs imply a lateralized process, yet this pattern can ema- (6). The most cohesive manner as to which to view the clinical significance
nate from both hemispheres as in the case of bilateral PLEDs or (BIPLED) of PLEDs is to assume that PLEDs are on an ictal-interictal continuum in
(Fig. 8.9). Although the most common cause of PLEDs is stroke, their oc- which seizures are likely to occur depending on a complex combination of a
currence in other conditions is frequent. In fact, CNS infections and status patient’s propensity to seize, underlying neuronal injury, and acute metabolic
epilepticus predominantly account for BIPLED patterns. PLEDs have also derangements. In essence, PLEDs are a spectrum EEG finding that may
been reported early in the Creutzfeldt-Jakob disease (CJD) and in patients connote both an ictal and interictal pathology depending on the individual
with subdural hematoma, MELAS (mitochondrial myopathy, encephalopa- situation. Specific etiologies associated with epileptiform activities will be
thy, lactic acidosis, and stroke-like episodes), nonketotic hyperglycemia, and discussed in the subsequent sections of this chapter.
occasional chronic lesions, especially in the presence of a superimposed
metabolic abnormality (6,8,9). Electrolyte abnormalities and nonketotic hy- SPECIFIC PATHOLOGIES
perglycemia have also been postulated as factors that contribute to PLEDs
appearing after acute stroke (8,10). Brain Tumors
Distinguishing ictal versus interictal PLEDs is a common clinical conun-
drum. PLEDs may at times be considered an ictal pattern, although this is a Cortical tumors commonly produce abnormal EEG recordings in the ma-
matter of ongoing debate. PLEDs plus is a term that has been introduced to jority of the time, with focal delta activity noted as a common finding.
designate PLED type patterns that are predictive of seizures. Morphologically, EEGs are abnormal in up to 87% of children with benign astrocytic and
Figure 8.7: FIRDA. The patient has a history of nonspecific cognitive

decline and multiple small WM changes on imaging.
oligodendrocytic tumors of the cerebral hemispheres (11,12). Electroen- were not as common among patients with meningeal tumors, even though
cephalogram findings are generally related to location of the tumor and they also had a fair amount of focal epileptiform activity on the EEG. Pa-
rapidity of growth. Most, but not all, studies associate rapidly growing tu- tients with multiple metastases may also have a good deal of epileptiform
mors with very slow delta range activity and more slowly growing tumors activity in their EEG; over 90% of patients with metastatic disease have
with arrhythmic theta range activity with occasionally intermixed epilepti- abnormal EEGs, including epileptiform activity, delta range activity, and
form spikes and sharp waves. It should be noted that up to one-third of pa- dysrhythmias (16).
tients with brain tumors have an epileptogenic focus remote from the tumor Focal delta and theta range activity correlates with WM involvement of
site, which may give rise to some confusion in localization. Meningiomas tumors. This includes tumors involving both gray and white matter, as well
and other slow-growing or midline tumors may be difficult to localize, al- as those involving WM only. Rhythmic delta activity may indicate involve-
though HV may reveal the focus of slowing not seen otherwise (2,3,12–14). ment of the thalamus, although involvement of deep frontal WM may pro-
Focal theta range activity can occur with any type of tumor, and one series duce similar findings.
noted it in 75% of patients with hemispheric tumors. In that study, focal In a seminal series, Gastaut and colleagues studied 127 cases of brain
delta range activity was most common in patients with glioblastoma multi- tumor using both CT and EEG. These included both malignant and benign
forme, although it also occurred with meningeal tumors (15). Activity in the tumors. Intermittent or continuous focal delta activity occurred in 62% of
delta range was less frequent with astrocytomas and focal sharp waves were the EEGs. The presence of surrounding edema, even when extensive, did not
more common. Focal epileptiform activity appears to be correlated gener- affect the EEG findings. Other investigators have found that cerebral edema
ally with clinical seizures in patients with astrocytomas. Clinical seizures does not contribute significantly to EEG findings (17–19).
Figure 8.8: PLEDs. The EEG shows an unusual case of

occipital PLEDs in a 32-year-old man with an occipital
infarction.
Large Hemispheric Brain Tumors Infratentorial Brain Tumors

Although the EEG may be normal in up to 40% of brain tumors, normal Most tumors in children over one year of age are infratentorial. Although
EEGs actually occur in only about 5% of large hemispheric tumors, which most of these patients have had an imaging study, the presenting symptoms
account for the majority of brain tumors in adults. In contrast, EEGs are can be so nonspecific, such as altered mental status that an EEG might be
normal in at least 25% of deep midline, basal, and infratentorial tumors. This obtained for other reasons in the course of a patient’s treatment. Therefore,
figure is higher in the absence of obstructive hydrocephalus and increased it is important to understand EEG findings in this context so that an ap-
intracranial pressure. When abnormalities are detected, there are a number propriate interpretation of the pattern can be made. Electroencephalograms
of common findings on EEGs in patients with hemispheric tumors. PLEDs are abnormal in only 30% of patients with brainstem tumors. However, spe-
(10,12) are frequently reported, with up to 18% of patients demonstrating this cific infratentorial locations may influence whether an EEG abnormality
finding. FIRDA is often seen with frontal tumors, whereas parietal and oc- is found. For example, over 80% of EEGs were abnormal in a series with
cipital tumors may affect the posterior basic rhythm. Nevertheless, tumor lo- cerebellar or fourth ventricular tumors (20). Abnormalities included 27%
cation does not always correlate with EEG localization. Posterior tumors can with posterior rhythmic delta waves, 32% had generalized bilateral bursts
show abnormalities in more anterior regions and unilateral temporal tumors of rhythmic slowing, 51% had posterior arrhythmic delta waves, and 11%
can produce bitemporal abnormalities, possibly leading to false localization. had rhythmic theta or delta waves on vertex or anterior quadrants (21).
Figure 8.9: BIPLEDs. The EEG displays BIPLEDs in a patient with a para-
neoplastic encephalitis.
Figure 8.10: PLEDs plus. The EEG shows an example of parasagittal

PLEDs plus. This patient had eyelid twitching with a correlation of the
central PLEDs plus pattern. Note the extra waveforms occurring after
the main spike wave.
Attenuation of background activity is seen in patients with high-grade glio- Subfrontal and diencephalic tumors are most likely to produce bilateral but
mas that have thalamic involvement, but may also be seen in regions with asymmetrical IRDA. Bilateral arrhythmic slowing with bursts of IRDA re-
extensive peritumoral edema, although this is a nonspecific finding. flects hydrocephalus or mass effect with shift. Parasellar and hypothalamic
Electroencephalogram abnormalities in tumors of the sellar region in- tumors do not cause EEG changes unless they obstruct the third ventricle or
clude temporal lobe abnormalities, unilateral delta range activity, and bi- extend into the temporal lobe on one side.
temporal dysrhythmia. It is important to remember this in the differential
diagnosis of temporal lobe abnormalities. In tumors that compress the third
ventricle, generalized slowing was noted and the degree of compression was Infections
the only factor that correlated with abnormalities in the EEG. In most case
series, EEG abnormalities do not predict tumor type. Brain Abscess
Hypothalamic hamartoma is a developmental malformation that fre- Because of the increased number of patients on immunomodulators or im-
quently presents with seizures including infantile spasms. The EEG in this munosuppressants after organ transplantation, there has been a resurgence
condition may be normal, similar to other deep-seated masses, although of brain abscess cases. A recent case series of patients with brain abscesses
over time, it may evolve through the appearance of focal and then general- mentioned both epileptiform activity such as focal sharp waves and PLEDs
ized seizures consistent with the clinical semiology. There may be associ- as the most common EEG abnormalities (Fig. 8.11) (25,26). Importantly,
ated autonomic features. Focal slowing or epileptiform activity over frontal although EEG is localizing in most cases, it has been reported to be falsely
and/or temporal head regions may be the initial appearance on the EEG, localizing in some patients with a cerebellar abscess. Thus, EEG may be use-
although this evolves into bilateral spike wave over time if treated (9,22). ful in localizing cortical abscesses in many cases, but it can also be mislead-
Eventually, a pattern consistent of generalized slow spike wave, paroxysmal ing or even normal in others.
fast, and electrodecremental patterns can occur reminiscent of the EEG in
Lennox Gastaut Syndrome. There is a possibility that the hamartoma in Encephalitis
some way generates abnormal activity that propagates through the cortex, Electroencephalographic findings are particularly important in the diagno-
leading to the various seizure types noted. In an important study of four sis of encephalitis caused by herpes simplex virus (HSV) type 1, and some
patients with hypothalamic hamartoma presenting with epileptic manifesta- reports have suggested a normal EEG excludes the diagnosis. Many types
tions, EEG source analysis based on scalp recordings was able to estimate of abnormalities have been described, including focal or diffuse slow-wave
that the epileptiform spikes have deep sources in the neighborhood of the activity, focal epileptiform discharges, electrical seizure patterns, localized
hamartoma, which later spread to the cortical area (23). A subsequent study attenuation of background activity, and PLEDs (27–29). Because HSV-1
from the same group of patients using simultaneous EEG and fMRI re- causes severe hemorrhagic necrosis, mainly the inferior and medial parts of
cordings of several seizures indicated that the epileptic activity appeared to the temporal lobes and the orbital frontal regions, focal or lateralized find-
originate in the area around the tumor and propagate to the left fornix to the ings that are maximal in these areas are highly suggestive of herpes encepha-
temporal lobe and later through the cingulate fasciculus to the left frontal litis and can also be helpful in determining the best site for brain biopsy. The
lobe (9,24). acute destructive nature of the lesions probably accounts for the frequency
It is obviously not possible to determine the type of tumor by EEG, but with which PLEDs are seen.
several general observations provide useful guidelines. Slow growing extra- PLEDs appear in the acute phase of the illness, usually between the 5th
axial lesions such as meningiomas usually produce the least changes on and 12th day after the onset of neurological symptoms. They consist of 100-
the EEG. Rapidly growing intraparenchymal lesions such as glioblastoma to 500-mV sharply contoured slow waves or polyphasic spikes that typically
multiforme, malignant gliomas, and other aggressive tumors result in the recur at 1.5- to 2.5-second intervals, although both slower and faster rates
pronounced abnormalities in terms of focal continuous polymorphic delta can be seen (30). The periodic complexes are usually unilateral, but they can
activity and localized attenuation of background activities (12). Bilateral also be bilateral and occur either independently or time-locked on the two
but lateralized slow-wave activities are characteristic of frontal lobe tumors. sides, such as in the case of BIPLEDs or generalized periodic epileptiform
A B
Figure 8.11: EEG in brain abscess. A: The EEG displays ongoing left hemispheric rhythmic activity consistent
with status epilepticus in a patient with a brain abscess resulting from a recent emergency surgery from de-
compression of a left frontal hemorrhage. B: MRI of the patient.
discharges (GPEDs). PLEDs usually appear before changes on head CT but neurodegenerative diseases characterized by rapidly progressive dementia
not before abnormalities on brain MRI. Although this periodic pattern is and neuropsychiatric symptoms. They are briefly discussed here as a type
usually seen in adults with herpes simplex encephalitis, it has been reported of encephalitis. Initial EEG changes are nonspecific and mild. However, as
in infants and children. the disease progresses, the EEG becomes more characteristic, consisting of
HSV type 2 causes encephalitis in neonates and this is associated with a continuous generalized, bisynchronous, periodic sharp waves occurring at
distinctive periodic EEG pattern. The periodic discharges are often not re- intervals of 0.5 to 1 second with a duration of 200 to 400 milliseconds. This
stricted to the temporal lobe and are multifocal. Discharges often have their pattern evolves with disease progression to a burst-suppression pattern and
own morphology and periodic interval depending on the cortical generator ultimately diffuses suppression (32).
from which it emanates. Focal spikes and seizures are also common. Other Subacute sclerosing panencephalitis (SSPE) is a late complication in
forms of focal encephalitis cause focal slowing and spikes, but PLEDs are children who survived a measles infection and is associated with rapid in-
rare (31). tellectual decline, anorexia, spasticity, seizures, and other symptoms. The
Two other encephalitidies have characteristic EEG patterns. Prion dis- signature EEG in this condition is characterized by periodic large-amplitude
eases such as CJD, fatal familial insomnia, and others are infectious complexes consisting of high-voltage, repetitive polyphasic and sharp- and
slow-wave complexes up to 2 seconds in duration, occurring several times present yet the patient has no signs or symptoms, there is a risk of vascular
per minute (33). occlusion and impending infarction.
Viral encephalitis from various pathogens may result in EEG abnor-
malities that range from mild generalized slowing to severe findings such as Hemispheric Stroke
burst-suppression patterns and other findings. These EEG results are not The most common cause of hemispheric ischemic lesion is atherosclerotic
specific or diagnostic. The best use of EEG in encephalitis management disease of the internal carotid artery or MCA. Size of infarct and clinical
is serial recording as this may provide some basis for prognostication for symptoms depend on localization and collateral circulation. An infarct
patient recovery. may encompass the entire territory supplied by carotid artery, followed
in a few days by severe edema, raised intracranial pressure, transtentorial
herniation, and even death. At the other extreme, occlusion of the carotid
Cerebrovascular Disease artery may occur without obvious clinical deficits because of adequate
Subdural Hematoma collateral circulation. In acute stages, EEG is usually the most sensitive
test demonstrating abnormality. Massive hemispheric infarcts due to ca-
Slowing of the background frequencies, such as a slow alpha rhythm and par- rotid occlusion causes marked EEG abnormalities (Fig. 8.12). These ab-
oxysmal slow activity and epileptiform discharges have been reported in most normalities can include the following (4,9,37): (a) Widespread arrhythmic
patients with acute subdural hematomas. Electroencephalographic abnor- delta activity occurring over the involved hemisphere, most prominently
malities may not be related to the size of the hematoma. One study suggested in the temporal or frontotemporal region. In patients with smaller hemi-
that acute and subacute hematomas are associated with changes in EEG am- spheric infarcts, EEG from an involved hemisphere usually remains nor-
plitude, while chronic hematomas are associated with changes in frequency, mal. (b) Ipsilateral alpha rhythm may be absent or of lower amplitude
that is, increased slow activity (34). Case series have mentioned PLEDs as a and slower frequency. Reactivity of the alpha rhythm may diminish or
common EEG finding in acute subdural hematoma, although they have been disappear. Sleep spindles may also disappear. (c) Extensive infarcts may
seen after subdural hematomas have been evacuated as well (35). markedly decrease or suppress normal and abnormal electrocerebral ac-
In a landmark study of patients with unilateral chronic subdural hemato- tivity over the affected hemisphere during the first few days. These may
mas and herniations who underwent Xenon CT and EEG, increased blood also cause ipsilateral voltage depression, and prominent contralateral slow
flow was noted in areas where alpha- and beta-range activities predomi- activity can lead to erroneous lateralization. (d) In patients with smaller
nated, while blood flow was decreased in areas where slower frequencies hemispheric infarcts, EEG from uninvolved hemisphere usually remains
predominated (36). Furthermore, electrical activity correlated with thalamic normal. (e) With extensive infarcts causing cerebral edema and displace-
rather than cortical blood flow, leaving the authors to conclude that the ment of midline structure, variable degrees of slow activity appear in con-
thalamus is the source of abnormal EEG activity in this population. Never- tralateral hemisphere, often with bilateral, intermittent, rhythmic, 2 to
theless, it is important to note that patients with chronic subdural hemato- 3 per second delta activity (IRDA), which may be marked in the frontal re-
mas can also have normal EEGs. gion such as FIRDA (Fig. 8.13). Marked diffuse EEG changes may make
lateralization difficult. With acute hemispheric infarctions, particularly
Transient Ischemic Attack embolic, epileptiform activity occurs commonly and tends to be periodic,
The EEG is usually normal in patients with transient ischemic attacks; how- such as PLEDs. Such patients are usually obtunded and have focal seizures
ever, if the EEG is performed at or in close proximity at the time a patient with corresponding neurological deficits. PLEDs and clinical manifesta-
is symptomatic, there will often be focal slowing in the appropriate vascular tions may resolve in 1 to 2 weeks.
territory even though CT or routine MRI scans are likely to be normal. In patients with large MCA infarctions, brain edema may lead to a malig-
Chronic ischemia within the middle cerebral artery (MCA) territory is as- nant course, with up to 80% mortality. An interventional treatment strategy
sociated with intermittent, low-voltage delta or theta activity, mainly over must be started before the deterioration begins. In one of the largest prog-
the temporal areas. When focal or lateralized slow-wave activities abruptly nostic studies of early EEGs within 24 hours after stroke onset in patients
Figure 8.12: Hemispheric slowing and PLEDs after a hemispheric stroke

involving the left hemisphere.
suffering a large MCA infarct, the results indicated the absence of delta stroke outcomes as validated on the National Institute of Health Stroke
activity and the presence of theta and fast beta activities within the stroke Scale (38).
area predict a benign course (16), whereas diffuse generalized slowing and Single lacunae or other discrete small subcortical lesions usually produce
slow delta activity in the ischemic hemisphere may point to a malignant little or no change in EEG acutely. Only 9% of lacunar infarcts are accom-
course. panied by ipsilateral slow-wave activity. Although 53% of patients with lacu-
Infarction due to the occlusion of the anterior cerebral artery is rare. nar infarcts will have mild EEG abnormalities, most of these reflect previous
EEG findings consist of ipsilateral frontal delta activity, either arrhythmic strokes or are unexplained.
or rhythmic or both, and depression of the anterior beta activity.
Frequency analysis and topographic EEG mapping may be superior Vertebrobasilar Ischemia
to routine EEG in detecting and localizing focal abnormalities following Ischemia in the vertebrobasilar territory includes infarction of the brain
stroke (Fig. 8.14). These methods also seem to correlate most closely with stem, diencephalon, or cerebellum, with varying neurological deficits de-
regional cerebral blood flow (37). Several recent studies suggest that quanti- pending on the specific artery involved and extent and location of the infarct.
tative EEG (QEEG) measures of cerebral pathophysiology in acute or sub- Less than one-third of patients with limited infarcts to the brain stem show
acute stroke might augment prognosis regarding patient outcomes. QEEG even slightly altered EEGs. Basilar artery occlusion infarcting ventral pons
delta power measures in acute stroke are highly correlated with ischemic but sparing the tegmentum causes a distinctive clinical picture which has
Figure 8.13: FIRDA. In this EEG, we see FIRDA after a left hemispheric
stroke. Note the generalized distribution of the rhythmic delta despite
the focal pathology.
been termed locked-in syndrome. Uncomplicated strokes or other lesions Rarely, lesions of the rostral brain stem show diffuse monorhythmic alpha
of the lower pons and medulla are not accompanied by EEG abnormalities. frequency activity that is a variation of the alpha coma pattern (Fig. 8.15).
Lesions of the rostral pons in midbrain have variable effects on the EEG, Jouvet (39) correlated sites of brain stem lesions with alterations in con-
largely dependent on the extent to which the reticular activating system is sciousness and changes in EEG activity. The following are general rules re-
damaged, for example, patients with infarcts that affect the ventral pons but garding the EEG and correlations with brain stem lesions: (a) Lesions of
spare the pontine tegmentum, producing the locked-in syndrome in which medulla oblongata and caudal pons usually do not alter consciousness or
the patient is mute and quadriplegic because of disruption of descending the EEG (39). (b) Extensive lesions of the upper pons and lower mesen-
motor pathways but fully conscious with a normal EEG because the re- cephalon involving more than one-half of the tegmentum usually causes
ticular activating system is spared. When the reticular activating system in coma. Electroencephalograms may show alpha activity that does not react
the rostral pons, midbrain, or thalamus is involved, patients are comatose, to external stimuli. Although vital in maintaining consciousness, mesopon-
their EEG shows various types of diffuse background abnormalities, in- tine regions seemingly contribute little to the genesis of EEG activity. (c)
cluding both rhythmic and arrhythmic frequencies, widespread paroxysmal Lesions of the rostral brain stem and caudal diencephalon cause not only
theta and delta waves, and abnormal absent reactivity to various stimuli. deep coma but also diffuse nonreactive theta and delta activity.
on arteriographic demonstration of the cause of lesion and partial depen-

dence on refined CT scan methods, there is no practical need for an EEG in
the search for the correct localization. The EEG, however, remains a valu-
able indicator of the general state of the cerebral functioning (27,40–43).
Prolonged vasospasm and a decrease of cerebral blood flow may lead to
dementia and diffuse cerebral atrophy. The area of massive vasospasm cor-
relates with an area of local EEG slowing.
Ruptured bifurcation aneurysms are the most common cause of sub-
arachnoid hemorrhage. Massive bleeding from a ruptured aneurysm into
the cerebral parenchyma is prognostically ominous and can be fatal within
less than an hour. The EEG patterns of ventral cerebral hematomas result-
ing from such bleeding are characterized by pronounced regional polymor-
phic delta activity. This delta activity is often more pronounced than what
would be expected from an acute MCA ischemic event.
In survivors of subarachnoid hemorrhages from aneurysms, epileptic sei-
zures have been found in almost 12%. Marked EEG changes with spikes
were also found. Scott and Cabral (44,49) stressed the frequent occurrence
of epileptic seizures following intracranial aneurysm surgery such as clip-
ping and wrapping.
AVMs are a cause of subarachnoid hemorrhage but can be much less se-
vere and less life-threatening than a bleeding from a ruptured aneurysm.
These malformations often give rise to focal or generalized epileptic seizures
that start between the ages of 10 and 35. The EEG of patients with AVM
Figure 8.14: EEG spectral analysis. The figure displays a typical EEG spectral has been described as abnormal in all observed cases. The interpretation of
analysis display. the abnormality is beset with problems because a sizable number of cases
may show an erroneous lateralization with slowing or focal activity over the
wrong hemisphere, that is, the hemisphere without the lesion. It is postu-
Thalamic Hemorrhage lated that the pathophysiological rationale for this observation is likely due
Thalamic hemorrhage usually causes temporary loss of consciousness. to an intracerebral steal phenomenon. This unusual EEG finding likely in-
Larger hemorrhages may give rise to ipsilateral delta activity. There is often dicates a lack of consistent of hypoxic injury to the involved cortical tissue.
a reduction to alpha rhythm in the case of anteroventral thalamic damage.
Lack of sleep spindles is not infrequent. Role of the EEG in Stroke
Currently, EEG plays only a limited role in the management of patients
Subarachnoid Hemorrhage, Intracranial with stroke. In the first 48 to 72 hours, the degree of focal slowing gener-
Aneurysms, and AVMs ally correlates with a clinical deficit. Clinical worsening as a result of stroke
The EEG in subarachnoid hemorrhage with acute meningeal signs typically progression or the consequences of developing edema and mass effect is
shows diffuse changes, disorganization, disruption of the alpha rhythm, and accompanied and sometimes preceded by deterioration of EEG activity.
excessive slow activity. Occasionally, lateralization of the slow activity may Marked hemispheric slowing following a transient ischemic attack, es-
be indicative of the primarily involved hemisphere. With total dependence pecially when routine head CT or brain MRI is normal, likely indicates
Figure 8.15: In this EEG of a patient with embolic stroke, we see left
hemispheric slowing and a nonreactive persistent nonresponsive EEG
over the right hemisphere.
marginal perfusion and chronic ischemia. This finding adds urgency to the was either continuous or nearly so. Other reports have also emphasized the
evaluation and to the consideration of surgical or endovascular interven- presence of focal polymorphic delta activity and rhythmic epileptiform dis-
tion. Epileptiform discharges, including PLEDs, are highly correlated with charges. In a minority of patients, abnormal fast-frequency rhythms were
clinical seizures occurring during the first few weeks following a stroke. Fi- also noted.
nally, EEG is essential to identify patients who, although are completely
paralyzed and unable to speak, are conscious and aware such as in the CONCLUSION
locked-in syndrome (45–47).
EEG serves an important role in the diagnosis and management of a va-
FOCAL CORTICAL DYSPLASIA riety of focal encephalopathic lesions. Focal lesions may produce both
nonepileptiform (i.e., focal slowing, morphological or amplitude changes)
Focal cortical dysplasia is a common cause of epilepsy, especially in chil- and epileptiform abnormalities such as PLEDs. Although imaging has re-
dren. In a seminal series by Raymond (48), 22 patients with localized cor- placed some aspects of EEG for certain pathologies, EEG still provides a
tical dysgenesis and seizures beginning in childhood from age 3 weeks to powerful noninvasive, inexpensive, yet important window to a variety of
10 years with the pathology were studied. The main EEG findings were neuropathologies. Recent advances in quantitative EEG promise to pro-
(a) age-appropriate background rhythms; (b) localized slow-wave activity vide novel ways to use EEG waveforms prognostication of recovery after
in half the patients; and (c) focal epileptiform discharges in a vast major- a stroke or predicting malignant courses that require immediate invasive
ity of patients. A distinctive feature of the epileptiform activity was that it therapy.
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9 Progressive Childhood Encephalopathy
DOUGLAS R. NORDLI JR. • DARRYL C. DE VIVO
Introduction Schindler Disease

Limited Repertoire of the Immature EEG Mucopolysaccharidoses
The EEG Hallmark of a Pediatric Progressive Neuronal Ceroid Lipofuscinoses
Encephalopathy Alpers Disease (Progressive Infantile Poliodystrophy)
A Red Flag for IEMs: Spectrum of Epileptic Congenital Disorder of Glycosylation
Encephalopathies Metabolic Disorders of Childhood and Adolescence
Age Categorization Homocystinuria
Neonatal Adrenoleukodystrophy
EME—A Red Flag for IEM Lysosomal Disorders
Other Important IEMs Causing Seizures in the Neuroaxonal Dystrophies
Newborn
Neuronal Ceroid Lipofuscinosis, Type III (Spielmeyer-
Metabolic Disorders of Early Infancy Vogt Disease or Late-Onset Batten Disease)
West Syndrome: A Red Flag for IEM Progressive Myoclonus Epilepsies
Lysosomal Disorders Dentatorubral-Pallidoluysian Atrophy
Disorders of Vitamin Metabolism Other Encephalopathies Manifesting in Infancy,
Glucose Transporter 1 Deficiency Syndrome Childhood, and Adolescence
Organic Acidurias Fragile X Syndrome
Aminoacidurias Angelman Syndrome
Menkes Disease (Kinky Hair Disease) Rett Syndrome
Progressive Encephalopathy with Edema, Down Syndrome
Hypsarhythmia, and Optic Atrophy The Role of the EEG in a Child with a Suspected
Metabolic Disorders of Late Infancy Progressive Encephalopathy
Metachromatic Leukodystrophy References
258
Progressive Childhood Encephalopathy 259
Introduction for age; multifocal spikes are present; and sometimes normal physiological
hallmarks, like sleep spindles, are lost. This pattern is etiologically nonspe-
This chapter will consider those progressive pediatric encephalopathies that cific and is frequently found in children with epileptogenic encephalopathies
present with seizures where electroencephalography (EEG) plays a large role (see pattern 4a in Chapter 10), of which only a subset will be caused by
in the diagnostic evaluation. The EEG can be useful in several ways. A care- IEMs.
ful examination of the background can help to confirm the clinical suspi- The most severe disorders will produce even more dramatic changes with
cion of an encephalopathy, even in mildly affected children. Furthermore, if some degree of discontinuity in the tracing. In certain cases, this may only
serial studies are performed, deterioration of the background may indicate a be apparent in the sleep tracing, but in the most severe, it will be present
progressive encephalopathy. Distinguishing static from progressive illness is in awake and asleep. In these conditions, the epilepsy itself may contrib-
a very useful clinical distinction, but EEG provides more information than ute to the encephalopathy and they are referred to as “epileptic encepha-
just confirmation of a progressive encephalopathy. There are certain EEG lopathies” (EEG pattern 4b in Chapter 10). There is a spectrum of these
patterns that are highly suggestive and should prompt an evaluation for disorders where the precise clinical and electrographic manifestations are
an inborn error of metabolism (IEM). In rare and selected circumstances, age-dependent. In neonates with severe conditions, a burst-suppression
the EEG findings may suggest a specific biochemical cause, or a discrete pattern is seen, whereas in infancy, hypsarhythmia predominates. It is
list of conditions. In addition to these diagnostic considerations, the EEG not until childhood that well-formed generalized spike-wave discharges
may be one of the most sensitive measures to gauge improvement in those (SWDs) are seen.
situations where effective treatment is possible (e.g., pyridoxine-dependent
epilepsy).
A Red Flag for IEMs: Spectrum of Epileptic
Encephalopathies
Limited Repertoire of the Immature EEG
The most important EEG patterns indicative of an IEM are seen in the
There is a very important caveat that must be stated before any further spectrum of severe epileptic encephalopathies. These extend from Oh-
discussion: in the majority of circumstances, the EEG features are not spe- tahara syndrome (early infantile epileptic encephalopathy or EIEE), to
cific for any particular disorder. Considering that there are over 200 IEMs West syndrome (WS), onto late infantile epileptic encephalopathy (LIEE),
associated with seizures, the range of EEG abnormalities seen in clinical to Lennox-Gastaut syndrome (LGS). This concept is explained in detail
practice is remarkably constrained. This may relate to the limited repertoire in Chapter 10. In these conditions, the electro-clinical expression is largely
of the EEG expression in the very young or to shared pathophysiological dependent on the age of the child, but there are several common EEG fea-
mechanisms in the advanced stage of many diverse conditions. While one tures. In nearly all cases, the backgrounds will be slowed and there will
might expect to see a much greater repertoire of abnormalities, experience be multifocal spikes with variable morphology (pleomorphic multifocal
teaches us otherwise; even the most skilled pediatric electroencephalo spikes). In addition, the background will show some degree of disconti-
graphers cannot suggest a specific diagnosis in most patients with IEMs nuity. In the most severe cases, it is a burst-suppression pattern, particu-
simply by examining the EEG. larly with those patients who present in the neonatal and early infantile
period. Those who present slightly later, approximately 6 months of age
and greater, will often have hypsarhythmia. It is rare to see a child present-
The EEG Hallmark of a Pediatric ing with LIEE and LGS as the manifestation of their IEM—they usually
Progressive Encephalopathy have symptoms before then, or conversely, milder conditions that present
with less dramatic EEG features. Children presenting later in childhood or
There is, instead, a remarkably similar pattern of EEG abnormalities in most adolescence often have multifocal or generalized spikes superimposed on
cases: the background is slowed; there is lack of the expected organization slowed but continuous backgrounds.
Age Categorization epileptic spasms, with a burst-suppression pattern. The burst-suppression

pattern often has variable intervals between the bursts and may be state
Given all this, it is helpful to organize progressive pediatric syndromes by dependent (Fig. 9.1). Published causes of EME include nonketotic hyper-
age of presentation, highlighting prototypic EEG presentations in each age glycinemia, methylmalonic academia, propionic academia, d-glyceric aca-
group. Wherever possible, we have underscored specific EEG features that demia, sulfite oxidase deficiency/molybdenum cofactor deficiency, Leigh
are particularly declarative. For a comprehensive listing or further details, syndrome, carbamyl phosphate synthetase deficiency, pyridoxine depen-
the interested reader is referred to resources such as Online Mendelian In- dency, Menkes disease, and peroxisomal disorders. An inspection of this
heritance in Man (OMIM—www.ncbi.nlm.nih.gov/omim). list shows that the majority of these are organic and aminoacidurias, and
the most prominent of these is nonketotic hyperglycinemia. One could sim-
NEONATAL plify this list to the following six considerations: organic/amino academies,
including nonketotic hyperglycinemia, urea cycle defects, mitochondrial dis-
There are four well-characterized epilepsy syndromes presenting in the new- orders, defects of the peroxisomes, Menkes disease, and pyridoxine depen-
born; two have largely normal EEG backgrounds and are not associated with dency (Tables 9.1 and 9.2).
IEMs: benign neonatal convulsions and benign familial neonatal convulsions.
Two others have markedly disorganized backgrounds with burst suppression: A Prototypic Cause of EME: Nonketotic Hyperglycinemia
early myoclonic encephalopathy (EME) and Ohtahara syndrome. EME is or Glycine Encephalopathy
the prototypic epilepsy syndrome in this epoch of life associated with inborn In this autosomal recessive inborn error of amino acid metabolism, also
errors. There are very rare case reports of IEM in Ohtahara syndrome. known as glycine encephalopathy, large amounts of glycine accumulate in
the body fluids because of a defect in the multienzyme complex for glycine
EME—A Red Flag for IEM cleavage. This mitochondrial enzyme system has four protein components
(P, H, T, and L). The most common mutation causes P protein dysfunction.
The neonatal epilepsy syndrome most clearly associated with IEM is EME. The pathophysiological processes have not been fully elucidated, but the el-
This syndrome is characterized by refractory seizures, often myoclonic or evated glycine level is believed to affect the central nervous system through
FIGURE 9.1: EME. This neonate was born at 38 weeks and had erratic
myoclonia. Note the burst-suppression pattern characteristic of this
condition.
TABLE 9.1 IEMs Causing EME its roles as an inhibitory transmitter in the brainstem and spinal cord and
excitatory transmitter acting upon NMDA receptors in the cortex. Glycine
Organic/amino acidurias may also impair cellular energetics by interfering with citrate synthetase
Urea cycle defects
function and mitochondrial electron transport.
From the early descriptions of this disorder in 1965 and 1968, it was ap-
Disorders of subcellular organelles
parent that affected neonates usually have lethargy, respiratory difficulties,
Peroxisomes
Mitochondria and seizures in the first 48 hours (1). Hiccoughs may be seen by fourth or
fifth day of life. Seizures are often myoclonic or spasms and accompanied
Menkes disease
by a burst-suppression pattern (2). As patients with these disorders ma-
Pyridoxine dependency ture, infantile spasms may persist, and the EEG often reveals hypsarhyth-
mia. Cortical malformations or corpus callosum defects may be present.
Recently, diffusion-weighted changes have been noted in the acute stages on
TABLE 9.2 Important Diagnostic Tests for EME MRI, which may be suggestive of the disorder (3).
Notably, a transient form of nonketotic hyperglycinemia exists with simi-
Complete blood count lar early clinical and biochemical findings. In this condition, however, gly-
Chemistry profile including liver function tests cine concentrations normalize between 2 and 8 weeks after birth, and the
Urine organic acids prognosis is favorable.
Amino acid profile in CSF, blood, and urine The characteristic EEG background is burst suppression. Synchronous
diffuse bursts are separated by several seconds of profound background
Lactate/pyruvate in CSF and blood
attenuation. The bursts themselves are composed of irregular slow-

Serum ammonia
wave activity with superimposed multifocal sharp transients. The period
Urine copper, serum cerruloplasmin (check for Menkes) between the bursts varies from moment to moment. The level of alertness
Very long chain fatty acids and age of the child can substantially modify the continuity of the tracing
Pyridoxine challenge, pyridoxal 5-phosphate challenge, or both (Fig. 9.2).
FIGURE 9.2: This tracing is from a 3-month-old infant with nonketotic

hyperglycinemia. There is still some hint of discontinuity to the tracing,
but it no longer meets criteria for burst suppression. In addition to myo-
clonia, the patient also had epileptic spasms (not shown here).
Other Important IEMs Causing Seizures TABLE 9.3 Epileptic Encephalopathies in the Newborn
in the Newborn
Nonketotic hyperglycinemia
Some newborns will not have a well-characterized epilepsy syndrome, while Isovaleric, methylmalonic, and propionic aciduria
others that do not fit into either Ohtahara or EME syndrome can be consid-
Maple syrup urine disease
ered to have an early onset epileptic encephalopathy (EOEE) (4). Still others
may show a mixture of focal, myoclonic, and tonic seizures, with back- Pyridoxine dependency, pyridoxal phosphate dependency
grounds that are abnormal but do not meet criteria for burst suppression. Biotinidase deficiency
As a consequence, virtually any neonate with persistent seizures without a D-2-hydroxyglutaric aciduria
clearly identifiable cause should be evaluated for an IEM and the newly dis-
3-Phosphoglycerate dehydrogenase deficiency
covered channelopathies.
IEMs that present in the newborn include nonketotic hyperglycinemia; Adenylosuccinate Lyase deficiency
isovaleric, methylmalonic and propionic aciduria; maple syrup urine d isease; MTHFR deficiency
pyridoxine dependency, pyridoxal phosphate dependency; biotinidase defi- GABA transaminase deficiency
ciency; d-2-hydroxyglutaric aciduria, 3-phophoglycerate dehydrogenase CDG
deficiency; Adenylosuccinate Lyase deficiency methylene tetrahydrofolate
reductase (MTHFR) deficiency; GABA transaminase deficiency; congenital Developmental DEND
disorders of glycosylation; developmental delay, epilepsy and neonatal dia- HIHA
betes (DEND); hyperinsulinism, hyperammonemia (HIHA); neonatal ceroid Neonatal ceroid lipofuscinosis with cathepsin deficiency
lipofuscinosis with cathepsin deficiency; creatine deficiency; peroxisomal Creatine deficiency
disorders, urea cycle disorders; dihydropyrimidine dehydrogenase deficiency;
Peroxisomal disorders
molybdenum cofactor deficiency; carnitine palmitoyltransferase types I and
II; pyruvate carboxylase deficiency; pyruvate dehydrogenase deficiency; and Urea cycle disorders
disorders of biotin. In short, every class of metabolic derangement may Dihydropyrimidine dehydrogenase deficiency
present in the very young, and most of these have few distinguishing clues Molybdenum cofactor deficiency
(Table 9.3).
Carnitinepalmitoyl transferase types I and II
Pyridoxine Dependency Pyruvate carboxylase deficiency
In this condition, refractory seizures typically develop within the first sev- Pyruvate dehydrogenase deficiency
eral days after birth characterized by infantile spasms or a variety of focal, Disorders of biotin
myoclonic, and atonic seizures (5). A recent review highlights the salient
features and summarizes the biochemistry (6). The condition is caused by
mutations in the antiquitin gene, which codes for an enzyme in lysine me- The EEG is characterized by generalized bursts of high-voltage delta with
tabolism (α-aminoadipic semialdehyde dehydrogenase). As a result a variety intermixed spike-and-sharp waves and periods of asynchronous attenuation
of substrates accumulate, including α-aminoadipic semialdehyde (AASA) (Fig. 9.3A). Since 1954, it has been known that treatment with high doses
and l-Δ1-piperideine-6-carboxylate (P6C). The latter undergoes a chemical (100 to 200 mg intravenously) of pyridoxine can have a dramatic early effect
condensation with pyridoxal 5-phosphate (PLP), thereby lowering PLP free on seizures and the resting EEG (5). There may be immediate cessation of
levels. Both AASA and P6C may be neurotoxic in and of themselves, and seizures, conversion of the EEG to a burst-suppression pattern, and later
low PLP levels most likely alter the balance between glutamate and GABA normalization of the EEG with subsequent doses (see Fig. 9.3B). Intrave-
since PLP is a necessary cofactor for glutamate decarboxylase function. nous (IV) treatment or even oral replacement can result in transient apnea;
so practitioners should be prepared to support respirations before admin- analysis of the same substances. Treatment regimens vary. The recom-
istering pyridoxine. The onset of this disease may occur after the newborn mended oral dose of either pyridoxine or PLP is 30 mg/kg/day (6,7). Since
period, making it a consideration in older infants with refractory seizures there is no readily available IV preparation of PLP, some authors administer
of any type. 100 mg of IV pyridoxine, and if there is no clear EEG response, repeat the
A related and recently characterized condition is pyridoxal 5′-phosphate- dose and then treat with oral PLP while the results of biochemical tests
dependent epilepsy (PLP-DE). This is most often due to mutations in the including CSF, serum markers, and urine markers of PDE and PLP-DE
gene encoding pyridoxine 5′-phosphate oxidase (PNPO). Like pyridoxine- return. Suspected cases can be confirmed with genetic mutational analysis
dependent epilepsy (PDE), this condition presents with intractable neonatal of either conditions.
or infantile seizures, but instead responds only to PLP, the active form of
pyridoxine. Molybdenum Cofactor Deficiency
and Sulfite Oxidase Deficiency
Evaluation and Treatment of PDE and PLP-DE These rare conditions manifest shortly after birth with a progressive enceph-
Plasma samples for pipecolic acid as well as urine and plasma samples of alopathy, feeding difficulties, hypotonia, and refractory partial, myoclonic,
AASA should be obtained in at-risk individuals. Some also advocate CSF or apparently generalized seizures. Dysmorphic features, lens dislocation,
Figure 9.3: Pyridoxine dependency.

A: EEG of a 4-week-old child with intrac-
table neonatal seizures. There are bursts
of high-voltage delta with intermixed
spikes and sharp waves and asynchro-
nous epochs of attenuation. B: EEG of
the same child after pyridoxine treat-
ment. The tracing is now continuous, and
only occasional epileptiform discharges
persist. (Courtesy of C. Stack, MD, and
L. Laux, MD, Children’s Memorial Hospi-
tal, Chicago, Illinois.) A
The EEG shows multifocal spikes with or without burst suppression.

Burst suppression may evolve in the second day of life and persist despite
treatment with anticonvulsant medications (12).
Peroxisomal Disorders
Disorders of the peroxisome have been divided into three categories: dis-
orders of peroxisomal biogenesis (Zellweger syndrome, neonatal adreno-
leukodystrophy [NALD], infantile Refsum disease); disorders of a single
peroxisomal enzyme (X-linked adrenoleukodystrophy, acyl-coenzyme A
[CoA] oxidase deficiency [AOXD]); and disorders with deficiencies of mul-
tiple peroxisomal enzymes (rhizomelic chondrodysplasia punctata). This
discussion will be limited to Zellweger syndrome, AOXD, and NALD.
Zellweger Syndrome
Zellweger syndrome is the most frequent peroxisomal disorder in early
infancy. It is caused by mutations in any of several genes involved in per-
oxisome biogenesis, resulting in severe brain dysfunction, craniofacial defor-
mities, liver disease, and absence of peroxisomes.
Dysmorphic features may be noted shortly after birth. Within the first
week, the affected child develops a severe encephalopathy, hypotonia, and
hyporeflexia. Findings on neuroimaging and pathological examination are
distinctive, with pachygyria or polymicrogyria localized to the opercular re-
gion and cerebellar heterotopias.
Patients with Zellweger syndrome have focal motor seizures of the arms,
B legs, or face. Their seizures do not usually culminate in generalized seizures.
Myoclonic seizures and spasms have also been described. Interictal EEGs
of the patients with Zellweger syndrome showed infrequent bilateral inde-
pendent multifocal spikes, predominantly in the frontal motor cortex and its
surrounding regions (13). Less frequently, hypsarhythmia is observed. Some
and hepatomegaly are characteristic (8–10). Neuroimaging may show poor have noted prolonged runs of vertex negative spikes (14,15).
differentiation between the gray and white matter, severe cerebral and cer-
ebellar atrophy, and multiple cystic cavities in the white matter (WM). The Neonatal Adrenoleukodystrophy
relatively more common molybdenum cofactor deficiency results from an NALD, an autosomal recessive disorder with pathological and biochemical
absence of the hepatic cofactor, which leads to a combined enzyme defi- findings resembling those of X-linked adrenoleukodystrophy, bears some
ciency of the three molybdenum-dependent enzymes: sulfite oxidase, xan- similarity to Zellweger syndrome but differs in some respects, including the
thine dehydrogenase, and aldehyde oxidase. Reduction in sulfite oxidase ability to synthesize plasmalogens in NALD (16). Distinguishing features in-
activity causes an accumulation of sulfite in the brain, which is toxic to its clude absent or minimal facial dysmorphisms, later onset of seizures, absent
function. This disease may be caused by mutations in the genes MOCS1, or minimal cerebral malformations, and longer life span. Described seizures
MOCS2, or gephyrin (GEPH) (11). include tonic, clonic, myoclonic, or epileptic spasms (17). No characteristic
EEG pattern has been defined, but descriptions have included high-voltage Maple Syrup Urine Disease
slowing, polymorphic delta activity, multifocal paroxysmal discharges, burst This disease, resulting from a defect in the branched chain α-keto acid de-
suppression, and hypsarhythmia. hydrogenase complex, was first reported by Menkes et al. (22) in 1954. The
Acyl-Coenzyme A Oxidase Deficiency enzyme defect leads to accumulation of the branched-chain amino acids—
valine, leucine, isoleucine—and their keto acids in the body tissues and flu-
AOXD was initially described in two siblings in 1988 (18). Clinical features ids. Pathological studies have revealed diffuse myelin loss and increased total
include hypotonia, pigmentary retinopathy, hearing loss, developmental de- brain lipid content. Cystic degeneration of the WM associated with gliosis
lay, adrenocortical insufficiency, absence of dysmorphic features, and onset is seen. Disordered neuronal migration may occur with heterotopias and
of seizures shortly after birth. Serum levels of very long chain fatty acids disrupted cortical lamination.
are elevated, with normal levels of pipecolic acid. Cortical malformations Feeding difficulties and lethargy are observed during the first to second
are generally absent, and the interictal EEG may show continuous, diffuse, weeks after birth. If left untreated, symptoms may progress to stupor, ap-
high-voltage theta activity. nea, opisthotonus, myoclonic jerks, and partial and generalized seizures. A
Urea Cycle Disorders characteristic odor can be detected in urine and cerumen, but this may not
be detectable until several weeks after birth.
There are six enzymes in the urea cycle that convert ammonia to urea; five of The EEG shows diffuse slowing and a loss of reactivity to auditory stim-
these may have defects that cause neonatal seizures. The associated diseases uli. A distinctive comb-like rhythm has been described, with excessive bursts
and their incidences are as follows: carbamoyl phosphate synthetase defi- of a centrally predominant mu-like rhythm, which resolve with dietary ther-
ciency, 1 in 800,000; ornithine transcarbamylase deficiency, 1 in 80,000; ar- apy (23,24).
gininosuccinate synthetase deficiency, 1 in 250,000; argininosuccinate lyase
deficiency, 1 in 70,000; and N-acetylglutamate synthetase deficiency, with
only a few cases reported. The clinical disorder resulting from a deficiency in Organic Acidurias
the sixth enzyme, arginase, manifests later in infancy. All of these disorders The disorders of organic acid metabolism comprise a large number of inborn
are autosomal recessive except for ornithine transcarbamylase deficiency, errors, including isovaleric aciduria and several ketotic hyperglycinemic syn-
which is X-linked dominant. dromes (propionic acidemia, methylmalonicacidemia, and α-ketothiolase
The clinical manifestations are similar and result, at least in part, from deficiency).
ammonia elevations. Typically, affected newborns exhibit poor feeding, Symptoms of isovaleric aciduria, which develop during the neonatal
emesis, hyperventilation, lethargy, or convulsions 1 to 5 days after birth. period in half of the affected children, include poor feeding, vomiting,
These signs give way to deepening coma with decorticate and decerebrate dehydration, and a progressive encephalopathy manifested by lethargy,
posturing and progressive loss of brainstem function. Brain imaging and tremors, seizures, and coma. Platelet and leukocyte counts may be de-
pathological studies reveal cerebral edema with pronounced astrocytic
pressed, and the odor of the urine has been described as similar to that of
swelling. Ammonium is taken up by the astrocytes and rapidly converted sweaty feet (100). Cerebral edema is present, and seizures are most often
to glutamine in an energy-dependent process. The edema is associated with focal motor or generalized tonic. The initial EEG may be normal, but
glutamine accumulation and energy depletion. In experimental models, later studies may show deterioration, including dysmature features during
blocking glutamine synthesis has prevented cerebral edema associated with sleep (25).
hyperammonemia (19). The symptoms of propionic acidemia also appear during the neonatal
The EEG shows a low-voltage pattern with diffuse slowing and multi- period, with seizures as the first symptom in a fifth of patients. Charac-
focal epileptiform discharges (Fig. 9.4A), and sometimes sustained mono- teristic features include vomiting, lethargy, ketosis, neutropenia, periodic
rhythmic theta activity (see Fig. 9.4B) (20). In acute neonatal citrullinemia, thrombocytopenia, hypogammaglobulinemia, developmental retarda-
a burst-suppression pattern has been described, correlating with the degree tion, and intolerance to protein. Patients may have very puffy cheeks and
of hyperammonemia (21). an exaggerated Cupid’s bow-shaped upper lip. Convulsions are the rule,
A B
Figure 9.4: EEGs of a 2-week-old child with ornithine transcarbamylase deficiency. A: There is marked attenu-
ation and disorganization of the background with multifocal spikes. B: Sustained monorhythmic theta activity
is present in the frontal regions. (Courtesy of C. Stack, MD, and L. Laux, MD, Children’s Memorial Hospital,
Chicago, Illinois.)
although more limited focal seizures have also been reported. The EEG mutase. Stomatitis, glossitis, developmental delay, failure to thrive, and sei-
shows background disorganization with marked frontotemporal and oc- zures are the major features, and lesions of the globus pallidus, visible on
cipital slow-wave a ctivity (25). In 40% of affected children, myoclonic computed tomography or magnetic resonance images, are the characteristics.
seizures develop in later infancy, and older children may have atypical Diffuse tonic seizures and focal seizures with secondary generalization are
absence seizures. the most frequent seizure types. Seizures may also be characterized by eyelid
Methylmalonicacidemia is the metabolic signature of seven biochemically clonus with simultaneous upward deviation of the eyes. As in many other
distinct entities, all of which show decreased activity of methylmalonyl-CoA epileptogenic encephalopathies, the described EEG findings are multifocal
spike discharges, depressed or slowed background activity, and sometimes pathological changes could be seen in immature animals that were com-
lack of sleep spindles (25). pletely deprived of nourishment) (32). Mutations in various mitochondrial
respiratory chain complexes (I, II, and V) as well as any of the three catalytic
Pyruvate Dehydrogenase Deficiency, Pyruvate Carboxylase subunits (E1, E2, or E3) of the PDC may result in the same phenotype (33).
Deficiency, and Leigh Syndrome In addition, rare causes of Leigh syndrome include myoclonus epilepsy with
Pyruvate dehydrogenase complex (PDC) is a multienzyme conglomeration ragged red fibers (MERRF), mitochondrial encephalomyopathy with lactic
of six subunits: pyruvate dehydrogenase (E1), dihydrolipoyl acetyltransfer- acidosis and stroke-like symptoms (MELAS), and mitochondrial DNA de-
ase (E2), dihydrolipoyl dehydrogenase (E3), an E3-binding protein (E3BP), pletion. Within the first year of life, classic features include failure to thrive,
pyruvate dehydrogenase kinase (PDK), and pyruvate dehydrogenase phos- lactic acidosis, and developmental delay. As the disease progresses, infants
phatase (PDP) (5,6). The latter two components serve regulatory function. develop spasticity, abnormalities of eye movements, and central respiratory
A majority of the mutations affect the E1 alpha subunit of the PDC, which failure. A variety of seizures may occur in Leigh syndrome, including focal
impairs either stability or enzyme efficiency. Epilepsy may be due to a com- and generalized (34). Cases of infantile spasms and hypsarhythmia (35) and
bination of structural abnormalities and energy failure, leading to clastic several cases of epilepsia partialis continua (36) have also been reported. As
lesions (26,27). is the case with the vast majority of epileptogenic encephalopathies associ-
There are various clinical manifestations of pyruvate dehydrogenase defi- ated with IEMs, EEG abnormalities, although present, do not appear to be
ciency, ranging from acute lactic acidosis in infancy with severe neurological distinctive enough to allow identification of the syndrome on electrographic
impairment to a slowly progressive neurodegenerative disorder (27,28). It is criteria alone (37).
one of the most common defined genetic defects of mitochondrial energy
metabolism. Structural abnormalities, such as agenesis of the corpus cal- Disorders of Biotin Metabolism
losum, can be visible on neuroimaging. Seizures frequently occur and may Early Onset Multiple Carboxylase Deficiency
take the form of infantile spasms and myoclonic seizures. In addition to (Holocarboxylase Synthetase Deficiency)
hypsarhythmia, reported electrographic findings include multifocal slow
This rare disorder manifests in the first week after birth with lethargy, respi-
spike-and-wave discharges. Treatment with the ketogenic diet helps with the
ratory abnormalities, irritability, poor feeding, and emesis. A rash is present
paroxysmal aspects of the disorder.
in more than 50% of patients. Generalized tonic convulsions, focal motor
Three clinical types of pyruvate carboxylase deficiency are recognized: an
seizures, and multifocal myoclonic jerks develop in 25% to 50% of cases. A
infantile form (type A), a severe neonatal form (type B), and an intermit-
deficiency in the enzyme holocarboxylase synthetase leads to a decrease in
tent/benign form (type C). The neonatal type manifests with severe lactic
holocarboxylase. Because this enzyme links biotin to four carboxylases in
academia, hepatomegaly, pyramidal tract signs, and death in the first few
the mitochondrial and one in the cytosol, an inactivity of all carboxylases
months of life. The infantile form is usually lethal in infancy or early child-
results. Electrographically, either multifocal spikes or a burst-suppression
hood and begins in the first 6 months of life with episodes of lactic acide-
pattern is seen (38).
mia precipitated by an infection. Individuals with the intermittent form have
normal or mildly delayed neurologic development and episodic metabolic
acidosis. Seizures in the more severe forms are related to the hypoglycemia, METABOLIC DISORDERS OF EARLY INFANCY
which occurs secondary to dysfunction of the Krebs cycle. Hypsarhythmia,
with or without infantile spasms, may be seen (29). Treatment with ACTH West Syndrome: A Red Flag for IEM
or the ketogenic diet can be very hazardous (30,31).
Leigh syndrome (subacute necrotizing encephalomyelopathy) may be The epilepsy syndrome most closely associated with IEM in infancy is WS
caused by various metabolic defects, including cytochrome c oxidase de- (Chapter 10). The classic triad of WS is infantile spasms, developmental
ficiency, and defects in other enzymes involved in energy metabolism. (In delay, and hypsarhythmia. A large variety of different factors can cause WS,
the discussion section of his case presentation, Leigh noted that similar including IEMs. The most commonly observed are pyruvate dehydrogenase
deficiency, pyruvate carboxylase deficiency, congenital disorder of glyco- galactosylceramidase. There are four forms of galactosylceramidase: infan-
sylation type III, organic and amino acidurias, perosxiomal disorders, and tile, with onset before the age of 6 months; late infantile, with onset between
lysosomal disorders. the ages of 6 months and 3 years; juvenile, with onset between the ages of 3
and 7 years; and adult, with onset after the age of 7 years (40). The majority
Nonsyndromic Infantile Epilepsies with IEMs of cases begin within 3 to 6 months of life with irritability, poor feeding, em-
Some infants have forms of epilepsy that do not yet fit into one of the recog- esis, and rigidity. Muscular spasms induced by stimulation are prominent.
nized syndromes. Those infants with unexplained, poorly controlled seizures Blindness and optic atrophy ensue. Initially, tendon reflexes are increased;
and encephalopathy should be evaluated for IEMs. Some additional causes then they gradual diminish as breakdown of peripheral myelin occurs. Fo-
of infantile seizures are GM1 and GM2 gangliosidoses; neuronal ceroid li- cal or generalized clonic or tonic seizures and infantile spasms are seen; they
pofuscinosis; infantile neuroaxonal dystrophy; Glut-1 deficiency; late-onset may be difficult to distinguish from muscular spasms (41,42). In contrast
multiple carboxylase deficiency; disorders of cerebral and peripheral folate to what is observed in many classic WM diseases, seizures occur early in
metabolism; disorders of neurotransmitter synthesis; arginase deficiency the course of 50% to 75% of infants with Krabbe disease. EEG character-
(urea cycle defect); amino and organic acidurias; and sialidoses. istics include a hypsarhythmia-like pattern with irregular slow activity and
multifocal discharges of lower amplitude than that typically seen with WS
Lysosomal Disorders (43). In a study of seven infants by Kliemann et al. in 1969, six children
had prominent beta activity independently occurring in the posterior tem-
Tay-Sachs Disease poral regions and vertex that was superimposed over slower, high-amplitude
GM2 gangliosidosis is a lysosomal disorder that invariably includes seizures waves. This activity was observed to be state dependent and to occur in long
as a prominent feature. The infantile form of GM2 gangliosidosis includes runs without any observed clinical manifestations. In the terminal stages of
Tay-Sachs disease, caused by deficiency of hexosaminidase A, and Sandhoff the disease, little electrical activity is detected.
disease, caused by deficiency of hexosaminidases A and B.
Tay-Sachs disease, an autosomal recessive disorder, is found in the GM1 Gangliosidosis, Type I and Type II
Ashkenazi Jewish population of Eastern or Central European descent. The The infantile form of this disorder, type I, is caused by a deficiency of
enzymatic defect leads to intraneuronal accumulation of GM2 ganglioside. β-galactosidase, which leads to the accumulation of GM1 ganglioside and
Development is normal until the age of 4 to 6 months, when hypotonia and degradation products in nerve cells and other tissues. Regression of develop-
a loss of motor skills occur. Within the next 1 to 2 years, spasticity, blind- ment begins at 3 to 6 months of age with rapid neurological deterioration
ness, and macrocephaly develop. The classic cherry-red spot is present in and seizures develop by 2 years of age. Clinical features may include coarse
the ocular fundi of more than 90% of patients. At this stage, frequent focal facial features, hepatomegaly, bone deformities (dysostosis multiplex), vi-
and atypical absence seizures develop, which respond poorly to medications. sual abnormalities, hypotonia, progressive microcephaly, and hematological
Myoclonic jerks are frequent and are often triggered by the exaggerated abnormalities. Examination of the ocular fundi reveals a macular cherry-
startle response to noise. The EEG is normal early in the course of the dis- red spot. A late-infantile/juvenile form is recognized, which presents with
ease. Gradually, background activity slows with bursts of high-voltage delta cognitive delay between 7 months and 3 years of age with slow progression.
waves and very fast central spikes (39). Diffuse spike-and-sharp-wave activ- Neurological deterioration in the adult form is generally slower than in
ity can be abundant, and acoustically induced myoclonic seizures appear. the others and presents with a progressive extrapyramidal disorder. In an il-
As the disease progresses, EEG voltage declines, and background activity lustrative example of the benefits of whole-exome sequencing, an individual
becomes undifferentiated. who had escaped diagnosis for more than a decade was diagnosed by this
technique (44).
Krabbe Disease (Globoid Cell Leukodystrophy) Cerebral manifestations with regression of developmental milestones and
Another lysosomal disorder occurring at this age is globoid cell leukodys- visual symptoms typically manifest by the age of 2 to 4 years. EEG features
trophy (Krabbe disease). This disorder is caused by a deficient activity of include background slowing with increasing, irregular slow activity as the
disease progresses (45). In older patients, a fluctuating 4- to 5-Hz temporal Defects in methionine biosynthesis are also associated with seizures.
rhythmic discharge has been observed. onvulsions are frequent and are predominantly generalized, although
C
myoclonic seizures with hypsarhythmia have been reported.
Disorders of Vitamin Metabolism
Glucose Transporter 1 Deficiency Syndrome
Biotinidase Deficiency
Disorders of vitamin metabolism with symptoms that appear in early in- The glucose transporter 1 (GLUT-1) deficiency syndrome (DS), previously
fancy include biotinidase deficiency and disorders of folic acid. Biotinidase referred to as the glucose transporter protein DS, was first described in 1991
deficiency is the second disorder that can produce multiple carboxylase de- (48). This may be considered the prototype disorder of energy failure pro-
ficiency. Early onset multiple carboxylase deficiency due to holocarboxylase ducing seizures and EEG abnormalities. Affected infants become encephalo-
synthase deficiency is the other and was discussed earlier. pathic with seizures and delays of motor and mental development. Seizures
are present in 90% of patients and typically begin after the second month of
Late-Onset Multiple Carboxylase Deficiency life. Initially, they may be characterized by subtle behavioral alterations con-
(Biotinidase Deficiency) sistent with infantile focal seizures. The initial EEG may be normal or may
Seizures are a prominent feature of late-onset multiple carboxylase defi- show interictal epileptiform discharges (IEDs) in the posterior quadrants,
ciency, occurring in approximately 75% of affected children, and are the but only 17% show a persistently normal features (49). As the child ma-
presenting clinical symptoms in one-third of cases. There is a distinctive or- tures, more generalized seizures occur, manifested by nonconvulsive events,
ganic acid pattern, reflective of the various carboxylase deficiencies. Onset myoclonic jerks, or atypical absence seizures. In a recent review, generalized
of the disease process begins at the age of 3 to 6 months with hypotonia and tonic-clonic seizures and absence attacks predominate and are seen in about
psychomotor delay. Seborrheic or atopic dermatitis and alopecia are com- half of patients. These same patients may exhibit 3-Hz spike-and-wave dis-
mon. As the disease progresses, intermittent ataxia, optic atrophy, and sen- charges that look very similar to those seen in childhood absence epilepsy
sorineural hearing loss develop. Associated seizure types include generalized (pyknolepsy) (50). On careful inspection of the individual spike components,
tonic-clonic, partial, myoclonic, and infantile spasms (46). EEG findings however, one may note some variability in the morphology and amplitude
may include a burst-suppression pattern, absence of physiological sleep pat- that in addition to a mild degree of background slowing may be important
terns, poorly organized and slow waking background activity, and frequent clues to the presence of a symptomatic epilepsy (Fig. 9.5). It is interesting
multifocal spike and diffuse spike-and-slow-wave discharges (46). to reflect on the early observations of Gibbs, Gibbs and Lennox in this con-
text (51). They showed a strong influence of blood sugar levels on absence
Methylene Tetrahydrofolate Reductase Deficiency seizures and bursts of 3-Hz SWDs. In GLUT-1 DS, acute hyperglycemia
MTHFR deficiency is the most common inborn error of folate metabolism. can produce a transient improvement in the background EEG features and
This causes insufficient production of 5-methyltetrahydrofolate, which is abundance of epileptiform discharges; so pre- and postprandial tracings
needed for the remethylation of homocysteine to methionine. As a result, might be suggestive of the condition (52,53). Other observed seizures in-
there is an accumulation of homocysteine and hypomethioninemia in blood clude focal, myoclonic, drop, tonic, and very rarely, infantile spasms (49).
and body fluids. A progressive neurological syndrome can develop in in- As is seen in most of the IEMs associated with epilepsy, the EEG features in
fancy with acquired microcephaly, hypotonia, lethargy, recurrent apneas, patients with GLUT-1 DS may change over time in a given individual (49).
and seizures. The latter are characterized by intractable infantile spasms,
generalized atonic and myoclonic seizures, and focal motor features. EEG Organic Acidurias
findings vary from diffuse slowing of background activity to continuous
spike-and-wave complexes or multifocal spikes to paroxysmal bursts of gen- Seizures in early infancy may be the presenting symptom of branched-
eralized polyspikes, followed by periods of relative attenuation with a pseu- chain organic acidurias. These include isovaleric aciduria, 3-methylcrotonyl
doperiodic pattern (47). CoA carboxylase deficiency, 3-methylglutaconic aciduria with normal
FIGURE 9.5: GLUT-1 DS. A burst of generalized SWDs are seen in this
sample of EEG from a 12-year-old child. Note the variability in the mor-
phology and amplitude of the individual waveforms. In contrast, the
bursts of 3-Hz spike-wave activity in childhood absence epilepsy are very
regular or stereotyped.
3-methylglutaconyl-CoA hydratase, and 3-hydroxy-3-methylglutaric acid- Type I glutaric acidemia is a more common autosomal recessive disor-
uria. Seizures, including convulsions and infantile spasms, tend to be promi- der of lysine metabolism, which is caused by a deficiency of glutaryl-CoA
nent in 3-methylcrotonyl CoA carboxylase deficiency. dehydrogenase. Seizures are often the first clinical signs of metabolic de-
Severe developmental delay, progressive encephalopathy, and seizures compensation after a febrile illness. EEGs are initially normal, but slight
are the most common features of 3-methylglutaconic aciduria with nor- background slowing may develop during times of seizure exacerbation (25).
mal 3-methylglutaconyl-CoA hydratase (54). Seizures occur in one-third of
cases, and infantile spasms have been reported early on. In another study,
eight patients with this disorder were studied, and the most typical finding Aminoacidurias
was mild to moderate slowing of the EEG background. One patient had
multifocal sharp-wave discharges as well (25). Phenylketonuria and Hyperphenylalaninemias
Seizures are the presenting symptom in 10% of patients with 3-hydroxy- One of the most frequent IEMs, occurring in 1 in 10,000 to 15,000 live births,
3-methylglutaric aciduria, a disorder caused by the deficiency of the lyase phenylketonuria is caused by a deficiency of hepatic phenylalanine hydroxy-
enzyme that mediates the final step of leucine degradation and plays a piv- lase. As a consequence of the metabolic defect, toxic levels of the essential
otal role in hepatic ketone body production. This disorder is one of an in- amino acid phenylalanine accumulate. If these toxic levels are left untreated,
creasing list of IEMs that clinically present as Reye syndrome or nonketotic severe mental retardation, behavioral disturbances, psychosis, and acquired
hypoglycemia. The odor of the urine may resemble that of a cat. In many af- microcephaly can result. Seizures are present in 25% of affected children.
fected patients, EEGs are normal between crises. EEGs in one girl with pro- The majority of children with phenylketonuria (80% to 95%) are found to
gressive encephalopathy showed multifocal spikes and intermittent episodes have abnormalities on EEG. An age-related distribution of EEG findings
of background attenuation between crises, and focal epileptiform activity and seizure types has been observed. Low et al. (55) described characteristic
during an episode of clinical deterioration (25). features in 1957. Infantile spasms and hypsarhythmia predominate in the
Infantile spasms have been reported in patients with 3-hydroxybutyric young affected infant. As the children mature, tonic-clonic and myoclonic
aciduria. Facial dysmorphism and brain dysgenesis are prominent seizures become more frequent, and the EEG pattern evolves to mild dif-
manifestations. fuse background slowing, focal sharp waves, and irregular generalized spike
and slow waves (56). An increase in delta activity has been seen as levels hypsarhythmia on the EEG. Later, other seizure types may be seen, includ-
increased during phenylalanine loading (57). ing tonic, tonic-clonic, and absence seizures. The EEG pattern may evolve
to a slow spike-and-wave pattern.
Tyrosinemia, Type III
An inborn error of tyrosine metabolism, type III tyrosinemia METABOLIC DISORDERS OF LATE INFANCY
(4-hydroxyphenylpyruvate dioxygenase deficiency), has been reported in
a newborn with intractable seizures and in children who later developed The EEGs of infants and young children who present beyond the first year of
infantile spasms (58). The EEG pattern has been described as low voltage life are less likely to show burst suppression or hypsarhythmia. Instead, there
with spike and polyspike discharges in the parietal-occipital regions. is background slowing, loss of normal architecture, and appearance of pleo-
morphic diffuse spikes in many cases. The interictal epileptiform activity re-
mains pleomorphic, whether it is multifocal or more diffuse in its topography.
Menkes Disease (Kinky Hair Disease)
This X-linked disorder of copper absorption was first described by Menkes Metachromatic Leukodystrophy
et al. (59) in 1962. A feature of this disorder is the “kinky hair” of the head
Metachromatic leukodystrophy is the result of a deficiency of arylsulfatase
and eyebrows. A characteristic twisting of the hair shaft is noted on mi-
A. Hypotonia, weakness, and unsteady gait suggestive of a neuropathy or
croscopic examination of these poorly pigmented hairs. A ffected boys may
myopathy are the most common presenting symptoms. These are followed
be premature, may have neonatal hyperbilirubinemia, or may have hypo-
by a progressive decline in mental and motor skills, with considerable phe-
thermia. Progressive neurological deterioration with spasticity manifests by
notypic heterogeneity. Seizures are common and may occur at any stage of
the age of 3 months, and affected children may have associated bone and
the illness, particularly in those with the juvenile form (62). EEG findings
urinary tract abnormalities as well. The disease has a rapidly fatal course.
include diffuse high-voltage slowing, which may be asymmetrical, and oc-
Seizures, in the form of intractable generalized or focal convulsions, are a
casional bursts of spikes.
prominent feature in Menkes disease. Stimulation-induced myoclonic jerks
are also present. Multifocal spike-and-slow-wave activity can be seen on
EEG, sometimes resembling hypsarhythmia (60). Schindler Disease
Schindler disease results from a deficiency of α-N-acetylgalactosaminidase
Progressive Encephalopathy with (63). Affected patients appear normal at birth, but progressive neurologi-
Edema, Hypsarhythmia, and Optic Atrophy cal decline becomes evident in the second year. Manifestations include
spasticity, cerebellar signs, and extrapyramidal dysfunction. Generalized
Progressive Encephalopathy with Edema, Hypsarhythmia, and Optic tonic-clonic seizures and myoclonic jerks are common. EEG abnormalities
Atrophy (PEHO Syndrome), described by R. Salonen and colleagues in 1991, include multifocal spikes and spike-and-wave complexes.
is characterized by infantile spasms, arrest of psychomotor development,
hypotonia, hypsarhythmia, edema, and visual failure with optic atrophy Mucopolysaccharidoses
(61). Characteristic features include epicanthal folds, midfacial hypoplasia,
protruding ears, gingival hypertrophy, micrognathia, and tapering fingers. The mucopolysaccharidoses are a family of lysosomal storage disorders
Edema develops over the limbs and face. The progressive decline seen with caused by the deficiency of several enzymes involved in the degradation
this disease is suggestive of a metabolic defect, although no biochemical of glycosaminoglycans. The various mucopolysaccharidoses share many
marker has been identified. It is presumed to be an autosomal recessive dis- clinical features, including a progressive course, multisystem involvement,
order by its pattern of inheritance. Neuroimaging shows progressive brain organ enlargement, dysostosis multiplex, and abnormal facial features. The
atrophy and abnormal myelination. Hypoplasia of the corpus callosum has most common mucopolysaccharidosis is Sanfilippo syndrome (mucopoly-
been reported. Seizures generally begin as infantile spasms with associated saccharidosis, type III), in which only heparitin sulfate is excreted in the
urine. Generalized seizures develop in about 40% of patients with Sanfilippo Type II NCL shares many clinical features with the infantile form. In con-
syndrome, but antiepileptic drug treatment may be successful in halting sei- trast to type I NCL, no ethnic predilection for type II NCL exists. Early
zures. Progressive dementia and severe behavioral disorders help to distin- development is normal or may be mildly delayed. By the age of 2 to 4 years,
guish from a primary generalized epilepsy. In a careful study of one patient, insomnia, an early clinical sign, and intractable seizures develop. Multiple
the EEG showed lack of normal sleep staging, absence of vertex waves and seizure types develop with staring spells and generalized tonic-clonic, myo-
sleep spindles, and an unusual alteration of low-amplitude fast activity clonic, and atonic components. As the disease progresses, irregular myo-
(12 to 15 Hz) with generalized slowing (64). clonic jerks evoked by proprioceptive stimuli, voluntary movement, or
emotional fluctuations become prominent. In this regard, the disorder could
be initially confused with myoclonic-atonic epilepsy as described by Doose;
Neuronal Ceroid Lipofuscinoses however, cognitive decline, ataxia, and visual failure with optic atrophy and
abnormal electroretinographic findings point to the true diagnosis. In ad-
The neuronal ceroid lipofuscinoses (NCLs) are a group of diseases that re- dition, the changes in the background slowing and marked variability of
sult in storage of lipopigments in the brain and other tissues. At least five the morphology of the epileptiform activity in NCL will help in the dif-
clinical subtypes and rare, atypical forms have been reported, and most are ferentiation (Fig. 9.6). A characteristic EEG pattern are occipital spikes on
transmitted as autosomal recessive traits. low-frequency photic stimulation (66). Giant visual-evoked responses and
The infantile form of NCL (type I) is predominantly found in Finland and somatosensory-evoked potentials are also seen.
typically manifests at the age of 12 to 18 months, with developmental regres-
sion, myoclonus, ataxia, and visual failure. Other features include incoordina- Alpers Disease (Progressive Infantile Poliodystrophy)
tion of limb movements, acquired microcephaly, and optic atrophy. Seizures,
in the form of myoclonic jerks and astatic, atonic, or generalized seizures, are Alpers disease is caused by autosomal recessive mutations in the gene en-
prominent. EEG features, which include an early, progressive loss of electro- coding the mitochondrial DNA polymerase Gamma. It is characterized by
cortical activity and attenuation of the background, aid in the diagnosis (65). psychomotor regression, seizures, and liver disease. Neuroimaging shows
FIGURE 9.6: NCL. This 7-year-old child with NCL type 2 show diffuse
background slowing and pleomorphic generalized or diffuse IEDs.
FIGURE 9.7: A: Early sleep in a 9-year-old boy. Fast activity of early sleep
is seen over both anterior quadrants. Vertex sharp waves (Channels 13 to
14) are prominent and repetitive and must be distinguished from epi-
leptiform potentials. B: Later in the same recording, localized spikes are
seen (Channels 7 to 8) over the right temporal region, with a vertex wave
recorded in the sixth second of this segment.
progressive brain atrophy with relative sparing of the WM. Seizure types disorders of O-mannosylation, which includes Walker-Warburg, Fukuyama
include myoclonic, focal, and generalized tonic-clonic convulsions. The in- muscular dystrophy, and eye-muscle-brain disease.
terictal EEG may be suggestive with abundant high-voltage rhythmic slow Type Ia, phosphomannomutase-2 deficiency, is the most common form.
waves with admixed polyspikes (67) (Fig. 9.7A,B). In addition, there is pro- Involvement of internal organs in infancy may be life-threatening, but later
gressive slowing of background and loss of the normal posterior dominant in childhood, cognitive impairment, ataxia, progressive neuropathy, retinal
rhythms. Some patients present with epilepsia partialis continua or refrac- degeneration, and skeletal deformities occur. Characteristic features include
tory focal status epilepticus have been observed and some have suggested inverted nipples, an unusual distribution of fat, and facial abnormalities.
rapid testing in this setting to allow an early diagnosis (68). Imaging studies reveal cerebellar hypoplasia (70). A coagulopathy likely
predisposes to stroke-like episodes. Clinical neurophysiological studies show
Congenital Disorder of Glycosylation giant somatosensory-evoked potentials and IEDs (71). Patients with other
subtypes of CDG may have infantile spasms and hypsarhythmia (72).
Congenital disorders of glycosylation (CDG) are caused by deficient glyco-
sylation of various tissue proteins and impact multiple organs, particularly METABOLIC DISORDERS OF CHILDHOOD
the brain, muscles, and gut. As a result, there is often cognitive impairment, AND ADOLESCENCE
ataxia, somatic abnormalities, including abnormal fat pads and inverted
nipples and coagulopathy. There are more than 70 disorders, which can be Homocystinuria
divided into two broad types, depending on whether they impair lipid-linked
oligosaccharide assembly and transfer (Type I) or alter trimming/processing Homocystinuria is often caused by cystathionine-β-synthase deficiency, and
of the protein-bound oligosaccharide (Type II) (69). In addition, there are this results in cognitive impairment, behavioral disturbances, and seizures.
Other clinical features include ectopia lentis, osteoporosis, and scoliosis infancy, which may cause it to be confused with the more common type I
(73). EEG features are relatively nonspecific, with slowing and focal interic- form of Gaucher disease. When neurological symptoms develop in child-
tal epileptiform (74). hood to early adulthood, it can be clearly distinguished from type I because
cerebral features are absent. Frequent myoclonic jerks and tonic-clonic sei-
Adrenoleukodystrophy zures ultimately develop. A supranuclear palsy of horizontal gaze is present
in the majority of cases and is an important diagnostic sign. Generalized
Adrenoleukodystrophy is a peroxisomal disorder with X-linked inheritance. rigidity, progressive cognitive decline, and facial grimacing may be present.
Symptoms usually appear in early childhood with focal motor seizures, Paroxysmal EEG abnormalities may be seen before the onset of convul-
often with secondary generalization. Patients may also present with vari- sions, with worsening as the disease progresses, and diffuse polyspikes and
ous forms of status epilepticus and epilepsia partialis continua. The EEG SWDs are present. The most characteristic EEG findings are rhythmical
is characteristic, with high-voltage polymorphic delta activity and loss of runs of 6- to 10-Hz spikes or sharp waves (79).
faster frequencies over the posterior regions (75).
Neuroaxonal Dystrophies
Lysosomal Disorders
Neuroaxonal dystrophies include infantile and juvenile forms of neuroax-
Sialidosis, Type I: Cherry-Red Spot—Myoclonus Syndrome onal dystrophy, Hallervorden-Spatz syndrome, and one type of Schindler
Sialidosis type I is inherited in an autosomal recessive fashion. Symptoms disease.
begin in late childhood, with progressive visual loss and seizures. Like other Infantile neuroaxonal dystrophy is an autosomal recessive disorder af-
forms of progressive myoclonus epilepsy, myoclonus can be provoked by fecting both the central and peripheral nervous systems and is one of the
movement, sensory stimulation, or excitement (76). Later, ataxia and cog- disorders caused by mutations in PLA2G6 gene (80). The characteristic
nitive impairment become manifest. There are no dysmorphic features or pathological features are axonal spheroids within the peripheral and central
organomegaly, which helps to contrast this disorder from sialidosis type II nervous system. Clinical manifestations begin between the ages of 1 and
and mucopolysaccharidosis. The EEG contains runs of positive rhythmic 2 years, with cognitive regression, hypotonia, and development of a pro-
vertex spikes superimposed on a low-voltage background (77). gressive sensorimotor neuropathy. Seizures occur in one-third of patients
with this disease, onset after the age of 3 years. The electrographic finding
Sialidosis, Type II/Galactosialidosis of high-voltage fast activity (16 to 24 Hz) that is unaltered by eye opening
Sialidosis Type II is the juvenile form and shares some features with type I or closure is characteristic of all children with this disorder, regardless of
sialidosis, including autosomal recessive inheritance. Type II is often caused the occurrence of seizures. During sleep, the fast activity may persist, and
by a reduction in β-galactosidase and neuraminidase activity (galactosiali- K-complexes are typically absent (81). Seizure types described with infantile
dosis). There tends to be less myoclonus than type I and hearing loss, coarse neuroaxonal dystrophy include myoclonic, tonic, and epileptic spasms (82).
facies, and corneal clouding are seen. The EEG contains moderate-voltage, A juvenile form of the disorder presenting with clinical and EEG features
multifocal SWDs (78). of progressive myoclonic epilepsy but with pathological features identical to
the infantile type has been described (83).
Gaucher Disease, Type III
Three types of Gaucher disease are known: type I, a chronic form with Neuronal Ceroid Lipofuscinosis, Type III (Spielmeyer-
adulthood onset; type II, a rare form associated with infantile death; and Vogt Disease or Late-Onset Batten Disease)
type III, a chronic form with neurological involvement. These disorders are
caused by a deficiency of glucocerebrosidase, which leads to the accumula- This syndrome with onset in early childhood begins between the ages of
tion of glucosylceramide in the lysosomes of reticuloendothelial cells. In 5 and 10 years, with visual failure, slow intellectual deterioration, and sei-
the type III form, hepatosplenomegaly may be present from birth or early zures. A diffuse rigidity later ensues. An autosomal recessive inheritance
pattern is seen with a worldwide distribution of the disorder. EEG changes Although the familial pattern can initially mimic an idiopathic form of
are nonspecific. In contrast to the Bielschowsky form of NCL, low-frequency epilepsy, the severity of the myoclonus soon suggests a form of progres-
photic does not evoke occipital spikes. sive myoclonic epilepsy. Myoclonus can become quite disabling, interfering
with speech and swallowing, and is often provoked by voluntary movement
Progressive Myoclonus Epilepsies and excitement. Cognition is generally retained, although a mild decline
may be observed later in the course of the disease. Cerebellar ataxia, hypo-
Progressive myoclonus epilepsies are a collection of rare disorders charac- reflexia, wasting of the distal musculature, and signs of chronic denerva-
terized by the triad of myoclonic seizures, tonic-clonic seizures, and pro- tion on electromyograms may occur. The EEG reveals progressive slowing
gressive neurological dysfunction, which often manifests as dementia and with generalized spike-and-wave-like bursts at a rate of 3 to 5 per second
ataxia. Onset generally occurs in late childhood to adolescence. If myoclonic that are frontally predominant (Fig. 9.8). Paroxysmal flicker responses and
features are not prominent, children with this syndrome may be erroneously generalized spikes and polyspikes with photic stimulation may be present
diagnosed with LGS (84). For this reason, a careful history for myoclonic (Fig. 9.9) (84).
features is important in children with intellectual deterioration and frequent
seizures.
MERRF and MELAS
Lafora Disease (EPM2) In MERRF, disease onset occurs before the age of 20 years, with ataxia
and seizures that are predominantly myoclonic. The inheritance pattern is
Although the biochemical is unknown, Lafora Disease is caused by a
compatible with maternal transmission. In the majority of cases, a point
defect in either EPM2 genes that encode for the proteins laforin and malin,
mutation at position 8344 of the mitochondrial gene for transfer ribonu-
respectively. The mean age at onset is 14 years, but symptoms may begin in
cleic acid (tRNA)-lysine has been identified. Affected patients may have
adulthood. Seizures may precede other clinical signs by months to years;
short stature, neurosensory hearing loss, optic atrophy, myopathy, or en-
multiple seizure types may occur in a previously normal person (76). Cogni-
cephalopathy. EEG findings include background slowing, focal epilepti-
tive decline and personality changes are prominent features. Seizure types
form discharges, and atypical spike- or sharp-and-slow-wave discharges
include tonic-clonic, myoclonic, and polymyoclonus. Occipital seizures with
that have a variable association with the myoclonic jerks (88,89). Suppres-
visual phenomena have been reported in 30% to 50% of cases. C erebellar
sion of these discharges during sleep is characteristic. As with many of the
ataxia, hypertonia, dyskinesias, and exaggerated tendon reflexes may
progressive myoclonic epilepsies, giant somatosensory-evoked potentials
develop later. The presence of spikes over the posterior regions is a distin-
are observed.
guishing feature that may alert the electroencephalographer for the diagno-
Classically, MELAS manifests during childhood with the sudden onset of
sis in the appropriate clinical setting (85). As the disease progresses, the EEG
stroke-like episodes (Fig. 9.10). Migraine-like headaches, progressive deaf-
pattern becomes increasingly disorganized. A photoconvulsive response can
ness, seizures, cognitive decline, and myopathic features may accompany
be seen with photic stimulation (86). On neuroimaging, cerebellar atrophy is
these symptoms. There may be epilepsia partialis continua and seizures
occasionally observed.
evolving into focal or generalized status epilepticus (90). Fujimoto et al. (91)
reviewed 79 EEGs in six patients with MELAS and two of their relatives
Unverricht-Lundborg Progressive Familial Myoclonic with mitochondrial myopathy, encephalopathy, and lactic acidosis, without
Epilepsy (Baltic Myoclonus or EPM1) stroke-like episodes. In the acute stage after a stroke-like episode, 10 of 11
This familial form of progressive encephalopathy is characterized by re- EEGs showed focal high-voltage delta waves with polyspikes. These dis-
lentless myoclonus and generalized seizures. It is caused by mutations in charges were interpreted as ictal phenomena. Later, focal spikes or sharp
CSTB, resulting in deficit function of cystatin B (87). Onset is in child- waves and 14- and 6-Hz positive bursts were frequently recorded. The ob-
hood or adolescence with seizures that are predominantly myoclonic and served seizures were characterized by focal clonic and myoclonic movements
frequently after awakening. Absence and atonic seizures are also observed. with migrainous headache. Four point mutations are predominantly seen
FIGURE 9.8: PME. This 17-year-old young woman has EPM1. This seg-
ment of EEG shows bursts of generalized SWDs that were the EEG ac-
companiment of myoclonia.
with MELAS. Three of these (3243, 3250, 3271) affect the mitochondrial Dentatorubral-Pallidoluysian Atrophy
DNA gene of tRNA-leucine. The other mutation involves a coding region
of complex I of the respiratory chain. An overlap between clinical charac- This rare autosomal dominant disease is seen predominantly in the Japanese
teristics of MERRF and MELAS can be seen with myoclonic features in population. The disorder is related to a trinucleotide (CAG) expansion in
both syndromes. ATN1. Clinical manifestations are dependent on the length of the unstable
FIGURE 9.9: PME. This 17-year-old young woman with EPM1 has a
photoparoxysmal response on her EEG seen at the start of photic

stimulation.
FIGURE 9.10: EEG of a 26-year-old man. Bilateral intermittent rhythmic

delta activity can be mixed with other abnormalities. Background rhythm
is also somewhat slow in this subject with Down syndrome, without any
evidence of a midline lesion or increased intracranial pressure.
trinucleotide repeats and vary from a juvenile-onset progressive myoclonic boys may show a characteristic pattern of centrotemporal spikes indistin-
epilepsy to an adult-onset syndrome with ataxia, dementia, and choreoathe- guishable from or very similar to those seen in children with benign epilepsy
tosis (92). The juvenile form can also be variable in its manifestation. In gen- with centrotemporal spikes. The features of these centrotemporal IEDs in-
eral, symptoms begin in infancy to early childhood, with myoclonus, ataxia, clude a stereotyped, diphasic morphological appearance with an apparent
dementia, opsoclonus, or seizures that can be generalized tonic-clonic, atypi- horizontal dipole, enhanced by drowsiness and sleep. Musumeci et al. (94)
cal absence, or atonic (93). Pathological features are striking, with neuronal studied 192 boys with fragile X syndrome and found that 18.2% had sei-
loss and gliosis in the dentatorubral and pallidoluysian structures. EEG char- zures. The onset occurred exclusively between the ages of 2 and 9 years and
acteristically shows bursts of slowing, irregular spike-and-wave discharges, the majority of affected boys demonstrated interictal centrotemporal spikes.
and multifocal paroxysmal discharges. A photoparoxysmal response is seen,
and myoclonic seizures can often be triggered by photic stimulation. Angelman Syndrome
OTHER ENCEPHALOPATHIES MANIFESTING IN Angelman syndrome is caused by loss of the normal maternal contribution
INFANCY, CHILDHOOD, AND ADOLESCENCE to a region of chromosome 15 by deletion of a segment of the chromosome,
uniparental disomy, or translocation. It may also be the result of a mutation
Fragile X Syndrome in the UBE3A gene, which codes for proteins in the ubiquitin pathway. Chil-
dren exhibit developmental delay, craniofacial abnormalities, ataxia, parox-
The clinical features of this condition are often characterized by moderate ysmal laughter, and seizures. Children may have atypical absence seizures,
mental retardation; large ears; macroorchidism; large chin; hyperkinesias; focal seizures, and myoclonus. Characteristic EEG findings are diffuse,
jocular, high-pitched speech; and associated speech and language disorders. bilaterally frontal dominant, high-amplitude (1- to 3-Hz) notched or tripha-
This X-linked condition is due to full FMR1 mutation. EEGs in affected sic slow waves (68) (Fig. 9.11). These appear as slow sharp-wave complexes
FIGURE 9.11: Sedated sleep tracing of a 1-year-old girl with a diffuse

encephalopathy. Many different epileptiform patterns can be recorded
in a single EEG when recordings are of adequate length. A: Sharp waves
and repetitive spike- and slow-wave complexes. The right-sided pre-
dominance of the epileptiform activity is difficult to appreciate easily in
this montage. B: Later, spikes of varying morphology are seen, including
triphasic and polyphasic spikes. The right-sided predominance is more
evident.
with a notch of epileptiform activity appearing on the descending portion of 2 and 10 years, seizures and neurological signs develop. At this stage,
of the slow wave (95). Similar discharges have been reported in the occipital the EEG shows IEDs and a progressive slowing and deterioration of the
region and were facilitated by eye closure (96). In a report on 20 patients background in 75% of patients (99). Characteristic EEG findings include
with Angelman syndrome, Minassian et al. (97) noted more severe epilepsy needle-like central spikes, activated by contralateral passive finger pulp
in those with maternally inherited 15q11-13 deletions than in patients with palpation (Fig. 9.12). In addition, an unusual and prominent rhythmic
loss-of-function UBE3A mutations, uniparental disomy, or methylation im- theta rhythm (4 to 5 waves per second or 5 to 6 waves per second) in the
print abnormalities. Angelman syndrome is the probable diagnosis when the waking state has been noted at the central vertex region and vicinity. This
characteristic clinical and electrographic features are present, but it must activity blocks with active or passive movements and suggests a slowed
also be considered in children with severe epilepsy and mental retardation, equivalent of the mu rhythm (100).
even when typical EEG features are not present (98).
Down Syndrome
Rett Syndrome
Children with Down syndrome are at increased risk for infantile spasms, ac-
Rett syndrome is observed only in girls. It is characterized by early psy- companied by hypsarhythmia, which is symmetrical and rapidly clears after
chomotor regression with autistic features, loss of purposeful hand func- IV administration of diazepam (101). Older children may exhibit a variety
tion, ataxia, and acquired microcephaly. The onset of the disease occurs of seizure types and EEG findings. Overall, epilepsy occurs in 5% to 6% of
between the age of 6 months and 3 years, most often before 18 months. patients (102). Similarly, in adults, a variety of seizures and EEG features
Affected girls next experience a rapid decline in function with irritabil- may be seen, including the sudden appearance of a late-onset myoclonic
ity and loss of purposeful hand use. In the third stage, between the age epilepsy with frontally predominant SWDs (103,104).
to confirm an encephalopathy by demonstrating diffuse background slow-

ing. The degree of tolerable slowing varies as a function of age and state
of the child. In very young children, unrecognized drowsiness can produce
abundant intermixed slowing and prolonged bursts of diffuse or posteriorly
dominant rhythmic slowing during transition states. In these circumstances,
other characteristics of the EEG can be helpful in evaluation, including the
frequency of the posterior dominant rhythm, voltage and frequency organi-
zation of the background, and sleep architecture.
If an encephalopathy is confirmed, then it should be determined whether
it is progressive or static. Progressive encephalopathies are suggestive of a
neurodegenerative process, an IEM, or some other type of progressive etiol-
ogy. Progressive encephalopathy, a family history of relatives with similar
unexplained neurological illnesses, and unexplained paroxysmal bouts of
obtundation, ataxia, or other neurological phenomena are all indicators
of IEMs and merit further investigation. The EEG may help to confirm
the presence of a progressive encephalopathy, particularly if serial studies
are performed. Deterioration of the background organization, progressive
slowing of the dominant rhythm, attenuation of the background, or the loss
of the usual signposts of maturation are reliable indicators of progressive
disease.
The EEG can help to localize the pathological process, thereby limiting
the differential diagnosis. Epileptiform discharges indicate the presence of a
potentially epileptogenic encephalopathy and implicate at least some degree
of gray matter involvement (as in Tay-Sachs disease, NCL, and Alpers syn-
drome). Conversely, slowing without epileptiform activity indicates dysfunc-
tion in the thalamocortical projections and is consistent with WM involvement
(as in NALD, metachromatic leukodystrophy, and Krabbe disease).
In rare circumstances, the EEG findings are so distinctive that they limit
FIGURE 9.12: EEG of a 15-year-old girl with Rett syndrome. Characteristic
the differential diagnosis. Examples include a burst-suppression pattern in
frontocentral needle-like spikes are present. (Courtesy of C. Stack, MD, and
L. Laux, MD, Children’s Memorial Hospital, Chicago, Illinois.)
nonketotic hyperglycinemia, phenylketonuria, maple syrup urine disease,
molybdenum cofactor deficiency, and sulfite oxidase deficiency, in addi-
tion to other disorders. A comb-like rhythm with 7- to 9-Hz central activ-
THE ROLE OF THE EEG IN A CHILD WITH A ity is present in maple syrup urine disease and propionic academia; vertex
SUSPECTED PROGRESSIVE ENCEPHALOPATHY positive polyspikes are present in type I sialidosis; bioccipital polymorphic
delta activity is present in X-linked adrenoleukodystrophy; and 16- to 24-Hz
When confronted with a child who is not meeting expected developmental invariant activity is present with infantile neuroaxonal dystrophy. Some
milestones or who exhibits cognitive difficulties, one of the first questions static encephalopathies have unusual and distinctive EEG patterns: for
that may arise is whether the patient has a diffuse encephalopathy. The most example, centrotemporal spikes in fragile X syndrome; needle-like central
important parts of the evaluation are the complete medical history and the spikes in Rett syndrome; and frontally dominant, rhythmic slow sharp com-
results of a comprehensive neurological examination. The EEG may help plexes in Angelman syndrome.
As was stated at the start of the chapter, the EEGs of most patients with 16. Farrell DF. Neonatal adrenoleukodystrophy: a clinical, pathologic, and biochemical
study. Pediatr Neurol 2012;47:330–336.
IEMs are not very distinctive. Instead, what we have observed is that there 17. Verma NP, Hart ZH, Nigro M. Electrophysiologic studies in neonatal adrenoleukodys-
is a recurring theme: multifocal spikes punctuate a diffusely slowed back- trophy. Electroencephalogr Clin Neurophysiol 1985;60:7–15.
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somes and a specific deficiency of acyl-CoA oxidase (pseudo-neonatal adrenoleukodys-
most common in the very young. As the child matures, it is possible to ob- trophy). Am J Hum Genet 1988;42:422–434.
serve generalized spike- and polyspike-wave discharges, indicating a greater 19. Willard-Mack CL, Koehler RC, Hirata T, et al. Inhibition of glutamine synthetase re-
organization and integrity of the nervous system. The astute EEGer can duces ammonia-induced astrocyte swelling in rat. Neuroscience 1996;71:589–599.
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linemia. Electroencephalogr Clin Neurophysiol 1991;78:222–227.
22. Menkes JH, Hurst PL, Craig JM. A new syndrome: progressive familial infantile ce-
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10 Pediatric Epilepsy Syndromes
DOUGLAS R. NORDLI Jr.
Introduction: Differential Diagnosis of Epilepsy Late-Onset Occipital Lobe Epilepsy

According to Prominent EEG Features Conditions Masquerading as Self-limited Epilepsies
The Familial Epilepsies (Epilepsies with Frequently with Focal Stereotyped Spikes
Normal Interictal Backgrounds) Epilepsies with Encephalopathy (Epilepsies with
Benign Familial Neonatal Epilepsy Slowed Backgrounds and Multifocal Pleomorphic
Benign Familial Infantile Epilepsy Spikes)
Autosomal Dominant Nocturnal Frontal Epileptogenic Encephalopathies
Lobe Epilepsy Epileptic Encephalopathies
Familial Lateral Temporal Lobe Epilepsy or West Syndrome
Autosomal Dominant Epilepsy with Auditory Late Infantile Epileptic Encephalopathy
Features Lennox-Gastaut Syndrome
Familial Mesial Temporal Lobe Epilepsy Focal Structural Epilepsies
Genetic Generalized Spike-Wave Epilepsies Infantile Seizures are Often Subtle
Myoclonic Epilepsy in Infancy The Terms, “Simple” and “Complex” Are Difficult
Myoclonic-Astatic Epilepsy (Doose Syndrome) to Apply
Childhood Absence Epilepsy Infantile Focal Seizures May Have “Generalized”
Epilepsy with Myoclonic Absences Clinical Features
Juvenile Absence Epilepsy Difficulty Lateralizing Based upon Clinical Features
Juvenile Myoclonic Epilepsy Types of Infantile Focal Seizures and Their
Masquerading Conditions Electroclinical Correlations
Self-limited Epilepsies with Focal Spikes Conclusions
Panayiotopoulos Syndrome References
Benign Childhood Epilepsy with Centrotemporal
Spikes or Rolandic Epilepsy
283
INTRODUCTION: DIFFERENTIAL DIAGNOSIS OF for diagnosis. These groupings provide some powerful information: if there
EPILEPSY ACCORDING TO PROMINENT EEG FEATURES are genetic predispositions, they predict the mode of inheritance, they in-
form about the general prognosis, they have strong treatment implications,
An unconventional but effective starting point for an organization of pe- and they could be used as the basis for referral to tertiary epilepsy centers.
diatric epilepsies is the interictal EEG. As shown in Table 10.1, the various Of course, this is the opposite of the way we as clinicians normally con-
patterns encountered in clinical practice may be reduced to five discrete in- duct our evaluations. A precise history and physical examination should
terictal EEG groups. There are two major domains: the organization of the always come first. It is the sine qua non portion of the epilepsy evaluation,
background and the characteristics of the epileptiform activity, most impor- the basis of all we do, and the most important daily activity of the child
tantly the morphology of the interictal epileptiform discharges (IEDs). By neurologist. A thorough history elicited with minimal interruption accom-
considering the age of onset, one can narrow down the epilepsy syndromes panied by close observation of the child and family allows us to make the
to two or three possibilities, and the predominant seizure type will easily interpersonal connections that are critical for trust and healing.
guide one to the final diagnosis. In a minority, most particularly the familial The interictal EEG, however, is a remarkably powerful tool and even
epilepsies, verification of other similarly affected family members is critical though it sits in second place to our clinical assessment, it nevertheless
informs us about the underlying pathophysiology in a manner that our
naked senses never could. For many years, our predecessors have appreciated
TABLE 10.1 Organization of the Epilepsies by EEG Characteristics
that the various epilepsy syndromes have different relative contributions of
EEG Epileptiform
genetic and structural components. These thoughts were codified in the 2010
Name background activity Inheritance publication of the International League Against Epilepsy’s Classification
Committee (1). In this chapter, we will see how the interictal EEG informs us
1. Familial epilepsies Normal None or rare Autosomal
dominant about these fundamental characteristics. The premise is simple: genetic and
structural factors have markedly different EEG signatures, which allows the
2. Genetic Normal Stereotyped Spikes are
EEG to effectively categorize the epilepsies. Indeed, the EEG findings can
generalized spike- general- strongly
wave epilepsies ized spike inherited; be used as an endophenotype to explore the genetic basis of susceptibility to
waves epilepsy less so epilepsy (2). This type of epilepsy syndrome organization is highly practical
3. Self-limited Normal Stereotyped Spikes are
and simultaneously it reveals some fundamental principles about the causes
epilepsies with focal and strongly inher- of the epilepsies. Another remarkable fact is that this can be usually accom-
focal spikes multifocal ited; epilepsy plished with a relatively brief sample of the awake and sleep interictal EEG.
spikes is minimally
4a. Epileptogenic Slowed Pleomorphic If genetic, often
encephalopathy multifocal de novo THE FAMILIAL EPILEPSIES (EPILEPSIES WITH
spikes mutations, FREQUENTLY NORMAL INTERICTAL BACKGROUNDS)
4b. Epileptic Slowed and Pleomorphic some autoso-
encephalopathies often discon- multifo- mal recessive One of the five broad categories of EEG features seen in children with epi-
tinuous (at cal spikes; disorders; usu- lepsy is a normal tracing. The precise percentage of normal EEGs seen in
least in parts) electrodec- ally not familial patients with epilepsy is difficult to determine, but it may be as low as 8%
remental (3). One reason for a repeatedly normal tracing may be a remote location
responses of an epileptogenic lesion—one that does not readily allow for detection us-
5. Focal structural Focal slowing, Pleomorphic Minimal genetic ing conventional scalp recording electrodes. Normal tracings are also seen
epilepsies attenuation, focal spikes contribution in certain distinctive epilepsy syndromes that share a common characteris-
or both tic: they are familial epilepsies that are inherited in an autosomal dominant
Pediatric Epilepsy Syndromes 285
fashion. These may be considered the best examples of familial epilepsies. channels, responsible for the M-current (9). This slowly activating current
Why these epilepsies most often present with normal interictal backgrounds regulates subthreshold neuronal excitability and therefore raises the pos-
is not entirely clear, but certainly, the normal background rhythms speak to sibility that a medication like retigabine may be helpful since it blocks the
the absence of cognitive impairment and disability in the vast majority of M-current. A closely related syndrome of benign neonatal-infantile sei-
individuals with these epilepsies. Here we encounter the first EEG-epilepsy zures has been associated with a missense mutation in the SCN2A gene,
paradox: even though these epilepsies are strongly genetically determined which encodes the alpha-2 subunit of the voltage-gated sodium channel
and spikes in other conditions have a strong genetic component (vide infra), (2q24) (10).
the most conspicuous feature of the background is the lack of interictal
epileptiform activity in these familial epilepsies. Benign Familial Infantile Epilepsy
There are familial epilepsies for every epoch of pediatric life starting
with the neonatal period, and continuing to infancy, childhood, and ado- BFIE and sporadic forms (which may be similar disorders) have been
lescence. These include benign familial neonatal epilepsy (BFNE), benign reported by several different investigators working in different regions of
familial infantile epilepsy (BFIE), autosomal dominant nocturnal frontal the world (11–14). Affected infants have focal seizures, which may present
lobe epilepsy (ADNFLE), autosomal dominant epilepsy with auditory fea- with subtle behavioral arrest or, on the other extreme, apparent bilateral
tures (ADEAF), and other autosomal dominant temporal lobe epilepsies. convulsive features. Eye version, staring, oral automatism, and oxygen
It is obvious from the titles of these epilepsies that they vary in age of pre- desaturation are other common elements, and these are commensurate with
sentation, the brain region commonly involved, and the clinical manifesta- the location of onset of the seizures. The interictal EEG is usually nor-
tions. Generally, the combination of the clinical features and family history, mal, though some BFIEs may have peculiar low- or medium-voltage vertex
along with the mostly normal interictal EEG data, is sufficient to make a spikes or sharp waves followed by a slow wave with a dome-like morphology
diagnosis, but if confirmation is required, genetic testing can help. By and (12,15). Ictal discharges often arise from the temporal region or posterior
large, the outcome is favorable, although there are published cases of severe quadrant. This finding is relatively nonspecific, since many focal seizures
phenotypes (4). in infants arise from the same region. These disorders are inherited in an
autosomal dominant fashion and several genes have been discovered, which
Benign Familial Neonatal Epilepsy often involve ion channels, but importantly, sometimes do not (16). Defects
in the ATP1A2 gene may cause familial hemiplegic migraine and associ-
BFNE usually begins on the second or third day of life and resolves within ated infantile seizures (17). When there is associated paroxysmal kinesigenic
the first few months. During seizures, neonates may have tonic posturing, dyskinesia, mutations in the proline-rich transmembrane protein (PRPT2)
automatisms, apnea, or focal or generalized clonic activity. The seizures have been reported (18). Similar mutations have been identified in Japa-
may rarely persist into adulthood. Typically, the interictal EEG is normal, nese children (19) and even, rarely, have been found in sporadic cases (20).
though it may have focal or multifocal sharp waves, an excessively discon- The fact that only 6 of the 16 probands in the Japanese study tested posi-
tinuous tracing for age or the theta-pointu alternant pattern. The latter is tive indicates that there are clearly other genetic causes of BFIE still to be
characterized by rhythmic 4- to 7-Hz activity, with admixed sharp waves, discovered.
with shifting laterality across the hemispheres, but it is by no means specific
for this disorder. Authors describe a clinical sequence starting with hyper- Autosomal Dominant Nocturnal Frontal Lobe Epilepsy
tonia and followed by apnea, autonomic signs, facial movements, and limb
clonus (5). In some of the recorded seizures, an electrodecrement heralds Patients with ADNFLE have sudden awakenings with dystonic movements
the event and may last up to 19 seconds, followed by 1- to 2-minute bilat- (tonic posturing) or violent movements. Since the EEG findings are usually
eral spikes or sharp waves (6), but focal seizures (7) and focal seizures with relatively bland, the seizures may be mistaken for sleep disorders, nocturnal
secondary spread have also been recorded (8). The disorder has been asso- paroxysmal dystonia, or nonepileptic seizures. Rarely, the interictal EEG
ciated with mutations in the KCNQ2 and KCNQ3 voltage-gated potassium may show focal features such as slowing and spikes (21). Ictal recordings
Figure 10.1: Ictal recording in a 10 year old boy with ADNFLE. Note the
sudden change in the background as he awakens from sleep. There is
some admixed low-voltage rhythmic fast activity in the frontal regions.
are more distinctive and are characterized by bifrontal beta activity or other symptoms is usually in adolescence of early adult life, but childhood onset
rhythmic discharges (22) (Fig. 10.1). The ictal discharges may lateralize or is also possible. It is characterized by subtle seizures with auditory hallucina-
even localize to a region, suggesting a focal structural lesion, and therefore, tions, infrequent nocturnal convulsions, and a good response to medications.
a careful family history is warranted before considering focal respective sur- Seizures may be triggered by voices or noises. The auditory hallucinations
gery in patients with nocturnal frontal lobe seizures. Genetic screening for may be humming, clicking, ringing, or other noises. Other sensory phenom-
the associated nicotinic acetylcholine receptor gene mutation (CHRNA4 ena may also occur. The interictal EEG is usually normal, though, as in the
and CHRNB2) is commercially available. other familial disorders, IEDs may rarely be found and sporadic cases ap-
pear to have a higher incidence of epileptiform discharges (25,26).
Familial Lateral Temporal Lobe Epilepsy or Autosomal
Dominant Epilepsy with Auditory Features Familial Mesial Temporal Lobe Epilepsy
Ottman described a pedigree in 1995 where most affected members re- The precise genetic cause of familial mesial temporal lobe epilepsy is not yet
ported seizures with auditory symptoms and named the syndrome autoso- known. This disorder usually presents in adults, never before age 10 years,
mal dominant partial epilepsy with auditory features (ADPEAF [OMIM and therefore, it will be only briefly mentioned here. Seizures tend to be in-
600512]) (23). Subsequently, it was found that mutations of the leucine-rich frequent, mild, and easily controlled with medication, contrasting them to
glioma-inactivated 1 LGI1 gene caused this disorder (24). The onset of other forms of mesial temporal lobe epilepsy (27). Seizures without alteration
of consciousness are more common than those with dyscognitive features. myoclonia (Jeavons syndrome), juvenile absence epilepsy (JAE), juvenile
Many cases show normal imaging and EEG findings, and the presence of MR myoclonic epilepsy (JME), and epilepsy with generalized tonic-clonic sei-
changes or interictal epileptiform activity appears to predict intractability (28). zures alone. Treatment is generally with broad-spectrum agents, with the ex-
ception of ethosuximide for CAE. Patients in this category will also usually
GENETIC GENERALIZED SPIKE-WAVE EPILEPSIES not require referral to a tertiary center, unless complications arise or special
circumstances present themselves.
Individuals with these forms of epilepsy have normal interictal backgrounds
with superimposed generalized spike-wave discharges (SWDs). These dis- Myoclonic Epilepsy in Infancy
charges will usually be 3 Hz or greater, though, at times, some slower spike-
wave activity, circa 2.5 Hz may be seen, particularly in the younger child. In The predominant seizure seen in MEI is myoclonus, as the name suggests. In-
all cases, these occur on the backdrop of a normally developing child. There fants who are developing normally have myoclonic jerks mostly of the head
may be associated photoparoxysmal responses and some of these epilepsies and proximal arms, occurring in isolation or in brief runs of recurrent jerks.
will show activation of spike waves with hyperventilation. Spikes may ap- The ictal EEG shows a burst of generalized or diffuse spike-wave activity
pear more irregular and demonstrate fragmentation in the sleep record. It is with the myoclonia, otherwise the interictal EEG is normal (33) (Fig. 10.2).
not unusual to see focal features (focal slowing and focal spikes), but these
will show shifting laterality from study to study. Myoclonic-Astatic Epilepsy (Doose Syndrome)
As stated, the interictal EEG background is normal, but there may be
some important exceptions: rhythmic activity may intermittently punctu- Myoclonic-astatic epilepsy may occur between late infancy and 6 years, but
ate the record. This may be seen as either intermittent rhythmic theta ac- most often starts between 2 and 4 years. Many children will have antecedent
tivity, which is often in the biparietal regions (prominent in many cases of febrile seizures. The prototypic seizure is a myoclonic-astatic attack, or now
myoclonic-atonic epilepsy described by Doose) or as intermittent rhythmic known as a myoclonic-atonic seizure (34). The seizure begins with a sudden
delta, seen in either the occipital or the frontal regions (occipital intermit- jerk of the head or body followed by a sudden loss of tone, causing a head
tent rhythmic delta activity [OIRDA] and frontal intermittent rhythmic drop or body drop. This may easily result in injury because of the combina-
delta activity [FIRDA], respectively). tion of the sudden propulsion from the myoclonus, the subsequent loss of
Generalized spike waves and other paroxysmal features found in the EEGs postural tone, and the inability to have a protective reflex. In addition to
of individuals with these epilepsies have been known for some time to be this seizure type, atonic seizures, isolated myoclonic jerks, absence seizures,
inherited in an autosomal dominant fashion with variable penetrance so that and generalized clonic-tonic-clonic seizures occur. Daytime tonic seizures
a high proportion of family members of individuals with primary general- are considered exclusionary by some, but nocturnal tonic seizures do occur,
ized epilepsy will have generalized spike waves (29,30). The clinical tendency even in patients with excellent outcome.
toward epilepsy has genetic contributors as well, but these are more complex The interictal EEG may show biparietal rhythmic theta activity, and this
than the inheritance of the EEG trait. Although the concordance rate for pri- may be the only abnormality early in the course of the illness (Fig. 10.3).
mary generalized epilepsy in twin studies are high (31), the recurrence risks in Bursts of 2- to 3-Hz generalized spike and polyspike-wave discharges fol-
first-degree relatives of patients with primary generalized epilepsies are much low and are often frequent. These occur in brief bursts, usually consisting
lower than the truly familial epilepsies with monogenic transmission (32). of isolated spike waves, couplets, or triplets. The repetition rate is therefore
This argues for a more complex polygenic or oligogenic mode of inheritance. difficult to accurately measure, but it is often variable between the bursts.
A wide variety of epilepsies are seen and the prognosis is generally very Photosensitivity is common.
favorable, although some will require treatment for prolonged periods. As- The ictal accompaniment of the myoclonic-astatic seizure is a burst of
sociated epilepsies include myoclonic epilepsy in infancy (MEI), childhood generalized polyspike-wave discharge, where the after-going slow-wave
absence epilepsy (CAE), epilepsy with myoclonic-atonic seizures (EMA) (as discharge appears to have some high-frequency attenuation or diminished
described by Doose), epilepsy with myoclonic absence, epilepsy with eyelid high-frequency activity (Fig. 10.4).
Figure 10.2: Benign myoclonic epilepsy of infancy. This infant had re-
peated myoclonic jerks associated with this burst of generalized spike-
wave activity. Generalized spike waves are very rarely seen in infants, and
this is one notable exception.
Figure 10.3: Myoclonic-atonic epilepsy as described by Doose. This

tracing was obtained in a 4-year-old and was punctuated by runs of bipa-
rietal rhythmic theta activity that occurred when the patient was clearly
not drowsy.
Figure 10.4: Doose syndrome. A: This youngster had a myoclonic-atonic

seizure accompanied by this EEG correlate. Note the burst of general-
ized polyspike activity is followed by a brief epoch of relative attenu-
ation. B: A 4-year-old with Doose syndrome had a clonic-tonic-clonic
seizure, which is the typical type of convulsive event. Note the rhythmic
spike waves at the start of this page corresponding to the clonic phase
of the seizure, which give way to the more rapid ictal discharges corre-
sponding with the transition to the vibratory tonic phase.
Childhood Absence Epilepsy Epilepsy with Myoclonic Absences

CAE generally begins between 2 and 10 years of age, with a peak in the early Epilepsy with myoclonic absences is a rare form of genetic generalized epi-
school-age years. From the very early observations of this form of epilepsy, lepsy (39). It may occur at any time in infancy to adolescence, with a peak in
it was appreciated that absences are usually frequent, with scores to hun- the early school-age child, usually around 7 years (40). Myoclonic absences
dreds of seizures in a day. This gave rise to the name pyknolepsy, signifying are characterized by tonic elevation of the arms, with repeated myoclonia of
many seizures (35). Each individual seizure is typically brief, usually less the shoulders, arms, and legs. The events may be asymmetric or even uni-
than 10 seconds. The clinical onset and offset is abrupt, with brief impair- lateral with resultant head deviation. Approximately two-thirds of children
ment of consciousness associated with unresponsiveness and interruption will also have tonic-clonic seizures.
of the ongoing activity. Some rhythmic eyeblinking may occur, but more The interictal EEG is normal at onset and about half of the cases show
pronounced myoclonus of the face or other body parts suggests a myoclonic brief generalized spike-slow-wave discharges, sometimes with fragmen-
form of epilepsy. tation. The ictal EEG shows rhythmic 3-Hz generalized polyspike-wave
The interictal EEG is normal except that rhythmic delta activity may be discharges (Fig. 10.7).
seen (Fig. 10.5). The attacks are accompanied by bursts of generalized 3-Hz
SWDs. These often have a frontal predominance and may have up to two Juvenile Absence Epilepsy
spikes per complex. The frequency may slow slightly as the ictal discharge
continues. Typical absence attacks often begin and end with rhythmic slow- JAE and JME are both discussed in the chapter on adult epilepsy and are
ing with a more restricted topography (Fig. 10.6). Seizures are easily acti- therefore only briefly mentioned here for completeness. This epilepsy has a
vated by hyperventilation, and are more frequent with lower blood glucose peak onset between 9 and 13 years of age and most often absence attacks
levels (36,37). Ethosuximide is the most effective medication with the least precede myoclonic jerks and generalized tonic-clonic seizures. The prognosis
side effects (38). is not as favorable as CAE (41).
Figure 10.5: CAE. This 8-year-old child has associated OIRDA.

Figure 10.6: A: CAE. The classic 3-Hz SWD is evident. This was asso-
ciated with unresponsiveness, confirming that it was a clinical absence
attack. B: Same ictal discharge displayed with a longer page duration
to reveal the whole discharge. Note how the first few discharges and
last discharges are different than the main ictal pattern. (Dr. Solomon
Moshé—personal comments.)
Figure 10.7: Myoclonic absence. This 6-year-old had an absence with

repeated subtle head nods and arm myoclonia. Note the slight stiffening
of the arm evident in the deltoid recording. There is an accompanying
burst of generalized spike-wave activity.
The interictal EEG background is normal, upon which are superimposed to Herpin’s work dating back to 1867 with the name “Impulsiv Petit Mal.”
fragments of diffuse spikes and polyspikes. During absence attacks, there JME is characterized by mild myoclonic, generalized clonic-tonic-clonic sei-
are 3- to 4-Hz generalized polyspike-wave discharges (Fig. 10.8). zures, and absence seizures. Delgado-Escueta and Greenberg (44) searched
for the genetic cause and in doing so highlighted the importance of this syn-
Juvenile Myoclonic Epilepsy drome in the United States. Onset is typically in adolescence, with myoclonic
seizures. The myoclonic seizures are usually bilateral but mild to moderate,
The history of JME has been recently reviewed (42). In 1957, Janz and in the sense that they may cause objects to drop but usually do not result in
Christian (43) established the essential components of JME and paid tribute falls. They typically occur after awakening and may precede or lead directly
Figure 10.8: JAE. Bursts of generalized SWDs are present.

into a convulsion. Seizures are aggravated by fatigue, sleep deprivation, or histories will usually allow for easy separation of these cases, but not al-
alcohol. Myoclonus may occur with brief absences, and myoclonic status ways. Some cases may escape detection, and therefore, the differential di-
epilepticus has been described. If untreated, generalized clonic-tonic-clonic agnosis should be kept broad in cases that do not show a good response to
seizures are frequent. initial treatment.
The interictal EEG in JME shows a normal background that is punctu-
ated by bursts of fast generalized spike- or polyspike-wave activity with a SELF-LIMITED EPILEPSIES WITH FOCAL SPIKES
repetition rate between 3.5- and 6-HZ spike (Fig. 10.9). During myoclonic
seizures, there are 10- to 16-Hz rapid spikes with slow waves. Photosensi- The epilepsies in this second group show two common features: they have
tivity is common. Like many generalized epilepsies, fragmentation of the normal interictal backgrounds and they contain highly stereotyped spikes.
epileptiform discharges including clearly focal spikes can occur while awake These may be found in a single focus, in homologous regions, or in multiple
or asleep (45). foci. In some circumstances, the multifocal spikes may appear almost simul-
JME, similar to JAE, may require life-long treatment (46). The calcium taneously. These have been referred to as “clone-like” and they appear to be
channel, voltage-dependent beta-4 subunit (2q24), chloride channel 2 driven by a primary spike generator, which is posterior located and often of
(3q26), GABA1RA (5q34), GABAR delta (1p36), and the EF-hand domain the smallest amplitude (47).
(C-terminal)-containing 1 (6p12-11) have been associated with JME. It is not difficult to find the spikes and they nearly always enhance with
drowsiness and sleep. Importantly, the epileptiform activity evident in sleep
Masquerading Conditions is identical to the activity while awake. On some occasions, the epileptiform
discharges can be elicited by special maneuvers such as temporary loss of
There are some conditions that will produce fairly well-formed generalized visual fixation or finger pulp tapping. There is a general pattern for the
spikes, but usually on an abnormal interictal EEG background. Examples spikes to be more posterior in the younger child and to “move” more an-
of this include GLUT-1 DS (Fig. 10.10), hyperinsulinemia with hyperam- teriorly with age. This was described by Gibbs et al. (48) and referred to as
monemia (Fig. 10.11), and various forms of progressive myoclonus epi- “migrating spikes.”
lepsy (Fig. 10.12). PME (e.g. EPM1, EPM2, mitochondrial cytopathies, These epilepsies have different clinical presentations depending upon
and neuronal ceroid lipofuscionses). The background slowing and clinical the age of presentation and the prominent location of the active focus.
Figure 10.9: JME. Note the fast repetition rate of the generalized epi-
leptiform discharges.
Figure 10.10: GLUT-1 DS. This 12-year-old child has bursts of g

eneralized
SWDs with a 3-Hz repetition rate. Note the slight irregular nature of the
spike waves and the variability of the waveforms.
Figure 10.11: Hyperinsulinemia and hyperammonemia (HIHA). This

5-month-old has bursts of spikes that are posteriorly dominant, but ulti-
mately will become generalized SWDs, similar to those seen in GLUT-1
DS—two conditions where the brain is not receiving adequate supply of
glucose.
Figure 10.12: Progressive myoclonus epilepsy. This 16-year-old girl

has EPM1 and her EEG shows bursts of generalized polyspike-wave
discharges. These were often associated with myoclonia, but also

occurred independently.
Panayiotopoulos uses the apt term “Benign Childhood Seizure Susceptibility spikes (BECTS) or RE, and late-onset occipital epilepsy (Gastaut type) (53).
Syndrome” or BCSSS for these conditions. They almost invariably have excel- There is no described neonatal form of these epilepsies.
lent outcome with regard to the cessation of seizures but may be associated The spectrum of these disorders is undoubtedly larger than these well-
with learning, behavior, or attention issues that cause havoc if not properly described syndromes. We have seen children in clinical practice who have
recognized and treated. For this reason, one might substitute “self-limited” for self-limited epilepsies with stereotyped spikes in other locations, including
“benign.” Some prefer the term “epilepsy” to “seizure syndrome,” which yields the frontal and parietal lobes, but these have not been as well character-
a shorter term: Self-Limited Epilepsies with Focal Stereotyped Spikes (SEFS). ized in the literature and apparently are not widely recognized. In addition,
The genetics of the EEG trait for the prototype of this category—rolandic there can be very severe forms of almost any epilepsy, and atypical benign
epilepsy (RE)—have been well worked out: spikes are inherited in an au- partial epilepsy is one such example for this group. Many highly regarded
tosomal dominant fashion with variable penetrance according to age (49). authorities also consider Landau-Kleffner syndrome and continuous spike-
A similar conclusion was reached with late-onset occipital epilepsy (50). The and-wave during sleep (CSWS) as extreme versions of these same disorders,
clinical predisposition to epilepsy, however, appears to have a relatively small though in 25 years of clinical practice, this author has not seen a single case
genetic component as substantiated by an analysis of several twin registries transform from ordinary RE to Landau-Kleffner syndrome (LKS).
(51). Based on this and other information, it has been estimated that the Imaging is not required for children with RE, and probably is senseless
genetic contribution to the clinical susceptibility is small and certainly not in those with multifocal stereotyped spikes, a normal background, normal
confined to just the transmission of the EEG trait (51). This is the second neurological examination, and concordant history for a self-limited epilepsy.
EEG-epilepsy paradox: while centrotemporal spikes are seen in all individu- The challenging cases are those children with unifocal occipital or frontal
als with RE and this trait has a genetic component, the trait alone cannot stereotyped spikes. Here, it may be prudent to image to exclude the possibil-
explain the genetic contribution and, moreover, the genetic contribution to ity of an underlying focal structural lesion, even if focal slowing and attenu-
the clinical susceptibility for epilepsy appears to be small (52). ation are not present.
Well-described self-limited epilepsies with stereotyped focal spikes include Most children with SEFS will not require referral to a tertiary center, as-
Panayiotopoulos syndrome (PS), benign epilepsy with centrotemporal suming the correct diagnosis is secured. Prophylactic treatment is generally
avoided, unless seizures are particularly bothersome and recurrent, but in occur, and very rarely, there may be an evolution to convulsive status epilep-
those children with prolonged seizures like PS, it would be wise to provide ticus. After the postictal period resolves, the child is perfectly normal. There
detailed instructions for an emergency plan, including administration of a has been one report of an association with SCN1A mutation, but this find-
rescue benzodiazepine for prolonged seizures. ing was not reproduced in another family (55,56).
Neuroimaging is likewise normal. In contrast, the EEG is very useful;
Panayiotopoulos Syndrome 90% of EEGs show multifocal stereotyped spikes and spike waves with
posterior accentuation (Fig. 10.13). In follow-up EEGs, 17% had a shift
PS is a childhood susceptibility to focal, mainly autonomic, seizures. Children of epileptiform activity from the occipital to centrotemporal areas and 3%
have normal physical and neuropsychological development, and peak age of to frontal areas (57). In PS, frontal spikes may be activated by occipital
onset is at 4 to 5 years of age, with a range from 1 to 14 years. The preva- foci (58), resulting in the synchronous occipital and frontopolar spike phe-
lence is about 13% among children, with a seizure onset between ages 3 and nomenon (59) (Fig. 10.14). The ictal EEG demonstrates rhythmic delta
6 years, and overall, about 0.2% to 0.3% of the general population of chil- activity intermixed with small spikes. Onset is unilateral and most often
dren may be affected. This figure may be much higher if children with atypi- posterior (57).
cal and inconspicuous presentation are included. The autonomic seizures
consist of pallor, nausea, retching, and vomiting. There may be associated Benign Childhood Epilepsy with Centrotemporal
papillary changes and incontinence. Cardiac, breathing, and thermoregu- Spikes or Rolandic Epilepsy
latory alterations may occur. Cyanosis is seen, and in some severe cases,
cardiac asystole has been reported (54). Most seizures are nocturnal. Many Benign childhood epilepsy with centrotemporal spikes or RE is a common
parents describe eye deviation and listlessness, but the seizures may end with form of childhood epilepsy with focal motor seizures, nocturnal general-
hemiconvulsions or a Jacksonian march. Autonomic status epilepticus may ized tonic-clonic seizures, and stereotyped centrotemporal spikes that are
Figure 10.13: PS. Note the abundant stereotyped occipital spikes in this
recording performed on a 4 year old.
Figure 10.14: PS. Spikes are not restricted to the occipital region in PS
and in this case, both independent frontal spikes and so-called Fp-O
spikes are visible.
superimposed on a normal background (60). The age range is typically 3 to Late-Onset Occipital Lobe Epilepsy
12 years, with the majority being children in the early school-age years. The
epilepsy spontaneously remits in nearly all cases, with or without treatment. This variant of occipital epilepsy was first described by Gastaut (68), and there-
Diurnal seizures often involve the face and are commonly accompanied fore, is oftentimes referred to by that name. There are several distinguishing
by an inability to speak (61). Sometimes there are poorly formed vocaliza- features that allow it to be separated from PS. Late-onset occipital lobe epilepsy
tions or guttural sounds. Despite this, children have preserved awareness occurs in children and adolescents, and there does not appear to be any per-
and can often recount details of the entire event to the surprise of their sistence into adult life. Seizures often begin with visual symptoms (amaurosis,
parents. Professionals seldom observe nocturnal seizures, so it is difficult phosphenes, or figurative hallucinations), which may be followed by hemiclonic
to determine if these begin as focal seizures or are generalized at the onset. attacks and other focal manifestations. Migraines often follow the seizure.
Spikes are distinctive (Fig. 10.15). They are stereotyped, medium to high The EEG shows very characteristic findings (Fig. 10.16). There are fre-
amplitude, diphasic maximal in the midtemporal and central (C3, C4) r egions quent runs of occipital rhythmic high-voltage spike and SWDs, which may
and have a horizontal dipole (62,63). Spikes are enhanced in light sleep and recur at 1.5 to 3 Hz. These may predominate on one side or the other, are
they maintain their same stereotyped morphology, which can help to distin- maximally expressed when the eyes are closed, and stop with visual fixation.
guish them from spikes from other etiologies. They may occur on one side, During a seizure, there are continuous unilateral occipital SWDs (68). In con-
both sides independently, or bisynchronously. In some patients, spikes can be trast to PS, late-onset occipital lobe epilepsy does not show photosensitivity.
blocked by active or passive contralateral hand movements (64). Spikes may
rarely be localized to the vertex (65). Parietal spikes may also be seen in some Landau-Kleffner Syndrome (Acquired Epileptic Aphasia)
children in response to tactile stimulation, and this may be another useful LKS is a rare epilepsy syndrome characterized by language regression
clinical neurophysiological feature in children with RE (66,67). and an abnormal EEG (69). In the classic presentation, LKS presents in a
Figure 10.15: A: There are abundant stereotyped centrotemporal

spikes evident in sleep. B: These spikes have a horizontal dipole evident
on the referential montage.
Figure 10.16: Late-onset occipital epilepsy (Gastaut). This 8-year-old

has prominent occipital spikes on either side (arrows) and also some
nearly simultaneous frontal spikes in association with the occipital spikes
(arrow head), so-called Fp-O spikes.
previously normal child older than 4 years, with apparent word deafness or Conditions Masquerading as Self-limited
“verbal auditory agnosia.” Seizures and behavior disturbances, particularly Epilepsies with Focal Stereotyped Spikes
hyperactivity, are common features. Many well-respected epileptologists
consider LKS to be the most extreme end of a spectrum of the self-limited Boys with Fragile X syndrome may also demonstrate monomorphic central
epilepsies with focal EEG features. In the author’s experience, it is very rare spikes, although this may be less than 10% of all patients (70). Central spikes
to see LKS developing in this context. Instead, many appear to have some may also be seen in girls with Rett syndrome and these spikes may block
preexisting abnormality and, therefore, neuroimaging is needed. with limb movements (64). In both Fragile X syndrome and Rett syndrome,
The term LKS variant refers to children without the classic features. the EEG background will often demonstrate slowing, and certainly the clin-
These include children with involvement of anterior language areas with ical features of both conditions are very different from those individuals
concurrent expressive aphasias or oral-motor apraxia, sialorrhea, seizures, with RE, so the practical distinction is not a difficult one. This observa-
and an abnormal EEG (stereotyped centrotemporal spikes). There are other tion has been used to support an inherent predisposition to seizures in these
children who present with pervasive developmental disorder (autism) with conditions rather than structural lesions (64).
language regression and abnormal EEGs. Finally, there is another group
of children with developmental language disorders and epileptiform EEGs.
The EEG in LKS shows bilateral, multifocal spikes and spike-and-wave EPILEPSIES WITH ENCEPHALOPATHY (EPILEPSIES
discharges, occurring usually in the posterior regions, especially the tempo- WITH SLOWED BACKGROUNDS AND MULTIFOCAL
ral region, with a marked activation during sleep. A careful review of the PLEOMORPHIC SPIKES)
EEGs in the author’s personal experience and published cases often shows
admixed focal slowing. This feature is common and suggests the presence In most epilepsies associated with an encephalopathy, the EEG back-
of an underlying focal structural lesion. IEDs may occur in many locations, ground reveals etiologically nonspecific abnormalities. Hundreds of
and may even be generalized. Some centers require electrical status epilep- different causes can produce the same EEG appearance, and the EEGs
ticus of slow-wave sleep to diagnose LKS, but at a minimum, most would usually share these common features: diffuse background slowing with
require some degree of sleep activation of the epileptiform discharges to pleomorphic multifocal epileptiform discharges. Beyond the first year of
make the diagnosis. life, many will also show diffuse spikes or polyspikes that are variable in
morphology. If repetitive, these diffuse epileptiform discharges will usu- reflective of the underlying pathophysiology, but for the time being we must
ally have a slow repetition rate. await a better characterization of this complex group of patients. It is frus-
Broadly speaking, there are two subtypes of EEGs found in children with trating work for even the most skilled pediatric electroencephalographers
encephalopathy and epilepsy. The first group has a continuous background because the EEGs by themselves seldom suggest a specific diagnosis.
and can be called the epileptogenic encephalopathies, meaning that the same (Notable exceptions to this would be ring chromosome 20, malignant

factor or factors that produced the encephalopathy also caused the epilepsy. migrating focal seizures of infancy, and Angelman syndrome.) Usually, it
The second group shows some element of discontinuity, often with admixed is the details of the clinical presentation that suggest the underlying cause
electrodecrements, and can be termed the epileptic encephalopathies signi- (e.g., Dravet disease, epilepsy in females with mental retardation, etc.)
fying that the epilepsy per se may be contributing to the encephalopathy. Ex-
amples of the latter include early infantile epileptic encephalopathy (EIEE), Dravet Disease
West syndrome (WS), late infantile epileptic encephalopathy (LIEE), and One could argue that what was previously considered Dravet syndrome
Lennox-Gastaut syndrome (LGS). should now rightfully be called Dravet disease, since a very high percentage
There may be various contributions of genetic, metabolic, and structural of children with the classic clinical characteristics have SCN1A mutations.
causes in each individual. When genetic, though, some general rules apply. This was first reported by Dravet and subsequently confirmed by Dalla Ber-
It is rare to find a familial predisposition to either the EEG features or the nardina et al. (71). Seizures begin in the first year of life (typically around
epilepsy per se in these patients. There are important genetic causes of the 6 months of age) in a previously normal infant who develops prolonged
encephalopathies, but for the most part, they are de novo mutations, and far generalized or unilateral febrile clonic seizures, followed by frequent afebrile
less frequently, diseases caused by recessive inheritance. Standard autosomal convulsive seizures. Subsequently, the child typically has other seizure types
dominant inheritance is very rare. Whole-exome scanning has led to the dis- including myoclonic seizures, atypical absence, and eye flutter attacks. There
covery of more patients with oligogenic causes, meaning that two or more may be a family history of febrile seizures or epilepsy.
gene mutations are conspiring to produce the precise phenotype. In the case The interictal EEG may initially be normal, although low-amplitude
of many epileptogenic encephalopathies, it is difficult to define a precise epi- occipital polyspikes in some infants are present within the first year of life
lepsy syndrome, but perhaps further work will lead to the discovery of new (Fig. 10.17). Multifocal spikes ensue and then generalized spikes, polyspikes,
electroclinical syndromes within this group. and spike-wave activity develop after the second year. Most often, but not
invariably, there is progressive background slowing, which does not strictly
Epileptogenic Encephalopathies correlate with the frequency of seizures or amount of interictal epileptiform
activity. Photosensitivity is common and develops in the first phase of the
The interictal EEG of patients with epileptogenic encephalopathies shows disease.
diffuse background slowing with superimposed multifocal pleomorphic Dravet disease is usually (at least 70% to 80% of cases) associated with
spikes. Diffuse spikes may also occur, but these will not appear uniform and mutations in the SCN1A gene (72). Psychomotor retardation occurs, usu-
will vary in morphology from one complex to the next. Background volt- ally beginning in the second year of life, with ataxia, interictal myoclonus,
ages, even in infancy, are below 300 μV. If severe, the backgrounds may lack and hyperreflexia. The seizures are typically treatment resistant.
an anterior to posterior voltage, and frequency gradient and sleep architec-
ture may be disrupted. In contrast to the true epileptic encephalopathies, Malignant Migrating Focal Seizures in Infancy
the backgrounds tend to be continuous and electrodecrements are not a Malignant migrating focal seizures in infancy is a severe condition that was
frequent feature. first described in 1995 (73). It is characterized by nearly continuous intrac-
There are few well-recognized syndromes in this category, and one could table electrographic and electroclinical seizures involving multiple indepen-
argue that this grouping contains a collection of specific diseases rather than dent areas of onset, beginning in the first 6 months of life in normal infants
a list of epilepsy syndromes. It is entirely possible, however, that new electro- with developmental delay. Previously, the cause was elusive, but more recent
clinical syndromes will be described as work advances, linking new genetic reports have identified likely pathogenic KCNT1 and SCN1A mutations
discoveries with the clinical presentation. Some broad themes may emerge, in affected infants (74,75). It is quite rare, with an estimated prevalence
Figure 10.17: Infant with Dravet syndrome. Spikes and polyspikes,

often, first become apparent in the posterior head regions. Later in life,
diffuse spike waves will be found.
of 0.11 per 100,000 (76). Most seizures are focal and are accompanied by reason to recognize this group is the possibility that the epilepsy, per se, can
autonomic manifestations or subtle version; many have motor manifesta- contribute to the encephalopathy, and therefore, these conditions have urgent
tions that migrate from one side of the body to the other. The outcome is treatment implications. These may rightfully be considered epileptic encepha-
very unfavorable: during short-term follow-up, 3 of 14 patients described by lopathies. Ohtahara conceptualized a spectrum with age-related differences in
Coppola and colleagues (73) died, although there may be a wider clinical clinical and EEG manifestations, but a common thread consisting of severe
spectrum of this disorder (77). Treatment is difficult, but there may be some EEG findings, epileptic encephalopathy, and refractory seizures including tonic
response to bromides, stiripentol with clonazepam, and levetiracetam (78). spasms (79). Examples include the early epileptic encephalopathies (including
The interictal EEG may be normal at the very onset but quickly becomes early myoclonic encephalopathy [EME] and EIEE), WS, LIEE, and LGS. The
abnormal in all cases with multifocal spikes and sleep abnormalities. The ictal additional importance of the electrodecrements is that they indicate a suscep-
EEG is characterized by monomorphic rhythmic theta or alpha activity pro- tibility to epileptic spasms, myoclonic-tonic, and generalized tonic seizures—
gressively involving multiple sites, moving from one area to another (thus the seizure types that do not respond well to conventional antiseizure agents.
term migrating) (Fig. 10.18). Additional seizures start in other areas without
any clear relationship to the original ongoing ictus so that the seizures do not Background Slowing and Disorganization Are Important
appear to simply spread to other regions, but to arise independently. Parts of the Epileptic Encephalopathy
What causes the epileptic encephalopathy? It is possible that IEDs momentarily
Epileptic Encephalopathies impair the brain’s ability to respond with agility (80), but the most conspicuous
feature of the EEGs in the patients is the background slowing and disorganiza-
As mentioned earlier, there is a second subgroup of epilepsies with encephalop- tion. In many different experimental settings, memory has been tied to brain
athy where the EEGs show some degree of discontinuity, manifested as a dis- oscillations, and so it stands to reason that slowing of these rhythms would
continuous background, with electrodecrements, or both. The most important have a devastating effect on cognition (81). This association of slowing with
Figure 10.18: Migrating focal (partial) seizures in infancy. A: An ictal

discharge is seen involving the right temporal lobe; B: Moments later,
there is an involvement of the left temporal region.
cognitive impairment has been well known to the clinical EEGer, but perhaps Early Epileptic Encephalopathies
has been misinterpreted as simply a marker of brain dysfunction rather than Two well-recognized neonatal epileptic encephalopathies are EME and
a potent contributor to that dysfunction. More research on epileptic encepha- EIEE. EME is quite rare and characterized by fragmentary or erratic partial
lopathies will hopefully provide additional clues to the cause of these devas- myoclonus, massive body myoclonus, focal motor seizures, and tonic spasms
tating effects and may provide novel therapeutic approaches where defects in (83). Massive myoclonus is not invariant and tonic spasms resembling infan-
learning can be targeted independent of interictal spikes and seizures (82). tile spasms usually appear around 3 months of age. Babies show a marked
encephalopathy with altered alertness, hypotonia, and hyperreflexia. Neuro- Portions of the EEG background show burst suppression, but unlike
imaging is usually unremarkable. The classic association is with nonketotic Ohtahara syndrome, this pattern may only be seen in sleep (Fig. 10.19).
hyperglycinemia, though other progressive metabolic and neurodegenera- There are abundant multifocal spikes scattered throughout the background.
tive disorders must be considered. The prognosis is very poor and many Although the bursts are synchronous, the spikes themselves show no bilateral
patients do not survive infancy. synchrony beyond the random chance of coinciding over the two hemispheres.
Figure 10.19: Early myoclonic encephalopathy. This infant has n onketotic

hyperglycinemia. A: Massive myoclonias were noted with these busts.
Note the burst-suppression pattern. B: In another portion of the tracing
with the infant more alert, the background is slightly more continuous.
This variability in the burst-suppression intervals differentiates the EEG
from that seen in Ohtahara syndrome.
A similar but distinct syndrome was described by Ohtahara and col- that manifest in infancy (1,88). The spasms themselves consist of sudden
leagues (84) and bears his name; it is also known as early infantile epilep- myoclonic and tonic phases, including brief head nods, with quick extension
tic encephalopathy (EIEE). It is also rare, but more common than EME and flexion movements of the trunk, arms, and legs, occurring in clusters
(in our experience) and characterized by tonic spasms in the first month and especially during transitions from sleeping to waking.
of life and an interictal EEG showing burst suppression (85). In contrast The classic interictal EEG finding, hypsarhythmia (89) was coined by Gibbs
to EME, the burst-suppression pattern occurs in both awake and asleep, and Gibbs. It is derived from the Greek word hypselos, which means “high,”
and the interburst interval tends to be relatively constant, often about 3 to indicating the magnitude of the voltage that generally predominates—usu-
5 seconds (Fig. 10.20). The prognosis is extremely poor, with a mortality ally above 300 μV. (Special note: the Gibbs’ used one “r” in hypsarhythmia
of 50% before the age of 1 month. Ohtahara syndrome has been associ- and we follow the same spelling to honor their description of the term.) In
ated with a de novo mutation in the gene encoding STXBP1 (also known as the classic form, bursts of very high-voltage slow waves occur in an irregular
MUNC18-1), a protein essential for synaptic vesicle release, as well as with fashion, superimposed on a completely disorganized background with no
the ARX mutation (86). anterior to posterior voltage/frequency gradient. There are abundant multi-
Transition into WS and LGS is common in the Ohtahara syndrome and focal and diffuse epileptiform discharges, which often have a posterior pre-
rare in EME (87). dominance (Fig. 10.21). The interictal epileptiform activity may consist of
spikes, sharp waves, repetitive spikes, polyspikes, and paroxysmal fast activ-
West Syndrome ity. The findings usually increase in sleep and therefore a sleep recording is
very helpful in the evaluation of infants with suspected spasms (90). From
WS is characterized by the triad of infantile spasms, hypsarhythmia, and time to time, and particularly in sleep, the background may suddenly be in-
developmental delay. The peak onset is between 4 and 7 months and always terrupted by a generalized electrodecrement, or less commonly in only a few
before 12 months of age. Infantile spasms are a subset of epileptic spasms EEG channels or over one hemisphere.
Figure 10.20: EIEE. Note the characteristic burst-suppression pattern.

Figure 10.21: WS. Hypsarhythmia is a high-voltage, disorganized

pattern with multifocal spikes.
Likewise, the ictal EEG, occurring at the time of the actual infantile Hypsarhythmia variants have been described and it is important to know
spasms may be variable, but usually has an electrodecremental response, that they exist, but the prognosis does not appear to correlate with any of these
lasting for several seconds (Fig. 10.22). There are four different components different patterns: increased interhemispheric synchronization, asymmetrical
to an electrodecrement: (a) a high-amplitude diffuse but vertex-maximal hypsarhythmia, hypsarhythmia with a consistent focus of abnormal discharge,
positive slow wave (the most common element) (91); (b) Admixed multifocal hypsarhythmia with episodes of attenuation, and hypsarhythmia comprising
IEDs “riding” on this underlying slow wave; (c) Diffuse attenuation of the primarily high-voltage slow activity with little sharp-wave or spike activity (85).
background lasting one to several seconds; (d) Low-voltage fast rhythms A large number of conditions can cause WS. In addition to anatomic
often with a posterior predominance. lesions, other disorders, especially metabolic and infectious, and now, an
Figure 10.22: WS. The EEG correlate of an infantile spasm is an electro-

decrement. Note the rhomboid shape discharge on the deltoid channel.
This is the common polygraphic correlate of an infantile spasm. Polygraphic
channels are very useful to quickly identify whether electrodecrements
have an associate clinical component.
expanding list of specific genetic disorders, need to be excluded (92). It is for many years and has gone by several names, including cryptogenic late-
important to note that apparently generalized spasms may stem from focal onset epileptic spasms, infantile epileptic encephalopathy with late-onset
lesions, such as tumor, stroke, or a focal cortical dysplasia (93). Practice spasms or LIEE (99–101). Myoclonic-tonic seizures are commonly seen,
parameters and consensus statements have stressed the importance of and resemble something between an epileptic spasm and a diffuse tonic
ACTH and vigabatrin over other treatments (94,95). A UK study showed seizure. There is a sudden myoclonic movement often involving the arms,
that ACTH and oral prednisone have a better efficacy than vigabatrin (96). head and trunk, followed by several seconds of tonic stiffening of the same
Vigabatrin may be especially effective when spasms are caused by tuberous body parts. The tonic phase does not last as long as a typical generalized
sclerosis (97). Modern protocols have resulted in a higher rate of patients tonic seizure, and yet has a duration longer than the typical infantile spasm.
that have been successfully treated, but developmental regression remains a Similarly, polygraphic recordings show an intermediate signature between
persistent problem (98). the rhomboid shape of an epileptic spasm and the prolonged rectangular
In addition to cessation of spasms, the other goal of treatment is normal- shape of a tonic seizure. Spasms or myoclonic-tonic seizures can occur sin-
ization or improvement of the EEG. In most cases, the EEG shows rapid im- gly, but sometimes occur in groupings with irregular time intervals between
provement when treatment is effective. Complete normalization may occur each individual spasm. This is in contrast to infantile spasms or periodic
and is the most gratifying response. Normalization may be only temporary, spasms in older children where the time interval between spasms is rather
and if abnormalities return, one must be on guard not only for the return of regular.
spasms but also for the potential of other seizure types to develop. In cases The interictal EEG shows slowing, multifocal spikes and a moderately
with a poor therapeutic response and especially in those with preexisting brain high-voltage background, but usually not above 300 μV (Fig. 10.23). During
damage, a transition to LIEE or LGS a transition to LIEE or LGS may occur. spasms or myoclonic-tonic seizures, there are electrodecremental responses
lasting several seconds (Fig. 10.24). The seizures are refractory to many
Late Infantile Epileptic Encephalopathy different treatments and the prognosis is severe with developmental delay
in the vast majority. A number of infants will go on to LGS (101). Like
Some infants develop or manifest epileptic spasms or seizures closely resem- its counterparts, EIEE, WS, and LGS, this condition is another epileptic
bling spasms beyond the first year of life. This entity has been recognized encephalopathy with age-related EEG and clinical manifestations.
Figure 10.23: LIEE. The background in LIEE is not as high voltage as in

hypsarhythmia, and there is typically more organization. Still, pleomor-
phic multifocal spikes are seen.
Figure 10.24: LIEE. A common seizure is myoclonic-tonic, which is often

associated with an abrupt relative attenuation of the background fol-
lowing a diffuse slow-wave transient (resembling, but different from a
typical electrodecremental response). The polygraphic channel shows
the myoclonic and tonic components.
Lennox-Gastaut Syndrome Just as in the other epileptic encephalopathies, there are many different
potential causes of LGS. Despite modern imaging, genetic evaluations and
LGS is another triad of intellectual disability, mixed seizures including metabolic testing there are still some cases where the etiology is unknown,
particularly nocturnal tonic seizures, and diffuse slow SWDs. The proto- but probably no one develops LGS on the backdrop of completely normal
typic seizure is nocturnal generalized tonic, but atypical absence is also development—instead there is almost invariably a history of antecedent
very common. Drop attacks or astatic seizures consisting either of tonic neurological abnormalities and developmental delay. LGS usually starts be-
or atonic components are another common feature and are troublesome tween the ages of 1 and 10 years, and about 10% to 20% of children with
because they can lead to substantial injury. Focal seizures also occur. LGS have passed through WS before LGS becomes evident (103).
While Gibbs and colleagues first noted a severe prognosis in patients with Gastaut and colleagues (104) divided tonic seizures into axial, axorhi-
slow spike-wave complexes (the so-called “petit mal variant”), in 1939 a zomelic, and global forms. All seizures are relatively short, lasting 5 to
detailed account of the clinical and EEG features of these patients was 20 seconds. With axial seizures, there is eye opening and some axial stiffness.
given by Lennox in 1960 and Gastaut in 1966. Niedermeyer (102) pro- Axorhizomelic seizures have additional involvement of the proximal limbs,
posed the term Lennox-Gastaut Syndrome in 1968 and followed this with a and global forms show diffuse involvement. Tonic seizures are common in
review years later. non-REM sleep and have bilateral synchronous fast or moderately fast spike
The interictal background is slowed and often lacks the normal organiza- activity of about 10 to 25 Hz of medium to high voltage and frontal accen-
tion. A well-developed and maintained posterior dominant rhythm may be tuation is the EEG concomitant of these attacks (“runs of rapid spikes”).
absent and there are abundant superimposed pleomorphic multifocal IEDs. Electrodecrements may also occur.
Many have to come to associate the slow spike-and-wave discharge (1.5 to In atypical absence seizure, the clinical onset and termination are less
2.5 Hz) as being the hallmark of LGS, but bursts of slow spike-wave activ- abrupt than in classical absences and are usually accompanied by diffuse
ity are also seen in other conditions (Fig. 10.25). Paroxysmal bursts of fast SWDs with a 2.5-Hz or slower repetition rate. Atypical absence status
rhythms (10 Hz) are common and typically occur during the tonic seizure epilepticus may occur. Astatic seizures are often accompanied by an

(Fig. 10.26). electrodecrement.
Figure 10.25: LGS. This segment of EEG shows abundant slow spike-
wave activity.
FOCAL STRUCTURAL EPILEPSIES lesions, regardless of their nature, are often associated with focal slowing,
attenuation, or both. In addition, IEDs tend to be pleomorphic with varia-
A common cause of refractory focal seizures in children is a focal struc- tions in their precise morphology and topography. This contrast with the
tural lesion involving the cortical grey mantle, and one of the commonest spikes is seen in those self-limited epilepsies with focal seizures—in the lat-
lesions seen at epilepsy surgery is a cortical malformation. Low-grade glio- ter, the spikes tend to be uniform or stereotypic. One way to remember this
mas and vascular lesions are other important etiologies. Focal structural distinction is to imagine spikes arising from any of a number of locations
Figure 10.26: LGS. Commonly seen are runs of rhythmic faster frequen-
cies, which may be associated with tonic seizures in sleep. This tonic
seizure was axorhizomelic.
surrounding a cortical lesion, whereas the self-limited epilepsies without habitual behavior may have difficulty identifying the onset of the event. The
focal structural lesions have an innate driver of the spikes that reproduces infant is unable to vocalize the presence of an aura, cannot be asked about
the spikes with fidelity from one instance to the other. A high-quality MRI his or her experiences during the event to determine consciousness, does not
with a careful clinical reading is of course most useful, but a considerable exhibit contralateral dystonic hand postures, and does not show ipsilateral
amount of information about the location of the lesion can be gleaned by a fine hand automatisms. Well-developed secondary generalization with syn-
careful inspection of the interictal and ictal EEG coupled with an analysis chronized clonic activity of both sides of the body is rare, particularly in
of the ictal semiology. This allows one to focus on a particular region of the those epilepsies with focal structural lesions (113).
MRI and that specificity helps to uncover subtle cortical lesions.
The ictal semiology in young children has some inherent limitations as it The Terms, “Simple” and “Complex”
relates to the ability to precisely localize lesions. The clinical manifestations Are Difficult to Apply
of seizures in infants and younger children differ markedly from those in
older children and adults; the net impact of these differences restricts our It can be extraordinarily difficult to reliably determine alteration of con-
ability to precisely localize an ictal discharge based solely on clinical features sciousness in most infants. For these reasons, the terms “simple” and “com-
(105,106). These differences relate, at least in part, to factors intrinsic to plex” are difficult to apply with any degree of certainty to most infantile
the immature brain, which bestow unique electrophysiological characteris- seizures, or for that matter, any child with a preexisting issue with commu-
tics, including the underlying normal brain development, the topography of nication. With adults, it is possible to ask the patient to follow commands,
brain metabolism, development of myelinated connections, and properties repeat phrases, and to recall test items. None of these can be performed in
of ion channels and their associated ion gradients. the preverbal child. Inattentiveness, such as not turning the head to alerting
As the child matures, the intrinsic properties of brain physiology change stimuli is not the same as altered consciousness.
and thereby alter the expression of seizures. Gradually, seizures take on char- As a result, Dravet and colleagues (114) studied infants with focal epilepsy
acteristics seen in adults. These changes occur in an orderly fashion so that and used the term undetermined partial seizures for three patients in whom
an ontogeny of ictal semiology can be described, just as one can characterize they experienced difficulty with this assessment. Duchowny (115) accepted
and predict normal child development (107,108). A general understanding the term complex partial in this setting, under the assumption that some
of these key differences and some detailed knowledge of the electroclinical disturbance of consciousness must have occurred, based on unsuccessful at-
correlation of infantile seizures allows the examiner to ask better questions tempts to influence attention by various maneuvers. In a study at The Cleve-
during the medical interview, aids the evaluation epilepsy surgery, and in- land Clinic Foundation, of videotaped seizures from infants under 2 years
creases the chances of making a correct epilepsy syndrome diagnosis. old with localization-related epilepsy, the authors found it impossible to be
as confident about level of consciousness, despite similar attempts (116).
Infantile Seizures are Often Subtle Nordli and colleagues (105) reached the same conclusions.
Many infantile seizures are subtle and lack declarative features seen in Infantile Focal Seizures May
adults (105,109). This is particularly true of those arising from the temporal Have “Generalized” Clinical Features
lobe and posterior quadrants: the infant may pause ongoing behaviors, sud-
denly stop his movement, and exhibit simplistic automatisms, like mouthing Seizures that appear to be widespread or diffuse are common in infants but
movements (110–112). These have been referred to as behavioral arrest, be- they do not necessarily have a diffuse or generalized EEG correlate. Two of
havioral change, or hypomotor seizures. Oxygen desaturation may accom- the most important features in this category are also diffuse tonic postures
pany these events, and if connected to an oxygen saturation monitor, the and infantile spasms. Diffuse tonic postures, even symmetric ones, are com-
change in the tone of the monitor may be the first sign alerting observers mon during infantile focal seizures, as are other symmetric motor phenomena
to the presence of the seizure. Parents reliably and quickly detect the pecu- (117). Several authors noted bilateral tonic stiffening or clonic or myoclonic
liar change in the infant’s behavior, but others unfamiliar with the child’s movements during focal seizures in infants (110,115).
Difficulty Lateralizing Based upon Clinical Features Hypermotor: Another very rare infantile focal seizure is a hypermotor sei-
zure. This is characterized by incessant nonpurposeful and disorganized
The ictal semiology provides fewer clues to the laterality of the seizure in movements. Its electrographic correlate is a unilateral hemispheric onset
infants when compared to older children or adults. This is largely due to the of rhythmic delta waves.
paucity of declarative features such as contralateral limb dystonia, ipsilat- Diffuse tonic-focal clonic: These seizures are characterized by a bilateral
eral hand automatisms, auras, and orderly secondary generalization. Also, symmetric tonic posture that followed or preceded unilateral or bilateral
the presence of diffuse postures or spasms obscures some other features and asymmetric myoclonic jerks. Electrographically, these may arise from
makes it difficult to discern subtle asymmetries. multiple regions and have variable ictal features, including rhythmic
spikes, fast spike waves, and low-voltage fast activity.
Spasms with focal features: This category includes spasms that are accompa-
Types of Infantile Focal Seizures nied by independent focal seizures and spasms that had markedly asym-
and Their Electroclinical Correlations metric features, either clinical or electrographic. These are commonly
seen, but may require careful inspection of the clinical and EEG features
In one study, a total of 2,112 patients were reviewed and the authors found
in order to be appreciated.
109 distinct seizures in 77 infants (118). Overall, 13 seizure types were identi-
fied, of which 10 types were seen in patients with focal structural epilepsy.
CONCLUSIONS
Behavioral arrest with version: These are one of most common forms of focal
seizure in infants. During the seizures, infants have a prominent behav- Most forms of pediatric epilepsy can be easily classified using clinical in-
ioral arrest and pronounced version of the head, eyes, or both. The vast formation and data from the routine interictal EEG. There are only five
majority have a unilateral focal onset arising from the temporo-parieto- discrete clusters that provide the necessary information to triage the patient,
occipital region. Often involving rhythmic activity at onset. More rarely, initiate care, and provide general prognostic information (Table 10.1). One
pure behavioral arrest without version may also be seen. can arrive at a more detailed diagnosis by considering the age of presenta-
Focal clonic: These seizures are characterized by unilateral or bilateral asym- tion and finally the predominant seizure type (Table 10.2). Not all EEGs are
metric myoclonic jerks of the limbs in all patients. The electrographic onset equally informative owing to random sampling and a variety of other fac-
is focal in all patients, and more specifically anterior (frontal, central, or tors that influence the yield of the routine EEG, so repeated EEG sampling
frontal-central) in about three-fourths of patients. Repetitive spikes were may be necessary to confidently classify. Also, the passage of time is very
observed in the majority of children with this seizure type, while other helpful in allowing other clinical manifestations to present.
patterns include low-voltage fast activity, attenuation, or rhythmic delta. Still, even with repeated follow-up, there will still be some children whose
Focal tonic: These seizures are characterized by a predominant asymmetric epilepsy cannot be precisely classified. In these situations, it is most helpful
tonic. The electrographic correlate can arise from various regions, and to fall back on simple principles and to consider the development of the
most often involved some type of rhythmic activity and less likely low- child and the nature of the interictal EEG.
voltage fast activity. The first three groupings of EEG patterns/epilepsies occur in the context
Focal tonic-clonic: These seizures are less commonly seen and are character- of a normally developing child with a normal EEG background for age and
ized by unilateral myoclonic jerks and asymmetric tonic posturing, which either no spikes or stereotyped spike morphology. These children generally do
either preceded or followed the former. Electrographically, these seizures well and usually do not require extensive evaluations and can likely be man-
are accompanied by a rhythmic discharge at onset. aged without special resources. (Table 10.3) (There are always exceptions to
Focal tonic-clonic with secondary generalization: These seizures are uncom- every rule. All infants and those children who fail to respond to the first one or
mon, particularly in the very young. They are characterized by an asym- two selected medications within these groups may benefit from special scrutiny
metric or symmetric tonic posture followed by unilateral or bilateral at a tertiary center.) Conversely, the fourth and fifth EEG patterns/epilepsies
asymmetric clonus. The electrographic onset is a run of unilateral spikes occur on the backdrop of developmental delays or focal neurological defi-
or rhythmic theta-alpha (RTA) pattern. cits, slowed EEG backgrounds, and pleomorphic spikes. These epilepsies raise
Table 10.2 Epilepsy Syndromes Organized by Interictal EEG Characteristics
Name EEG features Neonatal Infancy Childhood Adolescence

1. Familial Normal BFNE BFIE ADNFLE AD with auditory features
AD familial temporal lobe
2. Genetic generalized Normal background None MEI Doose syndrome Juvenile absence
spike-wave epilepsies Stereotyped GSW Childhood absence Juvenile myoclonic
Epilepsy with myoclonic
absence
Jeavons syndrome
3. Self-limited epilepsies Normal background None PS RE None
with focal spikes Stereotyped focal and Late-onset occipital
multifocal spikes epilepsy (Gastaut)
Atypical rolandic
LKS
4a. Epileptogenic Slowed background None Migrating focal Dravet syndrome Progressive myoclonus
encephalopathies Pleomorphic multifocal spikes seizures of epilepsies
infancy
4b. Epileptic Slowed background Early myoclonic WS LGS None
encephalopathies Pleomorphic multifocal spikes epilepsy LIEE
Some discontinuity, EIEE
electrodecrements
5. Focal structural Focal slowing/attenuation — — — —
epilepsies Pleomorphic focal spikes
Table 10.3 Outcome of Epilepsy Syndromes Organized by Interictal EEG Characteristics
Quick referral
Name EEG features Prognosis to specialist?
1. Familial Normal Mostly favorable No
2. Genetic generalized spike-wave Normal background Favorable, but some require long treatment No
epilepsies Stereotyped GSW
3. Self-limited epilepsies with focal Normal background Epilepsy is self-limited but may still have No
spikes Stereotyped focal and multifocal spikes co-morbid conditions
4a. Epileptogenic encephalopathies Slowed background Poor Yes
Pleomorphic multifocal spikes
4b. Epileptic encephalopathies Slowed background Severe Yes
Pleomorphic multifocal spikes
Some discontinuity, electrodecrements
5. Focal structural epilepsies Focal slowing/attenuation Variable Yes
Pleomorphic focal spikes
311
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11 EEG in Adult Epilepsy
MOHAMAD Z. KOUBEISSI • ELSON L. SO
Introduction Ictal EEG in Focal Epilepsy

Interictal Epileptiform Discharges Ictal EEG in Generalized Epilepsy
Focal IED Limitation of Interictal and Ictal Scalp EEG
Generalized IED Summary
Photo-Epileptiform Discharges (Photoparoxysmal References
Response)
Ictal EEG
Features of Scalp-Recorded Ictal Discharges
Introduction abnormalities “applies to distinctive waveforms or complexes resembling

those recorded in a proportion of human subjects suffering from epi-
The use of EEG in the evaluation of seizure disorders typically begins in the leptic disorders and in animals rendered epileptic experimentally” (1).
outpatient setting as a procedure performed using scalp electrodes during the Another definition of epileptiform waveforms or patterns is that they are
interictal period. Ictal EEG is now commonly performed with simultaneous EEG abnormalities that are associated with a predisposition to experi-
video recording, in either outpatient or inpatient setting. The objective of this encing or developing epileptic seizures. The word predisposition is used
chapter is to discuss the types of interictal epileptiform discharges (IEDs) and to indicate that the association between epileptiform abnormalities and
ictal discharges recorded from the scalp in adults. The emphasis of this chapter seizure disorders is not absolute. Presence of epileptiform discharges
is on the features of IEDs and ictal discharges and their clinical correlation. does not necessarily indicate that the patient has a seizure disorder (2).
However, the detection of epileptiform abnormalities does increase the
Interictal Epileptiform Discharges likelihood of an epileptic seizure disorder being present. When the find-
ing is taken together with the clinical history and other diagnostic test
According to the International Federation of Societies for Elec- results, epileptiform abnormalities help in establishing the diagnosis of
troencephalography and Clinical Neurophysiology, “epileptiform” epileptic seizure disorders.
315
Focal IED Spikes/sharp waves are often followed by a slow wave that can be smaller
or larger than the spike/sharp wave discharges themselves. The spike/sharp
Spikes/Sharp Waves wave with its after-going slow wave may be referred to as a “spike-and-slow-
Spikes are transient waveforms with pointed peaks when displayed at a screen wave complex” (i.e., a complex is a series of two or more individual waves).
resolution of approximately 30 mm per second (Fig. 11.1). By definition, du- The accompaniment of spikes/sharp waves by an after-going slow wave may
ration of spikes varies from 20 to 70 milliseconds, whereas sharp waves are not be constant in the same patient and at the same location. When the
wider with duration between 70 and 200 milliseconds (1). The distinction in spike/sharp wave is of negative polarity, as is most often the case, the after-
this regard between spikes and sharp waves is somewhat arbitrary. The two coming wave will be negative as well. Separating these two will be a deflec-
types of waves often occur in the same clinical disorder or the same patient. tion of positive polarity.
Spikes/sharp waves should have sufficient amplitudes to distinguish them
from the background, such as by a factor of two. They are often polyphasic, Focal Spikes/Sharp Waves
but the main component is usually surface-negative. Surface-positive IEDs Common locations of focal spike/sharp-wave discharges, in the approximate
are rare, and can occur at the site of craniotomy (3), particularly if lateral order of frequency, are temporal, frontal, centrotemporal, parietal, occipi-
convexity cortex is removed, but not more mesial cortex. Central positive tal, and midline central and/or paracentral. The clinical correlation of focal
sharp waves can be observed in infants with intraventricular hemorrhage or spikes/sharp waves is with focal epilepsy; however, the likelihood that a given
periventricular white matter injury, but the discharges are a better indication focal spike/sharp wave is associated with epilepsy varies with its location (5).
of encephalopathy than of epileptogenicity (4). For instance, the association is higher for temporal spikes/sharp waves than
Figure 11.1: Left midtemporal spike in a 33-year-old woman who had

been experiencing spells of smelling burnt rubber, followed by lip smack-
ing and behavior of confusion. This spike discharge is not followed by
an after-going slow wave. MRI showed a cavernous angioma at the left
temporal lobe, despite lack of left temporal slowing during wake EEG.
EEG in Adult Epilepsy 317
for rolandic or occipital spikes/sharp waves. Approximately 90% of children with periventricular hemorrhage or leukomalacia and in young children with
with anterior temporal spikes have seizures, whereas seizures are present in multifocal spikes/sharp waves, especially in the presence of global encepha-
only 38% of those with rolandic spikes. Temporal lobe tissues, especially the lopathy, such as with ischemic injury or lipid storage diseases (9,10).
hippocampus and the amygdala, are some of the most epileptogenic. The The identification of focal spikes/sharp waves is very important in the di-
temporal lobes are also frequently involved in pathologic conditions, such as agnosis of benign, age-related epilepsy syndromes (see Chapter 10). Spikes/
hypoxia, strokes, tumors, trauma, and vascular malformations. In contrast, sharp waves in these syndromes have distributions, morphology, and activa-
many children with occipital IED do not have epilepsy; in fact, about 60% of tion factors that are characteristic for each syndrome. The most common
children with occipital spikes do not have epileptic seizure disorders (6), and is benign epilepsy of childhood with centrotemporal spikes (also known as
occipital IEDs are even encountered in nonepileptic persons with migraine benign epilepsy with centrotemporal spikes, BECT, or benign rolandic epi-
disorders (7). Other occipital discharges, known as “needle spikes,” can be ob- lepsy). Other childhood syndromes of focal epilepsy are benign childhood
served in the EEG of children who have congenital blindness but not epilepsy epilepsy with occipital paroxysms and the syndrome of early-onset child-
(8). These occipital spikes are low in amplitude and sharp in configuration. hood seizures with occipital spikes (Panayiotopoulos syndrome) (11).
Most focal spikes/sharp waves are surface negative at the scalp. Positive
spikes/sharp waves are not common in the adult patient. They can be seen Multifocal Spikes
postoperatively when overlying convexity cortex is removed, but more mesial Multifocal spikes/sharp waves refer to the presence of multiple indepen-
cortex remains. Synchronous, but spatially separated, positive and negative dent foci of spikes or sharp waves that involve both hemispheres (Fig. 11.2).
spikes are evident when the spike voltage field is tangential rather than radial. Although this abnormality can be seen at any age, it is most frequently
Positive-polarity discharges are more frequently encountered in newborns observed in children aged 4 to 7 years (12). Background EEG slowing is
Figure 11.2: Multifocal spikes appearing at F4, F8, P8, O1, and bisyn-
chronously at the occipital regions. The patient had medically refractory
seizures since childhood. Note also the generalized slowing in the back-
ground. EEG is displayed in Laplacian montage. The patient had other
EEG abnormalities, which, together with the clinical history, suggest LGS
(see Figs. 11.7 and 11.9).
present in nearly all these patients, and 94% of them have seizures. General- distribution within a hemisphere, or more diffusely affecting a whole hemi-
ized motor seizures are the most common, occurring in 76% of patients (13). sphere. The temporo-parietal-occipital region is most frequently involved.
Seizures are typically frequent, with half of the patients experiencing daily PLEDs are highly associated with acute cerebral disorders, especially those
seizures. Concomitant neurological abnormalities are also common; 45% producing structural lesions such as stroke (infarct or hematoma), brain
of these patients have motor deficits and 82% have mental retardation and trauma, herpes encephalitis, tumor, and abscess. Rare causes include met-
developmental delay. The majority (71%) have underlying structural brain abolic encephalopathy, Creutzfeldt-Jakob disease, migraine, and toxic en-
abnormalities or a history of brain injury. cephalopathy (e.g., aminophylline or alcohol intoxication).
Fifty percent of patients with PLEDs will develop seizures, most often
Periodic Lateralized Epileptiform Discharges of a focal nature, with or without secondary generalization. Reiher and
Periodic lateralized epileptiform discharges (PLEDs) are epileptiform dis- colleagues (17) observed that PLEDs may be multiphasic and burst-like in
charges or complexes that recur with a regular periodicity in one hemi- appearance. PLEDs-plus is the term they coined for this type of periodic
sphere, usually every 0.3 to 4 seconds (14) (Fig. 11.3). This periodic activity activity, as opposed to the less complex morphology of PLEDs-proper.
may take the form of monophasic or polyphasic spikes or sharp waves, PLEDs-plus carries a much higher association with clinical seizures
which may or may not have accompanying slow waves (15,16). Although and status epilepticus. In fact, ictal activity is commonly recorded with
very focal PLEDs have been observed, usually the discharges are regional in PLEDs-plus.
Figure 11.3: Periodic lateralized epileptiform discharges (PLEDs) at

the right hemisphere in a 40-year-old man who had a small right frontal
tumor. The patient experienced a generalized convulsive seizure 12 hours
before the EEG recording was performed.
PLEDs are transient and they may transform over days or weeks into in- Nearly 90% of patients with multifocal PLEDs have seizures. Prognosis is
termittent monomorphic slow waves with or without sporadic spikes/sharp dependent on the underlying cerebral disorder. For example, patients with
waves. The interval between discharges typically lengthens over time as well. acute cerebral lesions or infections have a higher mortality than those whose
These intermittent slow waves eventually disappear, possibly leaving resid- PLEDs follow a bout of multiple seizures.
ual focal slowing, which reflects the sequela of underlying brain damage.
When PLEDs are recorded bilaterally, the term BIPLEDs is commonly Temporal Intermittent Rhythmic Delta Activity
used. These discharges may be temporally dependent or independent (18). Temporal intermittent rhythmic delta activity (TIRDA) consists of inter-
They are encountered in patients with severe hypoxic encephalopathy or mittent sinusoidal trains of rhythmic delta waves from the temporal region
bilateral hemisphere destructive lesions. BIPLEDs, particularly when inde- that typically last several seconds (Fig. 11.4) (20,21). The most common
pendent, are associated with a poor prognosis for survival or recovery of frequency is 2 to 3 Hz. Although anterior temporal is the predominant loca-
normal neurological functions. tion, posterior TIRDA can also be observed. TIRDA may appear in wake-
In multifocal PLEDs, there are at least three foci of periodic activity in- fulness or sleep, but it is often most easily identified in drowsiness. Reiher
volving both hemispheres (19). Multifocal PLEDs are encountered in pa- and colleagues (20) have demonstrated that TIRDA is highly correlated with
tients with severe and diffuse brain dysfunction or with multifocal lesions a history of temporal lobe seizures. In a case-control study, all patients with
of both cerebral hemispheres. Etiologies include multifocal strokes, infec- TIRDA were shown to have complex partial epilepsy (21), and the major-
tion, a state of seizure exacerbation, and toxic/metabolic encephalopathy. ity also had temporal spikes/sharp waves on their EEGs. Temporal depth
Figure 11.4: Temporal intermittent rhythmic delta activity (TIRDA; indi-

cated by a circle) at the right temporal lobe in a 32-year-old patient with
medically refractory epilepsy. MRI showed evidence of right mesial tem-
poral sclerosis, in the form of hippocampal atrophy and fluid-attenuated
inversion recovery (FLAIR) signal abnormality.
electrode recording during TIRDA on the scalp showed active spiking from (HV) or drowsiness. These bilateral bursts are synchronous in timing and
the amygdalohippocampal structures. TIRDA is commonly associated with symmetric in amplitude between hemispheres, although shifting asymmetry
underlying structural lesions. In fact, two-thirds of the patients in the study is common from burst to burst. On close inspection, latency differences be-
had pathology of the temporal lobe. tween hemispheres can be detected, but usually by no more than 20 millisec-
onds. The amplitude of these discharges may be upward of several hundred
Generalized IED microvolts and typically most prominent in the midline frontal region.
3-Hz spike-and-wave discharges are the EEG signature of absence epilepsy.
Generalized IEDs have a variety of forms—3-Hz spike-and-waves, atypical It is now known that even a brief burst can interfere with mental functioning.
spike-and-slow-waves, slow spike-and-wave discharges, hypsarhythmia, and The effect is subtle and may not be apparent by visual observation; however,
generalized repetitive fast discharge (GRFD). neuropsychological testing has demonstrated that even a 1- or 2-second burst
will briefly interrupt continuous motor tasks (22). Bursts of 3 seconds or
3-Hz Spike-and-Wave longer duration are more consistently accompanied by the clinical signs of
As the name implies, 3-Hz spike-and-wave discharges are runs of bilateral an absence seizure, namely, behavioral arrest, staring, and/or eye fluttering.
spikes and after-coming slow waves that repeat rhythmically at a rate of three HV is a standard procedure for activating absence seizures and 3-Hz
cycles per second (Fig. 11.5). Each burst typically lasts between 1 and 3 sec- spike-and-wave bursts during EEG recording. However, clinicians must be
onds, but longer runs occur, especially when activated by hyperventilation aware of pseudo-absence events that can occur in some children without
Figure 11.5: Hyperventilation-induced paroxysm of 3-Hz spike-and-

waves in an 11-year-old girl who had behavioral arrest and eyelid flutter-
ing during the paroxysm. (Interval between gridlines is 200 milliseconds.)
epilepsy (23). This nonepileptic phenomenon has EEG features of runs of bursts. The atypical spike-and-slow-wave pattern is more likely to occur as
high-voltage, semirhythmic to rhythmic, delta waves that may be slower than single bursts rather than in long repetitive runs. Drowsiness and non-REM
the usual HV buildup. This slowing is widely distributed, but often with a sleep activate generalized atypical spike-and-slow-wave discharges, and they
maximal amplitude at the anterior head regions. However, careful analysis may be entirely absent during wakefulness in some patients.
of the EEG in pseudo-absence spells shows that spikes are lacking, unlike The clinical correlation of the generalized atypical spike-and-slow-wave
real 3-Hz spike wave. Unfortunately, the clinical appearance of pseudo- abnormality is with primary generalized epilepsy, including benign myo-
absence spells can mimic that of genuine absence seizures (24). Accordingly, clonic epilepsy of early childhood, myoclonic-astatic epilepsy of early child-
an EEG recording is required to differentiate the two. hood, juvenile myoclonic epilepsy (JME) of Janz, juvenile absence epilepsy,
atypical absence epilepsy, epilepsy with grand mal on awakening, and pho-
Generalized Atypical Spike-and-Slow-Waves tosensitive epilepsy (26).
Generalized atypical spike-and-slow-wave discharges are bilaterally synchro- In patients with both 3-Hz and atypical spike-and-slow waves, it is not
nous complexes that resemble 3-Hz spike-and-wave discharges, but differ in uncommon for focal spikes of low amplitude to appear during drowsiness
that they have variable rates, although mostly close to 4 Hz. Also, the spike in the frontal or temporal regions. These do not indicate an accompanying
component of the complexes is often polyphasic (25) (Fig. 11.6). Moreover, focal seizure disorder, as long as they are not abundantly present at a single
the complexes vary greatly in amplitude and morphology within and between location during wakefulness or sleep.
Figure 11.6: Generalized atypical spike-and-slow-wave complexes in a

19-year-old woman who since age 13 years has had sporadic generalized
tonic-clonic seizures on awakening in the morning. The patient did not
have myoclonic jerks or absence spells, but the recorded paroxysms,
such as the one shown in this figure, were sometimes accompanied by
brief arrest of activity.
Slow Spike-and-Waves (Sharp-and-Slow-Wave Complexes) pattern is commonly seen as one of the EEG features of Lennox-Gastaut
As the name indicates, the slow spike-and-wave discharge pattern is charac- syndrome (LGS) in children and adults.
terized by complexes that occur slower than the “prototypical” 3-Hz spike-
and-wave discharge pattern of absence epilepsy (Fig. 11.7), namely, around Generalized Repetitive Fast Discharge
1.0 to 2.5 Hz. Moreover, the complexes are not as rhythmic, and the spike GRFD is also known as paroxysmal fast rhythm, generalized paroxysmal
component is replaced by longer-duration sharp waves (27). Compared to fast activity, or “runs of rapid spikes” (28,29). This pattern consists of bursts
3-Hz spike-and-wave pattern, persistent or fluctuating asymmetry of am- of repetitive spikes in the alpha or beta frequency range (Fig. 11.8). The
plitude between hemispheres occurs more commonly with the slow spike- bursts are generalized in distribution, typically last less than 10 seconds, and
and-wave pattern. This pattern is also more likely to occur during waking as are of low to medium amplitude.
a single discharge of one or a few complexes. However, drowsiness or non- Most GRFD occurs during sleep. It can be considered an ictal rhythm,
REM sleep may activate trains of repeating slow spike-and-wave complexes, because tonic seizure activity sometimes accompanies it. However, this tonic
sometimes similar to electrical status epilepticus during sleep (ESES). HV, seizure activity may be subtle and take the form of tonic slow eye opening.
but not photic stimulation, may enhance slow spike-and-waves, but not as GRFD may also be accompanied by transient apnea or bradycardia in some
reliably as it does the 3-Hz spike-and-wave pattern. The slow spike-and-wave children. A particular type of GRFD, referred to as an electrodecrement,
Figure 11.7: Slow spike-and-wave, also called sharp-and-slow wave (in-

dicated by arrow), in the patient in Figs. 11.2 and 11.9. (Interval between
gridlines is 200 milliseconds.)
Figure 11.8: GRFD during sleep, in the patient in Figs. 11.2 and 11.7.
(Interval between gridlines is 200 milliseconds.)
is characterized by a sudden, brief, generalized attenuation of background discharges are generally believed to be more highly associated with sei-
EEG. High-frequency, but low-amplitude, spiking is thought to underlie zure disorders; however, two studies showed no difference in seizure pro-
electrodecremental events. Patients with GRFD usually also have general- pensity (32,33).
ized spike-and-wave complexes or especially slow spike-and-wave discharges. Photo-epileptiform discharges can also be divided into four categories ac-
Bursts of GRFD may be preceded or followed by these other discharges. cording to their scalp distribution: (a) generalized (Fig. 11.9); (b) bilateral
GRFD is often associated with catastrophic epilepsy syndromes, especially posterior dominant (Fig. 11.10); (c) bilateral occipital; and (d) focal unilat-
in children, such as the LGS (29,30). eral (34). Of the four categories, generalized photo-epileptiform discharges
are the most common, and focal unilateral discharges are the least com-
mon. When focal, photo-epileptiform discharges usually occur in the occipi-
Photo-Epileptiform Discharges tal region, and they have a high association with a structural abnormality
(Photoparoxysmal Response) ipsilateral to the discharges. Up to 77% of individuals with generalized
photo-epileptiform discharges have seizure disorders, whereas epilepsy is
Photo-epileptiform discharges are spikes/sharp waves or complexes of less common in those with bilateral occipital discharges. In general, primary
spike-and-waves that are elicited by repetitive photic stimulation. Photo- generalized epilepsy is most commonly associated with photo-epileptiform
epileptiform discharges have been divided into two types—“self-limited,” discharges. Focal seizure disorders are rarely associated with this phenom-
if the discharges do not exceed the duration of the stimulation; and enon, but those rare instances when focal seizures are activated by photic
“self-sustaining,” if they outlast the stimulation (31). Self-sustaining stimulation, they usually begin in the occipital region.
Figure 11.9: Example of generalized photo-epileptiform discharge

(photoparoxysmal response).
Ictal EEG the EEG morphology of the metamorphic seizure pattern evolves through
different stages of the seizure. This pattern is most typical of focal seizures,
An EEG recording during a patient’s habitual episode and documenting an but it can be seen in both primary and secondary generalized tonic-clonic
ictal discharge are essential parts of the evaluation of patients with parox- seizures.
ysmal episodes, particularly for differentiating epileptic from nonepileptic Defining what constitutes an ictal pattern can be difficult. It is usually, but
spells. In patients with epilepsy, ictal EEG recording is often needed to help not always, associated with seizure symptoms or signs in the patient. Ictal
determine seizure type and epilepsy syndromes. Ictal recordings are also an onset is generally marked by a clear change in the background EEG rhythm,
indispensable part of the presurgical evaluation of patients with pharmaco- which may be manifested as an increase or decrease of the frequency, field,
resistant seizures (35). morphology or amplitude of activity as the seizure evolves. Seizures are
most recognizable when the EEG pattern consists of an organized rhythm
Features of Scalp-Recorded Ictal Discharges that is different from normal background activity and has apiculate or sharp
waveforms. Fortunately, ictal EEG patterns typically evolve through several
Seizure patterns can be isomorphic or metamorphic. Isomorphic patterns stages, which is an important distinguishing feature.
lack clear evolution between multiple phases of an ictal event. EEG mor- In certain situations, it may be difficult to distinguish EEG seizures from
phology changes little throughout the seizure. A typical example is the physiological or nonictal pathological findings. Specifically, EEG fea-
spike-and-slow wave discharge of an absence seizure. On the other hand, tures related to transition from sleep to wakefulness or transition between
Figure 11.10: Example of bilateral posterior dominant photo-

epileptiform discharge (photoparoxysmal response).
different depths of coma may resemble seizures. In addition, differentiating or signs, depending on the brain region affected. Seizure semiology is often an
frequent spiking from seizures may not be straightforward. The same pat- important indicator of the area of seizure onset. For example, elemental audi-
tern may represent ictal discharges in some patients (36,37). In comatose pa- tory seizures strongly suggest onset in Heschl gyrus, whereas elemental visual
tients, ictal-like activity may not have a clear clinical correlate, which further phenomena often originate from regions within or close to the primary visual
makes its designation as ictal more difficult. cortex. Other ictal symptoms, however, are less specific in indicating the loca-
tion of seizure onset, such as olfactory or psychic auras. While such auras are
Ictal EEG in Focal Epilepsy often seen in temporal lobe epilepsy, they may also be seen in orbitofrontal,
insular, or neocortical temporal epilepsy. When ictal activity is recorded by
Simple Focal Seizures scalp electrodes during simple focal seizures, it is often indistinguishable from
Simple focal seizures frequently occur without a detectable ictal correlate on that seen with complex focal seizures, namely, focal fast-frequency discharge
scalp EEG. The low electrographic yield is a consequence of the restricted in the alpha or beta frequency, focal rhythmic slowing in the delta or theta
nature of and limited propagation from the seizure focus. In one study, only frequency, or, less commonly, focal repetitive spike discharge. Focal, irregular,
21% of all simple partial seizures were associated with discernible ictal dis- nonrhythmic delta or theta activity is an unlikely ictal pattern.
charge on the EEG (38). The percentage was higher in those seizures that
involved motor manifestations (33%) and lower in seizures that had no motor Complex Focal Seizures
manifestations (15%). This may be explained by the fact that motor phenomena The EEG almost always shows changes in association with complex focal
frequently reflect a wider seizure propagation. Clinical manifestations of focal seizures, with the exception of some of frontal or parietal lobe origin (39).
seizures include motor, sensory, autonomic, cognitive, and psychic symptoms Inferring the location of the epileptogenic zone by using ictal scalp recordings
is not always straightforward. The morphologic appearance of the ictal and sphenoidal electrodes may not detect deviations from the baseline EEG.
pattern is not specific to the area of seizure onset. For example, the classic However, with the involvement of neocortical areas, the scalp EEG and the
theta frequency ictal discharge, often typical of mesial temporal genera- sphenoidal EEG are more likely to detect an ictal activity. The mesial tempo-
tors, can be seen in other focal seizures that later spread to the temporal ral structures are connected with numerous cortical regions. These include
lobe (40). One generally accepted rule is that the closer the recording elec- the orbitofrontal cortex, the insula, the frontal pole, the posterior cingulate
trode is to the ictal-onset zone, the higher the recorded frequencies. In con- area, as well as the temporal neocortex and temporo-occipital region (40).
trast, seizure generators that are deep in the brain or far from the recording Thus, in nonlesional cases that have seizures that are semiologically and clin-
electrodes tend to be associated with slower-frequency discharges on scalp ically consistent with temporal lobe epilepsy, intracranial electrode evalua-
EEG. Gloor (41) suggested that when faster frequencies are recorded early tion is often recommended to sample regions known to have connectivity
in the seizure, they reflect proximity of the recording electrodes to the site with the mesial temporal structures. For example, patients can have extra-
of origin, whereas slower frequencies often represent propagation from a temporal epilepsy, but with seizures that are clinically and electrographi-
distant site. Indeed, intracranial electrodes often record high-frequency cally typical of mesial temporal lobe epilepsy (40). The opposite scenario
activity when implanted at or close to the epileptogenic zone, whereas may sometimes occur when seizures of mesial temporal origin result in an
scalp-recorded ictal discharges start as slow waveforms before progressing initial scalp ictal discharge over a different brain region due to propagation
into higher frequencies. (Fig. 11.11). In some patients who have hippocampal sclerosis on one side,
In most complex focal seizures, evolution of the ictal EEG pattern is a but scalp-recorded seizure onset on the contralateral side, intracranial elec-
fundamental feature that helps differentiate a seizure from the stable mono- trode recording has revealed the seizure onset on the side of sclerosis (45).
morphic appearance of normal activity, such as benign variants. Typically, A 5- to 9-Hz ictal-onset rhythm recorded from the inferior temporal scalp
the evolution is from lower voltage and higher frequencies to higher-voltage electrodes has been reported to be highly associated with hippocampal
and lower-frequency waveforms as the seizure propagates to more brain onset seizures (46). Commonly, a synchronous positive polarity rhythm is
regions. However, some focal seizures, particularly those originating from observed at the vertex or parasagittal region, particularly in a common aver-
temporal neocortex, can begin as repetitive spikes or sharp waves. Progres- age reference montage. This represents the positive field maximum of the
sively slower spike and wave discharges commonly mark the ending of ictal inferior temporal dipolar source. On the other hand, seizures originating in
activity. A sudden termination is the hallmark of most such seizures. Post- temporal neocortex are often associated with irregular, polymorphic, 2- to
ictal EEG changes also help in distinguishing seizures from benign vari- 5-Hz lateralized activity. This pattern is sometimes preceded by repetitive or
ants. These changes may include generalized or focal slowing, amplitude periodic sharp-wave discharges at the temporal region.
attenuation, or an increase in the focal spike frequency (42,43). When pres- One of the early signs of ictal EEG changes in temporal lobe epilepsy is
ent, focal postictal slowing has lateralizing or sometimes localizing value diffuse attenuation of the EEG and cessation of IEDs (47). This pattern
for the ictal-onset zone (44). The latency between the first clinical sign of may have localizing value. Blume and colleagues (48) studied 66 seizures of
a seizure and the ictal EEG onset should always be assessed. If the onset temporal lobe origin and found that the initial EEG change consisted of
of ictal behavior precedes the EEG onset, it may signify that the ictal EEG attenuation in 10% of the seizures, rhythmic discharge without epileptiform
pattern is coming from a region to which the seizure has propagated, rather features in 43%, and repetitive epileptiform discharges in 41%. A typical ic-
than its origin. tal pattern that evolves shortly after onset in temporal lobe epilepsy is that
of a theta rhythm or organized spiking, often centered in the anterior-to-
Temporal Lobe Complex Focal Seizures mid temporal region or in sphenoidal electrodes (Fig. 11.12). This temporal
Temporal lobe seizures have been the most thoroughly studied because they rhythm is seen in 50% to 80% of the mesial temporal lobe seizures (49). Some
comprise the most common type focal epilepsy. These seizures often origi- seizures, however, may not be accompanied by clear EEG correlates at their
nate from the hippocampus or other mesial temporal structures and propa- onset. Neocortical-onset seizures are more likely to be of this category (46).
gate to involve the basal and lateral temporal lobe cortices, as well as frontal Intracranial EEG recordings typically provide better temporal resolu-
lobe regions. When the ictal discharge is limited to the hippocampus, scalp tion of seizure activity. Whereas scalp-recorded ictal discharges may lag
Figure 11.11: A 24-year-old man presented with a history of intrac-
table complex focal epilepsy since age 12. His risk factors include an
episode of meningitis at age 7 years. Video-EEG monitoring with scalp
electrodes suggest seizure onset in the left frontopolar region with later
propagation to the left temporal region. Because his brain MRI revealed
left hippocampal atrophy, invasive monitoring with depth electrodes
was conducted. This figure shows his seizure onset in two consecutive
EEG pages consisting of simultaneous scalp and depth electrode re-
cordings. His seizure onset zone proved to be in the left hippocampus,
with secondary spread to the left frontopolar region. The scalp record-
ings missed the initial high-frequency hippocampal discharge (inset), but
showed a frontopolar ictal discharge only after seizure propagation to
the frontal pole. M1–6 are medial frontopolar contacts, L1–6 are lateral
frontopolar contacts, HH1–3 are in the head of the hippocampus, and
HB1–2 are in the hippocampal body.
327
Figure 11.12: The patient is a 36-year-old, left-handed woman with a

history of epilepsy since 9 years of age. She has frequent generalized
tonic-clonic seizures preceded by cephalic auras lasting 10 to 20 sec-
onds. She had a normal brain MRI and routine EEGs in the past. Upper
panel of this figure shows EEG without, and lower panel with, sphenoi-
dal electrode recording. A: Interictal EEG showing low-voltage, poorly
defined spike at channel T7–P7, but simultaneous sphenoidal recording
shows high-amplitude spike activity. B: Ictal EEG showing rhythmic delta
discharge more obvious at the sphenoidal electrode recording than the
simultaneous scalp recording.
behind the clinical onset, intracranially recorded ictal discharges are often ictal-onset discharge of beta frequency is independently predictive of ex-
concomitant with, or appear before, behavioral signs. Indeed, interictal and cellent outcome following lesional or nonlesional frontal lobe surgery, with
ictal discharges that are limited to the hippocampus are often undetectable 90% of the patients becoming seizure-free (52). Unfortunately, only 25% of
by sphenoidal or scalp electrodes, and the ictal pattern becomes evident on frontal lobe surgery patients have this type of discharge that is visually de-
scalp recordings only after the seizure has involved significant portions of the tectable. Computer-aided power spectrum analysis of the EEG is sometimes
basal and lateral temporal neocortex (Fig. 11.13). The frequency of scalp- required (Fig. 11.15A and B).
recorded seizure discharges can be in the alpha, beta, or delta range (48). Parietal lobe seizures may be accompanied by sensory hallucinations, par-
Intracranial electrodes can record the higher-frequency and lower-amplitude esthesias, and rarely ictal pain. Scalp EEG recordings of parietal lobe sei-
beta or gamma activity, which is typical of the seizure onset, whereas scalp zures often do not show localizing findings and sometimes not even a clear
electrodes can appreciate only the slower frequencies that evolve with seizure ictal correlate (53).
spread. Occipital lobe seizures are often associated with semiology, which helps
identify the site of origin. These include elemental or complex visual hal-
Extratemporal Complex Focal Seizures lucinations and other eye movement phenomena such as eye deviation and
In contrast to patients with temporal lobe seizures, who often have auras, forced blinking (54). It is common for occipital lobe seizures or parietal
slowly developing automatisms, and postictal states, patients with frontal lobe seizures to propagate to the ipsilateral temporal lobe, as well as to
lobe seizures tend to exhibit no auras, abrupt hypermotor activity, rapid the contralateral temporal lobe (Fig. 11.16). Following propagation, the
propagation, and little or no postictal confusion. These contribute to the seizure semiology would include alteration of awareness and automatic be-
decreased EEG yield in frontal lobe seizures (50). Frontal lobe seizures have haviors typical of temporal lobe seizures. Propagation to the frontal lobe
a myriad of clinical manifestations and are often poorly localized by scalp and insula from occipital lobe foci has also been described. This is more
EEG (39) (Fig. 11.14). Only about half of the complex focal seizures origi- likely associated with clonic or tonic seizure behavior. Scalp recordings of
nating from the frontal lobe appear to show a clearly localizing EEG pat- occipital seizures commonly show a clear focal ictal pattern over the oc-
tern, and many simply movement and muscle artifact (51). However, a focal cipital region.
Scalp electrodes
Figure 11.13: The patient is a 44-year-old woman with history of intrac-
table epilepsy since age 19. Her seizures manifest as abdominal aura fol-
lowed by alteration of awareness and oral automatisms, and infrequent
secondary generalization. Her video-EEG monitoring with scalp elec-
Depth electrodes
trodes captured habitual seizures that electrographically appeared to be
of left temporal origin, but the ictal discharge occurred at least 20 seconds
after the clinical onset. Because she had a normal brain MRI, invasive
monitoring was performed with depth electrodes in the left temporal
lobe and other brain regions, including frontal, insular, and posterior cin-
gulate regions. Simultaneous depth and scalp recordings confirmed ictal
onset in the left hippocampus, which explained the delayed scalp EEG
Scalp electrodes
appearance. A: Seizure onset in the hippocampus (H1, 2) was associated
with normal tracings on simultaneous scalp EEG. B: Seizure propagation
to the amygdala (AM1, 2) also did not result in clear changes on scalp
EEG. C: Attenuation of the posterior basic rhythm and some evolving
rhythms started to manifest on the scalp EEG as the intracranial seizure
Depth electrodes
discharge involved temporal neocortical (TN1) regions. D: Further syn-
chronization of the ictal discharge over the temporal neocortex (TN1–4)
30 seconds after seizure onset, resulting in a clear rhythmic ictal discharge
at the scalp recording of the left temporal region.
Figure 11.14: This EEG is of a 38-year-old right-handed man with epi-

sodes of alteration of awareness since 15 years before. They were occa-
sionally preceded by “smelling sweet smells.” His interictal EEGs in the
past were normal. This figure shows scalp EEG during a nocturnal seizure
that manifested as right hand and mouth automatisms, facial grimac-
ing, and smiling. Awareness and language appeared to be preserved in
the immediate postictal period, typical of frontal lobe seizures. The ictal
EEG shows diffuse, frontal-maximum, delta-range rhythmic discharge
with no clear lateralizing features.
Secondary generalized seizures may evolve from complex focal seizures, used when a nongenetic, intra- or postnatal cause of the epilepsy is known.
which in turn may evolve from simple focal seizures. Scalp EEG of secondary “Cryptogenic” is used when a nongenetic cause is suspected but not clearly
generalized seizures is best distinguished from that of primary generalized identified.
seizures by the focal or lateralized onset, a focal or regional predominance
of the seizure pattern, and focal or lateralized postictal slowing. Idiopathic Generalized Epilepsy
Idiopathic generalized epilepsy includes juvenile and childhood absence
Ictal EEG in Generalized Epilepsy epilepsies, JME, and generalized tonic-clonic epilepsy. These syndromes
are associated with several seizure patterns. However, common characteris-
Generalized epilepsies are defined by the International League Against tics are that the ictal and interictal discharges are bilateral, symmetric, and
Epilepsy as epileptic disorders with generalized seizures. Generalized
consist of synchronous spike-and-slow-wave activity of varying frequencies.
seizures are defined as ones originating at some point within, and rapidly Because these are “primary” epilepsies without obvious brain damage, the
engaging, bilaterally distributed networks. These networks can include EEG background is typically within normal limits, and the bilateral ictal
cortical and subcortical structures, but do not necessarily involve the en- discharges typically appear and terminate abruptly. Although widespread
tire cortex (55). There are two major categories of generalized epilepsy: and termed “generalized,” the ictal discharge is often maximal over bilateral
idiopathic and symptomatic/cryptogenic. In the “idiopathic” category, in- superior frontal regions. As the run of spike-and-wave activity progresses,
terictal and ictal EEG findings are usually bilateral, synchronous, and sym- its frequency slows and the spike component may become less obvious. The
metrical. The etiology is presumably genetic. The term “symptomatic” is EEG returns to a normal baseline immediately after seizure termination,
Figure 11.15: A: Scalp EEG recording showing midline and left fron-
tal seizure discharge onset in the beta frequency (i.e., focal ictal beta
discharge), which soon develops into a higher-amplitude but lower-
frequency activity that spreads. B: Power spectrum analysis of the fre-
quencies of the same scalp-recorded seizure activity, showing peaks of
17-Hz beta-frequency activity (arrow) occurring just after the fifth second
at the left (F3–C3), but not at the right (F4–C4) fronto-central region.
except in cases of generalized convulsive seizures, when there will be postic- of the paroxysm, and only 4% had normal reaction times during the first
tal slowing. This seizure type tends to be readily responsive to medications, second of the discharge. The term “complex absence” describes absence sei-
although some may be medically intractable. zures with prominent automatisms (57).
The ictal discharge of an absence seizure is typically abrupt in onset and
Absence Epilepsy offset. There is no postictal slowing. In childhood absence epilepsy, the ictal
Most patients with absence seizures are neurologically and cognitively in- pattern consists of repetitive, spike-and-slow wave complexes at the aver-
tact, and the EEG at baseline is within normal limits. Absence seizures are age frequency of 3 Hz. These discharges typically have a higher frequency
often subtle in their clinical manifestation, and the distinction between in- at seizure onset (approximately 3.5 Hz) and a slower frequency by seizure
terictal and ictal behavior may be difficult. Discharges that last longer than termination (approximately 2.5 Hz) (see Fig. 11.5). Absence seizures can be
3 seconds will often have clinical correlates. Testing patient responsiveness brief or last tens of seconds. At times, there are polyspike and wave com-
with motor or verbal tasks may help assess the alteration of awareness in ab- ponents to the ictal pattern. Occasionally, the spike and waves may be more
sence seizures. Browne et al. (56) studied auditory reaction times and found prominent posteriorly (57). Absence seizures in other epilepsy syndromes
them to be within normal limits immediately prior to the epileptic discharge. may show irregular spike-and-wave complexes, slow spike-and-wave activ-
However, fewer than half the subjects had normal reaction times at the start ity, or generalized paroxysmal fast activity (58).
Figure 11.16: This EEG is of a 58-year-old man with seizures following a re-
mote history of intracerebral hemorrhage that necessitated surgical evacu-
ation. After years of seizure control, the patient presented with recurrent
seizures manifesting as decreased responsiveness and left facial twitching.
A: FLAIR MRI shows right parieto-occipital encephalomalacia. B: EEG sei-
zure onset consists of low-voltage, alpha-range rhythmic discharge over P4.
C: Discharge evolves in amplitude, frequency, morphology, and distribu-
tion within 30 seconds after seizure onset. D: Emergence of rhythmic activ-
ity at Fz–Cz and F4–C4, denoting seizure propagation into frontal regions.
E: Ninety seconds after seizure onset, EEG shows further seizure propaga-
tion into the whole right hemisphere, including the temporal region, and
also into the left hemisphere to a lesser degree. F: Heralding seizure ter-
mination, slowing and disorganization of the ictal discharge occurred at
approximately 120 seconds after seizure onset.
Juvenile Myoclonic Epilepsy will have a generalized photo-epileptiform discharge (photoparoxysmal

JME typically starts in the teenage years and is marked by myoclonic and response).
generalized tonic-clonic seizures. The EEG often shows bursts of bilateral, During myoclonic seizures, the EEG shows a high-voltage, 10- to 16-Hz
frontally dominant, irregular, spike-and-wave, and polyspike-and-slow-wave spike discharge. This may be preceded by irregular slow spike-wave com-
discharge with or without an associated myoclonic jerk (Fig. 11.17). Myo- plexes (at 2 to 5 Hz) (59). Absence seizures can be seen in JME, and its 3-Hz
clonic jerks tend to occur shortly after arousal, and some are induced by spike-and-wave discharge is indistinguishable from other absence epilepsies.
intermittent photic stimulation. Approximately one-third of the patients However, such discharges in JME may start as a rapid polyspike-and-wave
Figure 11.17: This EEG is of a 21-year-old woman with a recent history

of an episode of loss of consciousness and fall. She also had arm jerks
for several years, which were worst after sleep deprivation and when
she played video games. EEG shows a burst of generalized, bifrontal-
maximum, polyspike-and-slow wave discharges. Such discharges
occurred at times in association with myoclonic jerks. Both clinical h
istory
and EEG abnormalities are typical of JME.
activity before slowing to 3 Hz. Panayiotopoulos and colleagues (57) stud- generalized rhythms that gradually increase in amplitude and decrease in
ied absence seizures in patients with JME by using continuous video-EEG frequency to approximately 10 Hz (i.e., the “epileptic recruiting rhythm”).
monitoring. They found that clinical seizures were often subtle and notice- Another early EEG change in generalized tonic-clonic seizures is that of
able only if the patient was engaged in certain activities. Polyspike and wave paroxysmal fast activity at about 10 Hz, which increases in voltage (57). This
complexes of irregular frequencies were often the EEG correlate. paroxysmal fast activity becomes intermixed with rhythmic slow activity af-
ter approximately 10 seconds, and the blend gives rise to polyspike-and-slow
Generalized Tonic-Clonic Seizures wave complexes. With the evolution of the seizure, the ictal rhythm slows
Polyspike-and-slow wave discharges may herald the tonic phase of a gener- to approximately 4 Hz and tonic muscle contraction gives way to the clonic
alized tonic-clonic seizure. This tonic phase is associated with low-voltage, activity. During the clonic phase of the seizure, each spike burst is associated
high-frequency activity of 20 to 40 Hz. This pattern is often followed by with a bilateral muscular jerk, whereas the slow wave that follows the spike is
associated with muscle relaxation. Both the EEG and motor manifestations Atypical Absence Seizures
gradually slow and finally stop abruptly. Postictal EEG voltage attenuation Atypical absence seizures are characterized by a more gradual onset and
ensues, the length of which is a function of the seizure duration. Gradually, offset than childhood absence seizures. Atypical absence seizures may be as-
cerebral rhythms return, starting with diffuse delta activity, which in turn is sociated with decreased muscle tone (62). These seizures typically occur in
followed by more normal rhythms of increased voltage and frequency. The patients with diffuse brain disease and cognitive impairment. They usually
duration of the postictal phase varies from a few minutes to tens of minutes, begin between 1 and 8 years of age, and are they frequently refractory. Atypi-
but it tends to be longer in younger children and after longer seizures. cal absence seizures are common in LGS, as are tonic seizures, atonic seizures,
Clonic-Tonic-Clonic Seizures and, to a lesser extent, myoclonic seizures. The EEG can help to diagnose
LGS if it shows generalized, bifrontal slow spike-and-slow wave complexes
Clonic-tonic-clonic seizures are often seen in individuals with genetic gen- (1.5 to 2.5 Hz) (see Fig. 11.7). These seizures may initially resemble severe
eralized epilepsy (60). The initial clonic jerks are associated with a diffuse myoclonic epilepsy of infancy (Dravet syndrome) and m yoclonic-astatic
10- to 16-Hz spike discharge, which is followed by voltage attenuation with epilepsy (Doose syndrome). Other ictal patterns associated with atypical
superimposed low-amplitude, high-frequency activity of 20 Hz or more absence seizures include slow spike-and-wave activity, which may not be
during the tonic phase. During the second clonic phase, the EEG typically easily distinguished from the patient’s diffusely slow background EEG, and
shows diffuse high-voltage fast spikes interrupted by slow waves (59). hypersynchronous slow-and-spike-wave discharge (63). This generalized
Generalized Tonic-Clonic Seizures on Awakening slowing is indicative of diffuse encephalopathy associated with the second-
ary or symptomatic epilepsies in which there is obvious brain damage.
Generalized tonic-clonic seizures on awakening are rather uncommon type
of idiopathic generalized epilepsy. These patients semiologically have nei- Tonic Seizures
ther absence spells nor myoclonic jerks (58). Their EEG shows generalized In tonic seizures, there is a sudden and sustained contraction of muscle
bursts of 3 Hz or faster polyspike-and-slow wave discharges, which can be groups, which is commonly associated with falls and loss of consciousness.
irregular in morphology and frequency. They occur principally in individuals with global or multifocal brain impair-
ment. The most common ictal EEG correlate is diffuse low-voltage attenua-
Symptomatic Generalized Epilepsies tion with superimposed fast activity. This pattern may gradually increase in
These epilepsies generally start during infancy or early childhood, although amplitude as the frequency decreases, similar to the early phase of a gener-
they can present at any age. The clinical and EEG manifestations are vari- alized tonic-clonic event. Alternatively, the ictal discharge of tonic seizures
able and age-dependent. may consist of an initial high-voltage slow-wave discharge, followed by volt-
age attenuation (64).
Symptomatic Generalized Tonic-Clonic Seizures
Symptomatic generalized tonic-clonic seizures have EEG correlates that are Clonic Seizures
similar to those seen in idiopathic generalized tonic-clonic seizures. Clas- Patients seldom have clonic seizures alone. Clonic seizures result in less se-
sically, the tonic phase is associated with an electrodecremental pattern or vere metabolic dysfunction and postictal confusion than generalized tonic-
the paroxysmal fast-activity pattern (61). During sleep, these discharges are clonic seizures. The ictal pattern observed with clonic seizures resembles that
subclinical, whereas the pattern is more likely to be accompanied by clinical of the clonic phase of a generalized tonic-clonic seizure. These discharges
manifestations during wakefulness. The frequency of paroxysmal fast activ- are often generalized, repetitive, high-amplitude spike or sharp waves, usu-
ity ranges between 10 and 25 Hz, and its duration often averages 3 to 5 sec- ally with some degree of after-coming slow wave.
onds, before it gives rise to sharp-and-slow wave complexes. The amplitude
of spikes in the fast activity may decrease as the discharge progresses. These Atonic Seizures and Akinetic Seizures
patterns are bilaterally synchronous and frontally dominant, although they Atonic seizures present as brief loss of muscle tone in association with brief
may rarely be unilateral. loss of consciousness, thus often resulting in injurious falls. They last for a
Figure 11.18: This case is of a 7-year-old with LGS. His seizures started
at 5 days of age and have been resistant to multiple antiepileptic medi-
cations and the vagus nerve stimulation. His seizure types include clonic,
generalized tonic-clonic, and atonic. EEG during an atonic seizure
is characterized by head drop. Such seizures occur at a frequency of
20 times per day on average. Note the sudden electrodecrement with
superimposed fast activity that evolves within 2 seconds into a gener-
alized, frontal-maximum, alpha-range activity. This is followed by the
reemergence of the interictal pattern consisting of high-voltage gener-
alized slowing and slow spike-and-wave activity.
few seconds, with little or no postictal confusion. Atonic seizures tend to Scalp electrodes often fail to record an ictal discharge in seizures that do
occur in individuals with multifocal or diffuse brain disease (49). The ictal not involve an alteration of consciousness (67). Thus, the absence of ictal
EEG in atonic seizures consists of diffuse voltage attenuation with superim- EEG changes with simple focal seizures does not exclude epilepsy. The di-
posed generalized fast activity, generalized spike-and-slow wave discharges, agnosis of simple focal seizures, rather than psychogenic nonepileptic spell,
or generalized fast activity (Fig. 11.18). Paroxysms of multiple spike-and- commonly depends on the entire clinical presentation, including their ste-
slow waves or slow spike-waves have been described as well (65). Clinically, reotypical nature, their duration, and findings on brain imaging. Conversely,
atonic and myoclonic seizures may be difficult to distinguish from one an- seizures that include alteration of awareness usually show EEG changes (68).
other, if they are brief, and drop attacks may be due to tonic seizures instead Scalp EEG recordings are limited primarily because they can detect only
of atonic seizures. Akinetic seizures are characterized by the sudden onset a small portion of the underlying brain activity. Cortical discharges need be
of behavioral arrest with no impairment in the muscle tone. Their EEG cor- synchronized over an area of 10 cm2 or more before they can be detected
relates are similar to those of atonic seizures. by scalp electrodes (69), and the amplitude of recorded brain signals is in-
versely proportional to the square of the distance between the recording
Limitation of Interictal and Ictal Scalp EEG electrode and the cortical generator (70). Moreover, the impedance of the
meninges, cerebrospinal fluid, skull, and scalp will attenuate all intracranial
Scalp ictal recordings have limitations. In patients with a known brain le- frequencies as they behave like a high linear frequency filter and, together
sion, especially in the temporal lobe, spatial concordance between the lesion with the electrodes, function as an EEG averager (71).
and the scalp-recorded ictal discharge will often support resective surgery An additional important factor is the location and number of the elec-
and provide a good outcome (66). However, in nonlesional epilepsy, scalp trodes attempting to characterize the EEG dipole generator. Without suf-
ictal recordings can be insufficient or misleading, and intracranial electrodes ficient recording locations in both the top and bottom half of the head, the
implantation and recording are often required before resective surgery is angle subtended by any of the standard 10 to 20 electrodes with the cortical
possible. generator may be insufficient to measure its signal. This principle is also true
for intracranial electrode recording, although these electrodes are closer to 5. Kellaway P. The incidence, significance, and natural history of spike foci in children.
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12 EEG Voltage Topography and Dipole
Source Modeling of Epileptiform Potentials
JOHN S. EBERSOLE
Introduction Dipole Modeling of Seizures

EEG Spike and Seizure Sources Dipole Models for Specific Cortical Regions
Cortical Source Factors and Scalp EEG Potentials Temporal Lobe Sources
Dipole Models of Cerebral Sources Extratemporal Sources
Single-Moving Dipole Model Other EEG Source Models
Spatiotemporal Multiple-Dipole Model Clinical Studies Using Dipole Models
Interpretation of Dipole Models Conclusions
Coregistering Dipole Models with MRI, Realistic References
Head Models, and Spatial Sampling
Introduction assumptions, namely, that the cortical generator underlies the negative field
maximum, that a discrete source must produce a focal scalp potential, and
Of the clinical uses for EEG in the management of epilepsy, localization that a widespread potential means a diffuse or multiple sources. Unfortu-
of the epileptogenic focus is perhaps second in importance only to diagno- nately, none of these assumptions are necessarily true.
sis. This is particularly true for those patients with medically uncontrolled, Scalp EEG contains much more spatial and temporal information than
partial seizures, who may be surgical candidates. However, EEG analysis can be appreciated by eye. This information is now easily extracted by mod-
in most clinical epilepsy centers begins and ends with the visual inspection ern computer-assisted analysis techniques. This chapter will review the use
of EEG traces. Localization of spike and seizure sources is based on iden- of voltage topography and dipole source modeling in the characterization
tifying the electrode(s) recording the most prominent negative potential or and localization of epileptiform spike and seizure potentials. Dipole source
clearest negative rhythm, that is, the scalp negative field maximum. Little, if modeling is an advanced method of analyzing and interpreting EEG data.
any, attention is paid to the presence or location of any associated positive It is based, however, on simple principles that need to be understood before
field. This simplistic form of source localization is based on several false the technique can be fully appreciated. In reality, the EEG is a time series
338
EEG Voltage Topography and Dipole Source Modeling of Epileptiform Potentials 339
of continually changing voltage fields of differing polarity and magnitude potentials. Concerns for millimeter accuracy when dealing with epileptic foci
over the surface of the head. The EEG as most know it, namely, traces of thus make little sense because the actual cortical sources are multiple square
voltage potential difference over time between electrodes, is simply a cre- centimeters in size. Similarly, resolving two or more theoretical sources a
ation of measurement and display techniques. It is important to think of few millimeters apart in simulation studies is again hardly pertinent in the
EEG as voltage fields and not simply as lines on a display. This is because clinical arena, given the extended nature of real cortical generators of scalp
the contours of these fields and the location and amplitude of negative and EEG. This does not mean that discrete source models, such as dipoles, can-
positive field maxima convey all the information that is necessary for proper not be useful even though they do not accurately depict source area. It just
source localization. With the advent of digital EEG and advanced computer means that they have to be interpreted properly.
techniques, localization of epileptogenic foci is easily transformed from an
art form into a science. Cortical Source Factors and Scalp
EEG Potentials
EEG Spike and Seizure Sources
There are several properties of cortical sources that are influential in deter-
In order to model the cortical generators of EEG accurately and interpret mining the character of the scalp EEG field produced. They can be divided
the results of such modeling, you must know the typical characteristics of into physical factors (location, area, orientation) and functional factors
such sources. For example, what is the average size or range of sizes of corti- (amplitude, frequency, synchrony). Some are self-evident, such as source
cal sources that produce typical scalp EEG potentials? Unfortunately, there location and activity amplitude, while others are less obvious. Source area
have been few studies to determine these directly and in vivo. As reviewed has been discussed in Chapter 2 and is critical. Most cerebral potentials are
in Chapter 2, the widely quoted study by Cooper et al (1), which identified not recordable at the scalp because of insufficient source area, rather than
6 cm2 as the minimal area of a cortical source resulting in a scalp EEG source depth or activity amplitude. Source orientation is also a significant
potential, was in fact an in vitro experiment using a fresh piece of cadaver factor that is less well appreciated.
skull. Only simultaneous scalp and intracranial EEG recording affords the Being quite extended, spike and seizure sources typically involve several
opportunity for direct validation. lobar gyri and sulci. Although cortical convolutional geometry may be com-
Those who have evaluated patients with intracranial electrodes for pos- plex, fields produced by opposing walls of sulci will typically cancel each
sible epilepsy surgery have known for some time that patients have far more other. Voltage fields from unopposed gyral crowns tend to predominate in
ECoG spikes than scalp EEG spikes. Thus, much of the activity recorded any resultant scalp field. A reasonable simplifying assumption is that spike
from invasive electrodes is not visible from the scalp. A number of years and seizure scalp EEG fields appear as though arising from a smooth, lis-
ago, informal observations with simultaneous scalp and intracranial EEG sencephalic brain, with only the major invaginating fissures exerting a signif-
in epilepsy patients suggested that cortical sources of typical EEG spikes icant influence. Although usually curved, the patch of the cortex activated
and seizure rhythms were much larger than anticipated, sometimes exceed- in a cortical spike has some net orientation. The orientation of the voltage
ing 30 cm2 of gyral area (2,3). More recently, a rigorous investigation, again field of a spike from a given location is orthogonal to the surface orienta-
with simultaneous scalp and cerebral recordings, confirmed that 6 cm2 is tion of that cortex. Thinking about it in another way, it is the same as the
too small for the minimal source area (4). Rather, 10 cm2 of synchronously average orientation of the pyramidal cells in that cortical patch. Depending
active cortex is usually necessary to produce a recognizable scalp poten- on the net orientation of the cortical source, the resultant EEG field may
tial, and most prominent EEG spikes have source areas two to three times be radial, oblique, or tangential to the skull surface (Fig. 12.1). Only in the
greater (see Figs. 2.4 and 2.5 in Chapter 2). Thus, the actual sources of scalp- case of a radial source will the field maximum be directly above it. In all
recognizable epileptiform potentials are not discrete, but rather they are sub- other cases, the field maxima will be displaced to either side of the source. In
lobar at a minimum. the case of truly tangential sources, the negative and positive field maxima
Accordingly, this extended size for cortical foci must be taken into consid- will be equally displaced on either side of the source, and directly above
eration when interpreting dipole and other source models of epileptiform the source no potential will be recordable. Thus, assuming that the location
340 EEG Voltage Topography and Dipole Source Modeling of Epileptiform Potentials
Despite complex cortical geometry, resultant voltage fields of spike and sei-
zure sources at the scalp usually appear dipolar. If the source orientation is
radial and its location is high on the cortical convexity, only one field maxi-
mum will be recorded from standard scalp electrode placements because
Top Back
the opposite polarity maximum would only be recorded from the base of
the skull or throat. Usually both negative and positive field maxima are
recordable, particularly if supplementary subtemporal electrodes are used
Top Back to extend recording below into the “southern hemisphere” of the head.
A three-dimensional (3D) line connecting the two field maxima defines
the field orientation. This orientation is the same as the net orientation of
the pyramidal cells generating it, and, as previously noted, it is orthogonal
to the net orientation of the source cortex. The center of the source should
lie somewhere along this line, nearer to one or the other maximum in pro-
portion to the amplitude of each field maximum. Thus, typically the voltage
Top Back topography of an epileptic spike has a high-amplitude and steep-gradient
negative field maximum in the ipsilateral hemisphere and a lower-amplitude,
shallow-gradient positive field maximum in the contralateral hemisphere
(Fig. 12.2). All the information that is used by source modeling algorithms
is contained in this voltage topography over time.
If a spike source is spatiotemporally stable, the voltage field will rise and
fall in magnitude and reverse in polarity, but the maxima will not move or
Top Back substantially change in shape. If the spike source is unstable and propaga-
tion to the adjacent cortex happens, the geometry of the source will change
and the resultant voltage field will also change over time. In this case, the
Figure 12.1: Example cortical sources 1 to 4 depicted in a schematic head/brain
location and shape of maxima will move across the head over the course of
in coronal cross section. Typical pyramidal cell orientations are shown for each
source. Resultant scalp voltage field topography for superficial laminar depo-
the spike, in addition to changes in magnitude and polarity. This change in
larization is displayed above each source as isopotential lines of field strength the spatial distribution of a voltage field over time is the principal marker of
(speckled = negative, clear = positive). Typical dipoles modeling these sources propagation (see Fig. 12.2).
are depicted beneath each source. Note that simple and more complex corti- Radial fields are typically generated by the crowns of convexity cortex.
cal convexity sources (2 and 3, respectively) produce radial fields with negative However, many brain regions that are highly epileptogenic are not found on
maxima directly above them and positive maxima contralaterally. Radial dipoles the cortical convexity. This includes the entire base of the brain, in particu-
deep to the cortex model these sources. Interhemispheric source 1 and tempo- lar, orbitofrontal and basal temporal regions. These cortices produce EEG
ral base source 4 produce tangential fields with negative and positive maxima fields that are tangential to the head surface rather than radial. Similarly,
displaced on either side of the source and essentially no potential directly above epileptogenic foci in major fissures, such as Sylvian or interhemispheric,
them. Tangential dipoles deep to the cortex model these sources. produce tangentially oriented EEG fields. Such sources are important to
understand because little or no EEG potential is recorded directly above
of an epileptic focus is directly under the electrode, recording the maximal them, rather the negative and positive EEG fields on the head are displaced
potential can be dangerously inaccurate. on either side of the true source location. In such a situation, considering the
In reality, it is the spatial distribution of the voltage field over the entire negative field maximum as the source origin will result in false localization
head that conveys information about source location and orientation. and even a false lateralization in certain situations (see Fig. 12.1). Simply
Left Left Left
Figure 12.2: Scalp EEG tracing of a left temporal spike

is shown at left. Cursors mark three time points on the
rising phase to peak of this spike. Topographic maps
depict the scalp voltage fields at these three points in
isopotential lines (speckled = negative, clear = posi-
tive). A 3D line defining field orientation connects the Back Back Back
two maxima. Note that early in the spike, the field is

vertical and tangential. Later it is oblique, and at the
spike peak, the field is horizontal and radial. Such
changes in the location of voltage field maxima and
field orientation are the result of spike propagation
across the cortex. Dipole source modeling predicts
that the center of activity of the spike source (identi-
fied by a black dot) lies on this 3D line at a location
proportionally nearer the maxima of higher amplitude.
by inspecting the spike/seizure voltage fields over the head, one can gain of a convoluted source will add linearly and a simplified dipolar electrical
considerable information about the likely source of these fields. Such visual field will predominate. The physical and mathematical explanation for this
analysis is essentially a form of source modeling. is found in the multipole expansion. At a distance from the source, more
complicated field patterns, such as quadrapoles and octopoles, will dimin-
Dipole Models of Cerebral Sources ish, leaving only dipolar patterns. Accordingly, if one is attempting to model
cortical sources of EEG, it makes sense to use a model that is dipole-based.
As noted earlier and in Chapter 2, the cortical sources of EEG spikes or sei- It is important to appreciate, however, that a dipole is an unphysiological,
zure rhythms produce voltage fields on the scalp that are dipolar in nature, biophysical construct—a point-like source with a separation of negative and
possessing a negative and a positive field maximum. The geometry of a cor- positive charge that can produce a dipolar field in a conducting volume. The
tical source may be complex and comprised of several gyri and sulci; simi- dipole is not the source; it simply is a model of the source.
larly, the cortical voltage fields recorded by subdural electrodes may also be Dipole localization techniques are based on electric field theory applied
complex. However, above the cortex, including at the scalp, the voltage fields to volume conduction, which was developed by Helmholtz (5) in the
mid-nineteenth century. Nearly 100 years later, electroencephalographers location is made; the forward solution is performed, and the difference
began to consider the physical relationship between electric fields on the between the forward solution and the actual measured field is characterized.
scalp and their underlying sources within the brain (6–9). At the same time, Subsequent random movements of the dipole model attempt to minimize
Wilson and Bayley (9) developed a method for calculating the voltage field this difference. When the smallest difference is obtained, the putative dipolar
generated on a spherical volume conductor by a known dipole. In simple source has been identified. This method defines a single equivalent source
terms, if the location, orientation, and strength of a dipolar source within a for a voltage field at one point in time. Regardless of the complexity of the
spherical and homogenous conducting medium are known, one can predict real cerebral sources, the resultant compound activity is simplified into that
the shape and magnitude of the potential field that is measurable on its sur- of a single-dipole generator.
face. The answer to this type of problem has been called the “forward solu- Spike voltage fields evolve over time, but the instantaneous single-dipole
tion,” and it is unique. There is only one field that can be generated by a given technique models the field at only one instant. Temporal evolution of a volt-
dipole. However, the usual clinical problem is the opposite, namely, trying age field can, however, be described by a series of sequential single dipoles
to locate the intracerebral generator having measured the topography of a that can move in position and orientation over time, if the field changes. These
scalp potential. The answer to this is called the “inverse solution,” and unfor- can be displayed in one image as a “moving” dipole (17,18). For some spikes,
tunately, for any given voltage field there is no unique answer. Rather, there repeated dipole solutions are very consistent during the course of the poten-
are multiple possibilities because the fields of sources in a volume conductor tial, varying only in magnitude and little in position or orientation (Fig. 12.3).
sum linearly (the principle of superposition). Therefore, the field measured A single-dipole model fits these types of data well and suggests a discrete
by a given electrode array may well be a composite from a number of differ- cerebral generator or nearly synchronous activation of several generator
ent sources. regions. For other spikes, sequential solutions over the potential’s time course
Certain assumptions are necessary to apply dipole modeling to human show progressive drift in dipole location and rotation of vector orientation
EEG. First, the brain is often modeled as a sphere of uniform conducting (Fig. 12.4). Such behavior of the dipole model is incompatible with a single-
material (10), and concentric shells are added around this to imitate the skull generator region and suggests asynchronous activation of different cortical
and scalp (11–13). The brain and scalp are usually considered to be of equal areas.
resistivity and the intervening skull 20 to 80 times greater. Also, for ease of The direction of dipole movement can convey useful information about the
mathematical modeling, the source of the field is considered to be a point-like likely path of spike propagation, as long as it is simple and unidirectional.
dipole. Obviously, the generators of scalp spikes are not point sources, but Moving dipoles that spiral in a loop or make sudden turns in direction or posi-
rather large aggregates of neurons that extend over 10 to 30 cm2. However, the tion are usually the result of fields created by superposition of early source
combined activity of such a generator region may be modeled effectively by a repolarization and later source depolarization or several different asynchro-
single dipole. That is to say, the field that would be produced by this “equiva- nous sources. Therefore, one-dipole solutions can be misleading, particularly
lent dipole” is very similar to that of the real source. As a first approximation, at later latencies when propagation is likely to have occurred, resulting in
the equivalent dipole should reside close to the center of the real generator increased source complexity. Several investigators have concluded that mod-
area and have an orientation that is orthogonal to that of the cortex. eling the rising phase of the spike is more likely to represent the initial spike
source (2,3,19,20). Obviously, there is a trade-off because the earlier time
Single-Moving Dipole Model points typically have lesser signal-to-noise (S/N), which may make modeling
less accurate. Averaging closely similar spikes or sequential ictal waveforms
The most common form of source localization is the instantaneous, single- can improve the S/N, which will provide a more confident solution (21).
dipole inverse solution. This procedure takes the voltage values from all
electrodes at a given instant in time and searches for an equivalent dipole Spatiotemporal Multiple-Dipole Model
within a spherical head that could generate such a field. Various algorithms
exist for identifying an equivalent dipole source (14–16). Most of these algo- Although the moving single-dipole model will characterize simple propaga-
rithms use an iterative minimizing approach, whereby an estimate of source tion, it is overly simplistic to think that small brain regions are activated
Figure 12.3: Left: Scalp EEG of a right temporal spike with a horizon-
tal, radial field orientation. Cursor denotes 0 millisecond latency. Top
right: Sequential voltage topography of the spike. Note stable shape
of the fields over 40 milliseconds. Bottom right: Single and moving
dipole models of the spike. Note that voltage field stability and tight
cluster of the moving dipole model suggest a simple source for which
a single-dipole model is appropriate.
briefly in sequence. It is more reasonable that adjacent cortical areas are acti- obtained to calculate multiple dipoles from this positional constraint and
vated for a longer period, but not synchronously. Source modeling with sin- from modeling over several time points. The solution for a given data set
gle instantaneous dipoles cannot take into consideration such an overlap of reveals not only a best-fit location for the model, but also the putative activ-
activity of multiple generators, nor can it decompose the voltage fields pro- ity of each dipole over time in the form of a source potential (Fig. 12.5).
duced by this superposition. Spatiotemporal source modeling is, however, Because there is no unique solution when trying to identify several sources
an approach based on this rationale (22–24). Dipoles are fixed in location that may underlie a voltage field that is a composite, it is necessary to use
and orientation but can vary over time in strength and polarity to explain modeling strategies to constrain the solutions to those that are most real-
the temporal evolution of a voltage field. Sufficient degrees of freedom are istic. Two major categories of strategies include those based on sequential
Figure 12.4: Left: Scalp EEG of a left temporal spike

with an elevated, combined radial/tangential field ori-
entation. Cursor denotes 0 millisecond latency. Top
right: Progressive change in the sequential voltage to-
pography of the spike is evident. Bottom right: Single
and moving dipole models of the spike. Single dipole
at spike peak is oblique in orientation, while moving
dipole model shows a progression in dipoles from verti-
cal tangential to horizontal radial, suggesting propaga-
tion from base to lateral temporal cortex.
Left View
FIgure 12.5: Same EEG and sequential voltage to-

pography as depicted in Fig. 12.4. Bottom right: A
spatiotemporal dipole model with two dipoles, (1) ver-
tical tangential and (2) horizontal radial, can explain
the voltage field evolution over the time course of the
spike, if dipole 1 has the source activity of trace 1 and
dipole 2 has the source activity of trace 2. The spatio-
temporal dipole model also suggests spike propaga-
tion from base to lateral temporal lobe.
345
temporal activation of adjacent generator areas and those based on the ori- Dipole location identifies only the “center of activity” of the cortical
entation of the cortical areas likely to be involved in the process. Implicit in source and certainly not its extent. Because this point source model tries to
the “temporal” strategy is the idea that the earliest part of a spike waveform explain the scalp field resulting from an extended source, the model dipole
is more likely to be the product of a single source than are later segments. is typically located deep to actual source cortex. Dipole localization tech-
Accordingly, one should first attempt to model the early part of the field evo- niques are least accurate in depth determinations because this estimation
lution as a single dipole, rather than the spike peak, for example. Additional depends on the size of the generator region. Single-dipole solutions provide
dipoles are used in sequence to model the residual field left unexplained a reasonable approximation for superficial cortical sources, if their diam-
by the preceding dipole(s). If the initial equivalent source explains, in spa- eter is smaller than 2 cm, such as with somatosensory-evoked potentials
tiotemporal terms, the entire spike field evolution, the generator is rather (23). Activation of a larger area of cortex, as is the case of epileptiform
discrete or simple in character. Commonly, however, two or sometimes three spikes, produces a more diffuse scalp field that would have to be modeled as
dipoles are necessary to explain the time course of even “focal” spike data. a deeper equivalent dipole. Think of a flashlight producing an illuminated
The spatiotemporal technique attempts to find the fewest number of fixed spot on a wall. In order for the flashlight to produce a larger spot, equivalent
equivalent sources that can explain field evolution by a temporal overlap of to a larger field, it must be farther from the wall, or in the case of a dipole,
activity among them. deeper in the brain. Accordingly, one should not be concerned about dipole
Modeling strategies using anatomic constraints can also be useful. The models that localize to white matter.
mathematics of unconstrained inverse solutions considers any position within It is the dipole orientation that identifies the likely source cortex within
the spherical head model and any orientation of dipole vector to be equally the region (17,18,29). Dipole orientation conveys the net orientation of the
likely as a source. This is obviously not true biologically. Spikes arise from the pyramidal cells generating the field and this is orthogonal to the net orien-
cortex that has limited and definable locations and orientations. Of the two, tation of the generator cortex. A simple step in EEG dipole interpretation
it is more useful to specify the orientation of possible equivalent sources. As is to project the dipole vector out to the cortical surface. If the EEG field is
noted previously, it is reasonable to consider for purposes of modeling, only principally radial, this projection should intersect source cortex that has a
the orientations of major lobar surfaces. For the temporal lobes, these ori- net orientation that is orthogonal to the dipole vector (Fig. 12.6). If there is
entations are horizontal radial for the lateral convexity cortex, vertical tan- no cortex in the region of a dipole model that has an appropriate orienta-
gential for the basal cortex and superior temporal plane, and AP horizontal tion, the validity of the source solution should be questioned.
tangential for the temporal tip. One approach in using this strategy for the A large area of activated cortex also means that tangential fields from
temporal lobes is to create a priori a multiple spatiotemporal dipole model opposing sulcal walls will often cancel one another, allowing radial com-
of major lobar surfaces, based on specific orientations obtained from brain ponents to predominate. A reasonable simplification for interpreting spike
imaging studies, and to note from the source potentials to what extent each dipole models is to consider only sources on the major outline of brain
dipole can contribute to explaining spike voltage fields over time (25–28). lobes. Accordingly, a tangentially oriented dipole is more likely to reflect an
appropriately oriented major cortical surface or fissure, such as the tempo-
Interpretation of Dipole Models ral lobe base or tip or Sylvian fissure, rather than an individual sulcus. As
an example, the cortical surfaces temporal lobe has only a few basic orienta-
The clinical interpretation of dipole source models requires an apprecia- tions, when small sulci are disregarded. Dipole models of spikes from the
tion for the weaknesses in the modeling assumptions and the complexity lateral, infero-lateral, tip, and basal (or superior) cortex are orthogonal to
of source geometry and physiology. It is clear from studies of simultane- these surfaces, and thus they are radial, oblique, horizontal AP tangential,
ous scalp and intracranial EEG that the sources of scalp spikes and seizure or vertical tangential in orientation, respectively (Fig. 12.7).
rhythms are quite large, namely 10 to 30 cm2. A point source dipole is a Recently, Kobayashi et al. (30) tested the accuracy of dipole models when
simple model of this extended cortical generator, and in order for it to be applied to simulated EEG derived from cortical patches of different location
useful, it must be interpreted properly. As noted previously, EEG dipoles and area. They demonstrated that dipole models of small sources (6 cm2)
model major cortical surfaces, not individual gyri or sulci. or very large sources (>100 cm2) were misleading, whereas dipole modeling
sources between 18 and 36 cm2 were consistent and accurate. Dipoles are
thus a reasonable source model for focal spikes, given that Tao et al. (4)
showed that epileptic potentials appreciated on scalp EEG commonly had
source areas of 10 to 30 cm2. Plummer et al. (31) reviewed the state of affairs
regarding the acceptance of dipole and other forms of electrical source
imaging in the presurgical evaluations of focal epilepsy as of 2008.
Several ways have been used to determine the adequacy of a given dipole
solution. The simplest is the goodness of fit of the model to the actual data
at each time point or over a time range. For clinical studies, in particular
when individual spikes are used, a residual variance of 10% to 15% can be
reasonable. Averaged spikes or seizure potentials should result in a better
fit. The residual variance or other measures of fit quality should be com-
pared over time to the mean global field power. A good dipole model shows
a goodness of fit curve that matches the shape of the field power. Curve
mismatches, that is low goodness of fit during a period of high global field
power means an inadequate model. Under these circumstances, additional
dipoles may be needed to explain the data over time. Recently, Fuchs et al.
(32) have developed a means of visualizing the quality of a dipole solution
as a 3D ellipsoid confidence volume.
Coregistering Dipole Models with MRI,

Realistic Head Models, and Spatial Sampling
Dipole models display in 3D terms, the same information that a person
can perceive by visually inspecting the voltage fields as explained earlier.
In addition, these equivalent dipoles can be coregistered either with a head
schematic or with an actual 3D MRI to identify putative sources within the
brain. With a head or brain schematic, it is possible to identify the most likely
lobe or perhaps even sublobar area containing the source. It is very tempting
to coregister dipole model data with 3D MRIs, as is commonly done with
other functional imaging techniques. By digitizing in 3-space (3D), the scalp
electrode locations and certain head landmarks, such as the nasion and pre-
auricular points, the topography of scalp EEG fields can be coregistered
Figure 12.6: In order to simulate the broad scalp voltage field generated by a
with and superimposed on a 3D MRI reconstruction of the patient’s head or
large cortical source (lightened left temporal cortex), an equivalent dipole (black
dot) must be deeper in the brain. One method of interpreting this deep dipole is brain. In similar fashion, calculated dipole models can be coregistered with
to project its orientation vector out to intersect the overlying cortex. The net orien- the same 3D brain image (Fig. 12.8).
tation of the convoluted cortical source is appropriately orthogonal to that of the The problem with doing so is that dipole sources or, worse yet, colored
dipole modeling it. Note that opposed voltage fields from each side of activated blobs that are placed on a brain image take on a seductive pseudo-realism
sulci cancel each other, leaving that of gyral crowns to predominate. that, in reality, must be verified. In the case of EEG dipole models, sources
Front Right Front Right
Top Back Top Back
C
Left Front
Top Back
Figure 12.7: EEG traces, voltage topography, and

single-dipole models of typical temporal lobe spikes.
Isopotential lines in speckled areas of voltage maps de-
note negativity; those in clear areas denote positivity.
Top left: Subtemporal negative field maximum, vertex
positive maximum, and elevated, oblique dipole ori-
entation of a Type 1 temporal spike. Top right: Lateral
temporal negative field maximum, contralateral tempo-
ral positive maximum, and horizontal radial dipole of a
Type 2 temporal spike. Bottom left: Interior frontotem-
poral negative field maximum, posterior positive maxi-
mum, and horizontal AP tangential dipole of a temporal
tip spike.
The boundary element model (BEM) is the most commonly used of the
realistically shaped models of the head (Fig. 12.9) to compensate for the
errors of a spherical head model. It can account for the individual, nons-
pherical shape of the main intertissue boundaries of the brain, skull, and
scalp (38,41,42). Each of these surfaces is discretized into triangular ele-
ments to form a mesh (Fig. 12.9). BEM head models have the shortcoming
that conductivity is assumed to be piecewise constant and isotropic, whereas
cranial tissues are inhomogeneous and show anisotropy. More sophisticated
finite-element methods can overcome these problems, but require consider-
ably more computational effort (43). Also, the detailed conductivity infor-
mation of various brain, skull, and scalp elements needed to construct such
a model is not well-established. Accordingly, BEM realistic head models are
a reasonable compromise for clinical purposes.
Fuchs et al. (44) described the use of a standardized BEM head model
derived from the averaged Montreal MRI data set in order to provide simple
access to realistically shaped volume conductor models for source recon-
struction. Standardized and individualized BEM head models resulted in
more accurate and comparable dipole solutions than those derived from a
spherical model. They compared dipole modeling accuracy using spheri-
cal head models, individually derived realistic head models, and the stan-
dardized realistic head model in both source simulations and epileptic spike
Figure 12.8: Dipole solutions for a left temporal lobe spike are coregistered with data. Spherical head models resulted in dipole mislocation errors at the base
a 3D model of the patient’s brain MRI. Recording electrodes and voltage field of the brain, as previously noted. Standardized and individualized BEM
lines are also displayed in register. The lower dipole solution was calculated with head models resulted in more accurate and comparable dipole solutions. By
a realistic, boundary element head model, while the upper dipole was derived using a standardized head for the BEM setup, an easier and faster access
with a three-sphere head model. to the benefits of a realistically shaped volume conductor models can be
achieved.
in the cortical convexity are usually localized accurately. This is because even Figure 12.10 illustrates dipole solutions for a temporal lobe spike cal-
simple spherical head models used by source modeling algorithms work well culated with both spherical three-shell and BEM head models. Dipoles
in this most spherical part of the head and brain. However, when sources using a spherical model were misplaced 2 cm upward from those of a
were near the base of the brain, such as in the temporal lobe, systematic BEM model and their true temporal lobe source. Such an error can give
dipole location errors occur even for known sources (33,34). These system- the false impression that the spike/seizure source was of superior temporal
atic errors in dipole location, introduced when using a spherical head model, or frontal rather than anterior inferior temporal lobe origin. It is apparent
had been previously recognized (33–36). Later, investigators simulated EEG that realistic head models should be considered whenever dipoles are co-
dipole sources throughout the brain and found that spherical head modeling registered with MRI for interpretation. This is particularly true for basal
errors were worse for basal brain regions and in the Z or vertical direction frontal, temporal, and occipital sources where the brain cortex and skull
(37–39). These results were also confirmed using temporal lobe spike and departs most from a spherical shape. A simple way to determine whether a
seizure foci as the source and validating the true location of these foci with BEM model would be worthwhile in modeling spikes and seizures is to look
intracranial EEG (3,40). This error was typically in the vertical direction, at the voltage maps of the field maxima. If the normally dominant nega-
and it could be as great as two or more centimeters in magnitude, when a tive field maximum is only partially described and it rests near or below the
spherical head model was used (34,35,37). 10–20 system “equator,” in the “southern hemisphere” of the head, a BEM
Figure 12.9: Left: Shaded circle on a patient’s head

depicts the typical shape of a spherical head model.
Middle: Realistic BEM head model illustrating inner
and outer surfaces of the skull and scalp derived from
3D MRI reconstructions. Right: Tessellation of these
surfaces into a triangular mesh used in the source cal-
culations. Note the divergence of the brain and skull
base from the simple spherical shape.
model will be necessary to compensate for the nonspherical nature of the Dipole Modeling of Seizures
skull in this region.
Some have proposed on theoretical grounds that high-resolution EEG Dipole modeling can also be applied to seizure rhythms with some modifica-
requires hundreds of electrodes (45); however, others have concluded that the tions in the protocol used for spikes (2,3,19,29,48–51). The earliest recogniz-
gain beyond 40 to 64 electrodes is negligible for dipole models (37,46). This able seizure potentials should be preferentially modeled because they are
is particularly true for epileptogenic spike and seizure sources that tend to more likely to reflect the seizure origin than are later rhythms, which usually
be large spatially and produce scalp voltage fields of low spatial frequency, evolve only after significant propagation. In most instances, the EEG must
namely, dipolar. Lantz et al. (20) recorded spikes from patients with epilepto- be filtered with a narrow bandpass covering those frequencies that repre-
genic lesions with 128 electrodes and performed source modeling with various sent the cerebral seizure activity and not the accompanying artifact. For
down-sampled arrays. An increase in electrode number from 31 to 63 resulted partial seizures of the temporal lobes, this is approximately 2 to 10 Hz. For
in significantly improved localization, whereas only minimal additional pre- extratemporal seizures that commonly have a beta frequency component, a
cision was achieved with an increase in electrode number to 128. Given the broader 2- to 20-Hz bandpass is useful.
fact that the position and orientation/magnitude of a dipole model has only Because ictal-onset rhythms are typically of low amplitude and are com-
six unknowns, even a modest number of scalp electrodes provide an overde- monly confounded with movement and muscle artifact, averaging successive
termined solution. A larger number of electrodes (128 to 256) does, however, potentials may be necessary to increase the S/N. The key is to average seizure
improve largely underdetermined extended source models (47). waveforms with similar voltage topographies (Fig. 12.11); only these reflect
Figure 12.10: EEG traces, voltage topography, and single-
dipole models of the same left temporal spike in both 2D
and 3D MRIs. Dipole solutions in the upper panel were
calculated with a three-sphere (3S) head model; dipoles in
the lower panel were calculated with a realistic BEM head
model. Note that the 3S dipoles are approximately 2 cm
higher than the BEM dipoles. In this and subsequent similar
figures, the 2D MRI images are anatomical, that is, left on
left. Also, negative and positive field maxima are noted by
“−” and “+” in the voltage maps.
351
Left Right
Top Bottom
Back Front
Figure 12.11: Top: EEG traces showing a left temporal

seizure onset. Individual ictal waveforms are marked
by cursors. These ictal waveforms are averaged and
displayed at the left side of the traces. Voltage topog-
raphy of the averaged ictal waveform is displayed at
the right side. Bottom: Dipole models of the seizure
onset are coregistered with a 3D brain MRI of the pa-
tient. Dipoles in the top row were calculated using a
3S head model; those in the bottom row were calcu-
lated with a BEM head model.
the same source configuration. These periods of stable fields may last only a Commonly, spikes propagate locally across the adjacent cortex from their
few seconds. Alternatively, spatiotemporal modeling can be performed over origin or even distally over white matter tracts. When this happens, the
this stable epoch. One or more fixed dipoles possessing cyclic variations in geometry of the generator cortex changes and the voltage fields produced
the magnitude and polarity of their source potentials can often explain the evolve as well. As noted previously, in instances of a stable source, volt-
repeating evolution of an ictal voltage field. Temporal and orientation strat- age fields will rise and fall in amplitude but not change in scalp location or
egies are applicable in seizure modeling, just as in spike modeling. Modeling shape. Conversely, propagation from source of origin will result in a scalp
sequential epochs during the course of the seizure can provide insight about voltage field whose maxima move in location and change in shape. When
seizure propagation. propagation is simple and unidirectional, this can be modeled by sequential
The orientation of dipole models of ictal waveforms carries the same sig- or so-called moving dipoles (Fig. 12.16).
nificance as those of spikes, and it is most useful in identifying sublobar
sources (2,3,19,29,48–51). Temporal lobe seizures modeled by dipoles with
Extratemporal Sources
dominant horizontal radial, vertical tangential, or horizontal tangential AP
orientations are most likely associated with lateral temporal, hippocam- An increasing number of cases of extratemporal epilepsy are being seen in
pal/basal, or temporal tip seizures, respectively (Fig. 12.12). Additionally, epilepsy centers. Spikes and seizures from these patients can also be local-
many temporal lobe seizures are modeled best by dipoles having an anterior ized better with voltage topography and dipole modeling techniques. Given
oblique orientation, that is, a combination of all three of the previous ori- that much of the frontal and parietal cortex lay on the cortical convexity,
entations. In this case, the ictally active cortical region includes inferior, tip, radial sources are common (Figs. 12.17 and 12.18). These have the advan-
and anterior lateral temporal cortex. Multiple fixed-dipole models can also tage of being more easily interpreted, namely under the negative maximum
be used to identify the contribution of various sublobar cortical areas to is the source. However, fissures and deep sulci can produce tangential fields
seizure potentials. This technique has been used to determine temporal lobe that are confusing to visual inspection of EEG traces, particularly in bipolar
seizure origins and to predict surgical outcome following standard temporal montages (Figs. 12.18 to 12.20). False lateralization can occur if one pays
lobectomy (27,28). attention to only the negative field maximum. Voltage maps confirm the
tangential nature of these fields, and dipole models clearly show that the
source lies between the negative and positive field maxima. Source propaga-
Dipole Models for Specific Cortical Regions tion can be characterized by a moving dipole model (Fig. 12.21).
Temporal Lobe Sources
Other EEG Source Models
Perhaps the most common source of epileptiform activity in patients with
complex partial seizures is the temporal lobe. The anatomy of this lobe Within the past decade, there has been considerable development of new
affords the possibility of a number of spike and seizure voltage fields and techniques to expand the use of source modeling in the evaluation of epi-
thus several types of dipoles that model them. Typical temporal spike fields lepsy patients. Many of these involve new mathematical approaches to
have an anterior or mid-temporal negative maximum (Fig. 12.13). The infe- the decomposition of the data or to the reconstruction of a source model.
rior extent of this negative maximum, and more importantly, the location Because the number of cortical sources is not known when modeling spike
of the positive field maximum will determine if the orientation of the dipole or seizure potentials, some investigators feel that decomposing the data by a
is radial (horizontal), tangential (vertical or horizontal AP), or oblique variety of techniques is worthwhile before attempting to model them. Sev-
(in between radial and tangential) (Figs. 12.14 and 12.15). These dipole eral have chosen to use singular value decomposition (52) or independent
orientation, as well as location, differences confirm different sublobar spike component analysis (53–55). The likely number of component sources, or
sources. Dipole models can easily distinguish spikes that originate from at minimum the dominant component, can be estimated and their contribu-
lateral, inferolateral, basal, tip, and superior temporal cortex. tions to the voltage field and waveform separated without prior knowledge.
Front Right Front Right
Top Back Top Back
Left Front
Left Front

single-dipole models of typical temporal lobe sei-
Top Back
Top Back zures. Isopotential lines in speckled areas of voltage
maps denote negativity; those in clear areas de-
note positivity. Top left: Subtemporal negative field
maximum, vertex positive maximum, and elevated,
oblique dipole orientation of an anterior, inferolateral
temporal seizure. Top right: Lateral temporal nega-
tive field maximum, contralateral temporal positive
maximum, and horizontal radial dipole of a lateral
midtemporal seizure. Bottom left: Interior frontal
negative field maximum, posterior positive maximum,
and horizontal AP tangential dipole of a temporal tip
seizure. Bottom right: Subtemporal negative field
maximum, contralateral posterior positive maximum,
and oblique dipole of an anterior temporal seizure.
Figure 12.13: EEG traces, voltage topography, and dipole
models of typical temporal lobe spike sources in 2D and
3D brain MRIs. Top: Anterior subtemporal negative field
maximum, contralateral vertex positive maximum, and
oblique dipole of an anterior inferolateral temporal source.
Projection of dipole vector intersects inferolateral temporal
tip cortex. Bottom: Midtemporal negative field maximum,
contralateral positive maximum, and radial orientation of a
lateral, midtemporal source.
355
models of typical temporal lobe spike sources in 2D and
3D brain MRIs. Top: EEG traces in a longitudinal bipolar
montage show no phase reversals, however a phase-away
reversal is evident. Localization of the negative field maxi-
mum is unclear. Bottom: EEG traces in a common average
reference show more clearly the FP2 negative field maxi-
mum and T8 positive maximum that is evident in the volt-
age maps. Horizontal tangential dipole is consistent with an
antero-mesial temporal tip source.
356
models of typical temporal lobe spike sources in 2D and 3D
brain MRIs. Top: Posterior subtemporal negative field maxi-
mum, vertex positive maximum, vertical tangential dipole
of a temporal base source. Note that a weak negativity can
even be seen in the contralateral subtemporal electrodes.
Bottom: Posterior temporal negative field maximum, fron-
tal positive maximum, and oblique dipole of a posterior-
inferior temporal source.
357

dipole models of typical temporal lobe spike sources
in 2D and 3D brain MRIs. Note progressive change
in the location of the voltage field maxima over
40 milliseconds. The negative field maximum moves
from the inferior frontal to the midtemporal region,
while the positive maximum moves from the contra-
lateral posterior to vertex region. A moving dipole
model over the period shows source movement from
the left temporal tip to basal temporal cortex.
Others have devised techniques for systematically scanning the entire brain problem, however, if many local sources are to be calculated from mea-
space for possible sources (56,57). surements at relatively few electrode locations. Regularization is necessary
Although the dipole is a useful concept from which practical diagnos- to proceed in these circumstances. This represents a compromise between
tic information can be obtained, it is anatomically not very realistic. Brain the demands to explain the measured data and to meet certain source or
sources of spikes or seizures are extended cortical patches, not isolated points. boundary conditions. One such boundary condition is the minimum norm
Clinicians, in particular, are more comfortable seeing regions of cortical acti- criterion, in which the source constellation of lowest electrical power is cal-
vation, such as displayed in PET, SPECT, or fMRI images, regardless of the culated. Variations include the L2- or L1-norms (58) or the minimum spa-
physiological soundness of these representations. There has been considerable tial Laplacian, also called low-resolution tomography (LORETA) (59,60).
effort recently to go beyond dipole source models to more realistic extended Additional techniques for estimating multiple sources or single source with
source models. These take a variety of approaches; however, a common form extent include LAURA and EPIFOCUS (61,62), and VARETA (63). The
of source reconstruction works on the hypothesis that brain currents are usefulness of these techniques needs to be proven with clinical data and
located only at specified locations. Using the cortical surface, for example, is a further validated by intracranial EEG recording, however. One investigation
powerful reconstruction parameter that restricts the search space to a surface, demonstrated no advantage of current density reconstruction over source
which can be defined further by local orientation information. modeling with dipoles (64).
Algorithms have been devised that can calculate discrete approximations Another approach to the problem of unrealistic point-like dipoles is the
of the current density distribution on a defined surface. This is an ill-posed use of a “dipole patch” model. It is composed of many individual dipoles
dipole models of typical extratemporal spike sources
in 2D and 3D brain MRIs. Top: Lateral centro-temporal
negative field maximum, contralateral frontal positive
maximum, and radial dipole of a left frontal operculum
source. Bottom: Inferior frontotemporal negative field
maximum, ipsilateral vertex positive maximum, and
oblique dipole of a left orbitofrontal source.
359
Figure 12.18: EEG traces, voltage topography, and d ipole
models of typical extratemporal spike sources in 2D and
3D brain MRIs. Top: Ipsilateral occipital negative field
maximum, contralateral frontal positive maximum, and

radial dipole of a left occipital source. Bottom: Contralat-
eral occipital negative maximum, ipsilateral occipitotempo-
ral positive maximum, and tangential dipole of a left mesial
occipital source.
360

in 2D and 3D brain MRIs. Frontal vertex negative field
maximum, ipsilateral frontotemporal positive maxi-
mum, and tangential dipole of a mesial frontal source.
that are constrained to follow the surface of the patient’s own cortex, derived orientation (type 1) (see Figs. 12.3, 12.4, and 12.7). A variety of clinical
from 3D MRI reconstructions, in both position and orientation. This model correlations, as well as simultaneous scalp and intracranial EEG investi-
has a spatial extent that is adjustable to that known to produce scalp EEG gations, suggested that the type 2 field topography and its corresponding
potentials (4). The location of dipole patches was accurate at a sublobar horizontal radial dipole model originated from a lateral temporal cortical
level when compared to underlying cerebral sources, as validated by intra- source, whereas type 1 topography and its corresponding vertical tangential
cranial EEG (65). Other extended source models, such as those employing dipole model was associated with inferolateral and basal temporal sources.
current source density estimations, are not limited to realistic source areas, However, the type 1 spike field was not thought to reflect hippocampal or
nor are they constrained to anatomically contiguous cortex as is this model. amygdalar activity directly. It was shown that spikes confined to these struc-
tures did not generate scalp-recordable voltage fields due to the small source
Clinical Studies Using Dipole Models area and curved source shape, which favor voltage cancellation. Rather, it
was the common and preferred propagation of this epileptiform activity
The early 1990s marked the beginning of clinical studies of patients with from mesial structures into the entorhinal, fusiform, and other temporal
epilepsy using voltage topography and dipole modeling. It soon became basal cortex that resulted in a generator of sufficient area to produce scalp
apparent that the voltage field of spikes and seizure potentials could vary EEG potentials (2,68,69). Subsequent investigation demonstrated that a
considerably even if their origin was the same lobe. Ebersole and Wade rigid categorization of temporal spike topography was overly simplistic.
(66,67) first made the distinction between temporal lobe spikes with a radial Spike voltage fields commonly evolve over tens of milliseconds, which usu-
field orientation (type 2) and those with an oblique to vertical tangential ally signify a propagating spike source. A type 1 pattern may evolve into a
models of typical extratemporal spike sources in 2D and
3D brain MRIs. Top: EEG traces in a longitudinal bipolar
montage show no phase reversals; however, a phase-away
reversal is evident. Localization of the negative field maxi-
mum is unclear. Bottom: EEG traces in a common aver-
age reference show more clearly the Fz-Cz negative field
maximum and P4 positive maximum that is evident in the
voltage maps. The horizontal tangential dipole is consis-
tent with a lateral central sulcus source.
362

in 2D and 3D brain MRIs. Note progressive change in
the location of the voltage field maxima over 32 milli-
seconds. The negative field maximum moves from the
fronto-central to frontopolar region. A moving dipole
model over the period shows source movement from
the right fronto-central to frontopolar cortex.
type 2 pattern and vice versa. Spikes that originate in the basal temporal cor- scalp and intracranial EEG recordings, confirmed that dipole orientation
tex frequently propagate into the temporal tip cortex by the time sufficient was the major distinguishing factor to distinguish spikes originating from
cortex is activated to produce a scalp EEG field. Temporal tip cortex has baso-mesial temporal sources from those of lateral temporal origin. Merlet
a net anterior-facing orientation. Accordingly, spike sources in this cortex and Gotman (73,74) in a pair of papers validated dipole models of spikes
result in a voltage field with a frontotemporal to frontopolar negative maxi- or seizures with a later combination of intracranial and scalp EEG. They
mum and a posterior positive maximum (3,19,29) (see Fig. 12.7). concluded that only simple cortical sources could be well-modeled by one
By the mid-1990s, several other investigators began to apply EEG dipole dipole and that spike modeling yielded better and more frequent results than
modeling for the evaluation of epilepsy surgical candidates. In general, they seizure modeling. Numerous other publications began appearing in the late
confirmed findings from earlier studies. In a series of investigations, Boon 1990s that confirmed a good correlation between spike dipole models and
et al. (48–51) demonstrated that patients with medial temporal lesions had other localization tools such as intracranial EEG (75,76), positron emission
EEG spikes and early seizure rhythms that were modeled by dipoles having tomography (77), single photon emission tomography (77,78), and MRI
a elevated orientation above the horizontal (a combination of radial and lesions in both adults and pediatric patients (79).
tangential) similar to Ebersole type 1 spike, whereas patients with lateral Dipole source models were later shown by the Marseille group, headed
temporal or extratemporal lesions had EEG spike and early seizure rhythms by Chauvel, to be accurate not only for temporal, but also for frontal and
that were modeled by dipoles having a radial orientations similar to Ebersole posterior foci, if the geometry of the focus was not overly complex or multi-
type 2 spike. Lantz et al. (70–72), in a series of studies using simultaneous focal (80–82). Recently, both dipole and extended EEG source models have
shown to be particularly useful in patients with normal MRI, where accu- recognition of EEG traces recorded in a bipolar montage, rather than an
rate functional localization of the epileptic focus is key (83,84). understanding of the underlying voltage fields. For the most part, clinical
Ictal EEG dipole models have been correlated with intracranial EEG EEG localization has failed to advance beyond identifying the largest nega-
and surgical outcome (2,3,19,27–29,48–51). The results are similar to those tive potential and assuming that the source of that potential must underlie
found with spike dipole modeling. Patients with temporal lobe seizures mod- the electrode recording it, even though that assumption is bio-physically
eled by horizontal radial dipoles, which suggest a lateral cortex origin, do incorrect in most situations. Modern digital EEG machines and software
less well following a standard anteromesial resection and should be consid- can make the display of voltage fields and calculation of an equivalent
ered candidates for invasive monitoring and possibly tailored temporal lobe dipole as simple as a mouse click. That these data and models are not used
resections. Patients whose seizures are modeled best by dipoles with a verti- more often in clinical work appears to be mostly a matter of clinical iner-
cal, horizontal AP, or anterior oblique orientation have seizures originating tia and the unfounded concern that significant additional time and effort
probably in mesial structures, basil, entorhinal or temporal tip cortex, respec- will be required. With a more widespread appreciation for the strengths of
tively. All of these patients do well following surgery because these cortices voltage topography and dipole modeling and an understanding of how to
are customarily removed in the standard temporal lobe resection. Recently, interpret them clinically, these EEG analysis tools are ready to take their
ictal source modeling using both dipoles and several extended source algo- place among the routine practices for evaluating patients with epilepsy.
rithms were compared (85). Dipole modeling provided the closest concor-
dance (90%) with the ictal-onset zone as determined by intracerebral EEG.
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13 Subdural Electrode Corticography
JAMES TAO • JOHN S. EBERSOLE
Introduction Postoperative Care

Historical Perspectives EEG Acquisition
Technical Considerations Intracranial EEG Patterns
Subdural versus Depth Electrodes Normal Intracranial Physiological EEG
Characteristics of Subdural Electrodes Intracranial Interictal EEG
Localization of Intracranial Electrodes Intracranial Ictal EEG
Risks and Complications of Subdural Electrode High-frequency Oscillations
Placement Electrical Stimulation and Functional Localization
Clinical Indications of Subdural Electrode EEG Conclusion
Recording References
Postoperative Care and EEG Acquisition
Introduction component of epilepsy presurgical evaluation for localizing the epileptic

focus. When congruent with other noninvasive data, such as ictal semiology
Epilepsy is a chronic neurological disorder that affects approximately 1% and anatomic and functional neuroimaging studies, scalp EEG data can suf-
of the world’s population, including approximately 3 million people in the ficiently guide the surgical resection of an epileptic focus (4–9), particularly
United States and 60 million worldwide. Despite the significant advances in patients with unilateral mesial temporal lobe sclerosis (MTS) and concor-
of pharmacological treatment in the last several decades, 30% to 40% of dant interictal and ictal recordings (10).
patients continue to have seizures that are not adequately controlled by anti- However, scalp EEG has intrinsic limitations in its spatiotemporal reso-
epileptic drugs (AEDs) (1). Epilepsy surgery has remained the only treat- lution when attempting an inverse solution (11–13), that is, localizing the
ment that can achieve seizure freedom for pharmacologically refractory cortical source of a given potential. Cortical interictal spikes are typically
epilepsy patients (2,3). Scalp electroencephalography (EEG) is an essential heterogeneous in their source location, area, synchrony, and amplitude.
367
Only a few of those cortical spikes are associated with scalp-recognizable specific motor responses (24). This observation led Hughlings Jackson to
potentials. Simultaneous scalp and intracranial EEG recording has shown believe that focal epilepsy is a manifestation of cortical irritation. He sub-
that the cortical area required to generate scalp epileptiform discharges is sequently described Jacksonian seizures (or march) in the primary motor
considerably larger than commonly thought, namely 10 to 20 cm² (14). Both cortex (25,26), and further suggested treatment by removal of the irritating
sufficient cortical source area and synchrony are necessary for the spatiotem- focus. In 1886, Jackson collaborated with neurosurgeon Victor Horsley who
poral summation of voltage to produce a scalp EEG epileptiform potential. performed the first successful epilepsy surgery on a 22-year-old patient with
Additionally, different cerebral source configurations can generate a similar traumatic brain injury and focal motor seizure (27). Horsley subsequently
distribution of scalp voltage or magnetic fields. Thus, maximal activity at a reported 10 similar cases in the following year with mostly favorable out-
certain scalp electrode or sensor does not necessarily indicate that the gen- comes, namely, seizure freedom in two patients and seizure reduction in five
erators are located in the area underlying it (4,15). Moreover, because the patients (28).
skull attenuates fast frequencies more than slow frequencies, high-frequency This auspicious beginning of epilepsy surgery led to a surge of similar
and low-voltage rhythms (such as gamma) at ictal onset simply are not rec- cortical resections in the following decade. However, epileptogenic focus
ognizable with conventional scalp EEG. Accordingly, scalp ictal rhythms localization by seizure semiology (i.e., motor symptoms) and anatomi-
typically reflect propagation and recruitment, rather than indicate the loca- cal identification of the motor strip were notoriously unreliable. Epilepsy
tion of seizure-onset zone. False localization and even lateralization are not surgery was largely saddled with poor outcomes and high morbidity and
uncommon, such as in patients with temporal lobe epilepsy (TLE) asso- mortality (29). When phenobarbital was serendipitously discovered as an
ciated with early contralateral propagation, temporal-plus epilepsies, and effective anticonvulsant in 1912, epilepsy surgery suddenly lost its appeal
extratemporal epilepsy (16–18). Given these intrinsic limitations, scalp ictal and became largely forgotten.
recording is often used simply as a screening tool to select those requiring In 1929, Berger (30) reported the first human EEG recording, which fea-
intracranial recordings or to exclude certain patients from further surgical tured the alpha rhythm and alpha block response. EEG in the diagnosis
evaluation. and treatment of epilepsy evolved quickly after Berger’s work. Its usefulness
More than a half-century ago, Penfield and colleagues found that seizures was later confirmed by Adrian and Matthews (31) at Cambridge University
in epileptic patients could be cured by removing the brain region from which in 1934, and by Jasper and Carmichael (32) at Brown University in 1935.
localized abnormal discharges on EEG (19–22) originated. Since then, iden- In 1935, Foerster and Altenburger (33) performed the first intraoperative
tifying the seizure-onset zone on intracranial EEG has become the cor- electrocorticography (ECoG) during epilepsy surgery. This ECoG technique
nerstone or “gold standard” for localizing epileptic foci. Subdural and/or was soon adopted by Gibbs and Lennox (34–36). Later, Penfield and Jas-
depth electrodes are commonly used in this task of precisely localizing the per (37) used wires and “strip” electrodes during ECoG to localize epileptic
epileptogenic focus (23). Additionally, subdural electrodes are well-suited focus and determine the extent of surgical resection.
for direct electrical stimulation of the cortex to define the functional (i.e., However, intraoperative ECoG is mainly limited to recording interictal
sensory, motor, and language) areas. Thus, subdural electrodes are useful in discharges, and it is often compromised by anesthetic agents. In order to
achieving both objectives of intracranial EEG study, namely localizing the overcome these disadvantages, chronic intracranial EEG with depth elec-
epileptogenic zone and delineating important functional cortex. This infor- trodes was first employed in the late 1940s to record spontaneous seizures.
mation can subsequently guide a tailored, maximal resection of epilepto- Depth electrodes showed to be particularly suited to localize seizure onset
genic tissue, while sparing “eloquent” cortex. in patients with mesial TLE (38–40). Depth electrode recording was further
popularized by Bancaud and Talairach with the development of stereotactic
Historical perspectives technique, which can precisely target subcortical structures (41, 42). This
method became known as stereoelectroencephalography (SEEG).
The success of epilepsy surgery is related to a number of scientific and tech- In the meantime, subdural electrodes embedded in a flexible silastic
nological discoveries. In 1870, Gustav Fritsch and Eduard Hitzig found that membrane were also gaining in popularity due to a more extensive cover-
electrical stimulation of different areas on the cerebral cortex could produce age of cortical surface and easier placement without stereotactic equipment
Subdural Electrode Corticography 369
(43, 44). In conjunction with electrical cortical stimulation for functional in epilepsy centers in North America, whereas depth electrodes are com-
mapping of the motor, sensory, and language cortex, intracranial EEG with monly used in epilepsy centers in Europe. Combinations of subdural and
subdural and/or depth electrodes has become both an effective and safe pro- depth electrodes are sometimes used to optimize the yield of an intracra-
cedure for presurgical epilepsy evaluations. nial EEG study; however, this may also increase the accumulative risks of
morbidity.
Technical considerations
Characteristics of Subdural Electrodes
Subdural versus Depth Electrodes
Subdural electrodes are typically made of stainless steel or platinum-iridium
Several different types of electrodes can be used to record intracranial EEG. in the form of strips and grids. Subdural electrode arrays come in shapes and
These include subdural, depth, and epidural electrodes. Each type has its sizes that can be customized to the needs of individual patients (Fig. 13.1).
advantages and limitations. Subdural electrodes are placed directly onto the Strip electrodes consist of one to two rows of electrodes ranging from
brain in free-hand fashion to sample epileptic discharges from the cortical four to eight contacts, whereas subdural grids typically consist of four to
surface. They are commonly used to localize epileptogenic foci in the corti- eight rows of electrodes, typically ranging from four to eight contacts. The
cal convexity, basal cortex, and interhemispheric cortex. In addition, sub- contacts are discs mounted on a thin, flexible silastic sheet with 2- to 5-mm
dural electrodes, when implanted in large arrays, can determine the extent diameter exposed to the cortical surface. Intercontact separation is usually
of an epileptogenic zone for guiding a tailored surgical resection. Moreover, 5 to 10 mm. Strip electrodes can be inserted through burr holes. However, a
subdural electrodes are well-adapted for cortical mapping, that is, electri- large grid, such as 4 × 4 or 8 × 8 arrays, can only be placed through a size-
cal stimulation to localize sensory, motor, and/or language cortex. However, able craniotomy, which may increase morbidity, especially with a bilateral
both the implantation and removal of subdural electrodes require major grid placement.
surgery, and, particularly with grids, a large craniotomy. Also, these elec- The number of subdural electrodes used for a given patient is dependent
trodes cannot localize seizure generators in deep-brain structures. on the character of the putative seizure focus that was determined in the
On the contrary, depth electrodes are commonly used to identify deep noninvasive presurgical evaluation by seizure seimology, scalp EEG record-
epileptogenic foci, such as in the amygdala, hippocampus, insula, and sul- ing, magnetoelectroencephalography (MEG), and anatomic and functional
cal cortex. They can be also used to determine epileptiform activity in and neuroimaging studies. In one review and meta-analysis, the mean number
around hypothalamic hamartoma and periventricular heterotopia. Depth of implanted subdural electrodes varied from 52 to 95 electrodes, while the
electrodes are commonly placed with stereotactic and/or neuronavigation mean duration of monitoring may vary from 5 to 17 days, respectively (46).
guidance through small burr holes. These electrodes can be easily removed A larger number of electrodes, 100 to 200, can be placed using combination
at the bedside without significant discomfort. Although implantation of of strip and grid electrodes, particularly when cortical coverage of multiple
depth electrodes is technically more challenging, the procedure is better lobes is clinically indicated. Such a large number of electrodes can exert a
tolerated by patients and it has lower risks for morbidity. However, depth mass effect on the brain and cause a midline shift of several millimeters,
electrodes provide limited sampling of neocortex compared to subdural obviously increasing the risk of surgical complications.
electrodes, and they are less good in determining the extent and margins of Stainless steel and platinum (usually platinum-iridium) are the typical
an epileptogenic focus, particularly if it is necortical (45). In addition, they substrates for subdural electrode contacts. Platinum electrodes have advan-
are not well-suited for functional mapping of the cortex. tages over stainless steel electrodes in that they are nonferrous and thus
In practice, the type of electrode selected for intracranial study is depen- compatible with magnetic resonance imaging (MRI) and MEG studies. In
dent on the strengths and limitations of each type of electrode as deter- addition, the denser platinum electrodes have higher signal intensity on head
mined by the putative location of epileptic focus from noninvasive studies. CT images. This can be an important consideration for three-dimensional
Many epilepsy centers tend to have a preference regarding subdural versus (3D) CT/MRI coregistration of implanted subdural electrodes, as described
depth electrodes. For instance, subdural electrodes are commonly used in the following section.
36 cm
3 Digit ID#
A
1
6
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8
xxx
87 6 5 4 3 2 1
1 cm
1 cm
36 cm
B
3 Digit ID#
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15 13 11 9 7 5 3 1
xxx
16 14 12 10 8 6 4 2
1
8
Tantalum marker
1 cm
C 36 cm
3 Digit ID#
25
26
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29
30
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32
31 29 27 25 23 21 19 17
xxx
32 30 28 26 24 22 20 18
17
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9
15 13 11 9 7 5 3 1
xxx
16 14 12 10 8 6 4 2
1
Tantalum marker
1 cm
D 36 cm
3 Digit ID# 63 61 59 57 55 53 51 49
57
58
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60
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62
63
64
xxx
64 62 60 58 56 54 52 50
49
50
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52
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47 45 43 41 39 37 35 33
xxx
48 46 44 42 40 38 36 34
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40
25
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31 29 27 25 23 21 19 17
xxx
32 30 28 26 24 22 20 18 Figure 13.1: Commonly used subdural electrodes: (A) 1 × 8 strip; (B)
17
18
19
20
21
22
23
24
2 × 8 strip; (C) 4 × 8 grid; (D) 8 × 8 grid. The diameter of each electrode
10
11
12
13
14
15
16
9
15 13 11 9 7 5 3 1 contact is 4 mm. The contacts are spaced at 1.0 cm, center to center.
xxx
16 14 12 10 8 6 4 2 Smaller center-to-center measurements are available. As named, these
1
electrodes are typically placed subdurally or epidurally through a burr

Tantalum marker hole, if a strip, or through a craniotomy.
Localization of Intracranial Electrodes

From both research and clinical perspectives, the accurate localization
of implanted subdural electrodes is critical for delineating the seizure-
onset zone and eloquent cortex for planning a tailored resection. With the
advent of modern neuroimaging techniques, such as high-resolution MRI,
single-photon emission computed tomography (SPECT), positron emission
tomography (PET), MEG, and functional MRI (fMRI), the integration of
these multimodal diagnostic data has shown great promise in guiding the
epileptic focus resection and in improving surgical outcomes (47–49). Key
to this multimodal approach is knowing precisely where subdural electrodes,
which record epileptiform activity, are located relative to structural and
functional imaging results.
Traditionally, localization of intracranial electrodes involved estimating
their cortical position based on direct visual inspection through craniotomy,
sketches of the basic geometry of the implantation components, and lateral
skull x-rays. In the former instance, only the electrodes visible in the open
craniotomy can be located. Electrodes placed via burr holes or those posi-
tioned over hidden cortical areas, such as temporal tip and basal cortex,
cannot be localized reliably. Several advanced quantitative techniques have
been developed to locate all implanted intracranial electrodes. These include Figure 13.2: 3D visualization of subdural electrodes obtained from coregistra-
postimplant 3D MRI images (50), curvilinear reformatting of 3D MRI tion of a presurgical MRI and postimplant CT in a patient with left TLE. Note
(51), intraoperative digital photography (52,53), surface reconstruction of the thorough electrode coverage of the anterior and posterior temporal cortex.
CT Scan (54), 3D CT/MRI coregistration (53,55–58), and coregistration Combinations of subdural strip and grid electrodes were employed in this study.
of pre- and postimplant MR images (59). While there are advantages and
limitations to each method, the 3D CT/MRI coregistration technique is one of surface fiducial markers can be compromised by poor image quality (e.g.,
of the most commonly used. It has the advantage of a realistic display of motion artifacts) and/or a restrictive field view that precludes identifying
implanted electrodes relative to cortical anatomy without having electrode scalp landmarks. In such instances, the location error can be significantly
artifacts (55). Briefly, both preimplant brain MRI images with volumetric increased to 5 to 10 mm, which may pose an unacceptable risk in planning
sequences and postimplant head CT images (0.5- to 1.0-mm thin slicing) a tailored resection. Therefore, confirmation of electrode localization accu-
are obtained. Corresponding pairs of external fiducial anatomic markers racy when using any coregistration technique should be done with intraop-
(nasion, inion, and preauricular points) from both MRI and CT data sets erative digital photography prior to resection (Fig. 13.3).
are identified, and the two volumetric data sets are coregistered to produce
an image that shows the electrodes on a 3D cortex (Fig. 13.2). Risks and Complications of Subdural Electrode Placement
Subdural electrode localization via 3D CT/MRI coregistration can be
very accurate, but it is dependent on having reliable surface fiducial mark- Improvements in grid technology, surgical technique, and postoperative care
ers. In a clinical study, this technique was compared to intraoperative digital have resulted in significant reductions in complications following subdural
photography, using gyral/sucal patterns and cortical vasculature as ana- electrode implantation. Morbidity reported in the literature is generally low,
tomic markers. Localization error was only 2 to 4 mm or approximately half however, variable, ranging from 1% to 23% (60–63). Isolated cases of per-
the diameter of the electrode contacts (55,58). Clinically, this is generally manent neurological deficits (motor and language) and death have also been
acceptable for guiding a tailored resection. In practice, however, the location reported (61,64–66).
Figure 13.3: Validation of location accuracy of coregistered subdural

electrodes using intraoperative digital photography: A: 3D view of sub-
dural electrodes coregistered onto the patient’s cortex. B: Intraoperative
photograph of gyral/sulcal patterns and cortical vasculature visible in the
craniotomy prior to electrode placement. Arrow indicates the Sylvian fis-
sure. C: Zoomed-in view of coregistered electrode positions similar to
the intraoperative photo. D: Intraoperative view of subdural electrodes
in place. The diameter of subdural electrodes (4 mm) and the interelec-
trode distance (10 mm) were used for the measurement of coregistration
accuracy. For example, electrodes 6, 14, 22, and 30 are located on the
left superior temporal gyrus. Electrodes 15 and 23 are located on the left
frontal operculum. Estimated margin of error was approximately 3 mm.
In a recent systematic review and meta-analysis of 21 studies, including a total (>10 days), left-sided implantation, and elderly patients (62,64). Experience is
of 2,542 patients, by Arya and colleagues (46), the most common complica- also an important factor. For example, the Cleveland Clinic group reported a
tions were neurological infection (2.3%), skin/scalp infection (3.0%,), intracra- 33% rate for minor and major complications at the beginning of their epilepsy
nial hemorrhage (4.0%), and elevated intracranial pressure (2.4%). Five deaths program, which dropped to 19% in more recent years (64).
(0.2%) were reported as a direct consequence of the subdural EEG study due Given that subdural electrode placement can be associated with morbid-
to refractory elevated intracranial pressure (ICP). Other less-common adverse ity and mortality, careful presurgical planning and postimplant patient care
events included transient motor and language deficits, cerebrospinal fluid is necessary to minimize these. To prevent infection, it is useful to limit the
leakage, and pneumoencephaly. Electrode removal may be necessary to man- recording period to less than 10 to 14 days. Intraoperatively, the wires of
age these adverse events, which also results in the premature termination of the subdural electrodes should be tunneled subcutaneously and brought out at a
intracranial recording. Mild to moderate headache and nausea are also com- separate site, where tissues can be tightly sutured. This helps to prevent bac-
mon postimplantation, presumably secondary to increased ICP (67). Manage- teria from gaining access to the brain and meninges via the exiting wires. In
ment of this condition may require analgesics, fluid restriction, and sometimes addition, prophylactic use of perioperative antibiotics is a common practice
corticosteroids. In rare instances, subdural electrodes have also been pulled among epilepsy centers.
out by patients (66,68). The risk of complications commonly increases with Subdural hematomas are mainly caused by tearing cortical bridging
subdural electrode number (>100), longer duration of intracranial monitoring veins during the insertion of strip and grid electrodes. Such bleeding can be
reduced by assuring that coagulation parameters are appropriate prior to hemorrhage and cerebral edema. These neuroimaging studies are also used
surgery. Cerebral edema can also be a serious complication of invasive EEG to localize the implanted subdural electrodes, such as via 3D CT/MRI co-
recording. It may interfere with accurate epileptic focus and eloquent cortex registration (55). Although the choice of antibiotics and duration prophy-
localization. Moreover, cerebral edema that is refractory to intervention can laxis vary among different centers, antibiotics are commonly administered
provoke cerebral herniation and result in death. Administration of dexa- throughout the course of the intracranial study. Dexamethasone can be also
methasone following surgery and during intracranial monitoring can be use- used for patients with signs of increased ICP, such as significant headache
ful in reducing cerebral edema; however, it may also decrease the frequency and vomiting. Preoperative AEDs are commonly maintained during NICU
of habitual seizures and thus prolong the duration of intracranial monitor- care or at least until EEG monitoring is begun.
ing (69). Therefore, its use needs to be judiciously considered. In some cen- Patients are usually transferred from the NICU to the epilepsy monitoring
ters, dexamethasone is only administered during the first 72 postoperative unit (EMU) within 24 hours to begin EEG recording. AEDs are then typi-
hours in patients experiencing significant headache, nausea, or vomiting. cally weaned off gradually to facilitate the recording of habitual seizures. EEG
recordings are routinely performed 24-hours per day and 7 days per week
Clinical indications of subdural electrode until sufficient seizures are recorded. This usually necessitates a mean record-
EEG recording ing duration of 5 to 14 days. The presence of EEG technologists through-
out the course of intracranial EEG study is necessary to insure the technical
Currently, there are no universally recognized guidelines for when an intra- integrity and high quality of the EEG recording. Patient care is provided by
cranial EEG study is indicated. In practice, the following are common clini- a well-trained medical staff, who can provide a neurological evaluation to test
cal indications for invasive EEG studies (70,71): (a) lateralize ictal onset to a awareness, language, memory, and sensory-motor functions during and after
specific hemisphere, such as left versus right temporal epilepsy; (b) localize a seizure. It is also important to have continuous supervision to prevent the
ictal onset to a specific lobe, such as temporal versus frontal lobe epilepsy; patient from falling or pulling out intracranial electrodes during or after a
(c) localize seizure onset and determine the extent of seizure-onset zone seizure.
within a lobe, such as mesial versus neocortical or anterior versus poste-
rior TLE; and (d) functional cortical mapping, such as language mapping EEG Acquisition
in patients with dominant hemisphere TLE. The latter is particularly useful
when intraoperative functional mapping is not feasible. Methods for intracranial EEG recording are essentially identical to those
On the other hand, with the advent of modern neuroimaging studies, many used for scalp EEG. Data are routinely digitized at 200 to 250 Hz, which
epilepsy patients who have unilateral mesial temporal sclerosis or well-defined provides an accurate representation of common clinical EEG frequen-
structural lesions (i.e., glioma and cavernoma), which are concordant with cies, such as delta, theta, alpha, beta, and gamma. For these routine stud-
scalp interictal and ictal EEG localization, are usually eligible for direct surgery ies, band-pass filters are typically set at 0.3-Hz low-frequency filter and at
without the need for an intracranial EEG study (10). Also, subdural studies 70-Hz high-frequency filter. However, modern commercial amplifiers have
are not indicated in patients with evidence of multifocal or generalized seizure the ability to sample at much higher rates, ranging from 1,000 to 2,000 Hz.
onsets, since they are not considered good candidates for epilepsy surgery. This allows the faithful recording of high-frequency EEG patterns, such as
high-frequency oscillations (HFOs) (ripples and fast ripples) from 80 to 500
Postoperative care and EEG acquisition Hz. Obviously, to record these patterns, the high-frequency filter needs to set
much higher, such as at 500 Hz.
Postoperative Care The number of recording channels required is dependent on the num-
ber of implanted subdural electrodes. Although contemporary commer-
Subdural electrodes are implanted under general anesthesia in the operat- cial EEG equipment can simultaneously record 128 to 256 channels, many
ing room. Afterward, patients are commonly admitted to a neurointensive routine clinical intracranial EEG studies may only require 50 to 100 chan-
care unit (NICU) for a brief period of postoperative observation. A head nels. EEG channels are generally displayed in a logical montage according
CT and/or brain MRI are usually obtained to rule out acute intracranial to anatomic distribution (e.g., anterior to posterior, superior to inferior).
EEG data can be reviewed in either referential or bipolar montages. Each by intracranial EEG recordings (72). It is also reassuring to know that a
has advantages and disadvantages. given intracranial spike or seizure of interest produced the same scalp dis-
Referential montages display the absolute voltage perceived by an e lectrode charge that was recorded previously during long-term monitoring.
contact, either from a near-field or far-field generator, relative to that of the
reference. Because subdural electrodes are placed on the cortex, they record
exclusively from gray matter, and near-field signals from underlying cortex Intracranial EEG patterns
predominate. However, in referential recordings from depth electrodes in
white matter, there is no local EEG generator, so far-field signals predomi- Normal Intracranial Physiological EEG
nate. Referential recordings can be subject to a variety of external artifacts.
Therefore, it is important to choose a reference electrode that has minimal Normal physiological EEG frequencies and patterns commonly observed
signal, less likelihood of artifacts, and is less likely to be involved in seizure on the scalp EEG can be recorded with intracranial EEG. These include
activity. Either intracranial or extracranial electrodes can be used as the alpha and mu rhythms; vertex sharp waves, sleep spindles, lambda waves,
reference. Intracranial references are less influenced by external movement and positive occipital sharp transients of sleep (POSTs) (70), provided that
and muscle artifacts, but unless properly chosen, they may record a signifi- intracranial electrodes are placed on the pertinent cortical areas. However,
cant amount of epileptiform activity, thus potentially confusing the EEG there are also significant differences between scalp and cortical EEG record-
interpretation. Accordingly, intracranial contacts not touching the cortex ings (73–75). EEG potentials recorded from the cortex are higher in ampli-
and distant from likely epileptic sources are typically used for reference. The tude than those recorded on the scalp, and morphology of cortical EEG
amplitude of EEG signals recorded at the scalp is attenuated compared to potentials tends to be sharper or spikier. Some cortical EEG patterns such
that from the cortex, so a scalp electrode may be a good reference for intra- as high-frequency gamma rhythms simply cannot be recorded on the scalp
cranial EEG. For example, vertex scalp electrodes (such as CPz) are a good (76). While the difference between scalp and cortical EEG recording can,
choice for reference when evaluating TLE because they record little tem- for the most part, be accounted by signal attenuation due to the increased
poralis muscle artifact and are distant from temporal lobes. For opposite resistivity of the skull, the dynamic and variable interactions among cortical
reasons, earlobe electrodes A1 or A2 would not be recommended. source area, amplitude, and synchrony also influence whether or not certain
Bipolar montages with subdural electrodes display the difference in volt- intracranial EEG patterns are recordable on the scalp EEG (72).
age typically between adjacent electrodes on a strip or grid. Very focal, near-
field activity is accentuated, whereas broad near-field and far-field activity is Intracranial Interictal EEG
suppressed. Thus, little or no interictal or ictal potentials may be evident in a
channel composed of recordings from two highly, but similarly, active elec- Similar to scalp interictal epileptiform discharges (IEDs), intracranial IEDs
trodes. Bipolar montages may be more useful in depth electrode recordings can also be categorized as spikes, polyspikes, sharp waves, spike-and-wave
where there are few contacts in any given area of cortex, so in-phase cancel- discharges. Given that only patients with partial-onset epilepsy are con-
lation is minimized. This lack of signal on a bipolar depth electrode channel sidered for intracranial EEG studies, generalized IEDs are rarely recorded
may however be useful in identifying white matter because the far-field sig- or cannot be clearly characterized due to the limited intracranial EEG
nals from the distant cortex will be suppressed. Accordingly, it is important sampling. Cortical interictal spikes are commonly heterogeneous in their
to review intracranial EEG data with both referential and bipolar montages. source location, area, synchrony, and amplitude. Only a few of those corti-
ECG is typically recorded along with intracranial EEG. Other channels cal spikes with sufficient cortical area and synchrony are associated with
for oxygen monitoring or respiratory monitoring are recorded in some cen- scalp-recognizable potentials (Fig. 13.4). Cooper et al. (77) proposed in 1965
ters. A partial or full set of international 10 to 20 electrodes can be used to that 6 cm² of synchronized cortical activity was probably necessary for the
record scalp and intracranial EEG simultaneously. In our experience, there recording of a scalp EEG correlate. Their model, however, employed in vitro
is little increased risk of infection, and the overview of brain activity pro- measurements using a piece of fresh cadaver skull, a pulse generator con-
vided by scalp EEG can compensate for the “tunnel vision” often suffered nected to saline-soaked cotton balls placed on the inside of the skull, an
artificial dura made from a polyethylene sheet, and EEG recording elec- interictal recording likely provides a useful measure to predict the location
trodes on the exterior surface of the skull bone. The 6-cm² estimate of of seizure-onset zone. Indeed, using visual inspection or automated detec-
the necessary cortical sources was based on the area of multiple pin holes tion algorithms, several studies have suggested that the cortical areas associ-
punched into the polyethylene sheet when the artificial EEG signals were ated with maximal spiking frequency, highest amplitudes, and shortest spike
first recorded from the electrodes on the outside of the skull. duration often overlap with the seizure-onset zone. However, their relation-
Using simultaneous scalp and intracranial recording in epilepsy presurgi- ship to seizure-onset zone is not consistently strong. Asano and colleagues
cal candidates with TLE, cortical spikes with synchronized 6 cm² of source (81) found that electrodes with the maximal spike frequency identified the
area in the lateral temporal cortex did not produce recognizable scalp poten- seizure-onset zone in 100% (13 of 13) of patients, while Hufnagel and col-
tials (Fig. 13.5). Cortical spike sources having an area of 10 cm² or more leagues (82) found that maximal spike frequency of interictal spikes could
commonly resulted in scalp-recordable EEG spikes (Fig. 13.6). Further- identify the seizure-onset zone in only 53% (17 of 32) of patients. In another
more, prominent scalp interictal spikes were commonly associated with the study, electrodes with maximal spike frequency were found to be in seizure-
activation of 20 to 30 cm² of cortex, which is as extensive as 70% of temporal onset zone in 58% (11 of 19) of pediatric patients (83).
lobe gyral cortex (78) (Fig. 13.7). Therefore, cortical area of interictal spike Areas of spiking on subdural electrodes usually extend beyond the
generators is considerably larger than commonly thought. Synchronous or seizure-onset zone, and in some cases, they appear to originate from mul-
at least temporally overlapping activation of 10 to 20 cm² of gyral cortex is tiple independent spike generators (82,84). These independent spike gen-
commonly required to produce scalp-recognizable interictal spikes. erators may activate independently or synchronously to produce multifocal
Intracranial IEDs are far easier to record than seizures. The cortical distri- interictal spikes. For instance, in patients with mesial TLE, independent
bution of intracranial IEDs delineates the irritative zone (79,80). IEDs are spikes are commonly identified from mesial and anterior temporal, ipsi-
thought to be closely related to epileptogenesis and ictogenesis. Therefore, lateral orbitofrontal, and contralateral temporal cortex (Fig. 13.8). Several
Figure 13.4: Simultaneous intracranial and scalp EEG recording. A: Intra-

cranial EEG recording demonstrates a heterogeneous population of inter-
ictal spikes. B: Scalp EEG recording demonstrates that only two of the
intracranial spikes (labeled 1 and 2) generate recognizable scalp interic-
tal potentials. LOF, left orbital frontal; LAT, left anterior temporal; LIT, left
inferior temporal; LMT, left mid temporal.
Figure 13.5: Simultaneous intracranial (A) and scalp (B) EEG record-
ing of a left temporal spike (indicated by arrow). No scalp potential is
evident from this cortical source. Neither is there an organized scalp
voltage field associated with the intracranial spike (C). (D) illustrates the
subdural electrodes recording a synchronous negative depolarization
(black) during the spike. Note that the spike source area is approximately
6 cm². LOF, left orbital frontal; LFC, left fronto-central; LAT, left anterior
temporal; LIT, left inferior temporal; LMT, left midtemporal.
studies have showed that resections incorporating a “significant” portion of Interictal, rhythmic or arrhythmic, regional slowing is commonly
regions generating interictal spikes and sharp waves, in addition to the ictal- observed in patients with temporal and extratemporal lobe epilepsy dur-
onset zone, improved seizure freedom postoperatively (85–89). These studies ing intracranial EEG. Traditionally, regional EEG slowing was thought to
strongly suggested that interictal spikes are biomarkers of epileptogenesis. reflect an underlying structural abnormality of the brain (90–92). How-
Nevertheless, the role of intracranial interictal spikes in the localization of ever, interictal regional delta activity (IRDA) can be observed in epilepsy
seizure-onset zone has its intrinsic limitations. IEDs often provide an imper- patients without clear structural abnormalities on modern neuroimaging
fect representation of seizure-onset zone, and their interpretation needs to studies (93–95). Scalp EEG investigations have demonstrated that IRDA
be correlated with ictal recordings. Further studies are needed to determine has a similar lateralizing and localizing value as do interictal spikes in
if there is a predictable relationship between the region of IEDs, the seizure- patients with temporal epilepsy, and its presence is associated with a favor-
onset zone, and surgical outcomes. able surgical outcome (94,96). Simultaneous scalp and intracranial EEG
Figure 13.6: Simultaneous intracranial (A) and scalp (B) EEG recording
of a left temporal spike (indicated by arrow). Note the distinct associated
scalp potential and temporal scalp voltage field (C). The approximate
area of the cortical spike source is 13 cm². Active electrodes: black. LOF,
left orbital frontal; LFC, left fronto-central; LAT, left anterior temporal;
LIT, left inferior temporal; LMT, left midtemporal.
recordings demonstrated that cortical IRDA is typically a mixture of delta/ Intracranial Ictal EEG
theta slowing and cortical spike-slow wave potentials. In patients with
TLE, cortical IRDA is predominantly observed from basal and anterolat- Despite the important role of interictal spike analysis, recording seizures
eral temporal cortex. It is infrequently seen from mesial and posterolateral has always been the primary goal of an intracranial EEG study. Seizure
temporal cortex (Fig. 13.9). The cortical distribution of IRDA was shown onsets are typically categorized as focal or regional depending on the num-
to be highly correlated with the irritative zone and seizure-onset zone in ber of electrode contacts involved (14,98–102). However, what is “focal”
patients with neocortical TLE (97) (Fig. 13.10). These observations sug- versus “regional” has differed among investigations. In general, focal onset
gested that IRDA might be an intrinsic EEG pattern of the epileptic net- means only one to three electrode contacts involved, whereas regional onset
work. However, its value in localizing the epileptogenic zone remains to be means four or more active electrode contacts. One assumption is that the
clarified. fewer electrode contacts involved the more likely they are recording from
Figure 13.7: Simultaneous intracranial (A) and scalp (B) EEG recording
of a left temporal spike (indicated by arrow). Note the prominent associ-
ated scalp potential and temporal scalp voltage field (C). The approxi-
mate area of the cortical spike source is 25 to 30 cm². Active electrodes:
black. LOF, left orbital frontal; LAT, left anterior temporal; LIT, left inferior
temporal; LMT, left midtemporal.
Figure 13.8: Multifocal sources of intracranial interictal spikes in a

patient with left TLE: Interictal spikes are observed in the frontal, anterior
temporal, midtemporal, and posterior temporal cortices. Spike source
activity could be independent or synchronous. LOFS, left orbitofrontal
strip; LATS, left anterior temporal strip; LITS, left inferior temporal strip;
LMTG, left midtemporal grid; LPTS, left posterior temporal strip.
378
FIgure 13.9: Simultaneous scalp and intracranial EEG recording of interic-
tal temporal delta activity (ITDA). The scalp EEG shows rhythmic 3-Hz delta
slowing in the left anterior and inferior temporal regions from electrodes F9,
T9, F7, and T7. Intracranial EEG shows synchronous delta slowing, primar-
ily in anterior temporal and basal temporal regions. Lateral temporal and
posterior temporal regions are rarely involved. Heterogeneous intracranial
spikes are superimposed with delta slowing and are often not recordable at
the scalp. LMTG, left midtemporal grid; LATS, left anterior temporal strip;
LITS, left inferior temporal strip; LPTS: left posterior temporal strip; LPOS,
Left posterior occipital strip.
379
Figure 13.10: Intracranial EEG recording of cortical interictal temporal delta
activity (ITDA), interictal spikes, and seizure onset in a patient with left TLE. A
similar cortical distribution is observed for cortical ITDA, interictal spikes, (arrow)
and ictal-onset discharges, namely, anterior and basal temporal regions. LAT,
left anterior temporal; LMTG: left midtemporal grid.
380
the seizure-onset zone. On the contrary, multiple simultaneous electrode High-voltage, low-frequency seizure onsets are generally associated with
involvement may mean that they are recording propagated activity from a less-favorable surgical outcomes, compared to low-voltage, fast-frequency
“remote” seizure onset. In TLE, focal onset is commonly observed in mesial seizure onset. This may well be related to the fact that the etiologies of neo-
disease, whereas regional onset is more common in patients with neocortical cortical seizures, such as encephalitis, meningitis, or cortical dysplasias, pro-
epilepsy. Occasionally, focal and regional onsets are recorded independently duce more diffuse cortical damage and/or dysfunction. Other intracranial
in the same patient and within the same temporal lobe (Fig. 13.11). ictal-onset patterns, such as rhythmic sinusoidal pattern in theta and alpha
Intracranial EEG recording provides a unique window for better under- range (5 to 9 Hz) and periodic low-frequency 1- to 2-Hz spiking, have also
standing of seizure generation and propagation. Seizure-onset rhythms can been described (105,117). Focal or generalized electrodecremental patterns
be of nearly any EEG frequency band, including delta, theta, beta, alpha, can also be seen at seizure onset. They are commonly not considered to have
and gamma (103). The most common onset pattern is low-voltage beta and a localizing value in identifying the seizure-onset zone, and their physiologi-
gamma (15–40 Hz) activity (104–107). Such low-voltage fast activity is typical underpinnings are uncertain (118,119). Also, potentially confusing and
cal of both mesial temporal (Fig. 13.12) and extratemporal seizure onsets misinterpreted as seizure activity is intracranial EEG slowing at the time of
(76,99,108,109) (Fig. 13.13). It may or may not be preceded by changes of seizure onset, which can be seen distant from the focus. This slowing does
ongoing IEDs, such as an increment or a reduction in the spike frequency. not evolve into an ictal pattern over time, but rather subsides. Ipsilateral
Experimental findings in animal models of TLE suggest that low-voltage frontal lobe slowing is not uncommon with temporal lobe seizures (120)
fast activity observed at seizure onset is associated with the reinforcement (Fig. 13.15).
and synchronization of GABAergic inhibitory networks (107,110). This The character of cortical seizure propagation determines seizure semiol-
concept challenges the traditional theory that an increase in excitation and/ ogy and scalp EEG ictal patterns. Accordingly, the latter can provide use-
or a decrease in inhibition mark the transition to seizures in focal epilepsies. ful insight into seizure lateralization and localization. Seizures propagate
From a practical perspective, low-voltage fast activity at seizure onset has locally by gradually recruiting the cortex surrounding the onset zone. In
excellent localizing value (102,111,112). Moreover, the removal of the corti- temporal lobe seizures of mesial origin, focal, low-voltage, fast activity at
cal region that generates such activity is associated with favorable surgical seizure onset commonly slows to the alpha/theta range and propagates into
outcomes (106,113). basal, anterior, and lateral temporal cortex, and eventually into the extra-
High-voltage, low-frequency, delta and theta (1–5 Hz) rhythms are another temporal cortex (Fig. 13.15). Usually, sufficient source area and synchrony
common intracranial seizure-onset pattern (Fig. 13.14). Such low-frequency are achieved in the course of propagation to result in a recognizable scalp
ictal onsets are most common in neocortical TLE, although they can some- EEG rhythm. Scalp ictal onset is typically delayed by up to tens of seconds
times be observed in extratemporal epilepsy. This seizure-onset pattern often from the time of intracranial EEG seizure onset (14,121,122). Thus, scalp
appears as a short run of rhythmic, semi-rhythmic, or periodic spikes, sharp EEG patterns often reflect seizure propagation. By means of subcortical
waves, or spike waves. High-voltage, low-frequency seizure onsets are com- white matter tracks, seizures can spread to distant cortical areas or even
monly “regional.” In patients with TLE, this ictal-onset zone can be as large the opposite hemisphere without recognizable local cortical recruitment.
as 20 to 30 cm². Furthermore, these seizure patterns are recognizable on scalp This may result in poorly localized or even falsely lateralized scalp EEG
EEG from their very onset, unlike low-voltage fast patterns that typically take ictal rhythms (Fig. 13.16). Rarely, focal seizures can propagate explosively
cortical recruitment and a slowing of frequency to be evident (114). Although through both hemispheres, producing scalp EEG ictal onsets that cannot be
regional, and thus possibly reflecting seizure propagation from a distant source localized or lateralized (Fig. 13.17).
(115), several studies have suggested that the high-voltage, slow-frequency Controversy continues regarding the quantity and quality of intracranial
pattern does identify the onset zone of neocortical seizures (14,108,116). In EEG data that are needed to recommend surgical resection. No consensus
any given patient, electro-clinical correlation may provide some insights for exists as to how many seizures should be recorded. In patients with uni-
distinguishing these two possibilities. Commonly, EEG seizure onset tends focal interictal spikes and seizures on scalp EEG, recording three similar
to precede behavioral onset when intracranial electrodes record directly from seizures of similar onset may be sufficient for recommending a localized
the seizure-onset zone, whereas the opposite is true for propagated seizures. resection. However, in patients with multifocal interictal spikes, recording of
Figure 13.11: Focal and regional seizure onsets are seen in the same
patient with left TLE. Top: Focal, low-voltage, fast-frequency seizure
onset from left mesial temporal electrodes, LMTG 9, 17, 25. Bottom:
High-voltage, low-frequency, regional neocortical temporal seizure
onset. LMTG, left midtemporal grid; LATS, left anterior temporal
strip; LITS, left inferior temporal strip; LPTS, left posterior temporal
strip.
382
Figure 13.12: Subdural electrode recording of a left mesial temporal
seizure. Focal, low-voltage, fast beta and gamma frequency ictal-onset
rhythms are noted only from the antero-mesial temporal electrodes
(LATS1 and LITS1). The ictal discharge then propagates along mesial,
basal, lateral temporal and extratemporal pathways. Seizures were mani-
fested clinically by ipsilateral motor automatisms and contralateral dys-
tonic limb posturing.
Figure 13.13: Subdural electrode recording of a left parietal seizure.

Early involvement of electrodes LPTG 36, 42, 52 is noted in this focal,
low-voltage, fast beta frequency seizure onset. LPTG, left parietal tem-
poral grid.
383
Figure 13.14: Simultaneous intracranial (left) and scalp (right) EEG

recording of a left temporal lobe seizure. The ictal-onset zone is neocor-
tical (approximately 20 cm² in area), involving most of the inferolateral
and lateral temporal electrodes. Given that the cortical ictal discharges
are widespread and synchronous at onset, a 2-Hz left anterior inferior
temporal ictal rhythm appears simultaneously on the scalp (marked by
arrow). LMTG, left midtemporal grid; LATS, left anterior temporal strip;
LITS, left inferior temporal strip; LPTS.
a minimum of five seizures may be necessary in order to exclude multifocal (80 to 250 Hz) and fast ripples (250 to 500 Hz) have been recorded from
seizure onsets (71). In practice, however, intracranial recording cannot be microelectrodes and commercially available intracranial macroelectrodes
continued indefinitely due to increased patient morbidity, when monitoring (subdural and depth) in patients with intractable focal epilepsy (124–126)
is extended from days to weeks. (Fig. 13.18). HFOs in the range of 80 to 250 Hz (ripples) can be recorded in
Theoretically, complete removal of the epileptogenic zone, the brain region normal hippocampus and parahippocampus in both animals and humans
necessary and sufficient to generate seizures, is necessary to achieve long- (126). They are believed to reflect inhibitory field potentials, which facili-
term, complete seizure freedom (123). Unfortunately, there is no reliable bio- tate information transfer by synchronizing neuronal activity over longer
marker to define the extent of the epileptogenic zone at the present time. In distances. However, HFOs in the range of 250 to 500 Hz (fast ripples) seem
practice, the seizure-onset zone is commonly used as a surrogate indicator. to be linked to epileptogenesis. They have been found in the seizure-onset
However, the relationships between seizure-onset zone, epileptogenic zone, zone from human ictal and interictal recordings (127). HFOs commonly
and irritative zone remain poorly defined. Therefore, cortex of the seizure- occur with interictal spikes, but they are also found independently. It has
onset zone, which is involved in early seizure propagation, and adjacent tis- been shown that HFOs have a tighter spatial correlation with seizure-onset
sue with active interictal spiking are often targeted for surgical resection. zone than do interictal spikes. Accordingly, HFOs may be of greater value
in localizing the seizure-onset zone (128). In fact, a significant correlation
High-frequency Oscillations was found between the removal of cortex under electrode contacts with
high rates of HFOs and good surgical outcomes (129,130). These obser-
Recently, HFOs are being considered as a potential biomarker of the vations suggest that HFOs are a promising biomarker of epileptogenesis.
epileptogenic network. With the advent of powerful modern amplifiers Whether they prove to be clinically reliable in the localization of seizure
that can sample at a rate of 2,000 Hz or more, HFOs known as ripples focus remains to be seen.
Figure 13.15: Simultaneous intracranial (top) and scalp (bottom) EEG
recording of a left temporal lobe seizure. The cortical ictal-onset zone is
approximately 2 cm² in area and involves only the most mesial electrodes
(LATS1, LATS2). Ictal activity propagates gradually over the basal to infero-
lateral temporal cortex. When sufficient cortex is recruited into synchronous
involvement, a similar 8-Hz left anterior inferior temporal ictal pattern is seen
on scalp EEG (marked by arrow). Latency between intracranial and scalp ictal
onsets is 15 seconds. The rhythmic 4.5-Hz frontal burst noted earlier on scalp
EEG is a distant effect of the temporal lobe seizure onset. LFCS, left frontal
central strip; LATS, left anterior temporal strip; LITS, left inferior temporal
strip; LMTG, left midtemporal grid.
385
Figure 13.16: Simultaneous scalp (top) and intracranial (bottom) EEG recording
of a right temporal lobe seizure. Scalp EEG ictal rhythms are a confusing mixture
of bitemporal activity. The intracranial ictal-onset zone involves only the right
mesiobasal temporal electrodes, and the seizure remains focal for approximately
11 seconds. Ictal activity then propagates to both the contralateral and ipsilat-
eral temporal neocortex. Seizures were manifested clinically as mixed bimanual
motor automatisms and dystonic posturing.
386
Figure 13.17: Simultaneous scalp (top) and intracranial (bottom) EEG
recording of a left temporal lobe seizure. Scalp EEG ictal (as indicated
by arrow) was poorly localized and lateralized. Intracranial ictal-onset
zone involves only the mesial temporal electrodes (LMTG1, LMTG9,
and LMTG17). The ictal discharge remains focal for approximately 13
seconds and then abruptly spreads to the left lateral and posterior tem-
poral, left frontal and left parietal cortices. Seizures were manifested
clinically by hypermotor activity.
387
Figure 13.18: High-frequency oscillations (HFOs, 100 to 300 Hz) recorded

from mesial (electrodes LATS1, 2 and LITS1, 2) and basal (electrodes
LMTG12, 9, 10, 17, 18, 25, 26) temporal cortex with commercial subdural
electrodes in a patient with left TLE. The intracranial EEG was recorded at
a sampling rate of 2,000 Hz. HFOs were revealed with input filters of 100
to 500 Hz, a 60 mm per second timescale, and a sensitivity of 10 µV per
mm. LOFS, left orbitofrontal strip; LATS, left anterior temporal strip; LITS,
left inferior temporal strip; LMTG, left midtemporal grid.
Electrical stimulation and functional are difficult to achieve. Patients may have difficulties of staying awake or
localization can be easily fatigued, which will compromise the validity of testing. The
duration of testing and the modalities of stimulation are also limited. By
When placed in large geometrical arrays, subdural electrodes are well-suited comparison, electrical stimulation with chronically implanted subdural
for functional mapping of cortex. Electrical stimulation has been a reliable electrodes allows an extensive period of testing with more comprehensive
technique for functional localization over the last several decades (37,131). protocols. A high level of patient cooperation can be maintained through-
It can be performed intraoperatively under local anesthesia or by means out the course of testing over periods of hours or even multiple sessions
of chronically implanted subdural electrodes (132–134). While more con- over several days.
venient, intraoperative electrical stimulation is subject to significant limi- Electrical stimulation for functional localization is commonly per-
tations. It often requires a high level of patient’s cooperation, which may formed after sufficient habitual seizures have been recorded for localiz-
not be possible in certain patient populations, such as children or devel- ing the seizure focus. Because electrical stimulation of the cortex can also
opmentally delayed patients. Appropriate levels of sustained anesthesia provoke seizures, AEDs should be resumed prior to mapping. A short
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Williams & Wilkins, 2007.
Intracerebral Depth Electrode
14 Electroencephalography
(Stereoencephalography)
PHILIPPE KAHANE • FRANÇOIS DUBEAU
Introduction Indications for SEEG in Extratemporal Lobe Epilepsy

Historical Perspective Indications for SEEG in Lesional and Nonlesional
Technical Considerations Focal Epilepsies
Intracranial Electrodes: Overview When Intracerebral EEG Is Not Indicated
Intracerebral Electrodes: Characteristics, Insertion, Intracerebral EEG Monitoring: Interpretation
Placement, and Location of EEG Data
Advantages and Drawbacks of Intracerebral Normal Physiological EEG Activity
Depth Electrodes Artifacts
Risks and Complications Abnormal Interictal EEG Activity
Recording Procedure Seizures Onset (Seizure-Onset Zone) and Propagation
Technical Aspects Electrical Stimulation
Practical Aspects SEEG-Guided Radiofrequency Thermocoagulation
Indications of Intracerebral Depth Electrode Conclusion
EEG Recording Acknowledgments
Indications for SEEG in Temporal Lobe Epilepsy References
Introduction 1990s and during the onset of the 2000s, the overall proportion of patients
evaluated by invasive recordings was probably decreasing. It is our impres-
In spite of the increasing use of noninvasive and nonelectrophysiological sion, however, that over the more recent years, invasive EEG techniques have
tests in the presurgical evaluation of patients with refractory epilepsies (1), gained interest and are more widely and frequently used across c enters and
invasive EEG methods remain necessary in a number of patients. In the countries; notably, a number of cases that were not considered for epilepsy
393
394 Intracerebral Depth Electrode Electroencephalography (Stereoencephalography)
surgery in the past can nowadays benefit from such investigations (e.g., information, intracranial EEG helps in the planning of epilepsy surgery
MRI-negative cases). This apparently paradoxical trend is explained by the (localization and completeness of resection). Invasive EEG can be indi-
perception that invasive EEG methods are still considered the gold standard cated to determine the relationship existing between lesions and seizure
and the only approach that can provide direct and reliable indication of the generator; this relationship may vary with different types of developmental
epileptic generator. Invasive EEG is perceived as being able to provide spe- or acquired lesions (5–8). Intracranial studies can help in prognosis: for
cific or accurate localization of the epileptic generator and hence good sur- instance, in case of bilateral temporal lobe epilepsy (TLE), to determine
gical results with relatively small resections. Moreover, the techniques now if a predominance or laterality of epileptogenesis exists (9). Finally, given
appear safer, and the morbidity is acceptable. Intracranial EEG remains, the privileged access to human brain structures invasive EEG provides, the
however, an invasive procedure, is expensive and time-consuming, necessi- methods are often used to study and understand the mechanisms underly-
tating considerable human and technical resources, and therefore requires ing normal and abnormal neurophysiology, to measure evoked potentials,
proper justifications. Also, as we will see later, the use of invasive EEG often or to study neuronal or field potentials, in passive conditions or during
indicates by itself a poor surgical outcome. experimental paradigms (10,11).
The first motivation to use invasive EEG in patients with difficult-to-
treat focal epilepsies is the added value of invasive monitoring to precisely Historical Perspective
localize the seizure generator and to tailor surgical resections (2) (Table
14.1). Invasive EEG also permits to define seizure propagation and the Brain electrical activity was initially measured by direct intracranial re-
understanding of the neuronal networks involved during epileptic attacks; cording, and Caton, in 1875 (12), was probably the first to demonstrate the
in some centers, larger resections are performed to include not only the existence of brain electricity by inserting electrodes, through burr holes
area of seizure generation but also the area(s) containing the first or early (openings in the skull), in the gray matter of monkeys. Hans Berger in
propagation of the epileptic discharges (for a review of the “Epileptogenic 1929 (13), for the first time in a human, detected brain electrical potentials
Zone,” see Lüders and Kahane [3]). During acute or chronic invasive EEG, through a cranial bone defect and proposed the term “electroencephalog-
cortical electrical stimulation can be used to monitor cortical function (e.g., raphy” to describe the method of recording this brain electrical activity.
functional mapping for speech, motor, or sensory activities), to define the In 1935, Foerster and Altenburger (14) made the first direct recording of
cortical areas responsible for the ictal symptoms, the electrical stimulation epileptic activity during a craniotomy; the electrocorticography (ECoG)
mimicking the effects of a spontaneous epileptic discharges (4), or to de- was born and the method rapidly expanded due to the work of Gibbs
termine low-threshold area(s). By defining the seizure generator and the et al. (15) in Boston (1937), Penfield and Jasper (16) in Montreal (1954),
propagation pathways of the ictal discharge and by providing functional and Ajmone Marsan and Baldwin (17) in Bethesda (1958). This record-
ing method became extensively and widely used to detect abnormal brain
potentials and define the epileptic focus, and to determine the extension
TABLE 14.1 Indications for Invasive Electroencephalography
of the surgical resection in patients with refractory epilepsies. The ECoG
technique, usually performed under local anesthesia, also allowed de-
1. To define seizure generator and tailor surgical resection:
• The added value of invasive monitoring to precisely localize the termining the functional anatomy of the human brain and, particularly,
seizure generator. the mapping of the speech and sensorimotor areas, leading to the famous
• Definition of seizure propagation. homunculus (16).
• Electrical stimulation evoked clinical responses mimicking the effect Human intracerebral recordings in epileptic patients were introduced
of spontaneous epileptic discharges on cortex. in the late 1940s and used to study the pathophysiology of “grand mal”
• Comparison of afterdischarge thresholds. and “petit mal” epileptic seizures; electrodes were implanted in various
2. Mapping of cortical function. subcortical areas thought to be involved in the generation of these seizure
3. Relationship existing between lesion and seizure focus. types (18–23). Following these pioneered studies, clinicians began to use
4. For prognosis. chronically implanted “depth” electrodes in patients suffering from focal
Intracerebral Depth Electrode Electroencephalography (Stereoencephalography) 395
seizures in order to address the shortcomings of ECoG (24–31): ECoG observe and study seizure semiology with both scalp and intracranial EEG
allowed direct brain recording but required an a priori definition of the methods (47–49).
origin of seizures, influencing therefore the type of surgical approach and In parallel, the ECoG methodology evolved with the development of elec-
of the explored cortical regions. It appeared then that chronic intracere- trodes embedded in strips or grids that could be placed subdurally (or less
bral neurophysiological studies of the brain using “depth” electrodes would often epidurally) in chronic conditions, allowing seizure recording and elec-
permit a better access to any cortical and subcortical areas involved in the trical stimulation studies over large portions of the cortical surface (50,51).
epileptic process, and for a longer period of time. In these pioneering depth These recording methods are also now widely used and constitute, together
EEG recordings, electrodes were not inserted by stereotactic implantation with SEEG, the main approaches to directly record normal and abnormal
methods, and therefore could not precisely target the anatomical struc- brain activities in the epileptic patients.
tures. Also, neurophysiologists, as with ECoG, were looking mainly at the
interictal spikes. Technical considerations
The introduction by Bancaud and Talairach of atlases providing
spatial coordinates of the telencephalic structures and the develop- Intracranial Electrodes: Overview
ment of neurosurgical techniques that allowed to target and reach such
coordinates (32,33) permitted more accurate and safer (because they in- Different types of electrodes can be used to record the intracranial EEG
cluded the visualization of blood vessels) placement of the electrodes. activity, for example, intracerebral depth electrodes, subdural grids or strips,
They also demonstrated the importance of using electroclinical infor- and epidural electrodes (Table 14.2). Sphenoidal and foramen ovale elec-
mation obtained during spontaneous seizures (5,34–38); this approach, trodes are usually considered as semi-invasive and will not be discussed here.
referred to as “anatomo-electroclinical correlations,” was based on the Usually, clinicians develop an expertise with a method, become famil-
assumption that the chronological occurrence of ictal clinical signs re- iar with it, and use preferentially or only one type of approach. The in-
flects the spatiotemporal organization of the epileptic discharge within tracranial method is also selected depending on the question posed by a
the brain. By combining anatomo-electroclinical correlations together given epilepsy problem; an approach using intracerebral depth electrodes is
with the stereotactic placement of intracerebral electrodes, Bancaud and favored if the epileptic generator is thought to be located deep in the brain,
Talairach elaborated a comprehensive methodology, the stereo-electro- while cortical grids or strips are considered if the generator is thought to
encephalography, or SEEG, that allowed studying, in each individual, the be over the brain convexity, basal cortex, or the interhemispheric cortex.
origin and spread of ictal discharges. The implantation strategy was thus Combinations of electrode types, for example, grids and intracerebral elec-
“custom-tailored” and consisted in the simultaneous investigation, in all trodes, or subdural strips and intracerebral electrodes, or hybrid electrodes,
planes of the intracranial space, of brain structures that might give rise which contain both a depth and a strip (opercular) component, or epidural
to ictal clinical signs. electrodes and intracerebral electrodes, or scalp electrodes and intracerebral
Other intracerebral depth electrode EEG procedures and strategies were electrodes may be used to maximize the yield of the intracranial EEG study
developed (39–45) with the primary aim to demonstrate, for instance, the (52–55). There are very few studies that have addressed the value of each
side of seizure onset in TLE or to differentiate frontal lobe seizures from intracranial method in specific epilepsy problems (56–60); each technique
temporal lobe seizures. Intracerebral targets and electrode trajectories were has advantages and drawbacks, and selection of one method must consider
in such cases standardized to avoid biasing the exploration strategy in f avor the clinical hypothesis to be addressed, the technical limitations of each
of one’s preferred localizing hypothesis (46). The underlying concept of method, and the risk of morbidity or mortality. In our opinion, the choice
these depth electrode EEG recordings was different from the SEEG method of intracranial study should be determined by the expertise developed in a
of Bancaud and Talairach, but allowed to perform standardized surgical center (familiarity with a given method) and, more importantly, by a strict
resections, such as anterior temporal resections. The introduction of pro- adhesion to a clinical process primarily based on a careful evaluation and
longed video–EEG monitoring with computer-assisted detection of inter- correlation of seizure semiology, scalp EEG patterns, and location of a
ictal and ictal epileptiform discharges considerably increased our ability to lesion, when present.
TABLE 14.2 Intracranial Electrode Characteristics
Type Recording areas Advantages Disadvantages

Intracerebral depth electrodes Deep limbic and paralimbic buried Good sampling of deep structures; Limited sampling (especially of
(within cortex) structures: amygdala, hippocampus, findings can be standardized neocortical structures); not adapted
entorhinal cortex and parahippocam- in a common stereotatic space for exhaustive cortical functional
pus, insula; interhemispheric cortical allowing intersubject comparisons; mapping
structures; depth of the sulci; hypo- well-tolerated procedure and low
thalamus, thalamus, and basal ganglia; morbidity
deep-seated and periventricular
lesions
Grids (subdural surface) Cortical convexity, basal and interhemi- Large number of recording channels Large craniotomy; higher morbidity;
spheric neocortical (gyral) surface and broad coverage of neocortical no sampling from deep buried
areas; well-suited for mapping of cor- structures; needs to be immediately
tical function by electrical stimulation followed by resective surgery
Strips (subdural surface) Cortical convexity, basal and interhemi- Good coverage of neocortical areas; No sampling from deep buried
spheric neocortical surface low morbidity structures
Epidural electrodes Cortical convexity Easy to install with low morbidity and No sampling of basal and deep
(pial surface) satisfactory coverage of neocortical structures; no electrical stimulation
convexity
Intracerebral Electrodes: Characteristics, commercial electrodes usually have contacts of 3 to 5 mm2). Electrodes
Insertion, Placement, and Location contain between 5 and 18 contacts, 2 mm in length, 0.8 to 1.1 mm in di-
ameter, a surface of 0.8 to 5 mm2, and 1.5 to 5 mm apart. Electrodes can
Characteristics be customized according to the needs of the neurosurgeon and neurophysi-
Intracerebral depth electrodes are made as flexible, semi-rigid or rigid ologist, and now may contain, in addition to normal-size clinical contacts
wires or catheters that penetrate the brain tissue. They can be homemade (macrocontacts), microcontacts placed either at the tip of the electrode or
(Fig. 14.1A) or commercial (more likely now) (Fig. 14.1B) multicontact elec- interspaced between the macrocontacts (Ad-Tech Medical Instrument Cor-
trodes in different metals, including stainless steel, gold–chromium alloy, poration, Racine, Wisconsin) (Fig. 14.1C). Microcontacts (<0.3 mm2) are at
nickel–chromium composite, or platinum–iridium composite. Electrodes this time used for research purposes and measure multineuronal unit activ-
made of nickel–chromium composite are favored because they are nonmag- ity and local field potential oscillations, and cannot (because of their small
netic and compatible with magnetic resonance imaging (MRI). Silver and diameter and surface size) be used for neurostimulation (this aspect will be
copper electrodes are not used because of their toxic effects (53,61). Each discussed later). Contact impedances are measured between each electrode
electrode contains several contacts placed at regular intervals (usually 2 to contact and the reference, and are normally found to be in the range of 1
5 mm, sometimes 10 mm, apart) along the wire. Each contact lies within the to 10 kΩ for typical clinical macrocontacts (0.8 to 5 mm2), numbers that
brain substance either in the gray or in white matter (surface varies accord- have been measured quite systematically at the MNI, in both homemade
ing to the type of electrode: the homemade Montreal Neurological Institute stainless steel electrodes and commercial platinum–iridium (Dixi Médical,
[MNI] electrodes, for instance, have contacts of 0.8 and 0.85 mm2, while Besançon, France) electrodes. As for scalp EEG electrodes, we measure the
A B and connected by two EEG technologists in the recovery room immediately

after their insertion; one technician connects and the other verifies. Once the
connection is adequately completed, an EEG recording that includes all the
2 mm electrodes is done, first for the verification of the electrodes and contacts and
second for the choice of the recording electrodes and recording montages.
MNI electrode Typically, recordings are performed with 64- or 128-channel EEG machines.
0.8 mm
1.5 mm Insertion and Removal
Intracerebral depth electrodes are inserted under general anesthesia and the
procedure usually lasts several hours. They are inserted through a burr hole
C
and placed either with a stereotactic frame or with a frameless stereotactic
technique; since 1995, the frameless technique is used routinely at the MNI
(for a review, see Olivier and Boling [63], and Olivier et al. [64]). Depending
on the centers, neurosurgeons shave the head completely, others don’t but
they avoid selecting entry points outside the scalp in order to avoid any un-
sightly scar. Neurosurgeons usually prefer flexible or semi-rigid rather than
rigid electrodes, the former considered safer than the rigid ones (53). Flex-
ible electrodes are inserted with a semi-rigid introducer placed in the hollow
Figure 14.1: Types of intracerebral depth electrodes. A: Intracerebral MNI and
commercial multicontact electrodes. The MNI electrode is made of stainless steel core of a cannula-type electrode or alongside a wire. The flexible electrodes
and contained nine macrocontacts (arrows) 5 mm apart and two microcontacts can deviate through natural tissue planes around structures such as arteries,
(arrowheads). The MNI electrode is used since 1972; B: commercial intracere- which may lead to less precise placement but a reduced risk of hemorrhage.
bral electrode (DIXI Médical, Besançon, France); C: commercial hybrid intrace- When the electrode is in place, the introducer is removed (removal of the
rebral electrode combining macro- (1 to 6) and microcontacts (7 to 21) (Ad-Tech introducer may sometimes displace the electrode). When in place, flexible
Medical Instruments Corporation, Racine, Wisconsin). electrodes are less likely to damage the brain tissue even during a blow to the
head (electrodes move with the brain), whereas the brain is more likely to
move with respect to rigid electrodes and hence to cause injuries. Electrodes
impedance of each electrode contact by injecting a weak alternating current are removed under either general or local anesthesia at the operating room
of constant intensity (10 µA, 30 Hz) through a pair of electrodes, which (flexible electrodes can be removed at the bedside with little discomfort). In
includes the contact to be tested and a reference electrode (usually, the refer- our experience, a few patients have inadvertently pulled out—for instance,
ence consists of an epidural peg placed in the bone and over the most distant during ictal or postictal conditions—one or a few electrodes themselves
parietal area from the suspected epileptogenic zone. If the impedances are without harm or brain damage.
found to be diffusely high, the electrode contacts are paired with another
reference, presumably of acceptable impedance, and a current is injected Placement
again). Impedances tend to increase over time, and we found that they may Anatomical targets are usually assessed using a preoperative stereotactic
double at the end of the investigation compared to the beginning. This may MRI scan. Implantation of the electrodes is performed under the same
be of some importance during stimulation (risks of tissue damage related stereotactic conditions, using a lateral orthogonal trajectory or an oblique
to charges accumulation and dispersion [62]). An insulated wire runs from route (64). A specificity of some stereotactic procedures consists in using a
each contact to the end of the electrode, where it inserts into a connector computer-driven robot (64,65), with no mechanical limits concerning the
that can be plugged into a cable connected to the amplifiers of the EEG trajectory chosen. This is of particular interest when a nonorthogonal im-
recording machine. At the MNI, the intracerebral electrodes are identified plantation is decided because of anatomical constraints (e.g., presence of
vessels) or to reach targets such as the parasagittal frontal structures (SMA), Advantages and Drawbacks
the gyrus rectus, the orbitofrontal cortex, the insula, or a hypothalamic ham- of Intracerebral Depth Electrodes
artoma. For the evaluation of TLE, depth electrodes are usually inserted via
a lateral and orthogonal approach through the second temporal gyrus (a Intracerebral electrodes penetrate brain tissue directly; they are of a small di-
relatively avascular route) to reach the mesolimbic structures (at least two to ameter and include a number of leads at a variety of distances between each
six electrodes are needed to obtain a good sampling of these structures). In of them (see earlier). Depending on the regions to be studied, electrodes con-
some centers, electrodes are inserted posteriorly through the occipital lobe tain more or less leads. Such multilead electrodes provide an accurate cover-
and placed in the longitudinal axis of the hippocampus (45). This method age of all the brain structures that each electrode crosses along its trajectory,
has the advantage of placing several recording contacts in the mesial tem- from its site of penetration to its final impact point. Such an approach thus
poral structures with one depth electrode, but the disadvantage of ignoring provides a 3D assessment of the epileptogenic network throughout the ictal
the overlying neocortex. This disadvantage can be alleviated by combining discharge, from onset to full propagation, and may allow defining the rela-
intrahippocampal depth electrodes and neocortical strip electrodes placed tionships between the epileptic generator and a lesion, when present.
through burr holes. Compared to scalp EEG recordings, intracerebral electrodes and leads lie
closer to the cortex and hence are more likely to detect small interictal or ictal
Location epileptic generators (generating a weak signal or too far from the surface)
The spatial accuracy of intracerebral recordings depends on how precisely and, moreover, with a lesser possibility for artifacts, especially those generated
the localization of the electrodes is determined; the location of the electrode by muscle activity. With scalp electrodes, low-voltage fast frequencies (beta,
contacts can be reported onto a stereotactic scheme for each patient and de- gamma, and fast components of interictal and ictal activities) can be more eas-
fined by their coordinates in relation to the anterior commissure–posterior ily missed compared to higher-voltage slow frequencies in the delta and theta
commissure plane (Fig. 14.2A) (66). This method has the advantage of ranges. This is explained by the size of the cortical generator and its distance
standardizing each case into the same three-dimensional (3D) environment, from the scalp leads rather than by a “filtering effect of the skull and scalp tis-
allowing intersubject comparisons. MRI obtained after implantation of sue” as previously suggested (67). Recently, Cosandier-Rimélé and colleagues
electrodes (post-insertion MRI) (Fig. 14.2B) or computer-assisted matching (68) have shown, using a model-based approach, that rapid discharges (25 to
of a postimplantation computed tomography (CT) scan (also post-insertion 80 Hz)—a characteristic EEG pattern recorded at ictal onset—were clearly
CT) with a preimplantation 3D MRI (Fig. 14.2C) provides a direct visual- present in depth EEG signals but almost not visible in scalp EEG signals, a
ization of the electrode contacts with respect to the brain anatomy in each limit mainly explained by the surrounding background activity (low signal-
patient. Electrodes and contacts localization can also be determined by to-noise ratio). Conversely, compared to scalp electrodes, only a small por-
using post electrodes removal brain MRI (Fig. 14.2D), a method however tion of brain tissue can be sampled with intracerebral electrodes and contacts,
likely to be less accurate than preimplantation scans. therefore making this method potentially “blind” if the electrodes are placed in
In any case, hypotheses concerning the site(s) of seizure onset and the wrong or silent areas, or in insufficient numbers. Contrary to scalp electrodes,
pathways of preferential ictal spread determine the brain areas where in- however, the intracerebral electrodes can be in direct contact or very close to
tracerebral electrodes should be implanted. They are formed from a careful the cortical generators and hence can see them with very large potentials, even
analysis of all the data (seizure semiology, scalp EEG, functional and ana- with a very small generator (Fig. 14.3A). The ability of an intracerebral lead
tomical imaging) collected during the noninvasive presurgical investigations. to detect a generator depends on the size of the electrical field generated and
The placement and number of electrodes are designed according to these on the distance between this lead and the generator. Also, in keeping with the
hypotheses. If the preimplantation hypothesis is wrong, the placement of “solid angle” theory, intracerebral electrode leads can miss a generator even
intracerebral electrodes will likely be inadequate and the interpretation of close if the cortical region subtends a too small solid angle vis-à-vis the re-
EEG findings will reflect this misunderstanding: the interpretation of the cording lead (Fig. 14.3B). Finally, selected targeted areas for recording should
EEG findings can be erroneous, or the area responsible for the generation be explored with as large as possible number of closely spaced electrode con-
of seizures is not identified and only propagated discharges are recorded. tacts. We strongly recommend to read these two fundamental articles from
A B
1 2
VCP
VCA
CA-CP
Figure 14.2: Examples of localization methods R

3 4
of depth electrodes. A: stereotactic scheme of
a right temporo-perisylvian SEEG study. Lateral
and frontal views in relation to the anterior com-
missure (CA)—posterior commissure (CP) plane.
VCA, VCP: vertical planes passing through the
anterior and posterior commissures. Letters re-
fer to intracerebral electrodes, of which most are
implanted using a lateral orthogonal trajectory.
Note that the electrodes X and Y are implanted
using an oblique trajectory to reach the insular
C D
cortex. B: Post-insertion MRI. Images obtained
from four different patients showing electrode
positions in coronal (pt. 1), sagittal (pts. 2 and
3), and axial (pt. 4) views. C: Computer-assisted
A B C
matching of a postimplantation CT scan with
a preimplantation 3D MRI, showing how the
wise placement of an electrode investigates
the left pre-SMA region (A), the depth of the
F1–F2 sulcus (B), and the dorsal premotor cor-
tex (C), simultaneously.; D: Two MRI sequences
from the same patient. Left panel: axial T2
showing two temporal electrodes still in place
and one electrode trajectory (arrow) just after
the removal of this electrode. Right panel: Axial A B C
T1 performed months after electrodes removal,
showing electrode trajectory (arrow) in the right R R
orbitofrontal region.
Figure 14.3: Solid angle, field size, and volume of generator. A: In comparison
with an intracerebral depth electrode contact, in a scalp recording, a cortical gen-
erator must be several times larger to have a solid angle of the same size and
thus produce a potential of the same amplitude. B: Example of a generator in
the fundus of the sylvian fissure. Contact 4 is near the fundus of the fissure; it sees
the generator lying in the fundus with a large solid angle (−250°), which results
in a high-amplitude potential recorded at this contact. In contrast, the potentials
measure at other contacts (e.g., 3 and 5), even if they are also very close, are
small because the generator is seen both from the positive and negative sides
(the subtraction of these angles approaching zero). If contact 4 is moved by a few
millimeters away (for instance, downward and outside the fundus), the potential
for the same reason will nearly disappear. (Adapted from Gloor P. Contributions of
electroencephalography and electrocorticography to the neurosurgical treatment
of the epilepsies. Adv Neurol 1975;8:59–105.)
Gloor (69,70), discussing the relationship between the topography of extra- or Compared to epidural and subdural electrodes, intracerebral electrodes
intracerebral potential distribution and the location, extent, and configuration are best suited to record from deep, buried structures such as amygdala,
of the generator. To quote Gloor: “It is useful to remember that intracerebral hippocampus, planum temporalis or insula, as well as to record from the
recordings with depth electrodes suffer from some degree of tunnel vision, al- sulcal cortex (42,45,56,57,64,71–78). Intracerebral electrodes can also
though what they see through the tunnel is very distinct and precise.” target lesions in deep cerebral locations such as gray matter heterotopia
(79–81) or hypothalamic hamartoma (82,83). The spatial sampling of (location and number of electrodes and electrode contacts) r esults from an
intracerebral electrodes when compared with subdural grids or strips, adequate balance between the need to map the cortical regions where ictal
which cover a large cortical surface, can appear inferior since recordings discharges originate and propagate, the anatomical constraints, and the
are taken from a series of leads that, in a large proportion, seat in the white risks of parenchymatous damage or other complications.
matter and explore a very restricted part of the cortex. In neocortical epi-
lepsy and particularly when the generator is located over the convexity, Risks and Complications
intracerebral depth electrodes may suffer from a relatively poor sampling
compared to subdural electrode approaches. Also, intracerebral electrodes The morbidity reported by centers using intracerebral depth electrodes
are not well adapted to map functional areas during neurostimulation. varies from 0% to 7.5%, and is mostly related to hemorrhages or infections
Hence, if the generator is suspected to be located in the cortical language (57,59,71–78,84–86,89–96). In 13/21 of these studies (72,74–78,89,91–96),
areas, intracerebral EEG may be less suitable compared to cortical elec- 1,277 patients underwent intracerebral depth electrode insertions (with or
trodes. Combination of intracranial recording methods, especially depth without epidural pegs but no other electrode types) with similar morbid-
electrodes and subdural strips or depth electrodes and subdural grids, ity rates and permanent sequelae, including two patients (0.1%) who died
allows improved accuracy of localization due to additional sampling, with as a consequence of the procedure. Only two studies, and from the same
risks that are probably additive, but time and costs that are equivalent group (92,96), addressed specifically the indications and risks of SEEG
(52,54,56,57,59,73,84–86). In North America, many centers still use only in children; the procedure also appears safe in this age group, although
subdural electrodes and only a few use only intracerebral depth electrodes. one death was reported. To avoid transmissible diseases (e.g., Creutzfeld-
In Europe, and more especially in France and Italy, the approach is based Jacob disease), the standard of care is to dispose of all chronically intra-
more on the SEEG method, and clinicians often use only depth electrodes cranial depth electrodes after a single use, although such transmission
but incorporate more targets (87). has never been reported to the best of our knowledge. To minimize risks
A fundamental problem linked to the use of intracerebral EEG (and this of bleeding, antiplatelet drugs are avoided, and this includes the routine
is true for both intracerebral and cortical recording methods) is that a large withdrawal of sodium valproate or valproic acid at least 2 weeks before
portion of the brain volume remains unexplored. Halgren and colleagues implantation (97).
(88) have calculated that in order to sample the whole brain volume, with One of the largest published series (89,93,95) comes from the Montreal
the spatial resolution of few millimeters (3 to 5 mm) that usually character- Neurological Hospital and Institute, where 593 adult patients have been
ized intracerebral EEG procedures, about 10,000 recording sites would be implanted over a period of 40 years (1972 to 2012). In 2009, Tanriverdi
necessary. This calculation, however, includes the white and the gray matter and colleagues (95) reviewed 491 patients (studied between 1976 and 2006)
and largely overestimates the needs encountered in most of the clinical sce- and found an overall complication rate of 7.5% (37 patients): 9 patients
narios. Also, a 3- to 5-mm interelectrode space may be superfluous in corti- (1.8%) had infections (4 abscesses, 4 scalp infections, and 1 meningitis);
cal areas such as the first, second, or third temporal convolutions, in which 4 (0.8%) had intraparenchymal or subdural hematoma; 3 removed an elec-
a distance of 2 cm between two recording sites seems sufficient to account trode during a seizure or postictal confusional state, without consequences;
for the diffusion of the ictal discharge. Nevertheless, depth electrodes may 2 (0.4%) had hemiparesis, 1 permanent, occurring during preimplantation
be blind and useless, a risk that increases when implantations are performed angiography (in the early 1980s); 2 (0.4%) had cortical infarcts caused by
with inadequate a priori working hypotheses, leading to “fishing expedi- an electrode, one in a frontal lobe leading to a permanent cognitive defi-
tions.” Intracerebral EEG studies should be designed by selecting a dequate cit, and one in an occipital lobe causing a minimal non-disabling visual
targeting of electrodes, adequate number of recording electrodes and con- field defect; 1 was found with an electrode fragment in the brain and a
tacts, and adequate montage designs (EEG is acquired in referential using cold abscess 1 year after implantation; 12 patients had unusually severe
simultaneously all the electrode contacts available, and eventually events headaches explained by a persistent cerebrospinal fluid (CSF) leak; and
are played back using monopolar and bipolar montages defined according the remaining 4 patients had miscellaneous minor and reversible problems.
to their optimal use). In summary, an adequate depth electrode placement Only 2 patients (0.4%) had permanent significant sequelae explained by the
method. In addition, 26 (5.3%) patients presented transitory psychiatric Recording Procedure

problems during SEEG monitoring due to antiepileptic drug withdrawal,
seizures, or both. There was no mortality in this large series and none of the Technical Aspects
patients received blood transfusion.
In a recent study, Khoury and colleagues (98) looked at the frequency of The EEG technology and methods used to record and review intracranial EEG
iatrogenic seizures during intracranial EEG and presumably explained by are identical to those used for scalp EEG recordings. For routine recordings,
a direct effect of the electrodes. In 33 intracranial procedures (27 adult pa- the same filters are applied for intracerebral EEG as for scalp EEG (low-filter,
tients), depth electrodes were used in only 7 instances, subdural grids/strips 0.5 Hz; and high-filter, 70 Hz or above) at a sampling rate of 200 to 256 Hz.
only in 12, and a combination of depth and subdural electrodes in 14 cases. Sampling rates of 200 to 256 and 512 Hz provide adequate display of clinically
In 6/21 (28%) cases with intracerebral depth electrodes, peri-electrode va- relevant EEG signal and good recordings of oscillatory signals at frequen-
sogenic edema was observed on a preimplantation MRI. Three (3/21, or cies in the beta and gamma ranges, usually seen at seizure onset (100–103).
14%) exhibited discordant subclinical seizures, without clinical correlates, Amplifiers now allow sampling rates of greater than 1,000 Hz, which permits
recorded from the depth electrode showing this surrounding edema. There to record high-frequency oscillations (HFOs) in the range of 80 to 500 Hz
were no long-term adverse sequelae. In the series of the MNI, the same (ripples and fast ripples) if the high filter is set correctly (104,105), and even
phenomenon was observed in only two cases (0.4%): one patient had repeti- greater than 1,000 Hz (106,107). Signal amplitudes are higher in the intrace-
tive but transitory clinical and electrical occipital seizures recorded for few rebral EEG than in scalp EEG, and amplifier sensitivity needs to be adjusted.
hours; and another had a cluster of subclinical focal seizures followed by a The number of electrodes implanted is guided by the clinical problems to
clinical one and originating in one insula. In both cases, the seizures were be resolved, likely to be smaller in cases of TLE and higher in temporal-plus
discordant and never recurred. It is difficult to explain the difference in the (frontotemporal, insulo-temporal, or temporo-parieto-occipital), frontal
rate of such iatrogenic seizures between these two groups of patients. In the lobe, and posterior cortex epilepsies (Fig. 14.4); the range varies from 6 to
MNI, the two patients had clinical seizures which clearly captured the at- 16 electrodes in a single patient and, hence, approximately 50 to 150 record-
tention of the clinicians, while in the series by Khoury and colleagues, the ing sites located in the cortex or cortical gray matter, and a large propor-
patients had subclinical seizures only. At the MNI, per-insertion or immedi- tion in the white matter. Commercial EEG equipment permits simultaneous
ate postremoval MRI is not systematically performed, which certainly leads recording from 128 channels and even more (Fig. 14.5).
to an underestimation of the peri-electrode vasogenic edema and maybe of The selection of a reference electrode depends primarily on the imped-
these iatrogenic (often subclinical) seizures. ance of the electrode (should be the same as the other recording contacts)
In many centers, MRI or CT is used for postimplantation localization of and its location (ideally, in a region with no or little source of electrical
intracranial electrodes as it allows a good visualization of the electrode con- field—which very likely does not exist—and not contaminated by artifacts
tacts in relation to neuroanatomy. Head CT is associated with a high dose of caused by eye movements or muscle activity) (108). For instance, good elec-
ionizing radiation, and for this reason, MRI should be favored. On the other trode reference can be in the white matter, any inactive contact devoid of
hand, the inadequate use of MRI may expose patients to a significant risk artifacts, an epidural electrode fixed in the bone and far from the epileptic
of radiofrequency-induced thermal injury. Carmichael and colleagues (99) field. The choice of the reference electrode always remains a sensitive issue;
studied this problem at 1.5 and 3 T, and proposed that MRI for intracranial there is no “inactive reference,” and probably any reference can be used,
electrode localization can be performed safely in both conditions, provided providing that one knows the effect of the reference on the EEG display.
a head-transmitted coil is used, electrode leads are separated, and specific Intracerebral EEG activity is better displayed using bipolar recordings
absorption rate (SAR) limits are determined. The authors emphasized that between contiguous contacts; it cancels the influence of the reference elec-
each center should carefully define a specific imaging protocol, set local SAR trode, and the signal recorded at two adjacent contacts is less likely to include
limits, and allow a conservative safety margin to avoid interpatient varia- contributions from remote sources. One limitation of bipolar recordings,
tions in EEG electrode placement, scan prescriptions or r adiofrequency coil however, is that the signal is blind to fluctuations that affect equally the two
loading that may lead to excessive tissue heating. recording leads of the bipole (in-phase cancellation). Ideally, data should be
A B B M C
F E
J
H G 24
S
S R 23
Q R
22
U O 16
C 21
T 19 18 20
B A 17
E I 15 13
ET 14 12
M
B F
Y E 11
J
R H 10
X S G 9
Q
Y
R 8
C B O 3
A
7 5 4
6
E ET 2
1
Figure 14.4: Typical depth electrode implantation schemes in three different clinical scenarios. A: Temporo-
perisylvian epilepsy (a 10-year-old boy with right hippocampal sclerosis, same patient as in Fig. 14.21A).
Seizures are initiated by a gustatory aura, quickly followed by a sensation of tingling of the palate, palor,
oroalimentary automatisms without impairment of consciousness. Interictal scalp EEG showed right tem-
poral slow waves and spikes and ictal scalp EEG, anterior and temporo-basal discharges with secondary
spread to the anterior suprasylvian territories. The main issue in this case was to determine whether sei-
zures were starting from the sclerotic hippocampus before spreading to the insular cortex, or whether they
started first in the insula. B: Fronto-central epilepsy (a 6-year-old boy with negative MRI, same patient as
in Figs. 14.18B, 14.22A, and 14.23). Seizures are characterized by clusters of brief episodes of left oculo-
cephalic version with bilateral (L > R) tonic motor signs. Interictal scalp EEG showed spikes and bursts of
fast oscillations over the right fronto-central region (FP2–F4, F4–C4, Fz–Cz), and seizures started from this
area. The hypothesis was to demonstrate that seizures arose from the region of the right frontal eye-field.
C: Posterior quadrant neocortical epilepsy (a 24-year-old with negative MRI, same patient as in Fig. 14.12).
Seizures start without an aura, patient stares with loss of contact, mumbles and sometimes presents head
shaking, with postictal amnesia. Interictal EEG showed right parietal or temporoparietal sharp waves and
ictal scalp EEG suggested involvement of the right t emporo-occipital region. The hypothesis was centered
over the posterior temporo-basal neocortex. Letters (cases A and B) and numbers (case C) refer to intrace-
rebral electrodes. Most electrodes are inserted using a lateral orthogonal trajectory.
All channels (63) Selected TL channels (37) Selected Hc channels (16)

(TL: 50 uV/mm, ETL: 20 uV/mm) (50 uV/mm) (50 uV/mm)
A B C
Orbito-frontal
Ant. cingulate
Post. cingulate
Temporal pole
Amygdala
Mid-temporal (T3)
Ant. Hippocampus
Post. hippocampus
Figure 14.5: Different displays of SEEG recordings in the same nonlesional temporal lobe patient. A shows
a display of all electrodes (67 channels) recording from frontal, temporal, and posterior cingulate regions.
B shows the same recording obtained from the temporal lobe, and C from the two hippocampal electrodes.
Bipolar recording with seven or eight channels per electrode. Electrodes were inserted through orthogonal
or oblique approaches; for each electrode, upper channels refer to mesial structures and lower channels to
lateral structures.
reviewed with both bipolar and referential montages because of in-phase side effects. Additionally, the electrocardiography (to capture changes of
cancellation (bipolar montage) and the effects of active reference electrodes heart rate during periictal periods), EMG, and EOG (again for artifacts de-
(referential montage). tection and sleep staging) are usually monitored. The risk of SUDEP (sud-
Intracererebral EEG activity can be recorded along with a limited num- den unexplained death in epilepsy), although low, makes it reasonable to
ber of EEG electrodes placed over the scalp. A reason against the use of also monitor breathing and oxygen saturation to look at possible hypoven-
additional scalp electrodes is the risk of infections. Also, the position of tilation and oxygen desaturation that may occur during and after seizures.
scalp electrodes cannot be standardized due to the presence of intracerebral
electrodes. At the MNI, subdermal needle electrodes placed over the fronto- Practical Aspects
centro-parietal parasagittal regions are now used routinely (109,110). They
may provide information on the regions unexplored by the intracerebral The intracranial EEGs are reviewed with a high-resolution computer
electrodes, notably in the hemisphere contralateral to the side of investiga- screen. Because the number of channels can easily exceed 100, and
tion, and also help in sleep staging. This later point is of particular interest therefore beyond the limits of adequate visual resolution, bipolar and
when looking at events such as HFOs, which preferentially occur during referential montages are created according to the clinical problem, with a
slow-wave sleep (111). These subdermal electrodes are well tolerated by variable number of channels. The different montages can then be r eviewed
patients, remain operational for several weeks (110,112), and are without back-and-forth with a large or with a limited number of channels, at
ifferent sensitivities and timescales and in a logical framework (channels

d specific areas of interest (Fig. 14.6A, B). The continuous intracerebral
are grouped according to lobar location and according to the position of EEG is usually stored on a computer medium, which allows us to go back
the contacts from depth to surface). This approach allows first to get an at any time to review the tracings with a great flexibility. Measures of im-
overall impression of the EEG during an event, and then to focus on more pedance and routine EEG recordings can be performed at the beginning
L Amygdala
A
1
L Hippocampus 2
3
4
5
6
7
8
9
10
R Amygdala
R Hippocampus
R Orbito-frontal
R Frontopolar
R Pre-motorant.
Figure 14.6: Examples of seizure recorded with

large and limited sampling. A: a 55-year-old patient R Pre-motorpost.
with adult-onset bilateral temporal lobe epilepsy
and right anterior frontal area of encephalomalacia.
Patient was suspected to have independent tempo- L Amygdala 1
ral epileptic generators, right more active then left 2
side. Intracerebral evaluation was to demonstrate 3

4
that main seizure pattern arose from the right mesial
5
temporal regions, and to rule out the contribution
6
of the right frontal lesion. Each electrode contained
7
between 10 and 15 contacts for a total of 100 chan-
8
nels. In this example, selecting only the left amygdala
9
and hippocampal electrodes (inferior panel) shows 10
a clear focal seizure onset in the left hippocampus L Hippocampus 1
(recording reference, left parietal). B: A 33-year-old 2
patient with seizures since age 16 and a discrete right 3
mid-frontal convexity focal cortical dysplasia type 4
2b. Two electrodes (RF2 ant. and post.) were placed 5
along the axis of the abnormal sulcus and gyrus from 6
the depth to the surface. In this example, selecting 7
only these two electrodes (inferior panel) shows the 8
seizure onset involving most of their contacts found 9
in the brain. 10
B
L Ant. cingulate
L Mid. cingulate
R Orbito-frontal
R Ant. cingulate
R Mid. cingulate
R F2 (ant.lesion)
R F2 (post.lesion)
R Amygdala
R Hippocampus
R F2 (ant.lesion) 1-2
2-3
3-4
4-5
5-6
6-7
7-8
8-9
9-10
R F2 (post. lesion) 1-2
2-3
3-4
4-5
5-6
6-7
7-8
8-9
9-10 Seizure onset
and at the end of invasive evaluation to ensure the quality of the recording TABLE 14.3 Scheme for Intracranial EEG Decision in TL and Extra-TLE
(see later).
EEG recordings are performed over a mean period of approximately 1. Localized and lateralized epileptic generator:
2 weeks (in a recent survey—not published—obtained from six adult or pe- e.g., unilateral mesial TLE, unilateral and localized neocortical epilepsy
diatric centers, one Canadian, and five Europeans, the average number of 2. Localized but not lateralized epileptic generator:
days for evaluations varied from 2.5 to 15 days, with a range from 1 to 6 days e.g., side of mesial TL focus not determined (R versus L), bilateral TLE
in children and 3 to 32 days in adults), with a gradual reduction of patient’s or FLE
medication, and under different states (waking, after sleep deprivation, and 3. Lateralized but not localized epileptic generator:
during sleep). The duration of monitoring is tailored according to the pa- e.g., mesial versus neocortical TL focus, temporal “plus” epilepsy,
“pseudo-temporal” lobe epilepsy, frontal and central lobe epilepsy,
tient’s need (frequency of spontaneous seizures), risks of the procedure (e.g.,
posterior quadrant epileptic generator, insular lobe epilepsy
infections) and of drug withdrawal, as well as to expected increase in techni-
4. Not lateralized and not localized epileptic generator:
cal problems over time (electrodes and leads malfunctions). Patients are usu- e.g., widespread, diffuse or multifocal epileptic generator
ally monitored in a dedicated monitoring unit, where they are continuously
observed by a member of the epilepsy team. This allows obtaining from sei-
zure onset a precise description of subjective and objective patient experi-
ences, and an accurate neurological evaluation of test awareness, language, for example, TLE without lateralization or bilateral frontal epilepsy; (3)
memory, muscle tone and activity, and sensory–motor functions. EEG mon- lateralized but not localized focus, for example, right frontal versus right
itoring usually begins within 24 hours of surgical insertion and after a period temporal focus; and (4) nonlateralized and nonlocalized focus, for example,
of observation in the intensive care unit (ICU) or neurosurgery department. multifocal, diffuse, or widespread epileptic generator. With this scheme
In some centers, recordings are performed 24 hours per day and 7 days per in mind, invasive EEG would appear primarily indicated in categories 2
week, while in others, monitoring is restricted to daytime and weekdays. Re- and 3. Whether intracerebral electrode, subdural strip or grid recordings
cently, some centers have designed dedicated intracerebral EEG ICU moni- are used depends on the specific questions and the brain areas that are
toring suites for their epileptic patients with intracerebral EEG. suspected to be involved; each technique has advantages in specific situ-
ations, and selection must also consider their technical limitations. Also,
in children, intracerebral EEG methods are more difficult to perform, for
Indications of Intracerebral Depth technical reasons (thickness and rigidity of the skull, tolerance to long-
Electrode EEG Recording term monitoring) and for age-related semiological and neurophysiological
peculiarities, which make localizing hypotheses more complex and difficult
Invasive EEG recordings are considered when noninvasive studies are dis- to elaborate than in adults. Nevertheless, intracerebral EEG recording is
cordant or inconclusive. There are no set criteria that determine whether feasible, effective, and safe, even in children as young as 3 years of age, or
an invasive EEG evaluation should be performed, but factors such as the less (92,96).
presence of a lesion or the type of epilepsy (temporal versus extratempo-
ral) influence the decision for the need of invasive recordings. A simple
and intuitive scheme to help define the indications, or contraindications, Indications for SEEG in Temporal Lobe Epilepsy
for invasive EEG monitoring in patients with refractory epilepsies (113) is
to divide patients in categories determined on the basis that the epileptic Unilateral Mesial Temporal Lobe Seizures (Category 1)
generator can be localized and lateralized during adequate comprehensive In TLE, intracranial EEG is usually not indicated when presurgical clinical,
noninvasive evaluation. Following this scheme, four categories are de- functional, EEG, and imaging features converge, favoring a unilateral tem-
fined (Table 14.3): (1) localized and lateralized epileptic focus, for example, poral lobe focus, and are clear enough to propose a temporal lobe resection
unilateral mesial temporal epilepsy; (2) localized but nonlateralized focus, with an excellent postoperative long-term prognosis (114,115).
Nonlateralized or Bilateral Independent Temporal Lobe lobe seizures is often inaccurate, and that temporal lobe epileptogenic zones
Seizures (Category 2), and Mesial versus Neocortical may incorporate larger networks that extend beyond these traditional limits
Temporal Lobe Seizures (Category 3) (Fig.14.7) (116,117).
Long-term SEEG monitoring is indicated if a doubt persists on the side
of the temporal lobe generator, when bilateral TLE is suspected (6), or, Temporal “Plus” Epilepsy (Category 3)
when, within the temporal lobe, clinical arguments do not allow to dif- This term refers to a specific form of multilobar epilepsy in which seizures
ferentiate between a mesial and neocortical epileptic generator. Increasing involve a complex epileptogenic network that includes the temporal lobe and
evidence suggests that the distinction between mesial and lateral temporal the closed neighbored structures such as the orbitofrontal cortex, the insula,
1200 uV (* 600 uV)
1s (0.530-120 Hz band-pass filter)
TP *
AN *
Hc
HcG
T3
aT2
mT2
aT1
pT1
FusG
TOj
AG
pCG
TPj
Seizure onset
Figure 14.7: Example of a widespread mesial and neocortical temporal seizure onset: a right temporal lobe
seizure in a 16-year-old girl with negative MRI. Seizure semiology was characterized by a psychomotor arrest,
sometimes inconsistent speech, discrete chewing, and postictal amnesia. During SEEG, seizures involve a
large network from onset and start simultaneously in the mesiotemporal lobe structures (AN, amygdaloid
nucleus; Hc, hippocampus; HcG, hippocampal gyrus), the temporopolar cortex (TP), basolateral temporal
cortex (T3), and anterior part of the second temporal convolution (aT2). It spreads almost immediately to the
mid part of T2 (mT2), fusiform gyrus (FusG), lateral temporo-occipital junction (TOj), angularis gyrus (AG), and
posterior cingulate gyrus (pCG). The temporoparietal junction (TPj) is much less involved, and the first tempo-
ral convolution (aT1, pT1) is spared.
the frontal and parietal operculum, and the temporo-parieto-occipital junc- “Pseudo-Temporal” Seizures (Category 3)
tion. Barba and colleagues (118) compared the clinical and scalp EEG char- Invasive EEG is indicated in suspected “pseudo-temporal” epilepsy, a term
acteristics of patients proven to have TLE (n = 58) with a smaller group of that encompasses cases with mesial frontal and orbitofrontal seizures, mesial
patients with temporal “plus” epilepsy (n = 22, T+). They found that pa- parietal and temporo-occipital seizures, or insular lobe seizures (Fig. 14.9).
tients with T+ are difficult to differentiate from those with TLE on the basis The epileptic generator localized in these regions can be clinically silent until
of general clinical features or MRI data; even the presence of hippocampal the discharge propagates to adjacent temporal lobe structures, mimicking
sclerosis may not help in distinguishing the two groups. However, ictal clini- temporal lobe seizures both clinically and on scalp EEG (120). In the absence
cal symptoms and scalp EEG findings help differentiating TLE from T+ pa- of a structural lesion, this group of focal epilepsies can be difficult to identify
tients. For instance, patients with TLE more frequently present an ability to and attention must be paid to subtle ictal clinical symptoms that might point
warn at seizure onset, an abdominal aura, gestural automatisms, and postic- to extratemporal areas (121), to atypical EEG patterns (122), to posterior
tal amnesia. On the other hand, patients suffering from T+ epilepsies more abnormal MRI data (123,124), or to unusual ictal SPECT patterns (125).
frequently have gustatory, vestibular, or auditory aura; they more frequently
exhibit contraversive manifestations of the eyes or head, piloerection, and
ipsilateral tonic motor signs; and they are more often dysphoric during the Indications for SEEG in Extratemporal Lobe Epilepsy
postictal phase. Interictal EEGs of T+ patients more frequently exhibit
bilateral or precentral abnormalities, and ictal EEGs more frequently point Frontal Lobe Seizures (Categories 2 and 3)
over the anterior frontal, temporoparietal, and precentral regions. Hence, The large volume of the frontal lobe and its complex functional organization
a constellation of clinical and scalp EEG findings may be useful for identi- and connectivity explain the difficulty clinicians have to precisely define a
fying among patients suffering from atypical TL epilepsies, particularly in clear clinical hypothesis in frontal lobe seizures, particularly in nonlesional
the nonlesional cases, those who should undergo invasive recordings before cases. Frontal lobe seizures have a heterogeneous semiology and are classi-
surgery (Fig. 14.8). Interictal metabolic 18FDG-PET patterns might also be cally compartmentalized in anterior-posterior, superior-inferior, and lateral-
helpful to differentiate classical mesial TLE from T+ patients (119). mesial (126). This clinical classification of frontal lobe seizures has some
Seizure onset
Rectus G
OrbitoF
BasoLat Fcx
F pole
CG
DL preF
F operc
Insula
Figure 14.8: Left temporal “plus” seizure in a T1ant

50-year-old female patient with normal MRI. T1mid
The discharge is widely extended from the on- T1post
T2ant
set, involving not only the mesial and lateral T2post
temporal lobe structures (Tpole, temporal pole; T3
HcG, hippocampal gyrus; T2ant, post, anterior/ Tpole*
HcG
posterior part of the second temporal gyrus; FusG
T1ant, mid, anterior and mid part of the first tem- Hc
poral gyrus), but also the insula and orbitofrontal
cortex (OrbitoF). During the seizure, the patient 400 uV (* 200 uV)
was motionless, and thereafter amnestic. 1s (0.530-120 Hz band-pass filter)

Seizure onset
F op
C op**
P op *
Insula
orbitoF
T1
Tpole
aHc ***
aT2
pHc ***
pT2
HcG
T3
pCG****
500 uV (* 250 uV - ** 400 uV - *** 1200 uV - **** 2000 uV)
1s (0.530 -120 Hz band -pass filter)

Figure 14.9: Right pseudo-temporal seizure in a 41-year-old female patient with a right opercular scar (past
history of cavernoma surgery). Seizures were triggered by eating and started with a gustatory hallucination.
The SEEG discharge starts in the insular cortex and then involves, 2 seconds later, the temporal lobe, espe-
cially the hippocampus (aHc, pHc), giving rise to a “typical” temporal lobe semiology (loss of contact, oro-
alimentary automatisms, right hand automatisms, and left arm dystonic posturing and postictal confusion).
limitations because of the difficulty to ascribe a specific seizure pattern to a good synoptic electroclinical correlations should be able to provide enough
specific frontal region or functional area and the risk of overlap (127). This is information to define indications and types of intracerebral EEG evalua-
explained by (1) the size of the frontal lobe, which represents approximately tion. The frontal pole, the mesial premotor cortex, the dorsolateral frontal
two-thirds of the brain; (2) the large extent of the mesial, interhemispheric, cortex, and the orbito-cingulate region are anatomical areas of predilection
frontal structures where epileptic generators are inaccessible to scalp EEG; for frontal lobe seizures, with distinct features that can be recognized, and
(3) the extended connections within the functional divisions of one fron- should, with their efferents, be adequately sampled. H yperkinetic seizures of
tal lobe and between the two frontal lobes, and the fast spread of ictal dis- frontal origin, for instance (Fig. 14.10), often require investigating the gyrus
charges within the frontal lobe structures; and (4) the extended connections rectus and the orbital cortex, the lateral fronto-basal cortex, the anterior
with cortical and subcortical structures outside the frontal lobe. Typically, cingulate gyrus, and the anterior portion of the ipsilateral temporal lobe
frontal lobe seizures fall in categories 2 or 3 of our scheme (Table 14.3), and (128). They may also arise from the mesial surface of the premotor frontal
L orbito-frontal 1-2
2-3
3-4
L ant. insula 1-2
2-3
3-4
L ant. cingulate 1-2
2-3
3-4
L mid. cingulate 1-2
2-3
L hippocampus 1-2
4-5
6-7
1s
Figure 14.10: Orbitofrontal hyperkinetic sei-
zure in a 31-year-old patient with left nonlesional
frontotemporal epilepsy. Typical seizures were
characterized by a sudden onset of intense fear
followed by vocal automatisms and complex
motor behavior. The seizures were short but
followed by amnesia. The SEEG seizure starts in
the orbitofrontal cortex (first arrow), and possibly
at the same time in the anterior insula (rhythmic
2- to 3-Hz spike-and-wave discharge L orbito-
frontal 2-3 and 3-4 and L ant insula 2-3 and 3-4).
After few seconds, a low-voltage fast discharge
is seen in the same electrode contacts (second
arrow) and then in the anterior cingulate; it is at
this
moment that the hyperkinetic manifesta-
tions start (third arrow, inferior panel).
cortex and are better evaluated by targeting the rostral and caudal part of usually straightforward, with reliable localizing and lateralizing features.
the supplementary motor area, the pre-SMA, the cingulate motor area and Therefore, intracerebral EEG evaluation of the central sensorimotor cortex
the cingulate gyrus proper, and the primary motor cortex (129), or even from should be designed to demonstrate that seizures arise from this area and
outside the frontal lobe in the temporal lobe structures or in the insula (130). to provide relevant information on what part of this eloquent cortex can
be removed and what portion should be spared (Fig. 14.11). In the cen-
Central Cortex (Sensorimotor) Seizures (Category 1) tral region, intracerebral electrodes can sample the depth of the rolandic
The problem in this type of seizures is not so much the localization of fissure and the d escending motor and ascending sensory pathways (131).
the seizure generator as the sparing of function; the seizure semiology is A limitation, however, is that the rolandic fissure in the horizontal plane
Am 1-2
2-3
midT (T1) 1-2
2-3
M1 sup. 1-2
2-3
3-4
6-7
Seizure onset
M1 mid. 1-2
2-3
Figure 14.11: Sensorimotor seizure in a
3-4 47-year-old patient with multifocal right fronto-
4-5 centro-parietal nonlesional epilepsy. One sei-
zure pattern consisted of nocturnal seizures
S1 sup. 1-2 characterized by a sudden arousal, grimaces,
left arm ictal paresis, and a variable head-eyes-
2-3
body turn to the right with right arm stiffening.
S1 inf. 1-2 The seizure starts in the mid and superior aspect
of the primary motor cortex (M1 sup. and mid.)
2-3
and then involves, 2 seconds later, the primary
sensory cortex (S1 sup. and inf.; an intermediate
1s
Propagation S1 electrode was dysfunctional).
has an anteroposterior oblique orientation, and one single depth electrode EEG expressions of posterior seizures are often the result of propagation
cannot reach, by a lateral orthogonal trajectory, both the mesial and lat- (132,133). In addition, the semiology of occipital or parietal lobe seizures
eral aspects of the motor or sensory cortices. Also, the risk of significant is subjective, thus often not spontaneously or easily expressed by patients,
morbidity is important in this region, and hemorrhages caused by electrode capable of being masked by other symptoms (for instance, during occipi-
insertion may lead to important and irreversible motor and sensory deficits. totemporal propagation) or associated with anterograde amnesia. Seizures
originating in the posterior quadrant often fall again in categories 2 and 3
Posterior Quadrant Seizures (Categories 2 and 3) of our scheme (Table 14.3). Typical targets for depth electrode insertions are
As for frontal lobe epilepsy, seizures arising from the posterior neocortex the calcarine and pericalcarine cortices (in occipital lobe epilepsy), the infe-
(posterior temporal junction and parietal and occipital lobe structures) rior and superior parietal lobules and the posterior cingulate cortex (in pa-
have a heterogeneous semiology, an heterogeneity usually explained by the rietal lobe epilepsy), but also with emphasis on the evaluation of “junction
frequent simultaneous activations of the occipital, parietal, and posterior territories” such as the lingual lobule and fusiform gyrus, the angular and
temporal lobe structures, and by the multidirectional spread of the epileptic supramarginal gyri, the precuneus and posterior insular cortex. In addition,
discharge toward the central, frontal, and temporal regions. The clinical and because posterior seizures often propagate (and rapidly) anteriorly either
Seizure onset
mesioT 1
2
3
4
5
FusG 6
7
O-P mes
8
9
10
11
12
13
14
T2/T3/O lat
15
16
17*
18
19
20
21
T1/P lat
22
23
24
800 uV (* 400 uV )
1s (5.30-120 Hz band-pass filter)

Figure 14.12: Posterior quadrant seizure (same patient as in Fig. 14.4C). The seizure starts in the fusiform
gyrus (FusG) and involves, after few seconds, the mesio-temporal lobe structures (mesioT), the mesial
occipito-parietal cortex (O-P mes), and, to a lesser degree, the lateral temporo-occipital (T2/T3/O lat) and
temporoparietal (T1/P lat) junction.
toward the temporal lobe through the inferior longitudinal fasciculus connectivity with the surrounding frontal, temporal, perisylvian, and poste-
or toward the suprasylvian (fronto-central) structures through the superior rior cortical structures. Because the insula was considered not to be primar-
longitudinal fasciculus, temporal and frontal lobe structures are often other ily responsible for seizure generation and because of the surgical risk due
targets for electrode insertions (Fig. 14.12). Finally, posterior seizures tend to its localization deep in the brain surrounded by a dense vascularization,
to spread to the contralateral homologous regions, and therefore, bilateral neurosurgeons did not for some time consider this structure as a significant
implantation may be necessary. target in epilepsy surgery. Recently, however, lesional studies (134) and in-
tracranial EEG recordings (75) have revived a new interest in the insula and
Insular Lobe Seizures (Category 3) pointed that the insular cortex can be a primary focus in some forms of
The insula is known to have an important role in the propagation patterns focal seizures and plays an important role in the propagation of epileptic
of the epileptic discharge in a variety of focal seizures originating from discharges arising from different neighboring structures. Moreover, neuro-
different parts of the brain; this is explained by its localization and dense surgeons now feel that insular cortex surgery can be performed more safely
Moves his left hand Clinical onset of the seizure
orbitoF
DLFcx
SSOperc
1
2
Insula 3
4 3 4
1 5
7 6 6
7
TNeocx
*
mesioT **
400 uV (4-5 : 800 uV; * 200 uV; ** 100 uV)
1s (5.30 -120 Hz band -pass filter)
5
4 3
2
7
Figure 14.13: Insular lobe seizure (MRI-negative case, same patient as in Figs. 14.16B and 14.25). A typical
seizure triggered by repetitive movements of the left hand, which elicit spikes over the posterior part of the in-
sular cortex (contacts 4 and 5). These are followed by a polyspikes discharge, and by a low-voltage fast activity
that spread a little bit more anteriorly (contact 3). The patient describes a painful tingling sensation in the left
hand. Note the late involvement (arrows) of the dorsolateral frontal cortex (DLFCx) and suprasylvian operculum
414 (SSOperc). orbitoF, orbitofrontal cortex; TNeocx, temporal neocortex; mesioT, mesiotemporal lobe structures.
and with satisfactory results, even when MRI does not show any epilep- has nonlesional epilepsy (140): The rates among surgically treated patients
togenic lesion (135). Hence, in patients with suspected refractory insular range from 3% to 21% (141–143), and results of epilepsy surgery are also
lobe epilepsy, temporo-insular seizures or extratemporal neocortical-insular usually considered to be less satisfactory (144). Cases of nonlesional focal
seizures, intracranial EEG recordings are recommended using intracerebral epilepsy are more challenging and intracerebral recordings remain essential
depth electrodes. in a significant proportion of them: (a) there is a higher risk for misinter-
Ictal semiology of insular lobe seizures is far from homogeneous and it pretation of clinical and scalp EEG findings because different regions of the
appears that insular epilepsy can be a great mimicker (136): Although a brain may share the same clinical characteristics (and the presence of a le-
well-defined “perisylvian” clinical pattern has been individualized, insular sion can be used to help in the differential diagnosis); and (b) there is a high
seizures may manifest with temporal (75) or frontal lobe semiology (129). percentage of multilobar epilepsies in patients with nonlesional (invisible or
Moreover, the insula is a buried structure localized deep in the brain and in- occult) focal epilepsy (145). The delineation of extratemporal epileptogenic
accessible to scalp electrodes and even to intracranial grid or strip electrodes. network is much more difficult than that of temporal lobe seizure origin,
The SEEG method is better suited to study the insular cortex (Fig 14.13). and a larger proportion of patients suffering from MRI-negative extratem-
Electrodes can be inserted using a lateral orthogonal trajectory through the poral lobe epilepsy are likely to undergo invasive EEG recordings. A larger
frontoparietal and temporal operculum (75) or, to obtain a larger insular number of intracerebral electrodes might be necessary, and potentially with
sampling, using oblique trajectories through the frontal or parietal cortices a higher risk for complications, with, however, a similar rate of epileptic
(78,137,138). Combined depth and subdural electrodes or hybrid operculo- focus localization compared to lesional cases (146).
insular electrodes can be also used safely to investigate complex insular/
perisylvian epilepsies (54,56). When Intracerebral EEG Is Not Indicated
Indications for SEEG in Lesional There are epileptic conditions (category 4: multifocal, diffuse, or nonlo-
and Nonlesional Focal Epilepsies calizing hypotheses) where invasive EEG methods are unlikely to provide
additional information and the risks of the procedure outweigh the benefits.
Invasive EEG studies are at first not indicated in lesional focal epilepsies. In addition, invasive monitoring should be proposed only when it seems
However, invasive EEG is to be considered when contradictions exist be- reasonable to believe that a resective procedure will lead to a satisfactory
tween the semiology/EEG presentation and the lesion, suggesting that the surgical outcome, which does not necessarily mean that complete seizure
lesion is not epileptogenic per se, or solely. Intracerebral EEG in lesional freedom will be achieved. In the Montreal series of patients studied with
epilepsy may be considered if the extent of the lesion itself is unknown intracerebral EEG and also in a few other reports from the literature, be-
and it is felt that the part seen on MRI represents only a portion of the tween 7% and 31% of patients have their electrodes removed and, eventu-
epileptogenic anomaly (139). Intracerebral EEG may also be considered in ally, no resection (76,77,85,92–94). The reasons usually mentioned include a
multifocal epileptogenic lesions such as in tuberous sclerosis or cases of mul- combination of multifocal, nonlocalizing seizures and the proximity of the
tiple cavernous angioma where it may be difficult to determine which tuber eloquent cortex.
or cavernoma is responsible for generating seizures. Invasive intracerebral
EEG is probably indicated in most of the epileptic patients with refractory Intracerebral EEG Monitoring:
focal seizures associated with periventricular nodular heterotopia because interpretation of EEG data
of their frequent association with “pseudo-temporal” seizures (79,81,124).
Because of the limitations inerrant to depth electrode methods, intracerebral Intracerebral electrodes have the advantage of being able to detect very
EEG recording in lesional epilepsy is not primarily considered to perform small cortical generators located anywhere in the brain, including those in
electrical functional mapping of the cortex. deep buried regions. They can also sample different lobes simultaneously in
Despite major advances in neuroimaging, a significant proportion of pa- one or both hemispheres. As discussed earlier, however, depth electrode con-
tients with focal refractory epilepsy and presenting for presurgical evaluation tacts sample a very small volume of cortex, which, in a variety of conditions,
may leave a large portion of the brain unexplored. This limitation has to be TABLE 14.4 Study Protocol during Routine EEG in Patients with
considered when studying cortical areas felt, for instance, to be responsible Intracerebral Electrodes (Total Duration of 30 minutes)
for the generation of seizures (the seizure-onset zone), spikes (the irritative
zone), or slow-wave abnormalities (the lesional zone). The same intrinsic 1. Eyes opened 1 min, closed 1 min, opened 1 min, and closed 1 min.
limitation allows only a limited sample of the regions responsible to gener- 2. Saccades. Look to the right, to the left, upward, downward, 1 min.
ate normal physiological brain rhythms. 3. Clench left fist 5–10 s, right fist 5–10 s, few times.
4. Jaw clenching 5–10 s, few times.
Intracerebral depth electrode evaluations primarily aim to record seizures
5. Hyperventilation, 3 min, 3 additional minutes for relaxation.
in order to define an epileptic focus and the propagation pattern of the sei- 6. Intermittent photic stimulation at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 30,
zures in order to delineate the extent of the cortical epileptogenic network. 40, and 50 Hz.
Interictal epileptiform abnormalities are recorded usually in a much larger 7. Attention, (a) serial 7s (100 − 7, 93 − 7, 86 − 7, etc.), 1 min; (b) months
amount and with a more widespread pattern than what is normally seen of the year forward and backward, 1 min.
on scalp EEG. Nonepileptiform abnormalities are also present and often 8. Reading, 1 min.
difficult to interpret. Each intracerebral investigation is designed for a spe- 9. Writing, 1 min.
cific epilepsy problem and, hence, the structures evaluated and the type of 10. Various stages of sleep, if possible, in epochs of at least 1 min.
implantation may vary considerably. The intracerebral electrodes are still
placed in a somewhat uniform approach but never with a standardize frame
as for the 10–20 or 10–10 International Recording System used for scalp
EEG; the insertion of electrodes is usually asymmetrical or electrodes are brain swelling would have receded and the patient is unlikely to have had
not placed in the exact same homologous regions. As already mentioned, multiple seizures. Routine recording should happen at least 12 hours after
brain sampling is limited by the number of electrodes and recording sites the last seizure, preferably 24 hours. For each study, the time of the last sei-
used. Finally, depth EEG activity may vary, depending on the parts of the zure and the medication are noted. During the first routine study, a verifica-
brain that are recorded (different cortical regions have different physiological tion of all electrodes and contacts is performed, and during the two routine
activities, different thresholds, and different connectivity or networks), and evaluations, electrode impedances are measured (they usually increase from
is modulated by the state of vigilance, cognitive and sensorimotor activities, 1–5 to 5–10 kΩ, and sometimes >10 kΩ, between the first and the second
as well as by the antiepileptic medication. For all these reasons, EEG inter- studies).
pretation should be made cautiously, and comparison and interpretation The ability to record some of the well-known EEG patterns depends
of the normal and abnormal EEG activities between regions and sides can on the position of the intracerebral electrodes; normal alpha, beta, and
be difficult. To some extent, each patient should be considered individually gamma rhythms and slow-wave activity in the theta and delta ranges are
with his own neurophysiology with which we need to be well accustomed. often recorded with these electrodes (Fig. 14.14A, B). The amplitude (usu-
ally higher) and morphology (potentials are usually sharper) of these pat-
Normal Physiological EEG Activity terns may appear different compared to scalp EEG recordings because
of the closest relationship between the recording sites and the neuronal
Normal physiological EEG activity can be recorded, as for scalp EEG, with generators. Other normal activities seen during wakefulness and sleep
SEEG. At the MNI, a routine SEEG protocol is applied for each patient in are recorded such as mu rhythm, spindles, POSTS, or lambda waves (Fig.
order to define the baseline normal brain activity (Table 14.4). Subdermal 14.14C, D). It is not possible to perform good sleep staging or to obtain
electrodes are also placed, at least at positions Fz, Cz, Pz and F3, F4, C3, good polysomnography tracings, but, as mentioned, satisfactory sleep
C4, P3, P4, with EOG and EMG electrodes to facilitate sleep staging (110). staging can still be obtained with additional subdermal electrodes or with
The routine SEEG recordings are performed twice during evaluation, at EOG and EMG electrodes. The EEG obtained from the white matter
the beginning and at the end of investigation. The first study is usually shows flat channels or propagated activity from neighborhood cortical
performed 2 to 4 days after electrode insertion, at which time the patient’s generators (Fig. 14.14E).
Artifacts by a loosening of the electrode, by a CSF leak causing a short-circuit, and

by the movements of the electrode wires. Environmental artifacts can be
As for scalp EEG, artifacts recorded with intracerebral EEG are mostly frequent, but in the context of invasive EEG, the 60-Hz activity is the most
instrumental (recording equipment, electrodes, and their connections), en- frequent and explained by numerous possible sources, including all electrical
vironmental (external sources, i.e., mains line, other equipment around or equipment in the environment (cellular phones, computers and lap-top, TVs
connected to patient, electromagnetic, radiofrequency, and electrostatic sig- and radios, wall phones, beds, intravenous pumps, etc.). Intracerebral EEG
nals), or biologic artifacts (arising from the patient) (Fig. 14.15). Instrumen- recordings are more likely to be free of biologic artifacts. Pulsation artifact,
tal artifacts are often due to a loss of signal caused by the amplifier or a as well as the artifacts of muscle and body movements and eye movements
dysfunction in the jack-box. Artifacts due to electrodes or their connections can, however, be encountered. EMG artifacts are commonly seen in the
can be explained by a breakage of the electrode (often at the point where the most superficial contacts of the electrodes and can be easily confused with
electrode is locked onto a bone peg to prevent movement after insertion), fast oscillations. Intracerebral recordings in the temporal pole of implanted
A C
RPs1-ref
15-ref
2-ref
Figure 14.14: Normal physiological intracere- 16-ref
bral EEG patterns. A: Alpha rhythm recorded 3-ref
4-ref
from depth (RPs 7–13 macrocontacts and 5-ref
RPs17–18 microcontacts) and from surface (sub- 6-ref
7-ref
dermal electrodes Fz, Cz, and Pz) electrodes. 8-ref
Left parietal reference. B: Movement-related 9-ref
(patient was asked to close right fist) beta syn- 10-ref

17-ref
chronization in the motor cortex (same patient 11-ref
as Figs. 14.14E and 14.18A). Note the prominent 12-ref
18-ref
beta synchronization over the contacts exploring 13-ref
the anterior bank of the rolandic cortex (contacts Fz-ref
Cz-ref
7 to 11, circle). C: Neocortical spindles recorded Pz-ref
(bipolar recording) from a parietal electrode and
from subdermal electrodes. D: Hippocampal B closes right fist D 1s
Amygdala
1 1
spindles. Each electrode (amygdala, hippocam- 2

2
3
pus, and paraHc, parahippocampus) contains 3 4

5
eight channels labeled from 1 to 8, the deepest 4 6
7
located in the mesial structures. E: White mat- 5 8
6 Hc 1
ter activity. Recording obtained along the axis 7
2
3
of a 15-leads depth electrode (L’) exploring the I’ 8 4
mesial and lateral aspect of the left prefrontal

5
9 6
cortex (same patient as Figs. 14.14B and 14.18A). 10 7

8
L 11 paraHc
Monopolar (top right) and bipolar (bottom 12
1
2
right) montages. Note the low amplitude of the 600 uV

13
3
4
SEEG signal recorded within the white matter 1s

14 5
6
(contacts 5 to 9). Spikes are recorded from the 15 7
8
lateral surface (contacts 12 and 13).
1-ref
E 2-ref
3-ref
4-ref
5-ref
6-ref
7-ref
5 6 7 8 9 11 13 8-ref
1234 10 12 14
L’ 9-ref
10-ref
11-ref
12-ref
13-ref
14-ref
15-ref
1-2
2-3
3-4
4-5
5-6
6-7
7-8
R 8-9
9-10
10-11
11-12
12-13
800 uV 13-14
14-15
1s (0.530-120 Hz band-pass filter) Figure 14.14: (continued)
patients can be contaminated by saccadic eye muscle artifacts, resulting in as assessed on pathological specimens; the amount and amplitude of this
typical high gamma-band power increases (147): by analyzing data from electrical anomaly are far from homogeneous, and the relationship between
multiple depth electrodes, Jerbi and colleagues showed that this artifact is the areas generating slow waves and those where seizures originate may vary
confined to the pole of the temporal lobe and explained by its immediate from one case to another. The experience of Talairach and Bancaud in this
vicinity to extraocular muscles (rectus lateralis). field was summarized in an important book, EEG et SEEG dans les tumeurs
cérébrales et l’épilepsie (5), in which they described the topographic transi-
Abnormal Interictal EEG Activity tions from electrical silence found inside glial tumors to slow-wave patterns,
spiking, subclinical paroxysms, and seizure activity. The significance of the
Interictal nonepileptiform abnormalities include focal, regional or diffuse slow-wave activity as it is recorded from intracerebral EEG remains unclear,
slow-wave activity, focal loss of fast activities, focal loss of sleep patterns, but it probably needs to be carefully weighted when coming to the final
and attenuation of background activity (Fig. 14.16). In SEEG terminology, surgical decision, even in the absence of a corresponding MRI anatomical
the Lesional Zone refers to the brain area occupied by an abnormal slow- lesion.
wave activity, or by a major disturbance of background activity that implies Interictal epileptiform abnormalities consist of spikes, polyspikes, sharp
a macroscopic alteration of the neural tissue (148). This area coincides in waves, polysharp discharges, and spike-and-wave or polyspike-and-wave
many instances with the Epileptogenic Lesion of Rosenow and Lüders (149), complexes. Their extent delineates the Irritative Zone (148–150). They may
which is most often revealed on MR images. The location and distribution be very focal and detected over a very short distance by very few contiguous
of the slow-wave activity, however, do not always closely match with a lesion electrode contacts, or they may have a more regional, lobar or m
ultilobar and
A B
L TNeocx T1 1
2
3
4
5
R TNeocx T1 1
2
3
4
5
C D
Figure 14.15: Artifacts. A: Muscle artifact. Fast

activity due to muscle artifacts recorded from
epidural electrodes placed over the first tempo-
ral convolution (left and right TNeocx T1). This
activity was not picked up in the other channels
that were recording from contacts located in the
brain. B: Artifacts caused by “loose” electrode
contacts or wires (arrows). C: Artifact due to the
reference, which occurred when the examiner
was touching the patient, and which is visible
only on monopolar montage (upper channels).
D: 60-Hz artifact (when the patient uses his
i-phone), attenuated after applying a notch filter
(right panel).
B
Insula
Figure 14.16: Examples of SEEG interictal patterns of the lesional

zone. A: Electrical silence within a dysembryoplastic neuroepithe-
lial tumor; leads located within the lesion are silent (L’1, L’2, N’1,
N’2, K’1, K’2). B: Slow waves within the insular cortex persist during
eye closure (same patient as in Figs. 14.13 and 14.25), and spikes
500 uV are temporarily abolished. C: Extended and continuous slow waves
over the left temporal lobe in a patient with bilateral temporal lobe
1s Eyes opening epilepsy after viral encephalitis.
Left temporal lobe

Right temporal lobe
Figure 14.16: (continued) 10s
widespread or even diffuse distribution. There are often multifocal, and they and fast spike-and-slow wave or polyphasic potentials with variable polar-
can be generalized and synchronous in one or both hemispheres. Compared ity (they may be negative or positive alternatively during the same record-
to scalp interictal epileptiform potentials, spikes recorded from intracerebral ing epoch) are often recorded from the hippocampus. However, because
electrodes are less stable, showing variable frequency and localization. They of the localization and organization of the hippocampus, epileptic activity
are generally more abundant during slow-wave sleep. The morphology of is usually difficult to detect. Interictal discharges are also frequent in the
the intracerebral epileptiform potentials, although similar to those recorded amygdala, entorhinal cortex, posterior hippocampus or parahippocampus,
from scalp, often shows a higher amplitude, a higher f requency, and a more structures in which the epileptic discharges are synchronous or independent
complex and sharper configuration. For instance, very large amplitude (Fig. 14.17A–D). The mesial temporal structures are located deep in the
A B C
L Am 1-2 L Am 1-3
L Am 1-2
2-3
2-3
3-4
3-5
4-5 3-4
5-6
5-6 4-5
6-7
7-8 5-6
6-7
8-9
6-7
LH 1-2 7-8
2-3 7-8
3-4
8-9 8-9
4-5
5-6 LH 1-3
LH 1-2
6-7 2-3
7-8 3-5
3-4
L Hp 1-2
2-3 5-6 4-5
3-4
5-6
4-5 6-7
5-6 6-7
6-7 7-8
7-8
7-8
8-9 8-9 8-9
R Am 1-2 L Hp 1-2
R Am 1-3
2-3
2-3
3-4
3-5
4-5 3-4
5-6
5-6 4-5
6-7
7-8 5-6
6-7
RH 1-2 6-7
2-3 7-8
3-4 7-8
4-5 8-9
8-9
5-6
6-7 RH 1-3
R Am 1-2
7-8 2-3
8-9 3-5
3-4
R Hp 1-2
2-3 5-6 4-5
3-4
5-6
4-5 6-7
5-6 6-7
6-7 7-8
7-8
7-8
8-9 8-9 8-9
1s
Figure 14.17: Examples of SEEG interictal patterns of the irritative zone. A: Mesiotemporal spikes with posi-
tive polarity: one limited at LH1–2 (left hippocampus), no volume conduction, and not seen in the surface
contacts; and another recorded simultaneously from right amygdala (RAm) and hippocampus (RH, RHp), with
some propagation outside the mesial temporal lobe. B: Right hippocampal polyspikes and spikes with nega-
tive polarity. C: Left amygdala sharp discharges. D: Low-amplitude spikes recorded from the left entorhinal
cortex (Et’, arrows), and not seen in the amygdala (A’), anterior hippocampus (B’), posterior hippocampus (C’),
and parahippocampus (E’). E: Interictal train of spike-and-waves activity in the anterior temporal neocor-
tex (LAm 4–5 to 10–11 and LH 6–7 to 10–11). F: Isolated interictal spike-and-wave in the mid-post temporal
neocortex (LP 7–8 to 10–11).
D
A’
Et’
1s B’
C’
E’
E F
L Am 1-2 L Am 1-3
2-3
3-5
3-4
4-5 5-6
5-6 6-7
6-7
7-8
7-8
8-9 8-9
9-10 9-10
10-11
LH 1-3
LH 1-2
3-5
2-3
3-4 5-6
4-5 6-7
5-6
7-8
6-7
7-8 8-9
8-9 9-10
9-10
10-11
LP 1-3
R Am 1-2
3-5
2-3 5-6
3-4 6-7
4-5
7-8
5-6
6-7 8-9
7-8 9-10
8-9
10-11
9-10
10-11 RH 1-3
RH 1-2 3-5
2-3
5-6
3-4
4-5 6-7
5-6 7-8
6-7
8-9
7-8
8-9 9-10
9-10 10-11
10-11
Figure 14.17: (continued) 1s
423
brain and realize closed electrical fields with negligible volume conduction. Interictal epileptiform activity in extratemporal neocortical epilepsy also
Hence, and in spite of the high frequency of the discharges, the epileptic consists of potentials of variable morphology and distribution. It is usually
activity generated is usually not detected by cortical or scalp EEG electrodes present in frontal, central, parietal, occipital, or insular epilepsies and is
(151). In the amygdala, the interictal epileptiform anomalies are often sharp likely indicative of neocortical epileptogenesis. Again, however, interictal
waves with a triangular shape and of lower amplitude, and more difficult to epileptiform discharges often show a distribution and frequency (the Ir-
detect than the hippocampal spikes (Fig. 14.17C). This is explained by the ritative Zone) with a higher variability than in the scalp EEG, and they
intrinsic organization of the amygdala, where neurons are not aligned (as, do not necessarily correlate with the epileptogenic lesion or seizure-onset
for instance, the pyramidal cells of the hippocampus) and less likely to gen- zone (148,150,152). From a surgical perspective, it would probably be a
erate high-amplitude synchronized postsynaptic potentials (70). In TLE, the mistake to ignore the extent of interictal spikes, whether they are focal or
mesial temporal potentials (in the hippocampal formation and amygdala) not; they can provide additional confirmation of localization, and often
are much more frequent than in the neocortex; they are often associated with may be a marker of the extent of the epileptogenic tissue. This seems to be
polymorphic slow wave anomalies or abnormal background and with a focal the case, for instance, in focal cortical dysplasia type II, where a peculiar
reduction or loss of fast beta activity, indicating local neuronal destructive SEEG pattern (almost total absence of background activity and charac-
process or dysfunction. They are also often found independently in both teristic repetitive, high-amplitude fast spikes followed by high-amplitude
mesial temporal structures, and are frequently present even in extratemporal slow waves interspersed with relatively flat periods) is often observed (139)
lobe epilepsy. Neocortical temporal discharges are much less abundant even (Fig. 14.18). Similar patterns have been described with subdural and epi-
in cases of neocortical TLE, but they represent the electrical correlate of the dural (and sometimes also from the scalp) EEG recordings (153,154). Also,
spikes or sharp discharges seen in the scalp EEG (Fig. 14.17E, F). particular attention must be paid to those spikes that do not disappear at
A
400 uV (*250 uv- **1200 uV)
1s
(0.530-120 Hz band-pass filter)
*
*
Figure 14.18: Examples of interictal patterns in

type 2 focal cortical dysplasia (FCD2). A: Con-
tinuous or near-continuous interictal spikes
(*) well-localized in a rolandic FCD2 (circle).
B: Typical subcontinuous paroxystic SEEG pat-
tern of a FCD2 located in the frontal eye-field
(*M 5–6; same patient as in Figs. 14.4B, 14.22A,
and 14.23).
B
M Y1-2
Y8-9
R2-3
R6-7
G1-2
H1-2
E2-3
F1-2
W1-2
M W7-8
Z1-2
Z8-9
X1-2
X8-9
M1-2
* M5-6
G14-15
H13-14
E7-8
F7-8
E13-14
M 5-6 F12-13
M11-12
B1-2
J1-2
B13-14
J14-15
Figure 14.18: (continued) S7-8
the seizure onset; this suggests that these spikes do not depend on a com- contains the “minimal” amount of cortex necessary to generate the first
mon pathophysiological process related to the area(s) from where seizures clinical symptoms, or the area in which arises the first EEG change prior
arise and, therefore, that they might be part of another Potential Seizure- to or concomitant with the clinical onset of the seizure. The first defini-
Onset Zone (155). tion is electroclinical and overlaps with the Symptomatogenic Zone, that is,
Recently, interictal HFOs ranging from 80 to 500 Hz have been identified the area of cortex that when activated produces the initial ictal symptoms
as a putative marker of the epileptogenic brain tissue (156). HFOs can be re- or signs (149). The second definition is electrophysiological and encom-
corded in epileptic humans using macroelectrode contacts (Fig. 14.19), pref- passes subclinical (also described as asymptomatic or pure EEG seizures)
erentially during slow-wave sleep, during which the rate tends to increase. and clinical seizures. Subclinical seizures are ictal discharges without any
They may occur at the time or independently of interictal spikes, increase clinical accompaniment; this definition is subjective and highly dependent
during medication reduction but not after the seizures, and can have the on the mode of observation, that is, the presence and type of questioning
same spectral characteristics and spatial extent as fast activities at seizure (Fig. 14.20). Also, the occurrence of symptoms varies according to the
onset. They can be recorded in mesiotemporal lobe or neocortical epilepsies localization of the discharge and its electrographic pattern; this is notably
and do not seem specific to a particular type of epileptogenic lesion. They true in TLE, in which an ictal discharge can happen and remains confined
might therefore represent epileptogenicity per se, in line with the finding that to the amygdala or to the hippocampus without subjective or objective
surgical removal of HFOs generating tissue seems to correlate with a good clinical manifestations (72). Sperling and O’Connor (157) suggested that
postoperative outcome. at least in TLE, those subclinical or asymptomatic seizures recorded with
intracerebral electrodes and originating from the same structures and with
Seizures Onset (Seizure-Onset Zone) and Propagation the same morphology as the habitual electroclinical seizures have a high
localizing and prognostic significance. They concluded that their presence
The Seizure-Onset Zone (SOZ) is a concept that refers to the “area of cor- indicates a good localization of the SOZ and, also, functional inhibitory
tex that initiates clinical seizures” (149): it can be defined as the area that mechanisms.
A B
RPs 1-2
2-3
3-4
4-5
5-6
6-7
7-8
8-9
RLa 1-2
2-3
3-4
4-5
5-6
6-7
7-8
8-9
RLp 1-2
2-3
3-4
4-5
5-6
6-7
7-8
8-9
1s
High-pass 80Hz High-pass 250Hz
0.1s 0.1s
Figure 14.19: HFOs. A: interictal HFOs: ripples outside spikes (RH 1–2, 2–3). B: ripple and fast ripple bands at
the onset of a typical seizure (focal cortical dysplasia in the right precuneus, RLa and RLp).
The adequacy of the SEEG assessment of the SOZ depends on an a dequate a fast synchronizing discharge. The coincidence of these two criteria indicates
spatial sampling of the cortical structures responsible for the s eizure origin that the positioning of at least one or some electrodes is correct. Conversely,
and propagation. With this in mind, the first clear ictal electrical changes the absence of one of these two criteria suggests that the clinical assumption
recorded are likely to be highly localizing, provided that these changes occur is possibly wrong and that the electrodes are not adequately sampling the real
prior to the first unequivocal clinical manifestations and that they consist of SOZ but only the propagated discharge. Another criterion to consider is the
Am
Hc
Figure 14.20: A right mesial temporal SEEG

subclinical seizure starts in the hippocampus
with periodic high-amplitude spikes (Hc, 1st ar-
row) and involves, after few seconds, the amyg-
dala (Am, 2d arrow) without further propagation. 1s
extension of the EEG changes at the onset of a seizure; focal changes limited of intracerebral depth electrodes), the host (children versus adults),
to few contiguous recording contacts are more likely to indicate the exact and probably the type, amount, and withdrawal pattern of antiepileptic
SOZ than a nonfocal regional or even more diffuse onset (158,159). medication. Examples of ictal intracerebral EEG recordings with typical
Intracerebral ictal onsets have classically been described as a low- onset, propagation, and termination patterns for temporal and extratem-
voltage fast activity, in the beta and gamma bands (146,159,160), or poral seizures are found in Figs. 14.21 and 14.22.
as recruiting and periodic fast discharge of spikes (161–163). The dif-
ferent seizure-onset morphologies (Table 14.5) likely reflect a variety
TABLE 14.5 Intracerebral Depth Electrode Ictal-Onset Patterns
of interictal to ictal EEG transition mechanisms in different structures
in Temporal and Extratemporal Lobe Epilepsy
(e.g., mesial temporal lobe structures versus neocortex, temporal lobe
versus extratemporal lobe) and in different pathological conditions (e.g., 1. Low-voltage fast activity in the beta (13–30 Hz) and gamma (>30 Hz)
normal tissue versus mesial temporal sclerosis versus developmental frequency ranges.
cortical lesions such as focal cortical dysplasia versus atrophic/gliotic 2. Periodic and rhythmic high-amplitude spiking activity (1–5 Hz), followed
lesions). Hence, the two main factors that determined the ictal intrace- by low-voltage, fast activity pattern.
rebral EEG onset (and probably also the propagation patterns) are the 3. Spike-and-wave activity (>2 Hz).
affected lobe or brain structure and the underlying structural abnormal- 4. Rhythmic polyspike activity (>13 Hz).
5. Rhythmic sharp activity (<13 Hz).
ity. Other variables that can modulate these patterns are the type and
6. Rhythmic sinusoidal pattern in the alpha-theta ranges (5–9 Hz).
position of the recording electrodes and contacts (already discussed in 7. Irregular, semi-rhythmic slow-wave activity (<5 Hz).
sections on advantages and drawbacks and on risks and complications
Orbito-frontal cortex
Suprasylvia Operculum
Anterior Insula
Posterior Insula
1st temporal gyrus

2d temporal gyrus
3rd temporal gyrus Seizure onset
Temporal pole
Amygdala
Anterior Hippocampus *
Posterior hippocampus *
Hippocampal gyrus
Enthorhinal cortex
800 uV (* 1200 uV)

A
1s (0.530–120 Hz band-pass filter)
Insular spread
Figure 14.21: Ictal onsets (focal or regional) and propagation patterns in temporal lobe seizures. A: Typical
hypersynchronous focal onset beginning with low-frequency periodic high-amplitude spikes well-localized in
the hippocampus (and, to a lesser degree, in the amygdala); note in the same structures, the fast rhythms and
polyspikes just before the propagation of the discharge to the insular cortex—the patient at this moment warns
428 that a seizure is coming (same patient as in Fig. 14.4a).
LTP
LA
LT2
LHc
LT2
B 1s
RHc
RIns
LOF
LIns
LT1
Figure 14.21: (continued) B: A 40-year-old patient with left hippocampal sclerosis. The seizure starts with a
low-voltage fast activity first seen in the left amygdala (LA). The discharge then rapidly involves the temporal
pole (LTP) and hippocampus (LHc) before propagating to the second (LT2) and first (LT1) temporal convolu-
tions, then to the right hippocampus (RHc), left insular cortex (LIns), R insular cortex (RIns), and left orbitofron-
tal cortex (LOF). C: Regional temporal lobe onset in a 35-year-old patient with temporal pole atrophy. SEEG
seizure starts with a regional rhythmic 5- to 6-Hz activity which after 5 seconds is replaced by a fast polyspikes
discharge recorded from the hippocampus (LH and LHp), and a late insula (LIp) involvement.
C
Amygdala 1-2
2-3
5-6
8-9
Hippocampus 1-2
2-3
5-6
7-8
8-9
Post. Hippocampus 1-2
2-3
6-7
8-9
Temporal pole 1-2
2-3
4-5
6-7
Isthmus (post. cing.) 1-2
2-3
Orbito-frontal 1-2
2-3
Ant. cingulate 1-2
3-4
6-7
Seizure onset
8-9
parahippocampus post. 1-2
2-3
5-6
7-8
Insula 1-2
2-3
3-4
4-5
500µV
1s
There is still no established electrophysiological criteria to identify un- Resection of brain regions exhibiting such fast activity seems to predict sur-
equivocally the SOZ, and, moreover, the pattern and frequency of the re- gical outcome, therefore emphasizing their interest for defining the SOZ.
cruiting fast activity (the most consistent ictal-onset pattern seen in depth Following this, the concept of Epileptogenicity Index has recently been pro-
electrodes) differ in the mesial temporal lobe structures compared to the posed where spectral (12.4 to 97 Hz) and temporal information are mixed
neocortex and from one cortical region to another (158,164–166). Advances together, to quantify directly and unambiguously the implication of each
in signal analysis techniques now allow more objective measurements of the cortical site in the onset and early propagation of epileptic seizures (167).
SOZ. Increasing evidences suggest that seizures start with fast activities, typ- Yet, another quantification approach has been proposed utilizing neuroim-
ically in the beta and gamma bands, but sometimes as fast as 400 Hz (158). aging in order to generate statistical parametric maps of the epileptogenicity
A Ins
B8 M7 F9
E7
H10
mesial F-C
E7
F9
M7
B8
H10
7
M
lateral F-C
600 uV
R
1s
1
B 2
3
4
5
6
7
Figure 14.22: Ictal onsets (focal, regional, or 8
multilobar) and propagation patterns in neo- 9
cortical seizures. A: Low-voltage fast discharge 10
11
very well-localized over the right frontal eye- 12
field (electrode M7; same patient as in Figs.
13
14.4B, 14.18B, and 14.23). B: Regional onset in 14 *
the mesial premotor (channels 2 to 8) and motor 15
(channel 9) cortex in a 22-year-old patient with 16
17
a normal MRI. Note the very fast-but transient- 18
involvement of the insular cortex (mainly chan- 19
20
nels 23 and 24). Typical seizures consisted of a 21 **
tingling sensation and tonic contraction of the 22 **
right leg. C: Multilobar ictal onset in temporal 23
24
lobe (AM, Hc, and Hp), insula (Ins), and parietal 25 ***
lobe (Ps and Pi) in a patient with a diffuse right 600 uV (* 250 uV - ** 500 uV - *** 200 uV )
Clinical onset
hemispheric polymicrogyria. 1s (5.30-120 Hz band-pass filter)
C
Am 1-2
4-6
7-8
Hc 1-2
4-6
7-8
Hp 1-2
3-4
5-6
7-8
Cing 1-2
3-4
5-6
7-8
Ins (sup) 3-4

6-7
Ins (ant) 2-3

5-6
7-8
Ins ( inf ) 1-2

3-4
5-6
7-8
Ins (post) 1-2

3-4
5-6
7-8
Ps 1-2
4-6
7-8
Pi 1-2
3-4
4-5
6-8
Seizure onset 1s

A as speech, to imitate the effect of spontaneous epileptiform discharges, to

reveal neuroanatomical pathways, or to search for low-threshold areas—for
a review, see David and colleagues (170) and Lüders and Noachtar (171).
The modulatory effects of electrical stimulation on cortical activity, although
not well understood, depend on a variety of factors that include the intensity
of the stimulation (expressed in amperage or voltage); the frequency of the
stimulation—both low- (around 1 Hz) and high-frequency stimuli (around
50 Hz and over) can produce inhibitory or excitatory responses; the pulse
width; and the duration of the stimulation (short or long trains). The threshold
B
for neuronal excitability is another important modulatory factor, and depends
on the intrinsic neuronal activity (variable from a cortical area to another) and
the presence or not of an epileptogenic cortical environment that may facili-
tate the neuronal response and the propagation of the electrical discharge.
Acute electrical stimulation through intracranial depth EEG electrodes is
performed in the epileptic patients for two main reasons: (a) the first is to
right study evoked clinical responses mimicking the effect of spontaneous epileptic
discharges on cortex and reproducing patient’s aura or typical spontaneous
Figure 14.23: Epileptogenicity map. Same patient as in Figs. 14.4B, 14.18B, and seizures (4,172–176). Neurostimulation may also help to define epilepto-
14.22A. A: White indicates the highest value of activation in the 60- to 100-Hz genic regions by comparing afterdischarge thresholds in different cortical
frequency band at seizure onset. B: The extent of the cortical resection (patient areas (177); (b) the second is to study eloquent cortical areas and map, for
is seizure-free) closely matches the epileptogenicity map findings. instance, complex cortical functions such as language and sensory or motor
activities. The electrical stimulation defines the functional areas and assists
index, named epileptogenicity maps (168). The method is based on spectral in tailoring the surgery. Cortical electrodes and, particularly, subdural grids
analysis of fast activities ranging from 60 to 100 Hz at seizure onset, and are more suitable for functional mapping because they are made of arrays of
the significantly activated electrodes (compared to a baseline) are reported adjacent contacts placed over large cortical areas. Intracerebral depth elec-
on patient’s MRI to provide a 3D anatomical map of the seizure onset and trodes are not well adapted for this purpose for the simple reason that they
discharge propagation (Fig. 14.23). Statistics can be performed at the group are few leads in direct contact with the neocortex and comparison from one
level between seizures in the same patient or between patients suffering adjacent cortical area to the other is more difficult. They access, however,
from the same type of epilepsy using normalization of brains to a com- deep brain structures and can be used for activation procedures involving
mon anatomical atlas. The epileptogenicity maps can also be superimposed structures such as the mesial temporal lobe (4) and the insula (75,78). Also,
with other neuroimaging modalities in the same neuroanatomical space for they may help for defining the trajectory of white matter tracts (e.g., corti-
multimodal exploration of epilepsies. cospinal tract and arcuate fasciculus) (170).
Electrical stimulation is performed over 1, 2, or a few days under con-
Electrical Stimulation tinuous video-EEG monitoring during sessions that may last from 1 to few
hours (in some laboratories neurostimulation takes place early during the
Animal and clinical studies demonstrate that electrical stimulation of brain investigation, in others at any time, and in still others at the end of the in-
structures can reduce seizure frequency in patients with refractory epilepsy— tracranial investigation and when antiepileptic medication has been reintro-
for a review, see Saillet and colleagues (169). Electrical stimulation of the duced). The procedure can be tedious and patients often become tired and
cortex can also reproduce activation of the cortex in normal or pathologi- easily distracted when sessions are too long. During a typical stimulation
cal conditions, and is therefore used to study normal cortical functions such session, trains of a biphasic square-wave (alternating polarity) stimulus at
low (1 to 10 Hz; pulse width, 1 to 3 milliseconds per phase; trains’ duration, at low frequency and the second at high frequency. In other centers, only
30 to 40 seconds) or high frequency (50 to 60 Hz; pulse width, 100 microsec- high-frequency stimulation protocol is performed.
onds to 1 millisecond per phase; trains’ duration, 3 to 5 seconds) are applied The procedure of stimulation must take into account the objectives
between contiguous electrode contacts (bipolar stimulation) at various lev- of the study: (a) to evoke an aura or a typical electroclinical seizure; or
els of the electrode axis, and with stepwise increasing intensities until clinical (b) the localization of eloquent cortical areas. The type of stimulation
subjective or objective responses or afterdischarges are obtained. Bipolar (low or high frequency), the duration of the trains, and the current in-
stimuli are delivered using a constant current rectangular pulse generator tensity (0.2 to 8.0 mA) will vary depending on the level of cortical ex-
designed for a safe diagnostic stimulation of the human brain and accord- citability and the degree of the clinical manifestations expected by
ing to parameters proven to produce no structural damage (62). Stimulus stimulating a given structure. For instance, 50- to 60-Hz stimulations are
intensity varies according to the cortex studied: in the temporal lobe, cur- most frequently used to reproduce patients’ seizures (175), but 1-Hz stim-
rent intensities are typically in the range of 0.2 to 3.6 mA, while outside the ulation can be applied as it allows a better visualization of the EEG re-
temporal lobe, the range is from 0.2 to 8 mA. In some centers, stimulation cording at the onset of the induced discharge and during the stimulation
protocols systematically involve at least 2 days stimulation sessions, the first itself, though with a more uncertain effectiveness (177) (Fig. 14.24). For
A Biphasic square wave 1 Hz stimulus
B Biphasic square wave 50 Hz stimulus 15s

ES (5s) AD Post-excitatory depression
Figure 14.24: Low- (1 Hz) and high-frequency

(50 Hz) electrical stimulations (ES) applied within
a focal cortical dysplasia (same patient as in
Fig. 14.6b). An electroclinical seizure (AD) was
elicited at 50-Hz stimulation (B) but not at 1-Hz
stimulation (A); electrode R F2 (post. lesion)
channels 1–2, 2–3, 3–4, and 4–5. There was also a
transitory post-excitatory depression at the end
of the electrically-induced seizure.
functional mapping purposes, 1-Hz stimulation is preferred when study- is particularly true for language areas. In the primary sensory and motor
ing the motor cortex to avoid unpleasant sustained tonic motor signs. cortices, however, stimulation studies can be conducted along the axis of
In visual, sensory, auditory, language, and insular cortices, 50- to 60-Hz intracerebral electrode(s) placed in the vicinity of the rolandic fissure and
stimulation is applied cautiously, starting at low intensity (<1 mA) to of the motor and sensory pathways. These functionally eloquent structures
avoid disabling responses or sensations, and looking for stimuli that do can be embedded in a lesional process and their identification is essential to
not evoke afterdischarges. The duration of the stimulation (30 to 40 sec- ascertain the risks of a functional deficit.
onds for 1-Hz stimulations, and 3 to 5 seconds for 50-Hz stimulations)
can be shortened depending on the type of the induced manifestations;
they tend to increase progressively or build up during a train of stimuli SEEG-guided radiofrequency
(178). Finally, further adjustments of the current intensity may be per- thermocoagulation
formed in order to define the threshold that will give rise to clinical re-
sponses (without or with afterdischarges). Developed more than 30 years ago, the technique of stereotactic ra-
This type of stimulation protocol permits a fair degree of selectivity of diofrequency thermocoagulation (RFTC) lesioning has been recently
the response with a high degree of localization since the stimulus is delivered reassessed and applied during SEEG evaluations of patients in whom
in bipolar mode through adjacent contacts only 2 to 5 mm away from each conventional resective surgery for a variety of reasons could not be pro-
other (center to center). Such a bipolar stimulation is effective in producing posed (180,181). In the largest series published up to now (181), 20 out of
localized current flows, inasmuch as the stimulated contacts are not located 41 patients (49%) showed at least a 50% decrease in seizure frequency, and
on the pia-arachnoid but inside the cortex, to avoid shunting of the current one became seizure-free. No factor was significantly associated with the
(“a leak”) through the CSF (179), and also pain. This stimulation procedure outcome, but the best results were found in patients with a cortical devel-
of small cortical areas may give complementary data to those provided by opment malformation (67% of responders in this group of 20 patients).
the spontaneous seizures: for instance, by comparing, in adjacent or remote Three transient postprocedure side effects, consisting of paresthetic sen-
areas, the threshold levels for afterdischarges, adding further information sations in the mouth (2 cases) and mild apraxia of the hand (1 case), were
about the epileptogenic network; it can also allow to measure and to de- observed. RFTC could be an alternative option to resective surgery in a
termine the localizing value of various clinical ictal phenomena by creat- few well-selected cases in whom the ictal-onset zone is very restricted in
ing conditions that mimic the effects of a spontaneous focal paroxysmal space (182). The procedure could also be useful in well-localized but deep
discharge. Elicitation of auras, for instance, may be helpful to identify areas lesions such as periventricular nodular heterotopia (183) and hypotha-
essential for building up ictal clinical signs, when aura have disappeared dur- lamic hamartoma (184,185).
ing the course of the disease or manifest only occasionally and have not Guénot and colleagues (181) applied RFTC in the cortical areas show-
been documented spontaneously. Electrically evoked auras, however, can re- ing either a low-voltage fast activity or spike-wave discharges at seizure
sult from the activation of cortical and subcortical regions remote from the onset, but did not consider interictal epileptic activity for planning ther-
stimulation site, and caution is required in the interpretation of these find- mocoagulation lesions. All targets were first functionally evaluated us-
ings, particularly when a local ictal discharge has not been concomitantly ing electrical stimulation, and only those showing no clinical response
elicited (38) or when the same aura can be elicited from distant cortical brain to stimulation were selected for thermolesion. A total of 2 to 31 lesions
regions. Hence, even if we usually assume that triggering habitual auras or were performed in each of the 41 patients of their series. RFTC was per-
seizures by cortical stimulation indicates the location of the epileptic focus, formed without anesthesia at the end the SEEG procedure, before elec-
one has to be aware that this relationship is not strictly predictive from one trode removal; they used a 120-mA bipolar current (50 V) applied for
patient to the other. 10 to 30 seconds, each thermocoagulation causing a 5- to 7-mm-diameter
Finally, as already mentioned, the cortical surface that can be stimulated lesion (Fig. 14.25). SEEG-guided RFTC of epileptic foci appears to be a
by depth electrode leads is restricted, making difficult, but not impossible, safe therapeutic alternative for patients with drug-resistant nonoperable
to perform precise functional mapping, as with subdural electrodes. This partial epilepsies.
Pre-RFTC
Pre-RFTC
Post-RFTC
Post-RFTC Figure 14.25: Stereotactic radiofrequency

thermocoagulation (RFTC). Continuous spiking
activity is recorded over a few contacts within
L
the right posterior insular cortex (Pre-RFTC).
Disappearance of all the spikes post-RFTC in the
contacts that exhibited spikes before treatment.
Same patient as in Figs. 14.13 and 14.16B.
Conclusion electrodes EEG remains a gold standard to which other noninvasive meth-
ods still need to be compared to establish their specificity and accuracy and
Intracerebral depth electrode EEG, or stereoencephalography, is a remark- fields of usefulness. Also, the method is well adapted, and adaptable, to study
able tool to study directly brain neurophysiology. In spite of some drawbacks, in vivo mechanisms of epileptogenesis; the recent explosion of interests for
the invasiveness and risk for complications, the burden for the patients, fami- the HFOs is a good example. Invasive EEG is classically considered for epi-
lies, and treating teams, and the costs for the communities, this intracerebral leptic patients showing conflicting results during presurgical evaluations;
EEG method adequately applied provides precise and privilege information there is a need for better selection criteria to determine in which patients
on the epileptic focus and the networks involved during the generation and invasive EEG is indicated and in which patients it is not. Also, further stud-
propagation of the epileptic discharge. For this reason, intracerebral depth ies are needed to compare the yields of intracerebral depth electrodes EEG
and SEEG versus the other invasive EEG methods in temporal and extra- 10. Jerbi K, Ossandon T, Hamame CM, et al. Task-related gamma-band dynamics from an
intracerebral perspective: review and implications for surface EEG and MEG. Hum Brain
temporal lobe epilepsies, lesional or nonlesional, and to determine if one Mapp 2009;30:1758–1771.
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15 Evoked Potentials Overview
AATIF M. HUSAIN
Basics of Evoked Potentials Brainstem Auditory Evoked Potentials

Naming Convention Anatomy and Waveform Generators
Waveforms Methodology
Stimulation Interpretation
Recording Abnormalities
Interpretation Pediatric Considerations
Normative Data Clinical Correlations
Abnormalities Latency/Intensity Series
Visual Evoked Potentials Somatosensory Evoked Potentials
Anatomy and Waveform Generators Anatomy and Waveform Generators
Pattern Reversal Visual Evoked Potentials Methodology
Flash Visual Evoked Potentials Interpretation
Pediatric Considerations Abnormalities
Clinical Correlations Pediatric Considerations
Clinical Correlations
References
Evoked potentials (EP) are a unique type of neurophysiologic test in which a testing the functional integrity or physiology of that pathway. This is in distinc-
response to a stimulus is analyzed. Any stimulus can be used to generate an tion to magnetic resonance imaging (MRI) in which the anatomical structure of
impulse, which is transmitted through a neural pathway and is recorded as an the pathways is evaluated. In clinical medicine, three types of EP are routinely
evoked potential at a distance from which the stimulus is applied. This allows for used, visual (VEP), brainstem auditory (BAEP), and somatosensory (SEP).
442
Evoked Potentials Overview 443
Over the last 20 years, the use of EP has evolved. Prior to MRI becoming convention about negative potentials being displayed upward, EP have
widely available, EP were the mainstay of not only physiological, but also no such conventional display. Whether negative potentials are displayed
anatomical assessment of the nervous system, as better methods of the latter upward or downward is according to preference of the laboratory. Because
were not available. With MRI, anatomical assessment of the nervous system of this lack of standardization, the display should clearly note the polarity
can be done well; however, evaluation of the functional integrity of various convention used.
pathways remains problematic with neuroimaging. EP continue to be used EP waveforms are of low amplitude and sometimes difficult to obtain
when the functional impairment of these pathways is suspected but cannot despite optimal technique. Certain waveforms, however, are designated as
be confirmed with neuroimaging. Other uses for EP have emerged as well, “obligate” waveforms. This implies that absence of these waveforms is an
the foremost being neurophysiologic intraoperative monitoring (NIOM). In abnormality. Other waveforms that are not obligate may be absent, yet the
this chapter, basic principles of EP will be discussed, followed by a review of study may still be considered normal. Obligate waveforms for each modality
the VEP, BAEP, and SEP. are noted in the discussion on that modality.
Basics of Evoked Potentials Waveforms

EP can be produced by many types of stimuli. In the routine EP labora- Each EP has multiple waveforms. These waveforms are produced by various
tory, however, sensory stimuli are used to obtain EP. The visual system can neural structures along the pathway being evaluated. A waveform is typi-
be stimulated with either flashes of light (flash VEP, FVEP) or a patterned cally produced when an impulse travels along a fiber tract or passes through
stimulus (pattern reversal VEP, PRVEP). Various types of sounds can be a synapse (1). If a fiber tract abruptly changes direction, that can create a
used to stimulate the auditory system to produce auditory EP (AEP). AEP waveform as well. It is tempting to think that each waveform has a single
that occur within 10 milliseconds of stimulation are called brainstem audi- generator; however, it is likely that multiple neural structures contribute to
tory EP (BAEP), whereas those occurring after 50 milliseconds are referred each waveform, and one neural structure may contribute to more than one
to as long-latency AEP. Middle-latency AEP are between the BAEP and the waveform (2). Despite this, various nuclei and fiber tracts are associated
long-latency AEP. BAEP are the most reproducible and used clinically. Fur- with various waveforms to aid with localization and interpretation.
ther discussion of AEP will focus on BAEP. Peripheral nerves are stimulated The various waveforms recorded for each EP can be thought of as near-
with an electrical stimulus to produce SEP. Almost any nerve can be stimu- or far-field potentials. Near-field potentials are those for which the active
lated electrically to produce a SEP; however, most often, it is the median, recording electrode is placed on or very close to the generator site. The
ulnar, tibial, and peroneal nerves that are used. reference recording electrode is placed at a distance where the potential of
interest is not present. Near-field waveforms can be recorded only from gen-
Naming Convention erators that are close to the surface so that an electrode can be placed in
close proximity. Consequently, they are very sensitive to recording electrode
EP are a series of waveforms that are generated by various neural structures placement; minor changes in position of the recording electrode can change
in response to a stimulus. These waveforms are named according to their the amplitude and morphology of these waveforms dramatically. These
polarity and typical latency or sequential number in which they appear. VEP potentials are of higher amplitude than far-field potentials. Far-field poten-
and SEP waveforms are named according to the polarity/latency method. tials are recorded at a distance from their site of generation. The amplitude
Thus the P100 of the VEP is a positive waveform that typically occurs at and morphology of these waveforms do not change with slight changes in
100 milliseconds, while the N34 is a negative waveform that occurs approxi- recording electrode location. They are typically of lower amplitude than
mately 34 milliseconds after tibial nerve stimulation. BAEP waveforms I–V near-field potentials. BAEP and SEP contain both near- and far-field poten-
are labeled according to the order in which they appear. tials, while VEP contain only near-field potentials.
Negative and positive polarity waveforms are recorded in all types Waveforms can also be thought of as cortical, subcortical, spinal, or
of EP. Unlike in other types of neurophysiologic tests, which have a peripheral. As their name implies, they are generated from the respective
areas of the nervous system. Cortical waveforms are near-field potentials for BAEP. The typical rate of stimulation for BAEP is between 10 and 50 per
that are generated by cortical synaptic activity and thalamocortical projec- second, depending on the application (maximum would be 66.6 per second
tions. Subcortical waveforms are far-field potentials that are usually of low [1,000 milliseconds/15 milliseconds]).
amplitude and generated by various nuclei and fiber tracts. Spinal wave- As implied by the stimulation rate, each stimulus must be delivered repeat-
forms are near-field potentials generated by ascending volleys in the spinal edly and averaged to produce a recognizable EP (see later for discussion on
cord. Peripheral waveforms are also near-field potentials that are recorded averaging). The number of repetitions of the stimulus needed to produce a
from peripheral nerves. reliable and reproducible EP is inversely proportional to the amplitude of
the response and directly proportional to the noise. Increasing the stimu-
Stimulation lation intensity and duration can increase the amplitude of the response
within limits. Similarly, relaxing the patient and adhering to optimal techni-
The stimulation methodology varies depending on the type of EP being cal standards reduces the noise. Both of these will result in the need for fewer
obtained. There are some basic principles that are universal. Regardless repetitions. Once a waveform is obtained, it must be replicated to confirm
of how the stimulus for the EP is presented (visual, auditory, or somato- that all waveforms are reproducible. Every EP should be replicated at least
sensory), its parameters can be adjusted. Stimulation intensity is adjusted once. Repetitions should not be confused with replication.
to optimize the response being recorded. The amplitude of the response
increases as the intensity increases, though not linearly. This is because of Recording
“central amplification” (3). This refers to a greater number of central com-
pared with peripheral nerve fibers activated for each incremental increase As with stimulation, recording parameters vary with the EP modality. Basic
in intensity. Thus, all central fibers will be activated before all peripheral principles will be reviewed here. Though various types of electrodes can be
fibers, and cortical and subcortical waveforms will reach maximum ampli- used to record EP, most often surface or cup electrodes are used. These are
tude before peripheral waveforms. Stimulus duration refers to the time inter- the same types of electrodes that are used for recording electroencepha-
val for which each stimulus that is applied to the end organ. The longer this lograms (EEGs). They are usually applied with electrode paste, though at
time, the greater the degree of stimulation. This will also increase the ampli- times collodion can also be used. Rarely, needle electrodes can be used, but
tude of the response and is also subject to central amplification. these are invasive and painful for awake patients. At times, needle electrodes
The number of stimuli delivered per second is the stimulation rate. The are used in comatose patients in whom EP are being done to evaluate prog-
rate should not be an integer of 60 (50 in Europe) as that will make elimina- nosis. The placement of the recording electrodes depends on the type of EP
tion of electrical line artifact very difficult. Typically, the slower the rate of being performed. Interelectrode impedances should be matched and below
stimulation, the better the morphology, the higher the amplitude, and the 5,000 Ω (4).
shorter the latency of the waveform. However, the slower the rate of stimula- The amplifier is one of the most important parts of the recording system
tion, the longer it takes to obtain the EP. For each type of EP, a compromise for all neurophysiologic signals. It has many components, and one of the
rate is used, which produces reliable and reproducible waveforms without most important is the differential amplifier. The differential amplifier has
taking too much time. The rate of stimulation also depends on the typical two main inputs (G1 or active and G2 or reference) and one output that
latency of the waveforms being recorded. For VEP, the waveform of interest displays the difference between the two inputs. A third input is the ground.
is the P100, which occurs about 100 milliseconds after stimulation. Typically, Because the differential amplifier output shows the difference between the
the recording time after stimulation, or the “analysis time,” should be at two inputs, signal that is present in both inputs will be cancelled out. This is
least two times the last waveform of interest. Thus for VEP, the analysis time referred to as “common mode” signal. Signal present in only one input will
is at least 200 milliseconds, and stimulation rate is 1 to 2 per second (maxi- be displayed in the output. The ability of a differential amplifier to reject
mum would be 5 per second [1,000 milliseconds / 200 milliseconds]). On the common mode activity is called the common mode rejection ratio (CMRR).
other hand, for BAEP, the last waveform of interest occurs 6 to 7 millisec- This is defined as “the ratio of the amplifier output produced by a signal
onds after stimulation. An analysis time of 15 milliseconds is appropriate applied differentially to amplifier output produced by the same signal when
applied in common mode” (1). The CMRR should be at least 10,000:1 at the are compared with normative data. Ideally, the normative data should be
highest sensitivity of the amplifier (4). If the electrode impedances are high obtained in the same laboratory in which clinical studies are conducted.
or mismatched, the amplifier’s CMRR will be reduced and more artifact will However, if published normative data are used, methodology used by the
be present in the recording. reference laboratory must be followed closely.
Because EP signals are of low amplitude, often smaller than background The first step in interpreting an EP study is identifying the waveforms of
noise, they must be averaged to obtain reliable responses (5). Averaging interest. These are often tagged automatically based on preprogramed algo-
involves adding all the recordings and dividing the result by the number of rithms. Additionally, the technologist labels waveforms and calculates vari-
stimuli. Since the EP is produced at a constant latency and has a constant ous measurements. When the study is normal, these measurements are often
shape while background noise is by definition random, averaging results correct, but with abnormal studies, they may be inaccurate. Verification of
in gradual cancellation of the noise and appearance of the EP. As noted waveforms is thus always the first step in interpretation.
earlier, the number of stimuli needed to average to obtain a reliable and Waveforms are easy to identify when they are normal, but when they are
reproducible waveform depends on the amplitude of the response and back- abnormal, it can be much more complicated. Each EP has its own set of cri-
ground noise. teria for the identification of waveforms, but a few general principles should
In addition to improving the amplitude of the signal of interest and be remembered. Presence of waveforms should be established first. Wave-
reducing the background noise, filters and artifact rejection can be used to forms of higher amplitude are easier to identify, and higher amplitude can
reduce the number of repetitions needed to obtain a reliable EP. Low- and be accomplished by increasing stimulation intensity and duration. This is
high-frequency filters (LFF, HFF) are used to eliminate waveforms below especially true for SEP. However, sometimes intensity may be increased too
and above the frequencies of interest. The LFF is set to reduce the ampli- much and extraneous waveforms may appear. This can happen with BAEP
tude of the frequencies below the lowest frequency of interest; the HFF when waveforms beyond wave V appear. At times, a different montage may
does the same for high frequencies. Additionally, the 60-Hz filter (50 Hz be necessary to elucidate a waveform that is difficult to identify or appears
in Europe) can be used to eliminate electrical line artifact. These analog morphologically different. This may occur with VEP when the P100 wave-
filters can introduce phase shifts in the waveforms and affect latencies. Con- form appears bifid, and a different montage (MO-Au vs. MO-MF) may
sequently, EP should be obtained with filter settings that are consistent with resolve the issue.
how the filters were set when normative data was acquired. Digital filters Latency measurements are the most important parameter measured in EP.
are also available on EP machines. Unlike analog filters, digital filters have These measures are compared with normative data. Two types of latency
a very sharp cutoff frequency below or beyond which they filter. In many measures are used, absolute latency and interpeak latency (IPL). The abso-
instances, they do not introduce phase shifts. A special type of digital filter- lute latency, also known as the peak latency, is the latency from stimulus
ing is called “smoothing.” In this, 3 to 5 consecutive data points are aver- onset to a peak of interest. This is the time taken for the impulse to travel
aged to create one data point. This helps eliminate noise and “smooth” out from the end organ stimulated to the presumed generator of the waveform
the waveform (1). Amplifiers also have an artifact rejection feature. This of interest. This measurement includes conduction not only in the cen-
recognizes activity that is greater than a particular amplitude and automati- tral nervous system (CNS) but also in a peripheral nerve before it reaches
cally “rejects” that response, preventing it from being averaged. By excluding the CNS. Because of this, absolute latency measurements are not used as
such outlying responses, the averaging becomes more efficient. The artifact much as IPL measurements. The SEP P37 waveform latency measurement
rejection feature is set to an amplitude that is several times higher than the is an absolute latency. IPL is the latency between two peaks of interest. By
expected amplitude of the waveform of interest. choosing two peaks that arise from the CNS, peripheral conduction can be
eliminated from measurement, and the IPL becomes a measure of central
Interpretation conduction. The BAEP wave III–V IPL and various SEP latencies such as
LP-P37 are IPL that measure central conduction.
Interpretation of EP involves analysis of the presence of waveforms, their Amplitudes of various EP waveforms are also measured and compared
latency, amplitude, and morphology. Numeric features of these waveforms with normative data as well. The same caveats about normative data noted
for latency apply to amplitude measurement as well. Two types of amplitude data. The upper and lower limits of normal are defined as 2.5 or 3 standard
measurements can be obtained. Peak-to-peak amplitude is calculated most deviations above and below the mean. Details of how normative data are
often. This is the difference in voltage between two successive peaks. For any obtained are presented elsewhere (4).
given peak, its amplitude can be measured relative to the peak before or after
it, that is, ascending or descending limb of peak can be measured. Regard- Abnormalities
less of how measurements are made, the same technique that was used to
obtain normative data should be used. Amplitude ratios can also be used. As noted previously, latency prolongation is the most significant EP abnor-
Here, the amplitude of one peak is compared with that of another peak. An mality. It implies a lesion in the pathway but is nonspecific for the type of
example of this is in BAEP in which the wave V amplitude is compared with lesion. Prolongation of absolute latency can be due to lesions in the end
wave I amplitude. Additionally, the VEP amplitude of the P100 waveform organ stimulated, peripheral nerves, or the central pathways. Only in VEP
obtained after stimulation of one eye can be compared with its counter- is just the absolute latency evaluated. IPL can provide an assessment of
part obtained after stimulating the other eye. Amplitude abnormalities do central conduction. They are used more often to detect CNS lesions. Some
not have the same significance as latency prolongations. When they are seen IPL include parts of the peripheral pathway as well. Examples of the latter
without latency abnormalities, they may be of uncertain clinical significance. include BAEP wave I–III IPL and the median SEP EP-P14 IPL. The former
Various other measurements are also obtained with EP. These are related evaluates the cochlea and the auditory nerve, whereas the latter evaluates
to the modality being tested. For example, for VEP, visual acuity (VA) is the brachial plexus, dorsal nerve root, and the part of the dorsal column
tested and noted. Hearing thresholds are noted for BAEP, and peripheral pathway up to the nucleus cuneatus.
nerve conduction velocities are noted for SEP. It should be remembered Amplitude reduction can be an abnormality as well. This is not consid-
that these parameters are not measured under optimal circumstances. For ered as significant as latency prolongation. Often the amplitude reduction
example, with SEP, supramaximal stimulation of the peripheral nerves is and latency prolongation occur together. When amplitude reduction occurs
not used, and all nerve fibers of the nerve may not have been stimulated. If without latency prolongation, its significance is uncertain. Amplitude ratios
an abnormality is suspected, more definitive testing should be performed. are also evaluated to compare various waveforms within one EP. Amplitude
There may be considerable variability of EP even when obtained in the reduction in its most severe form causes loss of waveforms. Depending on
same patient at different time points. When patients are more alert, the cor- which waveforms are absent, this can be a significant abnormality. If one of
tical responses are of higher amplitude (6). This is particularly important the obligate waveforms is absent, it is considered a significant abnormality.
in tibial SEP; the response from one side may be obtained with the patient Technical problems must be excluded before loss of waveform is interpreted
awake, and by the time the other side is tested, the patient may have fallen as an abnormality. This is particularly important if the first and all subse-
asleep. The amplitude of the first response may be considerably greater than quent waveforms of an EP are absent. In this situation, it becomes uncertain
the second. if the end organ was adequately stimulated. If technical problems or severe
disease of the end organ prevented adequate stimulation, latter waveforms
Normative Data and the remainder of the pathway cannot be evaluated.
The morphology of the waveforms is also evaluated. Bifid waveforms can
EP interpretation involves comparing various measurements with norma- sometimes imply an abnormality. However, unusual morphologies may be
tive data. As noted previously, ideally normative data should be obtained due to normal variations as well. The P37 waveform may appear to have
for each modality in every laboratory in which it is performed. This data is an unusual morphology. Because this waveform is thought to be generated
obtained by evaluating patients that are disease free. If the data is normally at the somatosensory cortex of the foot area near the vertex of the brain,
distributed (Gaussian), at least 20 individuals should be tested. If the data is the vector of the waveform may project ipsilaterally, contralaterally, or to
not normally distributed, a greater number of subjects will need to be tested. the midline, making the waveform highly variable between patients. If an
Both sexes should be included in testing when determining norms. Addi- unusual morphology is present without latency and amplitude abnormali-
tionally, extremes of ages may require separate determination of normative ties, interpretation of abnormality should be made with caution.
Once abnormalities are identified in an EP, localization of the lesion can Anatomy and Waveform Generators
be attempted. Often an exact site cannot be determined; rather, two sites
may be identified between which the lesion is likely. IPL prolongations are The visual pathway begins at the retina. Images are inverted on the retina
the most useful in identifying the site of abnormality. For example, if the as light crosses behind the lens. Thus, light from the temporal visual field is
BAEP waves III–V IPL is prolonged and the waves I–III IPL is normal, reflected on the nasal aspect of the retina, and light from the superior visual
a lesion in the upper brainstem is likely. Absence of an obligate waveform field is reflected on the inferior aspect of the retina. The retina contains two
can also aid in localization. An example is the absence of the median nerve types of photoreceptor cells, cones and rods. Cones detect color vision in
SEP N20 waveform. This is suggestive of a lesion of the hand somatosen- bright light, whereas rods function better in dim light. While rods are found
sory cortex contralateral to the side of stimulation. Various types of EP at the periphery of the retina, cones are concentrated toward the center.
can be combined to further localize abnormalities. Further localization of The posterior aspect of the retina is called the macula, and the center of
abnormalities will be discussed in the relevant discussions of the individual the macula is the fovea. The fovea has the highest concentration of cones
modalities. and is the area of highest VA. This area represents the central 3° of vision.
Cones and rods project to bipolar cells that project to ganglion cells. Axons
Visual Evoked Potentials of the ganglion cells make up the optic nerve. The retina and the optic nerve
are considered a part of the CNS, and the optic nerve is wrapped in a cen-
VEP are obtained after stimulation of the visual pathway. These responses tral myelin sheath. A disproportionately large number of fibers in the optic
are unique in that they are large-amplitude responses that can often be seen nerve arise from the macula, and consequently, the macula has a dispropor-
in an EEG without averaging. Also, unlike other types of EP that contain a tionately large representation in the visual cortex.
mixture of near- and far-field potentials, VEP contain only near-field corti- Optic nerve fibers are arranged according to their site of origin in the
cal potentials. retina. Fibers from the nasal retina are present medially, while those from
Classification of VEP is based on the method of stimulation used to produce the temporal retina are present more laterally. As the two optic nerves meet
the response. Most often, a checkerboard pattern is used in which the dark and at the optic chiasm, fibers from the nasal retina decussate to the other side,
light squares alternate locations, and this provides the visual stimulation. This while fibers from the lateral retina remain ipsilaterally. The contralateral
is known as a PRVEP and is sensitive to lesions in the visual pathway. This nasal retina fibers join with ipsilateral temporal retina fibers to create the
type of VEP is performed most often in patients who can cooperate with test- optic tract. Nerve fibers of the optic tract travel to and synapse in the lateral
ing, and reliable normative data is available. A strobe light can also be used geniculate nucleus. From there, the optic radiation projects to the occipital
to provide a stimulus for VEP, and the response obtained with this type of cortex. Fibers from the contralateral visual field project to the tip of the
stimulation is known as an FVEP. FVEP is insensitive for minor lesions and temporal horn of the lateral ventricle before projecting back to the occipi-
can detect only severe disruptions in the visual pathway. Interpretation is usu- tal cortex. This is known as the loop of Meyer. The optic radiation enters
ally simply as present or absent. the primary visual cortex in the occipital lobe. Almost one-third of the
PRVEP are further subdivided based on the field of stimulation used to area of the primary visual cortex is devoted to fibers from the fovea. The
obtain them. Each eye is tested separately, and typically the entire visual field area representing the fovea and macula wraps around the posterior aspect
(nasal and temporal halves) is stimulated simultaneously. This is known as of the occipital cortex and extends to the medial surface. Because of this
full-field stimulation and is most useful for detecting prechiasmatic lesions. medial projection, the VEP vector projects to the contralateral hemisphere.
The nasal and temporal half fields can be tested separately, and this is called However, there is considerable anatomic variability of the exact location of
hemifield stimulation. Hemifields can be tested one eye at a time, or congru- projection of the optic radiation fibers, and consequently, projection of the
ous hemifields of both eyes can be tested together (monocular or binocular VEP vector (7).
hemifields). Hemifield stimulation is used for detecting chiasmatic and post- The VEP has a single important waveform that is positive in polarity, has
chiasmatic lesions. Since these lesions can be detected with neuroimaging, an average latency of 100 milliseconds, and is known as the P100 waveform.
hemifield stimulation is now seldom performed. This waveform is preceded and followed by lower-amplitude negative peaks
at approximately 75 and 145 milliseconds, called the N75 and N145 wave- Patient cooperation is essential in obtaining a PRVEP. The patient must be
forms. All three of these waveforms are recorded from electrodes placed on alert and seated comfortably. VA should be measured and corrective lenses,
the occipital area of the scalp. An electrode on the frontal area records a if used, should be worn. The latency of the P100 waveform can be affected if
negative potential at 105 milliseconds called the N105. A recording deriva- VA is not corrected (Fig. 15.1). Each eye is successively stimulated, while the
tion linking these occipital and frontal electrodes may produce a higher- other eye is covered to obtain a full-field PRVEP. The patient is instructed to
amplitude P100 waveform as it will take advantage of not only the positive look at the center of the stimulus. The technologist must watch the patient’s
potential from the occipital cortex but the negative one from the frontal eye to confirm that he/she keeps looking at the stimulus. Looking away from
region. the stimulus or intentionally defocusing the image by the patient will affect
All VEP waveforms are thought to have cortical generators. The N75wav- the response.
eform is thought to arise from the striate cortex, while the P100 waveform Several stimulus variables are important to consider as well. The stimu-
seems to be generated from the extrastriate cortex. The lateral occipital, lation rate should be between 1 and 4 per second. Since the last peak of
occipitoparietal, and temporoparietal cortices produce the N145 waveform interest in a PRVEP is the P100, the minimum analysis time should be 200
(8–10). The N105 waveform appears to arise from the prefrontal cortex (11). milliseconds. This means that the fastest rate possible would be 5 per second.
A large component of the generator of the P100 waveform is the extrastri- Slower stimulation rates result in more reliable responses with the shortest
ate cortex along the mesial aspect of the occipital cortex. When this area is latencies, highest amplitudes, and best morphologies. However, slow rates
activated, the VEP vector projects to the contralateral side. For example, take more time to complete an average, and this may lead to loss of attention
activation of the nasal aspect of the left retina results in the activation of the or defocusing on the checkerboard pattern. This will result in the prolonga-
right visual cortex, and the VEP is best recorded over the left hemisphere. tion of latency and worsening morphology. A common rate used that bal-
Full-field activation of one eye leads to the activation of both visual cortices. ances both of these competing issues is 1 to 2 per second.
Since the VEP vector projects contralaterally for both eyes, the waveform is The luminance, or brightness, of the screen on which the stimulus is pre-
best recorded over the midline. The exact projection of the VEP vector is sented and the contrast between the dark and light squares are related, and
variable between patients, some projecting more laterally while others proj- both can affect the PRVEP. Luminance can be measured with a photometer.
ect more medially, superiorly, or inferiorly. With very low luminance and contrast between the checks, the latency and
amplitude will be affected. However, once the contrast between the dark
Pattern Reversal Visual Evoked Potentials and light checks exceeds 40%, further changes in PRVEP measures are
slight. For most clinical studies, the contrast is kept between 95% and 99%.
Full-field PRVEP are the type of VEP performed most often and provide the It is important not to change the luminance of the screen after normative
most useful clinical information. In this section, the technique for obtaining data has been obtained and to check it periodically to make certain that it
and interpreting PRVEP will be discussed. PRVEP obtained with hemifield remains stable.
stimulation are infrequently performed. The checkerboard stimulus is presented on a computer screen. Most
laboratories obtained normative data using cathode ray tube (CRT) moni-
Methodology tors to present the stimulus. These displays are becoming less available and
The stimulation and recording techniques have a significant impact on VEP. are being replaced by liquid crystal display (LCD) monitors. The manner
It is especially important to adhere to the methods used in obtaining norma- in which both of these screens refresh is different, with the LCD being
tive data when performing clinical studies. considerably slower. Using even the fastest LCD monitors can result in
considerable prolongation of P100 waveform latency (Fig. 15.2) (12). CRT
Stimulation monitors should not be replaced with LCD monitors without recollecting
The method in which the stimulus for PRVEP is presented can greatly affect normative data.
the latency and shape of the response. Patient and stimulus variables are The size of the squares of the checkerboard has a major impact on the
important to consider. PRVEP waveform. The visual angle is the measure of the size of the image
Figure 15.1: PRVEP obtained from the right eye of a 41-year-

old patient with (A) and without (B) corrective lenses. The VA
was 20/20 with corrective lenses and 20/50 without correc-
tive. Notice that the P100 latency increases from 106 to 109
milliseconds without corrective lenses. (©AMH.)
of the square created on the retina, and is expressed as “a/b,” where “a” that can be readily distinguished should be used. Often this is 30´ visual
is the check size and “b” is the distance from the eye. Thus, larger check arc, but with poor VA, it may be 60´ and 15´ for individuals with excellent
sizes increase the visual angle, and increasing the distance decreases the vision.
visual angle. Check sizes are expressed in minutes of arc of the angle (1° =
60 minutes). Common check sizes used are 15´, 30´, and 60´. The smaller Recording
check sizes stimulate the central retina and fovea, whereas larger check sizes Recording techniques can affect the PRVEP waveform as well. There is some
stimulate more of the peripheral retina. Smaller check sizes produce shorter variability in recording methods, particularly in recording electrode posi-
latency waveforms as the fovea is selectively stimulated. However, if the tions. The number of channels used is also variable.
check becomes too small and the distinction between the dark and light Recording electrode placement is not standardized for PRVEP. Many
squares begins to blur, the latency starts to prolong. The smallest check size laboratories use the “Queen Square” method in which electrodes are placed
at a fixed distance from anatomical landmarks. Alternatively, the Interna- A four-channel montage is recommended for obtaining PRVEP (13).
tional 10–20 system for electrode placement can also be used. The recording This recommended montage is presented in Table 15.2. Often, additional
electrodes used and their labeling according to the Queen Square system is channels are added if the morphology is unusual and needs to be better
presented in Table 15.1. The corresponding International 10–20 system elec- defined. An additional channel that is often added is the MO-Au (both
trode positions are also noted. These electrode locations are also presented ears).
visually in Fig. 15.3. Notice that the Queen Square electrodes along the pos- The amplifier filters are set to 1 to 100 Hz, and the analysis time is set at
terior aspect of the head are at a slightly higher plane than the International 200 to 250 milliseconds since the last peak of interest is the P100. Because
10–20 system electrodes. In most patients, electrodes placed according to the P100 waveform is usually of high amplitude, many repetitions do not
the Queen Square method provide better PRVEP morphology and higher need to be averaged. Typically, a reproducible response is seen after 100 to
amplitude (13). 200 repetitions. Since there is no standardized polarity convention, the P100
A B
Figure 15.2: PRVEP obtained from the right eye of a neu-

rologically normal subject using a CRT monitor (A), LCD
monitors with 2 milliseconds (B), 8 milliseconds (C), and 30
milliseconds (D) refresh rate. The P100 latency changes from
109 milliseconds with the CRT monitor to 114 milliseconds for
the 2 milliseconds, 117 for the 8 milliseconds, and 156 for the
30 milliseconds refresh rate LCD monitors. (©AMH.)
C D
TABLE 15.1 PRVEP Recording Electrodes waveform can be displayed upward or downward. Whichever way it is
displayed must be clearly marked.
Queen square International 10–20
electrode Location system electrode Interpretation
MO 5 cm above inion Oz Interpretation of PRVEP involves determining the presence of expected
LO/RO 5 cm left/right of MO O1/O2 waveforms. The P100 waveform is the most important of these w aveforms
MF 12 cm above nasion Fz and is identified as the prominent positive potential in the occipital e lectrodes.
A1/A2 Left or right ear/mastoid A1/A2 The N75 and N145 waveforms precede and follow the P100 waveform and
are also best recorded from the occipital electrodes. The N105 waveform is a
Ground Vertex Vertex
small response noted in the frontal region.
MO, midoccipital; LO/RO, left and right occipital; MF, midfrontal; A1/A2, left and right The MO-MF derivation is often the best for recording the P100 waveform. It
ear/mastoid. takes advantage of the positive potential in the occipital region and the negative
Figure 15.3: Graphic representation of the

PRVEP recording electrodes; both Queen
Square and International 10–20 system loca-
tions are noted. (Adapted by Kale E, CNIM from
http://www.ir-ltd.net/uploads/posts/Infinite-
ZB_Shots.jpg. ©EK/AMH.)
TABLE 15.2 PRVEP Recording Montage Recommended peak latency to the P100 waveform in the MO-MF derivation is noted. If the
by the ACNS P100 waveform is better visualized in the MO-Au derivation, it can be used
instead. The typical latency of this waveform is between 90 and 115 millisec-
Channel 1 LO-MF onds (1). The latency should be compared with normative data. Normative
Channel 2 MO-MF data may be adjusted on the basis of head size. Head size is measured from
Channel 3 RO-MF the preauricular point on one side to the preauricular point on the other side
Channel 4 MF-A1 (P–P distance). Alternatively, some laboratories may have separate norms
for females and males. Sample normative data from the author’s labora-
LO, left occipital; MF, midfrontal; MO, midoccipital; RO, right occipital; A1, left ear. tory for various head sizes is presented in Table 15.3. In addition to deter-
American Clinical Neurophysiology Society. Guideline 9B: guidelines on visual evoked mining the peak latency, the latency difference between the P100 waveform
potentials. J Clin Neurophysiol 2006;23(2):138–156.
obtained after left and right eye stimulation is also determined. Even if both
are within normal limits but are asymmetric, the study is considered abnor-
mal. In the author’s laboratory, a latency asymmetry greater than or equal
potential in the frontal region, which occur at about the same latency, thus max- to 8 milliseconds is considered abnormal.
imizing the amplitude of the P100 waveform. The MO-Au derivation typically Amplitude of the P100 waveform is also measured; however, it is less
has a P100 waveform that is lower in amplitude, but it is a better reflection of important a measurement than the latency. The N75–P100 or the P100–
the true amplitude of this waveform since it does not have the N105 waveform N145 peak-to-peak amplitude is measured, or the average of the two is
contribution. The MF-Au derivation shows only the N105 waveform as that noted, per protocol of the laboratory. Rather than the amplitude serving as
is the only potential recorded from the frontal region. The parasagittal deriva- an absolute measure of abnormality, the P100 waveform amplitudes after
tions, LO/RO-MF, are useful for demonstrating the activation of one occipital left and right eye stimulation are compared. In the author’s laboratory, an
cortex, and their symmetry helps establish equal activation of both occipital interocular amplitude ratio greater than or equal to 2.0 is considered abnor-
cortices, as would be expected in a normal full-field PRVEP (Fig. 15.4). mal. The side with the lower amplitude is abnormal.
The P100 waveform latency is the most important parameter to measure The morphology and topography of the P100 waveform is important
in the PRVEP. Laboratories differ on how this is measured. Most often, the to analyze as well. As noted above, the normal P100 waveform consists
TABLE 15.3 PRVEP Normative Data from the Author’s Laboratory
P–P (cm) Latency (ms)a

30 106.5
31 107.5
32 109.0
33 110.0
34 111.0
35 112.0
36 113.5
37 114.5
38 116.0
39 117.0
40 118.5
Stimulation rate approximately 4 per second.

Interocular latency asymmetry less than 8 milliseconds.
Interocular amplitude asymmetry (larger/smaller) less than 2.0.
Parasagittal amplitude asymmetry (larger/smaller) less than 2.5.
a
Latency values least square fit + 3 SEM.
Abnormalities
Abnormalities of the P100 waveform can be in latency, amplitude, morphol-
ogy, and topography. Latency abnormalities are the most significant, but the
Figure 15.4: Normal PRVEP obtained with stimulation of the left eye of a others are important as well, particularly in identifying lesions of the optic
25-year-old patient. Notice that the highest amplitude P100 is present in the chiasm and optic tracts. Latency abnormalities are either prolongations
MO-MF derivation. The amplitude is slightly smaller in the MO-Au derivation. of the P100 waveform latency beyond the upper limit of normal or a side-
In these two derivations, the N75 and N145 are also seen. The N105 is seen to-side asymmetry. The side with the longer latency is abnormal. Unilateral
in the MF-Au derivation. The LO/RO-MF derivation show symmetric P100.
P100 waveform latency prolongation is most consistent with a prechiasmatic
(©AMH.)
lesion on the side of the stimulated eye. Bilateral latency prolongations are
harder to localize and may be prechiasmatic, chiasmatic, or postchias-
matic. Analyzing the topography and morphology of the P100 waveform
of a large positive wave preceded and followed by smaller negative waves. distinguishes between these possibilities.
Various derivations can be used to better visualize the morphology of the Amplitude abnormalities in their most severe form result in complete
P100 waveform. The amplitude of the P100 waveform in the parasagittal loss of the P100 waveform. Alternatively, abnormally low-amplitude or
derivations (LO/RO-MF) is also noted. In the author’s laboratory, the inter- side-to-side amplitude asymmetry may be present. Unilateral loss of
hemispheric P100 waveform amplitude ratio should be less than 2.5. The waveform is most likely due to a prechiasmatic lesion. Prior to attribut-
side with the lower amplitude is abnormal. ing an absent waveform to pathology, technical issues causing an absent
waveform must be ruled out. Unilaterally low amplitude is the same as r easons why this may occur (Fig. 15.5). Neither peak of the “W” should
a high side-to-side amplitude ratio. A unilaterally low-amplitude and be considered the true P100 waveform, and an attempt should be made to
prolonged latency P100 waveform is also most likely due to a prechi- identify the correct P100 peak. Typically, the W-shaped waveform is seen
asmatic lesion. When the amplitude is low and latency is normal, an in the MO-MF derivation. The P100 waveform in this derivation has con-
ocular abnormality should be considered. Bilaterally low amplitude of tributions from the P100 positive potential over the occipital region and
the P100 waveforms is of uncertain clinical significance. This pattern the N105 negative potential over the frontal region. If the latencies of the
can, however, be seen with prechiasmatic, chiasmatic, or postchiasmatic P100 and N105 waveforms are substantially different, the P100 waveform
lesions. in the MO-MF derivation has a W-shaped morphology. In this situation,
The morphology of the P100 waveform can be abnormal, but if that is the MO-Au derivation should be analyzed to see whether a single-peak
the only abnormality, the clinical significance is uncertain. The most com- P100 can be identified. Sometimes a W-shaped waveform results due
mon abnormality is the “W-shaped” P100 waveform, and there are several to activation of too much of the peripheral retina. Central retinal and
A B
Figure 15.5: PRVEP obtained after stimulation of the left eye

of a 46-year-old patient. A was obtained with 60-minute check
size. Notice the “W-shaped” waveform. Stimulation with a
30-minute check size (B) improved the morphology. (©AMH.)
foveal fibers conduct impulses faster than peripheral retinal fibers. Thus, The side with the lower amplitude is the abnormal side. If after stimulation
excessive peripheral retinal activation results in the PRVEP arriving at of both eyes, one side consistently has the lower amplitude (i.e., LO-MF has
the occipital cortices at different times, resulting in the bifid shape of lower amplitude than RO-MF after full-field stimulation of both left and
the P100 waveform. More focused stimulation of the central retina with right eyes), this is known as an “uncrossed asymmetry” and implies a post-
a smaller check size may improve the morphology. Retinal diseases may chiasmatic lesion contralateral to the side of the low amplitude (i.e., right
result in abnormal activation of fibers from the central retina, resulting postchiasmatic abnormality in the example mentioned earlier) (Fig. 15.6).
in an abnormal P100 waveform shape. Use of hemifield stimulation may Recall that the P100 waveform seen in the LO-MF derivation is a reflection
correct this problem. of the activation of the right occipital cortex and vice versa. Alternatively, if
Topographic analysis of the PRVEP involves comparing the P100 waveform the side with the lower P100 waveform amplitude changes after stimulation
amplitude in the parasagittal (LO/RO-MF) derivations after stimulation of of the left and right eyes (i.e., LO-MF has a lower amplitude after stimulation
each eye. If the interhemispheric P100 waveform amplitude ratio is greater of one eye and RO-MF has a lower amplitude after stimulation of the other
than or equal to 2.5, it is suggestive of a chiasmatic or postchiasmatic lesion. eye), that is known as a “crossed asymmetry” and implies a chiasmatic lesion.
A B
Figure 15.6: PRVEP obtained after stimulation of the left (A)

and right (B) eyes of a 74-year-old patient. This study shows
an “uncrossed asymmetry” of the parasagittal P100 waveforms.
The P100 waveform seen in the RO-MF derivation after stimula-
tion of both eyes has lower amplitude than the P100 waveform
seen in the LO-MF derivation. The LO/RO amplitude ratio after
left eye stimulation (A) is 2.7 and after right eye stimulation (B)
is 2.6. Both of these are abnormal, implying a left hemisphere/
optic radiation lesion. The left to right eye MO-MF amplitude
ratio is 1.4, which is normal. (©AMH.)
A graphic summary of topographic analysis is presented in Fig. 15.7. When a differentiate between the dark and the light squares. Differences between
chiasmatic or postchiasmatic lesion is suspected based on topographic abnor- FVEP and PRVEP will be highlighted in this section.
malities of the P100 waveform, further testing should be done to confirm this.
This may be in the form of hemifield stimulation or other types of imaging. Methodology
Neuroimaging is sensitive in detecting these lesions and is often preferred
A bright, noncolored light flash is used as the stimulus for FVEP. This is
over VEP obtained with hemifield stimulation. Thus, hemifield testing is sel-
produced with either light emitting diode (LED) embedded in goggles worn
dom performed clinically, and will not be discussed further in this chapter.
by the patient or a strobe lamp. LED goggles are preferred as they are placed
over the patient’s eyes and do not require any cooperation from the patient.
Flash Visual Evoked Potentials The patient’s eyes may be open or closed. If a lamp is used, the patient is
encouraged to look in the direction of the lamp, and this should be moni-
FVEP are obtained in situations where PRVEP are not possible. This is the
tored by the technologist. Stimulation frequency is 1 to 2 per second.
case in very young children or other patients who cannot maintain focus on
The recording montage is simpler than that used for PRVEP. Often a sin-
a checkerboard pattern or patients whose VA is so poor that they cannot
gle derivation is used, MO-Au (13). If a response is not seen in this deriva-
tion, others such as LO-Au, RO-Au, or vertex-Au can be considered. Filter
settings and analysis time settings are the same as for PRVEP. The response
is usually of high amplitude and relatively few repetitions are needed to gen-
erate a reliable response. Each response must be replicated, however.
Interpretation
Several peaks are seen in a FVEP. The first three peaks are best seen over
the occipital cortex, whereas subsequent ones are better seen over the v ertex.
A positive peak occurring between 50 and 100 milliseconds is the most
prominent peak and is called the P1 (14). A negative peak may precede and
follow this positive peak, and these are referred to as N1 and N2 (Fig. 15.8).
All of these peaks are highly variable within and between patients. Altera-
tion in alertness can affect the latency and amplitude. Because of the vari-
ability of the latency and amplitude of the FVEP, most laboratories do not
compare latencies of P1 responses with normative data. Rather, FVEP are
interpreted simply as being present or absent. The P1 latency and amplitude
can be compared between left and right eye stimulation, but any asymmetry
should be evaluated very cautiously.
FVEP provide only a very rudimentary assessment of the visual pathways.
A normal response, one in which a P1 is present, does not indicate normal
VA. Rather it simply implies that at least some parts of the visual pathway
Figure 15.7: Graphic representation of interpretation of amplitude and topo-
graphic abnormalities of the PRVEP. Lesion A is at the left optic nerve, lesion B is between the retinae and the occipital cortices are intact. Conversely, if technical
at the optic chiasm and lesion C is in the left optic radiation. The table shows the problems are excluded, an absent FVEP suggests lack of functional integrity
amplitude and topography of the P100 with left and right eye full-field stimulation between the retinae and the occipital cortices (Fig. 15.9). Presence of any vision
with each of these lesions. See text for details. V, normal amplitude P100; v, low in such a situation is extremely unlikely (15,16). Performing an electroretino-
amplitude P100; —, absent P100; LO/MO/RO, left, middle, right occipital. (©AMH.) gram (ERG) may help localize the lesion further. If the ERG is absent, the
Figure 15.8: A normal FVEP after stimulation of the left (OS) and right (OD) eyes Figure 15.9: An abnormal FVEP after stimulation of the left (OS) and right (OD)
of a 1-year-old patient. Notice the P1 response, which is preceded and followed eyes of a 1-year-old patient. Notice that there is no reliable, reproducible wave-
by smaller negative potentials (N1 and N2). (©AMH.) form present. (©AMH.)
lesion is likely in the retina, and if it is present, the optic nerve or more proximal for adults, there are significant issues relevant to maturation that must be
parts of the visual pathway are most likely the site of pathology (17,18). considered.
Maturational changes have been studied with FVEP as they are easier to
Pediatric Considerations obtain in small children than PRVEP. At 22 weeks conceptional age (CA), a
large negative peak can be seen at about 300 milliseconds. A few weeks later,
VEP are a useful way to assess the visual pathway in young children who a positive peak can be seen before this large negative peak. By term, the
may not be able to cooperate with other types of visual system testing. positive peak occurs at about 200 milliseconds. This positive peak becomes
While many of the interpretative criteria for children are similar to those bifid by 44 weeks CA, and the initial part of the waveform has a latency of
approximately 100 milliseconds. By 6 months of age, the positive peak at with preserved morphology is most likely to be due to demyelination of the
about 100 milliseconds becomes the dominant waveform and changes little optic nerve (Fig. 15.10) (23). Other neuropathies and compressive lesions can
thereafter. This is the P1 waveform (19). PRVEP changes in a similar man- also affect the optic nerve. Anterior ischemic optic neuropathy (AION) affects
ner, and a dominant P100 waveform can be seen by 6 to 8 months of age (20). the amplitude of the P100 waveform more than the latency (24). Other types
Stimulation for FVEP in children is similar to the technique described of primarily axonal optic neuropathies produce similar findings. Tumors also
previously. When PRVEP are used in young children, maintaining attention affect the amplitude of the P100 waveform more than the latency and cause
on the checkerboard pattern can be a challenge. However, PRVEP have been topographic abnormalities (side-to-side asymmetries) (25). Certain metabolic
successfully obtained in children as young as 4 to 6 weeks of age (21,22). In diseases, such as the leukodystrophies, can affect both the optic nerve and the
very young children, larger check sizes are used: less than 2 months of age, postchiasmatic visual pathway. Testing in these conditions is often with FVEP
120 minute check size; 2 to 3 months, 60 minutes; beyond 6 months, 30 and as patients with these conditions cannot cooperate with PRVEP. In Krabbe dis-
15 minutes (21). Stimulation rates should be slower than used for adults, ease, the FVEP is normal (P1 present) until later in disease course when severe
typically about 1 per second. disease results in loss of the P1 (26,27). Other types of leukodystrophies display
FVEP in children are interpreted as normal or abnormal depending on similar changes (28,29). Hysterical blindness does not result in changes in the
whether the P1 response is present or absent. Whereas a present P1 does PRVEP (30). However, the patient may not look at the checkerboard pattern or
not necessarily imply visual perception, an absent response makes visual may not attentively focus on it. This may result in an absent or morphologically
perception very unlikely. When the P1 is absent, an ERG may be helpful for abnormal P100 waveform. In these situations, the technologist must make sure
further localization of the pathology, as noted previously. PRVEP in chil- the patient is cooperative with the test. FVEP will be present in hysterical blind-
dren are interpreted the same way as for adults, with latency being the most ness even if the PRVEP is absent due to the patient’s inattention.
important parameter. Amplitude, morphology, and topography should also Chiasmatic lesions such as tumors of the sella turcica can produce
be considered, however. Ideally, each laboratory should have normative data changes in the PRVEP as they compress the optic chiasm. The most signifi-
for latency measurements for various age groups. Practically, this is very dif- cant change produced by these lesions is abnormal topography of the P100
ficult, and most laboratories use published norms. If this is done, the meth- waveform (31). There is interhemispheric amplitude asymmetry of the P100
odology used by the reference laboratory should be followed. waveform, and a “crossed asymmetry” of the parasagittal P100 waveform is
noted after stimulation of the left and right eyes (see earlier). The latency of
Clinical Correlations the P100 waveform may or may not be prolonged in these cases.
Any disease affecting the cerebral cortex diffusely can result in a post-
Neurologic and ophthalmologic problems can cause dysfunction of the chiasmatic lesion of visual pathways. This includes conditions such as
visual pathways. VEP are most useful in assessing the neurologic problems, stroke, tumors, and demyelinating and metabolic diseases. As noted previ-
and various ophthalmologic tests can be used to evaluate ocular pathology. ously, various metabolic diseases can affect pre- and postchiasmatic visual
Of the neurologic problems that are best evaluated by VEP are prechias- pathways. Similar to chiasmatic lesions, postchiasmatic lesions affect the
matic lesions. Lesions in this location are hard to visualize by neuroimaging. topography of the P100 waveform, resulting in a P100 waveform interhemi-
Chiasmatic and postchiasmatic lesions can also be evaluated by VEP; how- spheric amplitude asymmetry. However, with postchiasmatic lesions, there
ever, neuroimaging is more often used for this purpose. As with other types is “uncrossed asymmetry” of the parasagittal P100 waveform after stimula-
of EP, VEP abnormalities are seldom specific to a particular condition. tion of the left and right eyes. The latency of the P100 waveform is affected
They identify the presence of a problem but cannot identify the etiology. little in these cases (1). Diseases that affect the cerebral cortex symmetri-
Optic neuritis is a common prechiasmatic lesion for which VEP are often cally can cause symmetric changes in the P100 waveform, and an interhemi-
used. With acute optic neuritis, there may be complete loss of the P100 wave- spheric amplitude asymmetry may not be seen (31). When chiasmatic and
form. Over several weeks, the P100 waveform reappears at a very prolonged postchiasmatic lesions are suspected based on full-field PRVEP, this should
latency and gradually increases in amplitude. Even as vision improves, the P100 be confirmed with other methods of testing, such as hemifield stimulation
waveform does not shorten in latency. A unilaterally prolonged P100 waveform or imaging.
A B
Figure 15.10: PRVEP obtained after stimulation of the left

(A) and right (B) eyes of a 26-year-old patient. The PRVEP is
abnormal after stimulation of the right eye, showing P100
latency prolongation to 121 milliseconds and a normal
PRVEP after stimulation of the left eye (P100 latency of 109
milliseconds). Notice the preserved morphology of the P100
after right eye stimulation, despite the latency prolongation.
This is a typical finding in conditions that cause demyelin-
ation of the optic nerve, such as optic neuritis. (©AMH.)
Whereas VEP are not used to test ophthalmic disorders, they may be pres- Brainstem Auditory Evoked Potentials
ent and affect the VEP. The most common are refractive errors. These affect
VA, which may make obtaining PRVEP more challenging, and larger check Potentials elicited by stimulation of the auditory system are called auditory
sizes may be needed for those patients. Similarly, other ocular disorders can EPs (AEP). AEP can be classified based on their latency from stimulus onset
also affect VA and, in turn, the VEP. Patients presenting to the VEP labora- into short-, middle-, and late-latency AEP. Short-latency AEP (SLAEP) con-
tory should be asked about their vision history and VA with corrective lenses sist of a series of waveforms that arise from the cochlea and brainstem within
should be noted. Patients with advanced-stage cataracts can have dimming the first 10 milliseconds following acoustic stimulation. Waveforms arising
of vision. The luminance of the stimulus may be affected and causes changes from the cochlea are known as the electrocochleogram (ECochG), and those
in VEP amplitude and latency. arising from the brainstem are known as BAEP. BAEP are used most often
in clinical practice and will be the focus of this section. As noted previously, TABLE 15.4 Generators of BAEP Waveforms
AEP waveforms arising between 10 and 50 milliseconds are known as middle-
latency AEP, and those arising after 50 milliseconds are called long-latency Waveform Localization
AEP. These latter two types of AEP are not as reliable and reproducible as I Distal auditory nerve
BAEP and are not used clinically as much as BAEP. The remainder of this
II Proximal auditory nerve and cochlear nucleus
section will focus on BAEP.
III Superior olivary complex
Anatomy and Waveform Generators IV Lateral lemniscus, just caudal to inferior colliculus
V Inferior colliculus
The auditory pathway starts in the cochlea of the inner ear. Sound reaches
the cochlea by traversing the external auditory canal, tympanic membrane
(TM), and middle ear. Hair cell activation in the cochlea results in activa- negative potential and is recorded from the reference electrode placed on
tion of the auditory nerve. The auditory and the vestibular nerve join to the ear or mastoid. Its generator is the most distal part of the auditory
make the vestibulocochlear nerve (cranial nerve [CN] VIII). The auditory nerve. Waves II–V are all of positive polarity and are far-field potentials
nerve fibers synapse with neurons in the ventral and dorsal cochlear nuclei recorded from the active electrode at the vertex. The proximal part of the
in the rostral medulla. From these nuclei, fibers ascend on both sides of auditory nerve and cochlear nuclei give rise to wave II. Wave III arises from
the brain stem. One-half of the fibers decussate, while the other half do the caudal pontine tegmentum and superior olivary complex. The genera-
not. This decussation forms the trapezoid body in the ventral pons. The tors of waves IV and V are in close proximity, and the waves are often
fibers then synapse with the superior olivary complex in the pons. The fiber fused. The wave IV generator is the rostal part of the lateral lemniscus just
tract between the cochlear nuclei and the superior olivary complex is called before it gets to the inferior c olliculus. Wave V is thought to arise from the
the lateral lemniscus. Fibers from the superior olivary complex continue to inferior colliculus (33).
ascend in the lateral lemniscus to the inferior colliculus in the midbrain.
From there, auditory fibers ascend to the medial geniculate body, and then Methodology
on to the primary auditory cortex in the superior temporal gyrus (32).
Hearing from each side is represented bilaterally in the cortex because of Several issues in stimulation and recording methods must be considered as
only a partial decussation of the auditory pathway in the upper medulla they can affect BAEP interpretation. Stimulation and recording techniques
and lower pons. will be described separately.
The BAEP consists of five waveforms that are commonly analyzed for
clinical purposes. The most common recording montage is Cz-A1/Cz-A2. Stimulation
The waveform nomenclature is different than VEP and SEP. BAEP waves Stimulation technique involves not only understanding various parameters
are labeled according to the sequential number in which they appear, rather of stimulus delivery, but also patient-related factors that must be managed.
than with a polarity and latency designation. They are a combination of Patients must be relaxed and seated or lying comfortably. BAEP are of very
near- and far-field potentials. Wave I is a near-field potential and has a nega- small amplitude, and excessive neck muscle activity will make recording
tive polarity. Waves II–V are far-field potentials with a positive polarity at these potentials much harder. Since the level of alertness does not affect
the scalp. BAEP, patients are encouraged to fall asleep. This allows further relaxation
There is no single anatomical generator for a particular BAEP wave- of neck muscles and facilitates BAEP acquisition. The stimulus can be deliv-
form. Each wave receives contributions from several neural structures and ered to the patient through headphones or ear inserts. With headphones, the
many structures contribute to each waveform. However, assigning a neural transducer is placed adjacent to the ear being stimulated, and changes in the
structure as the most likely source of a waveform is helpful in localizing transducer’s diaphragm produce the sounds. These are bulky, and in small
possible lesions. A summary of the neural generators for each BAEP wave- children may cause collapse of the external ear canal. Ear inserts are used
form is presented in Table 15.4. Wave I is the only waveform that has a more often than headphones. The ear inserts attach to plastic tubing, which
attaches to the transducer. This introduces a slight prolongation in how long The stimulus polarity can affect BAEP latencies. When the initial move-
it takes for a stimulus to reach the ear. To compensate for this, if normative ment of the transducer diaphragm is toward the TM, the click acoustic
data was obtained with headphones, a latency increment of 0.9 to 1 millisec- polarity is called condensation (C). When the initial movement is away from
ond is added to the upper limit of normal for absolute waveform latencies. the TM, the click is called rarefaction (R). When successive clicks are of
It is recognized that BAEP are not done in soundproof rooms, but ambient opposite polarity, they are called alternating, which are useful for stimulus
noise should be kept to a minimum as that can affect the BAEP. artifact suppression. Subjectively, R and C clicks sound identical, and test
Characteristics of the stimulus can alter the BAEP waveform. Most often devices are required to determine click polarity. As will be noted later, there
a broadband click is used to produce a BAEP. Broadband clicks are 100-µs are differences in BAEP responses produced by different click polarities.
pulses that contain a wide band of frequencies, but it is their high-frequency Stimuli from monaural stimulation strike not only the ipsilateral TM but
content that produces the BAEP. They are useful for neurological assess- continue through the cranium to reach the contralateral cochlea. Transcra-
ments but not as good for audiological assessment. Speech and other com- nial attenuation is approximately 30 to 40 dB. Therefore, if 90 dBnHL clicks
mon sounds are low frequency, and testing for low-frequency parts of the are delivered to a totally nonfunctional cochlea, 50 to 60 dBnHL clicks will
cochlea requires stimulation in a selective frequency band. This can be done pass through the skull and brain to stimulate the opposite cochlea, which,
with filtered clicks or tone pips (34). if normal, will produce normal BAEP responses. This produces confusing
The intensity of stimulation is expressed as the actual stimulus intensity responses, and this can be avoided by delivering a white noise to the opposite,
compared with a reference value. The basic measure of sound intensity is the nonstimulated ear. Masking white noise, which is 40 dB less than that used for
decibel (dB). The hearing level (HL) is average threshold intensity for hear- stimulation, should be applied to the contralateral (nonstimulated) ear (36).
ing in young adults when tested with pure tones of 0.5-millisecond duration.
The hearing threshold for broadband clicks with a shorter pulse is called the Recording
normal hearing level (nHL). The sensory level (SL) is the hearing thresh- Three electrodes are used for recording BAEP, one at the vertex (Cz) and
old for a given patient. This parameter is used less often. BAEP stimulus one at each of the ear or mastoid (A1/A2, M1/M2) locations. A ground
intensity is expressed as “dBnHL,” and can be thought of as decibels above electrode is applied anywhere on the scalp, typically the forehead. The later
nHL. For example, if a stimulus intensity of 70 dB is desired, the patient’s BAEP components (waves II–VII) are of brainstem, far-field origin and
HL must first be determined, and 70 dB added to that level. Alternatively, have a widespread distribution over the vertex. Wave I is mostly a near-
the nHL can be used, and the desired stimulus intensity (dB) added to that field potential (negative near the stimulated ear). Because BAEP compo-
level. Thus if the nHL is 5 dB, a stimulus of 75 dB should be used. How- nents have different topographies at Ai (ipsilateral ear), Ac (contralateral
ever, this will be referred to as 70 dBnHL (35). As the stimulus intensity ear), and Cz, this leads to varying degrees of potentiation, attenuation, and
is increased, the BAEP waveforms increase in amplitude and have better apparent latency shift of the individual waves. As will be discussed later,
morphology. With very high stimulation intensity, extra waveforms may be waveform identification can proceed logically with an understanding of the
seen, making identification of waves I–V difficult. Reducing the stimulation topographic differences between the ipsilateral and contralateral channels.
helps resolve this. As the stimulation intensity is reduced, the amplitude of A typical montage used for BAEP is shown in Table 15.5. The Ai-Ac deriva-
the waves decreases. The last wave to disappear with decreasing stimulus tion helps in identification of wave I.
intensity is wave V (34). BAEP polarity convention is the opposite of the polarity conventions for
Slow and fast stimulation rates can be used for obtaining BAEP. Slow other types of neurophysiologic studies in which a negative event at the active
rates, between 8 and 12 per second, are used most often. They result in electrode causes an upward deflection. With BAEP, wave I has a negative
shorter latencies and better morphology of the waveforms. A fast rate of field at the reference electrode. The near-field, negative component of wave
50 per second causes a slight latency prolongation and lower amplitude. I, when recorded by an Ai electrode connected to second (G2) input of a dif-
Normative data change with a change of rate. The main advantage of the ferential amplifier, causes an upward deflection. The positive, far-field com-
fast rate is the shorter amount of time needed for data acquisition. In the ponents when recorded by the Cz electrode connected to first (G1) input also
author’s laboratory, if BAEP are abnormal with fast rate of stimulation, cause upward defections. Thus, all BAEP components are displayed upward,
the study is repeated with a slow rate to confirm the abnormality. but wave I is negative at the ear, while waves II–V are primarily positive at Cz.
TABLE 15.5 BAEP Recording Montage Recommended by the ACNS named IN, IIN, IIIN, IVN, and VN (37). The up-going, positive waves recorded
in the Cz-Ac derivation are called IIC, IIIC, IVC, and VC, and the valleys fol-
Channel 1 Cz-Ai lowing are INC, IINC, IIINC, IVNC, and VNC (Fig. 15.11). Notice that wave I is
Channel 2 Cz-Ac not identified in the Cz-Ac derivation. This is because wave I is a near-field
Channel 3a Ai-Ac
potential recorded from the Ai electrode. The Cz and Ac electrodes do not
record wave I, and so it is not seen in the Cz-Ac derivation.
a
This channel is not always used. It may help in identifying wave I. A normal BAEP may occasionally not have all five waveforms noted ear-
Ai=ipsilateral, stimulated ear; Ac=contralateral, nonstimulated ear. lier. Waves I, III, and V are present in virtually all audiologically and neuro-
American Clinical Neurophysiology Society. Guideline 9C: guidelines on short-latency logically normal individuals and are considered obligate waveforms (34,36).
auditory evoked potentials. J Clin Neurophysiol 2006;23(2):157–167.
Absence of any of these waveforms is considered an abnormality. Waves
II and IV may not be present in some normal individuals, and hence their
absence does not necessarily denote an abnormality. If the waveforms are
The recommended filter settings for BAEPs are 10 to 3,000 Hz (36). In difficult to identify, changes in stimulation and recording parameters can
the past, the majority of clinical studies were done with low-frequency filter help enhance certain waveforms.
settings of 150 Hz. Narrowing the band pass has surprisingly little impact
on data acquisition, with no increase in artifact rejection rate, but produces
obvious changes in response morphology. The higher low-frequency fil-
ter setting is not recommended. If it is used, separate normative data for
such filter settings is required for both latency and amplitude criteria of
abnormality.
The number of repetitions required to produce relatively artifact-free
BAEP varies between 1,000 and 4,000, depending on the signal-to-noise
ratio. When responses are large (>0.2 µV) and noise is relatively low in
amplitude, fewer responses are required. When low-amplitude responses are
present or noise components are relatively high in amplitude, there may be
significant residual noise despite 4,000 or more responses. Increasing the
intensity of stimulation will increase the amplitude of the response, particu-
larly wave I. Attention to electrode impedance and adequate sedation can
significantly reduce environmental artifact and electromyography (EMG).
An increased (often-double) number of stimuli are required to reduce
increased artifact. The BAEP must be replicated at least once.
Interpretation
Figure 15.11: Graphic representation of the BAEP waveform nomenclature
system. This shows seven BAEP waveforms; note that in routine clinical inter-
As with other types of EP, the first step in the interpretation of BAEP is
pretation, only the first five waveforms are used. In the Cz-Ai derivation, the up-
identification of waveforms. Five waveforms are reliably seen after stimula-
going peaks are labeled with Roman numerals I–V. The down-going valleys of
tion, and both Cz-Ai and Cz-Ac derivations are used to accurately identify this derivation are labeled with Roman numerals followed by a subscripted “N”
the waveforms. The up-going, positive peaks of major BAEP components because they have a negative polarity, with the exception of wave IN. In the Cz-Ac
recorded in the Cz-Ai derivation are named waves I, II, III, IV, and V. Occa- derivation, the up-going peaks are labeled with Roman numerals followed by a
sionally, additional positive waves are seen after wave V, called waves VI and subscripted “C,” and the down-going valleys are labeled with Roman numerals
VII. The down-going, negative valleys recorded in the Cz-Ai derivation are followed by a subscripted “NC.”
The amplitude of wave I can be increased by increasing stimulation inten- Waves I, III, and V are primarily evaluated. Absolute latencies of waves
sity and by slowing the rate of stimulation. Changing the polarity of stimu- I, III, and V are determined. Additionally, IPL of waves I–III, III–V, or I–V
lation from R to C clicks or vice versa will cause artifacts and the cochlear are also determined (36). In some cases, wave VC measurements are replaced
microphonic (a part of the ECochG) to change polarity but not wave I. This for wave V measurements. This is because the latency of VC is thought to be
may make wave I easier to identify. Having a Ai-Ac derivation may help in more consistent than V. This paradigm is used in the author’s laboratory.
identifying wave I better as well. Wave III is often a bifid waveform, as its Amplitudes of waves I, IV, and V are also determined. Wave IV amplitude
latency can be measured to either peak, as long as that is how the normative is determined as often it cannot be differentiated from wave V, and in that
data was acquired. A bifid wave III should be distinguished from a wave III case, the wave IV–V amplitude is determined. The wave IV–V/I amplitude
that is fused with wave II. The separation between waves II and III is bet- ratio is determined (36). In the author’s laboratory, all the above-mentioned
ter seen in the Cz-Ai derivation, and in the Cz-Ac derivation they are more values are evaluated except absolute latencies to waves III and V. That nor-
fused. Wave V is the most robust of the BAEP waveforms. As stimulation mative data is presented in Table 15.6. In addition to comparing the absolute
intensity is reduced, this is the last wave to disappear. It is best identified as latencies and IPL with normative data, they are also compared after left-
the positivity preceding a large negative deflection. Click polarity may alter and right-sided stimulation (side-to-side comparison). Normative data for
the prominence of wave V. Occasionally, wave IV and V fuse, and wave V side-to-side comparisons from the author’s laboratory is also presented in
appears as an inflection point on the downslope of wave IV in the Cz-Ai Table 15.6. If there is side-to-side asymmetry yet the absolute latencies or
derivation. In the Cz-Ac derivation, waves IV and V usually have more sepa- IPL fall within normal range, they are still considered abnormal.
ration, making wave V easier to identify. Wave I absolute latency is a measure of the peripheral auditory pathway
Correctly identifying BAEP waveforms is of the utmost importance. Incor- up to the distal auditory nerve. Wave I–III IPL is a measure of the auditory
rectly identified waveforms will lead to erroneous interpretations. Waveforms pathways in the lower brainstem, from the auditory nerve to the superior oli-
should not be identified on the basis of the sequential number at which they vary complex in the pons. The wave III–V IPL measures the pathway in the
appear, that is, the first waveform is not necessarily wave V. Nor should wave- upper brainstem, from the superior olivary complex to the inferior colliculus
forms be identified on the basis of their presumed latency, that is, a waveform in the midbrain. Wave I–V IPL measures the entire pathway. The wave IV–
at 1.5 milliseconds is not necessarily wave I. Both of these will lead to mis- V/I amplitude ratio should be at least 0.5. Isolated amplitude abnormali-
identification of waveforms. Interpretation of a BAEP requires identification ties, without concomitant latency abnormalities, are of uncertain clinical
of wave V first. This is the peak that precedes the most significant negative significance.
potential of the BAEP study and occurs approximately 5.5 milliseconds (6.4
milliseconds if ear inserts are used) after stimulation. As noted earlier, often
waves IV and V are fused, and wave V cannot be clearly identified. Analysis TABLE 15.6 BAEP Normative Data from the Author’s Laboratory
of the Cz-Ac derivation may be of value as the separation between waves IV
and V is clearer in that derivation. Decreasing the stimulation intensity may Wave Latency, Abs. or IPL (ms)a
be of help as well, as wave V is the most robust waveform and the last one I 2.0
to disappear with decreasing intensity of stimulation. Next, wave I is identi-
V 6.3
fied as one of the early waves that does not change polarity with changing
I–III 2.6
polarity of stimulation. Changing polarity of stimulation will also affect the
latency of wave I. Wave I is absent in the Cz-Ac derivation and is more prom- III–Vc 2.3
inent in the Ai-Ac derivation, both of which can greatly help in identifying I–Vc 4.6b
the correct waveform. Between waves I and V will be wave III. As noted ear-
Stimulation rate approximately 11 per second.
lier, wave III is often fused with wave II, especially in the Cz-Ac derivation;
For a rate of approximately 31 per second add 0.1 millisecond, and for approximately
evaluating wave III in the Cz-Ai derivation may help (35,37). 51 per second add 0.2 millisecond to latencies.
Once BAEP waveforms have been correctly identified, various peak laten- a
Latency values 3 SD beyond mean.
cies and IPL are determined. If some peaks are absent, that is clearly noted. b
Maximum I–Vc side-to-side latency asymmetry is equal to 0.4 millisecond.
It is difficult to lateralize the side of the lesion on the basis of unilateral Abnormalities
prolongation of IPL or amplitude abnormalities. Prolongation of the waves
I–III IPL is most likely to be ipsilateral to the side of stimulation. However, BAEP abnormalities can be due to the absence of obligate waveforms, latency
prolongation of the waves III–V IPL may be ipsi- or contralateral to the side prolongations, or amplitude abnormalities. Absence of waveforms denotes
of stimulation (38). This is because of the partial decussation of the audi- the most severe type of abnormality. If all waveforms are absent, technical
tory pathways. Most investigators consider this abnormality to be nonlater- problems must be excluded. If technical problems can be excluded, absence
alizing. The same is true if waves I–V IPL is prolonged without concomitant of all waveforms can be due to severe hearing loss and possibly severe brain-
prolongation of other IPL. An abnormally low wave IV–V/I amplitude ratio stem dysfunction. Absence of waveforms after waves I or II is most likely to
also cannot be lateralized. be due to severe brainstem dysfunction (Fig. 15.12). When only wave V is
A B
Figure 15.12: BAEP obtained from

left (AS, A) and right ear (AD, B)
stimulation of a 1-year-old patient.
Wave I is present, but there is loss
of all other waveforms after stimula-
tion of the left and right ears. Both
rarefaction and condensation clicks
were attempted but other than
wave I, no other waveforms were
noted. This implies severe brain-
stem dysfunction.
absent, the abnormality is most likely due to severe midbrain dysfunction. suggestive of a lesion between the auditory nerve and the superior olivary
As already noted, lateralization is difficult with loss of wave III or V. complex in the pons (Fig. 15.13). This prolongation is considered to indi-
Assessment of IPL abnormalities is very important as they measure cen- cate a lower brainstem lesion. Usually, the lesion is ipsilateral to the side
tral conduction and are more indicative of neurological disorders than of stimulation. Prolongation of the waves III–V IPL is indicative of lesion
prolongations of absolute latency. Prolongation of the waves I–III IPL is between the superior olivary complex and the inferior colliculus; such an
A B
Figure 15.13: BAEP obtained from left (AS, A) and right ear (AD, B) stimulation of an 80-year-old patient. Both rarefac-
tion and condensation clicks are shown. There is bilateral prolongation of the waves I–V IPL. The waves I–III IPL shows
greater bilateral prolongation than the waves III–V IPL, suggesting a greater involvement of the lower brainstem.
abnormality is considered to indicate an upper brainstem lesion (Fig. 15.14). IPL is prolonged and neither waves I–III nor III–V IPL is prolonged, the
As noted earlier, these lesions cannot be lateralized. Often, the waves I–V lesion is considered to diffusely affect the brainstem (Fig. 15.15). Lateraliza-
IPL is prolonged when either the waves I–III or III–V IPL is also prolonged. tion of such a lesion is also not possible.
If so, the interpretation is that the predominant dysfunction is in the lower The absolute latency of wave I should also be noted. Prolongation of
or upper brainstem, depending on which IPL is prolonged. If the wave I–V wave I results in comparable prolongation of the absolute latencies of all
A B
Figure 15.14: BAEP obtained from left (AS, A) and right ear (AD, B) stimulation of a 10-year-old patient. Both rarefac-
tion and condensation clicks are shown. There is bilateral prolongation of the waves I–V IPL. The waves III–V IPL shows
greater bilateral prolongation than the waves I–III IPL, suggesting a greater involvement of the upper brainstem.
A B
Figure 15.15: BAEP obtained from left (AS, A) and right ear (AD, B) stimulation of a 50-year-old patient. Both
rarefaction and condensation clicks are shown. There is prolongation of the waves I–V IPL after stimulation of
the left ear. However, the waves I–III and III–V IPL are individually within normal limits. Despite this, this study is
interpreted as abnormal after left ear stimulation, with the lesion affecting the brainstem diffusely. The BAEP
after right ear stimulation is normal.
other waveforms. Consequently, the IPL are not prolonged. Prolongation normally in the CNS. Such an abnormality can result from conductive and
of wave I absolute latency with normal IPL is suggestive of hearing loss sensorineural hearing loss. Before interpreting wave I latency as prolonged,
due to middle ear or cochlear pathology. The normal IPL indicate that whether headphone or ear inserts were used for stimulation should be deter-
once the cochlea is stimulated, transmission of the auditory impulse occurs mined. When the transducer is connected via tubes to ear inserts, 0.9 to 1
millisecond is added to the latency of wave I. Not taking this into account The methodology for obtaining BAEP in children is similar to that used in
may result in erroneous interpretation of wave I latency prolongation. Hear- adults. The ground electrode is placed on the forehead in adults, but in small
ing loss suspected with wave I latency prolongation should be confirmed children care must be taken not to place it on the anterior fontanel if it has not
with audiological testing. closed. It is placed anterior to this landmark. Headphones are typically not used
Reduced amplitude of the BAEP waveforms are more difficult to inter- to deliver the auditory stimulus as they are too bulky, and if they are too tight,
pret. The wave IV–V/I amplitude ratio is determined as it is a more sensitive they might collapse the external auditory canal (43). Ear inserts connected to a
measure than the absolute amplitude of any waveform. Whenever amplitude transducer are the preferred stimulation method. Stimulation should be started
abnormalities accompany IPL abnormalities, interpretation is straightfor- at an intensity of 70 dBnHL, and can be increased if reliable waveforms are
ward and consistent with the abnormality noted with the IPL. An abnor- not seen. However, stimulation intensity should not exceed 95 dBnHL (40).
mally low wave IV–V/I amplitude ratio indicates possible upper brainstem Amplifier settings are similar to that used in adults, except that the analysis
dysfunction. However, if the amplitude abnormality is the only abnormality time is longer, typically 15 to 20 milliseconds. This is to accommodate for the
noted, its significance is much less certain. Due to considerable variability in longer latency waveforms in children. As in adults, level of alertness does not
the amplitudes of the various waveforms, such a limited abnormality should affect the BAEP, so obtaining BAEP during sleep is acceptable, even preferred,
be very carefully interpreted (1,34). in pediatrics. Sedation may be used to enable patients to sleep during the study;
Side-to-side asymmetries between IPL are also considered significant even however, relevant conscious sedation guidelines must then be followed.
if both IPL are independently within normal limits. The side with the longer Interpretation of BAEP in children greater than 2 years is similar to that
latency is the abnormal one. The interpretation is the same as interpretation of adults. After this age, the BAEP waveforms and their latencies are similar
of prolonged IPL. to adults. In premature babies and young children, certain differences must
be considered. Absolute latency of wave I is not evaluated when assessing
Pediatric Considerations CNS function as it is frequently affected by hearing loss. Wave III is not
well formed, and consequently, only the waves I–V IPL is evaluated (45).
BAEP, more than most other types of EP, are often performed in pediatrics. The waves I–V IPL is compared with age-matched controls. Ideally, these
Not only do they evaluate the brainstem, they can also evaluate hearing in controls are obtained in the same laboratory; however, this is not always
small children in whom other types of audiological testing may be unreli- possible. If published norms are used, the reference laboratories technique
able. In this section, maturational issues, special technical considerations, must be followed. Waves I–V IPL norms are available for every few weeks of
and interpretation nuances will be discussed. The clinical uses of pediatric age starting at 33 weeks CA. The reader is referred to the references for these
BAEP will be discussed later in the chapter. normative data tables (40,46).
BAEP can be recorded as early as 30 weeks CA, and at this age waves III
and V may not be present (39). By term, waves I, III, and V are present, Clinical Correlations
but the amplitude is about one-half of adult BAEP. All five waves are pres-
ent by 3 to 4 months of age, but some waves are fused together. By 1 year, Neurologic and hearing problems can result in BAEP changes. BAEP are
the BAEP looks similar to that of an adult, and by age 4 to 5 years, the most often used to evaluate the functional integrity of the auditory pathways
amplitude also matches adults (40). Waves I and V have prolonged latency in the CNS. As with other types of EP studies, BAEP abnormalities are not
at birth. Wave I reaches adult latency values by 2 months, while wave V specific for a particular disease. In young children, hearing screening can
latency does not reach adult values until 2 to 3 years (41,42). This implies also be performed with BAEP. Previously, hearing assessments in children
that there is a gradual reduction of the waves I–V IPL up to 2 to 3 years. and adults were done with BAEP. This is called the latency/intensity (L/I)
The waves I–V IPL is 5 milliseconds in the preterm infant, 4.5 milliseconds series. Because more sensitive audiological tests are available to test hearing,
at 8 months, 4.2 milliseconds by 12 months, and 4.1 milliseconds at 2 years the L/I series is now seldom performed. This is discussed briefly later.
(43). Gender differences are insignificant in this age group and do not result BAEP can be helpful in the assessment of multiple sclerosis (MS). Any
in clinically meaningful differences in absolute latencies and IPL (44). of the IPL can be prolonged depending on the site of demyelination. The
BAEP abnormalities, seen most commonly in MS, include prolongation of prolongations of IPL and absolute latencies (34,38). Intrinsic brainstem
waves III–V IPL and wave V amplitude abnormalities (47–50). Wave I–III tumors, regardless of pathology, can produce BAEP abnormalities if they
IPL abnormalities are less common. involve the auditory pathways.
Other demyelinating and dysmyelinating conditions have been associated Vascular lesions of the brainstem produce BAEP abnormalities only if
with abnormal BAEP. In Krabbe disease, BAEP are affected early in the the auditory pathways are involved. If lesions are below the level of the
disease, with loss of waves III and V or prolongation of waves III–V IPL pontomedullary junction, the BAEP will usually be normal. This has been
being prominent findings (26). This is reflective of severe upper brainstem demonstrated by the presence of normal BAEP in patients with locked-in
dysfunction in these patients. Moreover, BAEP findings correlate with the syndrome due to lesions in the medulla (61). Various stroke syndromes with
severity of disease noted on neuroimaging (27). Other leukodystrophies such lesions above the pontomedullary junction may result in BAEP abnormali-
as adrenoleukodystrophy and metachromatic leukodystrophy have similar ties (62,63). Brainstem hemorrhages behave in a manner similar to isch-
findings, but they occur later in the disease course (29). emic lesions (64). Lower pontine lesions affect wave III and the waves I–III
Mass lesions of the cerebellopontine angle (CPA) can result in a variety IPL, whereas higher lesions leave wave III intact (65). BAEP have also been
of BAEP abnormalities depending on the size of the lesion. Many of these shown to be helpful in prognosticating outcome from infratentorial hemor-
lesions are tumors, such as acoustic neuromas and meningiomas, which rhages and primary subarachnoid hemorrhages; normal EPs imply good
manifest clinically by causing hearing loss by compressing the vestibuloco- prognosis, while absence of waveforms suggests poor outcome (66,67).
chlear nerve. About 75% of the nerve fibers need to be involved before hear- Various types of coma have been evaluated with BAEP. If the cause of
ing thresholds are affected (34). The sensitivity of BAEP in detecting CPA coma does not directly affect the auditory pathways, the BAEP will be
tumors has ranged from 93% to 100% in some studies and has been as low as normal. Coma due to metabolic dysfunction has little effect on the BAEP
75% to 76% in others (51–54). Acoustic neuromas, by virtue of their attach- (65). Patients in persistent vegetative state (PVS) have a normal BAEP,
ment to the vestibulocochlear nerve, produce hearing deficits earlier than presumably because the site of primary involvement is rostral to the thalamus
other CPA tumors. BAEP abnormalities commonly noted with CPA tumors (68–70). However, if supratentorial causes of coma cause distortion or pres-
include loss of all waves, loss of waves after wave I, II, or III, and prolonga- sure on the brainstem, BAEP abnormalities can be seen (38).
tion of waves I–III and I–V IPL. Waves III–V IPL may also be prolonged, In patients with brain death, BAEP are remarkably abnormal. There is
but this occurs with larger tumors and usually after the waves I–III and I–V either complete absence of all waves or presence of only wave I (71). When
IPL have already been prolonged (55,56). In these cases, waves III–V IPL all waves are absent, severe hearing loss and technical problems must be
from stimulation of the contralateral ear is also prolonged (57,58). These excluded. Additionally, absence of waves should not be assumed to be
abnormalities regress with tumor removal. consistent with brain death. Barbiturates in anesthetic doses sufficient to
Occasionally, patients with CPA tumors do not have wave I recordable cause an isoelectric EEG do not affect the BAEP (72). Thus, BAEP can be
by conventional methods (59). For these patients, additional effort should useful in confirming brain death in patients being treated with high doses of
be expended to determine the presence and location of wave I by increas- barbiturates or anesthetics.
ing the stimulation level to the maximum output available. This may reveal BAEP abnormalities have been demonstrated in a variety of other disor-
the wave I, making determination of IPL possible. If wave I still cannot ders such as myelomeningocele, Arnold-Chiari malformations, central sleep
be identified and wave V appears prolonged, corrections formulas for the apnea, various neurodegenerative disorders, and alcoholism (34). However,
absolute latency of wave V based on the degree of hearing loss have been BAEP are not routinely used to evaluate these disorders.
suggested (60). These can be used to help determine whether the wave V Hearing screening is currently recommended for all newborns (73). BAEP
absolute latency is prolonged only because of hearing loss or because of are a reliable way to perform this screening. They are done as close as pos-
brainstem pathology. sible to the day of discharge from the newborn nursery. Waiting a few days
Other types of brainstem tumors can also cause BAEP abnormalities. after birth to perform the neonatal BAEP screening allows for reabsorption
Brainstem gliomas, fourth-ventricle ependymomas, cerebellar tumors, of fluid from the middle ear, which may complicate testing. Normal hearing
pinealomas, thalamic gliomas, and brainstem metastatic tumors produce threshold in newborns is 25 to 30 dBnHL. Consequently, the BAEP testing
is performed with stimulation intensity of 25 to 30 dBnHL at a rate of 61 Somatosensory Evoked Potentials

per second. Presence of waves I and V are sought, and if they are present,
the child passes hearing screening. Only the presence of waveforms, not their SEP are obtained with electrical stimulation of peripheral nerves. Whereas
latencies, are considered important for hearing screening (39). However, if other sensory stimuli such as touch, position change, and vibration can also
the latencies are excessively prolonged, repeat testing in a few months should produce SEP, clinically only electrical stimulation is used. Any peripheral
be considered. If a reproducible BAEP is not seen at 25 to 30 dBnHL, hear- nerve can be electrically stimulated; however, practically, large mixed nerves
ing screening is failed and should be repeated in 3 months. If BAEP are not are usually chosen. SEP are classified on the basis of the site of stimulation
obtained at repeat testing, audiological assessment should be considered (39). or the nerve that is stimulated. In upper extremity SEP, the median and
Unfortunately, BAEP testing produces a large number of false-positive deter- ulnar nerves are frequently used to obtain SEP. The tibial nerve is used for
minations for hearing loss. Up to 20% of newborns may not have reproducible stimulation in the lower extremity. If the tibial nerve is not available, either
BAEP at birth, and only 1% to 5% of them will have persistent abnormalities by virtue of amputation or disease such as neuropathy, the common pero-
at 3 months (74). Despite the high number of false-positive tests, the number neal nerve at the knee can also be used (78). SEP from the stimulation of
of false-negative tests is very low, making BAEP a good screening test. other nerves, such as trigeminal and pudendal, have also been recorded, but
Automated AEP devices are also available for use in newborn hear- these are not used clinically in a nonoperative setting. After stimulation of
ing screening. The devices are handheld and require application of fewer the peripheral nerve, the electrically induced sensory impulse ascends in the
electrodes. They are easier to use and perform testing more quickly than dorsal column pathway through the spinal cord and brainstem to the cortex.
standard BAEP testing. The stimulus intensity is 35 dBnHL. Transient SEP waveforms are recorded from various points of this ascending pathway.
evoked otoacoustic emissions, which are sounds produced by the cochlea in The potentials recorded are short-latency EP, occurring within 30 to 50 mil-
response to broadband clicks, are also recorded by these devices. The hand- liseconds after stimulation, with both negative and positive polarities. Some
held devices also interpret the AEP and otoacoustic emissions. The sensitiv- waveforms represent near-field potentials, while others are far-field.
ity for detecting hearing loss for these automated devices is high, and few
patients are referred for additional audiological testing (75–77). Anatomy and Waveform Generators
Latency/Intensity Series Stimulation of mixed nerves with an electrical stimulus results in the activa-
tion of orthodromic and antidromic nerve fibers. Larger, more myelinated
A L/I series is used to evaluate the presence of hearing loss and determine fibers are activated before smaller fibers, and fibers closer to the stimulator
whether it is conductive or sensorineural. It can be considered when the are depolarized before fibers that are further away. Though both sensory
wave I absolute latency is prolonged, suggesting possible hearing loss. The and motor fibers are activated with an electrical stimulus, it is the ortho-
BAEP is performed first with a stimulation intensity of 70 dBnHL, and dromically ascending sensory fibers that produce the various components
the latency of the wave V is noted. It is repeated with decreasing stimulation of the SEP.
intensity by 20-dB increments down to 30 dBnHL. The wave V latency at Median or ulnar nerve stimulation results in the activation of sensory
each intensity is noted. As the stimulation intensity decreases, the latency of fibers that ascend to the dorsal root ganglia where their cell bodies lie. Axons
wave V prolongs. The latency change per dB is calculated in microsecond from these ganglia traverse the dorsal root and, without synapsing, ascend
per decibel. Conductive hearing loss is present if wave V is not seen at either in the dorsal column tract to the nucleus cuneatus. After synapsing on this
50 or 30 dBnHL. When wave V is present at all stimulation intensities, but nucleus, second-order neurons arise and decussate to the contralateral side
the latency change is greater than 60 µs per dB, sensorineural hearing loss and ascend in the medial lemniscus. The medial lemniscus ascends through
is suspected (36). The L/I series can also be performed using the latency the brainstem to the ventroposterior lateral (VPL) nucleus of the thalamus,
of wave I instead of wave V. Because more sensitive audiological tests are where another synapse occurs. Third-order neurons from the VPL nucleus
available to diagnose hearing loss and differentiate its type, an L/I series is ascend in the thalamocortical radiation to synapse in the hand area of the
seldom performed. primary sensory cortex (79).
In the lower extremities, tibial nerve stimulation produces activation of a TABLE 15.7 SEP Waveforms and their Generators
pathway very similar to the median/ulnar nerve stimulation. Sensory nerve
fibers in the tibial nerve ascend to the dorsal root ganglia, enter the dorsal Label Generator
horn of the spinal cord, and ascend in the dorsal column tract. The first Upper extremity (median and ulnar nerve)
synapse occurs in the nucleus gracilis, from where second-order fibers decus-
EP (N9) Brachial plexus
sate and ascend in the medial lemniscus. After synapsing in the VPL nucleus,
third-order neurons give rise to fibers that travel in the thalamocortical pro- N13 Cervical spinal cord
jections to the foot area of the primary sensory cortex. Since the foot area P14 Nucleus cuneatus/medial lemniscus
is over the convexity of the cerebral cortex, the near-field cortical waveform N18 Thalamus
may be recorded on the scalp ipsilateral to the side from which it was gener- N20 Somatosensory cortex
ated, contralateral to it or from the midline (80). Peroneal nerve SEP are very Lower extremity (tibial nerve)
similar to tibial nerve SEP, except that their absolute latencies are shorter. PF Tibial nerve in popliteal fossa
The SEP waveforms recorded represent the ascent of the volley of stimu-
LP Cauda equina/lumbar segments of spinal cord
lation. As with BAEP, each waveform is produced by contributions from
several neural generators, and many structures contribute to more than one P31 Nucleus gracilis/medial lemniscus
waveform. Nonetheless, it is useful to attribute waveforms to certain neural N34 Thalamus
structures that contribute in large part to that waveform. This allows for P37 Somatosensory cortex
localization of lesions when waveforms are absent or IPL are prolonged.
The nomenclature of the SEP waveforms includes the polarity and typi- EP, Erb’s point; PF, popliteal fossa; LP, lumbar potential.
cal latency of the waveform (i.e., the N13 waveform is a negative potential
typically occurring at 13 milliseconds after stimulation). In some cases, the
waveforms are named according to their site of generation (i.e., the LP is
the lumbar potential, arising from the cauda equina and lower spinal cord). Stimulation
The waveforms recorded after stimulation of the median or ulnar nerve The electrical stimulus used for eliciting SEP is uncomfortable, and patients
are the Erb’s point (EP, N9), cervical (N13), subcortical (P14 and N18), and must be informed about what to expect so that cooperation can be maxi-
cortical potentials (N20). The EP, N13, and N20 waveforms are near-field mized. Having the patient seated in a comfortable chair or lying in bed is
potentials, while the P14 and N18 waveforms are far-field potentials. After best. The level of alertness does not affect most SEP waveforms, and if
tibial nerve stimulation, the commonly recorded waveforms are the popliteal the patient becomes drowsy during the study, many of the waveforms will
fossa (PF), lumbar (LP), subcortical (P31 and N34), and cortical potentials not change appreciably. However, cortical waveforms may be affected (6).
(P37). The PF, LP, and P37 waveforms are near-field potentials, while the It is important to maintain the patient’s level of alertness when perform-
P31 and N34 waveforms are far-field potentials. The generators most often ing tibial SEP. Limb length should be noted, as very tall patients will have
associated with each of these waveforms are presented in Table 15.7. longer absolute latencies due to longer limbs. The IPL will not be affected.
The temperature of the limb should also be considered; cooling of the limb
Methodology results in slower peripheral conduction and longer absolute latencies; IPL
are affected much less (81). Peripheral conduction velocities may be much
There are several unique features about the methodology for SEP compared slower. Because the IPL are affected less, in most cases the limbs do not have
with VEP and BAEP. The stimulation technique is not altered; stimulation is to be warmed as in the EMG laboratory. Pathological factors must be con-
always with an electrical stimulus. The recording montage consists of several sidered as well. When distal peripheral nerves are diseased as in neuropathy,
channels, each assessing the volley of depolarization at different anatomical stimulation may require higher intensity. In severe cases, distal stimulation
locations. These features of stimulation and recording are discussed later. may not be possible, and stimulation is performed at more proximal sites
(i.e., lower limb peripheral neuropathy may make tibial nerve SEP impos- visualize the various waveforms (83). The electrodes applied and montage
sible to obtain, so peroneal nerve SEP are attempted). used are different for upper and lower extremities.
A variety of stimulating electrodes can be used to deliver the transcutane- The four-channel recording montages recommended by the American
ous electrical stimulus. The skin is prepared, and the contact impedance of Clinical Neurophysiology Society (ACNS) incorporate referential and bipo-
the electrodes is reduced to 5,000 Ω or less. This reduces the discomfort of lar recording derivations. Electrodes for referential derivations are placed
stimulation. EEG disc electrodes are commonly used and are secured to the such that the active electrode is as close to the neural generator as possible,
skin with paste or tape. Self-adhesive electrodes can also be used and have while the reference electrode is sufficiently far away that it is “silent” but not
the added advantage of being quicker to apply. Both cathode and anode so far as to introduce unwanted biologic signals and other artifacts. All the
are placed along the length of the nerve about 2 to 3 cm apart. The cathode waveforms recorded by the active electrode will be displayed in the deriva-
is placed proximally, and the anode distally. A surface ground electrode is tion because the reference electrode is “silent.” In a bipolar derivation, how-
placed between the cathode and the first recording electrode. Needle elec- ever, both electrodes record some waveforms of the SEP. The waveforms that
trodes can also be used for stimulation, but since they are invasive they are are common to both electrodes are cancelled (common mode rejection) by
seldom used in awake patients. the differential amplifier. Only unique waveforms are not cancelled and dis-
Placement of the stimulating electrodes is similar to that which is used in played in that derivation. Bipolar derivations are useful as they can clearly
the EMG laboratory. For stimulation of the median nerve, the cathode is identify a near-field potential by allowing cancellation of far-field potentials
placed 2 cm proximal to the wrist crease between the tendons of the flexor that occur at nearly the same time.
carpi radialis (FCR) and palmaris longus muscles. The cathode for ulnar The locations for placement of electrodes to record SEP from stimulation
nerve stimulation is also placed 2 cm proximal to the wrist crease but medial of upper extremity (median and ulnar) nerves are: Fz, CPi, CPc, C5 spine
to the FCR tendon. The tibial nerve is stimulated with the cathode between (C5S), Erb’s point contralateral, and Erb’s point ipsilateral. The montage
the medial malleolus and the Achilles tendon, and for the stimulation of recommended by the ACNS is presented in Table 15.8 (83). Each deriva-
the peroneal nerve, the cathode is placed laterally in the distal part of the tion of this montage is useful for displaying a specific waveform or group
PF, medial to the fibular head. The anode for each nerve is placed 2 to 3 cm of waveforms from a presumed neuroanatomic generator(s). The channels
distal to the cathode along the course of the nerve. of the montage are labeled 1 to 4 from bottom to top. Another derivation
Monophasic rectangular pulses are used to deliver the electrical stimulus.
Constant current stimulators are used most often, though constant voltage
ones can also be used. The stimulation duration is usually set at 100 to 300
µs, and intensity is increased until a visible twitch is noted. This is known as TABLE 15.8 Montage for Recording Median/Ulnar Nerve
the threshold intensity. In healthy nerves, a stimulation intensity of 5 to 15 SEP Recommended by the ACNS
mA is sufficient to induce a muscle twitch. However, diseased nerves may Montage Waveform(s) Localization
require substantially higher stimulation intensities. If a pure sensory nerve
CPc-CPi N20 Somatosensory cortex
is used to obtain an SEP (such as trigeminal or pudendal SEP), stimulation
CPi-EPc or Fz-EPc P14, N18 Nucleus cuneatus, medial lemniscus,
intensity is set at two to three times sensory threshold. A stimulation rate of
thalamocortical radiation
3 to 5 per second is commonly used (82).
C5S-EPc N13 Dorsal root, dorsal columns, cervical
Recording cord
SEP recording electrodes are placed so that the volley of depolarization can EPi-EPc EP/N9 Brachial plexus
be recorded at various locations as it ascends the nervous system. As with
CPc, centroparietal-contralateral; CPi, centroparietal-ipsilateral; EPc, Erb’s point contra-
stimulating electrodes, EEG disc electrodes are used most often and are lateral; Epi, Erb’s point ipsilateral; C5S, 5th cervical spine.
applied with paste or collodion. The electrode impedances should be below American Clinical Neurophysiology Society. Guideline 9D: guidelines on short-latency
5,000 Ω. A minimum of four channels should be recorded for each EP to somatosensory evoked potentials. J Clin Neurophysiol 2006;23(2):168–179.
that is commonly used is C5S-Fz. This derivation is discouraged, as the C5S the differential amplifier, and only the N20 waveform is displayed. A sample
electrode will record the N13, while the Fz electrode records the P14/N18. median nerve SEP is presented in Fig. 15.16.
The composite waveform will make it difficult to identify individual com- Adding additional channels to the standard montage that help elucidate
ponents (84). The recommended montage has both referential and bipo- difficult-to-identify waveforms may be useful. Examples of this may be add-
lar derivations. EPi-EPc, C5S-EPc, and CPi-EPc (Fz-EPc) are referential ing additional scalp electrode to more confidently identify the N20 wave-
derivations as the first electrode is active and records various components form in case of normal variations (83). An anterior cervical (AC) electrode
of the SEP, and the second electrode (EPc) is “silent” but is not so far as to placed above the thyroid cartilage records the P13 waveform. This is the
introduce excessive noise and artifacts. The CPc-CPi is a bipolar derivation positive end of the dipole of the N13 waveform, so a C5S-AC derivation
as both electrodes record the far-field subcortical potentials (P14, N18), but may make identification of this waveform easier.
only the first records the near-field cortical potential (N20). Because the SEP obtained by stimulation of lower extremity (tibial and common pero-
far-field potentials are in “common mode,” they are rejected (cancelled) by neal) nerves are recorded from electrodes placed in the following locations:
A B
Figure 15.16: Left (A) and right (B) median

nerve SEP obtained from a 32-year-old patient.
The typical montage used in the author’s labo-
ratory is shown. This has referential and bipo-
lar derivations recommended by the ACNS.
The study is normal with all obligate waveform
reproducibly present. (©AMH.)
Fpz, CPz, C5S, iliac crest (IC), T12 spine (T12S), popliteal fossa distal extremity SEP cortical waveform is that its scalp projection is highly vari-
(PFd), and PF proximal (PFp). The montage recommended by ACNS is able. It may be best recorded in the midline (CPz) or contralateral to side
presented in Table 15.9 (83). Along with the minimum recommended mon- of generation (ipsilateral to side of stimulation, CPi). Additional channels
tage, additional channels that are commonly used are also noted. As with can also be used for recording lower extremity SEP. A common additional
upper limb SEP, each derivation is useful for displaying a particular wave- derivation includes CPc-Fpz; this will provide another site for recording
form or group of waveforms from a presumed neuroanatomic generator(s). the cortical waveform in case it projects ipsilateral to side of generation
The C5S electrode is used differently in lower and upper extremity SEP. (contralateral to side of stimulation). T10 spine (T10S)-IC and L3 spine
Whereas with upper extremity SEP, the C5S electrode records the N13 (L3S)-IC are other derivations that may be useful. These record the LP
waveform, with lower extremity SEP it serves as a reference or “silent” elec- waveform as it ascends the dorsal column pathway. The LP waveform is a
trode. This is because the ascending SEP volley from the tibial and common small potential and difficult to record, and consequently, these latter elec-
peroneal nerves is too small to be recorded from the C5S electrode. The IC trodes are seldom used.
electrode serves the same purpose; it is a silent electrode on a nearby bony In the author’s laboratory, CPi-Fpz and CPc-FPz derivations are replaced
prominence. by CPi-C5S, CPz-C5S, and CPc-C5S derivations. All of these will show
The lower extremity SEP montage recommended by the ANCS includes the subcortical waveforms and varying degrees of the cortical waveforms.
referential and bipolar derivations (83). T12-IC and Fpz-C5S are referential Though ideally, subcortical and cortical waveforms should be visualized in
derivations in which the active electrode is referenced to a silent electrode. different channels, in this case seeing them together often helps with iden-
PFd-PFp, CPz-Fpz, and CPi-Fpz are bipolar derivations. PFd-PFp records tification of the cortical waveform. The CPc-C5S derivation often does not
a wave of depolarization as it is transmitted through the tibial nerve. This have the cortical waveform but has the subcortical one. Comparing it with
derivation is not used with peroneal nerve stimulation as the stimulating the other two derivations helps identify the cortical waveform (Fig. 15.17).
electrodes are very close to this recording location. CPz-Fpz and CPi-Fpz The CPz-Fpz and Fpz-C5S derivations are still used to visualize only the
derivations both record the cortical waveform. Both active and reference cortical and subcortical waveforms, respectively.
electrodes for these derivations are on the scalp and record the subcorti- SEP from common peroneal nerve stimulation are recorded in the same
cal waveforms. CPz and CPi also record the cortical waveform. With these manner as tibial nerve SEP. The major difference is that common peroneal
derivations, the subcortical waveforms are in “common mode” and thus nerve stimulation is more proximal than tibial nerve stimulation. Conse-
rejected. The rationale for using at least two electrodes to record the lower quently, the absolute latencies of the waveforms will be about 10 milliseconds
shorter. The PF response cannot be recorded, as PFd and PFp electrodes
cannot be placed in view of their proximity to stimulating electrodes. The
TABLE 15.9 Montage for Recording Tibial Nerve SEP various IPL are the same for both lower extremity SEP.
Amplifier setting for SEP recording has been recommended by the ACNS
Montage Waveform(s) Localization (83). The filter band pass should be 30 to 3,000 Hz. The analysis time for
CPi-Fpza
P37 Somatosensory cortex upper extremity SEP is at least 40 milliseconds and at least 60 milliseconds
CPz-Fpza P37 Somatosensory cortex
for lower extremity SEP. The number of repetitions that need to be averaged
a depends on the amount of noise, but 2,000 to 3,000 repetitions are common.
Fpz-C5S P31, N34 Nucleus gracilis, medial lemniscus
T12S-ICa LP Cauda equina, dorsal columns, lumbosacral
spinal cord
Interpretation
PFd-PFp PF Tibial nerve Interpretation of SEP involves first identifying the presence of all wave-
a
forms and whether they have been correctly identified and labeled. The
Channels recommended by the ACNS (83).
CPi, centroparietal-ipsilateral; CPz, centroparietal midline; Fpz, frontopolar midline; C5S, presence of obligate waveforms is determined. The obligate waveforms for
5th cervical spine; T12S, 12th thoracic spine; IC, iliac crest; PFd, popliteal fossa distal; upper- and lower extremity SEP are noted later. The latencies of the vari-
PFp, popliteal fossa proximal; LP, lumbar potential; PF, popliteal fossa. ous waveforms are noted. The absolute latencies are not a good marker
A B
Figure 15.17: Left (A) and right (B) median nerve SEP obtained
from a 13-year-old patient. The typical montage used in the
author’s laboratory is shown. This has referential and bipolar
derivations recommended by the ACNS and additional deriva-
tions to enhance various waveforms. The additional channels
include PFd-PFp, CPz-C5S, CPi-C5S, CPc-C5S. (CPi and CPc
are CP3 and CP4 depending on whether the left or right side
was stimulated.) The latter three channels help better identify
the cortical and subcortical waveforms (see text for details).
The study is normal with all obligate waveform reproducibly
present. (©AMH.)
for central conduction, and so IPL are also noted. The IPL that should one of these is considered an abnormality. The absolute latency of each
routinely be measured have been recommended by the ACNS guidelines of the waveforms should be determined, as that will allow the calculation
(83). The various latencies are compared with normative data to determine of IPL. However, the absolute latency of the EP waveform is important,
whether they are within the normal range. Even if absolute latencies and since its prolongation may indicate a peripheral neuropathy. The EP wave-
IPL are within normal limits, a side-to-side comparison should be made. form absolute latency and the distance from the stimulating and recoding
Significant asymmetry also indicates an abnormality on the side with the electrodes can be used to calculate the nerve conduction velocity of the
longer latency. Reduced amplitudes of the waveforms are of uncertain sig- median or ulnar nerve. However, a slowed conduction velocity should be
nificance and are not considered abnormalities unless IPL are also abnor- interpreted with caution as supramaximal stimulation is not used to elicit
mal. Normative data from the author’s laboratory for upper- and lower SEP, and consequently, the nerve’s fastest conducting fibers may not have
extremity SEP are presented in Table 15.10. been activated. Thus, the peripheral conduction velocity calculated in the
When evaluating upper extremity SEP, the obligate waveforms that EP laboratory is usually slower than that calculated in the EMG labora-
should be identified are: EP, N13, P14, N18, and N20 (83). Absence of any tory. The IPL that are determined include EP-N20, EP-P14, and P14-N20.
TABLE 15.10 SEP Normative Data from the Author’s Laboratory. Obligate waveforms for lower extremity SEP are LP, N34, and P37 (83).
The PF waveform is not considered an obligate waveform. Absence of any
Wave Latency, IPL or Abs. (ms)a Max. asymmetry of these waveforms is considered an abnormality. The absolute latency of
Median/ulnar (stimulation rate ≈ 5/s) each waveform should be determined to calculate the IPL. If the absolute
latency of the PF waveform is prolonged, a peripheral neuropathy may be
EP-P14 4.9 0.5
suspected. This latency can be used to calculate the nerve conduction veloc-
P14-N20 7.8 1.3 ity of the tibial nerve. However, the same caveats as noted for prolonga-
EP-N20 11.5 1.2 tion of the absolute latency of the EP waveform and slowing of conduction
EP 12.4 0.6 velocities of the median and ulnar nerves discussed earlier apply here as
N20 22.5 1.4 well. The IPL that are determined are LP-P37 and PF-P37. The LP-P37
Median/ulnar (stimulation rate ≈ 31/s) IPL evaluates the dorsal column pathway from the lower spinal cord to the
EP-P14 5.2 1.4
contralateral somatosensory cortex, while the PF-P37 evaluates the pathway
from the peripheral (tibial) nerve at the popliteal fossa to the contralateral
P14-N20 9.0 1.8
somatosensory cortex. The former is preferred, as it does not include con-
EP-N20 13.1 1.3 duction through the peripheral nervous system. However, since the LP can-
EP 12.9 0.6 not be recorded in even some subjects due to its low amplitude, the PF-37
N20 24.5 1.6 IPL is also evaluated. The absolute latency of the P37 waveform is also
Tibial (stimulation rate ≈ 5/s) determined. This is helpful if both the LP and the PF waveforms cannot be
LP-P37 20.2 3 recorded. Prolongation of this latency can suggest a lesion between the site
of stimulation and the contralateral somatosensory cortex. While this mea-
PF-P37 35.0b 4
b
sure is helpful if both LP and PF waveforms are absent, it does not differ-
P37 47.0 5
entiate between peripheral and CNS lesions. Peroneal nerve SEP are similar
For peroneal nerve stimulation, subtract 10 milliseconds from all values.
to tibial SEP. Key differences include the absence of the PF waveform and
a
Latency values 3 SD beyond mean. shorter absolute latencies of the waveforms by 10 milliseconds. The IPL are
b
Values may need to be height adjusted. the same as tibial SEP.
IPL, interpeak latency; Abs, absolute; Max, maximum.
Abnormalities
The N13-N20 IPL is also frequently calculated; this IPL is not used in the The most significant abnormality in a SEP is the absence of an obligate
author’s laboratory (83). The EP-N20 IPL evaluates the dorsal column waveform. This indicates a lesion of the neural generator that produces
pathway between the brachial plexus and the contralateral somatosensory that waveform or of the dorsal column pathway distal to this structure.
cortex. The EP-P14 IPL assess the pathway between the brachial plexus For example, absence of the P14 waveform indicates a lesion in the medulla
and the medulla (nucleus cuneatus) ipsilateral to side of stimulation, while or distally. The exact localization of the lesion depends on the presence or
the P14-N20 IPL assess the pathway between the medulla and the somato- absence of other waveforms and IPL. Technical adequacy of the EP study
sensory cortex contralateral to side of stimulation. Some laboratories pre- must be confirmed before absence of a waveform is considered abnormal.
fer the N13-N20 IPL as it assesses the dorsal column pathway in almost Prolongation of IPL is also a significant abnormality and implies a lesion
its entirety from the spinal cord to the somatosensory cortex and excludes between the generators of the corresponding waveforms. Prolongation of
peripheral contributions. Dividing this IPL by the distance from the C5S to the P14-N20 IPL suggests a lesion affecting the dorsal column pathway
the contralateral somatosensory cortex, the central conduction time (CCT) between the medulla and the somatosensory cortex. In some situations, pro-
can be determined. Normative values for CCT are also available (85). Pro- longation of the absolute latency of a waveform may be important. This
longation of any of these IPL suggests a lesion between the neural genera- latency measure usually includes peripheral nerve conduction and not nec-
tors for the respective waveforms. essarily central conduction. As an example, the absolute latency of the EP
response measures conduction in the median or ulnar nerves from the point neuropathies as they can be more completely evaluated in the EMG labora-
of stimulation to the Erb’s point, and its prolongation may imply a periph- tory. If only the EP waveform is present and has a normal latency but all
eral neuropathy. Amplitude decrement of the waveforms is not generally other obligate waveforms are absent, the lesion is in the dorsal column path-
considered a significant abnormality unless it is accompanied by a latency way proximal to the brachial plexus but distal to the cervical spinal cord (as
change. Details of upper and lower extremity SEP are discussed later. the N13 is absent). Presence of the EP and N13 waveforms and absence of
With upper extremity SEP, absence of any of the obligate waveforms usu- the others implies a lesion between the cervical spinal cord and the contra-
ally suggests an abnormality. As noted earlier, absence of a waveform sug- lateral somatosensory cortex. If the EP, N13, and P14 waveforms are pres-
gests a lesion of the corresponding neural generator or the dorsal column ent and N18 and N20 waveforms are absent, the lesion is more proximal,
pathway distal to it. If all the obligate waveforms (EP, N13, P14, N18, and between the medulla and somatosensory cortex likely contralateral to the
N20) are absent, the technical quality of the study must be checked. If it is side of stimulation. If only the N20 waveform is absent, the lesion is most
confirmed that there are no technical issues, such an abnormality suggests a likely between the thalamus and the somatosensory cortex contralateral to
lesion distal to the brachial plexus, such as a severe peripheral neuropathy. the side of stimulation (Fig. 15.18). If the EP and N20 waveforms are pres-
Upper extremity SEP are usually not performed for assessment of peripheral ent and of normal latency but the N13, P14, or N18 waveform is absent,
A B
Figure 15.18: Left (A) and right (B) median nerve SEP from
a 48-year-old patient. This study shows absence of the N20
waveform after stimulation of the right median nerve. The
EP-P14 IPL is normal. The left median nerve SEP is normal.
The localization of this abnormality is between the thala-
mus and the somatosensory cortex contralateral to the
side of stimulation (right side). This patient complained of
numbness of the left side of his face. Notice the additional
channels: AA-EPc and C5S-AA. AA is the Adam’s apple or
AC electrode and LEP/REP is the EPc electrode. Notice that
the N13 is more clearly identified (has higher amplitude) in
the C5S-AA derivation than C5S-EPc (see text for additional
details). (©AMH.)
the clinical significance is uncertain. In many such situations, the waveforms A B

may not be identified because those channels are contaminated by noise. In
such a situation, the study should not be interpreted as abnormal (83).
The most common IPL evaluated in upper extremity SEP are the EP-P14,
P14-N20, and EP-N20. Prolongation of the EP-P14 IPL suggests a lesion
between the brachial plexus and the medulla ipsilateral to the side of stimula-
tion. If the P14-N20 IPL is prolonged, the lesion is likely between the medulla
and the somatosensory cortex contralateral to the side of stimulation (Fig.
15.19). A prolonged EP-N20 IPL suggests a lesion anywhere between the
ipsilateral brachial plexus and the contralateral somatosensory cortex. When
such a prolongation is present, often the EP-P14 or the P14-N20 IPL is also
prolonged, helping further localize the lesion. However, even if one of the
latter IPL is not prolonged, the study is still considered abnormal, with the
location of the lesion interpreted as being more diffuse. Some laboratories
also evaluate the N13-N20 IPL, the prolongation of which suggests a lesion
between the cervical spinal cord and the contralateral somatosensory cortex.
In upper extremity SEP, the absolute latency of the EP waveform should
be noted. Prolongation of this may suggest a lesion distal to the brachial
plexus. Usually, this implies a peripheral neuropathy, but a plexopathy may
also be possible. The nerve conduction velocity should also be determined
by dividing the absolute latency of the EP waveform by the distance from
site of stimulation to the site of recording. Often when the absolute latency
of the EP waveform is prolonged, the nerve conduction velocity will also
be slow. However, several technical factors must be considered before inter-
preting the study as showing a peripheral neuropathy. When the limb being
stimulated is cold, the peripheral conduction can be slowed. In many labora-
tories, the limb being stimulated is not warmed prior to a SEP study. Addi-
tionally, supramaximal stimulation is not used to obtain SEP. Consequently,
Figure 15.19: Left (A) and right (B) median nerve SEP from a 51-year-old patient.
the fastest conducting fibers may not be stimulated.
This study shows prolongation of the P14-N20 and EP-N20 IPL after left MNS.
Low-amplitude waveforms are of uncertain significance for upper
The EP-P14 IPL is normal. The right median nerve SEP is normal. The localization
extremity SEP. When the amplitude of a waveform is reduced bilaterally but of this abnormality is between the medulla and the contralateral somatosensory
latencies are normal, it is generally not considered abnormal. Amplitude cortex (right side). This patient complained of decreased sensation in bilateral
asymmetry between the two sides may be significant. Usually, only the EP lower extremities, left worse than right. (©AMH.)
and N20 waveform amplitudes are considered since the other waveforms
often have small amplitudes. Before considering the amplitude asymme-
try, the intensity of peripheral nerve stimulation must be considered. Dif- stimulating electrodes to the nerve may be slightly different. This may pro-
ference in stimulation intensity will result in a difference in the number duce the amplitude asymmetry. Difference in level of alertness may affect
of nerve fibers activated and the amplitude of the EP waveform. Because the amplitude of the N20 waveform (6). If the patient falls asleep between
of central amplification (discussed earlier), the N20 waveform amplitude when the SEP of the two sides are performed, the N20 waveform amplitude
is affected less with intensity of stimulation. Even when peripheral nerves may be asymmetric. If the amplitude asymmetry is not due to technical
are stimulated with the same intensity of stimulation, the proximity of the issues, an abnormality may be present on the side of the lower amplitude. It
is interpreted the same way as if the waveform was absent, though without waveform is important to identify. If the LP waveform is present and of
as much certainty. normal latency, the lesion is between the lumbosacral spinal cord and the
Lower extremity SEP are interpreted in a manner similar to upper contralateral somatosensory cortex. When the PF, LP, and N34 waveforms
extremity SEP. Absence of obligate waveforms is considered an abnormal- are present but the P37 waveform is absent, the lesion is between the con-
ity. If all obligate waveforms (LP, N34, and P37) and the PF waveform are tralateral thalamus and the somatosensory cortex. If the PF, LP, and N34
absent and technical problems have been excluded, a lesion distal to the waveforms are absent, but the P37 waveform is present and has a normal
popliteal fossa is suspected. Most often this will be due to a peripheral latency, the interpretation is uncertain. Often, the former waveforms may
neuropathy. Absence of the LP, N34, and P37 waveforms with a present be absent owing to artifact contamination, in which case the study is still
PF waveform suggests a lesion between the popliteal fossa and the somato- considered normal.
sensory cortex contralateral to the side of stimulation (Fig. 15.20). The The IPL that are important to consider for lower extremity SEP are the
lesion in this case may be in the peripheral or CNS. In such a case, the LP PF-P37 and LP-P37 IPL. Prolongation of the PF-P37 IPL suggests a lesion
A B
Figure 15.20: Left (A) and right (B) tibial nerve SEP from a 53-year-old
patient. This study shows absence of waveforms above the PF and LP wave-
forms after stimulation of the left and right tibial nerves. The localization
of this abnormality is between the lower spinal cord and the somatosen-
sory cortices bilaterally. Whereas lesions of both somatosensory cortices
are possible, the more likely possibility would be a spinal cord or brain-
stem lesion. This patient complained of bilateral lower extremity weakness.
(©AMH.)
between the popliteal fossa and the contralateral somatosensory cortex. The The most important absolute latency to consider in lower extremity
preferred IPL to evaluate is the LP-P37 IPL as this excludes the peripheral SEP is the absolute latency of the P37 waveform. This latency is impor-
nervous system (PNS) for the potential site of abnormality. If this IPL is tant because often the PF, LP, and N34 waveforms may not be reproducible
prolonged, the lesion is between the lumbosacral spinal cord and the con- because of technical issues. An abnormal P37 waveform absolute latency
tralateral somatosensory cortex (Fig. 15.21). suggests a lesion anywhere between the site of stimulation and the contra-
lateral somatosensory cortex. As such, it does not exclude a PNS lesion.
A prolonged absolute latency of the PF may be considered as well, but this is
A B evaluated less often than other latencies. If prolonged, it suggests a periph-
eral nerve lesion.
Amplitude assessment of lower extremity SEP waveforms is similar to
upper extremity SEP. Amplitudes of the PF and P37 waveforms is consid-
ered. Much as in upper extremity SEP, asymmetric PF responses should raise
the issue of asymmetric stimulation of the peripheral nerve. Asymmetry of
the P37 is likely if there is a state change of the patient (i.e., patient becomes
drowsy or falls asleep) between left and right side stimulation. If these and
other issues already discussed for upper extremities can be excluded, a lesion
on the side of the lower amplitude is suspected. The interpretation is the
same as for an absent waveform, though the lesion is likely to be less severe.
IPL and absolute latencies of upper and lower extremity SEP must be
compared side-to-side as well. Even if the latencies are within normal limits
but there is a significant left to right asymmetry, the longer latency wave-
forms may be abnormal. If such an abnormality is noted, it is interpreted in
the same manner as if the latency was prolonged. Normative data obtained
by any laboratory should include maximum asymmetry allowable between
the two sides.
Often upper and lower extremity SEP are performed together. Absolute
latency and IPL from both studies can be considered together to further
refine the interpretation. For example, if after tibial nerve stimulation the
LP-P37 IPL is prolonged and the P14-N20 IPL is prolonged after median
nerve stimulation (MNS), the lesion is most likely between the medulla
and the contralateral somatosensory cortex. Because the LP-P37 IPL is
prolonged, an additional lower spinal cord lesion cannot be excluded, but
a single lesion would have to be in the former location to account for the
abnormalities in both median and tibial SEP. Another example of how the
median and tibial nerve SEP can be used together is presented in Fig. 15.22.
Figure 15.21: Left (A) and right (B) tibial nerve SEP from a 46-year-old patient.
This study shows prolongation of the LP-P37 IPL after stimulation of the left and
right tibial nerves. The localization of this abnormality is between the lower spinal Pediatric Considerations
cord and both somatosensory cortices. Whereas bilateral hemispheric lesions
could produce this finding, a more likely possibility would be a spinal cord or SEP can be a very useful test for evaluating the dorsal column pathway
brainstem lesion. This patient complained of lower back pain. (©AMH.) in children as this is difficult to assess clinically. However, SEP are more
A B
Figure 15.22: Left (A) and right (B) median and left (C) and right (D) tibial
nerve SEP from a 25-year-old patient. The tibial nerve SEP show absence of
all waveforms above the LP waveforms. The localization of this abnormality is
between the lower spinal cord and bilateral somatosensory cortices. However,
both median nerve SEP are normal. This makes the most likely localization of
the lesion between the lower spinal cord and the cervical spinal cord (below
the level evaluated by the median nerve SEP). This patient had spina bifida and
bilateral lower extremity weakness. (©AMH.)
uncomfortable than other types of EP and consequently are less often per- latencies of these waveforms increase until the late teen years on account of
formed in this age group. increasing limb length. Since limb length does not affect central conduction
Maturational issues of SEP are more complex than other types of EP. very much, the P14-N20 and N13-N20 IPL, both measures of only central
Three factors affect SEP maturation: increasing myelination of fiber tracts, conduction, reach adult values by 10 years and do not change much there-
maturation of synapses, and increasing limb length. Peripheral nerve con- after (87–89). Lower extremity SEP follow the same pattern of maturation
duction reaches adult values by 3 to 4 years, while central conduction does as upper extremity SEP. The latency of the LP waveform is about 16 milli-
not reach adult values until 5 to 7 years (86). Limb length can affect SEP seconds in the preterm infant, decreases to 8 milliseconds at birth, and then
latencies until 14 to 18 years. With median nerve SEP, the EP waveform increases to 14 milliseconds between 1 and 8 years. It increases further as the
latency remains stable from early childhood onward. The cervical, subcorti- child grows. The P37 follows a similar trajectory, decreasing in latency until
cal, and cortical waveforms decrease in latency until 2 to 3 years, reflect- about 8 years and thereafter increasing until full limb length is achieved. The
ing increasing myelination and improved synaptic efficiency. Thereafter, the LP-P37 IPL decreases in latency until 8 years when peripheral and central
C D
myelination is complete. Thereafter, since it is a measure of central conduc- for both the cathode and the anode. Because nerves are in close proximity,
tion, it changes only slightly with increasing height (90,91). stimulation intensity should be such that only the nerve intended is stimu-
The morphology of upper and lower extremity SEP also undergoes matu- lated. The hand twitch should be monitored to confirm that this is the case.
rational changes. The cortical waveforms, N20 and P37, are present in 85% Stimulation technique of the tibial nerve in children is similar to the case
and 50% of term infants after median and tibial nerve stimulation, respec- for adults. The stimulation rate may need to be decreased to 1 per second
tively. By age 3 months, the cortical waveforms are reliably present (88,90). and analysis time increased to make certain that even delayed responses are
The cortical waveforms in young children are broader than adults and reach recorded. Because cortical waveforms can change with state change, SEP
adult shape by about 5 to 8 years (86). should be performed in an awake child. The nomenclature of SEP waves
The methodology for obtaining SEP in children is the same as for adults. in pediatrics is the same as that in adults. Even though the N20 waveform
For stimulation of upper extremity nerves, the anode can be placed in the may normally occur at a much earlier latency than 20 milliseconds, it is still
palm or dorsum of the hand as there may not be enough space on the wrist called the N20.
Interpretation of SEP in children requires comparing latencies to age- absence of N20 waveforms makes the declaration of poor prognosis more
appropriate norms. Pediatric normative data can be found elsewhere (46,86– confident.
91). Prolongation of the IPL has the same significance as in adults. Absolute SEP have been used for many years in the evaluation of MS. They are
latencies of the peripheral potentials (EP and PF waveforms) should be particularly helpful in MS as they can help confirm the presence of sen-
evaluated to determine whether there is evidence of a peripheral neuropa- sory complaints, identify silent lesions, define the anatomic extent of the
thy. However, the caveats noted about evaluating these potentials should be disease, and monitor progress of the disease. With the ready availability of
considered. MRI, some of these reasons are not as important; however, SEP remain an
important test to consider in MS patients. In one analysis of MS patients,
Clinical Correlations 58% had upper limb and 76% had lower limb SEP abnormalities. Looked
at slightly differently, 77%, 67%, and 49% of definite, probable, and pos-
SEP evaluate a larger segment of the nervous system than other types of sible MS patients had SEP abnormalities (106). In many of these patients,
EP. They evaluate sensory pathways, the clinical examination of which is there were no symptoms referable to the SEP abnormality. The commonest
very subjective. SEP provide an object assessment for the clinical examina- abnormalities were loss of waveforms, particularly those after the EP wave-
tion. Median nerve SEP also have utility in predicting the outcome of coma. form after MNS (107). Various IPL are also often prolonged. When all three
Much like other types of EP, SEP are a sensitive indicator of lesions; how- EP modalities are compared, the rates of abnormality for VEP, BAEP, and
ever, the SEP abnormalities are not specific for a particular disease. SEP are 56%, 32%, and 60%, respectively (106). It is likely that SEP have
Median nerve SEP are useful in the evaluation of coma. Bilateral absence the highest rate of detecting abnormalities because they evaluate the longest
of N20 waveform after MNS is the most accurate predictor of poor out- pathway.
come of anoxic encephalopathy (92). This finding has been associated with Transverse myelitis can be differentiated from a more diffuse myelopathic
no false-positive cases, that is, no patient with absent bilateral N20 wave- involvement of the spinal cord in diseases like MS. The median SEP is
forms after MNS had a good outcome (93,94). The American Academy of normal while the tibial SEP is abnormal with a prolonged LP-P37 IPL in
Neurology (AAN) recommends median nerve SEP for the prognostic evalu- patients with transverse myelitis (108). In myelopathic MS, both the median
ation of anoxic encephalopathy 24 to 72 hours after cardiac arrest (95). One and the tibial SEP are abnormal.
study did note that in cardiac arrest patients with poor prognosis, the N20 Brainstem strokes and tumors can affect median and tibial SEP. SEP are
waveforms were rarely present 24 hours after cardiac arrest, but were absent affected when strokes involve the dorsal column pathway. For example, in
after 72 hours (96). Conversely, if the N20 waveforms are present bilaterally, cases with locked-in syndrome, median SEP may or may not be affected,
the SEP is not useful in prognosis. In other words, the presence of N20 does depending on whether the medial lemnisci are involved (1). If the medial
not necessarily suggest a favorable outcome. lemnisci are involved, the SEP will be abnormal. Similarly, brain tumors
In children, median SEP are also useful in determining outcome of coma. can affect SEP if the dorsal column pathway is affected. Depending on the
Absence of N20 waveforms after MNS has been noted to have a positive pattern of abnormality of the median and tibial SEP, further localization of
predictive value for poor prognosis of 100% after hypoxic-ischemic enceph- the tumor may be possible. SEP are now seldom used for the diagnosis or
alopathy in children as young as 2 months (97). In traumatic and other management of cerebrovascular diseases or tumors.
nontraumatic coma, similar findings have been noted (98–103). Some inves- SEP have been shown to be abnormal in various neurodegenerative con-
tigators have cautioned that in children, especially the very young, not all ditions. Friedreich ataxia is a condition in which there is selective loss of
patients with absent N20 waveforms have a poor prognosis (104). In some vibration and position sense, and pain and temperature sensation is main-
situations, the N20 waveforms may be absent if median SEP are performed tained. Median nerve SEP are lost early in the disease, suggestive of PNS
within 24 hours after the anoxic injury, but recover thereafter (105). This is involvement (109). Patients with motor system diseases such as amyotrophic
particularly true when considering coma from unusual causes, such as being lateral sclerosis (ALS) have been reported to have median nerve SEP with
struck by lightning (98). Before declaring poor prognosis in a very young prolonged EP-P14 IPL (110). However, others have noted that this may be
child, repeating the SEP study after a few days may be useful. The continued due to cervical spondylosis, which is common in these patients and may
also be confused with ALS (111). Abnormal SEP have also been reported in for NIOM. EP are also being used as tools for evaluation of the CNS during
various other neurodegenerative diseases; however, they are not commonly investigational drug trials (120). This use is likely to grow as EP provide a
performed for the diagnosis or management of these conditions. useful method of assessing the changing physiology of the nervous system,
In hereditary neuropathies, such as Charcot-Marie-Tooth disease type with both disease progression and therapeutic intervention.
I, the absolute latencies of the median SEP waveforms are prolonged, but
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16 Neurophysiologic Intraoperative
Monitoring
AATIF M. HUSAIN
Somatosensory Evoked Potentials Warning Criteria

Anatomy and Physiology Clinical Applications
Methodology Auditory Nerve Action Potential
Anesthetic Considerations Electroencephalography
Mechanisms of SEP Change Anatomy and Physiology
Warning Criteria Methodology
Clinical Applications Anesthetic Considerations
Motor Evoked Potentials Mechanisms of EEG Change
Anatomy and Physiology Warning Criteria
Methodology Clinical Applications
Anesthetic Considerations Quantitative EEG Analysis
Mechanisms of MEP Change Nerve Conduction Studies and
Warning Criteria Electromyography
Safety Anatomy and Physiology
Clinical Applications Methodology
Brainstem Auditory Evoked Potentials Anesthetic Considerations
Anatomy and Physiology Interpretation of NCS/EMG Findings
Methodology and Warning Criteria
Anesthetic Considerations Clinical Applications
Mechanisms of BAEP Change References
488
Neurophysiologic Intraoperative Monitoring 489
Many types of surgeries involve the risk of injury to the central or periph- the sensory fibers produces an orthodromic volley of nerve fiber activation
eral nervous system. This includes not only many types of neurosurgical, that produces the various components of the SEP waveform. These compo-
but also orthopedic, ENT (ear, nose, and throat), vascular, cardiothoracic, nents reflect the activation of the dorsal column pathways.
and other types of surgeries. Neurophysiologic intraoperative monitor- Stimulation of the median or ulnar nerves results in the activation of sen-
ing (NIOM) is performed during these surgical procedures and can help sory fibers that relay up to the respective dorsal root ganglia. The axons
reduce the morbidity associated with them. In this chapter, the principles of from the dorsal root ganglia travel through the dorsal roots of the spinal
the various techniques that are used to monitor the central and peripheral nerves into the dorsal column pathway in the spinal cord. They ascend to
nervous system during these surgeries will be discussed. synapse with second-order neurons in the nucleus cuneatus in the medulla.
Somatosensory, motor, and brainstem auditory evoked potentials (SEP, The second-order neurons decussate in the medulla to ascend in the contra-
MEP, BAEP), electroencephalography (EEG) and nerve conduction studies lateral medial lemniscus to the ventroposterior lateral (VPL) nucleus of the
(NCS), and electromyography (EMG) are used alone or in combination, thalamus where they synapse with third-order neurons. These third-order
depending on the part of the nervous system at risk. When two or more mo- neurons then ascend in the thalamocortical radiation to the hand area of
dalities are used, the monitoring is referred to multimodality NIOM. Many the sensory homunculus of the primary sensory cortex on the lateral aspect
of the same principles that apply to interpretation of the clinical modality of the postcentral gyrus. Tibial and peroneal nerve stimulation results in the
also apply to the interpretation of NIOM. There is one major difference. activation of the dorsal column pathway corresponding to these nerves. This
Whereas clinical studies are compared with normative data to determine pathway is very similar to that described for the median and ulnar nerves,
whether an abnormality is present, in NIOM data are compared with what except that instead of the first-order neurons relaying on the nucleus cunea-
was obtained at baseline to determine whether a change has occurred. tus, they synapse in the nucleus gracilis. Additionally, the thalamocortical
In the discussion that follows, an overview of the technique and interpre- fibers relay in the vertex region of the somatosensory cortex corresponding
tation of each of these modalities will be provided. to the leg and foot area of the sensory homunculus.
The SEP waveform reflects transmission of a volley of depolarization as
Somatosensory Evoked Potentials it ascends the dorsal column pathway. The waveforms are similar to those
recorded in the clinical laboratory, as are the montages. Each waveform
SEP monitoring has been used for monitoring spinal cord function for many receives contributions from several neuroanatomic structures, and various
years, and more recently has been used to monitor other parts of the neu- neuroanatomic structures contribute to several waveforms. Despite this, it is
roaxis as well. It is well suited to NIOM as it is typically “invisible” to the useful to think of various components of the SEP waveforms as arising from
surgeon, that is, it causes no significant disruption of surgical technique or general areas of the neuroaxis. This helps identify potential sites of com-
movement in the operative field. The responses are relatively robust and con- promise during surgery. The common waveforms recorded after stimulation
sist of various components that serve as markers of the integrity of v arious of an upper extremity nerve (median or ulnar) are the Erb’s point (EP, N9),
parts of the somatosensory pathways. Essential aspects of SEP monitoring cervical (N13), subcortical (P14 and N18), and cortical (N20) potentials.
are described here. After lower extremity nerve (tibial) stimulation, the commonly recorded
waveforms are the popliteal fossa (PF), lumbar (LP), subcortical (P31 and
Anatomy and Physiology N34), and cortical (P37) potentials. The generators most often associated
with each of these waveforms are presented in Table 16.1 (1).
SEP monitoring is performed with the stimulation of large peripheral nerves Since SEP monitoring is used most often to monitor the integrity of the
in the extremities. In the upper limbs, SEP are obtained with stimulation of spinal cord, it is important to understand the vascular supply of the spinal
the median or ulnar nerves, and in the lower extremities, they are obtained cord and how it may impact SEP NIOM. The spinal cord receives blood
with stimulation of the tibial or peroneal nerves. Electrical stimulation of supply through a network of one anterior and two posterior spinal arteries.
the peripheral nerves results in the activation of sensory and motor path- The single anterior spinal artery extends from the cervicomedullary junction
ways, with the largest fibers being activated preferentially. The activation of to the filum terminale. It is formed by branches from both vertebral arteries
490 Neurophysiologic Intraoperative Monitoring
TABLE 16.1 SEP Waveforms, Generators, and Montages of the anterior two-thirds of the spinal cord, affecting mostly motor path-
ways and sparing the dorsal column pathways. During NIOM, this would
Label Generator be manifest as preserved SEP but possible change in MEP (discussed later).
Upper extremity (median and ulnar nerve) Conversely, selective injury of the posterior spinal artery system can result
in infarction of the posterior one-third of the spinal cord, affecting mostly
EP (N9) Brachial plexus
dorsal column pathways and sparing the motor pathways. This type of in-
N13 Cervical spinal cord
P14 Nucleus cuneatus/medial lemniscus jury is much less common than selective injury to the anterior spinal artery.
N18 Thalamus Understanding the vascular anatomy of the spinal cord helps in explaining
N20 Somatosensory cortex the rationale for SEP and MEP monitoring.
Lower extremity (tibial nerve)
PF Tibial nerve in popliteal fossa
Methodology
LP Cauda equina/lumbar segments of spinal cord
P31 Nucleus gracilis/medial lemniscus
The discussion of SEP methodology will involve stimulating and record-
N34 Thalamus ing techniques. Differentiating artifact-induced change in SEP signals from
P37 Somatosensory cortex surgical changes is one of the main functions of the interpreting physician.
EP, Erb’s point; PF, popliteal fossa; LP, lumbar potential. Stimulating Techniques
SEP used in NIOM are obtained after stimulating large peripheral nerves.
This section will review the types of electrodes that can be used for stimulat-
and receives perforators from the aorta. In the embryo, radicular arteries ing peripheral nerves and stimulation parameters.
arise from the aorta at each segmental level and divide into anterior and
posterior branches. The anterior branches supply the anterior spinal artery. Stimulating Electrodes
At the time of birth, only two to eight of these segmental radicular arter- The requirements for a stimulating electrode used for NIOM are that it must
ies remain; two to three arise from cervical levels and one to three from the be easy and quick to apply, remain stable during patient movement and po-
thoracic levels (2). A large segmental radicular artery arising most often be- sitioning, and provide consistent stimulation of the peripheral nerve. There
tween T9 and T12, known as the artery of Adamkiewicz, supplies the caudal are many different types of electrodes that can be used; however, three main
part of the spinal cord. The actual number of radicular branches that sup- types are used most frequently. These are EEG discs, adhesive pads, and
ply the spinal cord is highly variable in adults. The midthoracic spinal cord subdermal needles (Fig. 16.1). Each has advantages and disadvantages, and
is the least well supplied, and consequently is most prone to ischemic injury their selection will depend on the type of surgery to be monitored. EEG disc
(3). The anterior spinal artery supplies the anterior two-thirds of the spinal
cord, which includes the lateral and anterior corticospinal tracts. A B C
The paired posterior spinal arteries also arise from the vertebral arter-
ies. These arteries receive posterior branches of the radicular arteries. While
there is an extensive anastomotic network between the paired posterior
spinal arteries, such an anastomotic network does not exist between the
posterior spinal arteries and the anterior spinal artery (2). The posterior
spinal arteries supply the posterior one-third of the spinal cord, including
the dorsal column pathways.
Given the vascular distributions of the anterior and posterior spinal artery Figure 16.1: Illustration of EEG cup (A), adhesive pads (B), and subdermal
systems, selective injury to the anterior spinal artery can result in infarction needle (C) electrodes used for stimulating peripheral nerves.
electrodes are stable and are secure when applied with collodion. The cup is Stimulation Parameters
filled with a conductive gel. They can be applied before the patient is anes- Suggested parameters for stimulating peripheral nerves to obtain SEP for
thetized. The major disadvantage of these electrodes is the time required to NIOM have been recommended by the ACNS (4). A constant-current stim-
apply them, especially when collodion is used. Collodion also mandates ade- ulator is recommended as it compensates for changes in tissue impedance. A
quate ventilation as the fumes may be bothersome to both staff and p atients. rectangular pulse between 100 and 300 µs duration is used. An intensity of
During long surgeries, the conductive gel may dry, hindering adequate stim- stimulus is used that provokes a visible muscle twitch. It is generally a good
ulation. If paste is used instead of collodion, the electrodes may become idea to increase the intensity a little more than that required for a twitch to
dislodged with patient positioning. ensure adequate stimulation. Usually a stimulus intensity of 30 to 40 mA
Adhesive pad electrodes are easy and quick to apply. They are available in will be needed; however, if the nerve is diseased, higher intensities may be
different sizes and are stable after application. They are not easily dislodged required. When needle electrodes are used, considerably less stimulus inten-
with patient movement and positioning. Like EEG disc electrodes, they can sity is needed to produce adequate stimulation. Even with high stimulation
be applied prior to the patient being anesthetized. The adhesive pad elec- intensities, tissue damage does not occur. The recommended stimulation
trodes come prepackaged with conductive gel; however, during long surger- rate is 2 to 8 per second (5.7 is common). As with all types of evoked poten-
ies, the gel may dry, impairing proper stimulation. Another disadvantage is tials, an integer of 60 should be avoided to maximize cancellation of 60-Hz
their price. electrical noise. The electrode impedance is kept below 5,000 Ω. Unilat-
Experienced technologists can apply subdermal needle electrodes very eral stimulation is preferred as bilateral stimulation can mask a unilateral
quickly. They require less stimulation intensity. If accidentally removed, change in potentials. Modern NIOM equipment is capable of independently
they can be reapplied more easily than EEG disc electrodes. The major dis- stimulating both sides in an interleaved manner so that both responses are
advantage of subdermal needle electrodes is that they are invasive and must obtained simultaneously.
be applied after the patient has been anesthetized. Though they can be se-
cured, they can also be pulled out more easily during patient movement and Recording Techniques
positioning. A summary of the advantages and disadvantages of the various Various electrodes, sites, and montages can be used to record SEP wave-
electrodes is presented in Table 16.2. forms. This section will review these as well as recording parameters.
Recording Electrodes
EEG disc and subdermal needle electrodes can also be used for record-
TABLE 16.2 Advantages and Disadvantages of Various Types ing SEP. Additionally, corkscrew and epidural electrodes can also be used
of Stimulating Electrodes (Fig. 16.2). EEG disc electrodes have many of the same advantages and dis-
Electrode type Advantages Disadvantages advantages as when they are used for stimulation. Subdermal needles are
often used for recording as well. In addition to the advantages and disadvan-
EEG disc/cup Secure Longer application time
Stable Desiccation tages mentioned already, they record large amplitude responses.
Applied before Dislodgment if paste Corkscrew electrodes have the advantage of being very secure and do not
anesthesia used move with patient movement and positioning. They are also quick to ap-
ply. However, their invasive nature mandates that they be applied after the
Adhesive pad Stable Desiccation
Quick application Expensive patient has been anesthetized. Although they can be used for recording SEP,
Applied before they are used more often as stimulating electrodes for MEP.
anesthesia Epidural electrodes, as the name implies, are placed in the epidural
Subdermal needle Quick application Invasive
space. These electrodes record directly from the surface of the spinal
Less current used Dislodgement cord, and consequently, have robust and large signals that require very
few repetitions to produce reproducible waveforms. Because of their
A B TABLE 16.3 Advantages and Disadvantages of Various Types

of Recording Electrodes
Electrode type Advantages Disadvantages
EEG disc/cup Secure Longer application time
Stable Desiccation
Applied before anesthesia Dislodgment if paste used
Subdermal needle Quick application Invasive
Large responses Dislodgement
Corkscrew Quick application Invasive
Secure
Epidural Large responses Placed by surgeon
Quick reproducibility Displaced easily
Figure 16.2: Illustration of corkscrew (A) and epidural (B) electrodes. Anesthetic insensitivity
quick reproducibility, feedback to the surgeon is quicker with epidural

electrodes. Epidural responses are also insensitive to anesthetics. The dis- Peripheral responses, the EP and PF responses, as their names imply, are
advantage of these electrodes is that they are invasive and must be placed recording from the Erb’s point and popliteal fossa. These responses identify
and anchored by the surgeon. Movement of the electrode, which is not adequacy of stimulation of the peripheral nerve. The responses are of high
uncommon, can significantly change the morphology of the response. amplitude and easily reproducible. Since they are peripheral responses, they
These electrodes also cannot be used in the cervical region and when an do not reflect problems with the central nervous system (CNS).
anterior approach is used. Other types of invasive electrodes, such as nee- Cervical (N13) and lumbar (LP) responses represent the first CNS volley
dle electrodes that are placed in the ligamentum flavum, have many of of the SEP obtained after stimulation of the upper and lower extremities,
the advantages and disadvantages of epidural electrodes. All these elec- respectively. Since electrodes needed to record these responses are placed on
trodes in the past were also used to stimulate the spinal cord and produce the cervical and thoracolumbar spine, they are often in the surgical field and
what were thought to be MEP from lower extremity muscles. Since spinal cannot be used.
cord–induced MEP are now thought to be mostly mediated by sensory Since subcortical potentials (P13/14 and N18 after upper extremity stimu-
pathways and with the availability of transcranial MEP, epidural, and lation; P31 and N34 after lower extremity stimulation) are far-field poten-
other similar electrodes are now seldom used for stimulation. A summary tials, they are recorded from the same set of electrodes. Typically, the active
of the advantages and disadvantages of various recording electrodes is electrode is placed on the scalp and the reference on the mastoid, ear, or
presented in Table 16.3. contralateral EP. Subcortical potentials are relatively insensitive to inha-
lational anesthetics, making them useful in determining when a change in
Recording Sites and Waveforms cortical potentials is due to anesthetics versus surgical intervention. Their
SEP waveforms are recorded at various points along the neuroaxis. This biggest limitation is their small amplitude. This makes them difficult and
provides redundancy in recording the responses, as well as provides better time consuming to record. They are recorded best with muscle relaxants as
localization of problems when waveforms are lost. Though recorded from that diminishes muscle activity, increasing the signal-to-noise ratio (SNR).
mostly different sites, SEP waveforms from the upper and lower extremities Unfortunately, excessive muscle relaxation precludes the use of MEP. False-
are largely congruous. Each recording site is particularly useful for recording positive changes in subcortical potentials are not uncommon and must be
a particular SEP waveform. recognized in order to avoid unnecessary delays in surgery.
Cortical potentials (N20 after upper limb and P37 after lower limb stim- In recording upper extremity SEP, a four- to five-channel montage is usu-
ulation) are near-field potentials. The optimal recording location for the ally used. The CPc-CPi (c = contra, i = ipsi) derivation is useful for recording
N20 potential is between the C3/4 and P3/4 electrode (referred to as the the cortical N20 waveform. Since both electrodes are on the scalp, subcor-
CP3/4 electrode), contralateral to the side of stimulation. This is refer- tical components cancel out. The CPi-EPc and Fz-EPc derivations both
enced to the congruous contralateral electrode. The best location for re- have one scalp and one nonscalp reference electrode. The scalp electrodes
cording the P37 potential is more variable. At times, it is best recorded are distant from the activated somatosensory cortex and consequently do
over CPz, whereas in other patients, it is of higher amplitude over CP not record the cortical waveform. However, they do record the subcortical
ipsilateral to the side of stimulation. Fz or CP contralateral to side of responses since they are referenced to an electrode (EPc), which is “silent.”
stimulation is used as a reference electrode. The variable topography of, The C5S-Fz derivation is used less often as it displays the N13 and P13/14
particularly, the P37 may necessitate additional recording electrodes (5). and N18 complex in a single channel. Separating the cervical (N13) from
Cortical potentials are usually of high amplitude and easy to reproduce. the subcortical (P13/14 and N18) becomes difficult. The C5S-EPc derivation
Inhalational anesthetics have a profound effect on cortical potentials. This records activity from the cervical spine (N13). The C5S electrode is often in
can be an advantage (to provide an indication of anesthetic management) the surgical field, so this derivation is often not used. The Epi-EPc records
or a disadvantage (false positives). the potential as it passes through the brachial plexus.
Lower extremity SEP are also recorded with a four- to five-channel
Recording Montages montage. The CPz-Fpz and CPi-CPc (or C1′-C2′) derivations record the
Montages must be designed to maximize the SNR of the SEP waveforms cortical P37 potentials. In both derivations, electrodes are on the scalp;
to allow rapid feedback to the surgeon. Peripheral, subcortical, and cortical subcortical potentials are not seen as they cancel out. Two derivations are
potentials should be displayed whenever possible. Modern NIOM machines used to record the cortical waveform as its topography is variable, and if a
have 8 to 32 channels and allow such a display, depending on which other single derivation is used, the best waveform morphology may not be seen. A
modalities are being monitored. The ACNS has recommended montages for more thorough approach to find the best derivation can be undertaken and
upper and lower extremity SEP (4). These, along with the author’s modifica- is described elsewhere (5). Identifying the set of electrodes that maximizes
tions, are presented in Table 16.4. the SNR of the P37 waveform will increase the speed with which reproduc-
ible responses can be obtained, thereby increasing speed of surgical feed-
back. The Fz-C5S derivation is used to record the subcortical waveforms;
there is a scalp electrode removed from the activated somatosensory cortex
TABLE 16.4 Typical Montage Used for Upper and Lower referenced to a “silent” electrode (C5S). The C5S electrode is silent when
Extremity SEP recording lower extremity SEP. This is not the case when recording upper
Upper Extremity Lower Extremity extremity SEP. The T12-IC (iliac crest) derivation is useful for recording
the LP potential. However, as with the C5S electrode, the T12 electrode is
Montage Waveform Montage Waveform
often in the surgical field and thus often not used. The PFd-PFp records
CPc-CPi (CP3/CP4) N20 CPz-Fz P37 the traveling wave of depolarization as it passes in the tibial nerve under the
Alternate: CPc-Fz PFd electrode. This latter derivation cannot be used if the peroneal nerve
CPi-EPc P13/14, N18 CPi-CPc (CP3/CP4) P37 is used for stimulation.
Alternate: C1′-C2′
Fz-EPc P13/14, N18 Fz-C5S P31, N34 Recording Parameters
Alternate: C5S-Fz Recording parameters have been recommended in the ACNS guidelines (4).
C5S-EPc N13 T12-IC LP These guidelines have suggested that 500 to 1,000 repetitions should be ob-
EPi-EPc EP PFd-PFp PF
tained for each upper extremity SEP and 1,000 to 3,000 repetitions for each
lower extremity SEP. Others have suggested that fewer repetitions should be
used if reproducible responses are seen earlier as this will increase the rapid- Inhalational Agents
ity of feedback to the surgeon (5). There are several types of halogenated gases, and they differ in their potency.
The time base for recording (time displayed on the screen) is usually set to Isoflurane, desflurane, and sevoflurane are more potent than halothane and
twice the duration of the last peak of interest. Consequently, for upper ex- enflurane. Generally, the more potent the agent, the greater the effect on
tremity SEP, the time base is 30 to 100 milliseconds, while for lower extremi- SEP. Cortical components of the SEP are affected most by halogenated
ties it is 75 to 150 milliseconds. Filters are used to minimize noise and activity gases, and the higher the dose, the greater the effect (8). Subcortical compo-
that is not of interest. This enhances the SNR, and when set appropriately, nents are affected less, and peripheral responses are unaffected (Fig. 16.3).
filters can increase the rapidity with which reproducible waveforms are seen. With less than 0.5 MAC of any halogenated gas, usually subcortical wave-
A filter setting of 30 to 3,000 Hz is usual. Dropping the low-frequency filter forms can be reliably reproduced and followed in spine surgeries. It should
to 1 Hz introduces excessive baseline fluctuation, making it more difficult be remembered that changes in SEP lag behind changes in end-tidal concen-
to resolve waveforms. Increasing this filter too high (to 75 Hz) reduces the trations of inhalational agents. This is because there is a 15- to 20-minute lag
amplitude of slow components of the SEP (6). between equilibration of lung and brain concentrations.
The effects of nitrous oxide on SEP are similar to those of halogenated
Anesthetic Considerations gases. It causes a significant decrease in the amplitude of the cortical po-
tentials and has less effect on subcortical potentials. An equipotent dose
Anesthetics can have a profound effect on SEP, and these must be recognized of nitrous oxide produces more amplitude suppression of cortical poten-
to provide appropriate interpretation of changes (7). The higher the dose of tials than halogenated gases. If cortical potentials are necessary to record,
an anesthetic, the more it depresses the SEP. Since synapses are affected most nitrous oxide should be avoided.
by anesthetics, those SEP waveforms produced prior to any synapses are af-
fected least, while those occurring after several synapses are affected most. Intravenous Agents
Thus, cortical responses are more sensitive to anesthetics than subcortical Propofol is an intravenous (IV) agent that has become very popular as part
and peripheral responses. Anesthesiologists can use several different medica- of total intravenous anesthesia (TIVA). It suppresses the cortical potentials
tions, and a summary of their effects will be presented here and in Table 16.5. much less than inhalational agents and only at high doses. Similarly, it causes
minimal change in subcortical potentials. It has become the agent used most
TABLE 16.5 Summary of Effects of Anesthetics on SEP often if cortical potentials must be recorded and when MEP monitoring is
being considered.
Anesthetic Cortical Subcortical Peripheral Fentanyl and other IV opioids are useful adjuncts to propofol in TIVA.
Halogenated gases ↓ Latency Minimal change No change They also cause minimal depression of the cortical and subcortical wave-
Amplitude forms and can be used successfully with MEP monitoring. Opioids, how-
↑ Latency ever, cannot be used in isolation as they do not provide sufficient sedation.
Nitrous oxide ↓ Amplitude Minimal change No change Sedatives such as benzodiazepines are often used during induction and to
- Latency reduce anesthetic recall. At low doses, they have little effect on cortical and
subcortical potentials. However, at high doses, they can suppress cortical
Propofol Minimal change Minimal change No change
potentials. If benzodiazepines are used only during induction, even at high
Opioids Minimal change Minimal change No change doses, they are seldom problematic during the critical portions of the surgery.
Benzodiazepines Minimal change Minimal change No change
Neuromuscular Junction Blocking Agents
Muscle relaxants ↑ Amplitude ↑ Amplitude No change
- Latency - Latency Rather than suppressing SEP waveforms, neuromuscular junction blocking
agents (NMJBA) often appear to increase amplitudes of particularly the sub-
↓, decrease; ↑, increase; -, no change. cortical waveforms. This is because they suppress the underlying muscle activity,
Figure 16.3: SEP recording showing loss of

cortical waveforms with little effect on subcorti-
cal waveform when isoflurane dose is increased
(triangles).
and thereby improve the SNR (Fig. 16.4). It should be remembered, though, 2 milliseconds (10). A drop in blood pressure induces relative ischemia of
that use of NMJBA can complicate MEP monitoring, as will be discussed later. the spinal cord, and increasing the blood pressure has been associated with
improvement in SEP (Fig. 16.5). In one study in 9 of 11 patients in whom an
Mechanisms of SEP Change alert was raised due to reduced SEP amplitude, an increase in blood pressure
improved the responses (11).
There are many different reasons why SEP waveforms can change during Impairment of blood supply to the nerve being stimulated to obtain a
surgery (9). Some are related directly to the surgical intervention, while oth- SEP can result in loss of amplitude of the SEP. This will usually be ac-
ers are due to changes in the physiologic milieu, and still others are due to companied by loss of the peripheral (PF or EP) response as well and will
technical issues. be limited to one extremity (Fig. 16.6). This can happen if an ace wrap is
applied too tightly or if a cannula is placed in a large artery supplying the
Ischemia and Anoxia/Blood Pressure limb, making it ischemic.
There are few data on the changes in SEP induced by ischemia of the spinal
cord. However, there are considerable data on the effect of ischemia on pe- Acute Trauma
ripheral nerves. After about 20 minutes of ischemia, nerve potentials drop Acute trauma that is not severe enough to cause axonal disruption can cause
by 50% owing to temporal dispersion. The latency also prolongs by 1 to an increase in extracellular potassium (9). The more severe the trauma, the
Figure 16.4: SEP recording showing worsening

subcortical waveforms as muscle relaxant wears
off (triangles). The muscle relaxant was given
5 minutes prior to the first tracing shown.
more remarkable the increase in potassium. The extracellular potassium in- baselines were obtained immediately after induction (Fig. 16.8). In such a cir-
hibits conduction of action potentials. As a result, with trauma, there is cumstance, it may be appropriate to reset the baseline after the temperature
loss of amplitude and prolongation of latencies of SEP waveforms. This is has stabilized. If cold irrigation is used during spinal surgery, the spinal cord
the mechanism by which transient mechanical injury to the spinal cord can may be cooled directly. This may significantly prolong latencies of the SEP
be detected with NIOM; correction of the problem can lead to complete waveforms. The cortical potentials are affected most by temperature, with the
recovery (Fig. 16.7). However, with severe or prolonged injury, axonal dam- N20 waveform prolongation being 1.56 milliseconds for every degree Celsius
age can occur, resulting in more significant changes in SEP and possibly drop in temperature (12).
irreversible deficits.
Technical Issues
Temperature Technical issues are a common cause of significant SEP change in spi-
A drop in temperature has remarkable effects on nerve conduction and SEP. nal surgeries. These must be recognized and fixed if possible. The myriad
The absolute and interpeak latencies are prolonged. Amplitude is affected of technical problems that can occur are beyond the scope of this chap-
less with temperature changes. Soon after the patient is anesthetized, the body ter. Several broad categories should be remembered. Problems may occur
temperature drops, and this may shift SEP latencies and alter amplitudes if with the stimulating system ranging from the software to the stimulator.
Figure 16.5: SEP recording showing a decrease

in amplitude of the cortical and subcortical
waveforms after tibial nerve stimulation with
decreasing mean arterial blood pressure (tri-
angles), with recovery as the pressure increases
(arrows).
Figure 16.6: SEP recording showing loss

of peripheral and cortical responses due to
ischemia of the right tibial nerve (arrows).
The recording system, in particular the amplifiers, may be at fault. Fac- an amplitude drop greater than 50% and latency prolongation greater than
tors local to the stimulating and recording electrodes should also be con- 10% is considered significant (6). A change in amplitude is more signifi-
sidered. Edema or ischemia around the site of stimulation may prevent cant than a change in latency. A change in SEP that is considered sig-
adequate stimulus delivery (Fig. 16.9). The electrodes may have been dis- nificant should be reproduced to ensure that the change was not due to
lodged. Similarly edema at the recording site, such as scalp edema, may artifact. The need to confirm a change has to be balanced with the need
cause a decrease in the amplitude of the response. Artifacts, such as elec- to immediately inform the surgeon so that corrective action can be taken
trocautery, can cause obliteration of the SEP response if averaging is not immediately.
stopped during its use. Technical issues must be ruled out first when SEP Brief or transient loss of SEP is compatible with a good outcome. Even
changes are noted. with a complete and persistent loss of SEP, only 50% of patients will have
motor weakness (13). This is considered acceptable as in NIOM specific-
Warning Criteria ity is often compromised for sensitivity. To minimize “false-positive” SEP
changes, subcortical waveforms can be evaluated. They are more resistant
The surgeon should be alerted to changes in SEP if they are of sufficient to anesthetic and other physiologic changes that may occur during sur-
magnitude to result in tissue injury. How much the SEP needs to vary be- gery. However, when TIVA is being used, cortical SEP can be used and are
fore the change is considered significant is unclear. Somewhat, empirically, preferred. This is because anesthetic agents used in TIVA do not suppress

subcortical waveforms after stimulation of both
tibial nerves with excessive distraction during
scoliosis surgery (triangles). The responses im-
proved with release of the hardware (arrows).
Note that the bottom of the figure is earlier in
the surgery and the top is later in the surgery.
the cortical waveform significantly. Its large amplitude allows a favorable stimulation intensity, and problems with recording electrodes, to name a
SNR and quicker reproduction of the response. few. Physiological causes such as anesthetic change, blood pressure fluc-
When SEP changes are noted, the cause can be technical, physiological, tuations, temperature variability, and preexisting conditions can affect the
or surgical. An attempt must be made to eliminate technical and physiologi- response. Some inadvertent physiological changes, such as excessively low
cal causes for the change before ascribing it to the surgery. As discussed blood pressure, which compromises spinal cord perfusion, can be detected
previously, many technical factors can cause significant changes in SEP. by changes in SEP. Excessive muscle activity can reduce the SNR of the
Examples include machine problems, stimulator problems, reduction of subcortical potentials, reducing their amplitude. These changes can help
Figure 16.8: SEP recording showing a prolon-

gation in latency and decrease in amplitude of
the cortical potential with a drop in temperature
(triangle). Toward the end of surgery, the tem-
perature returns to baseline, and the latency
and amplitude of the cortical response improve
(arrow).
alert the anesthesiologists to excessively low blood pressure or to a patient from .72% to .55% (13). Moreover, this study showed that centers with more
whose anesthesia is too light. Of course, surgical manipulation, intentional experience with SEP monitoring had better outcomes than those with little
or inadvertent, of neural tissue can also cause changes in the SEP. A list of experience. For many other types of spine surgeries, such as anterior cervi-
nonsurgical and surgical causes of SEP change is presented in Table 16.6. cal decompression and fusion and intra and extramedullary spinal cord
tumor surgery, there are smaller, uncontrolled series documenting u tility
Clinical Applications of SEP NIOM.
SEP monitoring has also been used for surgeries beyond the spinal cord
There are several types of surgeries for which there are unequivocal and vertebral column. For surgery for brainstem tumors, median nerve SEP
data that SEP NIOM reduces neurologic morbidity. A recent American monitoring is used in conjunction with cranial nerve monitoring. SEP can
Academy of Neurology (AAN) Practice Parameter established the util- be used during cerebral aneurysm surgery to confirm that clipping does not
ity of SEP (and MEP) NIOM in a variety of spinal surgeries (14). A few cause critical ischemia. In surgery on descending aortic aneurysms, vascu-
of the types of surgeries for which SEP and MEP NIOM are useful are lar supply to the spinal cord is often interrupted, and SEP monitoring can
discussed here. be used to alert the surgeon when this is occurring. Few data are available
A survey of the Scoliosis Research Society showed that SEP monitoring for use of SEP in nerve root, peripheral nerve, plexus, tethered cord, and
in scoliosis significantly reduced the incidence of all neurological deficits movement disorder surgeries.

peripheral and cortical response after stimula-
tion of the left tibial nerve due to local edema
(triangles). Increasing stimulation intensity
results in return of the SEP (arrows).
Motor Evoked Potentials of waveforms below the site of surgery confirms integrity of the motor
pathways.
MEP are obtained by stimulating the motor pathways rostral to the site MEP and SEP monitoring are often performed together as they provide
of surgery. Activation of the motor pathways can be measured by re- complementary information. Whereas SEP assess the dorsal column path-
cording waveforms as the impulse descends in these fiber tracts. Presence ways and the posterior aspect of the spinal cord, MEP monitoring provides
information about the function of the corticospinal pathways and the lateral
and anterior spinal cord. Before MEP monitoring was routinely performed,
TABLE 16.6 List of Causes of Significant SEP and MEP Change SEP monitoring alone was used during surgeries in which the spinal cord was
at risk. It was assumed that SEP served as a surrogate marker of injury to mo-
Nonsurgical causes Surgical causes tor pathways. Several studies, however, showed that motor deficits could occur
Anesthesia Trauma to cord without any change in SEP signals (13,15). Since MEP directly assess motor
Blood pressure Traction pathways, they provide a more sensitive marker of injury to these pathways.
Temperature Cord compression
Preexisting conditions Cord stretch with spinal distraction Anatomy and Physiology
Variability of response Vascular insufficiency
Embolism or thrombosis
Stimulating the motor pathways in the brain or spinal cord can evoke MEP.
For many years, MEP monitoring was performed by electrically stimulating
the spinal cord rostral to the site of surgery and recording muscle MEP be recorded from the extremities. However, a train of three to nine electrical
from the lower extremities. Stimulation was performed with an electrode stimuli applied at 2- to 8-millisecond intervals results in summation of de-
placed in the epidural space during surgery or percutaneously before the polarization on the alpha motor neurons, resulting in their activation. This
start of the procedure. It was thought that epidural electrical stimulation results in a recordable muscle MEP response from the extremities. It is this
of the spinal cord resulted in activation of the motor pathways. However, train of stimuli and recording of muscle MEP responses that is used most
it has been shown with collision studies that this type of stimulation results often when contemporary MEP monitoring is performed.
in retrograde activation of the dorsal column axons. Collaterals from these Though most types of stimulation in clinical neurophysiology are cath-
axons synapse on anterior horn cells and activate muscle action potentials. odal, with TES anodal stimulation is more effective. The cell body and axon
Consequently, motor pathways in the spinal cord remain unmonitored with hillock, the sites of stimulation for TES, are more sensitive to anodal stimu-
this technique. lation. Thus, anodal stimulation is used during TES and is more reliable
Transcranial stimulation results in the activation of motor neurons in the than cathodal TES.
cortex. This provides selective activation of the motor pathways and motor Both the lateral and the anterior corticospinal pathways are in the an-
pathway monitoring. Transcranial stimulation of motor pathways can be terior two-thirds of the spinal cord and are supplied by branches of the
accomplished with magnetic or electrical stimulation. Magnetic stimulation anterior spinal artery (see earlier discussion). Consequently, selective injury
involves high-intensity magnetic stimulation delivered with a coil placed to this vascular supply results in injury to the anterior two-thirds of the
near the cortex. The magnetic stimulus results in depolarization of cortical cord, resulting in motor weakness with preservation of sensory modalities
interneurons, which results in activation of the motor pathways. It is pain- mediated by the dorsal column pathways.
less and can be performed in an awake patient. However, transcranial mag-
netic stimulation is very sensitive to anesthetics because of its reliance on Methodology
interneurons, and involves the use of bulky stimulating equipment. These
issues prevent its routine use during surgery. The methods used to stimulate motor pathways and techniques used to
In the last few years, transcranial electrical stimulation (TES) has become record the descending volley of activation will be discussed in this section.
available as a means for obtaining MEP. A single electrical stimulus deliv- The techniques used most commonly will be discussed in detail.
ered to the cortex, directly or through the scalp, results in the activation of
the cortical pyramidal neurons and a descending corticospinal tract volley. Stimulating Techniques
This volley travels in the corticospinal tracts in the midbrain and pons and MEP can be obtained by stimulating the motor pathways at the level of the
then decussates to the contralateral side in the medulla. In the spinal cord, cortex or spinal cord. Because of the issues discussed earlier with spinal cord
the corticospinal tract has lateral and anterior components. The lateral cor- stimulation, this technique is not used regularly and will not be discussed
ticospinal tract contains most of the descending motor fibers. Fibers from further. Magnetic transcortical stimulation will also not be discussed further
both lateral and anterior corticospinal tracts synapse on the anterior horn due to its limited utility during surgery. The remainder of the discussion will
cells of the ventral roots of the spinal cord gray matter. From here arise focus on TES.
motor fibers that travel through anterior roots of the spinal nerves to form
motor nerves that innervate muscles. Stimulating Equipment
The descending volley of depolarization produced by activation of the cor- A stimulator that is used for TES must be capable of delivering a high-
tical pyramidal neurons can be recorded as a “D” (direct) wave with an epi- intensity electrical stimulus to the scalp. Constant-voltage stimulators are
dural electrode placed on the spinal cord. Following the D wave, several “I” used most often, and most have the capacity to deliver at least 1,000 V
(indirect) waves can also be recorded, and they represent activation of cortical and a train of nine rectangular pulses. The actual current delivered de-
interneurons, which cause recurrent excitation of the corticospinal pathway. pends on the impedance of the electrodes being used for stimulation. Dig-
A single transcranial electrical stimulus does not result in sufficient depo- itimer was the first stimulator to obtain FDA approval for TES and was
larization of alpha motor neurons to cause a muscle (“M”) MEP that can designed specifically to deliver a high-intensity TES. Other manufacturers
TABLE 16.7 Characteristics of Commercially Available

Nz
TES Equipment
Maximum Stimulation Intensity (V) FPZ
FP1 FP2
0.05-ms Pulse 0.075-ms Pulse
Vendor Duration Duration AF7 AF8
AF3 AFZ AF4
Digitimer D185 Ltd. 1,000 N/A F9 F10
F7 F8
Cadwell TCS1000/TCS4 1,000 800 F5 F3 F1 F2 F4 F6
FZ
Axon Systems Eclipse 1,000 ?
XLTEK Protektor 32 1,000 N/A FT9 FT7 FT8 FT10
FC5 FC3 FC1 FC2 FC4 FC6
FCz
Nicolet Endeavor CRa 400 N/A
a A2
Nicolet Endeavor CR does not have a separate FDA-approved transcranial MEP stimu- A1 T9 T7 C5 C3 C1 CZ C2 C4 C6 T8 T10
lator, which is why the stimulator available only goes to 400 V. It does allow for variation
of the duration and has a BNC connection for attaching a secondary stimulator.
CP3 CP1 CPZ CP2 CP4 CP6
TP7 CP5 TP8 TP10
TP9
P3 P1 PZ P2 P4 P6
P5
P7 P8
have subsequently made similar stimulators. Currently, many brands of P10
P9
commercially available NIOM equipment offer built-in TES capability PO3 POZ PO4 PO8
PO7
(Table 16.7).
O1 O2
OZ
Stimulating Electrodes
Several types of stimulating electrodes can be used to deliver the electrical
IZ
stimulus to the scalp. Spiral needles (also known as corkscrew electrodes),
straight needles, and surface EEG cup electrodes have been used. The aver-
Figure 16.10: Possible locations for placing MEP stimulating electrodes. Com-
age impedances of these electrodes are 500, 800, and 1,100 Ω, respectively. mon sites are at C1 and C2 (gray squares) or C3 and C4 locations (gray circles).
The impedance of the electrodes is an important consideration as the MEP Moving the electrodes 1 to 2 cm anterior to these landmarks may result in bet-
threshold is directly proportional to the electrode impedance above 460 Ω ter responses. Electrodes at Cz − 1 cm and Cz + 6 cm (gray triangles) have also
(16). Consequently, higher current will be needed to elicit MEP when sur- been shown to result in good responses in some patients. (Adapted from refer-
face EEG cup electrodes are used compared with spiral needles. Most com- ence Journee HL, Polak HE, de Kleuver M. Influence of electrode impedance on
monly, spiral and straight needles are used. Pictures of these electrodes are threshold voltage for transcranial electrical stimulation in motor evoked potential
presented in Figs. 16.1 and 16.2, and their advantages and disadvantages are monitoring. Med Biol Eng Comput 2004;42(4):557–561. Epub August 24, 2004.)
presented in Tables 16.2 and 16.3.
better responses. Additionally, electrodes can be placed at Cz − 1 cm and
Electrode Placement Cz + 6 cm. Montages that can be used for stimulation and their advantages
Stimulating electrodes are placed on the scalp at sites that overlie the mo- are listed in Table 16.8.
tor cortex as specified by the International 10–20 system. Typically, elec- Most commonly, MEP monitoring is performed with C1-C2/C2-C1
trodes are placed at C1 and C2 or C3 and C4 locations (Fig. 16.10) (17,18). or C3-C4/C4-C3 pairs. Using the latter pair may result in deeper, axonal
At times, displacing electrodes 1 to 2 cm anterior to these sites results in stimulation of the motor pathways and shorter D wave latencies. Often,
TABLE 16.8 MEP Stimulating Montages and Their Advantages Facilitation

Occasionally, a muscle MEP response may be difficult to obtain in the lower
Montage Advantage extremity. Facilitation refers to enhancing the depolarization at the ante-
C1-C2/C2-C1 Best for obtaining lower extremity responses rior horn cells prior to the target stimulus arriving. This can be done by
C3-C4/C4-C3 Best for obtaining upper extremity responses delivering a priming stimulus to the anterior horn cells. Manual stimulation
C3-Cz/C4-Cz Best for obtaining lateralized responses of the sole of the foot can provide such a priming stimulus, but this is dif-
Cz − 1 cm − Cz + 6 cm Best for obtaining bilateral lower extremity ficult to perform in the operating room. There are more practical methods
responses of delivering the priming stimulus during surgery.
Double Train Stimulation. As the name implies, two trains of stimuli are
applied to the scalp in rapid succession. The first, priming train precedes the
the high current intensity used for MEP results in a large stimulus artifact, target train by a set interval. The priming train causes partial depolarization
making it harder to identify a response. Disconnecting the SEP recording of the anterior horn cells, and the target train completes the depolarization,
electrodes from the head box or moving the MEP stimulating electrodes resulting in a muscle MEP. Both trains can have similar stimulation param-
1 to 2 cm anterior to their typical location may reduce the stimulus arti- eters, or the priming train may have fewer stimuli. The intertrain interval
fact. Some stimulators have switch boxes that automatically disconnect (ITI) should be less than 10 milliseconds or greater than 100 milliseconds.
SEP electrodes when the electrical stimulator is activated and vice versa to ITI between 10 and 100 milliseconds has been shown not to result in signifi-
minimize artifacts. cant facilitation (20).
Stimulation Parameters Posttetanic Stimulation. Tibial nerve stimulation can also depolarize the
anterior horn cells by antegrade transmission of the stimulus through mo-
As noted previously, a train of stimuli is needed to evoke a muscle MEP. tor nerve fibers. This depolarization can result in facilitation of the MEP as
A train of at least three stimuli is needed, and most stimulators can deliver well. Tetanic stimulation of the tibial nerve at 50 Hz for 5 seconds followed 1
up to nine stimuli. In a patient with a normal nervous system, three to four second later by MEP stimulus has been shown to result in higher-amplitude
stimuli are enough to elicit a muscle MEP in the hand, and five stimuli are MEP responses in not only tibial innervated muscles, but muscles in the
needed for leg MEP. The exact number of stimuli needs to be adjusted dur- other limbs as well (21). Many new NIOM machines can be programed to
ing the surgery to maximize the responses of interest. deliver the tetanic stimulus followed by a MEP stimulus.
The interval between the stimuli, the interstimulus interval (ISI), can be
adjusted between 1 and 8 milliseconds. Longer ISI allow summation of all
the I waves. However, the depolarization produced by the D waves begins Recording Techniques
to subside by the time all I waves summate. When the ISI is too short, MEP can be recorded from the spinal cord, nerves, and muscles. Each
subsequent stimuli may fall within the absolute or relative refractory pe- recording site requires specific electrodes and has advantages and
riod of the pyramidal neurons, causing a diminished response. Thus, like disadvantages.
the number of stimuli, the ISI must be individualized to maximize the
response. With light anesthesia that allows expression of I waves, long ISI
may be preferable. With standard anesthesia, an ISI of 4 to 5 milliseconds Recording Electrodes
may be optimal. A short ISI of 2 milliseconds has been shown to result Recording electrodes are selected depending on the site of recording. Spe-
in optimal hand muscle MEP (19). In most cases, when both upper and cialized epidural electrodes are available, which can be inserted percutane-
lower extremity MEP monitoring is needed, an ISI of 4 milliseconds, a ously or placed intraoperatively by the surgeon. These electrodes will record
train of five stimuli, and a stimulation intensity of 300 V serve as a good D and I waves. Surface and needle electrodes are used to record MEP from
starting point (18). nerves and muscles. Surface electrodes can be applied in an awake patient,
but application is time consuming. Needle electrodes are applied after the temporal dispersion and desynchronization of D waves, making them not
patient has been anesthetized and can be inserted directly into the muscle recordable.
of interest. When recording MEP from nerves, needle electrodes can be in-
serted in close proximity to the nerve, resulting in a higher-amplitude re- Muscle Recordings
sponse. The advantages and disadvantages of various types of electrodes are Muscle MEP recordings are used most commonly. Typical parameters are
presented in Tables 16.2 and 16.3. Nerve MEP are seldom recorded and will listed in Table 16.9. They are most often recorded with needle electrodes,
not be discussed further. which result in polyphasic responses. Subsequent responses are variable
and dependent on how many and which motor units were activated. Conse-
Spinal Cord Recordings quently, averaging is not performed. Muscle MEP are most easily recorded
Typical parameters for spinal cord recordings are listed in Table 16.9. As the from distal limb muscles, such as the abductor pollicis brevis, abductor di-
stimulation intensity increases, the D wave amplitude increases and latency giti minimi, abductor hallucis, and tibialis anterior. A typical montage for
decreases. I waves start to appear with still higher stimulation intensity, and recording muscle MEP is presented in Table 16.10.
finally the D wave becomes bi-fed. For optimal recording, the stimulation There are several advantages of recording muscle MEP over spinal cord
intensity should be increased to maximize the amplitude of the D wave but MEP. Muscle MEP can be recorded with needle electrodes that can be placed
not so high that it becomes bi-fed or polyphasic. D waves are most easily re- by the monitoring staff. Several muscle groups can be monitored, and selec-
corded in the cervical region and are difficult to record at lumbosacral levels. tive localization of injury is possible. When D waves are not recordable, as
Reliable D waves have not been recorded in children less than 21 months of with tumors, muscle MEP may still be present. The disadvantages of muscle
age (18). At times, D waves are of low amplitude and have to be averaged to MEP include their variable morphology, which precludes averaging, high
discern a reproducible response. In such situations, 10 to 20 repetitions are sensitivity to inhalational anesthetics and NMJBA, and lack of consistent
usually enough to obtain a response. interpretation criteria. An example of muscle MEP recordings is presented
The advantages of D wave recordings are their high SNR, reproducibil- in Fig. 16.11.
ity, and constant morphology. Often a single stimulus, rather than a train,
can elicit a D wave response; though, as noted earlier, sometimes D waves
need to be averaged. Additionally, anesthetics have little effect on D waves. Anesthetic Considerations
However, the recording electrodes must be placed by the surgeon or percu-
taneously in the epidural space. The electrode, because of its size, cannot Anesthesia has a profound effect on MEP monitoring. As noted earlier,
be placed in the high cervical region, and recordings are not possible in magnetic MEP monitoring cannot be performed in the operating room since
the lumbosacral region, thereby limiting the sites from where D waves can
be recorded. Demyelination or tumors within the spinal cord may cause TABLE 16.10 Typical Muscle MEP Recording Montage
Upper Limb Lower Limb

TABLE 16.9 Typical Spinal Cord and Muscle MEP Recording
Parameters APB-ADM AH-ADQ
FCU-FCR AH-TA
Spinal Cord Recording Muscle Recording
TA-TA
Time window (ms) 10–20 100 TA-MG
Low-frequency filter (Hz) 100–500 20 VM-VL
High-frequency filter (Hz) 2,000 2,000
Averaging Sometimes No APB, abductor pollicis brevis; ADM, abductor digiti minimi; FCU, flexor carpi ulnaris;
Response Consistent Variable FCR, flexor carpi radialis; AH, abductor hallucis; ADQ, abductor digiti quinti; TA, tibialis
anterior; MG, medial gastrocnemius; VM, vastus medialis; VL, vastus lateralis.
Figure 16.11: Example of a muscle MEP. Notice the variable morphology

of successive responses. This variable morphology precludes averaging of
muscle MEP.
Figure 16.12: MEP responses from right upper (left) and lower (right) extremi-
the anesthetic agents prevent adequate stimulation. Anesthetics affect syn- ties. Isoflurane (1%) was being used toward the start of this tracing (top) and was
apses and consequently have a greater effect on MEP, which are dependent discontinued around 12:26:11. Notice the appearance of reproducible muscle
on synaptic transmission. MEP responses in the lower extremity after isoflurane was discontinued.
Inhalational Agents Approximately 60% of neurologically normal patients have recordable

All inhalational agents suppress cortical neurons and anterior horn cells. muscle MEP at 0.6% isoflurane, and only 20% have MEP at 0.8% iso-
This makes obtaining muscle MEP difficult and unreliable (Fig. 16.12). flurane (22). A low concentration of an inhalational anesthetic, usually
less than 0.5%, may be permissible with MEP monitoring. However, if the etiology of the change. The upper limb MEP serve as controls in this
responses are small and unreliable, alternate anesthetics should be con- situation; whatever affects both upper and lower limb MEP is likely a sys-
sidered. Inhalational anesthetics have no appreciable effect on D wave temic factor, while when only lower extremity MEP are affected, the cause is
recordings. more likely to be surgical. The most common reasons for MEP change will
be discussed here. Many of the factors that cause a change in SEP can also
Intravenous Agents affect MEP (see Table 16.6).
Propofol is the IV anesthetic used most often with MEP monitoring. Doses
up to 25 mg/kg/hour do not cause significant changes in the MEP ampli- Ischemia/Blood Pressure
tude. When compared with inhalational agents, doses of propofol caus- Ischemia of the spinal cord can result in loss of MEP (Fig. 16.13). The
ing comparable suppression of the bispectral index (BIS) do not cause any gray matter of the spinal cord is more susceptible to reduced blood supply
change in MEP, while inhalational agents make them mostly not recordable than the white matter. Surgeries involving clamping of the aorta suggest that
(22,23). Propofol is supplemented by a narcotic analgesic such as fentanyl. muscle MEP are lost within 2 to 5 minutes of onset of ischemia, whereas
In doses typically used in the operating room, fentanyl and similar narcotic SEP take 7 to 30 minutes to be affected (3). If only the anterior spinal cord is
analgesics do not cause significant changes in the MEP. When robust muscle affected by ischemia, SEP may not change at all. A drop in the mean arterial
MEP must be recorded, a TIVA technique is useful, incorporating propofol pressure during surgery can have a similar effect on MEP.
and a narcotic analgesic. Peripheral nerves may also be affected by ischemia and result in loss of
muscle MEP responses from muscles supplied by the ischemic nerve. This
Neuromuscular Junction Blocking Agents may occur when a tourniquet or wrapping is applied tightly around a limb,
When muscle MEP are recorded, NMJBA should be used only with cau- compromising the vasa nervosum. A similar situation may arise when large-
tion. Persistent use of these drugs will eliminate the muscle MEP. However, bore catheters are placed in blood vessels. This may result in ischemia of the
D waves can still be recorded. If TES produces excessive movement that distal limb, leading to loss of MEP from that limb (26). In this situation, the
must be limited, a partial neuromuscular blockade can be used with an muscle MEP disappears after the SEP peripheral response has disappeared.
IV infusion of a short-acting NMJBA. Intermittent boluses of a NMJBA
should not be used as that causes excessive variability of the MEP, mak- Acute Trauma
ing monitoring unreliable. When an infusion is used, at least two out of Trauma to the spinal cord, as may occur during vertebral column manipula-
four twitches must be present in a train-of-four (TOF) stimulation for reli- tion, can cause MEP changes. The mechanism underlying this change has
able MEP monitoring (24). The TOF should be monitored by the NIOM been discussed earlier with SEP monitoring. If the trauma is detected early, it
team in the limb from which the muscle MEP is being recorded. The use of may be reversible if the intervention that produced the change can be reversed.
partial neuromuscular blockade, however, adds considerable complexity to
monitoring and risks, making MEP monitoring unreliable if the infusion Temperature
of the NMJBA is not tightly controlled. Administration of magnesium and MEP are affected by changes in core body temperature. MEP obtained in
α2-receptor agonists such as ketanserin can also potentiate neuromuscular animals with spinal cord stimulation were found to be affected if the tem-
blockade and suppress muscle MEP amplitudes (25). perature changed as little as 2°C to 2.5°C. At a temperature of 28°C, MEP
cannot be recorded (27). If substantial temperature alteration occurs after
Mechanisms of MEP Change the start of the surgical procedure, new MEP baselines may need to be set
prior to start of the critical phase of the surgery.
As with other types of monitoring, the main causes of change in MEP
monitoring can be surgical intervention, changes in the physiologic milieu, Anesthetics
or technical issues with the monitoring. For surgeries on the spinal cord, As discussed previously, muscle MEP monitoring is very sensitive to an-
recording muscle MEP in the upper and lower limbs can aid in determining esthetics. Inhalational anesthetics can significantly reduce MEP amplitude
Figure 16.13: Sudden loss of lower extremity

muscle MEP with preservation of upper extrem-
ity MEP during resection of tumor around de-
scending aorta (arrow). A major blood vessel
supplying the anterior spinal artery was likely
inadvertently cut.
even at a low concentration. Though propofol is the preferred agent for in variable amplitudes and morphologies. Slight changes in blood pressure
MEP monitoring, very high doses of this can also reduce MEP amplitude. and anesthetics can also cause changes in muscle MEP amplitude, making
NMJBA should be used only as a continuous infusion, as a bolus will cause small changes in amplitude difficult to interpret. When a significant change
a sudden drop in MEP amplitude, making interpretation difficult. in muscle MEP is noted, and the surgeon takes corrective measures, the re-
sponse can reappear with no postoperative motor deficit.
Technical Issues Others have argued that partial injury to the motor pathways is likely to
Many technical issues can lead to MEP changes. Common technical issues cause partial decrement in muscle MEP amplitude. A 50% drop in amplitude
involve problems with stimulating electrodes. If straight needles are used, has been suggested as being significant; however, this is considered by most
they can become dislodged during surgery. Not only will this result in loss to be overly sensitive and not very specific. The need to increase the stimula-
of MEP, but if the needles are reinserted in a slightly different position, tion intensity by 100 V to maintain the muscle MEP amplitude is also used
the MEP may appear to be of different amplitude and morphology. If the to indicate potential motor tract injury (29). This threshold method does not
needles are closer to the C3-C4 position, the upper limb MEP amplitude account for changes in stimulation intensity that may be needed based on
may be greater, whereas if they are inserted closer to C1-C2, lower limb scalp electrode impedance changes, changes in physiologic milieu (particu-
responses may be larger. Problems may occur with the stimulator itself. larly during a long surgery), and variability of the number of D and I waves
If a stimulator is used that cannot deliver sufficient charge to the scalp, that occur with each train of stimuli. Consequently, most practitioners use
MEP may not be recordable. The recording system may also cause MEP the all or none approach for warning surgeons of a significant change.
changes. If the recordings are performed with needle electrodes, these may Regardless of which interpretation paradigm is used, it is most important
become dislodged, changing the morphology of the response or obliterat- to be aware of changes in muscle MEP during monitoring. If the muscle
ing it completely. If the SEP recording electrodes are not removed from MEP is consistent during the surgery, a 30% to 50% change in amplitude
the jack box prior to TES, a stimulus artifact may make it impossible to may be significant. However, if the responses have been inconsistent and
visualize the muscle MEP. As with other types of monitoring, technical variable, even an 80% to 90% change in amplitude may not be meaningful.
issues must be considered before raising an alert about the change in MEP As with other types of monitoring, a change is significant only when the
monitoring. responses have been stable before the change.
Muscle MEP signal “fade” has been noted in long surgical procedures.
Warning Criteria Fade refers to gradual muscle MEP amplitude loss or stimulation thresh-
old increase that cannot be explained by changes in anesthesia, tempera-
Warning criteria for D wave changes are well defined. A drop in amplitude ture, blood pressure, etc. An example of fade is shown in Fig. 16.14. Fade
of the D wave of greater than 50% is associated with a greater likelihood also affects SEP waveforms. The gradual loss of amplitude lowers extremity
of permanent motor deficit. Preservation of the D wave correlates highly muscle MEP and tibial SEP more than upper extremity MEP and median
with good outcomes (18). D wave changes should be interpreted with cau- or ulnar SEP. It has been estimated that to keep muscle MEP amplitude
tion during scoliosis surgeries. Changes in the position of the epidural elec- greater than 50 µV, stimulation intensity needs to be increased by 11 V per
trode with vertebral column straightening can cause substantial changes in hour in neurologically normal patients and by 23 V per hour in myelopathic
D wave amplitude which do not signify spinal cord injury (28). individuals (30). Fade has not been reported for D waves.
There is considerably less agreement regarding interpretation of muscle
MEP. Many practitioners prefer the “all or none” approach. A significant Safety
change is considered a greater than 90% decrement of the muscle MEP
that has been consistently present. Increasing the intensity of stimulation There has been considerable concern regarding the safety of TES be-
is not able to overcome this change (18). This approach is favored by many cause of the high-intensity stimulation applied to the scalp. Despite high-
in view of the variable nature of the muscle MEP; successive trials result intensity stimulation applied to the scalp, the current reaching the cortex
Figure 16.14: Muscle MEP responses from the right upper (left) and lower (right) extremities are shown.
Notice the gradual decrease in size of the muscle MEP response from the lower extremity (thick arrow), which
improves with increase in stimulation intensity (thin arrow).
is smaller than that used for direct cortical stimulation during brain map- decide whether the benefits of MEP monitoring with TES outweigh the
ping. The commonest complication of TES for MEP monitoring is the potential risks.
occurrence of tongue and lip lacerations in less than 0.2% of cases (31).
Because of the potential for this complication, bite guards are routinely Clinical Applications
used when TES is being performed. Other complication such as cardiac
arrhythmias, seizures, mandibular fractures, intraoperative awareness, and MEP monitoring has been used during many types of surgeries in which
scalp burns are much less common. The frequency of these complications the motor pathways are at risk of injury. As noted earlier with SEP, a recent
is presented in Table 16.11. AAN Practice Parameter notes the utility of SEP and MEP NIOM in vari-
Thermal injury, such as scalp burns, remains a theoretical concern with ous types of spinal surgeries (14). Some of the more common surgeries for
TES due to the high-intensity electrical stimulation delivered to the scalp. which MEP NIOM is useful are discussed here.
The maximum electrical stimulator output considered safe is 50 mJ over Considerable data are available regarding the utility of NIOM during con-
a 1,000 Ω resistance. Long pulses of 0.5 millisecond cannot deliver greater ventional and endovascular descending thoracic aorta surgery (3,26). MEP
than 50 mJ and are unlikely to cause burns. However, short pulses of 0.05 show changes much sooner than SEP when blood supply to the anterior
millisecond of 1,500 V can deliver up to 75 mJ to the scalp, depending on spinal artery system is impaired. If this hypoperfusion is corrected rapidly,
electrode impedance (18). In this latter scenario, burns can occur. Conse- MEP return and good outcome is possible (32).
quently, using the lowest possible stimulus intensity to obtain a reliable Monitoring muscle MEP has been shown to reduce postoperative mor-
MEP is recommended. bidity for spinal cord tumor surgeries. When combined with D wave record-
Several contraindications for TES have been noted. These include history ings, muscle MEP can guide the extent of surgical resection (33). Surgeries
of seizures, cortical lesions, increased intracranial pressure, pacemaker, for cervicothoracic spinal deformities and scoliosis can be made safer with
skull defect/breach, metal plate in scalp, deep brain stimulator, vascular MEP monitoring. Since paraplegia is the most dreaded complication in
clips, and implanted devices (such as cochlear implants). Increasingly, only these surgeries, MEP monitoring is a logical adjunct to SEP monitoring.
vascular clips and implanted devices serve as absolute contraindications, Additionally, MEP adds redundancy to SEP monitoring in these procedures
and many patients with other potential contraindications have been moni- (34). MEP monitoring can also be helpful in cerebral vascular disease sur-
tored without incident. Ultimately, the surgeon and neurophysiologist must gery. Though SEP monitoring can detect cortical ischemia in these surgeries,
ischemia to the motor pathway deep to the cortex may be undetected with
SEP. MEP monitoring is more sensitive to motor pathway ischemia and ap-
TABLE 16.11 Complications Associated with TES pears to be a valuable adjunct in these procedures (35). MEP monitoring
has also been used for many other types of surgeries, such as posterior fossa
Complication No. (n ∙ >15,000) surgery, tethered spinal cord surgery, brachial plexus reconstruction surgery,
Tongue/lip laceration 29
and others. Its utility in these surgeries is less clearly established.
Cardiac arrhythmias 5
Brainstem Auditory Evoked Potentials
Seizures 5
Minor scalp burns 2 BAEP are obtained by stimulating the vestibulocochlear nerve (cranial
Mandibular fracture 1 nerve [CN] VIII). As the stimulation volley ascends the brain stem auditory
pathways, BAEP waveforms are obtained from various neurologic struc-
Intraoperative awareness 1
tures. BAEP monitoring is useful when integrity of the cochlea, CN VIII,
Data from reference James ML, Andersen ND, Swaminathan M, et al. Predictors of or brain stem auditory structures is at risk. The most rostral aspect parts of
electrocerebral inactivity with deep hypothermia. Ann Cardiothorac Surg 2013;
the auditory pathway, however, are not monitored by the BAEP as the last
2(2):184–193. waveform recorded is from the caudal midbrain.
Anatomy and Physiology helpful in localizing possible lesions. Most BAEP waveforms have a positive
polarity when recorded at the scalp. The one exception to this rule is wave I.
BAEP are a type of auditory evoked potentials (AEP). As their name im- This waveform is a near-field potential recorded from the reference electrode
plies, AEP are produced when an auditory stimulus is applied to the ears. that is placed on the ipsilateral ear or mastoid. Because this waveform is of
AEP are classified on the basis of latency of the waveforms recorded. Short- negative polarity in the reference electrode, the deflection will be in the same
latency AEP, or BAEP, include waveforms that have a latency of less than direction as the remaining waveforms that are of positive polarity at the ac-
10 milliseconds and are generated by structures in the ear, CN VIII, or the tive electrode.
brain stem. Long-latency AEP include AEP with latencies greater than For clinical purposes, five waveforms are recorded in a BAEP using a Cz-
50 milliseconds, whereas middle-latency AEP include waveforms between A1/Cz-A2 derivation. Each of the waveforms is numbered according to the
short- and long-latency AEP. Both middle- and long-latency AEP are gener- order in which it appears. The putative site of generation of each of the
ated by structures in the cerebral cortex (36,37). Middle- and long-latency waveforms is shown in Table 16.12. Wave I is generated by the most distal
AEP are variably reproducible and suppressed by many sedative medica- part of the auditory nerve, whereas wave II most likely arises from the proxi-
tions, particularly anesthesia. Consequently, these are not used in NIOM. mal part of this nerve and the cochlear nuclei. Wave III is best seen in the
Further discussion will focus on BAEP as they are most useful clinically. Cz-ipsilateral ear derivation and receives the most contribution from caudal
Auditory stimulation is usually applied to the ear in the form of a click pontine tegmentum and the superior olivary nucleus. Waves IV and V are
or a tone pip. After traversing the external auditory canal, the tympanic often fused and their anatomical generators are likely in close proximity.
membrane, and the middle ear, the sound reaches the cochlea. Activation of The wave IV generator is the rostral part of the lateral lemniscus just before
the hair cells of the cochlea leads to activation of the auditory nerve, which it gets to the inferior colliculus. Wave V is thought to arise from the inferior
joins with the vestibular nerve to form CN VIII (vestibulocochlear nerve). colliculus (38). As noted previously, all except wave I are positive waves as
The auditory nerve fibers synapse with neurons in the ventral and dorsal co- recorded from the derivation Cz-A1/A2.
chlear nuclei in the rostral medulla. From these nuclei, fibers ascend on both
sides of the brain stem. These decussating auditory fibers form the trap- Methodology
ezoid body in the ventral pons. About one-half of the fibers decussate and
one-half ascend ipsilaterally to synapse with the superior olivary complex in To successfully obtain BAEP in the operating room, proper stimulation and
the pons. The fiber tract between the cochlear nuclei and the superior oli- recording techniques must be employed. Adequate aural stimulation must
vary complex is called the lateral lemniscus. Fibers from the superior olivary be assured at all times, and the recording apparatus must reliably reproduce
complex continue to ascend in the lateral lemniscus to the inferior colliculi the waveforms. This section will review the techniques used for stimulation
in the midbrain. From the inferior colliculi, auditory fibers ascend to the and recording of BAEP waveforms.
medial geniculate body, which is a part of the thalamic nuclei. Finally, from
the medial geniculate body, fibers ascend to the primary auditory cortex in
the superior temporal gyrus (36). Secondary auditory processing areas re- TABLE 16.12 Sites of Origins of Various EP Waveforms
ceive the auditory input thereafter for further analysis of the sound. Because
of only partial decussation of the auditory tract in the upper medulla and Waveform Localization
lower pons, hearing from each side is represented bilaterally in the brain.
I Distal auditory nerve
Consequently, hearing loss is unlikely from lateralized brain stem pathology.
BAEP waveforms are a series of negative and positive waves arising from II Proximal auditory nerve and cochlear nucleus
various parts of the auditory pathway. Much like SEP waveforms, generally III Superior olivary complex
no one anatomical area gives rise to a particular BAEP waveform, and no IV Lateral lemniscus, just caudal to inferior colliculus
waveform has a single contributing neural structure (except wave I). How- V Inferior colliculus
ever, assigning a neural structure as the most likely source of a waveform is
Stimulating Techniques A negative potential at the reference electrode is similar to having a positive
Stimulation is performed with broad band clicks. While these clicks include potential in the active electrode.
sound in a wide range of frequencies, it is the high-end frequencies that Waves II–V are far-field potentials that have a positive polarity when
result in cochlear activation and the BAEP response. The click stimulus is a recorded from the scalp. The most robust of these waveforms is wave V,
square wave pulse that has a duration of 100 to 200 µs. Both rarefaction and which is the last BAEP waveform to disappear as click stimulation intensity
condensation clicks can be used, and each has its advantages. Rarefaction decreases. Wave V is best seen in the Cz-Ac derivation. In this derivation,
clicks produce a better wave I, whereas condensation clicks result in a more waves IV and V are more clearly separated. Waves II and III, on the other
reliable wave V. Often, however, a high-intensity click is used in the operat- hand, are more likely to be fused in this derivation. These latter waveforms
ing room, and to minimize the stimulus artifact, an alternating click is used. are more clearly separated from each other in the Cz-Ai derivation. An ex-
An alternating click produces a stimulus artifact of opposite polarity, thus ample of BAEP waveforms obtained in the Cz-Ai and Cz-Ac derivations is
causing cancellation of the artifact. presented in Fig. 16.16.
In the operating room, a high stimulation intensity is used for eliciting The recording amplifier filters settings are kept between 150 and 1,500
BAEP. Typically, a 60 to 80 dBnHL stimulus is applied to the tested ear, Hz. The broadband click stimuli are applied at a rate of 30 per second.
while a 40 dBnHL masking stimulus is applied to the contralateral ear to Often 1,000 to 3,000 repetitions must be performed to obtain reliable BAEP
serve as masking. Masking prevents bone conduction of the stimulus to the waveforms.
contralateral ear and allows for truly unilateral stimulation of the auditory
pathways.
In the outpatient laboratory, BAEP stimulus is commonly applied to the Anesthetic Considerations
ear with headphones over the ears. These are too large and obtrusive for
the operating room environment. Consequently, instead of headphones, ear Anesthetic agents affect cortical responses more than subcortical and pe-
inserts are used. These attach to a plastic tube that connects to the source ripheral response. BAEP do not have cortical responses, and the waveform
of sound generation. The plastic tube is kink proof so that it does not get represents signals recorded from only cranial nerve and brainstem struc-
obstructed during the surgical setup and procedure. Once the ear insert is tures. As such, anesthetics have little effect on BAEP. Inhalational anesthetic
secured in the external auditory canal during NIOM setup, a water proof agents have no significant effect on the BAEP waveform. When the con-
seal is applied around the insert. This entire setup is then covered with a centration of halogenated agents is very high, the BAEP waveforms may
dressing. Preventing water seepage into the external auditory canal is impor- increase in latency and decrease in amplitude. Nitrous oxide and IV agents,
tant as it can prevent adequate stimulation from being delivered to the ear. such as propofol, do not appreciably affect the BAEP. NMJBA also do not
A typical setup for BAEP monitoring is shown in Fig. 16.15A–D. affect the BAEP; however, they do reduce background EMG activity. This
results in an improvement of the SNR and makes it easier to average BAEP.
This may give the illusion that these agents result in an increase of the BAEP
Recording Technique amplitude. Instead, the BAEP is simply made more prominent as the back-
Electrodes for recording the BAEP are placed on Cz, A1, and A2. Sub- ground noise is reduced. Of all EP recorded in the operating room, BAEP
dermal needle electrodes are most often used for recording potentials. A and NAP are the most insensitive potential to anesthetics.
two-channel recording montage is typically used: Cz-ipsilateral ear and
Cz-contralateral ear (Cz-Ai, Cz-Ac). The Cz-Ai derivation shows a promi-
nent wave I as well as waves II–V. As noted earlier, though wave I has a Mechanisms of BAEP Change
negative polarity and the other waves have a positive polarity, they all are
deflected in the same direction. This is because wave I is a near-field po- Changes in BAEP waveforms during surgery can occur for several rea-
tential produced by the auditory nerve (nerve action potential, NAP). It sons (39). Most concerning are changes due to surgical intervention that
has a negative polarity and is best recorded by the ear (reference) electrode. affect parts of the auditory pathway. However, changes may also occur for
A B
C D
Figure 16.15: Setup of BAEP stimulat-

ing electrode. In A notice the ear insert
and the tubing attached to it. After ear
insert has been applied, a water seal is
applied, and the ear insert is covered
with gauze (B–D).
technical reasons or as a result of physiological changes not related to sur- Cochlear Injury
gery. It is important to differentiate between these changes so that appropri- Injury to the cochlea can occur in several ways during surgery. During drill-
ate alerts can be raised. ing for exposure, the inner ear and cochlea may be inadvertently injured.
This results in loss of all BAEP waveforms since even wave I is generated
Surgery-Induced Changes more proximally than the cochlea. It is important to distinguish this change
Surgery in and around the brain stem and CN VIII can affect the auditory from change due to technical problems, particularly stimulation failure. The
pathway and results in changes to the BAEP. The specific changes in the latter also results in loss of all BAEP waveforms.
BAEP and the waveforms affected can help determine the site of injury. Interruption of the vascular supply to the cochlea can result in BAEP
A summary of the BAEP changes and their localization is presented in changes as well. The internal auditory artery, branch of the anterior inferior
Table 16.13. cerebellar artery, supplies the cochlea and lies in close relation to CN VIII (40).
TABLE 16.13 Patterns of Surgery-Induced Changes in BAEP
Location Cause Effect on BAEP

Cochlea Trauma, ischemia ↑ Latency of all waves,
↓ amplitude of wave I
Proximal CN VIII Stretch from retraction, Wave I preserved, others
mechanical, vascular, ↑ latency, ↓ amplitude
thermal
Lower pons Compression, thermal, Wave I preserved, others
vascular ↑ latency, ↓ amplitude
Mid pons to lower Compression, thermal, Wave I and III preserved,
midbrain vascular wave V ↑ latency, ↓
amplitude
Rostral to lower Compression, thermal, BAEP may not detect
Figure 16.16: A sample BAEP waveform obtained with Cz-A1 and Cz-A2 montage midbrain vascular damage
after stimulation of the left ear. Notice that wave I is seen only in Cz-A1 (ipsilateral
to side of stimulation), while wave V and waves IV and V separation is better seen
in the Cz-A2 derivation. See text for description of advantages of both derivations.
noted, the surgeon is alerted, who typically pauses the surgery and lessens
the traction on the cerebellum to allow the nerve to recover.
During dissection, if the internal auditory artery is damaged, infarction of CN VIII may also undergo mechanical or thermal injury during dissec-
the cochlea occurs. This results in sudden loss of all BAEP waveforms. This tion. This is particularly common during surgery for tumors of CN VIII
type of injury causes a more sudden change in BAEP than other types of or around it. Direct trauma during dissection and thermal damage from
injury, and it is very unlikely that the BAEP will recover during the remainder electrocautery can damage the nerve and result in BAEP changes. Addi-
of the surgery. Hearing loss is common after vascular injury to the cochlea, tionally, injury to the vascular supply of CN VIII can cause nerve infarc-
particularly if the BAEP remains absent for at least 15 minutes (41). tion. Since these injuries are typically to the proximal part of the nerve, the
BAEP changes are very similar to those described earlier for traction injury.
Injury of CN VIII Recently, however, concern has been raised about whether BAEP changes
During surgeries on the cerebellopontine angle, the cerebellum has to be should be interpreted the same way regardless of whether the surgery being
retracted for adequate exposure. This retraction causes traction and stretch performed is for microvascular decompression or tumor resection (43). This
of CN VIII. This stretch injury can result in hearing loss and was the major will be discussed further later in the chapter.
morbidity of microvascular decompression surgeries for trigeminal neural- Manipulation of CN VIII can cause vasospasm of the vasa nervosum
gia and hemifacial spasms. BAEP monitoring has resulted in a significant supplying the nerve. This results in ischemia and loss of BAEP waveforms.
reduction of this complication (42). This type of traction injury results in Papaverine has been used locally to avoid this vasospasm. However, loss of
compromise of the proximal CN VIII. This results in latency prolongation BAEP waveforms after papavarine use has been reported and noted by the
of waves II–V with a reduction of amplitude. Wave I is preserved as it is gen- author (44). An example of this is presented in Fig. 16.17. This, however,
erated from the distal CN VIII. Since wave V is the most robust of the BAEP does not appear to cause long-term hearing problems.
waveforms, it is the waveform evaluated most closely in cerebellopontine At the cochlear end, CN VIII divides into very small fascicles that at-
angle surgeries and serves as the surrogate marker for the health of CN VIII. tach to the cochlea. Traction on these fascicles can result in damage with
When significant latency prolongation or amplitude reduction of wave V is consequent loss of hearing. This type of damage can occur when tumor
the auditory pathways and cause BAEP changes. This is true for open and
endovascular procedures.
If the injury to the brain stem is below the level of the caudal midbrain,
at least wave V of the BAEP will have prolonged latency and reduced ampli-
tude. If the area of the superior olivary nucleus is involved, waves III and V
may be affected. Wave I is typically preserved when the injury is in the brain
stem as wave I is generated by the peripheral CN VIII.
It should be noted, however, that if the brain stem injury does not involve
the auditory pathways, the BAEP may remain unaffected but the patient
may have significant morbidity. Additionally, injury to auditory pathways in
the brain stem does not always result in hearing loss as hearing has bilateral
representation in the brain stem.
Physiological Changes
Many types of physiologic changes can affect the BAEP. These must be con-
sidered before raising alerts to the surgeon. Usually, physiologic changes
affect BAEP bilaterally, making identification that the change is due to
physiologic, nonsurgical issues easier.
Temperature
Change in body temperature can profoundly affect the BAEP. With cooling,
the latency of wave I and the interpeak latencies increase. This change in
Figure 16.17: BAEP operative monitoring waveforms for a surgical procedure latency is nonlinear; at lower temperatures, the changes in latency are more
in which papaverine was injected at the end to enhance blood supply. This re- severe (12). The amplitude of the various BAEP waveforms initially increase
sulted in loss of all BAEP. These findings persisted postoperatively as evaluated
as the temperature is reduced. However, more significant temperature reduc-
by a routine BAEP. The patient did not have hearing loss, however.
tion results in a drop in amplitude. Various authors have reported disap-
pearance of BAEP waveforms at different temperatures, but in the author’s
is being scraped off CN VIII. If the traction occurs in the direction of the experience, BAEP waveforms are difficult to appreciate below 20°C (46).
brain stem, CN VIII roots attaching to the cochlea can be easily avulsed With rewarming, the BAEP reappears and gradually increases in amplitude
(45). Scraping the nerve is much safer when done from the brain stem out- and shortens in latency. The temperature at which the BAEP disappears and
ward toward the cochlea. If CN VIII is avulsed from the cochlea, all BAEP reappears does not need to be the same. An example of gradually changing
waveforms will be lost as the injury to the auditory pathways is very distal. BAEP with changing systemic temperature is shown in Fig. 16.18.
The temperature changes noted earlier are extreme and seen typically in
Brain Stem Injury cases in which systemic hypothermia is used. In typical cases where there
Surgery on the brain stem that affects auditory pathways can produce is only mild temperature reduction, only slight latency prolongations of
changes in the BAEP. During resection of brain stem tumors, mechanical the BAEP may be evident. Sometimes, the surgically exposed CN VIII
trauma, thermal injury, and injury from a cavitational ultrasonic surgical undergoes more cooling than its counterpart. In these circumstances, the
aspirator may cause BAEP changes. Resection or repair of vascular lesions asymmetrical prolongation of the BAEP waveforms may be confused with
of the brain stem can result in ischemia or infarction of critical parts of surgery-induced changes.
Figure 16.18: Changes in BAEP during cooling

and rewarming. The earliest waveforms are at
the top of the figure. Notice wave V gradually
prolongs in latency and finally disappears at
09:47:30. The temperature at this point is 25.3°C.
With rewarming, the wave V gradually reap-
pears at 11:35:23 at a temperature of 20.1°C. As
the temperature increases further, the wave V
latency shortens and amplitude increases.
Anesthesia
The effects of anesthesia on BAEP have been described in detail earlier.
Most anesthetic agents have minimal to no effect on BAEP. Halogenated
inhalational agents in high doses can cause prolongation of BAEP latencies
and a reduction of amplitudes.
Technical Issues
Many technical issues can cause problems with recording BAEP. These must
be differentiated from surgery-induced changes so that the surgery is not
halted unnecessarily. Broadly, technical issues can be divided into problems
with stimulation and problems with recording.
Ineffective Stimulation
Anything that interferes with delivery of clicks to the ear can affect BAEP.
Examples of issues that can cause this are equipment malfunction, prob-
lems with tubing or inserts, use of incorrect programs or operator error. A
technical issue that is peculiar to BAEP is kinking of the plastic tubing lead-
ing from the ear insert to the click transducer. This can happen soon after
draping the patient if a skin hook is inadvertently applied over the tubing
(Fig. 16.19). Unkinking of the tubing or removing whatever is obstructing it
results in rapid improvement of the BAEP.
Other technical factors can result in changes similar to those seen with
kinked stimulator tubing. Dislodgement of the ear insert will result in loss
of BAEP waveforms. Fluid accumulation in the middle ear from seepage
from the surgical site will result in loss of amplitude and possibly loss of
BAEP (Fig. 16.20). Making sure that the ear insert is secured well in place
and a water-tight seal is obtained around the insert will ensure that these Figure 16.19: Sudden loss of BAEP after application of a skin hook during
patient draping. Notice that all BAEP waveforms are robust and present at
technical issues do not result in interpretative challenges.
the start of the case at 09:36:35. When BAEP are repeated after draping at
When stimulation is ineffective, regardless of cause, a predictable change 10:26:29, no BAEP response is noted. Drapes are removed at 10:36:55, and
in BAEP occurs. Initially, there is a gradual prolongation of the wave I la- by 10:46:57 baseline BAEP responses have returned. Removing the drapes re-
tency with loss of amplitude. With more severe changes, wave I is completely sulted in removal of skin hooks that were kinking the BAEP stimulator tubing.
lost, and often the subsequent waveforms are also lost. However, wave V Note that the montage is listed as A2-Cz and A1-Cz—this should read Cz-A2
may persist slightly longer than wave I and is often the last waveform to and Cz-A1.
disappear (see Figs. 16.19 and 16.20). BAEP changes due to inadequate
stimulation can be distinguished from traction or stretch injury to CN VIII
by the loss of wave I with inadequate stimulation and preservation of this result in loss of all BAEP waveforms. Only a thorough survey of technical
waveform with traction injury. However, injury to the cochlear (traumatic or setup and an understanding of what is happening in the surgical field will
vascular) is more difficult to differentiate from technical problems as both help differentiate these two possibilities.
Figure 16.20: Loss of BAEP due to gradual ac-

cumulation of fluid in the middle ear. When the
surgery starts at 14:57:12, a robust wave I and V
are present. After the start of closing, the wave
V amplitude starts to decrease, and there is mild
prolongation of latency. In addition to wave V
losing amplitude, wave I also loses amplitude
and disappears before the loss of wave V. This
type of gradual change is typically due to slow
fluid accumulation in the middle ear. Note that
the montage is listed as A2-Cz and A1-Cz—this
should read Cz-A2 and Cz-A1.
Ineffective Recording types of electrocauteries and the cavitational ultrasonic surgical aspirator
As with ineffective stimulation, problems with the recording system can re- (39). Many amplifiers can be programed to stop averaging when such de-
sult in ineffective recording of the BAEP. These changes can range from vices are turned on. However, often such automatic settings do not work
problems with the electrodes or electrode wires, high impedances of the re- well, and manually pausing averaging becomes the most effective way of
cording electrodes, amplifier problems, or operator error. Several medical preventing these high-amplitude artifacts from obliterating the BAEP.
devices in the operating room generate various types of high-amplitude ar- A relatively unique artifact seen in BAEP recordings is that caused
tifact that can make averaging of BAEP very difficult. This includes various by drilling. Drilling of bone causes a loud sound that can exceed 90 to
and dislodged electrodes as well as drilling will cause a rapid change in

the BAEP. Various types of artifacts from other medical equipment can
cause a sudden or gradual loss of BAEP depending on the amplitude and
persistence of the artifact. Once the cause of ineffective recording is recti-
fied, the BAEP return to baseline quickly. BAEP changes from ineffective
stimulation must be differentiated from other causes of loss of all BAEP
waveforms.
Warning Criteria
BAEP monitoring has been used for many years and has been shown to
clearly reduce the risk of postoperative hearing loss. Despite this, clear cri-
teria for warning surgeons when a significant change has occurred are not
well established. It is generally agreed upon, however, that the BAEP wave
V latency and amplitude are used to determine whether significant neural
compromise is occurring. Wave V is the most robust waveform and the last
to disappear in case of hearing loss. Moreover, it is the last waveform evalu-
ated and provides assessment of as much of the auditory pathway as pos-
sible with BAEP. Interpeak latencies are not typically evaluated, though the
I–V interpeak latency may also serve to indicate compromise of the auditory
pathway.
The BAEP criteria most often used to raise an alert is wave V latency
prolongation of 1.0 millisecond or amplitude decrease of 50% (48). How-
ever, other criteria such as wave V latency prolongation of 0.5 millisecond
or complete loss of wave V have also been proposed (49–51). All of these are
empiric criteria. However, studies have shown that when the latency of wave
V increases by 1.0 millisecond, the probability of audiologically determined
hearing loss is higher than if such an increase is not noted (47).
Figure 16.21: Example of continued averaging during drilling. Notice that at Warning criteria may need to be modified depending on the type of sur-
the start of this study, a robust BAEP was noted. However, since the recording
gery being performed. With microvascular decompression surgeries, clinical
was not stopped during drilling, the response obtained on 09:11:04 resulted in
considerable loss of amplitude of all waveforms. Once the drilling was stopped
hearing loss is noted when wave V is completely lost (43). Prolongation of
at 09:20:25, the BAEP returned to baseline. Note that the montage is listed as wave V latency by 1.0 millisecond or drop in amplitude of 50% is often not
A2-Cz and A1-Cz—this should read Cz-A2 and Cz-A1. associated with any appreciable change in hearing. However, for cerebello-
pontine angle tumor surgery, a 0.5-millisecond latency prolongation of wave V
100 dBnHL (39). This sound is louder than the clicks being used. Conse- may be associated with hearing loss. Consequently, a “sliding scale” approach
quently, the clicks are overshadowed out by this noise, and effective cochlear to warning the surgeon has been suggested, depending on the pathology. A
stimulation is compromised, resulting in loss of BAEP (Fig. 16.21). It is best reasonable approach is to alert the surgeon when a 0.5-millisecond prolonga-
to pause averaging of the BAEP when drilling is ongoing (47). tion of wave V latency or 50% drop in amplitude is noted, particularly if the
Ineffective recording results in loss of all BAEP waveforms. The loss of surgery is for a tumor. If the wave V further deteriorates, additional alerts
BAEP can be gradual or sudden, depending on the etiology. Broken wires should be issued. In all cases, a wave V prolongation of 1.0 millisecond
should merit an alert to the surgeon, even if the surgery is for microvascu- The auditory NAP represents potentials from the same neurologic structure
lar decompression. Loss of wave V, of course, should also be immediately as wave I of the BAEP, the auditory nerve.
reported. Such a change is frequently associated with hearing loss, but it The major advantage of the auditory NAP is that it can be obtained rap-
should be recognized that even persistent loss of wave V does not mean idly. It has a high SNR, and often only 20 to 30 repetitions are required to
inevitable loss of hearing; its presence also does not guarantee preserved see a reproducible response. This takes only a few seconds. BAEP require
hearing (52,53). up to 4,000 repetitions, which can take up to several minutes (59). There are
some disadvantages, however. The electrode requires surgical placement and
Clinical Applications cannot be placed until after exposure of CN VIII. Thus, this cannot be used
to monitor nerve function during exposure. Previously, it was difficult to
BAEP monitoring assesses the auditory pathway from the cochlea to the keep the electrode in place, but newer electrode designs have enabled better
caudal midbrain. It is routinely used to reduce the incidence of hearing electrode stability. Despite this, small electrode movements can result in large
loss in surgeries involving the auditory pathway up to the midbrain. Sur- changes in the NAP response, making interpretation difficult. The electrode
geries compromising CN VIII, such as surgeries on the cerebellopontine could also traumatize the nerve, as the nerve is very delicate. Finally, since
angle for microvascular decompression that cause traction on the nerve, can the electrode is in the surgical field, it can obstruct the surgeon (60).
have a high incidence of hearing loss. BAEP monitoring has been shown to Changes in the auditory NAP can occur for many of the same reasons
remarkably reduce this morbidity (54). as BAEP changes occur. Whenever a change is noted, technical issues in-
Surgeries for resection of acoustic neuromas and other cerebellopontine volving problems with stimulation and recording should be considered. If
angle tumors can cause hearing loss. There are various approaches that can averaging is performed during drilling, the noise from drilling can impair the
be used to resect these tumors, translabyrinthine, suboccipital, or middle ability to record auditory NAP. Traction on CN VIII, such as with cerebellar
fossa. Each has its benefits and risks, the discussion of which is beyond the retraction, can also cause auditory NAP latency prolongation and reduction
scope of this chapter. Regardless of the approach used, BAEP monitor- in amplitude. Nerve trauma, such as with dissection of tumor off the nerve,
ing has been used to reduce hearing loss associated with these procedures can cause similar changes. Interruption of the vascular supply to CN VIII
(47,54,55). As already noted, the warning criteria used in these types of can cause a sudden loss of the NAP that, in most cases, is irreversible (47).
surgeries are not clearly defined. Auditory NAP recordings are used most often during dissection of acous-
Brainstem vascular malformation and tumor surgeries have also used tic neuromas and other cerebellopontine angle tumors. The recording elec-
BAEP monitoring to reduce injury to auditory pathways in particular and trode is placed proximal to the tumor—between the tumor and the brain
brainstem in general (35,47,56). In these surgeries, BAEP monitoring is of- stem. This allows surgical changes to be reflected in the NAP recording. If
ten used in conjunction with SEP, MEP, and other cranial nerve monitoring. the auditory NAP is preserved after surgery, there is a high likelihood of
BAEP monitoring has also been used in skull base surgery in which several preserved hearing (61). Conversely, loss of the NAP correlates very strongly
cranial nerves are at risk and in middle and inner ear surgery to reduce risk with postoperative hearing loss (49). Auditory NAP recording has also
of injury to the cochlea. been used in microvascular decompression surgeries and has been shown to
further decrease the incidence of hearing loss (62).
Auditory Nerve Action Potential
A NAP can be recorded directly from the auditory (cochlear) nerve. Such
recordings can be performed rapidly and increase the speed with which feed- EEG has been used for many decades to assess cerebral function during
back can be provided to the surgeon. This involves placing a specially de- surgical procedures. It is different from other types of NIOM in which EP
signed electrode on the auditory nerve near its entry into the brain stem (57). are used as there is no stimulus used to elicit the recorded waveforms. Ini-
Stimulation is the same as that used to obtain BAEP, with broad band clicks. tially, EEG monitoring was used to determine adequacy of cerebral perfu-
In fact, often auditory NAP and BAEP are obtained simultaneously (58). sion and the need for a shunt during carotid endarterectomy (CEA) surgery.
More recently, EEG monitoring has been used to monitor cerebral func- Electrical grounding should be only at one site, and the diathermy return is
tion during various cerebrovascular and cardiovascular procedures as well. placed as close as possible to the surgical site.
In this section, the anatomical and physiological basis of EEG signal gen- Amplifier settings in the operating room are similar to those used for rou-
eration, methodology of performing EEG in the operating room, effects of tine EEG. The high-frequency filter is set at 70 Hz. The low-frequency filter
anesthesia on EEG, mechanisms of EEG change, warning/interpretation is set at 0.3 Hz to maximize the ability to record slow wave activity, which is
criteria, and clinical uses will be discussed. of primary importance in the operating room. An appropriate electrical line
(notch) filter should be available (60 Hz in the US). Artifact rejection should
Anatomy and Physiology be able to reject high-amplitude activity, and it should be automatically trig-
gered when a surgical cautery is activated (65). The sensitivity is usually set
The EEG is a useful tool to evaluate the functional integrity of the relatively between 3 and 7 µV per mm and will need to be adjusted depending on the
large area of the cerebral cortex. Inhibitory and excitatory postsynaptic po- amplitude of the recorded signal. It may be useful to set the screen display to
tentials (IPSP, EPSP) of the cortical neurons generate the EEG waveforms show 15 to 20 seconds (approximately 10 to 20 mm per second) at a time, as
seen on scalp recordings. Although these potentials are of low amplitude, opposed to the 10-second (approximately 30 mm per second) display used in
they have a long duration. This allows many IPSP and EPSP to summate evaluating routine EEG. Focal slowing can be better appreciated on a slower
and be represented on the scalp as EEG waveforms. Although action poten- “paper speed.”
tials are of much higher amplitude than IPSP and EPSP, they are of much At times, the intraoperative EEG is performed with NIOM equipment.
shorter duration and do not summate. Consequently, they are not repre- This is usually done when fewer channels are needed. The features noted
sented on scalp EEG. Pyramidal neurons in layers 3, 5, and 6 of the cortex earlier for EEG equipment should also be present for the NIOM equip-
contribute most to the IPSP and EPSP that are recorded on EEG. Each ment on which EEG will be performed. However, when NIOM equipment
electrode evaluates a spherical area about 2 to 3 cm in diameter (63). Addi- is being used, it is for multimodality monitoring that includes EEG, various
tional details of the physiology of EEG can be found in recent reviews (64). types of EP, and possibly EMG monitoring.
There are many reasons for EEG patterns to change. At times changes
are physiologic, such as when the patient has a change in state (sleep vs. Electrodes
awake). In the operating room, anesthetics can alter EEG patterns. Often, Various types of EEG electrodes can be used to record intraoperative EEG.
the change in EEG patterns due to anesthesia follows a predictable course. Regardless of the type of electrodes used, they must be securely applied and
Most importantly, ischemia can induce changes, depending on the severity have an impedance of less than 5 kΩ to minimize electrical artifact. Com-
of blood flow reduction. These changes are discussed later in this chapter. monly, standard surface disc or cup electrodes are used (see Fig. 16.1A).
These are noninvasive and can be applied when the patient is awake. How-
Methodology ever, application can be time consuming. Conductive paste must be present
between the electrode and the scalp. The conductive paste may dry out dur-
Several methodological and technical issues must be taken into account ing a lengthy procedure, compromising electrode impedance. Needle elec-
when considering intraoperative EEG monitoring. These include features of trodes may be used as well (see Fig. 16.1C). These are quicker to apply than
the EEG machine, type and number of electrodes to use, and the montages surface electrodes as skin preparation is not needed. However, these can
used to display the EEG activity. be dislodged more easily and may be uncomfortable to apply in an awake
patient. Consequently, these are usually applied after the patient has been
The EEG Machine anesthetized.
EEG machines that are used for intraoperative monitoring must be rated for When surface disc or cup electrodes are used, they can be applied with
use in the operating room, which ensures that certain safety requirements collodion or paste. Collodion application results in more securely applied
are met. This includes a leakage current no greater than 10 µA from the electrodes that are difficult to dislodge, have lower impedances and bet-
chassis of the machine. All patient contacts should be optically shielded. ter recording characteristics than needle electrodes (66). This becomes an
important advantage for long surgeries. However, in view of fumes and its Anesthetic Considerations
flammable nature, some operating rooms may restrict its use. Additionally,
collodion application requires an air pump and more time than paste ap- Anesthetics have a profound effect on EEG. The effect can differ on the
plication. Paste application is quicker than collodion application; however, type of anesthetic; inhalational agents affect the EEG differently than IV
electrodes can be more easily dislodged. If electrodes are being applied in agents. Different agents within the same class of agents also vary on the se-
the operating room after the patient has been anesthetized, paste application verity of change produced. Among the inhalational agents, the halogenated
may be preferred. On the other hand, if application is done the night be- agents are more potent and effective at a lower concentration than nitrous
fore the surgery or before the patient goes to the operating room, collodion oxide. These agents alter specific ion channels on cell membranes to produce
application may be preferred. their anesthetic effect. As noted previously, within this class of agents, their
EEG electrodes are placed on the scalp according to the standard Inter- lipophilicity determines relative potency.
national 10–20 System of electrode placement. Whether the entire set of 21 When inhalational agents are used, a predictable series of changes oc-
electrodes is applied or not depends on the NIOM laboratory, the reason for curs on the EEG with increasing depth on anesthesia (7). With induction,
EEG monitoring, and the montage that will be used. At times, certain elec- there is an increase in faster, 12- to 18-Hz, activity most prominent in the
trodes may need to be left off, such as Fp1 and Fp2 if there are other probes frontal midline regions. With gradually increasing anesthetic dose, this ac-
on the scalp that preclude the application of these electrodes. tivity soon becomes more generalized and slows to about 8 to 14 Hz. This
activity is known as the WAR pattern—widespread, anteriorly dominant,
Montages rhythmic activity (Fig. 16.22). The next pattern seen consists of intermittent
The montage used for displaying EEG data depends on the type of sur- slow waves that are maximum anteriorly. This is known as the AIS pattern—
gery being monitored and the reason for obtaining the EEG. Commonly, anteriorly maximum, intermittent slow waves (Fig. 16.23). Further increases
16 to 21 channels of EEG are monitored. In many laboratories, midline in anesthetic dose result in more high-amplitude, diffuse slow wave activity,
electrodes (Fz, Cz, Pz) are left off. An anterior-posterior bipolar (double known as the WPS pattern—widespread, persistent slow wave (Fig. 16.24).
banana) montage with regular interelectrode distances is used (67). Some These waves are typically less than 1 Hz, low amplitude, and most promi-
investigators have suggested using long interelectrode distances as that may nent posteriorly. Increase in anesthetic concentrations beyond this level can
increase the sensitivity of recording changes. Some of the long interelec- lead to pharmacologically induced burst-suppression pattern and then ECI.
trode derivations that have been evaluated include Fp2-O2, F4-O2, and F4-P4. In most types of surgeries, a burst-suppression or ECI pattern is not reached
These are reviewed elsewhere (65). Others have used a double-distance mon- as such a high dose of anesthesia is not required.
tage similar to what is used in electrocerebral inactivity (ECI) (brain death) IV drugs have a variable effect on the EEG. While benzodiazepines are
recordings (68,69). As few as two to four channels have also been employed commonly used during induction of anesthesia, opioid analgesics and pro-
when EEG monitoring is used only to assess depth of anesthesia. Whichever pofol are common components of total IV anesthesia, commonly used
EEG montage is selected, it is usually sufficient for the entire monitoring. during NIOM. Barbiturates, dexmedetomidine, etomidate, and ketamine
This is because the objective of monitoring is to see whether there is a re- are used less often. Dexmedetomidine effects on EEG are unclear. Barbi-
gional disturbance, such as reduced blood flow, not to localize individual turates cause slowing of the EEG, followed by burst suppression and ECI
spike discharges. as the dose is increased. Benzodiazepines initially result in increased high-
The anterior-posterior bipolar montage is frequently used for monitoring frequency activity, and with higher doses cause EEG amplitude suppression
EEG during CEA surgery. However, other montages may be more sensitive and later a burst-suppression pattern. ECI is uncommon with benzodiaz-
in detecting focal slowing during carotid clamping. A Cz reference mon- epines. Propofol initially causes high-frequency activity followed by ampli-
tage has been noted to be the most sensitive. In this montage, EEG changes tude suppression and a burst-suppression pattern at a relatively low dose
are seen most frequently in electrodes in the anterior quadrant ipsilateral to (Fig. 16.25). Higher doses result in ECI. Opioid analgesics cause theta slow-
the side of the carotid artery that is clamped. Specifically, this includes the ing; however, burst suppression and ECI are unlikely with the typical doses
following electrode pairs referenced to Cz: F3/F4, F7/F8, C3/C4, T3/T4 (70). used in anesthesia (71). Ketamine and etomidate result in theta slowing and
Figure 16.22: This tracing is showing the

WAR pattern—widespread, anteriorly domi-
nant, rhythmic pattern. EEG is displayed in the
anterior-posterior bipolar montage. Notice the
absence of Fp1 and Fp2 electrodes due to other
probes occupying those positions.
burst-suppression pattern at a higher dose. Both of these agents may also Ischemia
have proconvulsant properties (7). Ketamine can cause delirium upon emer- Sudden global loss of blood supply to the brain can cause abrupt loss of
gence from anesthesia, while etomidate can rarely cause adrenal suppres- all EEG activity and cause ECI. Most often, ischemia is gradual and EEG
sion. A summary of the effects of various anesthetics on EEG is presented changes progressive. With ischemia, there is initially loss of faster frequencies.
in Table 16.14. A loss of 50% of the faster frequencies is considered suspicious for ischemia,
especially if it is unilateral (Fig. 16.26) (66). Thereafter, there is an increase
Mechanisms of EEG Change in theta frequencies, and a 50% increase in theta frequencies is considered
significant. Further, ischemia leads to increasing delta activity and, finally,
Other than anesthesia-induced changes, there are two main mechanisms by ECI. Studies have correlated the severity of EEG changes with the degree of
which EEG changes can occur during monitoring. Focal or diffuse reduc- reduction in cerebral perfusion (72–74). This is shown in Table 16.15.
tion in blood supply (ischemia) can cause focal or widespread EEG changes. It is important to have a baseline EEG obtained prior to critical periods
Systemic temperature and induced hypothermia can also have widespread during surgery when ischemia might occur. This allows a more accurate as-
changes. Changes in the physiologic milieu can also affect the EEG, but these sessment of the degree of loss of faster frequencies or slowing. Anesthe-
changes are not as remarkable as those induced by ischemia and temperature. sia can also produce changes such as slowing that mimic ischemic changes.
Figure 16.23: This tracing is showing the AIS

pattern—anteriorly maximum, intermittent slow
wave. EEG is displayed in the anterior-posterior
bipolar montage. Notice the absence of Fp1
and Fp2 electrodes due to other probes occu-
pying those positions.
It is important to remember, however, that most anesthetics will initially Hypothermia

cause an increase in faster frequencies, while the first ischemic change will be A slight decrease in temperature can occur inadvertently during any surgi-
a loss of faster frequencies (65). Focal slowing may be present on the base- cal procedure. This change usually does not have an appreciable effect on the
line EEG on account of prior neurologic insults. Anesthesia may exacerbate EEG. During cardiac and aortic surgeries, cerebral perfusion is transiently
this slowing. It is important to appreciate that this finding was present prior interrupted. During this period of circulatory arrest, cerebral metabolism is
to vessel clamping as in CEA surgery to prevent erroneous interpretation of reduced to minimize oxygen requirement and prevent neurologic injury. To
the EEG. accomplish this, hypothermia is induced until the EEG reaches ECI. This is
Emboli arising from the carotid artery or aorta may also cause ischemic known as deep hypothermic circulatory arrest (DHCA). DHCA is achieved by
changes and result in focal changes. This phenomenon can be seen in CEA cooling blood circulating through the cardiopulmonary bypass machine (75).
surgery or during cardiac or aortic surgeries. In CEA surgeries, this may A predictable series of changes occurs on the EEG as cooling progresses
occur after the clamp on the artery has been released. If the EEG changes (Table 16.16) (76). As the nasopharyngeal temperature decreases to about
are temporary, postoperative deficits are unlikely. However, if the changes 30°C, periodic complexes appear (Fig. 16.27). These can be unilateral
persist, postoperative stroke symptoms may be present. The same findings or bilateral. It is important to realize that these complexes do not imply
may occur during cardiac and aortic surgeries. epileptogenicity, despite being sharply contoured. A further decrease in
Figure 16.24: This tracing is showing the WPS

pattern—widespread, persistent slow wave.
EEG is displayed in the anterior-posterior b
ipolar
montage.
temperature results in reduction of the amplitude of the EEG and gradual cause an increase in the amount of theta and delta activity seen on the EEG.
appearance of a burst-suppression pattern at a temperature of about 24°C. Similar changes may be seen with profound blood loss and anemia during
ECI is reached at a mean temperature of 17.8°C; however, the range of tem- surgery. Generally, during surgery the hemoglobin concentration is kept at
perature at which ECI has been reported is very wide (10.4°C to 27.2°C) about 8 g per dL and in some cases as high as 10 g per dL (71).
(Fig. 16.28) (76,77). This broad range of temperatures at which ECI is noted
for any given patient underscores the need for EEG monitoring to determine Warning Criteria
the degree of cooling necessary for each patient. As the patient is rewarmed,
the same EEG patterns occur in reverse (78). One of the most common applications for EEG monitoring in the operating
use is during CEA surgery. Changes that occur on the EEG are often used to
Other Factors determine the need for a shunt. Ischemic changes described earlier will typi-
There are a variety of other factors that can affect the EEG. These include cally occur lateralized over the hemisphere ipsilateral to the carotid artery
carbon dioxide concentration and hematologic factors. Hyperventilation, being operated upon. If severe bilateral carotid stenosis is present without
which causes a reduction in the carbon dioxide concentration, can become adequate vertebrobasilar collateral circulation, unilateral carotid clamping
necessary in the operating room to reduce intracranial pressure. This can can cause bilateral EEG changes. Also, it is important to have a baseline
Figure 16.25: This tracing shows a burst-

suppression pattern induced by propofol
0.15 mg/kg/minute. Notice the absence of Fp1
and Fp2 electrodes due to other probes occupy-
ing those positions.
TABLE 16.14 EEG Changes with Commonly Used Doses of Anesthetic Agents
Increased Frequency Increased Amplitude Suppressed Electrocerebral Silence
Barbiturates (low dose) Barbiturates (moderate dose) Barbiturates (high dose) Barbiturates (high dose)
Benzodiazepines Benzodiazepines (high dose)
Etomidate Etomidate Etomidate
Propofol Propofol (high dose) Propofol (high dose)
Ketamine
Halogenated agents (<1 MAC) Halogenated agents (1–2 MAC) Halogenated agents (>2 MAC)
Opioids
(Adapted from James ML. Anesthetic considerations. In: Husain AM, editor. A Practical Approach to Neurophysiologic Intraoperative Monitoring. 1st ed. New
York: Demos; 2008. p. 55–66.)
Figure 16.26: This tracing is from a right CEA

surgery and shows greater than 50% loss of
faster frequencies over the right hemisphere,
approximately 10 seconds after the right carotid
artery was clamped. It is displayed at a slow
speed, with 60 seconds on one screen. This fa-
cilitates interpretation by making loss of faster
frequencies and appearance of slow waves
more prominent. Notice the absence of Fp1 and
Fp2 electrodes due to other probes occupying
those positions.
TABLE 16.15 Effect of Cerebral Blood Flow on EEG
Estimated Cerebral
Blood Flow (mL/100 g TABLE 16.16 EEG Changes with Hypothermia
Brain Tissue/Minute) EEG Findings
Temperature (°C)
35–70 Normal
25–35 Loss of beta frequencies EEG Pattern Minimum Maximum Mean
18–25 Increase in theta frequency <25% Periodic complexesa 21.5 34.2 29.6
Decrease in amplitude of all frequencies >50% Burst suppressiona 15.7 33.0 24.4
12–18 Increase in theta frequency >25% Electrocerebral inactivitya 12.5 27.2 17.8
Increase in delta frequency <25% Electrocerebral inactivityb 10.4 24.9 15.5
Decrease in amplitude of all frequencies >50% a
Data from reference Stecker MM, Cheung AT, Pochettino A, et al. Deep hypothermic
8–12 Severe suppression of all frequencies circulatory arrest, I: effects of cooling on electroencephalogram and evoked potentials.
<8 Electrocerebral inactivity Ann Thorac Surg 2001;71(1):14–21. Epub February 24, 2001.
b
Data from reference James ML, Andersen ND, Swaminathan M, et al. Predictors of elec-
Adapted from reference Jameson LC, Sloan TB. Neurophysiologic monitoring in neuro- trocerebral inactivity with deep hypothermia. J Thorac Cardiovasc Surg 2013. Epub April
surgery. Anesthesiol Clin 2012;30(2):311–331. Epub August 21, 2012. 16, 2013.
Figure 16.27: This tracing is from a patient un-

dergoing DHCA. The temperature at the time
of this tracing was 29.1°C. Notice the bilateral
independent periodic discharges. They are
sharply contoured but do not necessarily imply
epileptogenicity. Notice that 15 seconds of EEG
is displayed in this tracing.
EEG prior to clamping to know exactly which changes are due to the clamp- If the EEG is being used to determine whether a shunt will be used,
ing and which findings predate the surgery. the timing of EEG changes after the carotid artery is clamped is impor-
Ischemic changes that may occur during CEA surgery can be classified tant. Unilateral or bilateral major changes that occur in less than one
into moderate and major changes (79). A moderate change is attenuation minute after the clamp is applied are thought to be due to the clamp,
of faster frequencies to 50% of preclamp baseline and an increase in delta and a shunt is inserted. When changes are delayed and are transient,
activity greater than 1 Hz (see Fig. 16.26). A major change is attenuation of they might be due to anesthesia fluctuations or a small embolus. This
all activity by 75% or 100% increase in delta activity less than 1 Hz. The sur- will likely not have postsurgical consequences. However, if the delayed
geon should be alerted to both moderate and major changes; however, only change is permanent, it is likely due to a large embolus or if shunt was
major changes have a high likelihood of resulting in a stroke if not corrected used, due to shunt occlusion. Postoperative focal neurologic deficits may
and may require a shunt (80). It should be noted that there is no agreement result (66,79,80).
about whether even major changes necessarily need a shunt. It has been EEG monitoring is also used to determine when ECI is reached during
argued that the EEG may be too sensitive a marker and overestimates the DHCA. In these situations, a warning is not being raised; rather the surgeon
need for intervention (81). Moreover, interpretation of EEG is difficult with is being alerted to adequacy of cerebral protection for circulatory arrest.
general anesthesia that may increase the amount of diffuse and focal slow- The sensitivity setting of the EEG should be at 2 µV per mm to ensure that
ing, misleading the interpreter (72). Consequently, practices vary widely in low-amplitude activity is not overlooked. When no discernible EEG activity
regard to whether EEG monitoring is used during CEA surgery. is noted at this sensitivity for at least 3 minutes, the surgeon is alerted to the
Figure 16.28: This tracing is from a patient un-

dergoing DHCA. The temperature at the time
of this tracing was 13.5°C. The sensitivity is set
at 2 µV per mm. Notice that there is no discern-
ible EEG activity. Notice the absence of Fp1 and
Fp2 electrodes due to other probes occupying
those positions.
presence of ECI (see Fig. 16.28) (75). The use of anesthetics is discontinued Clinical Applications
around 25°C so that they do not interfere with the EEG determination of
ECI. At the author’s institution, at least 15 minutes are allowed to pass after The types of surgeries for which EEG monitoring is used have been noted
anesthesia is discontinued before ECI determination to allow for washout previously in this chapter. Although EEG monitoring is used frequently dur-
of the anesthetic. EEG monitoring is continued during rewarming, and the ing CEA surgery, opinions vary regarding its utility. In one study in which
inverse pattern of EEG changes occurs. If new lateralized slowing is noted the surgeons never used shunting but agreed to perform EEG monitoring
during rewarming, the surgeon is alerted to ensure adequate perfusion of (though not use it), major EEG changes occurred in 22 of 293 surgeries
both carotid arteries. New, persistent, focal slowing during rewarming is (8%), and of these 4 (22%) patients developed postoperative deficits (82).
concerning for a postoperative stroke. Additionally, 2 out of 50 patients (4%) who had moderate changes and 3 out
Occasionally, a few channels of EEG are monitored to determine the of 221 (1%) who had no EEG changes also developed postoperative defi-
depth of anesthesia. This is done when other types of NIOM are also being cits. In a very large study of 1,145 patients undergoing CEA surgery, EEG
performed that are sensitive to anesthetic depth, such as MEP. In this situa- monitoring was found to be useful in helping decide who needed a shunt,
tion, low-amplitude faster frequencies correlate with lighter anesthesia and and the monitoring always predicted who would emerge from surgery with
high-amplitude slow waves with increasing anesthetic depth (“fast and small a new deficit (83). When shunts are used for all patients undergoing CEA
awake, slow and tall asleep”) (73). Excessive high-amplitude slow wave may surgery, the morbidity is higher than when shunts are used selectively (84).
make monitoring difficult. Shunt insertion is not a benign procedure and may result in embolic strokes.
Frequent false-positive findings have also been reported with EEG moni- Several other analysis paradigms have been proposed, and their review is
toring for CEA (81). As noted earlier, anesthesia can make interpretation of beyond the scope of this chapter. Quantitative EEG analysis is also covered
EEG difficult as slowing may be seen with both anesthetic agents and isch- in the Intensive Care Unit Monitoring chapter.
emia (72). Still others prefer to use SEP monitoring. There remains consid-
erable controversy regarding the utility and need of EEG monitoring during
all CEA surgeries. Nerve Conduction Studies
EEG monitoring has also been used for other types of cerebrovascular and Electromyography
surgeries. Cerebral ateriovenous malformation and cerebral aneurysm sur-
geries can also be monitored with EEG; however, there are few data for these NIOM of the peripheral nervous system (PNS) involves determining the
procedures. When focal slowing is noted during surgery, corrective measures integrity of cranial and peripheral nerves using NCS or EMG. NCS can
such as increasing the blood pressure can be attempted. Persistent slowing, be performed by stimulating the nerve in the operative field proximally
however, is suggestive of postoperative focal deficits (35). and recording distally. The response generated is a NAP. Nerves can also
Cardiac and aortic surgeries that require DHCA are frequently monitored be stimulated in the surgical field and recordings made from a distal mus-
with EEG. While some investigators believe that cooling for a fixed amount cle. Such a response is known as a compound muscle action potential
of time or to a fixed temperature yields adequate results, studies have shown (CMAP). The process of obtaining a CMAP after stimulation is known
considerable patient-to-patient variability in the temperature at which ECI as stimulated EMG. EMG can also be recorded from muscles whose nerve
occurs (75,77). Centers that have used EEG monitoring have reported better supply is at risk during surgery; this is known as free running EMG. This
patient outcomes than the average reported in the literature (77). section will review the basics of NCS and EMG monitoring in the operat-
ing room.
Quantitative EEG Analysis
Anatomy and Physiology
Interpretation of EEG monitoring data requires considerable training
and expertise. Quantitative EEG analysis converts the raw EEG data to a An understanding of the anatomy of the PNS is important to consider
graphic format that is more easily understood by nonexperts. One of the when designing an NIOM paradigm to use in a surgery that puts periph-
most common methods of analysis is compressed spectral array (CSA). eral nerves at risk. Most surgeries in which PNS monitoring is needed put
CSA quantifies the power of each EEG epoch into various frequency cranial or peripheral nerves or spinal nerve roots at risk. A review of the
bands and displays them graphically. Each epoch can be from seconds to anatomy of various cranial and peripheral nerves and the muscles they
minutes. Trends can be evaluated reasonably well with CSA; however, it is supply is beyond the scope of this chapter, and the reader is referred to
more difficult to determine minute-to-minute variability. Minor changes standard neuroanatomy textbooks. A few relevant principles are presented
in EEG frequency may also be difficult to assess. Artifacts are also ana- later.
lyzed and included in the CSA computation. Thus, it is generally recom- Each spinal nerve root innervates a group of muscles. This group of mus-
mended that CSA only be used as an adjunct to raw EEG interpretation cles is called a myotome. Each muscle is innervated by several nerve roots.
(66,85,86). This provides a system of redundancy of innervation to each muscle, so if
Quantitative methods have been proposed for evaluating EEG during one nerve root is damaged, the entire muscle is not paralyzed. It is important
CEA surgery. The brain symmetry index, which is a measure of hemispheric for the neurophysiologist to know which myotomes correspond to which
EEG frequency asymmetry, has been used to detect changes associated with nerve roots so that appropriate muscles can be monitored during surgery. In
carotid artery clamping during CEA surgery (87,88). Whereas this technique Table 16.17, muscles commonly used for monitoring various cranial nerves
appears sensitive in evaluating asymmetry, it is not clear whether it offers an and spinal roots are noted (69).
advantage over analysis of raw EEG. Moreover, if it is too sensitive, it may The stimulation threshold of a nerve depends on its size and degree of
lead to further complications by encouraging more shunts than necessary. myelination. Larger nerves with a greater degree of myelination have lower
TABLE 16.17 Selected Muscles Innervated by Cranial Nerves and Spinal Nerve Roots
Cranial nerves Muscles

III, IV, VI Extraocular muscles (superior oblique by CN IV, lateral rectus by CN VI)
V Masseter, temporalis
VII Frontalis, orbicularis oculus, orbicularis oris
IX Stylopharyngeus
X Pharyngeal muscles except stylopharyngeus and vocal cords
XI Sternocleidomastoid, trapezius
XII Tongue
Spinal nerves Muscles
C4 Trapezius, levator scapulae
C5 Deltoid, biceps brachii
C6 Pronator teres, flexor carpi radialis, extensor carpi radialis longus
C7 Extensor digitorum, extensor indicis, extensor carpi ulnaris, anconeus
C8 Flexor digitorum sublimis, pronator quadratus, dorsal interossei, abductor pollicis brevis
T1 Dorsal interossei, abductor pollicis brevis, flexor carpi ulnaris
T2-T6 Intercostals, paraspinals
T6-T8 Upper abdominus rectus, paraspinal muscles, intercostal muscles
T8-T10 Middle abdominus rectus, paraspinal muscles, intercostal muscles
T10-T12 Lower abdominus rectus, paraspinal muscles, intercostal muscles
L1 Quadratus lumboratum, paraspinals, cremaster
L2 Iliopsoas, quadriceps femoris, adductor longus, adductor magnus
L3 Quadriceps femoris, adductor longus, adductor magnus
L4 Tibialis anterior, quadriceps femoris, adductor longus, adductor magnus
L5 Tibialis anterior, peroneus longus
S1, S2 Gastrocnemius, abductor hallucis
S2-S5 Anal sphincter, urethral sphincter
Adapted from reference Minahan RE, Mandir AS. Basic neurophysiologic intraoperative monitoring techniques. In: Husain AM, ed. A practical approach to
neurophysiologic intraoperative monitoring, 1st ed. New York, NY: Demos, 2008:21–44. This is not an all-inclusive list; those can be found in EMG texts.
stimulation thresholds. However, a diseased nerve may have a high stimu- The motor unit consists of a single axon and all the muscle fibers it sup-
lation threshold regardless of its size and myelination. The orientation of plies. The number of muscle fibers each axon supplies depends on the mus-
the stimulating electrodes (i.e., whether the cathode or anode is proximal) cle and its function. Muscles that are responsible for fine motor movements,
can affect stimulation threshold also. These factors are important consider- such as extraocular muscles, have a small number of muscle fibers in each
ations when stimulating nerves in the operative field. motor unit. Larger muscles, such as limb muscles, that perform gross motor
movements have much larger motor units. Anywhere from 3 to 500 muscle surgical field. However, monopolar stimulation results in a greater stimulus
fibers may be present in a motor unit. Depolarization of an axon or a group artifact and stimulus spread. When stimulation artifact is especially promi-
of axons results in the activation of their motor units. These m
otor units nent, a tripolar (cathode, anode, cathode) electrode is used (89). Stimulus
can be recorded with needle electrodes and are called motor unit a ction spread may lead to the activation of neural structures near the nerve of
potentials (MUAP). Each MUAP appears a spike. When many m otor units interest, which may lead to the misinterpretation of findings.
are activated, a burst of MUAP appears. During NIOM, MUAP are pre- When stimulating in the surgical field, constant-voltage stimulators are
sented visually on a screen and through a speaker. Different patterns of preferred over constant-current stimulators. Because of the fluids in the sur-
MUAP activation represent different types of stimulation of the nerve. gical field and potentially changing contact of the stimulator to the nerve,
These patterns are discussed later in this section. constant-voltage stimulators provide more reliable current delivery. Regard-
less, constant-current stimulators are widely used for this purpose as well.
Methodology The stimulation threshold range for a healthy cranial nerve is from 0.05 to
0.2 V (0.2 to 1.0 mA) with 0.05- to 0.2-millisecond duration, and it is slightly
There are three main techniques for performing PNS monitoring: NCS, higher for healthy peripheral nerves. However, when nerves are diseased, the
stimulated EMG, and free running EMG. Each technique has its utility, and stimulation threshold may be around 1.0 V (5 mA). Still higher stimulation
often more than one of these techniques are done together. The nuances of intensity, up to 10 V, may be needed to stimulate nerves through dura or
performing these studies are discussed later. when a nerve is wrapped by a tumor (66). Higher-current intensity is needed
when using a bipolar stimulator compared with a monopolar stimulator.
Nerve Conduction Studies When obtaining NAP along the length of a nerve, a sudden increase in the
Intraoperative NCS are performed by stimulating a nerve in the operative stimulation threshold may mark the site of injury.
field and recording distally from the exposed nerve also in the operative NAP are usually of low amplitude. Averaging 10 to 20 repetitions may
field. This is known as a NAP. This technique measures the integrity of a be needed to obtain a reproducible response. The stimulation intensity is
nerve along the segment that is tested. Presence of a NAP implies continuity gradually increased until a maximal response is obtained. This ensures that
of at least some of the nerve fibers. This technique can also be used to local- all nerve fibers have been stimulated. Stimulation rate of 1 to 5 Hz is often
ize a lesion along the length of a nerve by performing a modified “inching” used. A sweep speed of 2 to 10 milliseconds per division and sensitivity of
technique that is typically done in the EMG laboratory. A sudden change in 50 to 1,000 µV per division is used (adjusted depending on size of response).
the latency or amplitude of the NAP indicates the site of the lesion. Many different types of stimulators are available for various clinical sce-
Nerve stimulation can be performed with a bipolar or monopolar stimu- narios. Electrode tips of 1 mm are needed for cranial nerve stimulation.
lator. Both types of stimulators are handheld by the surgeon. With a bi- Larger tips are needed for larger nerves, and 5-mm tips are often used for
polar stimulator, both the cathode and the anode are placed on the nerve, peripheral nerve stimulation. The shape of the electrode tips can also be
with the cathode being closer to the recording electrodes. Alternatively, in changed to provide optimal stimulation. A variety of different stimulation
monopolar stimulation, the anode is placed at a distance, often in subcuta- tips are shown in Fig. 16.29. Curved, or hook, electrodes are useful to lift a
neous tissue in the surgical wound. There are advantages and disadvantages nerve up and away from fluid. Hook electrodes are large and cannot be used
to both types of stimulation. With bipolar stimulation, because both elec- for cranial nerve stimulation or stimulation in small areas. Surgical forceps
trodes are in close proximity, the current delivery is very focal with minimal can also be adapted into a stimulating electrode. It can then be used for dis-
spread. This also makes the stimulus artifact smaller, allowing for a better section and stimulation.
recording. However, if there is fluid in the surgical field, stimulation may fail NAP are most often recorded in the surgical field, so recording electrodes,
because of current shunting. Bipolar stimulators are also larger than mono- like stimulating electrodes, are also handheld by the surgeon. The active and
polar stimulators, so it is harder to introduce them into small surgical fields. reference recording electrodes are 2.5 to 3.0 cm apart when recording NAP
Monopolar electrodes are smaller, and because the anode is away from the from peripheral nerves. Hook electrodes work well for recording as they allow
cathode, are not as susceptible to current shunting when there is fluid in the the surgeon to lift the nerve away from nearby tissue. When recording NAP
A E
D
Figure 16.29: Many types of tips are available
for stimulating electrodes. Some of them are dis-
played here. A–D are various bipolar tips. A and
C are straight electrodes with straight or rounded
tips. B and D are hook tips. E is a monopolar elec-
trode with a straight tip.
from cranial nerves, smaller, monopolar wick electrodes are used with a distant also the same. However, recordings are much different, and different types
reference electrode. of electrodes are used.
CMAP are recorded directly from muscles and are much larger in amplitude
Stimulated EMG than NAP. Averaging is not necessary with CMAP, and in certain cases, may
Stimulated EMG is obtained by stimulating a nerve in the surgical field adversely affect the response. Three types of recording electrodes can be used to
and recording a CMAP distally from a muscle innervated by that nerve. record CMAP: surface, subdermal, and needle (Fig. 16.30). Surface electrodes
Presence of a CMAP implies at least some innervation of the muscle by are most useful if it is important to measure the amplitude of the CMAP. This
the nerve being stimulated. This monitoring technique is also very helpful is because the response is monomorphic and easily reproducible. In this situa-
when a nerve needs to be identified in the surgical field. CMAP activation at tion, stimulation intensity is increased to maximize the CMAP response. The
low stimulation intensity implies close proximity to the nerve supplying the stimulation intensity is further increased by 10% to ensure all nerve fibers are
activated muscle. Stimulation is very similar in this technique as described activated. Monitoring is continued at this intensity, and the surgeon is alerted if
earlier for NCS, including the types of electrodes used. Display settings are significant amplitude changes occur. The active electrode is placed on the belly
A B C
Figure 16.30: Three main types of electrodes

are used for recording CMAP. A are surface
electrodes, B are subdermal needles, and C are
intramuscular needles.
of the muscle of interest, and the reference electrode placed 4 to 5 cm away Fibrillations, fasciculations, complex repetitive discharges, and other types
or on the muscle tendon. Monitoring with surface electrodes, however, will of spontaneous activity can be detected; however, the activity of most inter-
not allow the detection of spontaneous activity within the muscle. Application est is neurotonic discharges. Other types of spontaneous activity predate
of surface electrodes takes longer than other types of electrodes. When small the surgery, while neurotonic discharges occur owing to nerve irritation and
muscles are being monitored, surface electrodes do not offer muscle selectivity, injury during surgery.
and the CMAP recorded may actually be an aggregate of two or more muscles. Free running EMG is best recorded with needle electrodes. Surface and
Surface CMAP recordings are seldom used in NIOM. subdermal electrodes are not reliable in detecting this activity (90). Needle
Subdermal and needle electrodes are invasive and are applied after the pa- electrodes are of many different types. Bipolar EMG needles have both the
tient has been anesthetized. Thereafter, these electrodes can be applied quickly. active and reference electrodes in the same needle. The advantage of these
As is evident in Fig. 16.30, subdermal electrodes are shorter than needle elec- is that only a single needle needs to be placed in each needle for recording.
trodes. Consequently, they may not be long enough to penetrate fat and reach Monopolar EMG needles can also be used, and two of them need to be
muscle. Often, they stay within subcutaneous tissue and do not accurately placed in each muscle. Both bipolar and monopolar EMG needles are bulky
record CMAP. Needle electrodes are recommended as they can more reliably and hard to secure because they often have large hubs. For NIOM, most
record directly from muscle fibers (90). CMAP recorded from needle elec- often, monopolar wire electrodes are used. They have a diameter of 0.1 mm
trodes are polyphasic and represent activation of motor units closest to the and have an insulating coating with only the tip being bare. These are in-
needle. Activation of a different group of motor units will change the shape of serted into the muscle with the aid of an introducer needle. The tips of the
the CMAP, and consequently, CMAP recorded with needle electrodes should wire electrode are hooked, and after the introducer needle is withdrawn, the
not be averaged. Needle electrodes can be inserted directly into the muscle of hook keeps the wire in place. Two wire electrodes are placed in each muscle.
interest and allow for selective recordings. Because needle electrodes are in Additional wire electrodes may be inserted in a critical muscle to further in-
close proximity to the motor units, they are much better than other electrode crease the sensitivity of monitoring for that muscle. In many situations, the
types at recording spontaneous activity, such as neurotonic discharges (de- same needle electrodes used for monitoring free running EMG can be used
scribed later) (90). Subdermal electrodes do not reliably record such sponta- for recording stimulated EMG (CMAP) and muscle MEP.
neous activity since they often do not penetrate beyond subcutaneous tissue. Pharmacologic neuromuscular blockade (MNJBA) should ideally not be
Surface electrodes cannot be used to record spontaneous activity. used when free running EMG is important to monitor as it reduces sensitivity
of monitoring. If the use of such drugs is imperative, it is important to main-
Free Running EMG tain a constant infusion. Recurrent boluses make the monitoring unreliable.
EMG activity is frequently recorded from muscles that are at rest. This “free The display settings used for free running EMG are similar to what is used
running” EMG is useful for recording spontaneous activity from the muscle. in the EMG laboratory. The sensitivity is set to 100 to 500 µV per division,
and the sweep is 10 milliseconds per division. Low- and high-frequency fil- erroneously negative results may be noted (89). In these situations, consider-
ter settings are 32 Hz to 16 kHz. The sound is usually kept on so that when ation should be given to reverse the neuromuscular blockade. Finally, even
spontaneous activity is noted, the neurophysiologist and surgeon can get though stimulated CMAP can be recorded with 50% to 75% neuromuscular
real-time feedback (66). blockade, it is not certain whether spontaneous activity, such as neurotonic
discharges, can be recorded with the same degree of reliability (95). When it
Anesthetic Considerations is critical to record spontaneous activity, it is best not to use NMJBA.
NCS and EMG are not significantly affected by inhalational and IV anes- Interpretation of NCS/EMG Findings
thetics. However, MNJBA can have a profound effect on both stimulated and Warning Criteria
and free running EMG. Even these agents will not affect NCS, though.
Stimulated and free running EMG are best recorded without any NMJBA; Several measurements can be performed on NAP and CMAP obtained dur-
however, this is not always possible. Stimulation of nerves during testing ing NIOM. It is best to obtain maximal stimulation of the nerve to ensure
can cause unacceptable patient movement, especially during microsurgery, that all available nerve fibers are stimulated, and the highest possible NAP
when no NMJBA are used. Often multimodality NIOM is used, and MEP or CMAP amplitude is obtained. Both the amplitude and latency of these
stimulation can also cause patient movement. Moreover, patient movement waveforms is evaluated. If a nerve injury location is being sought, stimula-
can result in EMG activation that may mimic spontaneous activity leading tion is initially performed distally and amplitude of NAP or CMAP noted.
to erroneous interpretation. Consequently, in many types of surgery, some Progressively more proximal stimulation is performed at 1- to 2-cm inter-
degree of neuromuscular blockade is used. vals. The site at which a disproportionately greater reduction in amplitude
Successful stimulated EMG monitoring can be performed with 50% to or prolongation in latency is noted is the site of nerve injury. In some situ-
75% neuromuscular blockade (66,91). The degree of neuromuscular block- ations, simply recording a NAP or CMAP confirms the presence of some
ade is measured with TOF stimulation. In this, a peripheral nerve not in the regenerating nerve fibers supplying the muscle. Because some nerve fibers
surgical field is stimulated and CMAP recorded from a muscle supplied by are present and conducting, the surgeon may prefer to perform a neurolysis
that nerve. When no NMJBA are used, a TOF will result in four CMAP. instead of a nerve graft or other more radical procedure.
With increasing amount of neuromuscular blockade, fewer CMAP will be CMAP recordings are preferred to NAP recordings in most instances
seen. A 50% neuromuscular blockade implies two CMAP after TOF stimu- because of their significantly larger amplitude. When CMAP are recorded
lation, and a 75% blockade results in one CMAP. However, the TOF test- with needle electrodes, amplitude measurements become unreliable. In these
ing should be done with a nerve near the area of interest (92). Nerves and instances, latency measurements must be relied upon. Alternatively, if the
muscles far removed from the surgical field may have different sensitivities CMAP is being recorded only to confirm some conduction through the
to NMJBA, and can give an erroneously low impression of the degree of nerve being stimulated, detailed latency and amplitude measurements may
neuromuscular blockade (93). not be necessary. Simply the presence or absence of CMAP is noted.
A few caveats must be remembered when using NMJBA during surgery in Technical problems should be considered when a significant change in
which EMG activity will need to be monitored. When NMJBA are used in NAP or CMAP amplitude or latency is noted or when these responses are
these surgeries, a constant level of infusion is necessary to result in a constant not seen. The stimulator may not be making adequate contact with the nerve.
level of neuromuscular blockade. Bolus dosing of these drugs will result in Current shorting may occur when a bipolar stimulator is used and both the
erratic effects on CMAP. Chronically diseased nerves may have increased cathode and anode are submerged in fluid. The recording electrodes may
sensitivity to NMJBA, and low doses of these medications may result in an not be making adequate contact with the nerve or may become dislodged
unexpectedly high degree of neuromuscular blockade (94). When testing from muscle. A stimulus artifact may obscure the response. If neuromuscu-
pedicle screws with electrical stimulation, if a borderline threshold is noted lar blockade is used, CMAP may become more difficult to obtain. If MN-
(7 to 11 mA), testing should be repeated with lower stimulation thresholds. JBA are administered as an intermittent bolus, CMAP amplitude variability
However, when stimulation intensity is reduced and NMJBA are being used, may become difficult to interpret (66).
Many types of spontaneous activity can be seen on free running EMG Many other types of spontaneous activity may be seen that must be
and must be accurately interpreted. The most important spontaneous activ- differentiated from neurotonic discharges. Normal muscle activity can
ity that must be recognized is neurotonic discharges. These occur as a result mimic neurotonic discharges; however, it is seen when the patient is under
of traumatic, thermal, metabolic, or other types of nerve injury. The sur- light anesthesia and the firing pattern is regular. Other types of sponta-
geon can be alerted to nerve injury in real time when neurotonic discharges neous activity, such as fibrillation potentials, myokymic discharges, and
are noted. They are thought to occur beacause of reflex activation of the complex repetitive discharges, can often be readily recognized as they
anterior horn cells due to nerve injury (96). look and sound the same as in the EMG laboratory. Various artifacts can
Neurotonic discharges are classified as occurring in bursts or trains. also mimic neurotonic discharges. Electrical equipment in the operating
Bursts are short, lasting less than one second, while trains can continue for room can produce a 60-Hz artifact that may sound like a neurotonic
several seconds to minutes (Fig. 16.31). These discharges consist of 1 to discharge. Often, these artifacts are easily distinguished from neurotonic
10 motor units that fire irregularly at a rate of 30 to 200 Hz (97). Neurotonic discharges.
discharges occur in response to any type of nerve irritation or injury, and the Technical problems may arise when recording free running EMG. If
more severe the injury, the longer the discharge. One exception to this is that subdermal needle or surface electrodes are used, it may be difficult to
if the nerve undergoes a very fine cut, no neurotonic discharge may be seen. detect neurotonic discharges (90). Recording electrodes may be faulty
Because of the frequency of the discharges and their irregular nature, trains and fail to record potentials. The use of NMJBA may allow for success-
of neurotonic discharges have a “dive bomber” sound. Trains are more often ful NAP and CMAP recording, but recording neurotonic discharges be-
associated with postoperative nerve injury (98). comes very difficult (95).
Figure 16.31: This tracing is from a patient undergoing

tethered cord release. Lower extremity muscles and the
anal sphincter are being monitored with free running
EMG. Notice the high-frequency discharge arising from
the LAT (left anterior tibialis) and LH (left hamstrings)
channels. This discharge lasts less than 1 second and is
classified as a burst. Display settings are 1 second/full
screen, 100 µV per division.
Clinical Applications TABLE 16.18 Stimulation Thresholds Used When Testing for Pedicle
Breach in Lumbar Spinal Instrumentation Surgeries
NCS and EMG monitoring can be used in many different types of surger-
ies in which different parts of the nervous system are at risk. Discussing all Breach (mA)
types of surgeries where NCS and EMG monitoring can be used is beyond Probable Possible Unlikely
the scope of this chapter. A few common applications will be mentioned. Hole <5 5–7 >7
Screw <7 7–10 >10
Spinal Surgery with Instrumentation
Spinal surgery involves manipulation of the vertebral bodies and insertion Adapted from reference Minahan RE, Mandir AS. Basic neurophysiologic intraoperative
of hardware to help maintain alignment and stabilize the spine. While SEP monitoring techniques. In: Husain AM, ed. A practical approach to neurophysiologic
and MEP monitoring has been shown to be helpful in reducing injury to the intraoperative monitoring, 1st ed. New York, NY: Demos, 2008:21–44.
spinal cord, nerve roots are also at risk during instrumentation (14). Instru-
mentation involves inserting screws into pedicles; various types of stabilizing
hardware are anchored to these screws. Pedicles are narrow and drilling, and Several caveats should be considered when testing pedicle guide hole and
insertion of screws into them can injure nerve roots. If the screw is diverted screws. Whenever the expected (preferred) result of monitoring is absence of
medially, it can breach the pedicle wall and invade the spinal canal. This can a response (such as lack of CMAP activation at screening stimulation inten-
result in injury to nearby nerve roots. In addition to manual palpation, a sity), a control stimulus should be used to confirm that the NIOM system
breached pedicle screw can be evaluated by fluoroscopy and SEP, but EMG is working correctly. This can be done by stimulating a nearby nerve root at
NIOM has been shown to be more sensitive than both of these (99,100). the start of surgery to confirm that activation can be noted (89). A normal
The setup for spinal instrumentation surgery involves placing needle nerve root activation threshold is about 2 mA. A chronically diseased or
electrodes in muscles supplied by nerve roots that may be injured. In many injured nerve root has a higher stimulation threshold than a healthy root.
cases, this involves lumbosacral roots, and the needle electrodes are placed Lack of activation of the nerve root at the screening stimulation intensity
in lower extremity muscles and anal sphincter. Guide holes are drilled in the may be a false negative. If this is suspected, it is best to test a nerve root
pedicles and screws inserted into these holes. When optimally placed, electri- by stimulating it directly in the surgical field. Its stimulation threshold is
cal stimulation of the hole and screw does not elicit a CMAP as a layer of noted, and then the screening stimulation threshold determined (92). Newer
bone separates the hole and screw from nearby nerve roots. However, if the screws are coated with different substances, such as hydroxyapatite, to help
hole or screw is misplaced and the pedicle wall breached, the screw will lie with fixation. The coating material used may alter the stimulation threshold
close to the nerve root, and electrical activation of the root will occur with (103). Stimulation thresholds also vary depending on the spinal level. Tho-
stimulation (101). racic pedicles have thinner bone; using lower screening stimulation inten-
Confirmation of appropriate placement of the guide hole and screw is sity at these levels may be appropriate (104). Finally, as noted earlier, when
recommended. If low thresholds are noted with stimulation of the hole, it NMJBA are used, erroneously high thresholds may be noted, particularly
can be redirected before the screw is inserted. Also, even if the hole does if nerve roots are diseased. It is best not to use any NMJBA when pedicle
not breach the pedicle, placing a screw in it might. Thus, both should be screw testing must be performed.
tested. Testing can be performed in various ways. A screening stimulation
intensity of 10 mA can be used for lumbar pedicles to see whether activation Peripheral and Cranial Nerve Surgery
is noted. If activation is noted with this intensity, closer examination should Peripheral nerve injuries may be neuropraxic, axonotmetic or neurotmetic.
be conducted to see if a breach has occurred (102). The typical stimulation In neuropraxic and axonotmetic injuries, the internal nerve fiber bundle
intensities at which point a breach is suspected is presented in Table 16.18. is generally intact, and nerve grafting is not necessary as spontaneous
Free running EMG is also monitored to detect any spontaneous activity nerve regeneration will likely compensate. With neurotmetic injury, there
during spinal instrumentation. is substantial disruption of the nerve fiber bundle requiring nerve grafting.
The extent of nerve injury may not be evident extraoperatively and has to injury to the nerve can result in neurotonic discharges, which further as-
be determined intraoperatively so that appropriate therapy can be instituted. sist the surgeon in dissection. Long trains of high-frequency, low-amplitude
The major purpose of NIOM during peripheral nerve surgery is to determine neurotonic discharges (so-called “A trains”) are associated with postopera-
whether the extent of nerve injury is such that spontaneous nerve regeneration tive facial nerve paresis (107). At the end of surgery, if a CMAP can be re-
is likely to eventually result in reinnervation of affected muscles. If so, only corded with facial nerve stimulation at a low threshold, favorable outcome is
neurolysis is needed, and if not, nerve grafting may be necessary. likely (108). Monitoring free running and stimulated EMG has been shown
During NIOM for peripheral nerve surgery, NCS, stimulated EMG and to reduce facial nerve injury during surgery (98).
free running EMG are used. After dissection of the affected nerve, it is NIOM involves the use of many different modalities. Many modalities are
tested for integrity. This can be done by stimulating the nerve proximally used together to provide the assessment for various pathways of the nervous
and recording a NAP distally. The presence of a NAP confirms early rein- system at risk during surgery. Attention to detail is critical as many of the po-
nervation (105). If a focal area of nerve injury is suspected, stimulation can tentials recorded are of very low amplitude and easily obscured by the hostile
be moved more proximally in 1-cm increments to see if a sudden change in electrical environment of the operating room. NIOM is a team effort; coordina-
amplitude or latency occurs. If this happens, it isolates the point of nerve tion is important not only between the technologist and neurophysiologist but
injury. Stimulating the nerve and recording a CMAP from a muscle supplied among all members of the surgical team. Changes made by the surgeon or an-
by that nerve can also determine integrity of the nerve. The same principles esthesiologist can affect the monitoring. Frequent communication and mutual
as noted for recording NAP apply to recording CMAP. Free running EMG respect between all members of the team are necessary for successful NIOM.
is also monitored. Neurotonic discharges may occur if the nerve is irritated
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17 Continuous EEG Monitoring
in the Intensive Care Unit
SAURABH R. SINHA • LAWRENCE J. HIRSCH
Introduction Quantitative EEG Analysis

Scientific Basis for Continuous EEG Recording Clinical Applications
Historical Context Clinical Applications, Status Epilepticus
Technical Considerations Clinical Applications, Nonconvulsive Seizures
Personnel Requirements Clinical Relevance of NCS in Critically Ill Patients
Electrodes and Electrode Applications Clinical Applications, Ischemia
Montages Clinical Applications, Anoxic Brain Injury
Artifacts and Hypothermia
Clinical Factors That Confound Multimodal Brain Monitoring
Reviewing Data Future Directions
EEG Interpretation and Nomenclature References
INTRODUCTION in neurological status may not be clinically apparent. Furthermore, many

types of neurological insults (e.g., hypoxia or ischemia, increased intracra-
The use of EEG in critically ill or hospitalized patients to assess for changes nial pressure, cerebral edema, seizures) require early detection to maximize
in neurological status or to detect/monitor seizures or their treatment is a the chance of successful intervention and prevention of secondary injury.
rapidly growing field. In the intensive care unit (ICU) setting, several fac- Other techniques for monitoring neurological status have more limited tem-
tors necessitate the use of surrogate measures of neurological function. This poral resolution, such as CT, MRI, transcranial Doppler, angiography, and
includes the fact that the patients often have altered or suppressed mental cerebral perfusion measures. EEG has long been recognized as a potentially
status. The use of sedative and paralytic agents often further limits the clini- useful tool for monitoring brain function because it has several desirable
cal examination. In these circumstances, subtle and even substantial changes characteristics. It is noninvasive and fairly inexpensive. EEG is closely linked
543
544 Continuous EEG Monitoring in the Intensive Care Unit
to cerebral perfusion and metabolism, making it sensitive to most causes For the reasons mentioned earlier, the utilization and availability of con-
of cerebral injury, including ischemia and hypoxia. It has moderate spatial tinuous EEG (CEEG) is rapidly expanding (Fig. 17.3). However, there
resolution and very good temporal resolution. EEG sensitivity is such that remain several barriers to optimal use of CEEG for monitoring critically
neuronal dysfunction can often be detected at a stage where it is still revers- ill patients for seizures and for changes in neurological status. These include
ible, especially during ischemia. Lastly, EEG is the best available method the technical challenges of long-term recording in the critical care environ-
for detecting clinical or subclinical seizure activity. In recent years, there ment on patients undergoing multiple other types of monitoring and proce-
has been increasing recognition of the fact that seizures are common occur- dures. In addition, there are the logistical challenges of providing a service
rence in critically ill patients, especially those with neurological injury, and that ideally requires around-the-clock availability of technical and clinical
that most seizures in critically ill patients are subclinical or nonconvulsive personnel to perform and interpret the recordings. Lastly, there is the chal-
(Figs. 17.1 and 17.2) (1,2). Such seizures are likely to go unrecognized with- lenge of appropriately interpreting the collected data and integrating CEEG
out the use of continuous EEG monitoring. results into the overall management of the patient. In this chapter, we will
Figure 17.1: Percentage of patients with seizures de-

60 tected on CEEG based on admitting diagnosis. Tumor,
brain tumor; Infection, CNS infection; CSE, convulsive
status epilepticus; Hypoxic, hypoxic/anoxic injury;
50 ICH, hemorrhagic stroke; CVA, ischemic stroke; SAH,
subarachnoid hemorrhage; TBI, traumatic brain injury.
(Data from aClaassen J, et al. Quantitative continu-
40 ous EEG for detecting delayed cerebral ischemia in
patients with poor-grade subarachnoid hemorrhage.
Patients (%)
Clin Neurophysiol 2004;115[12]:2699–2710. bSwisher

30 CB, et al. Baseline EEG pattern on continuous
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the control of convulsive status epilepticus. Epilepsia
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Claassen et al.a
Claassen et al.a
Claassen et al.a
Claassen et al.a
Claassen et al.a
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Vespa et al.h
DeLorenzo et al.e
Swisher et al.b
Swisher et al.b
Swisher et al.b
Swisher et al.b
Swisher et al.b
Swisher et al.b
Carrera et al.c
Dennis et al.g
Shafi et al.d
Shafi et al.d
Shafi et al.d
Shafi et al.d
Shafi et al.d
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Vespa et al.f
after intracerebral hemorrhage: a factor in progressive

midline shift and outcome. Neurology 2003;60[9]:
1441–1446. gDennis LJ, et al. Nonconvulsive status
epilepticus after subarachnoid hemorrhage. Neuro-
surgery 2002;51[5]:1136–1143; discussion 1144. hVespa
PM, Nenov V, Nuwer MR. Continuous EEG monitor-
Tumor Infection CSE Hypoxic ICH CVA SAH TBI
ing in the intensive care unit: early findings and clinical
Admitting diagnosis efficacy. J Clin Neurophysiol 1999;16[1]:1–13.)
Continuous EEG Monitoring in the Intensive Care Unit 545
50
40
Patients (%)
30
20
10
0
Jordana
Young et al.b
Pandian et al.c
Murthy et al.d
Privitera et al.e
Towne et al.f
Claassen et al.g
Kilbride et al.h
Oddo et al.i
Saengpattrachai et al.j
Jette et al.k
Shahwan et al.l
Abend et al.m
McCoy et al.n
Williams et al.o
NICU AII ICU MICU Ped ICU
Patient location
Figure 17.2: Percentage of patients with seizures detected on CEEG based on location. *This study excluded any patients with known acute brain injury. NICU,
neurological intensive care unit; AII ICU, airborne infection isolation intensive care unit; MICU, medical intensive care unit; Ped ICU, pediatric intensive care unit. (Data
from aJordan KG. Neurophysiologic monitoring in the neuroscience intensive care unit. Neurol Clin 1995;13[3]:579–626. bYoung GB, Jordan KG, Doig GS. An assessment
of nonconvulsive seizures in the intensive care unit using continuous EEG monitoring: an investigation of variables associated with mortality. Neurology 1996;47[1]:83–89.
c
Pandian JD, et al. Digital video-electroencephalographic monitoring in the neurological-neurosurgical intensive care unit: clinical features and outcome. Arch Neurol
2004;61[7]:1090–1094. dNarayan JT, Murthy JM. Nonconvulsive status epilepticus in a neurological intensive care unit: profile in a developing country. Epilepsia 2007;
48(5):900–906. ePrivitera M, et al. EEG detection of nontonic-clonic status epilepticus in patients with altered consciousness. Epilepsy Res 1994;18[2]:155–166. fTowne AR,
et al. Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology 2000;54[2]:340–345. gClaassen J, et al. Quantitative continuous EEG for detecting
delayed cerebral ischemia in patients with poor-grade subarachnoid hemorrhage. Clin Neurophysiol 2004;115[12]:2699–2710. hKilbride RD, Costello DJ, Chiappa KH.
How seizure detection by continuous electroencephalographic monitoring affects the prescribing of antiepileptic medications. Arch Neurol 2009;66[6]:723–728. iOddo M,
et al. Continuous electroencephalography in the medical intensive care unit. Crit Care Med 2009;37[6]:2051–2056. jSaengpattrachai M, et al. Nonconvulsive seizures
in the pediatric intensive care unit: etiology, EEG, and brain imaging findings. Epilepsia 2006;47[9]:1510–1518. kJette N, et al. Frequency and predictors of nonconvul-
sive seizures during continuous electroencephalographic monitoring in critically ill children. Arch Neurol 2006;63[12]:1750–1755. lShahwan A, et al. The prevalence of
seizures in comatose children in the pediatric intensive care unit: a prospective video-EEG study. Epilepsia 2010;51[7]:1198–1204. mAbend NS, et al. Nonconvulsive sei-
zures are common in critically ill children. Neurology 2011;76[12]:1071–1077. nMcCoy B, et al. Predictors of nonconvulsive seizures among critically ill children. Epilepsia
2011;52[11]:1973–1978. oWilliams K, Jarrar R, Buchhalter J. Continuous video-EEG monitoring in pediatric intensive care units. Epilepsia 2011;52[6]:1130–1136.)
1,600
1,400
1,200
1,000
No. of days of CEEG
800
600
400
200
Figure 17.3: Growth in number of days of

0 CEEG recording at Duke University Hospital
2004 2005 2006 2007 2008 2009 2010 from 2004 through 2010. (Unpublished data
Year from Dr. Bradley Kolls.)
discuss the technical and clinical considerations in performing and inter- Thus, it is a sensitive, albeit nonspecific, reflection of brain dysfunction.
preting CEEG in acutely or critically-ill patients. Furthermore, EEG is very sensitive to ischemia and hypoxia. It can detect
cerebral dysfunction due to ischemia or hypoxia at a reversible stage (3–8),
SCIENTIFIC BASIS FOR CONTINUOUS EEG RECORDING when interventions still have the potential to prevent permanent damage.
EEG abnormalities (decreased alpha and beta activity followed by increased
Before EEG was largely relegated to the evaluation and detection of seizure delta) are prominent at cerebral perfusion rates of 20 to 25 mL/100 g tis-
activity, it was recognized as a useful tool for the monitoring of brain activ- sue/minute; however, synaptic activity continues until 17 mL/100 g tissue/
ity for several reasons. First, activity on the EEG is closely linked to cerebral minute and energy failure and cell death do not occur until rates of 10 to
metabolism. It is a complex signal that reflects neuronal activity, which in 12 mL/100 g tissue/minute (Table 17.1). Furthermore, EEG changes related
turn is impacted by the many factors that influence cerebral metabolism. to ischemia are very fast, almost instantaneous. Thus, EEG monitoring
TABLE 17.1 Effect of Cerebral Blood Flow on EEG causality between seizures and outcome has not been established. The desire
to detect electrographic seizures in critically ill patients has been the major
Cerebral Blood Flow driving force in the rapid growth in popularity and availability of CEEG.
(mL/100 g/min) EEG Change Reversibility
35–70 Normal No injury HISTORICAL CONTEXT
25–35 Loss of beta activity Reversible
18–25 Theta slowing Reversible Although much of CEEG recording today is for the purpose of detect-
12–18 Delta slowing Reversible ing seizures or monitoring the treatment of seizures, early applications of
8–10 Suppression Irreversible CEEG were actually aimed at monitoring neurological function. Early
systems were complicated and cumbersome. Cerebral function monitors
From Astrup J, Siesjo BK, Symon L. Thresholds in cerebral ischemia—the ischemic
penumbra. Stroke 1981;12(6):723–725.
(CFMs) usually employed data compression techniques to display crude
trends in EEG activity on a very compressed time scale, in order to avoid
the need for very large volumes of paper. Maynard et al. (13) developed a
CFM that recorded and displayed the peak-to-peak amplitude of the EEG
provides a potential therapeutic window where cerebral perfusion is low on a logarithmic scale. This monitor was able to assess only crude changes
enough to cause changes on the EEG that may trigger changes in manage- in the EEG over long periods of time. It was applied to monitoring cerebral
ment prior to irreversible brain damage. The combined ability to continu- activity in post-anoxic patients to follow trends in cerebral activity—routine
ously monitor cerebral activity at bedside and the rapidity of its response to EEGs were performed every 24 hours to obtain more detailed data (14).
ischemia distinguish EEG from other tools that can monitor cerebral perfu- Actual continuous EEG from a limited electrode set was recorded from
sion such as transcranial Doppler, functional scans such as PET or SPECT patients with fulminant hepatic failure using Ag/AgCl surface electrodes or
scans. Although many of these modalities respond quickly to changes in platinum needle electrodes and displayed on an oscilloscope (15); however,
cerebral perfusion, they cannot be performed on a continuous basis. only intermittent samples were printed out for storage and later analysis. In
Beyond ischemia, there are several other potential mechanisms for addi- 1983, analog tape recorders were used to record and store two channels of
tional brain injury in critically ill patients. In these situations, EEG again EEG, one channel of ECG and one channel for respiration from neonates
has the potential to detect injury at an early, potentially reversible stage. (16,17). Using this system, seizures could be recorded in neonates who were
For example, in a series of 124 brain trauma patients, 91% suffered second- critically ill and paralyzed. Twenty-four hours of data could be stored on a
ary injuries due to factors such as increased intracranial pressure, hypoten- 20-minute cassette tape for later review. Continuous recording using six elec-
sion, or hyperthermia (9). Such secondary insults are often associated with trodes and a paper machine (running at a paper speed of 15 mm per second)
increased mortality (9,10). While other modalities can directly measure such was also demonstrated (with significant help from nursing and ICU staff
changes, the EEG is uniquely suited to measuring the impact of such factors to maintain the recording) (18). Quantitative EEG techniques, specifically
on cerebral function and doing so continuously. Fourier analysis of EEG epochs displayed as a compressed spectral array
Lastly, no other modality is as well-suited for the detection of seizure (CSA), were applied to display EEG trends over time (19–21).
activity as EEG. The high incidence of seizures, especially nonconvulsive By the early 1990s, there was a growing appreciation of the fact that neu-
seizures, in critically ill patients (11) has been a major driving force behind rophysiological monitoring could be an important addition to monitoring
the rapid increase in the use of continuous EEG in the ICU setting. Elec- in the neuroscience ICU (11). Specifically, there were clear demonstrations
trographic seizures with their inherent increased metabolic demand and of its potential role in detecting nonconvulsive seizures, guiding treatment
production of potentially toxic substances are another source of secondary of status epilepticus, aiding in prognostication of critically ill patients, and
damage in patients with brain injuries. For example, in patients with trau- in monitoring cerebral function. However, owing to technical and other
matic brain injury, electrographic seizures are independently associated with limitations, availability and use of CEEG was initially limited to a few aca-
worse clinical outcome independent of other variables (12), although true demic centers. With increased appreciation for its clinical role, especially
detection of nonconvulsive seizures, and wider availability of digital EEG, intermittently—during times of interest or at predefined epochs. However,
remote monitoring and other techniques, CEEG has become one of the it was the advent of digital EEG recording and storage that truly permitted
fastest growing areas of clinical neurophysiology. widespread development and use of CEEG.
Performing CEEG has several basic technical requirements, starting
TECHNICAL CONSIDERATIONS with the availability of adequate EEG equipment so that a machine can be
devoted to a single patient for a prolonged period of time. The actual EEG
Technical, personnel, and cost considerations have been the major limi- machine required for CEEG is the same as those used for epilepsy moni-
tation in performing CEEG. This includes the basic availability of EEG toring. Ideally, the EEG equipment should record time-locked video/audio
equipment. A CEEG study requires use of an EEG machine for a prolonged along with the digital EEG and EKG. The video and audio are necessary
time, often several days or more for a single patient. This was a major issue for the characterization of clinical events and for the proper interpretation
in the past when even large academic centers may have had only a handful of an EEG signal that is often marred by electronic and physical artifacts,
of EEG machines. In addition, the collection, review, and storage of large for example, manipulation of the patient by nurses, chest physical therapy,
quantities of data with analog equipment and paper machines were difficult. etc. EEG equipment with the smallest possible footprint is desirable in the
This did not prevent many early demonstrations of CEEG, as discussed pre- crowded environment of the ICU. Most EEG vendors now have equip-
viously. In addition, critically ill patients were frequently monitored using ment that allows for having only the EEG head-box, amplifier, and c amera/
intermittent EEG recording, for example, repeating a routine EEG daily microphone in the patient room. All data are sent over a local network to the
or even more frequently. In other situations, electrodes and EEG recording recording computer that may be located elsewhere in the hospital, for exam-
equipment were left attached to the patient, but data were only acquired ple, in a control room (Fig. 17.4). In such solutions, a monitor to display the
Remote
Review
Station
Firewall
Camera
Figure 17.4: Schematic of typical setup for

CEEG. The headbox/amplifier and camera are
Head EEG EEG Review located in the patient room. Data is collected by
Box Machine Server Station
an EEG machine, which is located either within
the patient room or connected to the camera/
headbox through the hospital network. Data is
Beside
then transferred to an EEG server for storage
Monitor and analysis. A review station is used for data
review and analysis. Older data is archived to
Archive online or offline mass storage units. In many
systems, remote review of data is available to
allow for review from outside the hospital.
raw EEG signal, and possibly quantitative EEG trends, is still located in the (events of interests, representative samples) and only a portion is stored.
patient room; a local hard drive is often employed for backup in case of net- Owing to cheaper storage and the time required to clip EEG files, most insti-
work failure. These data are intermittently transferred to a server for storage tutions save the entire EEG. This is ideal for answering clinical questions
and review if not recorded directly to the server. Depending on the system, that may arise later and also for research uses. The video may be stored for
the data may be transferred very frequently (every few seconds) or infre- even a smaller subset of the data, for example, for clinical events. In most
quently (a few times per day). From the server, the data may be reviewed cases, it is prudent to wait at least a few days, if not longer, before data are
either on dedicated review stations or using web-based software that allows clipped and the original data are deleted. Data may be stored off line on
for remote access. For systems that only infrequently transfer data from the media such as DVDs or tape; however, it is increasingly possible to store vast
acquisition machine to the server, it is important to also have remote access amounts of data online, where they may be accessed quickly.
to the acquisition station. This allows for review of data as they are being
acquired; for example, during a suspected clinical event. In the future, there PERSONNEL REQUIREMENTS
will likely be solutions where an individual computer is not required for each
patient; instead, the data are directly recorded by and to a server that is The personnel requirements for performing CEEG are substantial. Neurodi-
simultaneously recording from multiple patients. agnostic technologists who have experience in performing long-term record-
Information regarding clinical events, interventions, and drug administra- ings and are comfortable working with critically ill patients in the complex
tion is also a necessary part of the recording. Without such information, it ICU environment are needed. Although the basics of performing a CEEG
can be very difficult to determine the significance of changes in the CEEG. study are similar to a routine study, there are some special requirements.
Ideally, this information is integrated into the CEEG record, either auto- Advanced knowledge of EEG patterns and techniques are necessary and
matically via electronic medical records or via manual entry into the acquisi- some competency standards have been proposed (22). Currently, there is no
tion station via typing or preset single button presses. In some situations, it specific registration requirement for neurodiagnostic technologists engaged
must be acquired from other hospital systems such as the electronic health in CEEG. However, as recognition of the special skills required for CEEG,
record or paper charts. In such situations, it is important that the clocks the CLTM (Certification Examination in Long-Term Monitoring) credential
being used by personnel and other monitoring equipment/modalities be syn- offered by the American Board of Registration of Electroencephalogram and
chronized with the clock in the CEEG equipment. Evoked Potential Technologists (ABRET) encompasses technologists per-
Adequate personnel are needed to perform the recordings, including forming both epilepsy monitoring and ICU-EEG monitoring. ABRET now
potentially applying/removing electrodes and starting/stopping recording also accredits laboratories that meet certain standards and practices for long-
at unusual times, often on an urgent basis. Analysis of such large volumes term monitoring (LTM), including epilepsy monitoring and ICU/critical
of data in a timely fashion is another challenge (discussed later). Because care EEG monitoring or both. Requirements include personnel and volume
CEEG data cannot usually be easily interpreted by personnel available at requirements, as well as standardized policies and protocols for recording
bedside (i.e., nurses and other ICU staff), remote access is essential for CEEG procedures, review of data, handling complications, and archiving of data.
recordings. This allows for a neurophysiologist or technologist to review the Owing to the uncertain nature of working with critically ill patients, one
data as they are being collected without necessarily being at bedside. Usu- technologist is unlikely to be adequate for a CEEG program. The start,
ally, the data can be accessed remotely without being in the hospital. stop, and interruption of studies are dictated by many factors, including the
Data management and storage are a major concern in CEEG. A single clinical course of the patient and the need for other studies or interventions.
patient being recorded with video and a standard set of EEG electrodes Thus, studies are often initially requested outside of regular work hours and
(approximately 21 electrodes) generates approximately 8 to 10 GB of data must be interrupted or stopped at unusual hours. Most centers that perform
per day (about 90% from the video). The volume of data generated over any significant amount of CEEG find it necessary to have a technologist
weeks and months can be huge. As the cost of storage capacity has declined, available in-house or on call at most, if not all, times.
the potential for permanently storing all collected data exists, especially all Some centers employ technologists or other trained personnel for the pur-
EEG data. However, at some institutions, after review, the data are clipped poses of monitoring studies, reviewing studies, and clipping/maintaining
data. In an ideal case, CEEG data from multiple patients could be moni- subdermal wire electrodes require little skin preparation and may actually
tored at a central location by a trained observer (a technologist or someone offer superior recording with less artifact compared with collodion-applied
else trained in the basics of ICU-EEG and quantitative EEG) who could scalp disc electrodes (26). They are inserted via a small needle, but the needle
respond to automated alarms, note changes in the EEG, and note when is removed, leaving only the wire in place (as with sphenoidal electrodes).
the study was in need of maintenance. As will be discussed later, reviewing The use of such electrodes allows for continuous recording without inter-
CEEG data is a time-consuming process; some centers are using technolo- ruption for imaging procedures; such interruptions have the potential for
gists to perform an initial review of the CEEG, which is then reviewed and missing clinically important events, such as seizures (27). Subdermal wire
finalized by a neurophysiologist. In academic centers, this task is often per- electrodes also require less daily maintenance for continuous use; further-
formed by neurophysiology fellows or other trainees. more, the same set of electrodes, once applied, may be used for prolonged
The neurophysiologist also requires some additional expertise. Interpreta- periods of time—up to 60 days in one case report (28). Concerns about the
tion of CEEG data is sufficiently different from routine EEGs and epilepsy slightly invasive nature of these electrodes are less of an issue in the critically
monitoring that the neurophysiologist should have some specific knowledge ill patient; however, they have still led some users to use reduced numbers
and training in CEEG interpretation. Some of the specific challenges associ- of electrodes, 6 to 10 electrodes instead of a full headset. Owing to issues of
ated with the interpretation of CEEG are discussed later. Another issue is infection control, disposable or single-use electrodes are also an attractive
availability. Ideally, a CEEG would be reviewed continuously, but at a mini- option for CEEG recordings.
mum, it should be reviewed twice daily. In addition, urgent review is often Another safety issue relates to skin breakdown. CEEG is often performed
necessary for clinical events or changes in neurological function. Thus, it is for prolonged periods of time in patients whose mental status prevents them
very difficult for a single neurophysiologist to cover a CEEG service. from indicating discomfort. Thus, it is essential to routinely monitor them
for skin breakdown. This is especially true in patients with sensitive skin;
ELECTRODES AND ELECTRODE APPLICATIONS for example, neonates. Longer recording durations are also associated with
breakdown (29). Sometimes, it may be necessary to stop recording for a
A variety of electrode types and application techniques are used with CEEG. period of time to minimize such injuries.
Most commonly used are cup electrodes with electrode paste, which are also Electrode application is most commonly by the International 10–20 sys-
the most commonly used for routine scalp recordings. These can be applied tem. A1 and A2 electrodes are usually not applied. Midline electrodes are
simply using the electrode paste. However, this technique is prone to drying sometimes not used; however, they can be extremely useful as this is a loca-
out of the electrodes and movement/displacement of electrodes. Collodion tion that is often free of artifact (especially muscle) and most devices, such
is often used to hold electrodes in place for longer recordings. Needle elec- as drains, are located laterally. The presence of surgical scars, traumatic
trodes are also occasionally used in the ICU setting, especially in sedated or lesions, or devices such as drains or pressure monitors often necessitates
comatose patients. These are often easier to apply (requiring minimal skin leaving off certain electrodes. However, these electrodes are often those
preparation) and offer well-balanced impedances. However, owing to their lying closest to damaged neural structures that warrant close monitoring.
lower surface area, they actually have higher impedance. In addition, there A preferred approach is to displace these electrodes to the nearest avail-
is a risk of needle sticks. able location. It may also be desirable to displace the corresponding elec-
One issue that comes up with CEEG recording is the need for neuroimag- trode over the contralateral hemisphere to an equivalent location to still
ing in these patients. With traditional electrodes, this usually necessitates the allow for side-to-side comparison. An alternative solution is to have the
removal and reapplication of electrodes. Several electrode options are now surgeons place a needle or subdermal wire electrode in the perioperative
available that are MRI and/or CT compatible. MRI compatibility generally area sterilely.
requires non-ferromagnetic electrodes, often made from carbon fiber with Application of electrodes using the standard 10–20 system is often the
sintered silver/silver chloride leads. CT compatibility requires electrodes rate-limiting step in the initiation of a CEEG study and requires a trained
that have low density. This includes subdermal wire electrodes and silver- technologist or neurophysiologist. This has led to attempts to use alter-
epoxy-coated conductive plastic electrodes (23–25). Like needle electrodes, native electrode placement methods. These can be divided into two basic
techniques: using landmarks to place the electrodes without actually MONTAGES

measuring the head and using templates to apply electrodes in locations
approximating the 10–20 system. Examples of the former include hairline Most often, recordings are displayed using a longitudinal bipolar montage;
or sub-hairline montages. In these, electrodes are placed along the hairline the other montage that is commonly used is an average reference montage.
without using any measurement tools. Kolls and Husain (30) reviewed data The latter montage is especially useful in situations where certain electrodes
using only Fp1, Fp2, F7, F8, T3, T4, T5, and T6 electrode data from tra- are either absent or not in their usual location because of scars, lesions, or
ditionally acquired EEG to calculate the sensitivity of a hairline montage. other instruments/devices. For example (Fig. 17.5), in a traditional longitu-
Sensitivity varied by the montage used (longitudinal bipolar or ipsilateral dinal bipolar montage, a missing F4 electrode will make both the Fp2-F4
ear reference were superior to contralateral ear reference). However, the and F4-C4 channels uninterpretable; however, with an average reference (or
sensitivity for seizures was only 72% and for periodic discharges, it was other referential montage), Fp2-Avg and C4-Avg will still be interpretable,
even lower at 54%. For detecting a normal EEG, the sensitivity was 91%. only F4-Avg will be affected (though F4 will need to be deleted from the
Specificities were generally higher, ranging from 84% to 99%, depending on average reference calculation, as well as its homologue F3). Other montages,
the activity and montage used. In a prospective study using a commercially with limited electrode sets or simplified electrode placements, have been used
available 4-channel EEG recorder and hair electrodes placed on the anterior mainly been used as a means of expediting the application of electrodes (see
hairline, Young et al. (31) found a sensitivity of 68% and a specificity of foregoing discussion).
98% for seizure detection. For epileptiform discharges or periodic lateral-
ized epileptiform discharges, their sensitivity was 39% and specificity was
92%. Also, using reformatted data, Karakis et al. (32) showed a sensitivity ARTIFACTS
of 92.5% and a specificity of 93.5% using electrodes that could be approxi-
The ICU is an electromagnetically hostile environment that makes even rou-
mately placed using anatomical landmarks—Fp1, Fp2, T3, T4, O1, O2, and
tine EEG recording difficult. In CEEG, electromagnetic noise is compounded
Cz, although the actual study was done using electrodes placed traditionally.
by many other sources of artifact and noise. CEEG is prone to both physi-
Montages included a double diamond (Fp1-T3, T3-O1, Fp1-Cz, Cz-O1) on
ological (muscle, movement, cardiac, tongue movement, sweat, shivering,
the left (and equivalent on the right), circumferential, and Cz reference.
pulse, and eye movements) and nonphysiological (line noise, electrode arti-
Electrode templates or nets offer another means of simplifying and expe-
facts, ventilators, chest physical therapy, other equipment and patient contact)
diting the placement of electrodes. These templates usually consist of elastic
artifacts. As opposed to routine EEG, which is performed in an optimized
or otherwise adjustable harnesses that are placed on the head using land-
environment with minimal disturbance, CEEG occurs in an environment of
marks such as the nasion, inion, and ears. The template then indicates the
constant activity, movement, and other instruments. All of these can cause
approximate location for electrodes—sometimes with a color-coded scheme
artifacts that limit the interpretability of CEEG studies (Figs. 17.6 to 17.11).
that facilitates connection of the electrodes to the EEG amplifier headbox.
In many situations, it is very difficult to determine the nature of an artifact,
Either needle or surface cup electrodes can then be placed at these loca-
although video is often useful and can prevent misinterpretation. It is often
tions. Such headsets have been shown to produce recordings that are not
necessary to actually examine the CEEG environment to seek out specific
distinguishable from those made with traditionally-applied electrodes with
sources of artifact.
much greater speed (33). Although their actual performance, with respect
to sensitivity, has not been compared with traditionally applied electrodes,
there is no obvious reason why they should be significantly less sensitive. CLINICAL FACTORS THAT CONFOUND
Where such approximate techniques are likely to face problems are in the
detection of asymmetries and regional/focal abnormalities, where precise There are several clinical factors that can also confound CEEG interpreta-
and balanced electrode placement is much more crucial. There are several tion. These include the presence of other monitors and devices that may
newer materials and methods under development for rapid placement of limit electrode placement and introduce noise into the recording. Surgical
electrodes, so progress in this area is likely in the near future. or traumatic scars may also limit electrode placement. Dressings may limit
A
Figure 17.5: A: Artifact due to missing F4 electrode—not placed by technician due to presence of a ventricu-
lar drain. Ideally, the electrode should have been placed at a displaced location and F3 moved to the equiva-
lent location over the left hemisphere. B: By using an average reference, Fp2 can be more easily evaluated as
the artifact now only impacts one derivation (F4-AVG). LFF = 1 Hz, HFF = 70 Hz, notch off.
552
access. Skull defects may lead to breach rhythms or an asymmetric appear- event are essential for the interpretation of CEEG. Multimodal monitoring,
ance of background activity (Fig. 17.12). where data from other monitors (e.g., intracranial pressure, oximetry, etc.) is
Another set of factors are those related to manipulations of the patient integrated with the CEEG recording, may offer a means for improved cor-
(physical and pharmacological) by other clinicians. This can include diverse relation of changes in CEEG with systemic factors.
factors such as changes in medications, especially continuous infusions
used for sedation or pain control, medical procedures such as hemodialysis, REVIEWING DATA
changes in systemic factors such as ventilation (hypoxia or hypercarbia) or
blood pressure. Even simple manipulations like repositioning of the patient CEEG produces very large volumes of EEG and, in most cases, video data.
or arousal of the patient due to examinations can have major impacts on Ideally, these data would be reviewed in real time to provide immediate feed-
the CEEG recording. Maintaining a log of such events and the availability back to the medical team caring for the patient (34). However, this is gener-
of video to investigate whether a CEEG change correlates with a clinical ally not feasible, as in most situations, proper interpretation requires review
by a trained neurophysiologist. Thus, CEEG data are usually interpreted requiring a minimum of 30 minutes to review 24 hours of data (for a dis-
on an intermittent basis. At our institution, for example, all CEEG data are play page of 10 second per page reviewed at a rate of 5 pages per second),
reviewed within one hour of the start of the study. After this, it is reviewed assuming there are no events or significant abnormalities that require closer
at a minimum of 6-hour intervals throughout the day and 8-hour intervals review. Closer examination of the EEG or video during seizures or other
at night. If any of the reviews reveal seizures, epileptiform activity, or sig- events of interest will significantly increase the time required for review. The
nificant changes from prior reviews, the EEG is reviewed more frequently, use of quantitative EEG trends (discussed later) can speed up the review
usually at 1- to 2-hour intervals. Because many seizures are nonconvulsive process, sometimes dramatically, especially in comatose patients, although
or subtle, the entire record must be reviewed by either reviewing the full the specificity and sensitivity of such tools remain poorly established.
raw EEG or selected segments based on quantitative EEG and detection There are several potential options to improve the review process to allow
software. Review of the full raw EEG can be a very time-consuming process, for continuous interpretation as well as continuous recordings, including
Figure 17.6: Sinusoidal artifact due to chest

percussion (in this case built into the ICU bed).
A: The artifact builds gradually in amplitude
over the left parietal head regions, giving an
impression of possible evolution. However, in
B: page, it continues to show the same fre-
quency, monomorphic activity, indicating its ar-
tifactual nature. Video confirmed that this was
due to a rapidly oscillating bed (automatic chest
percussion). LFF = 1 Hz, HFF = 70 Hz, notch off.
technologists sitting at a centralized location and reviewing multiple CEEG EEG INTERPRETATION AND NOMENCLATURE
recordings. Beyond placing additional demand on staffing, questions of
necessary training and sensitivity/specificity when monitoring multiple Interpretation of CEEG can be divided into three components: back-
patients simultaneously, especially for more subtle events, remain unsettled. ground; periodic patterns and rhythmic activity; and seizures. Inter-
This person could also respond to automated alarms, which could then be pretation of the background is similar to that for routine EEGs with
set at a more sensitive level as frequent false positives would be acceptable. some important distinctions. In the American Clinical Neurophysiology
Another approach is the use of quantitative EEG analysis trends (discussed Society’s (ACNS) published standardized terminology for periodic and
later) at the bedside, which may allow nursing or other ICU personnel to rhythmic patterns seen in the critically ill, the authors also outline some
detect events or at least periods of concern, which can then be reviewed by specific areas that should be included in the description of the back-
the neurophysiologist urgently. ground EEG; see Table 17.2 (35,36). This is an attempt to standardize
Figure 17.7: Widespread artifact, mainly over

the left hemisphere related to the ECG (arrows).
Note that the apparent spikes are time-locked
with the ECG at the bottom of the figure. LFF =
1 Hz, HFF = 70 Hz, notch off.
nomenclature and reporting of CEEG data. The applicability, ease of During the course of hours or even days of recording, the background
use, and reproducibility of the background EEG portion of this nomen- can change markedly. This can be related to changes in the neurological
clature have not been investigated. Other scoring systems for EEG also condition of the patient (e.g., evolving injury, ischemia, or improvement) or
exist (37) but are not targeted for ICU-EEG recordings. The SCORE to pharmacological or physical factors (e.g., level of sedation or body tem-
(standardized computer-based organized reporting of EEG) system perature). Thus, a single description of the background is often inadequate;
is being developed in Europe under the auspices of the International moreover, knowledge of the timing of changes in the patient’s clinical state
League Against Epilepsy and the International Federation of Clinical and interventions by the ICU team is necessary for proper interpretation.
Neurophysiology. The software attempts to standardize not only descrip- Isolated epileptiform discharges (i.e., those not part of a periodic pattern)
tions of the EEG, but also clinical and demographic information. There should be described with some indication of quantification. The proposed
are plans to incorporate the ACNS nomenclature into the SCORE sys- ACNS guidelines suggest: “abundant” for greater than 1/10 second; “fre-
tem and software. quent” for greater than 1 per minute but less than 1/10 second; “occasional”
Figure 17.8: Semirhythmic sharp waves at F7

(box) giving the impression of an evolving sei-
zure are actually due to left-beating nystag-
mus based on clinical examination. LFF = 1 Hz,
HFF = 70 Hz, notch off.
for greater than 1 per hour but less than 1 per minute; and “rare” for less proposed version of the guidelines (38). Periodic patterns are described
than 1 per hour. using two main terms. The first describes the spatial extent of the activity
Periodic patterns constitute a frequent and prominent feature of CEEG (generalized, lateralized, bilateral independent, or multifocal); the second
recordings (Figs. 17.13 to 17.17). A multitude of descriptive terms, such describes the morphology (periodic discharges, rhythmic delta activity, or
as periodic lateralized epileptiform discharges (PLEDs), generalized peri- spike-wave/sharp-wave). The distinction between periodic and rhythmic
odic epileptiform discharges (GPEDs), and triphasic waves, have been relies on whether or not the repeating activity is separated by a definable
used to describe such patterns. However, there is wide variability in how interval between consecutive waveforms (periodic) or not (rhythmic). In
these terms are applied and many have clinical connotations that are addition to the main terms, there is a large group of proposed modifi-
best avoided in an objective description of an EEG. Thus, the ACNS has ers, including prevalence (percentage of record that includes the pattern),
developed, solicited feedback, modified, and published standardized ter- duration (for patterns that are not continuous, the typical duration of the
minology (Table 17.3) (35,36), which has been modified from an earlier pattern), frequency, number of phases, sharpness, amplitude, polarity,
Figure 17.9: High-amplitude rhythmic polyphasic

artifact related to ventilator. This is commonly re-
lated to fluid in the tubing and often resolves when
this is removed. LFF = 1 Hz, HFF = 70 Hz, notch off.
stimulus-induced versus spontaneous, evolving/fluctuating, and “plus” The clinical significance of periodic discharges is controversial (reviewed in
(indicating features that suggest greater ictal appearance of the pattern). A [41]). It is clear that they are highly associated with seizures (Fig. 17.15); the
crucial test for such guidelines is inter-rater agreement among neurophysi- exact incidence is unclear, but frequency of seizures in patients with (PLEDs)
ologists using the guidelines. For the earlier guidelines, this agreement was ranges from 58% to 100% (1). In a retrospective analysis of 118 patients with
only fair to moderate (39). The modified guidelines showed greater than periodic epileptiform discharges (PEDs) on EEG, the incidence of acute sei-
95% inter-rater agreement for the main terms (96% for main term 1; 98% zures was 70.3% for PLEDs, 43.4% for patients with bilateral independent
for main term 2) and greater than 80% for amplitude (93%), frequency periodic epileptiform discharges, and 29.4% for patients with GPEDs (42).
(80%), and plus (82% to 88%) modifiers (40). The other modifiers have not In a smaller case series, the incidence of seizures in patients with periodic dis-
been specifically evaluated for inter-rater agreement. Additional modifica- charges was higher—82% of 45 patients with PLEDs and 78% of 18 patients
tions were made after the Mani et al. inter-rater study to attempt to further with bilateral independent periodic discharges (43). In a retrospective, case-
improve inter-rater reliability. control study of 200 patients with generalized periodic discharges (GPDs)
Figure 17.10: Paroxysmal rhythmic pattern due

to chest percussion by a respiratory therapist.
LFF = 1 Hz, HFF = 70 Hz, notch on. (With per-
mission from Hirsch LJ, Brenner RP. Atlas of EEG
in critical care. West Sussex, UK: John Wiley &
Sons, 2010:334.)
compared to 200 matched (age, etiology and level of consciousness) controls, This increased metabolic demand associated with periodic discharges may be
the incidence of seizures was 46% for cases versus 36% for controls (44). Fur- a potential cause of additional injury; however, the increased cerebral blood
thermore, for the patients with GPDs, the incidence of nonconvulsive seizures flow could be an adaptive response to the increased activity, possibly even
(27% vs. 8%) and nonconvulsive status epilepticus (22% vs. 7%) and mortal- improving recovery. In a small retrospective study of comatose patients, the
ity (after excluding cardiac arrest patients, 36.8% vs. 26.9%) was higher. The presence of prolonged periodic discharges (5 consecutive days, 25 patients)
question is whether periodic discharges are causing additional injury to the or intermediate periodic discharges (1 to 5 consecutive days, 21 patients) had
brain or simply are an indicator of injury that has already occurred. The no impact on mortality or recovery of consciousness at discharge compared
presence of periodic discharges has been associated with significant mortal- with patients without periodic discharges (21 patients) (51). The prolonged
ity, although most such studies have lacked a control or comparator group, periodic discharge group did show a significantly higher incidence of electro-
leaving open the possibility that the high mortality reflects the underlying graphic seizures and an increased number of AEDs administered. In another
condition and not the presence of periodic discharges (42,45–47). In addi- retrospective analysis of 200 adult patients with GPDs on CEEG compared
tion, some studies have found regional increases in cerebral blood flow, oxy- with 200 matched controls, patients with GPDs had a higher incidence of
gen consumption, or metabolism associated with periodic discharges (48–50). seizures (46% vs. 34%), nonconvulsive seizures (27% vs. 8%), nonconvulsive
Figure 17.11: EEG of 92-year-old man with

mental status changes and renal failure shows
rhythmic artifact (boxes) predominantly involv-
ing the anterior head region, mainly Fp1 and
Fp2, more marked on the right. The discharge
is also present in T4-T6, indicating that it is
not due to eye movement. The artifact is due
to dialysis utilizing slow continuous ultra filtra-
tion (SCUF). (With permission from Hirsch LJ,
Brenner RP. Atlas of EEG in critical care. West
Sussex, UK: John Wiley & Sons, 2010:334.)
status epilepticus (22% vs. 7%), and increased mortality (36.8% vs. 26.9%, research purposes, are shown in Table 17.4. Evolution of the EEG pattern,
when cardiac arrest patients were excluded) (44). However, on multivariate especially when the background EEG contains periodic discharges, can be
analysis of the entire cohort, the presence of GPDs was not a predictor of difficult to define/recognize. Evolution implies more than just a change in
worse outcome. frequency; the change should be gradual and not a just a sudden jump from
In CEEG recording, even the detection of seizures is not straightforward. one frequency to another. A definition requiring a minimum of two sequen-
A subset of patients does show classic electrographic patterns with rhythmic tial changes in frequency, each by at least 0.5 Hz, has been proposed. Most
activity arising out of a nonrhythmic background and showing evolution authors have used a minimum duration of 10 seconds in order to classify
in frequency and/or spatial distribution. However, the significantly abnor- a pattern as ictal. Obviously, this is an arbitrary criterion that serves as a
mal background EEG activity of many patients, including the presence of proxy for the real issue: is the EEG pattern causing additional neuronal
rhythmic activity and PEDs, can make distinguishing an ictal pattern from injury and is it contributing to the patient’s clinical condition or simply an
an abnormal background difficult. Moreover, there is a lack of complete epiphenomenon related to the underlying condition.
agreement regarding which patterns constitute an ictal pattern. Several Defining the end of a seizure can be equally challenging. Although the
authors have proposed EEG criteria for defining nonconvulsive seizures basic concept that a seizure is deemed to have ended when there is return of
(11,41,52). Criteria that are currently most commonly used, especially for non-ictal EEG activity sounds fairly simple, it can be difficult to apply in a
Figure 17.12: EEG of 36-year-old woman dem-

onstrating high-voltage beta activity, particularly
in the right central region (long box). Activity is
also of higher voltage and slower over the right
side, especially in the frontotemporal region.
The patient had a right-sided craniotomy. This
is a breach rhythm (long box) with underlying
dysfunction, as indicated by focal slowing (two
smaller boxes). (With permission from Hirsch LJ,
Brenner RP. Atlas of EEG in critical care. West
Sussex, UK: John Wiley & Sons, 2010:334.)
situation where ictal activity alternates with interictal rhythmic or periodic focal clinical seizures are elicited (54). The clinical significance of isolated
activity. A minimum duration of 10 seconds of non-ictal EEG has been sug- SIRPIDs remains uncertain, although they often occur in conjunction with
gested (Fig. 17.18). non-stimulus-induced electrographic seizures. There is substantial variabil-
Of note, the presence of clinical signs of seizure activity, even if subtle, ity among neurophysiologists in assigning clinical significance to such pat-
associated with an EEG pattern will lead to classifying that pattern as ictal; terns. To date, there is no evidence that the stimulus-induced nature of these
for example, periodic discharges associated with time-locked jerking, even patterns implies any difference in significance. In the new ACNS nomencla-
though the EEG pattern does not meet the above-mentioned criteria. Fur- ture, the prefix “SI” is used when any of these patterns can be repeatedly
thermore, changes in patient state or alerting stimuli may lead to changes in elicited by alerting stimuli.
the background that may satisfy the above-mentioned criteria. One example There are only limited data on inter-rater reliability in diagnosing seizures
is the changes in EEG, especially periodic patterns that occur with stimula- using such criteria. In one study of nine clinicians with different levels of
tion. The term SIRPIDs (stimulus-induced rhythmic, periodic or ictal dis- experience in clinical neurophysiology, the overall kappa score was 0.5 for
charges) was coined for this phenomenon, which was reported in 22% of 150 the experienced raters and 0.29 for the less experienced raters (55). How-
consecutive patients undergoing CEEG (53). Nearly half of these patients ever, one crucial limitation of this study was that raters assessed presence or
showed SIRPIDs that fulfilled criteria for ictal discharges. On occasion, absence of seizures based only on 10-second epochs of EEG.
TABLE 17.2 ACNS Guidelines for Description of Background EEG for Critically Ill Patients
Symmetry 1. Symmetric
2. Mild asymmetry: consistent asymmetry in amplitude of 50% on referential recording or in frequency
of 0.5–1 Hz
3. Marked asymmetry: 50% amplitude or 1 Hz frequency
Posterior dominant “alpha” rhythm Must be demonstrated to modulate with eye opening/closing; frequency to 0.5 Hz or absent
Predominant background EEG frequency Describe predominant frequency, including multiple frequency bands, if present
Anterior-posterior (AP) gradient Present if clear/persistent gradient (1 min) of voltage and frequencies (higher frequencies/lower volt-
ages anteriorly and lower frequencies/higher voltages anteriorly). A reverse AP gradient may also be
described
Variability Yes, no or unknown/unclear/not applicable
Reactivity Change in activity in response to stimulation. Yes, no or unknown/unclear/not applicable
Voltage Of background (not of periodic patterns or epileptiform discharges)
1. Normal
2. Low (most or all activity 20 μV on longitudinal bipolar montage)
3. Suppressed (all activity 10 μV)
Stage II sleep transients 1. Normal (K-complexes and spindles both present and normal)
2. Present (at least one) but abnormal
3. Absent (both absent)
Continuity 1. Continuous
2. Nearly continuous with attenuation (10% of record with periods of attenuation, which are periods of
lower voltage that are 10 mV but 50% of background voltage)
3. Nearly continuous with suppression (10% of record with periods of suppression, which are periods
of lower voltage that are 10 mV)
4. Discontinuous: 10%–49% of record consists of attenuation/suppression
5. Burst-attenuation/burst suppression: 50% of record consists of attenuation or suppression. Include
typical duration of bursts and suppression. Include description of contents of burst
6. Suppression: entire record consists of suppression
From Hirsch LJ, et al. American Clinical Neurophysiology Society’s standardized critical care EEG terminology: 2012 version. 2012. Available from http://www.acns.org/pdfs/ACNS-
2012Nomenclature-2of5_Text_Final-03_Jun.pdf. Accessed July 8, 2012. Hirsch LJ, et al. American Clinical Neurophysiology Society’s standardized critical care EEG terminology: 2012
version. J Clin Neurophysiol 2013;30(1):1–27.
QUANTITATIVE EEG ANALYSIS detecting seizures, describing the background and detecting fairly sud-
den changes in the EEG. However, there are several problems; the most
Traditional EEG analysis consisting of page-by-page review of the raw obvious of which is how time-consuming the process is and the lack of
EEG is the time-honored way of interpreting routine, long-term, and continuous feedback to the ICU team caring for the patient. In addition,
CEEG data. With a trained interpreter, it is a very reliable means of it may not be very sensitive to gradual changes in the background EEG
Figure 17.13: Left occipital periodic discharges

(LPDs, a.k.a. PLEDs, boxes; at approximately
1 Hz) in a 64-year-old patient with history of
stroke who presented with right-sided weak-
ness and language problems. MRI revealed
acute infarct in the left occipital region. LFF = 1
Hz, HFF = 70 Hz, notch off.
that may occur over hours and days (56); for example, changes related underlying raw EEG be reviewed to confirm findings; this requires a
to delayed cerebral ischemia after subarachnoid hemorrhage, gradual trained electroencephalographer.
wearing off of drug effect, or changes related to fluctuations in intracra- There are many different QEEG tools available, as any mathematical
nial pressure. Quantitative EEG provides a potential tool for overcom- operation/analysis performed on EEG data is QEEG. Historically, the tools
ing some of the challenges inherent in CEEG interpretation. For post available were largely dependent on available technology, starting with hard-
hoc analysis, QEEG can allow for more rapid review of large quantities ware instruments that analyzed analog EEG signals. In fact, some QEEG
of data and for spotting subtle trends. During data collection, QEEG tools were actually developed as a means to display long-term analog EEG
trends may be able to immediately and automatically detect events such data in a compressed fashion (13). Today, almost all QEEG consists of
as seizures or cerebral ischemia. Lastly, during data collection, QEEG can software algorithms operating on digital EEG signals.
provide a simplified view of EEG data that can be evaluated and used Time domain analysis refers to tools that describe how the EEG signal
by non-neurophysiologists. However, it is paramount that the associated varies over time. One example that is frequently used in CEEG, especially
Figure 17.14: A: Left  right occipital periodic discharges (LPDs) in a 65-year-old patient with left parieto-
occipital infarct (boxes). B: Example of evolution into a brief electrographic seizure (boxes; note faster time
scale for this panel). LFF = 1 Hz, HFF = 70 Hz, notch off.
in neonates, is amplitude-integrated EEG (aEEG). In this case, the raw for brief seizures (40%), and poor for slowly evolving seizures (20%) (58)
EEG is filtered, rectified, smoothed, and then displayed on a compressed using aEEG.
time scale. For each epoch, both maximum and minimum amplitude of the Frequency domain analysis refers to analysis of the contribution of dif-
smoothed signal are plotted, connected by a vertical line. aEEG has been ferent frequencies to the EEG signal. Filtering of the EEG signal is a sim-
applied extensively to the analysis of CEEG in neonates (57). Another ple example. Calculating the Fourier spectrum of the raw EEG is another
time domain tool is envelope trend analysis: raw EEG is first filtered example: the EEG for a given epoch is represented as the weighted sum of
within a specified frequency range (e.g., 2 to 6 Hz), and the median ampli- sine waves of different frequencies. For each frequency, there is an amplitude
tude of the waveforms in a given epoch (e.g., 10 to 20 seconds) is plotted. (the magnitude of the contribution made by the sine wave at that frequency)
In neonates, experienced users had a fairly high sensitivity for detecting and a phase (the starting point of the sine wave of a given frequency). The
prolonged seizures (>58 seconds duration, 88% sensitivity), intermediate plot of the amplitude versus frequency is the Fourier spectrum. Power refers
to the area under the Fourier spectrum amplitude curve within a given below which a certain percentage of the total power resides, typically 90%,
frequency range. For example, the alpha power would be the area under can potentially be used to monitor for both level of sedation (60) and cere-
the curve from 8 to 13 Hz. This may be expressed as absolute power or bral ischemia (61).
relative power (e.g., normalized by the total power in all frequency bands). Time-frequency analysis refers to how the contribution of different
Power ratios are the ratio of the power in two different frequency bands. frequencies to the EEG signal varies over time. Because the EEG is a
For example, the alpha to delta ratio (ADR) is the ratio of the power in nonstationary signal (one whose frequency composition is not constant
the alpha frequency band to that in the delta frequency band. ADR has over time), its Fourier spectrum also varies with time. Time-frequency
been used to monitor for ischemia in both intraoperative monitoring and in tools are used to describe this variation. CSA and density spectral array
the ICU (59). The spectral edge frequency (SEF), defined as the frequency (DSA) are tools for displaying the power spectrum over time. For CSA,
Figure 17.15: A: Lateralized periodic discharges

(LPDs, a.k.a. PLEDs) with superimposed fast ac-
tivity (LPDs  F) in the right hemisphere, central
maximum (boxes). B: An example of intermit-
tent evolution into semirhythmic faster activity
(boxes). This shows clear evolution but is not
long enough to be considered an electrographic
seizure. These are sometimes referred to as
BIRDs (brief ictal rhythmic discharges) or simi-
lar names. C: Longer event consistent with an
electrographic seizure. LFF = 1 Hz, HFF = 70 Hz,
notch off.
the power spectrum for each epoch is displayed as a line graph; CSAs tracing signifies gradual change in the frequency of the rhythmic pattern,
are rarely used now. Instead, DSAs, where the amplitude of the Fourier fairly specific for an evolving seizure. Examples of QEEG are shown in
spectrum is encoded in different colors and displayed over time, are used. Figs. 17.19 to 17.23.
Measures of rhythmicity have also been utilized. For example, “rhythmic Some quantitative EEG software packages include automated detec-
run detection and display” is a proprietary QEEG tool based on wave- tors and alarms. However, most of these tools were developed for seizure
let analysis (Persyst, Inc., Prescott, Arizona). It highlights the frequency detection in patients with relatively normal background EEGs and rapidly
components of the DSA that are the most regular in repetition pattern evolving seizures seen in epilepsy monitoring units or ambulatory EEG
(i.e., rhythmic or periodic) at a given time. It can help to highlight the recordings. Their utility for CEEG recordings remains largely unestab-
rhythmic activity associated with seizures. A diagonal appearance in this lished. In one small study (24 patients) comparing a novel seizure detection
algorithm with two commercially available, automated seizure detectors, the With regard to comparison of different QEEG techniques, there are few
commercially available software showed limitations (62). The Reveal algo- studies to date. In a retrospective study of 27 CEEG recordings from pedi-
rithm (Persyst) had a sensitivity of 12.9% with 1.036 false detections per atric ICU patients, DSA and an EEG showed median sensitivity for sei-
hour; the IdentEvent algorithm (Optima Neuroscience) had a sensitivity of zure identification of 83.3% and 81.5%, respectively, with a very low false
10.1% with 0.013 false detections per hour. By comparison, the novel algo- positive rate (64). However, sensitivity was very different from patient to
rithm developed by the authors had a sensitivity of 90.4% with 0.066 false patient, ranging from 0% to 100%, suggesting that some combination of
detections per hour. This algorithm and others being developed (63) may be seizure electrographic characteristics (many missed seizures were of low
promising tools for CEEG monitoring in the future if their sensitivity and amplitude), background EEG, and other factors determine the actual
specificity can be confirmed in novel and larger data sets. sensitivity. More complex algorithms, often based on combinations of
quantitative EEG parameters, are being developed and tested for their CLINICAL APPLICATIONS
ability to correctly analyze and not only detect seizures but also classify
the EEG into different categories, such as normal, low voltage, burst sup- There are several common indications for CEEG in the ICU (Table 17.5)
pression, slowing, periodic discharges, and seizures (65). Such algorithms (66,67). These include detection of subclinical seizures in patients with fluc-
have shown promising results in initial studies, but await larger tests and tuating mental status or unexplained altered mental status. A simple sum-
validation. mary of the highest-risk patients is those with acute brain injury or clinical
The potential utility of QEEG tools for detecting delayed cerebral seizure with persistently impaired or fluctuating consciousness. CEEG can
ischemia in patients with subarachnoid hemorrhage has been demonstrated also be useful for evaluating spells (i.e., posturing, tremors, twitching, nys-
(see later) (59). tagmus, paroxysmal changes in vital signs such as tachycardia, or rises in
Figure 17.16: A: Bilateral rhythmic delta ac-

tivity (GRDA in ACNS nomenclature), anterior
predominance in a 12-year-old patient who
had resection of fourth ventricular mass with
persistent change in mental status following
surgery. The pattern did not show any evolu-
tion and there were no electrographic seizures.
Fp2-F4 and F4-C4 have been suppressed owing
to missing F4, which was not placed due to the
presence of a drain. B: The same page is shown
in average reference. This permits Fp2 to be
interpreted. LFF = 1 Hz, HFF = 70 Hz, notch off.
intracranial pressure) to rule out possible seizures as the underlying cause. had an incidence of approximately 20%, including brain tumors, recent
CEEG is also necessary for the management of anesthetic coma, especially neurosurgery, hypoxic-ischemic encephalopathy, subarachnoid hemorrhage,
when being used to treat seizures or elevated intracranial pressures. Lastly, traumatic brain injury, toxic-metabolic encephalopathy, and unexplained
CEEG can be used to detect ischemia or other deteriorations of cerebral decrease in consciousness. Intracerebral hemorrhages (ICHs) and ischemic
functions in patients with limited neurological exams. strokes had a lower incidence of seizures on CEEG, 13% and 11%, respec-
Certain diagnoses are more commonly associated with seizures. In a series tively. Other factors that have been associated with a higher risk of NCSz
of 570 consecutive patients undergoing CEEG for the detection of subclini- include the following: hippus, remote history brain injury (stroke, traumatic
cal seizures or to investigate the cause of unexplained decrease in level of brain injury), epileptiform discharges on EEG, burst-suppression pattern on
consciousness, the incidence of seizures was highest in patients with a his- EEG, nystagmus, unexplained eye deviation, coma, younger age, and clini-
tory of epilepsy (33%) and CNS infection (29%) (68). Most other diagnoses cal seizure prior to initiation of EEG.
Figure 17.17: Impact of stimulation on gener-

alized rhythmic delta activity (GRDA, reactive).
A 20-year-old patient with brief cardiac arrest.
EEG showed rhythmic delta activity with a fron-
tal predominance. With stimulation (arrow), this
activity subsides as shown on the right side of
this page, and is thus a reactive EEG. LFF =
1 Hz, HFF = 70 Hz, notch off.
In neonates, factors that have been associated with increased risk for pro- The duration of CEEG recording is highly variable and depends on
longed subtle or nonconvulsive seizures on EEG include Apgar less than or the clinical circumstances and the initial findings on CEEG. For seizure
equal to 5 at 5 minutes, umbilical cord or blood pH less than 7.2 during first detection, routine EEGs, even when repeated, clearly miss a substantial
hour of life, CNS infection, symptomatic sepsis, congenital cerebral abnor- portion of seizures in critically ill patients (72), and CEEG significantly
malities, grade III or IV intraventricular hemorrhage, encephalopathy, clinical increases the detection rate of nonconvulsive seizures and nonconvulsive
seizures or suspected seizures, apnea of unknown etiology, and use of paralytic status epilepticus (73). In a series of 110 patients who had seizures during
agents (summarized from [34]). Of note, in neonates, the use of EEG is partic- CEEG (68), factors that predicted time to first seizure included whether
ularly important as the majority of seizures recorded on EEG have no clinical the patient was comatose or not and whether or not PEDs were pres-
correlate, possibly as high as 80% to 90% (69,70), and even clinical seizures can ent. Slightly greater than 50% of seizures were detected in the first hour
be difficult to distinguish from non-seizures, even by trained observers (71). of CEEG (Fig. 17.24). For non-comatose patients, 95% had their first
TABLE 17.3 ACNS Guidelines for Description of Periodic Patterns TABLE 17.4 Criteria for Nonconvulsive Seizures
Main 1. Generalized (G)—bilateral, bisynchronous, and symmet- Primary Criteria

Term 1 ric. Specify predominance (anterior, posterior, midline, or 1. Repetitive generalized or focal epileptiform discharges at a rate
generalized) of 3 Hz
2. Lateralized (L)—includes unilateral, bilateral synchronous 2. Repetitive generalized or focal epileptiform discharges at a rate of 3
but asymmetric, focal, regional, and hemispheric patterns. Hz and the secondary criterion
Specify unilateral vs. bilateral asymmetric. Specify lobes 3. Sequential rhythmic, periodic, or quasiperiodic waves at 1 Hz and
3. Bilateral independent (BI)—two independent unequivocal evolution in frequency (gradually increasing or decreasing
[asynchronous] lateralized patterns, one in each by at least 1 Hz), morphology, or spatial extent. Excludes evolution in
hemisphere. Specify symmetric vs. asymmetric amplitude alone or change in sharpness alone
4. Multifocal (Mf)—three or more independent [asynchronous] Secondary Criterion
lateralized patterns with at least one in each hemisphere
1. Significant improvement in clinical state or appearance of previously
Main 1. Periodic discharges (PD)—periodic refers to a repeating absent normal EEG patterns in response to acute administration of a
Term 2 waveform with a quantifiable interdischarge interval and rapid-acting AED, such as a benzodiazepine
recurrence at nearly regular intervals. Discharge is a wave-
form with no more than three phases or a waveform lasting Definition of Evolution
0.5 s regardless of number of phases 1. Frequency: at least two consecutive changes in the same direction by
2. Rhythmic delta activity (RDA)—repetition of a waveform at least 0.5/s, e.g., from 2 to 2.5 to 3/s, or from 3 to 2 to 1.5/s
with relatively uniform morphology and duration, without 2. Morphology: at least two consecutive changes to a novel morphology
an interval between consecutive waveforms. For RDA, 3. Location: sequential spreading into or sequentially out of at least two
frequency 4 Hz. different standard 10–20 electrode locations
3. Spike-and-wave or sharp-and-wave (SW)—polyspike, In order to qualify as present, a single frequency or location must persist for
spike, or sharp wave with a slow wave occurring in at least three cycles. The criteria for evolution must be reached without
regularly repeating pattern with no interval in between. If the pattern remaining unchanged in frequency, morphology, or location
there is an interval, it would be classified as a PD. for 5 min
Modifiers 1. Prevalence
2. Duration It is important to note that these are criteria for definite NCSzs. If a pattern does not
3. Frequency—specify typical and range fulfill these criteria, it does not mean that NCSzs have been ruled out; it only means that
4. Number of phases NCSzs cannot be ruled in definitively.
5. Sharpness Based on Chong DJ, Hirsch LJ. Which EEG patterns warrant treatment in the critically ill?
6. Amplitude—specify in standard longitudinal bipolar Reviewing the evidence for treatment of periodic epileptiform discharges and related
montage using 10–20 recording patterns. J Clin Neurophysiol 2005;22(2):79–91.
7. Polarity
8. Stimulus-induced
9. Evolving or fluctuating
10. Plus—refers to features that suggest that a periodic pattern seizure within 24 hours of recording, but only 80% of comatose patients
may be more ictal. “F” applies to both PDs and RDAs and did. After 48 hours, these numbers were 98% for non-comatose patients
indicates superimposed fast activity. “R” applies to PDs and 87% for comatose patients. Thus, for non-comatose patients, even
only and indicates superimposed rhythmic delta activity.
2 days of CEEG recording may not capture all seizures, although the clini-
“S” applies to RDA only and indicates superimposed sharp
waves or spikes or sharp-contoured activity
cal significance of such seizures is uncertain. Similar results were found
in critically ill children, with 52% of seizures noted in the first hour, 87%
Adapted from Hirsch LJ, et al. American Clinical Neurophysiology Society’s standardized noted in the first 24 hours, and 93% within 48 hours (Fig. 17.24) (74). Some
critical care EEG terminology: 2012 version. J Clin Neurophysiol 2013;30(1):1–27. recent studies have suggested that the initial background pattern on CEEG
Figure 17.18: Example of seizure terminating

with lateralized periodic discharges (LPDs) in a
45-year-old man with left parietal hemorrhage.
Background EEG showed periodic discharges at
P3/T5 and intermittent electrographic seizures
over the left hemisphere. This panel shows the
termination of a seizure with return of periodic
discharges. LFF = 1 Hz, HFF = 70 Hz, notch off.
is highly predictive of whether or not a patient will have seizures. In a ret- with seizures in [76]), possibly leading to an underestimation of seizures in
rospective study of 242 consecutive patients undergoing CEEG, only 3% of this group. Based on such work, it may be reasonable to terminate CEEG
the 110 patients who did not have epileptiform abnormalities on their initial quickly when the baseline study reveals a normal background, diffuse slow-
30-minute screening EEG later went on to have seizures (75). In another ing, or pattern suggestive of metabolic encephalopathy, such as triphasic
series of 243 consecutive patients undergoing CEEG, no patients with dif- waves, especially with limited resources and other patients who may be at
fuse slowing or triphasic waves on their initial EEG went on to have sei- higher risk of nonconvulsive seizures. In situations where the purpose of
zures (76). However, although all patients in both studies were recorded CEEG is not purely seizure detection, but instead monitoring neurological
for a minimum of 18 to 24 hours, patients with more benign initial EEGs function to detect changes (e.g., monitoring for delayed ischemia in patients
were likely to be disconnected from the EEG earlier (e.g., median dura- with subarachnoid hemorrhages), clinical circumstances dictate the dura-
tion of recording of 1 day for those without seizures vs. 4 days for those tion of recording.
Figure 17.19: A 78-year-old man with a remote

history of a left-sided subdural hemorrhage who
presented with persistent change in mental sta-
tus. The routine EEG is shown on a compressed
time scale at the top. The Fourier Transform
of the EEG signal is shown as a DSA at the
bottom (left hemisphere on top, right hemi-
sphere on bottom). For the DSA, the vertical
axis represents frequency (0 to 20 Hz) and the
horizontal axis represents time. The colors rep-
resent power. Two electrographic seizures are
present—arrow indicates the onset of the first
one, and the location of the raw EEG sample
above. The onset is associated with an increase
in power at all frequencies, but especially at low
frequencies, less than 5 Hz, mainly on the left
but with some spread to the right.
The true utility of CEEG, that is, its impact on outcome in critically the fact that during this period when CEEG was becoming widely used
ill patients, is somewhat uncertain. As discussed in the coming sections, at their institution, there was an improvement in outcome (as measured
CEEG is clearly useful for detecting nonconvulsive seizures in critically ill by Glasgow Outcome Scale), with decreased overall cost of hospitaliza-
patients, detecting ongoing seizure activity after treatment of convulsive tion and decreased length of stay, although, admittedly, no other factors
seizures, and potentially for detecting additional cerebral injury in patients that may have changed during this time period were accounted for. Fur-
with different forms of preexisting neuronal insults (e.g., traumatic brain thermore, in their estimation, the cost of CEEG comprised only 1% of
injury (TBI), stroke, etc.). However, the actual impact of CEEG on out- the overall cost of the hospitalization. In another retrospective analysis
come in such patients is less certain. The data acquired by CEEG clearly of 300 consecutive CEEG studies, the findings led to a change in antiepi-
impacts decision-making: in one early study, CEEG in the neurological leptic drug prescribing in 52% of the cases: 14% had initiation of therapy,
ICU had a decisive or contributing impact on medical decision-making in 33% had modification of therapy, and 5% had discontinuation of therapy
82% of patients (11). In a series of 300 consecutive patients who under- (78). Detection of electrographic seizures led to a change in antiepileptic
went CEEG monitoring for various indications between 1993 and 1997, drug therapy in 28% of the studies. In a prospective series of 100 critically
Vespa et al. (77) reported an impact on clinical decision-making in greater ill children, CEEG led to specific changes in clinical management in 59
than 90%. They also argued that clinical efficacy was demonstrated by (79). In a continuation of the same prospective series with 200 critically
Figure 17.20: A 63-year-old man with prior

right parieto-occipital stroke with seizures at
that time. He presented 6 years later with focal
motor seizures involving the left arm and leg.
He continued to have episodes of confusion in
spite of being on levetiracetam and phenytoin.
These seizures are clearly seen on all three
QEEG tools shown—DSA at the top, followed
by amplitude-integrated EEG (aEEG), followed
by the rhythmicity spectrogram. Samples of ictal
and interictal EEG are shown later. While these
seizures are easy to recognize on the raw EEG,
the QEEG tools would permit identification of
seizures by a nonexpert and would permit rapid
identification of all seizures in a prolonged
recording.
ill children, only the 43 patients with electrographic status epilepticus CLINICAL APPLICATIONS, STATUS EPILEPTICUS
had a significantly increased risk of mortality (odd ratio 5.1) or pediatric
cerebral performance category worsening (odds ratio 17.3), whereas the Both GCSE and NCSE are fairly common after acute brain injuries from
41 patients with electrographic seizures had no significant increased risk different etiologies, including trauma, intracranial hemorrhage, cerebral
for either (odds ratios of 1.3 and 1.2, respectively) (80). Intuitively, it cer- ischemia, hypoxia/anoxia, metabolic, and toxic causes. The utility of EEG
tainly makes sense that knowledge and potential treatment of seizures that in managing convulsive status epilepticus is well established; in fact, it is
would otherwise go unnoticed or warning of impending cerebral injury mandatory for management of refractory status epilepticus according to the
should improve outcome. However, actually demonstrating this in a het- Neurocritical Care Society and others. When generalized convulsive status
erogeneous, critically ill population is difficult and has not been done in a epilepticus has been partially treated or has been going on for a prolonged
controlled fashion. period, the clinical signs may be subtle. Up to 20% of patients continue to
Figure 17.21: An 86-year-old woman with a

history of multiple ischemic strokes and a prior
cerebellar hemorrhage who presented with
multiple seizures and was intubated for respira-
tory distress. QEEG is shown at the top and the
raw EEG (at the vertical line) during a subtle sei-
zure from the left temporal lobe is shown in the
bottom. Even these subtle seizures have a clear
signature on two of the QEEG tools displayed,
rhythmicity spectrogram (top) and DSA (mid-
dle). This permits the easy identification of five
seizures during the epoch displayed. However,
note that the aEEG tool does not show these
seizures clearly.
have nonconvulsive seizures and NCSE after the clinical GCSE has sub- and outcome. However, the occurrence of NCSE after GCSE may indepen-
sided (6,7). If both nonconvulsive seizures without status epilepticus and dently increase the odds of mortality and poor outcome; the occurrence
NCSE are included, as many as 48% of patients continued to have seizure of nonconvulsive seizures did not. Because much of this seizure activity is
activity in the 24 hours after cessation of clinical seizure activity (7). Mor- without obvious clinical correlate, an EEG is necessary in this situation to
tality and chance of poor outcome are significantly higher for patients with evaluate for ongoing seizures. Such ongoing seizures and NCSE warrant
ongoing ictal activity compared with those where GCSE truly subsided. For treatment.
the group without ongoing ictal activity, mortality was 13% and poor out- NCSE is also being increasingly recognized as a common occurrence in
come was 20%; for patients with NCSE, these percentages were 51% and patients with acute neurological insults or unexplained change in mental
58%, respectively; for patients with ongoing seizure activity, but not NCSE, status. Because of the difficulty in making this diagnosis without EEG,
the percentages were 32% and 46%, respectively. Owing to the size and het- diagnosis is often delayed (81). For example, in patients with subarach-
erogeneity of the population in this study, multivariate analysis was difficult noid hemorrhages, in one series of 233 patients, where only a subset of the
but did suggest that age and etiology were important predictors of mortality 101 patients who had stupor/coma underwent CEEG monitoring, 8 were
Figure 17.22: A 65-year-old man with history

of right parietal glioblastomamultiforme who
had persistent change in mental status after
partial resection of the tumor. QEEG is shown
at the top along with samples of interictal and
ictal EEG during a seizure from the right pari-
etal region at the bottom. This seizure is most
clearly seen on the aEEG from the right side
(middle panel of QEEG) and much less appar-
ent on the DSA or rhythmicity spectrogram.
found to be in nonconvulsive status epilepticus (82), giving a rate of 4% to treat/control, and most patients were transitioned to comfort care and
for patients with stupor/coma and subarachnoid hemorrhage (SAH). The expired in the hospital.
diagnosis of NCSE was made an average of 18 days after the SAH (range CEEG is necessary to guide the treatment of refractory status epilepticus
5 to 38 days). In another series of 389 consecutive patients with SAH, 3% of all kinds. As mentioned previously, without CEEG, it is very possible that
were found to have nonconvulsive status epilepticus, on average 10 days undertreatment may occur, that is, electrographic seizure activity persists
after the bleed (range 2 to 20 days) (83). However, for both series, this likely even though clinical seizure activity has subsided. This is especially the case
represents an underestimation, as only patients where there was a clinical when sedatives or neuromuscular junction blocking agents are being used.
suspicion for seizures underwent continuous EEG monitoring. In both Thus, CEEG monitoring is necessary to alert the treating team if the seizure
series, the patients with NCSE tended to be older and had higher Hunt does not stop. In addition, CEEG guides the dosing of anesthetic agents as
and Hess or Fisher grades. Furthermore, the NCSE was extremely difficult clinical signs of efficacy are lacking. The continuous or intermittent infusion
Figure 17.23: A 59-year-old man with coronary

artery disease who was found unresponsive at
home. MRI brain showed T2 hyperintensities in
the cerebellum and bilateral occipital head re-
gions. He had persistent change in mental sta-
tus with some fluctuations. EEG on hospital day
3 showed frequent electrographic seizures from
the right posterior temporal/occipital region.
EEG during one of these seizures is shown at
the bottom. QEEG trends are shown at the top.
These seizures are apparent on the aEEG and
rhythmicity spectrogram from the right hemi-
sphere but not on the DSA.
of agents such as propofol, midazolam, or pentobarbital is adjusted on the CLINICAL APPLICATIONS, NONCONVULSIVE SEIZURES
basis of CEEG to obtain either a desired level of burst suppression or at
least seizure cessation. Overtreatment, with associated cardiovascular or Seizures are a common occurrence in the neurological ICU setting (see
respiratory compromise, is possible without CEEG monitoring. Fig. 17.2). Early series of continuous EEG monitoring revealed a very high
In critically ill patients, the appropriate treatment of NCSE depends on prevalence of seizures, up to 34% (11), with a substantial proportion (76%)
many factors. Deciding on the appropriate treatment and even whether or exhibiting NCSE. Furthermore, there was recognition that most of these
not treatment should be undertaken requires integrating many clinical fac- seizures were nonconvulsive, that is, without clear clinical signs other than
tors. These include the underlying etiology and prognosis, the likelihood of change in mental status. Thus, without the use of EEG, they would go unrec-
response to treatment, the morbidity of the treatment, and others. In spe- ognized. In the pediatric population, the incidence may be even higher (see
cific clinical situations, these factors can combine in multiple ways to dictate Fig. 17.2). In a series of 100 critically ill children with acute encephalopathy,
the appropriateness of a particular intervention (84). 46% had seizures and/or status epilepticus, 19% had nonconvulsive status
100
TABLE 17.5 Indications for Continuous EEG Monitoring
I. Detection of subclinical seizures
Patients seizures detected (%)

a. Fluctuating mental status 75
b. Unexplained alteration of mental status
c. Acute supratentorial brain injury with altered mental status
d. After convulsive status epilepticus
II. Characterization of spells 50
a. Episodic posturing, other paroxysmal or repetitive movements Adults
b. Subtle twitching, nystagmus, eye deviation, chewing Children
c. Paroxysmal autonomic spells, including tachycardia
25
III. Assessment of level of sedation and following trends
IV. Management of burst suppression and anesthetic coma
V. Detection of ischemia
0
a. After subarachnoid hemorrhage Start of <1 <6 <12 <24 <48 <72 <168 >168
b. During and after vascular neurosurgical or interventional CEEG
neuroradiology procedures Duration of CEEG (h)
c. In patients with hemodynamic lesions and borderline flow
Figure 17.24: Time to detect first seizure in critically ill adults (Data from Claas-
d. In other patients at risk for in-hospital acute ischemia
sen J, et al. Detection of electrographic seizures with continuous EEG monitoring
VI. Prognostication in critically ill patients. Neurology 2004;62[10]:1743–1748.) and children. Vertical
axis represents cumulative percentage of all patients in whom a seizure was de-
tected. (Data from Abend NS, et al. Nonconvulsive seizures are common in criti-
cally ill children. Neurology 2011;76[12]:1071–1077.)
epilepticus (74). Furthermore, of the 46 children with seizures, 32 had only

nonconvulsive seizures. In a prospective series of 100 critically ill children
(aged 2 months to 17 years) who had a suppressed level of consciousness of clinical seizures ranges from 5% to 17% (86,87). Incidence is higher for
(GCS < 8) for any reason, seizures were found in only 7 patients, of whom 6 larger strokes and cardioembolic strokes. Additionally, incidence is higher
had a history of epilepsy and had witnessed seizures prior to the CEEG (85). in hospital-based studies compared with population- or community-based
All seizures were recorded within the first 3 hours of the CEEG. The reasons studies. Not surprisingly, the incidence of nonconvulsive seizures is signifi-
for the low incidence and early detection of seizures in this series are unclear, cantly higher. In 57 consecutive patients admitted to the ICU with a stroke,
although it may partially relate to the fact that patients did not necessarily 26% had nonconvulsive seizures (8). However, the incidence was substan-
have a neurological diagnosis, just suppressed level of consciousness. Also, tially lower in another study, only 6% (3 of 46 patients) (12).
CEEG was only performed for a median of 20 hours. CEEG was helpful in For hemorrhagic strokes, the reported incidence of early clinical seizures
ruling out epileptic seizures in 14/18 patients suspected of having seizures by ranges from 4.3% to 12% (88–90); however, in studies where hemorrhagic
the ICU team. and ischemic strokes are compared directly, the risk of seizures is sig-
Certain specific clinical situations are commonly associated with noncon- nificantly higher for hemorrhagic strokes, by approximately a factor of 2
vulsive seizures in critically ill patients. After ischemic strokes, the incidence (90,91). Factors such as location of bleeds (cortical > subcortical), mental
status (confused > normal), etiology (vascular malformation > spontane- As mentioned previously, such seizures are often associated with poorer
ous) may have predictive value in determining patients at higher risk for outcome (110,111).
seizures. The incidence of nonconvulsive seizures, using CEEG for detec-
tion, is substantially higher, 28% (18 of 63 patients) (12). In the same study Clinical Relevance of NCS in Critically Ill Patients
of patients with nontraumatic ICH, nonconvulsive seizures were associated
with neurologic worsening as measured by the NIH stroke scale and increase An issue that comes up frequently in any discussion of seizures in the ICU is
in midline shift on imaging compared with a control group with the same the relevance of finding/treating such seizures in critically ill patients. Both
size hemorrhages but no NCSz. There was a trend toward an increase in clinical and experimental data suggest that seizure activity has the potential
poor outcome in the patients with nonconvulsive seizures. In another study for further injuring a brain that may already be injured. In experimental sta-
of patients with ICH, the incidence of seizure was 31% (32 of 102 patients); tus epilepticus in rats, seizure activity without motor convulsions is associ-
over half of these were nonconvulsive (92). Clinical seizures are a common ated with increases in cerebral blood flow and necrosis of neurons (112,113).
occurrence in patients with SAH. Estimates of clinical seizures in patients Furthermore, NCSE of approximately 90-minutes duration, elicited in adult
with SAH generally range from 3% to 5% (93–97), although reported esti- rats by pilocarpine after LiCl pretreatment, led to persistent motor deficits
mates were significantly higher in older studies (98). and disturbances in social behavior 2 months after the NCSE (114). In a rat
TBI is another clinical scenario where the incidence of clinical and model of large strokes (middle cerebral artery occlusion), the occurrence
subclinical seizures is high. The incidence of early clinical posttraumatic of nonconvulsive seizures following the injury was associated with larger
seizures ranges from 2.1% to approximately 10% (99–102). All studies dem- infarct size and increased mortality (115). Antiepileptic drugs that reduced
onstrate an increasing incidence of clinical seizures with increasing severity the number of nonconvulsive seizures reduced mortality.
of head injury, usually defined by degree of cerebral injury as manifested In humans, there is some suggestion that nonconvulsive seizures might
by focal neurologic deficits or duration of loss of consciousness or amne- increase neuronal injury and worsen outcome. In many studies, the pres-
sia, climbing as high as 15% with the most severe injuries. This incidence ence of seizures in critically ill patients has been associated with poorer
is generally highest in the first few days after the injury. When CEEG was outcomes, even when attempts are made to control for other factors, such
applied to 94 consecutive patients with moderate to severe TBI (defined as as severity of injury or comorbidities (52,110,111,116–118). In patients
GCS ≤12), seizures occurred in 21 patients (22%), six of whom had status with ICH and seizures, seizures were associated with increased mass effect
epilepticus (103). More than half (52%) had only nonconvulsive seizures. and shift on head CT, even after accounting for the size of the bleed (12).
The group with seizures had a higher mortality, even though there were no Although not significant, there was a trend toward poorer outcome in
obvious clinical features that distinguished the two groups (e.g., presence of patients with seizures.
early hypoxemia or hypotension or initial GCS). The incidence of seizures In patients with TBIs, there are also data to suggest that seizures poten-
was 33% (23 out of 70 patients) in nonconsecutive patients with TBI admit- tially cause additional injury and long-term negative consequences. Non-
ted to an ICU (104). convulsive seizures and NCSE in TBI patients are associated with increases
In the pediatric population, the incidence of seizures may be significantly in intracranial pressure and lactate/pyruvate ratio (both acutely during sei-
higher, although data is still limited. In a series of 117 monitored children, zures and persistently for several days after cessation of seizures [119]). In
44% had seizures and 39% had nonconvulsive seizures (105). In 115 consecu- another study, TBI patients with repeated nonconvulsive seizures or non-
tive pediatric patients (>1 month old) who underwent CEEG recording, 27% convulsive status epilepticus demonstrated hippocampal atrophy, especially
had seizures; however, only patients felt to be at significant risk for seizures ipsilateral to the side of seizures, compared with matched TBI patients
were monitored (106). In another series of 100 children undergoing CEEG, who did not have seizures (120). This suggests potential long-term changes
seizures occurred in 46% and were exclusively nonconvulsive in 32% (74). induced in the brain of TBI patients by added insult of nonconvulsive sei-
In neonates with perinatal asphyxia or hypoxic-ischemic encephalopa- zures. Neuronal specific enolase (NSE), a biomarker for neuronal injury,
thy (HIE), electrographic seizures or status epilepticus occur in a large is increased in critically ill patients with NCSE or NCS compared to those
fraction, a substantial number of which are nonconvulsive (18,74,107–109). without seizures (121).
In 24 patients with nonconvulsive seizures (most with NCSE) who had a background that is being modulated by the environment and the patient’s
poor outcomes, Jordan (11) judged that 58% had an underlying cause that state. Thus, studies looking for DCI have relied on quantitative EEG trends.
could explain the poor outcome; however, in 33% the underlying disease The specific trends that have been found most useful have included total
was judged as not being of sufficient severity to entirely explain the poor power (from 1 to 30 Hz) (96), variability in relative alpha power (variability
outcome, suggesting that the nonconvulsive seizures may have contributed. in power from 6 to 14 Hz, normalized to total power from 1 to 20 Hz) (95),
Another finding that suggests that NCSE is harmful is that seizure duration alpha/delta ratio, and a composite alpha index (product of standard devia-
and time to diagnosis are predictors of outcome, independent of etiology tion and average of the power from 8 to 15 Hz over the anterior quadrants)
(52). If diagnosis occurred in less than 30 minutes from onset, mortality was (123). Vespa et al. (95) were able to detect changes up to 2.9 days prior to
36%; by means of comparison, mortality was 75% if the delay to diagnosis clinical deterioration. In the last study, even though the sensitivity of the
was greater than 24 hours. If duration of NCSE was less than 10 hours, composite alpha index was only 67% for predicting clinical deterioration, in
60% of patients were discharged to home and 10% died; for NCSE duration 3/12 patients, it was able to make the prediction greater than 24 hours before
greater than 20 hours, no patients were discharged to home and 85% died. clinical change. Claassen et al. (59) demonstrated the potential for detecting
CEEG monitoring has recently been extended to patients in medical ICUs DCI (due to vasospasm) in patients with poor-grade SAH (Figs. 17.25 and
without a known underlying neurological insult. In 201 consecutive patients, 17.26). Although several quantitative EEG parameters were analyzed, the
60% of whom had sepsis and 48% of whom were comatose, the incidence best was the trend in the alpha/delta power ratio following an alerting stimu-
of electrographic seizures was 10%, and the combined incidence of electro- lus, which showed a median decrease of 24% in patients with DCI compared
graphic seizures and/or PEDs was 17% (116). Approximately two-thirds of with only 3% in those without. Useful thresholds were a drop of greater
the seizures were nonconvulsive. Sepsis was the only significant predictor than 10% on 6 consecutive recordings (sensitivity 100%, specificity 76%)
of seizure activity, with an odds ratio of 4.6 (95% confidence interval 1.9 to or greater than 50% on one recording (sensitivity 89%, specificity 84%).
12.7). The presence of electrographic seizures or PEDs was a strong predic- Another small study used a derived parameter, the composite alpha index
tor of death or severe disability (odd ratio 19.1, 95% confidence interval 6.3 (CAI), to improve prediction of DCI (123). The CAI was calculated as the
to 74.6), even after controlling for other known determinants of outcome product of the mean and standard deviation of the power in the alpha fre-
(age, coma, renal or hepatic failure, and circulatory shock). quency range for each 30-second sample, calculated over 30 minutes. Data
from the electrode pairs covering the left and right anterior regions were
CLINICAL APPLICATIONS, ISCHEMIA combined. This tool was shown to significantly improve the ability to predict
both DCI (from 40% to 67%) and clinical improvement (from 8% to 50%)
Because EEG activity is quite sensitive to changes in cerebral perfusion, when combined with clinical data, compared with clinical data alone. Of
CEEG monitoring has the potential for being used as a tool to detect cere- note, significant attention was required for obtaining artifact-free s egments
bral ischemia in critically ill patients. There are several intriguing examples of data in order to perform this analysis.
demonstrating the possible use of CEEG to detect ischemia at a reversible
stage. Early examples from intraoperative monitoring during carotid endar-
terectomy demonstrated the utility of EEG to detect ischemia in the internal CLINICAL APPLICATIONS, ANOXIC BRAIN
cerebral artery territory at a stage where it could be reversed with increas- INJURY AND HYPOTHERMIA
ing mean arterial pressure (122). In patients with ischemic or hemorrhagic
strokes, the EEG (in this case total power in the band from 3.5 to 20.7 Hz) Routine EEGs have long been used in patients with anoxic or hypoxic events,
can reflect drops in cerebral perfusion pressure (61). especially cardiac arrest, for prognosis as well as diagnosis of myoclonic
Most recent demonstrations of using CEEG to detect ischemia have jerks and epileptic seizures. Nonconvulsive seizures are fairly common in
been in patients at risk for delayed cerebral ischemia (DCI) secondary to patients with anoxic injury, with reported prevalence ranging from 20% to
vasospasm after a SAH. However, looking for subtle changes in the back- 53% (68,75), although many seizures in this population are associated with
ground over hours/days can be difficult, especially when superimposed on myoclonic jerks or other clinical activity. For prognostic purposes, a routine
EEG performed at least 12 to 24 hours after return of spontaneous circula-

Left tion has typically been used for prognostication, with burst suppression or
anterior
0.5 severe suppression being highly predictive of poor outcome (124).
(F3-C3)
Therapeutic hypothermia (TH) is an increasingly utilized treatment for
anoxic injury. Cooling of the core body temperature to approximately 32°C
to 4°C is achieved by various external or internal means; neuromuscular
Right blockade or other pharmacological manipulations are sometimes needed to
anterior 0.5 maintain hypothermia. CEEG monitoring is often a part of these protocols.
(F4-C4)
Because of the need for neuromuscular blockade in many of these cases,
CEEG is especially needed to diagnose seizures (Fig. 17.27). The incidence
of seizures during and immediately following TH ranged from 9% to 23% in
Left 1.0 retrospective series of adult patients (125–127). The use of neuromuscular
posterior blockade during TH in this study meant that the seizures could be diagnosed
(P3-O1)
only on CEEG. In a series of 19 pediatric patients undergoing TH after car-
diac arrest, the incidence of seizures was significantly higher at 47%, with
32% in status epilepticus (109). Two-thirds of these patients had purely non-
Right 1.0 convulsive seizures. In both adult and pediatric populations undergoing TH,
posterior
(P4-O2) seizures can occur both during hypothermia and after rewarming. Thus, it
is important to monitor these both during TH and for a period of time
after rewarming (typically 24 hours). The presence of seizures (126,128) or
14
SIRPIDs (128) in patients undergoing TH after cardiac arrest is associated
EEG 1
GCS 7 with poor outcome, although, these may be a reflection of the severity of
EEG 2 the injury.
In addition to detecting seizures, CEEG contributes to making prognostic
Hour 10 12 14 16 18 20 12 14 16 18 20 22 24 6 8 determinations in patients undergoing TH after cardiac arrest (Fig. 17.28).
SAH day 6 7 8 However, it is not clear that it does so in any way significantly different from
a routine EEG. In children, for example, Kessler et al. (129) classified the
Neurological exam: CT: Angiography: right CT: background EEG into three grades: grade 1 for continuous and reactive,
decreased level of right internal MCA vasospasm, widespread
consciousness capsule and infusion of infarction grade 2 for continuous but nonreactive, and grade 3 for discontinuous, burst
with left arm drift hypothalamus Papaverine and suppression, or lack of cerebral activity. A grade 2 or 3 EEG had a positive
and dysarthria infarction Verapamil predictive value for an unfavorable outcome of 88% (CI 77% to 98%) if it
occurred during hypothermia, and 91% (CI 81% to 100%) if it occurred
Figure 17.25: Illustration of detection of DCI in a patient with SAH. The alpha/delta after return to normothermia. Similar findings have been reported in adults
ratio was calculated every 15 minutes. The figure illustrates the ADR over different (126,130,131). In adults (age 16 years), an EEG that was nonreactive or
head regions along with Glasgow coma scale for days 6 to 8 after presentation for
showed burst suppression was never seen in patients who were alive at 2
Hunt and Hess grade IV SAH due to right posterior communicating artery aneurysm,
which was clipped on day 2. The alpha/delta ratio progressively declined on right
months, giving a positive predictive value for mortality of 100% and nega-
starting on day 6, well before any detectable clinical change (GCS). Angiography on tive predictive value of 83%. A reactive EEG was actually a better predictor
day 7 confirmed right middle cerebral artery vasospasm. In spite of treatment with of survival at 30 days than the lack of bilaterally absent median nerve SSEPs
papaverine and verapamil (with transient improvement in the alpha/delta ratio), the (0.83 vs. 0.70), even though the SSEP did have the same 100% positive pre-
patient continued to worsen clinically and died on day 9. (With permission from dictive value for mortality (131). The presence of epileptiform discharges of
Claassen J, et al. Quantitative continuous EEG for detecting DCI in patients with
poor-grade subarachnoid hemorrhage. Clin Neurophysiol 2004;115[12]:2699–2710.)
Figure 17.26: Example of detecting DCI after SAH with scalp and intracranial EEG. The main panel shows 16 hours of QEEG in a 70-year-old woman s/p Hunt and Hess
grade III–IV SAH. Samples of the scalp and intracranial EEG recorded at different time points (A, B, C, D) are shown in the corresponding panels. During this time period,
the patient developed sepsis, bilateral vasospasm, and bilateral infarcts. The top four panels are based on scalp EEG; with the two panels showing the spectrogram for the
left and right hemisphere and the next panel absolute and relative asymmetry indices from the scalp electrodes as well. The bottom four panels are based on intracranial
EEG recorded from a miniature, eight-contact, cortical mini-depth electrode placed in the right frontal lobe (see scout x-rays in panel E). On the scalp EEG, major changes
are not apparent until the second half of the recording, when asymmetry increased and the suppression ratio eventually rises. On the depth QEEG tracings, changes can
be seen much earlier and more clearly, both in the QEEG and in the sample tracings. The QEEG tracings based on the intracranial depth triggered automatic alarms: drop
in total power in the depth (labeled “depth power alarm”), rise in suppression ratio (labeled “depth suppression ratio alarm”). By the second half of this time period, the
depth EEG pattern is nearly flat. The patient developed bilateral anterior and left middle cerebral artery infarcts with rising intracranial pressures. She died 2 to 3 days later.
A: EEG at point A: diffuse slowing in scalp EEG, continuous epileptiform activity in the depth EEG. B: EEG at point B: diffuse slowing and attenuation on the scalp and burst
suppression in the depth EEG. C: EEG at point C: depth EEG recording is now flat, and scalp EEG shows some muscle artifact and diffuse attenuation. D: EEG at point D:
scalp and depth recordings are now flat. E: skull x-ray (scout views from a CT scan) showing the eight-contact depth electrode in the right frontal lobe with a ventricular
catheter next to it. F: CT scan before vasospasm and infarcts; artifact in the right frontal lobe is due to the ventricular catheter and electrode. G: CT scan after vasospasm and
infarcts, showing bilateral infarcts, worse on left. (With permission from Hirsch LJ, Brenner RP. Atlas of EEG in critical care. West Sussex, UK: John Wiley & Sons, 2010:334.)
A
584
C

585
E F

any type is significantly associated with poor outcome (42,132); however, status and other physiological parameters. Multimodal brain monitoring
there is a false positive rate of 0.09 (95% confidence interval 0.02 to 0.21). has been applied combining techniques such as CEEG, intracranial pres-
Unlike prognostication after cardiac arrest in patients who did not receive sure, cerebral blood flow, transcranial Dopplers, tissue oxygen tension, and
TH, incomplete recovery of brainstem reflexes (pupillary, oculocephalic, intracerebral microdialysis monitoring (133). The addition of cardiac and
and corneal) or absent/extensor motor responses may have a nonzero false other parameters, especially if all are collected in a time-locked fashion so
positive rate in the setting of TH, that is, some patients who had absent that different modalities can be correlated with each other, may permit addi-
reflexes or poor motor responses showed recovery (132). tional clinical insights into critically ill patients (134). An example of such
monitoring is shown in Fig. 17.29. However, the process for collecting and
MULTIMODAL BRAIN MONITORING analyzing such a complicated data set is daunting and the clinical utility
remains to be investigated (135).
Although CEEG by itself can provide significant information about seizures Another novel technique extending the scope of CEEG is the use of
and neuronal functioning in critically ill patients, additional information may intracortical EEG (ICE) in patients with neurological injury to detect elec-
be gained by combining EEG with other modalities to monitor neurological trographic seizures (136). By using an eight-contact mini-depth electrode,
Figure 17.27: EEG during and after hypothermia protocol for cardiac arrest in a 72-year-old patient with car-
diomyopathy who had a prolonged cardiac arrest (>30 minutes). A: Initial EEG (during hypothermia with core
temperature of 34°C) showing diffuse suppression of cerebral activity. B: During rewarming, the EEG showed
GPDs with a central predominance. C: Intermittently, these discharges evolved into electrographic seizures.
A 16-second seizure is shown. There were no clinical signs during this seizure. LFF = 1 Hz, HFF = 70 Hz,
notch off.
Waziri et al. (136) were able to detect clinically relevant findings in 12/14 from scalp EEG recordings (137). Such findings suggest that intracranial
patients, including electrographic seizures that were not apparent on scalp multimodal monitoring may have a future role in monitoring the neuro-
EEG. Furthermore, in two patients, ICE demonstrated attenuation of logical status and function of patients in neurocritical care units; however,
activity at least 2 hours before other modalities and more than 8 hours the risks, benefits, and potential applications have not been established,
before clinical deterioration. The alpha/delta ratio calculated from ICE and the techniques are not widely available yet (138). In addition, there
electrodes placed in poor-grade SAH patients showed a significant decline are several published examples of nonconvulsive seizures recorded with
(>25% for >4 hours) 1 to 3 days prior to angiographic confirmation of intracranial electrodes that are not apparent on simultaneously recorded
vasospasm, which was superior to this and other parameters calculated scalp EEG (Fig. 17.30).
Intracranial recordings have also been used to demonstrate and explore metabolic demand in tissue already with borderline function; this places the
the phenomenon of spreading depolarizations, a form of cortical spreading tissue at risk for permanent damage (139). When subdural electrodes have
depression, which requires substantial energy for recovery (repolarization). been used to record depolarizations (requires direct current recording—no
These depolarizations occur spontaneously and commonly after various or minimal low frequency filtering), the presence of prolonged spreading
forms of brain injury, including ischemia, hemorrhage, and trauma. In per- depolarizations (especially when associated with absence of spontane-
manently damaged tissue, this can reflect a persistent state with electrocor- ous activity) has been associated with poor outcome after brain trauma
ticographic depression. In healthy tissue, this leads to increased perfusion (140,141). Such depolarizations may precede additional neuronal injury
and is transient; however, in damaged tissue, it may lead to an increase in in some situations. For example, in patients with major SAHs, these were
Figure 17.28: A: EEG of a 73-year-old patient after cardiac arrest. EEG was performed 14 hours after return
of spontaneous circulation. B–D: Consecutive panels showing a nonconvulsive seizure arising from a back-
ground of burst suppression. These patterns indicated a poor prognosis for functional recovery; the patient
died after withdrawal of care. LFF = 1 Hz, HFF = 70 Hz, notch off.
observed in 13 out of 18 patients and were highly associated with delayed upon to help answer this question? Can CEEG be used reliably and practi-
ischemic neurological deficits (positive predictive value of 86% and nega- cally to detect changes in neurological function beyond seizures, such as
tive predictive value of 100%) (142). Electrocorticographic seizures have also DCI? Can non-neurophysiologists be adequately trained to monitor CEEG
been associated with cortical spreading depolarization in patients with acute or at least QEEG trends? Can QEEG trends be used to speed up/improve
brain injury (143). In a subset of patients, the spreading depolarization was review of data? Can other monitoring modalities be integrated with CEEG
immediately preceded by a prolonged nonconvulsive seizure, lending fur- to provide additional meaningful information regarding neurological and
ther support to the idea that such seizures may lead to additional damage in systemic function in critically ill patients? Lastly, what is the true clinical
patients with brain injury. impact of CEEG monitoring—does it truly improve patient outcomes?
Will it do so when done in real time with improved automated detection
FUTURE DIRECTIONS algorithms? If so, will this be cost effective? The use of biomarkers of neu-
ronal injury and individualized, physiology-driven decision-making may
Even though CEEG has grown rapidly, the field is still evolving and many play a role in determining the utility of CEEG and interventions based on
questions remain unanswered or only partially answered. These include CEEG. Finally, systematic collection and analysis of data about CEEG,
what type of patients should undergo CEEG? Once CEEG is initiated, how likely in large multicenter cohorts, is needed to answer these questions in a
long should it be continued, and can the initial findings on EEG be relied meaningful way.



Figure 17.29: Relationship of physiological variables with quantitative EEG

parameters during ictal events. During the repetitive seizure events, partial brain
tissue oxygen tension (PbtO2, arbitrary units) consistently decreased followed by
a surge in intracranial pressure, brain temperature, and cerebral blood flow (CBF,
arbitrary units). In addition, total power on the EEG is well synchronized with the
rhythmicity index and the existence of rhythmicity medium- to high-frequency
waves in the spectrogram, followed by lower frequency waves, suggesting an
evolving ictal rhythm. (Figure courtesy of Dr. Jan Claassen, New York, New York.
© Jan Claassen.)
Figure 17.30: Cyclic seizure on intracranial EEG only. EEG

sample from an older woman with Hunt and Hess grade
III subarachnoid hemorrhage and a left frontal mini-depth
electrode. During a 5-hour period, she had cyclic seizures
in the depth electrode only, each lasting about one minute
and recurring every few minutes. A typical seizure is shown.
The bottom six channels from the depth electrode show a
clearly evolving seizure; the upper channels of scalp EEG
show no hint of a seizure. (With permission from Hirsch LJ,
Brenner RP. Atlas of EEG in critical care. West Sussex, UK:
John Wiley & Sons, 2010:334.)
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18 Sleep Disorders: Laboratory Evaluation
RODNEY A. RADTKE
Polysomnography: Technical Aspects Multiple Sleep Latency Test

EEG Sleep Recording MSLT Procedure
Anterior Tibialis EMG MSLT Interpretation
Respiratory Monitoring Maintenance of Wakefulness Test
Recording Montage MWT Procedure
Ambulatory PSG Recording MWT Interpretation
Computerized PSG and Computer-Assisted Scoring Clinical Evaluation of Sleep Disorders
Polysomnography: Interpretation Evaluation of Excessive Daytime Sleepiness
EEG-Related Variables Approach to Nocturnal Behavioral Events (Parasomnias)
Respiratory-Related Variables Approach to the Patient with Insomnia
Movement-Related Variables References
The rapid growth of sleep disorders medicine in the United States has led decades. The use of prolonged EEG recording to investigate sleep was pio-
to an increasing role for clinical electroencephalographers (EEGers) in the neered by Kleitman and culminated in his historic discovery (with Aserinsky)
evaluation of sleep and its disorders. However, most clinical neurophysiol- of rapid-eye-movement (REM) sleep in 1953 (1). In the 1960s, early investi-
ogy training programs still do not incorporate the neurophysiologic or clini- gations described sleep-onset REM periods in narcolepsy (2,3), and defined
cal aspects of sleep disorders into their curriculum. In this chapter, I will sleep apnea (4,5). Important progress in standardizing sleep investigation
provide an introductory overview to the sleep laboratory evaluation of sleep occurred in 1968 when a committee of sleep researchers published a manual
disorders that is aimed at the practitioner or trainee in clinical EEG. for scoring sleep; this system, known by the editors’ names Rechtschaffen
The investigation of sleep and its disorders is a comparatively new medical and Kales (R&K), became the accepted standard as the basis for the scor-
discipline, with the greatest development having occurred in the last three ing of sleep stages today (6). The American Sleep Disorders Association
599
(ASDA) was formed in 1976 to enhance patient care and standardize the behavioral or respiratory events can be reviewed. The machines used are
practice of sleep disorders medicine. This group of clinical sleep special- similar to the commonly used digital EEG machines, but also have the abil-
ists created an extensive classification system for the diagnosis of sleep and ity to transfer other digital information (e.g., Sao2, CPAP pressure) to the
arousal disorders, which was initially published in 1979 (7) and has been recording.
serially revised (8). The ASDA (which subsequently changed its name to the The patient is scheduled to arrive for the nocturnal study 60 to 90 min-
American Academy of Sleep Medicine, AASM) also spearheaded the devel- utes before his usual bedtime. During electrode application, the technolo-
opment of a free-standing certification board in sleep medicine, known as gist reviews the patient’s history and offers an explanation of the study
the American Board of Sleep Medicine. More recently in 2007, sleep medi- procedure. Medical information from the referring physician should be
cine became a subspecialty board exam under the direction of the American available at the time of the study to assure that the correct procedure is
Committee on Graduate Medical Education (ACGME). Eligibility requires performed, to assist in decision-making during the study, and to comple-
a 1-year training fellowship in sleep in an ACGME-approved fellowship. ment the subsequent interpretation. Patients are usually asked to complete
That same year the AASM published the scoring manual that has mark- sleep questionnaires and Epworth Sleepiness Scale (ESS), which are then
edly improved the standardization of polysomnography and its interpre available to the interpreting physician to assist in assessing the clinical sig-
tation (9). An update to that scoring manual has recently been published by nificance of the PSG findings. The usual study duration is 6 to 8 hours,
that same organization (10). depending on the specific clinical problem. When the patient awakens
Clinical investigation of sleep disorders relies primarily on two major in the morning, the technologist obtains the patient’s impression of the
techniques: the overnight polysomnogram (PSG) and the multiple sleep night’s sleep and how it may have varied from his usual night’s rest. This
latency test (MSLT). The overnight PSG allows the evaluation of nocturnal information may be important in the clinical correlation of the sleep study
sleep and focuses primarily on identification and characterization of respi- results. Sleep studies are visually scored by the sleep technologist. The
ratory abnormalities in sleep. PSG is also useful in the evaluation of move- sleep study tracing and scored data are then reviewed by a polysomnogra-
ment disorders, parasomnias, and nocturnal sleep disruption. The MSLT pher, who provides the interpretation and clinical correlation.
offers (a) an objective assessment of daytime sleepiness, and (b) a determi- Digital EEG technology has proven to be an extremely useful tool for PSG
nation of possible early-onset REM sleep. These two study techniques serve studies. It has simplified the handling and storage of such large amounts of
as the “gold standard” of sleep evaluation and will be reviewed in detail. The physiologic data. The ability to expand the number of channels also allows
maintenance of wakefulness test (MWT), an adaption of the MSLT, has a greater sampling of EEG, which can then be reviewed at “routine EEG
also begun to be used more, particularly in medicolegal situations, where the paper speed” (30 mm per second) to allow better assessment of a possible
documentation of normal alertness is required for employment in a patient epileptic event that can be very difficult to interpret when EEG recordings
with an identified sleep disorder. A brief overview of the initial assessment were available only at PSG paper speed (10 mm per second) (11). The digi-
of patients presenting with complaints of excessive daytime sleepiness, talization of the information lends itself to computer analysis. However, at
unusual nocturnal behavior, or insomnia will also be presented. this time, it is still the standard to do visual scoring of sleep stages according
to the AASM Scoring Manual, given the unreliability of most sleep staging
POLYSOMNOGRAPHY: TECHNICAL ASPECTS programs (9,12). Improvement in computer-aided sleep scoring may make
sleep study scoring a less laborious task in the future. Computer analysis
Overnight sleep studies are usually performed in a facility dedicated to sleep also has a potential to go beyond the standard (and somewhat arbitrary)
investigations. Most sleep laboratories have one or more bedrooms in which epoch-by-epoch scoring of sleep and capture information about the micro-
environmental noise, ambient temperature, lighting, and decor are con- structure of sleep that may have important clinical or research implications.
trolled, thus facilitating the patient’s sleep. The technologist and polygraphic Minimal polygraphic requirements to score sleep adequately include two
equipment are located in a separate room to minimize any disruption to channels of EEG, one channel for the electrooculogram (EOG) and one
the patient’s sleep. An intercom is used to monitor and communicate with channel for the submental electromyogram (EMG). Routine PSG utilizes
the patient as needed. Most laboratories also videotape the night’s sleep, so additional channels to assess respiration, leg movements, oxygenation, and
Sleep Disorders: Laboratory Evaluation 601
cardiac rhythm. The following is a brief review of “standard” technology

involved in PSG recordings. Other reviews of PSG technique may also be
helpful to the reader (13,14).
EEG Sleep Recording

As with routine EEG, nonpolarizable silver-silver chloride or gold elec-
trodes are standard and are attached with collodion to maintain adequate
contact for the 6 to 10 hours required for an overnight study. The interna-
tional 10–20 system is used for electrode placement (15), but a much more
limited EEG montage is selected as outlined later. Early sleep investigators
were limited by channel availability and could commit only one channel to
EEG recording (central EEG lead to contralateral ear, e.g., C4-A1). As a
result, the scoring manual of Rechtschafen and Kales was based on that
single lead derivation. However, the poor sampling of waking alpha activity
by this montage led most investigators to add at least one additional channel
(occipital lead to more anterior reference, e.g., O1-A2) for better separa-
tion of wakefulness from stage 1 (drowsiness). The recent AASM Scoring
Manual recommended a minimum of three EEG channels: F4-M1, C4-M1,
O2-M1 (9). The use of the F3 or F4 electrode recognizes that sleep spindles
and vertex waves are often seen more prominently in a frontal derivation.
In addition, many laboratories commit at least two additional channels to
EEG. A transverse vertex montage (e.g., T3-Cz, Cz-T4) is often preferred
because it is sensitive to the identification of sleep spindles and vertex waves.
Bilateral central, occipital, and ear electrodes are routinely placed so that in
the event of electrode failure, the homologous contralateral derivation can
be used without disturbing the patient. Occasional patients, such as those
with possible nocturnal seizures, require a more extensive EEG montage for
adequate assessment, usually a minimum of 16 channels (11).
Routine “paper speed” or recording display for the PSG is 10 mm per
second (6). This is initially disconcerting to the EEGer trained using a dis-
play of 30 mm per second. The slower paper speed was chosen to reduce
paper use and to improve visualization of events (e.g., apneas) that occur
over a relatively long period of time. Displaying the PSG using “slow
paper speeds” still allows clear visualization of alpha rhythm and sleep Figure 18.1: EEG activity characteristic for each of the sleep stages. The activity
spindles. In fact, the characteristic appearance of sleep spindles, “saw is recorded from the usual sleep study derivation (C4-A1) and displayed at 10 mm
tooth” waves, and eye movements is more easily recognized at slower per second. Delta sleep is an alternate name for what is now termed stage N3.
paper speeds once the interpreter has adjusted to the altered appearance (From Hari P. The sleep disorders. Kalamazoo, MI: Upjohn Co., 1982:5–62.)
(Fig. 18.1). EEG filter settings are low-frequency filter (LFF) of 0.3 Hz
and high-frequency filter (HFF) of 35 Hz. The extended low-frequency
band is important to assess the prominent slow wave activity seen during and 1 cm superior to the outer canthus and referred to the ipsilateral ear.
deeper stages of NREM sleep. Amplifier sensitivity is usually 5 to 10 μV A second channel records activity from a location 1 cm lateral and 1 cm
per mm, with 7 μV per mm used most commonly. Because voltage of the inferior to the contralateral outer canthus referred to the ipsilateral ear. This
delta range activity is important in determining sleep stage, it is impera- two-channel derivation shows eye movements as out-of-phase potentials,
tive that any change in EEG channel sensitivity be clearly “flagged” to thus increasing the interpreter’s confidence in correctly identifying REMs
avoid sleep scoring errors. (Figs. 18.2 and 18.3). Sensitivity and filter settings for the EOG are similar
to those used for EEG recording.
Electrooculogram REMs are defined as conjugate, irregular, sharply peaked eye movements
The EOG is obtained primarily to identify phasic bursts of REMs that con- with an initial deflection of less than 500 milliseconds (9). REMs are char-
stitute the cardinal sign of REM sleep. In addition, these electrodes allow acteristic of stage R sleep (stage REM) but are also seen in wakefulness,
identification of slow lateral eye movements, which are often the first and particularly with eyes open. Most commonly, the sharp slope of a REM is
most dependable manifestation of drowsiness (16). Gold-plated or silver- shorter than 300 milliseconds. Slow eye movements (SEMs) are conjugate,
silver chloride EEG cup electrodes are used to record EOG, but collodion somewhat regular, sinusoidal eye movements with an initial deflection last-
should be avoided because of possible corneal injury. EEG electrolyte paste ing greater than 500 milliseconds (9). The sinusoidal SEMs usually have a
with additional sticky tape over the electrodes offers adequate attachment frequency of 0.25 to 0.5 Hz compared with REMs that are usually very
and avoids the risk of eye injury. The most common montage to record eye irregular and commonly have a frequency greater than 1 Hz. Obviously, the
movements (and as recommended by the AASM manual) is a referential rate of return to baseline of any EOG waveform is dependent on the alter-
recording with the first channel recording from an electrode 1 cm lateral nating current (AC) filter setting and the superimposition of any additional
Figure 18.2: Slow eye movement (SEMs). Note the slow rolling eye movements appearing as out-of-phase activity in EOG channels. SEMs accompany the appear-
ance of mixed-frequency theta activity typical for stage 1 sleep. K complex near end of epoch denotes onset of Stage 2. K complex appears as in-phase activity in
EOG channels, reflecting its cerebral origin. (From Rechtschaffen A, Kales A, eds. A manual of standardized terminology, techniques, and scoring system for sleep
stages of human subjects. Los Angeles, CA: UCLA Brain Information Service/Brain Research Institute, 1968.)
Figure 18.3: REM sleep with relatively low-

voltage, mixed-frequency EEG, REMs, and tonic
EMG at lowest level during sleep. Note series of
typical sawtooth waves at onset of REM activity.
(From Rechtschaffen A, Kales A, eds. A manual of
standardized terminology, techniques, and sco
ring system for sleep stages of human subjects.
Los Angeles, CA: UCLA Brain Information S
ervice/
Brain Research Institute, 1968.)
eye movements. Thus, the abrupt slope of the EOG waveform is the most adjustments should be avoided during the night to permit comparison of
reliable differentiating feature. EMG activity during different portions of the record. Typical sensitivity
of the EMG is 2 μV per mm, with filters set at LFF = 10 and HFF = 100.
Axial Electromyogram
Submental (chin) EMG activity reflects axial muscle tone and is used as Anterior Tibialis EMG
one criterion for identifying REM sleep and movement arousals. Submental
EMG is recorded by placing regular EEG electrodes over the mylohyoid Anterior tibialis EMG activity is monitored to detect periodic leg move-
muscle. One electrode is placed 1 cm above the tip of the jaw, and the second ments (17,18). Regular EEG electrodes are placed over the anterior tibialis
electrode is placed 2 cm below the inferior edge of the mandible and 2 cm muscle bilaterally. The anterior tibialis muscle can be easily identified on
off of the midline. This second electrode should be placed bilaterally, func- the anterior lower leg by having the patient dorsiflex his foot against resis-
tioning as a backup electrode from which to select the most reliable EMG tance. Two electrodes 3 cm apart are placed over each anterior tibialis. A
recording. bipolar recording from each anterior tibialis is usually obtained. Sensitivity
Tonic EMG activity from axial musculature gradually decreases from and filter settings are similar to those described for submental EMG record-
wakefulness through stages N1-N3 of sleep and is usually entirely absent ing. A semi-standardized baseline is obtained before the study by asking
during REM sleep. Sensitivity of the submental EEG channel should the patient to dorsiflex a foot gently. Figure 18.4 is an example of periodic
be adjusted during drowsiness to reflect moderate activity. Subsequent leg movements of sleep recorded from the anterior tibialis EMG electrodes.
Figure 18.4: Periodic limb movements of sleep (PLMS). The anterior tibialis EMG recording demonstrates bursts of periodic EMG activity associated with EEG arous-
als. (From Hari P. The sleep disorders. Kalamazoo, MI: Upjohn Co., 1982:5–62.)
Respiratory Monitoring Airflow Monitoring

Thermistors/Thermocouples
Inasmuch as the suspicion of sleep apnea is the most common indication
for overnight PSG, respiratory monitoring is arguably the most impor- Thermistors or thermocouples are the least expensive and most commonly
tant technical aspect. Although measurements of airflow and ventilatory used method of monitoring airflow (13,19). Thermistors are small glass
effort are technically the most difficult of all polysomnographic vari- beads or wires whose electrical resistance changes as a function of tem-
ables, they are essential to the adequate assessment of breathing during perature. When powered by a 1.5-V battery, the voltage drop across the
sleep. Both airflow and a measure of ventilatory effort must be recorded thermistor varies with temperature. Expired air warms the thermistor and
in order to distinguish among central, mixed, and obstructive apneic produces a signal that can be displayed on a polygraph. A thermocouple
events (Fig. 18.5). In a central (or nonobstructive) apnea, the absence of consists of two dissimilar metals in electrical contact, which produces
respiratory drive causes all mechanical efforts to cease, and no airflow a low-voltage signal that varies with the temperature change caused by
occurs at the nose or mouth. In an obstructive apnea, ventilatory efforts expired air.
continue but no airflow occurs; this is due to occlusion of the airway. Small, lightweight thermistors (or thermocouples) are taped to the face
A mixed apnea begins as a central apnea (without ventilatory effort or under each nostril and in front of the mouth. It is crucial to monitor both
airflow), but then the picture of obstructive apnea develops (ventilatory nostrils and mouth because the airflow path frequently changes during the
effort without accompanying airflow). Apneas are arbitrarily defined as night as a function of patient position. Activity from the thermistors can
cessation of airflow for 10 seconds or longer (19). In addition, hypopneas be summed and displayed in a single channel. Patient movement may dis-
(decreased airflow) are also clinically significant. Specific scoring criteria turb the position of the thermistors and result in loss of signal. Thus, care-
for respiratory events are discussed in the section on polysomnographic ful attention needs to be paid to thermistor position throughout the night.
interpretation. All measures of airflow or ventilatory effort use a LFF of Thermistors and thermocouples are less sensitive to airflow changes than the
0.1 Hz and a HFF of 15 Hz. nasal pressure transducers discussed later. Therefore, hypopneas (reflecting
a decrease in airflow) are scored from the nasal pressure transducer record-
ing, while apneas are scored off the thermistor/thermocouple channel.
Nasal Pressure Transducer

In the last decade, nasal pressure transducers (NPTs) have become a stan-
dard technique in monitoring airflow during polysomnography (9,20,21).
Nasal cannula pressure systems generate a respiratory waveform signal by
detecting the fluctuations in pressure caused by inspiration and expiration.
Unlike the inspiratory and expiratory fluctuations recorded due to temper-
ature changes from a thermocouple or thermistor, these NPT signals are
truly proportional to flow and are able to note changes in airway resistance
and more modest changes in airflow (Fig. 18.6). Consequently, airflow
Pressure
Glottic
Normal Contour
Intermediate Flattened Contour
Cannula
Flow
0 5 10 15 20 25
No Flow Limitation Flow Limitation
Inspiratory Flow
Inspiratory Flow
Inspiratory Flow
Driving Pressure Driving Pressure Driving Pressure
Figure 18.6: Pressure/flow relationships from nasal cannula/pressure transducer

during a single respiratory event. The x-axis shows time in seconds. Breaths
with normal, intermediate, and flattened flow contours are labeled and a plot
Figure 18.5: Examples of obstructive, central, and mixed apneas. Compare air- of the driving pressure/flow relationship is shown. The flattened flow/time con-
flow (measured by CO2 analysis) and ventilatory effort (measured by intraesopha- tour shows a nonlinear flow/pressure relationship characteristic of flow limita-
geal balloon). (From Hari P. The sleep disorders. Kalamazoo, MI: Upjohn Co., tion. (From Hosselet JJ, Normal RG, Ayappa T, et al. Detection of flow limitations
1982:5–62.) with a nasal cannula/pressure transducer system. Am J Respir Crit Care Med
1998;157:1461–1467.)
as measured by NPT is far more sensitive and accurate in the capture of manometry was available as well, but limited in its use due to its invasive
hypopneas and “Respiratory Effort Related Arousals” (RERAs) (22). This nature and potential impact on sleep. In the 2007 AASM Scoring Manual,
increased sensitivity is routinely seen on PSG recordings and has led to the the recommendation was for use of calibrated or uncalibrated IP or esopha-
AASM recommendation to use NPT in tandem with thermistors or thermo- geal manometry for the detection of respiratory effort (9). This has led to
couples for monitoring of airflow during a PSG (9). IP as the primary technique for monitoring respiratory effort. However, in
the most recent update to the scoring manual in 2012, new information led
CO2 Detectors to the piezoelectric belts being listed as an acceptable method of monitoring
Measuring the carbon dioxide (CO2) of expired air can serve as an alter- respiratory effort as well (10,25).
native method of monitoring airflow (19,23). It is based on the principle
that exhaled air contains 6% to 7% carbon dioxide, whereas inhaled air con- Inductive Plethysmography
tains negligible amounts of CO2. In order to sample CO2 content, a can- IP utilizes a conductive wire that is sewn into an elastic band or mesh that
nula is inserted just inside the nostril and is connected to an infrared or encircles the chest or abdomen. With expansion of the body wall, the circle
mass spectroscopy analyzer. For routine clinical PSG, the small increase in of wire enlarges and the inductance of the loop is changed. When an AC
sensitivity for detecting air movement using CO2 detectors does not usually current is applied to this wire, the variable inductance can be displayed on an
warrant the added expense and technical demands. However, end-tidal Pco2 AC or DC polygraph channel. This technique is much more powerful than
(Petco2) monitoring is an essential component of assessing sleep-disordered the early techniques utilized inasmuch as it provides a quantitative measure
breathing (SDB) in children. The clinical importance of Pco2 monitoring in of airflow. This method also permits more accurate determination of lung
pediatric sleep apnea has led to its wide application in pediatric sleep labo- expansion regardless of patient position (26,27). The instrument is carefully
ratories. The Petco2 is prone to providing falsely low values in patients who calibrated so that the sum of the chest and abdominal signals will be pro-
are mouth breathers or who have a high degree of nasal obstruction. The portional to the volume of airflow. If the airway is obstructed, no air will be
use of supplemental O2 or CPAP also makes the recording inaccurate. End- exchanged; any change in chest volume will be associated with an opposite
tidal CO2 is often supplemented by transcutaneous Pco2 monitoring. How- change in abdominal volume (paradoxical respiration), and the sum of the
ever, the transcutaneous method provides only a semiquantitative measure two will be zero (representing no airflow) (Fig. 18.7). Theoretically, com-
of alveolar ventilation and varies significantly from measured Paco2 (23). plete ventilatory monitoring can be accomplished with two bands around
the chest. The three-output channels are rib-cage movement, abdominal
Pneumotachography movement, and total volume. Obstructive apneas are recorded as continued
Pneumotachography is the only method that allows direct quantification of respiratory movement of both thorax and abdomen, but with no signifi-
ventilation during sleep. Pneumotachography uses a technology very simi- cant change in total volume signal (Fig. 18.8). In central apneas, all three
lar to the NPT devices discussed earlier. However, the technique involves signals are suppressed. Mixed apneas, as expected, show a central pattern
an uncomfortable tight-fitting mask and a flow-to-pressure transducer that followed by an obstructive picture. Hypopneas may also be quantified by
offers considerable resistance to respiration. While technically superior to this technique. Theoretically, an independent measure of airflow (thermis-
the other methods of monitoring airflow, the sleep disruption and increased tor) is unnecessary. However, because of difficulties in calibration (especially
respiratory resistance preclude the routine use of pneumotachography in in obese patients) and slippage of coils, this technique usually requires an
clinical PSG (24). additional monitor of airflow. Although it increases cost and is more tech-
nically demanding, IP offers significant advantages over other methods of
Ventilatory Effort Monitoring monitoring respiratory effort.
For many years, there was a great deal of variability in the use different
techniques to monitor respiratory effort. Early techniques included inter- Esophageal Pressure Monitors
costal EMG and strain gauges. More recently developed techniques An esophageal pressure monitor (EPM) can be either a catheter-tip or balloon
included inductive plethysmography (IP) and piezoelectric belts. Esophageal transducer that is placed through the nose into the distal esophagus (28).
Figure 18.7: Obstructive apnea. Note the de-

velopment of out-of-phase or paradoxical move-
ment of thoracic and abdominal monitors during
period of obstructive apnea. (From Mendelson
WB. Human sleep. New York, NY: Plenum Press,
1987:159.)
The output signal of the pressure/voltage transducer shows absolute pres- electrode board or input cable. It incorporates good sensitivity to ventilatory
sure (with a DC amplifier) or variations in pressure (with an AC amplifier) effort along with simple and reliable technical application (25).
on the polygraphic record. EPMs measure pleural pressure swings and are
the most accurate devices for assessing ventilatory effort. However, the inva- Intercostal EMG
sive placement and the inability of many patients to tolerate their use make Intercostal EMG can be recorded using surface electrodes placed in the
EPMs less than ideal for routine PSG. However, in difficult cases, intra- intercostal space. The technique identifies thoracic ventilatory movements,
esophageal pressure measurement can accurately resolve ambiguities as to but it is frequently inadequate in obese patients. While sometimes useful as a
the nature of the apnea. complementary technique, intercostal EMG alone is not an adequate index
of ventilatory effort.
Piezoelectric Belts
This device incorporates a piezo crystal element transducer in an elastic belt. Arterial Oxygen Assessment
When stretched, the piezo crystal element provides a voltage signal propor- Determination of arterial oxygen desaturation is an important adjunct in
tional to the stress applied. It requires no power and connects simply to the assessing the severity of apneic episodes (29–31). Finger pulse oximetry is
the technique that is most commonly utilized. It measures oxygen satura-

tion (Sao2) by light transmission through the fingernail bed. Sao2 values
obtained from pulse oximetry are continuously recorded on the record.
The accuracy of pulse oximetry is compromised by the presence of car-
bon monoxide, hyperbilirubinemia, O2 saturations below 50%, dark skin
pigmentation, or significant hypotension. The AASM guideline requires
that the maximum acceptable signal averaging time is 3 seconds. It is
important to note that the change in Sao2 associated with a respiratory
event appears 20 to 40 seconds after the actual event. Incorporated in the
delay are both circulation time to the finger and machine measurement
delay.
Electrocardiogram
The ECG is monitored during sleep studies to detect arrhythmias that may
be associated with SDB events. Documentation of an associated cardiac
arrhythmia can affect treatment decisions in a patient with sleep apnea. In a
PSG, the ECG is usually derived from two electrodes placed over the ante-
rior chest wall. This avoids much of the movement artifact seen with the use
of limb leads alone. The AASM guidelines recommend the use of a modi-
fied ECG Lead II during PSG recordings. This is achieved by placing one
electrode in the second intercostal space between sternum and right shoulder
and the second electrode in the sixth intercostal space above the left hip.
In morbidly obese patients, movement artifact can sometimes be limited by
placing this second electrode in the second intercostal space on the left, again
halfway to the shoulder. This one channel recording is adequate to monitor
heart rate, extrasystoles, and other arrhythmias. However, the differences in
recording display, along with the limited derivation, will often not allow ade-
quate assessment of P-wave and QRS abnormalities. If the precise rhythm
disturbance cannot be determined from the PSG alone, then independent
evaluation using an ambulatory ECG monitor or other dedicated ECG
recording device is required. Routine filter settings for ECG are LFF = 0.3
Figure 18.8: Recording demonstrating paradoxical motion of rib cage and ab-
and HFF = 70, with a sensitivity of approximately 50 μV per mm.
dominal signals along with absence of significant volume signal [VT(RC  ABD)]
indicating decreased or absent airflow. Note accompanying oxygen desatura-
tion. (From Cohn M. Respiratory monitoring during sleep: respiratory IP. In: Guil- Recording Montage
leminault C, ed. Sleeping and waking disorders: indications and techniques.
Menlo Park, CA: Addison-Wesley, 1982:213–223.) PSG montages are selected depending on the clinical question. For screen-
ing studies of patients with possible sleep apnea, PSG variables recorded
should include EEG, EOG, axial EMG, anterior tibialis EMG, ECG,
TABLE 18.1 Screening PSG Montage Ambulatory PSG Recording
Sensitivity Filters Historically, ambulatory recording of sleep in the home environment for the
Channel (µV/mm) (LFF/HFF) (Hz) evaluation of sleep disorders has not been commonly utilized owing to the
1. C4-A1 7 0.3/35 inherent limitations of the technique and the lack of third-party reimburse-
2. F4-A1 7 0.3/35 ment (32). With the recent CMS (Centers for Medicare and Medicaid Ser-
3. O2-A1 7 0.3/35 vices) approval for coverage and the push to control health-care costs, the role
4. T3-Cz 7 0.3/35 of ambulatory or home sleep tests (HSTs) is being reevaluated and is being
5. Cz-T4 7 0.3/35 used with increasing frequency (33). The various technologies available have
6. Left outer canthus—A1 7 0.3/35 been classified into four separate types of sleep studies dependent on what
7. Right outer canthus—A1 7 0.3/35 parameters are recorded and whether a technologist is in attendance. In-lab
8. Submental EMG 2 10/100 PSG with the recording of seven or more channels and attended by a tech-
9. ECG 70 0.3/70 nologist is the gold standard for the evaluation of sleep disorders and is clas-
10. Left anterior tibialis EMG 3–7 10/100
sified as a type 1 study. A full but unattended PSG (seven or more channels,
11. Right anterior tibialis EMG 3–7 10/100
12. Snore monitor — 10/100
including the recording of EEG) is classified as a type 2 study. Type 3 studies
13. Nasal pressure transducer — DC or 0.03/100 have four to seven channels and focus on the evaluation of respiratory param-
14. Oronasal thermistor — 0.1/15 eters. Type 3 studies do not record EEG and therefore do evaluate sleep stages,
15. Thoracic movement — 0.1/15 arousals, or sleep duration. Type 3 studies have been the focus in the increasing
16. Abdominal movement — 0.1/15 use of ambulatory HSTs. A type 4 study is a one- or two-channel overnight
17. Sao2 (oximetry) — DC/70 recording, with at least one of them being oximetry. Type 4 studies have not
been demonstrated to be a reliable screen for sleep-related breathing disorders
LFF, low-frequency filter; HFF, high-frequency filter; EMG, electromyogram; Sao2,
oxygen saturation. in any patient population (34).
The usual routine for HSTs is for the patient to present to the lab the
day of the study. The patient is educated regarding appropriate use of the
equipment and placement of electrodes and recording devices. That night,
airflow, ventilatory effort, and Sao2. A representative montage is outlined after preparing for bed, the patient places the recording sensors and pushes
in Table 18.1. If there is a more specific clinical question, the montage can a button as they get into bed. The button is pressed again upon awakening
be adjusted accordingly. For example, if the primary concern is involun- in the morning and a total recording time is determined. This is supple-
tary motor activity during sleep, additional channels recording arm and leg mented by a brief sleep log from the patient outlining any sustained periods
EMG can be added. To evaluate a patient for possible nocturnal seizures, of wakefulness or other important information that may impact on the clini-
additional EEG channels are needed (11). Present-day digital machines cal interpretation of the data. Recorded parameters usually include: nasal/
with expanded channel capabilities (e.g., 32 channels) allow greater flex- oral airflow, respiratory effort, Sao2, body position, snoring, and heart rate.
ibility in recording all the usual physiologic variables but also allow a choice The studies are scored by automated scoring systems, but the data should be
of which variables to focus on in review. In general, assessment for noc- reviewed and edited by a technologist to assure that artifactual information
turnal seizures is best performed using dedicated video-EEG monitoring is discarded and that the results represent a reasonable interpretation of the
designed for recording seizures. If sleep laboratory equipment is used for data. From this recording, an estimate of an apnea-hypopnea index (AHI)
such a purpose, additional channels of EEG accompanied by simultaneous and oxygen desaturation index is obtained.
time-locked video are required and should be able to be displayed at 30 mm The recent guidelines from the AASM for unattended sleep studies outline
per second. minimal technical expectations for portable monitoring (35). HSTs should
at a minimum record airflow, respiratory effort, and blood oxygenation, and in clinical sleep studies has attempted to model itself after the visual sleep
should use the same sensors that are used in the laboratory studies. Accurate analysis. While extremely useful for quantifying easily identified events (e.g.,
data collection is paramount to the successful use of the techniques, so the oxygen desaturations), computerized scoring’s inability to adjust to hostile
device should not be used by technologists or physicians that are inexperi- “pathologic states” such as frequent apneas, disrupted sleep, and movement
enced in sleep disorders and their evaluation. The devices must also allow artifacts has limited its clinical application. Although much of the commer-
review of the raw data to allow manual scoring and/or adjustment of the cially available PSG equipment does come with computerized analysis of
automated scoring algorithms. sleep stage, the clinical standard remains visual scoring by a trained tech-
The advantages of HSTs include lower cost and greater patient accessibil- nologist or, at least, the review and overscoring of the computerized sleep
ity. Patients who cannot access in-lab studies due to lab backlog or physical staging by a technologist. Similarly, computerized identification of respira-
immobility can be evaluated with a HST. Other patients with irregular or tory or movement events also requires review and editing by a technologist.
unusual sleep-wake cycles can also have an evaluation that does not have During the creation of the AASM Scoring Manual, a critical evidence-
to fit into the usual lab schedule. The primary disadvantage is unreliable based look at computerized analysis of PSG was carried out. The consensus
or lost data, which may require repeating the test. In addition, the lack of of the review suggested that “computer scoring and quantitative analysis is
any assessment of sleep stage or quality may lead to a significant underes- still in the formative stage of development” and have not been proven to be
timation of apnea severity (due to inclusion of prolonged wakefulness) or useful in clinical practice (36).
more importantly, the lack of recognition of hypopneas if significant oxy- The real strength of computerized analysis of sleep is in its ability to look
gen desaturations are not present (34). at sleep as a continuum, rather than the arbitrary definitions provided for
Because of the obvious limitations, portable or ambulatory sleep studies identifying N1, N2, N3, and stage R sleep. Similarly, information regarding
are not appropriate in many clinical settings. These limitations are recog- the microstructure of sleep is likely lost in the use of a 30-second epoch. It
nized by the CMS guidelines as well as those of the AASM. Both bodies will be interesting to explore how computerized analysis may contribute to
agree that the HST may be used as an alternative to in-lab PSG for the diag- potential new methods for understanding sleep and its disorders (37).
nosis of obstructive sleep apnea (OSA) in patients with a high pretest proba-
bility of moderate to severe OSA. If positive, the caregiver can move forward POLYSOMNOGRAPHY: INTERPRETATION
with therapy for the significant respiratory abnormality. Additionally, HSTs
can be helpful after CPAP therapy has been initiated to assess adequacy of The clinical interpretation of polysomnographic sleep studies is based
treatment if there is a concern regarding response to therapy (33–35). primarily on the analysis of three main variables: EEG-related variables
However, HST is not indicated for use in patients with significant comor- (sleep stage, arousals); respiratory-related variables (apneas or hypop-
bidity (e.g., chronic obstructive pulmonary disease, congestive heart failure, neas); and movement-related variables (periodic leg movements). This dis-
and neuromuscular disease) as the coexistence of these disorders may lead cussion will focus on the guidelines for the scoring of these variables and
to a greater degree of inaccuracy. HST has not been evaluated in asymp- the subsequent assignment of clinical significance. The development of the
tomatic but high-risk individuals such as bariatric surgery patients or com- AASM Scoring Manual (and its recent update) has markedly improved the
mercial truck drivers. standardization of PSG recording techniques and interpretation, which
improves the ability to compare sleep study results obtained in different
laboratories (9,10).
COMPUTERIZED PSG AND Despite the improved standardization, a great deal of uncertainty persists
COMPUTER-ASSISTED SCORING as to the clinical significance of many of the observations noted during PSG
recordings. While the International Classification of Sleep Disorders has
Visual sleep scoring has been the gold standard for analyzing sleep, and labeled an AHI greater than 5 as abnormal, a large number of healthy, non-
all subsequent standardizations of sleep scoring have emphasized visual complaining individuals will have significant elevations of their AHI. Simi-
analysis of the PSG (6,9). Any attempt to utilize computerized sleep scoring larly, a movement index of greater than 15 is listed as abnormal, but occurs
in many normal subjects, and its clinical significance is unclear. Exactly CHILDREN
where one should draw the line in attaching clinical significance to various AWAKE
PSG results remains uncertain. I will provide guidelines in this area based on REM
my own standard of practice, but with the understanding that other experi-
SLEEP STAGES
1
enced practitioners may have different opinions and that these standards are
continually evolving. 2
EEG-Related Variables 4
Basic Sleep Scoring 1 2 3 4 5 6 7

In 1968, the publication of the Rechtschaffen and Kales sleep scoring atlas
YOUNG ADULTS
(6) represented the consensus agreement between sleep researchers of the AWAKE
time in an effort to standardize the scoring of sleep stages. It is truly remark-
REM
able that our most recent sleep scoring criteria (as published in the AASM
SLEEP STAGES
Scoring Manual) vary only limitedly from this original document (9,10). 1
The nomenclature of sleep stages has changed from those described in R&K
2
Atlas. NREM stage 1 is now called stage N1, and NREM stage 2 is now
stage N2. What had previously been NREM stages 3 and 4 (or slow wave 3
sleep) is now unified into a single Stage N3. Stage REM is now labeled as 4
stage R.
Normal sleep has a clearly defined architecture that is relatively stable
1 2 3 4 5 6 7
from childhood through senescence (38). Sleep onset begins with a transition
from wakefulness to stage N1. Stage N1 is normally brief and is followed ELDERLY
by stage N2. Stage N3 (slow wave sleep) follows and is usually sustained, AWAKE
especially in children and young adults. Sleep then briefly lightens to stage REM
N2 before an initial brief REM period. This first period of stage R occurs
SLEEP STAGES
1
approximately 90 minutes after sleep onset and completes the first sleep
cycle. This complete cycle is then repeated three to five times during the 2
night, but the amount of stage N3 diminishes during ensuing cycles, while
3
the amount of stage R increases. Histograms are useful to visually display
the ultradian cycle within a night’s sleep (Fig. 18.9) (39). 4
Predictable changes in sleep architecture occur with age. Beginning in
middle age, Stage N3 becomes less prominent, the number of awaken- 1 2 3 4 5 6 7
ings increase, and sleep efficiency decreases. Published information on HOURS OF SLEEP
normal sleep can serve as an outline for normal values in PSG (39,40)
Figure 18.9: Histograms representing normal sleep cycles for age. REM sleep
(Table 18.2).
(darkened area) occurs cyclically throughout the night at intervals of approxi-
Scoring is usually done on an epoch-by-epoch basis, with epoch lengths mately 90 minutes. REM sleep shows little variation in the different age groups,
standardized at 30 seconds. Epochs are scored according to the AASM whereas stage N3 (labeled here as stages 3 and 4 sleep) can be seen to decrease
guidelines, and each epoch is scored as the stage that occupies greater than with age. Note also the frequent awakenings and increase in total wake time
seen in the elderly. (From Kales A, Kales J. Sleep disorders: recent findings in the
diagnosis and treatment of disturbed sleep. N Engl J Med 1974;290:487–499.)
TABLE 18.2 Average Values for Healthy Adults of Different Ages activity. Phasic EMG activity may occur, but tonic activity must be at a level
that is as low as, or lower than, that during any other time in the study. Sleep
Age (y) spindles and K complexes are absent. Series of 2- to 5-Hz vertex-negative
“sawtooth waves” occur, particularly just before phasic REM activity. The
Index 21–30 41–50 61–70
requirements to score sleep as stage R are the presence of REMs, low or
Time in bed (TIB) (min) 480 480 456 absent axial EMG, and the typical mixed-frequency EEG recording that does
Total sleep time (TST) (min) 446 395 350 not preclude the scoring of stage R (e.g., no sleep spindles can be seen).
Sleep efficiency (TST/TIB, %) 95 85 81 Movement time: Movement time is no longer scored, but rather any epoch
Stage N1 (%) 9 14 16 for which over 50% of the epoch is obscured by movement or EMG is scored
Stage N2 (%) 54 52 46 according to the following guidelines: If alpha activity is present for any part
Stage N3 (%) 13 7 3 of the epoch, score the epoch as stage W; if no alpha is present, but either
REM (%) 19 14 15 the preceding or following epochs are scored as stage W, then the epoch is
Arousal index 10.8 (±4.6) 16.5 (±5.6) 21.9 (±6.8) scored as stage W; otherwise, score the epoch as the same stage as the epoch
that follows it.
REM, rapid eye movement. Additional sleep values: Additional sleep parameters are determined from
From Bonnet MH, Arand DA. EEG arousal norms by age. J Clin Sleep Med 2007;3(3): each PSG and are used in the clinical interpretation of the study. These
271–274. additional variables include the following:
1. Recording time (RT)—is the time elapsed between “lights out” and
“lights on” at end of study.
50% of that epoch (Fig. 18.1). The following is a summary of the rules of
2. Total sleep time (TST)—is the total time occupied by stages N1, N2,
sleep scoring:
N3, and R.
Stage W: Stage W corresponds to the waking stage and is characterized
3. Sleep efficiency—is defined as TST/RT and is expressed as a percentage.
by alpha activity or low-voltage mixed-frequency EEG activity. REMs, eye
4. Sleep latency—is the time from “lights out” to the first epoch scored as
blinks, and tonic EMG activity are usually present.
sleep. Some clinicians prefer to use the first epoch of stage 2 in order to
Stage N1: Stage N1 is scored when greater than 50% of an epoch is low-
be more confident about identifying the onset of sustained sleep. How-
voltage 2- to 7-Hz activity. Vertex waves (<0.5 second in duration) may
ever, when sleep is very disrupted, there may be an extended period of
occur in late stage N1. Slow rolling eye movements lasting several seconds
time from recognition of stage N1 until an epoch that can be scored as
are routinely seen early in stage N1, but K complexes and sleep spindles are
stage N2.
absent by definition. Tonic EMG activity is usually less than that of relaxed
5. REM latency—is the time from sleep onset (as described earlier) to the
wakefulness.
first epoch scored as REM. Some authors advocate subtracting out any
Stage N2: Stage N2 requires the presence of sleep spindles or K com-
intervening epochs scored as wakefulness, but this is not done in most
plexes, and less than 20% of the epoch should contain scorable delta activ-
clinical laboratories.
ity. Spindle activity in the range of 11to 16 Hz must last at least 0.5 second
6. Sleep stage percentages (stages N1%, N2%, N3%, and R%)—are deter-
before it can be scored a sleep spindle. K complexes are defined as biphasic
mined by dividing time recorded in each sleep stage by TST.
vertex sharp waves with a total duration of greater than 0.5 second.
7. Wake after sleep onset (WASO): time spent awake after sleep onset.
Stage N3: Stage N3 is scored when greater than 20% of an epoch consists
of delta activity that is 2 Hz or slower and that is greater than 75 μV in
amplitude. Sleep spindles may or may not be present in stage N3. Arousals/Awakenings
Stage R: Stage R is characterized by relatively low-voltage mixed-frequency In the R&K Atlas, an awakening was defined as a return of the patient’s
EEG activity with episodic REMs and absent or markedly reduced axial EMG waking background for at least 30 seconds (6). An arousal, by R&K criteria,
was scored when a patient’s waking alpha activity returned for more than with at least 10 seconds of stable sleep preceding the change. Scoring
3 seconds but less than 30 seconds. However, most arousals from sleep are of arousals during REM requires a concurrent increase in submental
more subtle than that just described, and for many years there were no exact EMG lasting at least 1 second. (Figs. 18.10 to 18.14)
definitions as to how to identify and score these “mircroarousals.” The tran-
It should be noted that these EEG arousal criteria are based on EEG
sient nature of these arousals led to their being overlooked in the standard
changes alone with one exception; an increase in submental EMG is required
30-second epoch sleep scoring system. These brief arousals are usually char-
for demonstration of arousal from REM sleep (Fig. 18.13). The criterion
acterized on a standard PSG by an abrupt change in EEG frequency with or
of defining arousal as being 3 seconds or greater in duration is simply a
without a brief increase in EMG amplitude. With the increasing recognition
methodologic one and does not have specific physiologic significance. It was
that arousals result in fragmented sleep, which in turn leads to increased
simply chosen to allow reliability between observers for scoring arousals.
daytime sleepiness, the need for specific and reliable criteria for the identifi-
The present EEG arousal scoring rules may underestimate the frequency
cation of arousals became sorely evident (41). In 1992, the Sleep Disorders
of arousals. Specifically, they ignore rhythmic delta activity or a series of
Task Force of the AASM published carefully defined rules for scoring an
vertex waves as an arousal (Fig. 18.14). These events, particularly when
arousal (42). This guide to scoring arousals has been simplified in the recent
accompanied by another change in the PSG (i.e., increase in submental
AASM Scoring Manual:
EMG or return of ventilation) almost assuredly represent a comparable
Score arousal during sleep stages N1, N2, N3, or R if there is an physiologic arousal. However, the same EEG changes can be seen without
abrupt shift of EEG frequency including alpha, theta, and/or frequen- other evidence of arousal, and the judgment was made not to include this
cies greater than 16 Hz (but not spindles) that lasts at least 3 seconds, EEG pattern as a scorable arousal.
Figure 18.10: This is a greater than 3-second

EEG change with frequencies greater than
16 Hz and alpha activity. This EEG arousal
also has increased EMG amplitude. There are
greater than 10 seconds of sleep preceding
this event, and it is scored as an arousal. (From
Bonnet M, Carley D, Carskadon M, et al. EEG
arousals: scoring rules and examples. Sleep
1992;15:173–184.)
Figure 18.11: The EEG frequency change in

this epoch of NREM is scored as an arousal
despite the absence of an EMG ampli-
tude increase. (From Bonnet M, Carley D,
Carskadon M, et al. EEG arousals: scoring
rules and examples. Sleep 1992;15:173–184.)
Figure 18.12: The EEG frequency change

in this epoch of REM sleep is scored as an
arousal as there is both an EMG amplitude
increase and EEG change of greater than
3 seconds duration. (From Bonnet M, Carley
D, Carskadon M, et al. EEG arousals: scoring
rules and examples. Sleep 1992;15:173–184.)
Figure 18.13: The EEG frequency change

on this epoch of REM sleep (arrow) is not ac-
companied by an increase in EMG amplitude
and thus is not scored as an arousal. (From
Bonnet M, Carley D, Carskadon M, et al. EEG
arousals: scoring rules and examples. Sleep
1992;15:173–184.)
Figure 18.14: The delta burst of this example

(arrow) is not scored as an arousal as there is no
arousal-type EEG, although there is an EMG
amplitude increase. (From Bonnet M, Carley D,
Carskadon M, et al. EEG arousals: scoring rules
and examples. Sleep 1992;15:173–184.)
Respiratory-Related Variables obstructive component. It should be emphasized that obstructive apneas

with feeble accompanying inspiratory efforts may be incorrectly labeled as
An apnea is defined as a cessation (or 90% decrease) of baseline airflow central apneas by all commonly used techniques for assessing ventilatory
from nasal and mouth thermistors or thermocouples that persists for effort. When there is doubt, the use of esophageal pressure monitoring can
10 seconds or more (19) (see Fig. 18.5). Baseline airflow is defined by the clarify whether any respiratory effort is present as identified by intrathoracic
airflow preceding and following the respiratory event in question. There pressure swings (43). Apneas are not scored from the NPT channel as it is
is no requirement for any minimum oxygen desaturation or EEG arousal very sensitive to changes in airflow and often appears flat when there is clear
in the scoring of an apnea. The event is scored as an obstructive apnea if airflow registered on thermistor/thermocouple channel (Fig. 18.15).
there is evidence on chest and abdominal monitors of continued or increas- Physiologic apneas occur in nearly every study. These are brief (10 to
ing respiratory effort throughout the period of apnea. The event is scored 20 seconds) central apneas that occur during the transition from wakeful-
as a mixed apnea if there is no apparent ventilatory effort at onset of the ness to sleep or during bursts of phasic REM activity during REM sleep.
apnea followed by return of ventilatory effort during the apneic period. These events are scored and contribute to the calculation of the AHI.
Central apnea is scored if no respiratory effort can be detected throughout Consensus as to how to score hypopneas has long been lacking, leading to
the entire period of apnea. An apparent central apnea that is consistently a difficulty in extending results from one laboratory to another. Even with
terminated by a loud “snort” should be reviewed carefully to exclude any the publication of the AASM Scoring Manual in 2007, there were still two
Figure 18.15: PSG showing prominent flat-

tening of nasal pressure transducer channel
(labeled PTAF) while flow channel (from oro-
nasal thermocouple) demonstrates no definite
decrease in airflow. This respiratory event would
be labeled as a hypopnea.
definitions put forth. The “recommended definition” was a 30% decline in in pre-event breathing. The event is scored as a central hypopnea if none of
airflow as measured in the NPT channel that lasts at least 10 seconds and those three criteria are present.
is accompanied by at least a 4% decline in Sao2. This was adopted as the Monitoring of Sao2 via pulse oximeter is part of a standard PSG. Sev-
recommended definition as it was consistent with that used by Medicare. eral measures of oxygen desaturation have been employed. Most sleep
However, the “alternative definition” was actually more commonly used as report programs are able to generate a convenient graphical format of the
it was much more sensitive to the identification of hypopneas and eliminated cumulative Sao2 histogram (Fig. 18.16). From this oximetry data, several
the need to score RERAs. The alternative definition defined a hypopnea as parameters are usually derived, including desaturation index (number of
requiring a 50% decline in airflow in the NPT channel that lasts 10 sec- desaturations of at least 3% per hour of sleep), mean arterial saturation,
onds and is accompanied by either a 3% or more decline in Sao2 or an EEG minimum arterial saturation, and percent time spent below 88%. The oxy-
arousal. More recently, in the 2012 update, there is only one definition for a gen desaturation index is an important complement to the AHI in determin-
hypopnea. The updated definition for a hypopnea requires a 30% decrease ing disease severity. Of note, the desaturation index assumes even greater
in airflow from the NPT channel that lasts greater than 10 seconds and is importance in pediatric patients as it is more sensitive to SDB than scorable
accompanied by either a 3% or greater desaturation or an EEG arousal. apneas or hypopneas.
Regardless of the definition of a hypopnea, there are sometimes other
events that are presumed to be respiratory in character, and that are Diagnosis of Sleep Apnea
unscorable by the criteria described earlier. These events have been labeled The diagnosis of sleep apnea has traditionally been based on recording five
as RERAs. The definition of a RERA is a sequence of breaths lasting at or more respiratory events (apneas plus hypopneas) per hour of sleep (AHI
least 10 seconds, characterized by either increasing respiratory effort or flat- > 5) (46). This standard is derived from investigation of a small popula-
tening of the inspiratory portion of the NPT tracing or PAP device that tion of middle-aged control subjects free of sleep complaints. Recent stud-
is accompanied by an EEG arousal from sleep. The scoring of RERAs is ies, however, indicated that a significant percentage (approximately 40%) of
optional per the AASM Scoring Manual, and is not practiced by most labs normal elderly subjects over the age of 60 have sleep apnea when using that
as the sensitivity of the NPT to decreased airflow has led to the identifica- criterion (47–50). Most studies have not been able to identify any associated
tion of most of these events as hypopneas. neuropsychologic or medical complications in the patients identified with
In the early 1990s, Guilleminault and colleagues (44,45) coined the term mild apnea in these screening studies. Therefore, the rigid application of
“upper-airway resistance syndrome” to encompass those patients who have AHI greater than 5 as diagnostic of sleep apnea may lead to the overdiagno-
clinical manifestations of sleep apnea in the absence of truly scorable respi- sis of the sleep apnea syndrome, particularly in an elderly population (47). A
ratory events. However, with the widespread use of the NPT recordings for more reasonable criterion may be an AHI of 10 in middle-aged patients and
airflow and the associated increase in sensitivity to the scoring of hypop- a AHI of l5 in patients over the age of 60. In our experience, AHIs below
neas, patients with an upper-airway resistance syndrome presentation have this cutoff are uncommonly associated with daytime complaints. However,
become uncommon. there are data in the literature, documenting that patients with an AHI
In patients who have recurrent hypopneas, no attempt has been made to greater than 15 to 20 do have a significant increase in subsequent long-term
characterize these events as central or obstructive, as most observers did cardiovascular morbidity (51).
not believe accurate identification was possible. However, in the new 2012 Multiple factors must be analyzed in determining the severity of sleep
Scoring Manual (10), definitions of obstructive and central hypopneas are apnea. Certainly, the AHI is of great importance, but apnea duration, degree
provided. The guidelines list the scoring of obstructive or central hypopneas of O2 desaturation, and associated cardiac dysrhythmias must be incorpo-
as an optional scoring technique and do not require its practice for lab certi- rated into the decision-making process. The positional nature needs to be
fication. An obstructive hypopnea is scored if any of the following are pres- assessed, as many patients will have severe apnea on their back, but dem-
ent: (a) snoring during the event; (b) flattening of the NPT or PAP device onstrate little or no apnea on their side. The exact factors that contribute to
flow signal is noted as compared with baseline breathing; or (c) paradoxical long-term morbidity or mortality of sleep apnea have not been identified.
thoracoabdominal movements occur during the event and are not present Surprisingly, the degree of sleepiness is not closely correlated with the AHI
Figure 18.16: Sleep histogram, CPAP pressure, apneas, hy-

popneas, and oxygen desaturation displayed for overnight
PSG. Note prominent oxygen desaturations associated with
recurrent hypopneas. More severe desaturations (arrows) are
noted during REM sleep (darkened line). Marked improve-
ment in respiratory events and oxygen desaturations noted
with CPAP pressure of 8 cm H2O and above. Slightly higher
CPAP pressures were required to control desaturations in
REM sleep.
or degree of O2 desaturation. Rather, sleepiness is more closely correlated of 20 to 40 as representing moderate sleep apnea, and an AHI greater than
with the degree of sleep fragmentation, as reflected by an increase in awaken- 40 as being severe sleep apnea.
ings, arousals, and stage Nl% with an accompanying decrease in stage N3%
(52–54). In defining severity of sleep apnea, the AHI is the center of that Pediatric Sleep-Disordered Breathing
assessment. The AASM task force recently published their categorization The foregoing discussion focuses on evaluating adult patients. The diagnosis
for OSA severity. The AASM defines an AHI of between 5 and 15 as repre- and sleep laboratory evaluation of pediatric patients for OSA is much more
senting mild sleep apnea, an AHI of 15 to 30 as being moderate sleep apnea, challenging.
and an AHI of less than 30 as severe sleep apnea. The AASM does recognize Clinically, the patients usually present with witnessed snoring and struggling
that there are no current prospective studies to validate these criteria (19). nocturnal respiration. They are much less likely to be obese or to be sleepy
My personal approach is to label an AHI of 5 to 10 as evidence of minimal during the day. The abnormalities identified on PSG in pediatric patients are
sleep apnea, an AHI of 10 to 20 as representing mild sleep apnea, an AHI much less profound and require a greater degree of clinical judgment.
In a study by Rosen and colleagues (55), the investigators examined hypoventilation (55). The AASM Scoring Manual takes a more conserva-
olysomnographic data from 20 children who had clinical evidence of
p tive approach of a Petco2 greater than 50% for greater than 25% of TST.
upper-airway obstruction during sleep (loud snoring and labored breath- The new Scoring Manual outlines scoring rules for pediatric patients.
ing) and who had accompanying O2 desaturations during sleep. These Most of these apply to patients under the age of 13, as post-pubescent chil-
children were felt to confidently represent a clinical syndrome of OSA in dren usually present in a fashion similar to adult patients. Technical specifi-
children. Remarkably, the mean apnea index was only 2 in this population. cations are similar to adult recordings except for the use of transcutaneous
This was despite the fact that they experienced an average of 175 O2 desat- CO2 and end-tidal CO2. In pediatric patients, an obstructive apnea is scored
urations greater than 5% each night and with an average minimum Sao2 if the event lasts at least the duration of two breaths in the baseline breath-
of 66%. The authors concluded from this study that episodes of complete ing and is associated with respiratory effort throughout the period. A central
airway obstruction are generally rare in children even in the setting of seri- apnea is scored if inspiratory effort is absent throughout the period and is
ous sleep-related upper-airway obstruction and that the adult criteria for accompanied by one of the following: (a) the event lasts at least 20 seconds;
OSA failed to identify the majority of children with serious upper-airway (b) the event lasts the duration of at least two breaths and is associated with
obstruction. The presence of any obstructive apneas lasting 10 seconds in a 3% oxygen desaturation or an EEG arousal; (c) the event is associated with
a child should be met with suspicion of indicating significant airway com- a decrease in heart rate to less than 50 beats per minute for at least 5 seconds.
promise. Similarly, greater attention needs to be paid to any episodes of O2 A mixed event is scored when the event lasts at least the duration of two
desaturation. breaths and has both a period of absent respiratory effort and a period of
The polysomnographic evaluation of normal children also indicates that persistent respiratory effort. The rules for scoring a hypopnea in a pediatric
apneas are much less frequent in children than in adults. In 50 normal chil- patient are the same as in an adult, except the duration requirement is at
dren studied by Marcus and colleagues (56), the mean apneic index was 0.1. least two breaths. Hypoventilation is scored when greater than 25% of TST
The mean number of desaturations greater than 4% per hour of sleep was has a Pco2 greater than 50 mm Hg (as recorded by arterial Pco2, transcuta-
0.3. Only 9 (18%) children had any obstructive apneas identified and only 2 neous Pco2, or Petco2).
(4%) children had apneas lasting 10 seconds. Only one child had more than The indications for PSG evaluation in a pediatric population have evolved
two obstructive apneas in a night’s sleep. Out of these data, the authors during recent years and were recently summarized in a practice parameter
recommended a “normal value” for an apnea index in a child is less than 1. published in 2011 by the AASM (58). The main indication, as in adults, is
In addition, the mean minimum Sao2 was 96% and only one child ever went the evaluation of possible OSA. PSG may be appropriate before adenoton-
below 90% O2 saturation. The authors, recommended value for the minimum sillectomy (AT) if moderate to severe OSA is suspected owing to a greater
Sao2 in children is greater than 92%. The recommended normal value for the degree of perioperative complications in this population. PSG evaluation
number of desaturations greater than or equal to 4% per hour of sleep was of residual OSA after AT is indicated if moderate to severe OSA was pres-
less than l.4. A subsequent study of normal children yielded remarkably ent preoperatively. PSG is also indicated for evaluation of possible central
similar results and reinforced these observations (57). This second study by alveolar hypoventilation syndrome or sleep-related hypoventilation due to
Uliel and colleagues recommended limits for normal values (based on ±2 neuromuscular disorders or chest wall deformities.
standard deviations) as follows: OA index 1; CA index 0.9; minimum oxygen
desaturation 89%; baseline Sao2 92%. Movement-Related Variables
Given the lack of overt apneas and the possible lack of sensitivity of O2
changes, additional markers of SDB have been sought in pediatric patients. Periodic limb movements in sleep (PLMS) are repetitive, stereotyped move-
The most useful measure identified to date is the end-tidal CO2. Several ments of the lower extremities that occur during sleep (59–61). They were
defined guidelines have been provided, but the most useful appears to be previously called nocturnal myoclonus, but this term has been replaced by
defining the persistence of a Petco2 equal to or greater than 45 mm Hg PLMS because the movements are not truly myoclonic and also because
for greater than 10% of the TST (56,57). Investigators believe this value there might be confusion with other true myoclonic events that can occur
to reliably distinguish snoring from clinically significant obstructive during sleep. PLMS are characterized by tonic extension of the great toe,
with occasional superimposed clonic activity, variably accompanied by does not play a role in the diagnosis. It is important to emphasize that PLMS
ankle dorsiflexion and knee flexion. Lower-extremity movements are scored are present in a broad range of sleep disorders, and their pathophysiology
as PLMS when anterior tibialis EMG activity lasts 0.5 to –10 seconds and and exact clinical significance remain poorly understood (17,60).
at least four movements occur in a cluster with an intermovement inter-
val of 5 to 90 seconds. The most common intermovement interval is 20 to MULTIPLE SLEEP LATENCY TEST
40 seconds (see Fig. 18.4). The minimum amplitude for the EMG increase
is defined as 8 μV. The MSLT is a multiple-nap trial designed to quantify the patient’s
Movement-associated arousals (also termed PLMS-associated arousals, sleepiness and assess the presence of sleep-onset REM periods (SOREM)
PLMSAr) are routinely scored with each PLMS if there is no associated (66–69). It serves as the “gold standard” for the assessment of excessive
respiratory dysrhythmia and if the EEG arousal follows the movement daytime sleepiness (EDS), but clearly has significant limitations. Other
within a few seconds. Oftentimes, EEG arousal will vary in its relation to measures of sleepiness (pupillometry [70], ESS [71,72]) are either too techni-
anterior tibialis EMG activity. It may occur just before, synchronous with, cally cumbersome or too subjective to warrant widespread clinical use. The
or just after EMG activity (62). The Scoring Manual defines an arousal and MSLT provides an objective quantification of “sleepiness” and is useful in
a PLMS as associated with each other when there is less than 0.5 second the clinical determination of pathologic hypersomnolence. Opportunities to
between the end of one event and the onset of the other, regardless of which nap are given at 2-hour intervals across the day, thereby allowing the inves-
is first. Obviously, care needs to be taken to be sure that no other cause tigators to obtain a sampling of the diurnal variation of the patient’s sleep
(e.g., recurrent hypopneas) exists that may underlie these recurrent arousals. tendency.
While arousals that immediately precede the leg movements may not seem
to be “movement-associated,” Lugaresi and colleagues (60) have postulated MSLT Procedure
an internal “pacemaker” that gives rise to both the arousal and the leg move-
ment. As such, the leg movement and EEG arousal often occur in a mildly The patient obtains a usual night’s rest prior to the study. Most investigators
asynchronous and variable fashion. require that the preceding night’s sleep be documented by PSG to ensure
Scored PLMS events are counted and divided by hours of sleep to yield adequate sleep and exclude sleep disruption (e.g., sleep apnea, PLMS) as a
a PLMS index (PLMSI). The number of PLMS-associated arousals is also contributing etiology to the complaints of EDS. TST of less than 6 hours on
divided by the hours of sleep to yield a PLMS arousal index (PLMSArI) the preceding overnight PSG may impact on subsequent mean sleep latency
(59,63). and effect clinical interpretation. Many labs require a sleep log to be kept the
The basis for labeling an individual as suffering from Periodic Limb Move- week prior to the MSLT to document preceding sleep–wake schedules. Stim-
ment Disorder (PLMD) was originally determined to be five movements per ulants and REM-suppressing medications should be stopped 2 weeks prior
hour of sleep (18). However, it soon became apparent that there was a large to the study. Urine drug screening the morning of the study may be appropri-
population of asymptomatic individuals who had more than five move- ate to ensure that the sleepiness is not pharmacologically induced. Patients
ments per hour (59). Bixler et al. (64) demonstrated an 11% incidence of are asked to abstain from caffeine consumption on the day of the study.
PLMS (using a PLSI > 5) in normal subjects and noted a marked increase The patient arrives at the laboratory in time to allow the application of
in incidence with age. However, none of these subjects had more than five electrodes. At a minimum, electrodes are placed to monitor central and
arousals per hour related to these leg movements. Other studies have shown occipital EEG, submental EMG, EOG, and ECG. A sample montage is
that in patients with hypersomnolence, the degree of sleep disruption is cor- displayed in Table 18.3. The first nap trial is initiated 1.5 to 3 hours after
related with the severity of excessive daytime sleepiness (46,65), although the patient has awakened from nocturnal sleep. Four or five scheduled nap
this has not been a consistent observation. times are scheduled during the day (i.e., 9:30 a.m., 11:30 a.m., 1:30 p.m.,
The present definition of PLMD requires a PLMS index of greater than 3:30 p.m., and 5:30 p.m.). At each trial, the patient lies down in his street
15 (>5 in children), a complaint of disturbed sleep or daytime fatigue, and clothes and assumes a comfortable sleep position. To standardize physical
the absence of a potential alternative etiology (e.g., OSA). The PLMSArI activity, a 15-minute quiet period immediately precedes each nap. The sleep
TABLE 18.3 MSLT Montage (awakening) is defined as two consecutive epochs of wakefulness after sleep
onset. All scoring is done using the criteria of the AASM Scoring Manual.
Sensitivity Filters Each nap is reviewed for evidence of stage R sleep (Fig. 18.17). Stage R is
Channel (µV/mm) (LFF/HFF) (Hz) scored as per AASM criteria and is determined by the first epoch scored
1. C4-A1 7 0.3/35 as REM sleep. REM latency (latency to REM onset after sleep onset) is
2. F4-A1 7 0.3/35 usually determined, but the most important observation is the presence or
3. O2-A1 7 0.3/35 absence of REM during each nap trial. Each nap is terminated when: (a)
4. T3-Cz 7 0.3/35 20 minutes after the trial started if no sleep has occurred, (b) after 15 min-
5. Cz-T4 7 0.3/35 utes of continuous sleep as long as sleep-onset criteria are met before the
6. Left eye-A1 7 0.3/35 end of 20 minutes, or (c) after 20 minutes if the patient awakens, even if less
7. Right eye-A1 7 0.3/35 than 15 minutes of sleep has occurred. The patient is instructed to maintain
8. Submental electromyogram 2 10/100 wakefulness (and is observed if possible) between each nap period.
9. Electrocardiogram 75 0.3/70
LFF, low-frequency filter; HFF, high-frequency filter. MSLT Interpretation
The interpreter determines the latency to sleep onset and the presence or
room should be quiet, dark, and free of environmental noise. As the trial absence of REM sleep for each nap trial. Sleep onset is usually taken as the
is about to begin, the technician instructs the patient to “close your eyes first 30-second epoch of stage 1 sleep or deeper sleep stage. A 30-second
and attempt to sleep,” turns off the lights, exits from the room, and begins epoch is scored as wakefulness if the majority of the 30-second period
recording. demonstrates a waking pattern. Stage N1 is determined if the majority of
The MSLT is routinely scored in 30-second epochs. Sleep onset is defined the 30-second epoch is stage N1 sleep. Thus, a brief return of alpha activity
as the first 30-second epoch scored as stage 1 or deeper sleep. Sleep offset for 5 to 10 seconds does not result in an awakening, nor does it necessarily
Figure 18.17: Sleep-onset REM (SOREM) period. PSG record demonstrates the appearance of a low-voltage, mixed-frequency EEG, accompanied by the abrupt loss
of tonic EMG activity and the appearance of REM activity. (From Hari P. The sleep disorders. Kalamazoo, MI: Upjohn Co., 1982:5–62.)
prevent the scoring of an epoch as sleep. In subjects who have an identi- mean in this normal population, the “normal” MSL range would be between
fied alpha rhythm, stage N1 is scored when greater than 50% of an epoch 2 and 20 minutes. The MSL for patients with narcolepsy is 3.1 ± 2.9 min-
has loss of the alpha rhythm, which is replaced by low-amplitude, mixed- utes. Given this large overlap, the MSLT result alone should not be the sole
frequency activity. In subjects who do not generate an alpha rhythm, stage criterion for determining the presence or absence of EDS. The assessment of
N1 is scored when any of the following occur: (a) 4 to 7 Hz activity is seen a patient’s sleepiness should include integration of clinical history, objective
that is at least 1 Hz slower than waking background frequencies; (b) vertex test results, and other medical information.
sharp waves; (c) SEMs. These findings need to be present for over 50% of Nonpathologic factors importantly affect the MSLT. MSL is related to
the epoch in question. the amount of sleep on one or several preceding nights, age, continuity of
Individual sleep latencies are then averaged to determine mean sleep latency sleep, time of day, and drug use (74–78). It is therefore necessary to review
(MSL). MSLT results in different populations are shown in Table 18.4. An carefully, preferably using a sleep diary, the patient’s sleep pattern over the
MSL of less than 5 minutes is labeled indicative of pathologic hypersomno- 7 to 10 days before the study. It is this need to ensure adequate noctur-
lence. It is a direct indication of the individual’s vulnerability to falling asleep nal sleep for accurate MSLT results that has led most sleep clinicians to
in a low-stimulus situation and is associated with performance decrements require overnight PSG the night prior to the MSLT. However, sleep depri-
and unintentional episodes of sleep. An MSL of greater than 10 minutes is vation occurring only the night before the study must usually result in less
“normal” and does not reflect significant sleepiness. An MSL between 5 and than 5 to 6 hours of total sleep to significantly affect MSL (74). Drugs also
10 minutes is the “gray zone” into which some normal and some hypersom- affect sleep latency (sedative-hypnotics, antihistamines, and stimulants) or
nolent patients fall. There is no consensus as to the clinical significance that REM latency (tricyclic antidepressants, MAO inhibitors, and stimulants)
should be applied to results in this range. Labeling an MSL of greater than (79). Therefore, withdrawal from these medications is recommended before
5 but less than 10 minutes as suggestive but not diagnostic of pathologic the MSLT is performed. A 2-week period of drug abstinence is empirically
hypersomnolence is probably the most reasonable approach. If a single cut- required, although there are no good data on the exact time course of medi-
off value is utilized, some authors suggest 8 minutes as a rational dividing cation withdrawal effects.
point between normal (>8 minutes) and abnormal (<8 minutes) (73). Somewhat surprisingly, the MSLT has not been an effective measure of
A well-defined normative range for the MSL is limited by the large stan- treatment response in most narcolepsy patients. Treated narcoleptic patients
dard deviation, which results in a large overlap between MSL values for con- do not have a significant change in MSL even though they report improved
trols and patients with excessive sleepiness. Pooled data from normal subjects alertness. Mitler and others, in an attempt to be more sensitive to this
of all ages give a MSL of 10.4 ± 4.3 minutes for the 4 nap protocol and 11.6 ± improvement, devised a MWT (80,81). The main difference from the MSLT
5.2 minutes for the 5 nap protocol. Using two standard deviations from the is that the subjects are instructed to remain awake during each trial. This
results in some increased sensitivity to treatment effects. The MWT protocol
is discussed more completely in the next section of this chapter.
TABLE 18.4 MSL Test (Five Nap Trials) Premature onset of REM sleep in narcoleptic patients was first noted by
Vogel (82) and linked to narcolepsy by Rechtschaffen (2). A single daytime
Number of REM-Sleep nap to detect early-onset REM was used initially, but it proved to be less
Episodes (% of Group) than ideal because of its insensitivity in identifying REM-sleep pathol-
ogy. The MSLT was developed to allow repeated sampling of sleep and to
Group MSL (min) 0 1 2 or more
increase the sensitivity to SOREMs. When first described by the Stanford
Narcoleptics (n = 49) 2.9 (±2.7) 2 2 96 University sleep group, each nap allowed a 10-minute period of sustained
Non-narcoleptic, non-sleep 8.7 (±4.9) 92 8 0 sleep, and two of five naps had to demonstrate REM-sleep onset in order to
apneic EDS (n = 63) be diagnostic of narcolepsy. The recommended protocol for the MSLT was
Controls (n = 13) 13.4 (±4.3) 100 0 0 subsequently changed to allow the patient a 15-minute period of sustained
sleep (64). Because SOREMs are extremely rare in normal rested individuals,
some clinicians interpret a single REM-onset nap as support for the diag- remains awake or is terminated after three consecutive epochs of stage N1
nosis of narcolepsy. However, just as many factors affect MSL, there are sleep. Three additional trials are then carried out at 2-hour intervals. Preced-
circumstances other than narcolepsy that may result in SOREMs (54,83). ing overnight PSG is not required before a MWT, but may be performed as
Medications, sleep deprivation, and time of day have all been described to per the judgment of the referring physician. Urine drug screen are routinely
affect the incidence of SOREMs (79). Nonetheless, a single SOREM, with done on the morning of the study to assess for stimulant medication use.
documentation of adequate and uninterrupted sleep the night prior to the As with the MSLT, the MWT is scored by 30-second epochs, and sleep
study, is certainly unusual but needs to be assessed in light of the clinical his- onset is defined as the first epoch scored as stage N1 or deeper sleep. If no
tory or other diagnostic studies. Two REM-onset naps are clearly abnormal sleep is recorded, a 40-minute sleep latency is used for that nap. The four tri-
and consistent with abnormal REM pressure. Most commonly, this is due als are averaged to determine the MSL.
to narcolepsy but also has been described in sleep apnea, drug withdrawal,
severe depression, and myotonic dystrophy (79,84,85). MWT Interpretation
MAINTENANCE OF WAKEFULNESS TEST Normative values are derived from a small number of studies using the proto-
col described (86,87). The MSL in those studies was 30.4 ± 11.2 minutes. Those
The MWT was developed in an attempt to be a more sensitive measure of studies demonstrated that 59% of normal subjects will remain awake for all four
the response to treatment effects in someone with excessive sleepiness. Its trials and have a MSL of 40 minutes. Comparatively, only 2.5% of normal sub-
primary application is in evaluating the alertness of individuals with sleep jects had a MSL of less than 8 minutes. Staying awake for all of the 40-minute
apnea or narcolepsy who are employed in occupations involving public safety trials provides the strongest objective data supporting the individual’s ability to
or transportation. The MWT, which measures the ability of the individual stay awake. Based on these data, a MSL of less than 8 minutes is abnormal and
to stay awake, has greater face validity than the MSLT, which measures the suggests residual daytime sleepiness. The large area between 8 and 40 minutes is
ability to fall asleep. However, the predictive value for the MWT MSL for more difficult to deal with in terms of its clinical significance (86).
assessing accident risk and safety in real-world circumstances has not been A recent study looked at a functional task (in patients with sleep apnea)
established. Just as with the MSLT, the wide range of normative data makes and compared their performance with their results on the MWT 40-minute
using the MWT in isolation as a predictor of daytime function problematic. protocol (87). Their results support that patients with an MSL of greater
The recommendation is to use the MWT results in combination with other than 33 minutes performed as well as those with a MSL of 40 minutes.
findings such as clinical history and compliance with therapy in making a Patients with an MSL of less than 8 minutes clearly performed in an impaired
judgment regarding the safety of an individual in the workplace. fashion on the driving simulator task. With these results, my own personal
approach is to interpret an MWT with an MSL of greater than 33 minutes
MWT Procedure as indicative of normal daytime alertness. Those noted to have an MSL of
less than 8 minutes are judged to have EDS. Those in the gray area between
Several MWT protocols have been used, but the AASM recommends the 8 and 33 minutes are in a “diagnostic gray area,” and no strong clinical judg-
use of the 40-minute protocol. Similar to the MSLT, the initial trial of the ment as to their daytime alertness is possible. As emphasized here, the MWT
MWT begins 1.5 to 3 hours after the patient’s wake up time. The first nap is a limited test and should not be used in isolation in determining the func-
usually begins at 8 and 10 a.m. A recording similar to the MSLT montage tional safety of an individual with possible daytime sleepiness.
is utilized. The patient is placed in a quiet dark room that is shielded from
external light. A light source (7.5 W night light) is placed behind the patient. Clinical Evaluation of Sleep Disorders
The patient is seated in a comfortable padded chair. The patient is then
instructed to “Please sit still and remain awake as long as possible.” Patients The most common sleep-related complaints seen in a sleep center are EDS,
are not allowed to use extraordinary measures (singing, hitting oneself) in disturbed nocturnal breathing, unusual nocturnal behavior (parasomnia), and
order to remain awake. The trial is continued for 40 minutes if the patient difficulty with initiating or sustaining sleep (insomnia) (88). Following are brief
discussions of the clinical approach to evaluating patients presenting with these The initial assessment of a patient’s sleep–wake complaint is usually aided
common complaints. Comprehensive reviews that include discussion of patho- by the completion of sleep diaries for 1 to 2 weeks prior to the appoint-
physiology and treatment of these disorders are available elsewhere (89–91). ment. These are particularly helpful in identifying sleep restriction or sleep
cycle abnormalities that may be contributing to the patient’s complaints.
Evaluation of Excessive Daytime Sleepiness Routine medical evaluation is appropriate for all patients with EDS. Screen-
ing for general medical concerns (e.g., hypothyroidism) is appropriate before
A wide range of diagnoses must be entertained in evaluating EDS. Sleep sleep center evaluation. Attention to possible psychiatric symptoms is also
apnea is by far the most common diagnosis in patients presenting with appropriate. Many patients with EDS will frequently present with a picture
daytime sleepiness. Other primary sleep pathologies include narcolepsy, that resembles depression, and as such the differentiation sometimes is quite
idiopathic hypersomnia, and PLMD. It is important to exclude other con- difficult. However, if no overt medical problem is identified and the patient
tributing factors, including sleep restriction or the effects of medications has a history clearly suggestive of pathologic sleepiness, sleep laboratory
or drugs. Figure 18.18 presents a diagnostic algorithm, as proposed by evaluation is appropriate.
an ASDA task force, that can be applied to the clinical assessment of the The usual recommendation is for overnight PSG and possibly an MSLT.
“sleepy” patient (92). If there is a strong clinical suspicion of OSA, usually a PSG alone is ade-
The initial evaluation of a hypersomnolent patient focuses on the patient’s quate. If on the overnight PSG, an adequate explanation for the patient’s
history. Care must be taken to ensure that the patient’s complaint of EDS EDS is documented, an MSLT is not usually performed.
is manifested as inappropriate and undesired sleep as opposed to lethargy, If the PSG does not demonstrate an obvious etiology for EDS, then an
fatigue, or tiredness that can be reported in a large number of psychiatric MSLT can be performed the following day to quantify the degree of sleepi-
and medical conditions. In patients with moderate to severe sleepiness, the ness. An overnight PSG prior to the MSLT is usually required to assure that
history should include episodes of actual inappropriate sleep (e.g., falling sleep deprivation or sleep disruption has not artifactually contributed to an
asleep at a stoplight). While the character of the patient’s sleepiness often abnormal MSLT result. If an MSLT is performed without proceeding to
varies among these disorders, there is significant overlap that prevents a PSG, careful historical assessment (e.g., sleep diary) of the preceding night’s
confident diagnosis based on the character of the patient’s sleepiness alone. sleep is required at the time of testing.
An observer history is helpful to corroborate the reported sleepiness and MSLT results can be used to confirm the diagnosis of narcolepsy and
to report on the possible presence of loud snoring, witnessed apneas, or idiopathic hypersomnolence or to refute the complaint of hypersomnolence
excessive motor activity in sleep. Patients frequently deny or underestimate (67). If the patient has an MSL of less than 5 minutes and at least two REM-
the degree of sleepiness present and are usually unaware of any snoring or onset nap periods, a diagnosis of narcolepsy can be made if there are no other
nocturnal apneas. factors that might explain the finding (e.g., drug withdrawal). It is important
The presence of cataplexy is essentially a pathognomonic feature of narco- to emphasize that the diagnosis of narcolepsy requires both EDS and docu-
lepsy. Cataplexy is the sudden development of muscle weakness affecting the mentation of REM abnormality. The REM pathology can be represented by
head, neck, or entire body. It is usually precipitated by strong emotion (e.g., cataplexy or by SOREMs on the MSLT. If a single SOREM is documented,
laughter, anger) and is not associated with impairment of consciousness. it adds to the clinical suspicion of narcolepsy, and consideration can be
The muscular weakness lasts from seconds to minutes and then resolves. A given to repeating the MSLT in an attempt to find additional confirmatory
history of unambiguous cataplexy in combination with EDS is sufficient to evidence of REM pathology. If the MSLT documents hypersomnolence but
diagnose narcolepsy, and further sleep study evaluation is not necessarily no REM abnormality, the diagnosis is idiopathic hypersomnia (previously
indicated. However, care must be taken not to overlook the possible coexis- called idiopathic CNS hypersomnolence). This is an unfortunate, but neces-
tence of other sleep pathology (sleep apnea, PLMS) that may also be clini- sary, “waste basket” category at the present time. Some of these patients
cally significant. Sleep paralysis and hypnagogic hallucinations are the other may have narcolepsy, but the REM abnormality has not yet become clini-
auxiliary symptoms of narcolepsy, but they are less specific to narcolepsy cally evident. Another group of patients appear to have a syndrome charac-
and do not serve as pathognomonic markers of the disease. terized by EDS, which can be resisted more successfully, resulting in fewer
EDS (Sleepiness that

interferes with
activities of daily
living)
and
Heavy Snoring
Yes No
Cataplexy or
Perform PSG (per
hypnagogic
SRBD protocl*)
hallucinations
Yes No
Witnessed apnea,
Perform PSG and
choking, or breathing
MSLT (per narcolepsy
irregularities during
protocol)
Yes sleep No
Positive history and

sleep diary suggesting
Perform PSG (per circadian rhythm
SRBD protocol) disorder or insufficient
Yes sleep No
PSG not indicated,

perform evaluation and Perform PSG (per
provide treatment for SRBD protocol) and
circadian rhythm next day MSLT
disorder or insufficient
Figure 18.18: Algorithm for the sleep
evaluation of patient presenting
with a chief complaint of EDS. PSG findings of OSA
EDS, excessive daytime sleepi- or UARS suffiecient
ness; PSG, polysomnography; enough to explain
the patient’s
SRBD, sleep-related breathing Yes sleepiness No
disorder; MSLT, multiple sleep la-
tency test; OSA, obstructive sleep PSG findings of
PLMs sufficient
apnea; UARS, upper-airway resis- Evaluate and treat
for OSA or UARS enough to explain
tance syndrome; PLMs, periodic Yes
the patient’s
sleepiness No
limb movements; PLMD, periodic
limb movement disorder. (From
Evaluate and treat
ASDA Polysomnography Task for PLMD Perform MSLT on
Force. Practice parameters for the morning after PSG for
other evaluation of
indications for polysomnography EDS symptomology,
and related procedures. Sleep especially idiopathic
hypersomnai
1997;20:406–422.)
episodes of daytime sleep (89). These patients are not refreshed by daytime Approach to Nocturnal Behavioral Events (Parasomnias)
naps and respond poorly to stimulant medications. Many also have head-
aches, syncope, and peripheral vascular complaints, raising the possibility By virtue of their intermittent nature, the parasomnias are less easily
of accompanying autonomic nervous system dysfunction. investigated with PSG studies. As such, historical information assumes
More problematic is what to do with the patient in the “gray zone” with a greater importance. The differential diagnosis in an individual suffering
MSL of between 5 and 10 minutes. Clinical judgment is needed to assess the from unusual nocturnal behaviors includes somnambulism, night terrors,
appropriateness of stimulant or wakefulness-promoting drugs in this set- confusional arousals, seizures, REM behavior disorder, and nightmares.
ting. Repeating the MSLT may offer more definitive information. An MSL Table 18.5 lists characteristics that can be useful in differentiating these
of greater than 10 minutes does not support the diagnosis of EDS, and nocturnal events. If the nocturnal events are ambiguous or occur with pre-
treatment is not generally warranted. In the patient with a convincing clini- dictable frequency, PSG with closed-circuit television recording and more
cal complaint of EDS but in whom hypersomnolence is not documented, extensive EEG recordings will usually permit diagnosis.
one must consider syndromes producing episodic hypersomnolence and the Somnambulism and night terrors are disorders of arousal, classically
possible need to repeat the MSLT. occur during the first part of the night, and demonstrate a normal wake
TABLE 18.5 Differential Diagnosis of Common Parasomnias
Usual Age Sleep Postictal Effect of Recall of

at Onset Time of Night Stage Type of Behavior Confusion Stimulation Event Duration
Somnambulism Childhood First half NREM Clumsy, trance-like Absent Stops episode Minimal Seconds-minutes
Night terrors Childhood First third NREM Intense terror, Absent Variable Minimal Seconds-minutes
vocalization, auto-
nomic changes
Nightmares Variable Variable REM Terror in response Absent Stops episode Dream Seconds-minutes
to dream content, content
limited autonomic
changes
REM behavior Elderly Last third (most REM Acting out of dream Absent Stops episode Dream Seconds-minutes
disorder common) content, frequently content
aggressive
Confusional Variable First third NREM Confusion, incom- Present Variable Minimal Seconds-minutes
arousal (usually plete responsive-
childhood) ness, automatic
behavior, rarely
aggressive
Epileptic seizure Variable Variable Variable Stereotyped, variable Present No effect Minimal Seconds-minutes
complexity (often
agitation)
EEG or paroxysmal slow wave pattern during the event (93–96). Night Hysterical dissociative reactions including fugue states demonstrate an
terrors resemble nightmares, but the child has intense autonomic arousal alert patient (with normal waking EEG) who manifests complex purpose
and subsequently is amnestic for the event and cannot recall any precipi- behaviors out of apparent sleep that can last for hours or even days (95).
tating dream content. Nightmares are seen in patients of all ages and are Activity resembling sleepwalking or night terrors in an elderly patient is fre-
manifest by emotional upset due to disturbing dream content with only quently associated with underlying organic intellectual impairment and is
limited autonomic arousal. Confusional arousals (also called nocturnal simply an episode of confusion resulting in nocturnal wandering (107).
sleep drunkenness) arise in individuals of all ages, who are frequently
considered “deep sleepers” and again are thought to be due to an inabil-
ity to arouse from NREM sleep. During these events, the individual may Approach to the Patient with Insomnia
manifest several minutes of bizarre, confused behavior for which they are
subsequently amnestic (97). Violent or aggressive behavior is much less PSG plays a more limited role in the clinical evaluation of patients com-
common with confusional arousals than that seen with the REM behavior plaining of difficulties in initiating or maintaining sleep. The differential
disorder. diagnosis includes a wide range of psychiatric and psychological problems
REM behavior disorder (RBD) is believed to arise due to the loss of that do not routinely require PSG evaluation. However, sleep apnea and
the usual muscle atonia of REM sleep, which results in the acting out of periodic movements of sleep (with or without restless leg syndrome) has
dream content (98,99). This disorder may be a human analogue of an been identified in 5% to 29% of patients with insomnia (108–110).
animal model described by Jouyet and Delorme in 1965 (100,101). These Our own experience in 100 consecutive chronic insomniac patients evalu-
authors observed complex motor activity in cats during REM sleep after ated with ambulatory cassette PSG revealed that 34% of the studies provided
they received pontine tegmental lesions. However, in humans only a few useful information that was not otherwise available and that sometimes con-
patients have had identifiable brainstem pathology, although RBD may tradicted historical evidence (111). Twenty-five patients had PLMD (PLMI
serve as a heralding symptom for Parkinson disease or other synucleopa- = 48, PLMArI = 23). Three patients had significant OSA (mean AHI =
thies (e.g., dementia with Lewy bodies, multiple system atrophy). Patients 22) subsequently confirmed with laboratory PSG. Six patients had only
with this disorder are most commonly men older than 60 years, with no subjective insomnia because PSG sleep time was five times greater than the
other underlying neurologic or psychiatric illness. These patients present amount they had self-reported; four of these patients reported no sleep dur-
with wild dream enactment behaviors that are frequently violent and result ing the study night even though their TST ranged from 190 to 401 minutes!
in injury to themselves or their spouses. PSG with video analysis demon- Age was an important factor in identifying a population more likely to ben-
strates that the motor activity is restricted to REM sleep and may allow efit from PSG. Forty-five percent of patients over the age of 40 had sleep
confirmation of the diagnosis. apnea, PLMS, or subjective insomnia identified on PSG, in contrast to 15%
Epileptic seizures may be accompanied by an ictal discharge on scalp of patients under the age of 40.
EEG followed by postictal slowing. However, the limited EEG montage and Although there is disagreement among sleep specialists regarding the
slow paper speed used in PSG impairs the identification of ictal and interic- necessity of PSG evaluations in patients with insomnia, our data argue
tal epileptic activity. Use of expanded EEG montages and a paper speed of for at least selective use of PSG. Certainly, insomnia patients having clini-
30 mm per second are necessary in order to evaluate possible epileptic events cal evidence of possible sleep apnea or PMS should be evaluated by a
properly. Even with these adjustments, however, many nocturnal epileptic PSG. In other insomnia patients, the decision to conduct PSG should
events have no or ambiguous scalp correlates (11,96,102–104). Absence of be individualized depending on the chronicity and severity of the sleep
an EEG correlate during behavioral nocturnal events results in a much more problem as well as the age of the patient. In most patients with insom-
difficult diagnostic process, but the stereotyped behavior between episodes nia, it is reasonable for the sleep clinician to initially pursue treatment
suggests an epileptic etiology. In addition, nocturnal seizures occur at any with both p harmacologic and behavioral therapy before considering PSG
time of night and often will occur multiple times in a night (105,106). evaluation (112,113).
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INDEX
Note: Page numbers followed by f indicate figures; page numbers followed by t indicate tables.
A Acute electrical stimulation, 433 Adult epilepsy, EEG in, 315–336 Alpha squeak, 92
AAN. See American Academy of Neurology Acute trauma ictal EEG, 324 Alpha to delta ratio (ADR), 566
(AAN) motor evoked potential change, 507 in focal epilepsy, 325–330 Alpha variants, 151, 152f, 153
Abnormal interictal EEG activity, 418–425, somatosensory evoked potential change, in generalized epilepsy, 330–335 Alternating (sinusoidal) circuits, impedance
420–425f 495–496 limitations of, 335–336 and, 52, 52f
focal cortical dysplasia type II, 424, Acyl-coenzyme A oxidase deficiency scalp-related ictal discharges, features American Academy of Neurology (AAN), 483
424–425f (AOXD), 265 of, 324–325 American Board of Registration of
high-frequency oscillations, 402, 425, 426f ADCs. See Analog-to-digital converters (ADCs) interictal epileptiform discharges, 315 Electroencephalogram and Evoked
irritative zone, 418, 422–423f, 424 Adolescence focal, 316–320 Potential Technologists (ABRET), 549
lesional zone, 418, 420–421f metabolic disorders of, 273–277, 275f, 276f generalized, 320–323 American Clinical Neurophysiology Society
potential seizure onset zone, 425 in neonatal EEG interpretation, 143 limitations of, 335–336 (ACNS), 472, 472t
ABRET. See American Board of ADPEAF. See Autosomal dominant epilepsy photo-epileptiform discharges, 323–324 American Electroencephalographic
Registration of Electroencephalogram with auditory features (ADPEAF) AEDs. See Antiepileptic drugs (AEDs) Society, 80
and Evoked Potential Technologists Adrenoleukodystrophy, 274 Age. See also Conceptional age American Sleep Disorders Association
(ABRET) neonatal, 264–265 effects on BAEPs, 468 (ASDA), 599–600
Absolute latency, in BAEPs, 465 somatosensory evoked potentials in, 484 effects on VEPs, 457–458 task force, 624
Acidemia Adult EEG (normal), 90–124, 91t Aicardi’s syndrome, 165 Aminoacidurias, 270–271
methylmalonic, 265 activating procedures, 99–101, 101f, 102f AION. See Anterior ischemic optic Amplitude
propionic, 265 bandwidths in neuropathy (AION) of cortical activity, 32–33
ACNS. See American Clinical alpha rhythm, 92–94, 94f Airflow monitoring, polysomnography in, symmetry, 129, 129f, 130f, 131
Neurophysiology Society (ACNS) beta rhythm, 96, 96f, 97f 604–610, 605–608f, 609t Amyotrophic lateral sclerosis (ALS), 483
Acoustic neuroma, BAEPs in, 469 delta frequency, 97–98, 99f, 100f AIS pattern, 523, 525f Analog filters, for EEG, 54, 54f, 82
Acoustic stimulation, for BAEPs mu rhythm, 94–96, 95f Alcoholism, BAEPs in, 469 Analog-to-digital converters (ADCs),
masking in, 461 theta frequency, 97, 98f Aliasing, 55 57, 57–58f
sound intensity methods, 461 benign variants of uncertain significance, antialiasing filter, 56f, 61 Anatomo-electroclinical correlations, 395
stimulus delivery, 460 104, 106, 108–112, 110–115f example of, 55f Angelman syndrome, 277–278, 278f
stimulus polarity, 461 misinterpreted, 114–115, 117–122f, 120, Alpers disease, 272–273, 273f Anoxia
stimulus type, 462 122, 122t Alpha coma frequency pattern, 224 brain injury, clinical applications of,
Acquired epileptic aphasia. See parameters of recording, 91–92 in anoxic encephalopathy, 224f 581–587, 587–589f, 590–593f
Landau-Kleffner syndrome (LKS) sleep architecture, 101–104, 103–109f clinical correlation, 225 motor evoked potential change, 507
Action potential currents, 4–5 variations of, 112, 114, 116f pathophysiology, 225 somatosensory evoked potential
Activating procedures, in EEG, 99–101, warning signs for an overinterpreted EEG prognosis, 225 change, 495
101f, 102f report, 122t Alpha harmonics, 94 Anterior cervical (AC) electrode, 473
Active conductances, 6 waveform characteristics and identifying Alpha rhythm (alpha activity), 92–96, 94f, 148 Anterior dysrhythmia, in neonatal EEG
Activité moyenne (average activity) pattern, 135 suspicious features in, 122t focal cerebral lesions and, 240 interpretation, 148, 149f, 150f
631
DESIGN SERVICES OF
# 151788 Cust: LWW Au: Ebersole Pg. No. 631 K
632 Index
Anterior ischemic optic neuropathy Autosomal dominant nocturnal frontal lobe Bilateral independent temporal lobe absolute latency, 466–467
(AION), 458 epilepsy (ADNFLE), 285–286, 286f seizures, 408 amplitude in, 468
Anterior tibialis EMG, in polysomnography, Awakening(s), polysomnographic scoring of, Bilateral latency prolongations, 453 interpeak latency in, 465–466, 465–467f
603, 604f 612–613, 613–615f Bilateral periodic lateralized epileptiform obligate wave absence in, 464, 464f
Antialiasing filter, 56f, 61 Axial electromyogram, in discharges (BIPLEDs), 245, 248f in acoustic stimulation, 459
Antiepileptic drugs (AEDs), 373 polysomnography, 603 Bilateral rhythmic central theta activity, 156 in alcoholism, 469
discontinuation of, 574 Axonal plexus, 6 Binding problem, 12 anatomy and physiology, 512, 512t
effects on EEG activity, 214 Biotin metabolism, disorders of, 267 anatomy and waveform generators, 460,
AOXD. See Acyl-coenzyme A oxidase Biotinidase deficiency, 269 460t
deficiency (AOXD) B BIPLEDs. See Bilateral periodic lateralized anesthetic considerations, 513
Apnea, sleep, diagnosis of, 617–618 Baltic myoclonus epilepsy, 275 epileptiform discharges (BIPLEDs) in Arnold-Chiari malformations, 469
Arousal Bancaud phenomenon, 240, 242f Bipolar montages, 40, 41f, 42f, 86, 89, 98f auditory nerve action potential, 521
activity of, 193–194 Bandwidth(s), frequencies in EEG and, 92t with subdural electrodes, 374 in brain death, 469
in infants and children, 192 alpha rhythm, 92–94, 94f Bipolar stimulation, 533 in cerebellopontine angle tumors, 469
polysomnographic scoring of, 612–613, beta rhythm, 96, 96f, 97f Bit-depth, 56 change, mechanisms of, 513–520, 515t,
613–615f delta frequency, 97–98, 99f, 100f Black box, 2 516–520f
postarousal hypersynchrony, 194–195, mu rhythm, 94–96, 95f Blood glucose level, to hyperventilation physiological changes, 516–518
194–195f theta frequency, 97, 98f response, 187 surgery-induced changes, 514–516
spontaneous, 195 Basket cells, parvalbumin-expressing, 6, 8–9 Blood pressure. See Anoxia technical issues, 518–520
Arterial oxygen assessment, for ventilatory gamma activity, 9 Boundary element model (BEM), 349 clinical applications, 521
monitoring in polysomnography, 607–608 gap-junction coupling in, 9 Brachial plexus trauma, 539 clinical correlations, 468–470
Arteriovenous malformation (AVM), focal in high-frequency oscillations, 9 Brain in coma, 469
encephalopathies in, 239t, 254 BCSSS. See Benign Childhood Seizure abscess, focal encephalopathies in, 239t, interpretation, 462–464, 462f, 463t
Artery of Adamkiewicz, 490 Susceptibility Syndrome (BCSSS) 249, 250f latency/intensity series, 470
Artifact(s) Behavioral arrest with version, 310 electrical activity, 394 methodology, 512–513, 514f, 515f
in continuous EEG in ICU, 551, 554–560f BEM. See Boundary element model (BEM) electrical flow in, 2, 3f recording technique, 461–462, 462t, 513
environmental, 234 Benign childhood epilepsy with action potential currents, 4–5 stimulating techniques, 460–461, 513
eye movement, 240, 242f centrotemporal spikes, 295, 296–297, 298f active conductances, 6 in multiple sclerosis, 468–469
high-frequency ventilator, in infant with Benign Childhood Seizure Susceptibility gap-junction coupling, 6–7 in myelomeningocele, 469
persistent pulmonary hypertension, 173f Syndrome (BCSSS), 295 nonneuronal currents, 7 in neurodegenerative disorders, 469
instrumental, 417, 419f Benign epileptiform transients of sleep synaptic currents, 5 pediatric considerations, 468
interpretation of EEG data, 417–418, 419f (BETS), 109–110, 113f maps, 36 warning criteria, 520–521
in intracerebral depth electrodes EEG, Benign familial infantile epilepsy (BFIE), 285 stem injury, 516 Brainstem dysfunction, EEG manifestations
417–418, 419f Benign familial neonatal epilepsy stem lesions, EEG correlation with, 253 of, 214
nonphysiological, 551 (BFNE), 285 tumors Breach rhythm, 239, 240f, 241f
patting, in infant with sepsis, apnea, and Benign variants of uncertain significance, focal encephalopathies in, 239t Breathing, sleep-disordered, pediatric,
seizures, 142 104, 106, 108–112, 110–115f infratentorial, 247, 249 polysomnographic scoring of, 618–619
physiological, 234 Beta activity, 154–155 large hemispheric, 247 Brief ictal rhythmic discharges (BIRDs), 177
rhythmic extracerebral, 177 focal attenuation of, 240 Brain death Brushes. See Delta brushes, in neonatal EEG
sucking, 142 focal enhancement of, 239–240 BAEPs in, 469 interpretation
ASDA. See American Sleep Disorders Beta coma frequency pattern, 225–226 checklist for, 234t Burst-suppression pattern, 159, 160f,
Association (ASDA) Beta rhythm, 96, 96f, 97f electrocerebral inactivity, 233–234 232, 233f
Asynchrony, 131, 132f BETS. See Benign epileptiform transients of clinical correlation, 234
Atonic seizures, 334, 335f sleep (BETS) technical requirements, 234–235
Atypical absence seizures, 334 BFIE. See Benign familial infantile epilepsy in infants, 161, 164f C
Auditory nerve action potential, 521 (BFIE) Brainstem auditory evoked potentials C5S electrode, 474
Autosomal dominant epilepsy with auditory BFNE. See Benign familial neonatal epilepsy (BAEPs), 459–460 CAE. See Childhood absence epilepsy (CAE)
features (ADPEAF), 286 (BFNE) abnormalities CAI. See Composite alpha index (CAI)
DESIGN SERVICES OF
Index 633
Calibration, 81–82 sleep-disordered breathing in, Continuity, of EEG background, 207–208 Cortical source factors, and scalp EEG
Capacitance (C), 47, 47f, 49, 66 polysomnographic scoring of, 618–619 Continuous EEG monitoring potentials, 339–341, 340f, 341f
Capacitor(s), 47–48, 47f, 49 somatosensory evoked potentials in, 482–483 artifacts in, 551, 554–560f Cortical spike sources, 375
Carbon dioxide detectors, for airflow spikes and sharp waves in, 186–187 clinical applications of, 569–575 Cortical waveforms, 444
monitoring in polysomnography, 606 Ciganek rhythm, 114 anoxic brain injury, 581–587, 587–589f, Cranial nerve (CN)
CDG. See Congenital disorders of Circuit(s) 590–593f surgery, 538–539
glycosylation (CDG) differential amplification, 50–51, 50f hypothermia, 581–587, 587–590f VIII injury, 515–516
Cellular basis of EEG. See filters, 52, 52–54f ischemia, 581 Creutzfeldt-Jakob disease (CJD), 220–221
Electroencephalogram (EEG), cellular impedance and alternating (sinusoidal), nonconvulsive seizures, 572t, 578–581 Ctenoids, 109, 113f
basis of 52, 52f status epilepticus, 575–578 Currents, nonneuronal, 7
Central cortex seizures, 411–412, 412f input impedance, 50, 50f clinical factors confounding, 551–553, 561f Cz-A1/Cz-A2 montages, 460
Centrotemporal delta activity, in neonatal time-varying, 51–52, 51f data review, 553–555
EEG interpretation, 147 voltage divider, 49, 49f electrodes in, 550–551
Cerebellopontine angle tumors, BAEPs CJD. See Creutzfeldt-Jakob disease (CJD) future directions, 590 D
in, 469 Clonic seizures, 334 historical context, 547–548 Daytime sleepiness, excessive, evaluation
Cerebral blood flow, on EEG, 547t Clonic-tonic-clonic seizures, 334 in ICU. See Intensive care unit (ICU), of, 624–626, 625f
Cerebral death, technical standards for EEG CMRR. See Common-mode rejection ratio continuous EEG monitoring in Decibel normal hearing level, 461
recording in, 235t (CMRR) interpretation and nomenclature, 555–561, Deep hypothermic circulatory arrest
Cerebral edema, 373 CN. See Cranial nerve (CN) 562t, 563–571f, 573f (DHCA), 525
Cerebral function monitors (CFMs), 547 Cochlear injury, 514–515 montages in, 551, 552–553f Deep sleep, 103
Cerebral sources, dipole models of, 341–342 Collodion, 59 multimodal brain monitoring, Delta brushes, in neonatal EEG
Chattering neurons, 22 Coma 587–590, 594f interpretation, 144–147f, 148
Cherry-red spot (myoclonus syndrome), 274 alpha, 224–225, 224f personnel requirements, 549–550 Delta frequency(ies), 97–98, 99f, 100f
Childhood BAEPs in, 469 quantitative analysis of, 562–569, Dentatorubral-pallidoluysian atrophy, 276–277
and adolescence, metabolic disorders of. beta, 225–226 574–578f Depressed and undifferentiated background,
See Metabolic disorders, of childhood sleep. See Spindle coma scientific basis, 546–547, 547t 161, 161f
and adolescence Common-mode rejection ratio (CMRR), 50, technical considerations for, 548–549, 548f Depth electrodes, 60, 368
and infancy, EEG background activity 444–445 Continuous spindling, 198 subdural vs., 369
in. See Pediatric EEG, infancy and Common reference montage, 41 Corkscrew electrodes, 491, 492f DHCA. See Deep hypothermic circulatory
childhood Complex focal seizures, 325–326 Cortical after discharges, 389 arrest (DHCA)
progressive encephalopathy. See Composite alpha index (CAI), 581 Cortical currents, anatomical organization of Diffuse tonic-focal clonic seizure, 310
Progressive childhood encephalopathy Conceptional age, 126 basket cells, 8–9 Digital EEG, 40, 82
Childhood absence epilepsy (CAE), 290, excessive discontinuity for, 159, 161t hippocampal anatomy, 7–8 recording, 81
290f, 291f in neonatal EEG interpretation neocortical anatomy and thalamic technology for PSG, 600
Children 24 to 29 weeks, 131, 134 connections, 9–11 Digital filters, 82
alpha rhythm frequency in, 148 30 to 32 weeks, 134–135, 136f Cortical generators and EEG voltage fields Digital recording, issues related to, 80–81
brainstem auditory evoked potentials 33 to 34 weeks, 135 EEG source Digitization, 81
in, 468 35 to 36 weeks, 135, 137f, 138 characterization, 34–37 digitizer electronics, 57, 57–58f
fast activity during early stages of sleep 37 to 40 weeks, 138, 139f, 140f potentials, 28–30, 29–30f of signals, 54
in, 200 41 to 44 weeks, 138 effect of reference on EEG fields, 42, 43f, 44 time discretization, 55–56, 55–56f
flash visual evoked potentials in, 457–458 45 to 46 weeks, 138, 141f electrode location and nomenclature, voltage discretization (signal resolution),
hyperventilation response in, Condensation, definition of, 461 38, 39–40f, 40 56–57, 57f
186–187, 187f Conductance, 2, 47, 48 factors determining scalp EEG, 30–34, Digitizer
paroxysmal slow bursts during drowsiness Cone waves, 140 32–35f digital processing, 62
in, 188, 191–192, 193f Congenital disorders of glycosylation montages, 40–42, 41f digital transfer/storage, 62
with perinatal injury, 484 (CDG), 273 from specific cortical regions, 37–38, 38–39f electronics, 57, 57–58f
sharp-wave, vertex transients in, 195–196, Constant-voltage stimulators vs. Cortical interictal spikes, 367–368, 374 finite impulse response filtering, 62, 63
196–201f, 198, 200, 202 constant-current stimulators, 533 Cortical seizure propagation, character of, 381 infinite impulse response filtering, 62, 63
DESIGN SERVICES OF
634 Index
Dipole localization techniques, 341–342, 346 ECI. See Electrocerebral inactivity (ECI) Electrocorticography (ECoG) technique, 394, epileptiform activity
Dipole patch model, 358, 361 ECoG. See Electrocorticography (ECoG) 395. See also Intracranial EEG microelectrode arrays, ictal discharges
Dipole source modeling, of epileptiform EEG. See Electroencephalogram (EEG); Electrode(s), 58–59, 59f and penumbra, 17–19, 18f
potentials, 338–364 Electroencephalography (EEG) anterior cervical, 473 neural activity during epileptiform
assumptions of, 342 EGA. See Estimated gestational age (EGA) common types of, 59–60, 60f discharges, 14–17, 15f, 16f
of cerebral sources, 341–342 EIEE. See Early infantile epileptic continuous EEG in ICU and, 550–551 surround inhibition, 19, 20f, 21f
clinical studies using, 361, 363–364 encephalopathy (EIEE) corkscrew, 491, 492f oscillations, 11–12
coregistering EEG data with MRI, Electric charge, 46 depth, 60, 368 and cellular activity, relationship
realistic head models, and spatial Electric potential, 46 for electroencephalography, 522–523 between, 13–14
sampling, 347, 349–350, 349f, Electrical fields, 78–89 epidural, 369, 491–492, 492f hierarchical phase-amplitude
350f, 351f calibration in, 81–82 grid, 60 coupling, 14
for extratemporal sources, 353, 359–363f cerebral generators of EEG potentials in, high-resolution, flexible, active electrode high-frequency, EEG markers of
interpretation of, 346–347, 347f, 348f 78–79, 79f array, 61, 61f ictal territories, 19–24, 20f, 23f
of seizures, 350, 352f, 353, 354f conventions and sensitivity/filter settings, intracranial, 60 structure of, 12–13
single-moving, 342, 343f, 344f 80–85 localization of, 371, 371f, 372f uses of, 2
spatiotemporal multiple, 342–343, electrode placement in, 79–80, 80f for motor evoked potentials continuous monitoring. See Continuous
345f, 346 filters in, 82, 82–85f, 85 recording, 504–505 EEG monitoring; Intensive care unit
for temporal lobe sources, 353, 355–358f issues related to digital, 80–81 stimulating, 490f, 491–492t, 503 (ICU), continuous EEG monitoring in
Discontinuous EEG, in premature montages in, 85–86, 87–88f, 89. See also needle, 535, 535f description and interpretation, 214
infant, 157 Montage(s) nomenclature and location, 38, localization, 214
Doose syndrome. See Myoclonic-astatic polarity conventions in, 81 39–40f, 40 reactivity, 215–217
epilepsy sensitivity in, 81–82 pattern reversal visual evoked potentials digital, 40, 82
Double-grounding, electrical safety, Electrical flow, in brain, 2, 3f recording, 451t recording, 81
66, 68, 68f action potential currents, 4–5 placement of, 79–80, 80f technology for PSG, 600
Double train stimulation, 504 active conductance, 6 platinum vs. stainless steel, 369 engineering aspects of, 46
Down syndrome, 205, 278 gap-junction coupling, 6–7 potential, 58 focal, 238–255. See also Focal
Dravet disease, 300, 301f nonneuronal currents, 7 scalp cup, 59, 60f encephalopathies, EEG in
Drowsiness, 208 synaptic currents, 5 silver chloride, 58 monitoring, utility of, 213
defined, 187 Electrical safety, 64, 68t for somatosensory evoked potentials for normal adult, 90–124, 91t
monorhythmic slow activity, 187–188, double-grounding, 66, 68 recording, 491–492, 492f activating procedures, 99–101, 101f, 102f
189–190f exacerbating factors in, 68, 68t stimulating, 490–491, 490f, 491t bandwidths in
paroxysmal slow activity, 188, 191–192, improper grounding, 65 subdermal, 535, 535f alpha rhythm, 92–94, 94f
192f, 193f leakage currents, 66 subdural, 60 beta rhythm, 96, 96f, 97f
Dysrhythmia, anterior, 148, 149f regulations, 68 bipolar montages with, 374 delta frequency, 97–98, 99f, 100f
Electrical stimulation, 470 depth vs., 369 mu rhythm, 94–96, 95f
for functional localization, 388–389 in intracranial EEG, 367–389, 370f, theta frequency, 97, 98f
E intracerebral depth electrodes EEG and, 371f, 372f, 375f, 376f, 377–380f, benign variants of uncertain
Early infantile epileptic encephalopathy 433–435, 434f 382–388f significance, 104, 106, 108–112,
(EIEE), 303, 304f of peripheral nerves, 489 surface, 534–535, 535f 110–115f
Early myoclonic encephalopathy (EME), Electro-oculogram, in polysomnography, Utah Intracortical Electrode Array, misinterpreted, 114–115, 117–122t,
260–261, 260f, 302, 303f 602–603, 602f 60–61, 61f 120, 122
cause of, 260–261 Electrocerebral inactivity (ECI), 233–235, Electrodecrement, 305 parameters of recording, 91–92
diagnostic test for, 261t 523 Electroencephalogram (EEG). See also sleep architecture, 101–104, 103–109f
inborn error of metabolism causing, 261t brain death, checklist for, 234t Encephalopathy, generalized variations of, 112, 114, 116f
Early onset epileptic encephalopathy clinical correlation, 234 cellular basis of, 1–27 safety rules for performing, 68t
(EOEE), 262 technical requirements, 234, 235t cortical currents, anatomical source characterization
Early onset multiple carboxylase Electrocerebral silence. See Electrocerebral organization of, 7–11 propagation, 37
deficiency, 267 inactivity electrical flow in brain, 2–7, 3f, 6f voltage field analysis, 34–36
DESIGN SERVICES OF
Index 635
-specific acquisition early infancy, 46 weeks to 1 year, 138, in neonates, 250 low-voltage and suppressed
antialiasing filter, 61 140, 142 viral, 251 patterns, 232
electrodes, 58–59, 59f late infancy, 1 to 2 years, 142 Encephalogram (EEG) burst-suppression, 232, 233f
common types of, 59–60, 60f pediatric. See Pediatric EEG acquisition, 373–374 generalized suppression, 232
high-resolution, flexible, active potential, cerebral generators of, association and electrographic neonatal parameters for, 215t
electrode array, 61, 61f 78–79, 79f seizures, 186t periodic patterns, 220
Utah Intracortical Electrode Array, quantitative analysis, 531 disc electrodes, 472 generalized periodic discharges,
60–61, 61f sleep recording, 601–603, 601f, 602f fields, effect of reference on, 42, 43f, 44 220–222, 221f
preamplifiers, 61 voltage topography intracranial recording, 374–377, 375f, triphasic waves, 222–224, 223f
spindle coma frequency pattern, cortical source factors and scalp 376f, 377–380f slow patterns, 217
225–226, 226f potentials, 339–341, 340f, 341f isoelectric, 206 generalized high-voltage delta
in ventilatory monitoring in other source models, 353, 358, 361 markers of ictal territories, 19–24, 20f, 23f activity, 219
polysomnography, 608 spike and seizure sources, 339 neonatal, background, classification and generalized slowing, 217–218
warning signs for an over interpreted EEG warning criteria, 526–530 implications of, 205–206, 205t generalized theta activity,
report, 122t Electrographic neonatal seizures (ENSs), and organized approach to visual analysis of, 218–219, 218f
waveform characteristics and identifying clinical correlations, 177–205 207–209 intermittent rhythmic delta activity,
suspicious features in, 122t activity of drowsiness, arousal and sleep, abnormalities, 208–209 219–220, 219f
Electroencephalography (EEG), 188, 187–205, 188–204f continuity and state concordance, glycine, 260–261
521–522 characteristics 207–208 progressive childhood, 258–280
adult epilepsy in, 315–336 amplitude, 182, 185f, 186 gradient and principal components, 208 Encoches frontales, 165, 167, 167f, 208
anatomy and physiology, 522 duration, 177, 181–182f, 182 special features, 208 Engineering principles, 45–77
anesthetic considerations, 523–524, location, 177, 179–180f symmetry and synchrony, 208 aliasing in, 55, 55f
524–527f morphological appearance, 182, potentials, sources of, 28–30, 29–30f circuits and, 49–54, 49–54f
change, mechanisms of, 524–526, 183–184f Encephalopathy(ies), 208 digital EEG, 40
527–528t, 529–530f, 532t computer-based, 186 epilepsies with, 299–308 digitization, 54–57, 55–58f
hypothermia, 525–526 sharp waves and spikes in infant and child, epileptic encephalopathies, 301–308 digitizer, 62–64, 63–66f
ischemia, 524–525 186–187, 187f epileptogenic encephalopathies, display considerations, 64, 67f
other factors, 526 Electromyography (EMG) 300–301 EEG-specific acquisition, 58–61, 59–61f
clinical applications, 530–531 anterior tibialis, in polysomnography, focal, 238–255, 239t electrical basics, 46–47, 46t
hyperventilation for, 526 603, 604f generalized, 213–236 electrical safety, 64–66, 68, 68f, 68t
intracerebral depth electrodes, 393–437 axial, in polysomnography, 603 caveats in using EEG for prognosis, evoked potentials. See Evoked potentials
intracranial, 367–389 clinical applications, 538–539, 538t 232–233 fundamental electrical components,
methodology, 522–523 cranial nerve surgery, 538–539 clinical correlations of encephalopathic 47–49, 47–48f
electrodes, 522–523 peripheral nerve surgery, 538–539 EEG patterns, 215t ENSs. See Electrographic neonatal seizures
machine, 522 spinal surgery with instrumentation, 538 EEG description and interpretation (ENSs)
montages, 523 free running, 535–536 localization, 214 Environmental artifacts, 417
neonatal. See Neonatal EEG intercostal, for ventilatory monitoring in monitoring, utility of, 213 EOEE. See Early onset epileptic
ontogeny, overview of, 134f polysomnography, 607 patterns associated with, 214t encephalopathy (EOEE)
adolescence, 143 interpretation of, 536–537, 537f reactivity, 215–217, 216f, 217f Ephaptic interactions, 6
childhood, 2 to 10 years, 142 stimulated, 534–535 electrocerebral inactivity, 233–235, Epidural electrodes, 491–492, 492f
conceptional age Electronics, digitizer, 57, 57–58f 234t, 235t in intracranial EEG, 369
24 to 29 weeks, 131, 134 Electroretinogram (ERG), 120, 456–457 fast frequency patterns, 224 EPIFOCUS technique, 358
30 to 32 weeks, 134–135, 136f EME. See Early myoclonic encephalopathy alpha coma, 224–225, 224f Epilepsy, 367, 373. See also Seizure(s)
33 to 34 weeks, 135 (EME) beta coma, 225–226 adult, 315–336
35 to 36 weeks, 135, 137f, 138 EMG. See Electromyography (EMG) spindle coma, 226–227, 226f ictal EEG, 324–336
37 to 40 weeks, 138, 139f, 140f Encephalitis, 249 ICTAL patterns, 227 interictal epileptiform discharges,
41 to 44 weeks, 138 causes of, 249–250 nonconvulsive status epilepticus, 315–324, 335–336
45 to 46 weeks, 138, 141f focal encephalopathies in, 239t 227–231, 228t, 229–231f clinical studies of, 361, 363–364
DESIGN SERVICES OF
636 Index
Epilepsy (continued ) Epileptogenic encephalopathies Excessive asynchrony, 165 Flash visual evoked potentials (FVEPs),
EEG in diagnosis and treatment of, 368 Dravet disease, 300, 301f Excessive daytime sleepiness, evaluation of, 456–457, 457f
with encephalopathies, 299–308 malignant migrating focal seizures in 624–626, 625f fMRI. See Functional magnetic resonance
epileptic encephalopathies, 301–308 infancy, 300–301, 302f Excessive discontinuity, of abnormal imaging (fMRI)
epileptogenic encephalopathies, EPM2 gene, 275 pediatric EEG backgrounds, 157, Focal brain injury, 161
300–301 EPs. See Evoked potentials (EPs) 158f, 159 Focal clonic seizure, 310
extratemporal, 353, 409–415 EPSPs. See Excitatory postsynaptic abnormal asymmetry, 161, 165 Focal cortical dysplasia, 239t, 255
familial, 284–287 potentials (EPSPs) abnormal interhemispheric asynchrony, 165 Focal encephalopathies, EEG in,
focal structural, 308–310 Equivalent dipoles, 342, 347 abnormal maturation, 165, 166f 238–255, 239t
generalized, 330 ERG. See Electroretinogram (ERG) abnormal voltage, 159, 161 epileptiform abnormalities, 243–244
idiopathic generalized, 330–334 Esophageal pressure monitors, for ventilatory for age, 159, 161t focal cortical dysplasia, 255
interictal regional delta activity in, 376 monitoring in polysomnography, 606–607 burst-suppression pattern, 159, 160f historical background of, 238–239
juvenile myoclonic. See Juvenile myoclonic Estimated gestational age (EGA), 126 isoelectric tracing, 161, 164f nonepileptiform abnormalities, 239–243
epilepsy Evoked potentials (EPs), 442–484 persistent low voltage, with or without background rhythms, changes in,
lesional and nonlesional focal basics of lack of differentiation, 161, 162f, 163f 239–241
epilepsies, 415 abnormalities, 446–447 Excitatory postsynaptic potentials (EPSPs), focal slow-wave activity, 241–243
with myoclonic absences, 290 interpretation, 445–446 14, 29 periodic lateralized epileptiform
pediatric. See Pediatric epilepsy naming convention, 443 Extracellular secondary current, 29 discharges, 244–245, 247f
syndromes normative data, 446 Extracellular transfer functions, 4 specific pathologies, 239t, 245
surgery, 368 recording, 444–445 Extratemporal complex focal seizures, brain abscess, 249
symptomatic generalized, 334–335 stimulation, 444 328–330, 329–332f brain tumors, 245–249
temporal lobe, 377 waveforms, 443–444 Extratemporal epilepsy, 353 encephalitis, 249–251
focal onset in, 381 brainstem auditory, 459–460 Extratemporal lobe epilepsy, indications for hemispheric stroke, 251–252, 252f, 254f
indications for SEEG in, 407–409 abnormalities, 464–468, 464–467f SEEG in, 409–415 subarachnoid hemorrhage, 254
Epileptic encephalopathies, 301–308 anatomy and waveform generators, 460, subdural hematoma, 251
background slowing and disorganization 460t thalamic hemorrhage, 254
in, 301–302 clinical correlations, 468–470 F transient ischemic attack, 251
early, 302–304 interpretation, 462–464, 462f, 463t Facilitation, 504 vertebrobasilar ischemia, 252–254
late infantile epileptic encephalopathy, latency/intensity series, 470 Familial epilepsies, 284–287, 286f stroke, 254–255
306, 306–307f methodology, 460–462, 462t Familial lateral temporal lobe epilepsy, 286 Focal polymorphic delta activity, 241–242
Lennox-Gastaut syndrome, 307, 308f pediatric considerations, 468 Familial mesial temporal lobe epilepsy, Focal spikes/sharp waves, 316–317
in newborn, 262t somatosensory 286–287 Focal structural epilepsies, 308–310
West syndrome, 304–306, 305f abnormalities, 476–480, 477–482f Fast activity, of sleep, 200, 201f, 202 Focal tonic-clonic seizure, 310
Epileptic spikes, 30 anatomy and waveform generators, Fast frequencies. See Beta rhythm with secondary generalization, 310
Epileptiform activity 470–471, 471t Fast-spiking interneurons, 8 Focal tonic seizure, 310
abnormalities of, 239, 243–244, 315 clinical correlations, 483–484 Fatal familial insomnia, 250 Forward solution, 342
cellular basis of, 14 interpretation, 474–476, 475f, 476t Field(s), EEG, effect of reference on, Four-channel montages, for PRVEP, 450, 472
microelectrode arrays, ictal discharges methodology, 471–474, 472t, 473f, 474t 42, 43f, 44 4-hydroxyphenylpyruvate dioxygenase
and penumbra, 17–19, 18f pediatric considerations, 480–483 Filters, 52–54, 52–54f, 61, 63–64, 63–65f, 82, deficiency. See Tyrosinemia type III
neural activity during epileptiform visual 82–85f, 85 14- and 6-Hz positive bursts, 109, 113f
discharges, 14–17, 15f, 16f anatomy and waveform generators, Finite-element methods, 349 Fragile X syndrome, 277, 299
surround inhibition, 19, 20f, 21f 447–448 Finite impulse response filtering, 62 Free running electromyography, 535–536
depth electrodes for, 369 clinical correlations, 458–459, 459f vs. infinite impulse response (IIR) Friedreich ataxia, 483
potentials, dipole source modeling flash, 456–457, 457f filtering, 63 Frontal intermittent rhythmic delta activity
of, 338–364 pattern reversal, 448–456, 449–456f, FIRDA. See Frontal intermittent rhythmic (FIRDA), 219f, 220, 242, 243f, 245f, 253f
Epileptiform potentials, dipole source 451–453t delta activity (FIRDA) Frontal lobe seizures, 409, 410–411, 410f
modeling of. See Dipole source modeling, pediatric considerations, 457–458 Firing patterns, in neuronal classes, 4 Frontal sharp waves, 167
of epileptiform potentials Exaggerated spindles, 198 Flash analog-to-digital converter, 57, 57f Frontal spindles, 198, 200
DESIGN SERVICES OF
Index 637
Frontal theta activity, 155–156 Glial syncytial networks, 7 Hyperglycinemia, nonketotic, 260–261, 261f IFCN. See International Federation of
Frontocentral theta activity, 155–156 Globoid cell leukodystrophy. See Krabbe Hyperinsulinemia and hyperammonemia Clinical Neurophysiology
Full-field stimulation, 447 disease (HIHA), 293 IIR filtering. See Infinite impulse response
Functional localization, electrical stimulation Glucose transporter 1 (GLUT-1) deficiency Hypermotor focal seizure, 310 (IIR) filtering
for, 388–389 syndrome, 269, 270f, 293, 294f Hyperphenylalaninemias, 270–271 Impedance and alternating (sinusoidal)
Functional magnetic resonance imaging Glycine encephalopathy, 260–261 Hyperventilation, 526 circuits, 52, 52f
(fMRI), 371 GM1 gangliosidosis, type I and type II, response, in children, 186–187, 187f Improper grounding, electrical safety, 65
Fusiform bursts, in sleep, 200 268–269 Hypnagogic state, 187–188 Impulsiv Petit Mal, 292
FVEPs. See Flash visual evoked potentials GM2 gangliosidosis, 268 Hypothalamic hamartoma, 249 Inborn error of metabolism (IEM), 259
(FVEPs) GPEDs. See Generalized periodic discharges Hypothermia causing EME, 261t
(GPEDs) clinical applications of, 581–587, 587–590f nonsyndromic infantile epilepsies
GRFD. See Generalized repetitive fast EEG changes with, 528t with, 268
G discharge (GRFD) mechanisms for electroencephalography, seizures in newborns and, 262–267
Galactosylceramidase, 268 Grid electrodes, 60 525–526 acyl-coenzyme A oxidase deficiency
Gamma activity, 9 Ground fault, 66 Hypsarhythmia, 304, 305f in, 265
Gamma rhythm, 16f Ground loop, 66, 68, 68f biotin metabolism, disorders of, 267
Gap-junction coupling, 6–7, 9 GSW. See 6-Hz generalized spike-and-wave Leigh syndrome, 267
Gaucher disease, 274 discharges (GSW) I maple syrup urine disease in, 265
Generalized atypical spike-and-slow-wave Ictal discharges, 17–19, 18f molybdenum cofactor deficiency,
discharges, 321, 321f Ictal EEG, 324 263–264
Generalized epilepsies, 330 H dipole models, 364 neonatal adrenoleukodystrophy in,
Generalized epileptiform discharges, 142 Head models, realistic, coregistering EEG in focal epilepsy, 325 264–265
Generalized high-voltage delta activity, 219 data with, 347, 349–350, 349f, 350f, 351f complex focal seizures, 325–326 organic acidurias in, 265, 266–267
Generalized periodic discharges Head trauma, 227 extratemporal complex focal seizures, peroxisomal disorders, 264–265
(GPEDs), 221f Head ultrasound examinations, for 328–330, 329–332f pyridoxine dependency, 262–263,
clinical correlation, 220–221 premature infants, 206 simple focal seizures, 325 263–264f
pathophysiology, 222 Hearing screening, 469 temporal lobe complex focal seizures, pyruvate carboxylase deficiency, 267
prognosis, 221 Hematomas, subdural, 372–373 326–328, 327–329f pyruvate dehydrogenase deficiency
Generalized repetitive fast discharge Hemifield stimulation, 447 in generalized epilepsy, 330 in, 267
(GRFD), 322–323, 323f Hemispheric stroke, focal encephalopathies idiopathic generalized epilepsy, 330–334 sulfite oxidase deficiency, 263–264
Generalized seizures, 330 in, 239t, 251–252, 252f, 254f symptomatic generalized epilepsies, urea cycle disorders in, 265
Generalized slowing electroencephalogram, Herpes encephalitis, focal encephalopathies 334–335 Zellweger syndrome in, 264
217–218 in, 239t. See also Encephalitis intracranial, 377, 381, 382–384f, 384, Inductive plethysmography, for ventilatory
Generalized suppression pattern, 232 Herpes simplex virus (HSV), 249, 250 385–387f monitoring in polysomnography, 606,
Generalized theta activity, 218, 218f High-frequency oscillations (HFOs), 19–24, limitations of, 336–337 607f, 608f
Generalized tonic-closure seizures, 333–334 20f, 23f, 384, 388f scalp-recorded ictal discharges, 324–325 Inductor(s), 48, 48f, 49
on awakening, 334 High-pass filter, 85 Ictal penumbra, 17–19, 18f Infant(s). See also under Neonate(s);
Generator(s), cortical. See Cortical High-resolution, flexible, active electrode ICU. See Intensive care unit (ICU) Pediatric EEG
generators array, 61, 61f Idiopathic generalized epilepsy, 330–334 Alpers disease, 272–273
Genetic generalized spike-wave HIHA. See Hyperinsulinemia and absence seizure, 331 aminoacidurias in, 270
epilepsies, 287 hyperammonemia (HIHA) clonic-tonic-clonic seizures, 334 congenital disorders of glycosylation, 273
childhood absence epilepsy, 290, 290f, 291f Hippocampal anatomy, 7–8 generalized tonic-closure seizures, 333–334 fast activity during early stages of sleep
epilepsy with myoclonic absences, 290 Hippocampal ripples, 22 on awakening, 334 in, 200
juvenile absence epilepsy, 290, 292f Hjorth source montages, 44 juvenile myoclonic epilepsy, 332–333, 333f glucose transporter 1 (GLUT-1) deficiency
juvenile myoclonic epilepsy, 292–293, 293f Hodgkin-Huxley model, 4, 6 IEC 60601 standards, for electrical safety, 68 syndrome, 269
masquerading conditions, 293 Holocarboxylase synthetase deficiency, 267 IEDs. See Interictal epileptiform discharges GM1 gangliosidosis, type I and type II in,
myoclonic-astatic epilepsy, 287, 288–289f Homocystinuria, 273–274 (IEDs) 268–269
myoclonic epilepsy in infancy, 287, 288f HSV. See Herpes simplex virus (HSV) IEM. See Inborn error of metabolism (IEM) Krabbe’s disease in, 268
DESIGN SERVICES OF
638 Index
Infant(s) (continued) data review, 553–555 Intermittent rhythmic delta activity, 219–220, Intracranial EEG, 367–389
lysosomal disorders in, 268–269 electrodes in, 550–551 219f, 242–243 acquisition, 373–374
Menkes’ disease in, 271 future directions, 590 International 10–20 system of electrode chronic, 368
metachromatic leukodystrophy in, 271 historical context, 547–548 placement, 38, 39–40f, 40, 79–80, 80f, electrical stimulation and functional
mucopolysaccharidoses in, 271–272 interpretation and nomenclature, 555–561, 126, 151f, 550 localization, 388–389
neuronal ceroid lipofuscinoses in, 562t, 563–571f, 573f International Federation of Clinical electrodes, 60
272, 272f montages in, 551, 552–553f Neurophysiology (IFCN), 79, 556 high-frequency oscillations, 384, 388f
organic acidurias in, 269–270 multimodal brain monitoring, Interpeak latency (IPL) in BAEPs, 445 historical perspectives, 368–369
PEHO syndrome in, 271 587–590, 594f Intracerebral depth electrodes ictal, 377, 381, 382–384f, 384, 385–387f
Schindler’s disease in, 271 personnel requirements, 549–550 encephalography, 393–437 interictal, 374–377, 375f, 376f, 377–380f
sharp waves and spikes in, 186–187 quantitative analysis of, 562–569, electrical stimulation, 433–435, 434f localization of intracranial electrodes, 371,
Tay-Sachs disease in, 268 574–578f historical perspective, 394–395 371f, 372f
vitamin metabolism disorders in, 269 scientific basis for, 546–547, 547t indications for SEEG, 407t normal physiological, 374
West syndrome in, 267–268 technical considerations for, in extratemporal lobe epilepsy, 409–415 postoperative care, 373
Infantile focal seizures 548–549, 548f in lesional focal epilepsies, 415 recordings, of seizure activity, 326
clinical features of, 309–310 Intercostal electromyography, for ventilatory in nonlesional focal epilepsies, 415 subdural electrodes
simple and complex, 309 monitoring in polysomnography, 607 scheme for intracranial EEG in characteristics of, 369, 370f
as subtle, 309 Interhemispheric asynchrony, abnormal in temporal lobe, 407t vs. depth electrodes, 369
types and electroclinical correlations of, 310 neonatal EEG, 165 in temporal lobe epilepsy, 407–409 EEG recording, clinical indications
Infantile spasms, in infancy, 304 Interhemispheric fissure, 340 interpretation of EEG data, 415–416 of, 373
Infinite impulse response (IIR) filtering, 62 Interhemispheric symmetry abnormal interictal EEG activity, placement, risks and complications of,
finite impulse response (FIR) filtering amplitude, 129, 129f, 130f, 206 418–425, 420–425f 371–373
vs., 63 waveform composition, 129 artifacts, 417–418, 419f Intracranial electrodes, 60
Infratentorial brain tumors, 247, 249 Interhemispheric synchrony, in neonatal normal physiological EEG activity, 416, characteristics of, 395, 396t
Inhalational agents, 523 EEG interpretation, 131, 133f, 165 417–418f localization of, in intracranial EEG, 371,
for motor evoked potentials, 506–507 Interictal epileptiform activities, 271, 304 propagation, 425–433 371f, 372f
for somatosensory evoked potentials, 494 in extratemporal neocortical epilepsy, 424 seizure-onset zone, 425–433 Intracranial IEDs, 374, 375, 376
Inhibitory postsynaptic currents (IPSCs), 8 Interictal epileptiform discharges (IEDs), 13, study protocol during EEG, 416t Intraoperative digital photography, 371, 372f
Inhibitory postsynaptic potentials 186, 315, 374 recording procedure, 402 Intraoperative ECoG, 368. See also
(IPSPs), 29 focal, spikes/sharp waves, 316–317, 316f practical aspects, 404, 405–406f, 407 Electrocorticography (ECoG) technique
Insomnia, evaluation of, 627 generalized, 320 technical aspects, 402, 403–404f Intraoperative monitoring, neurophysiologic.
fatal familial, 250 atypical spike-and-slow-wave stereotactic radiofrequency See Neurophysiologic intraoperative
Instrumental artifacts, 417 discharges, 321, 321f thermocoagulation lesioning, monitoring
Instrumental phase reversal, 40 photo-epileptiform discharges 435, 436f Intravenous (IV) agents
Instrumentation amplifier, 51 (photoparoxysmal response), technical considerations for motor evoked potentials, 507
Insular lobe seizures, 413, 414f, 415 323, 324f advantages of, 398, 400–401, 400f for somatosensory evoked potentials, 494
Insulator(s), 47f, 48 repetitive fast discharge, 322–323, 323f characteristics, 396–397 Invasive EEG, 92, 409, 415, 436
Intensive care unit (ICU), continuous EEG slow spike-and-wave discharge pattern, drawback of, 401 clinical indications for, 393, 394t
monitoring in, 543–594, 544f, 545f, 546f 322, 322f insertion and removal, 397 complication of, 373
artifacts in, 551, 554–560f 3-Hz spike-and-wave discharges, intracranial electrodes, 395–396 motivation to use, 394
clinical applications of, 569–575 320–321, 320f location, 398, 399f recordings, 407
anoxic brain injury, 581–587, 587–590f limitations of, 336–337 placement, 397–398 Inverse solution, 342, 346, 367
hypothermia, 581–587, 587–590f multifocal spikes, 317–318, 317f risks and complications, 401–402 IPL in BAEPs. See Interpeak latency (IPL)
ischemia, 581 periodic lateralized epileptiform scalp electrodes, 398, 400f in BAEPs, 445
nonconvulsive seizures, 572t, 578–581 discharges, 318–319, 318f types of, 397f IPSCs. See Inhibitory postsynaptic currents
status epilepticus, 575–578 temporal intermittent rhythmic delta Intracortical EEG (ICE), multimodal brain (IPSCs)
clinical factors confounding, activity, 319–320, 319f monitoring, 587–588 IPSPs. See Inhibitory postsynaptic potentials
551–553, 561f Interictal regional delta activity, 376–377 Intracranial aneurysm, 254 (IPSPs)
DESIGN SERVICES OF
Index 639
Ischemia, 498 Late-onset batten disease, 274–275 Masking, for BAEPs, 461, 513 Midline central (Cz) theta activity, 156–157
and anoxia/blood pressure, 495, 507 Late-onset multiple carboxylase deficiency, Median nerve stimulation (MNS), 480 Midline theta rhythm, 114, 116f
chronic, 251 268, 269 MEI. See Myoclonic epilepsy in infancy MNS. See Median nerve stimulation (MNS)
clinical applications of, 581 Late-onset occipital lobe epilepsy, (MEI) Molybdenum cofactor deficiency, 260,
mechanisms of 297, 299, 299f MELAS syndrome, 245, 267, 275–276, 277f 263–264, 279
for electroencephalography, 524–525 Lateral lemniscus, 460, 460t, 512 Menkes disease, 260, 271 Monomorphic, rhythmic 6- to 7-Hz voltage
motor evoked potentials change, 507 Laura technique, 358, 364 MEPs. See Motor evoked potentials (MEPs) activity, 156, 156f, 157f
somatosensory evoked potentials Leakage currents, 66, 522 MERRF syndrome, 275 Monorhythmic occipital delta activity, in
change, 495 LED goggles. See Light emitting diode Mesial vs. neocortical temporal lobe seizures, neonatal EEG interpretation, 135,
vertebrobasilar, 252–253, 255f (LED) goggles 408, 408f 143, 144f
Isoelectric EEG, 206 Leigh syndrome, 267 Metabolic disorders Monorhythmic slow activity, 187–188,
Isoelectric tracing, 161, 164f Lennox-Gastaut syndrome (LGS), 249, 259, of childhood and adolescence, 273–277 189–190f
Isolation amplifier, 51 300, 307, 308f, 322 adrenoleukodystrophy, 274 Montage(s), 44, 472t, 504t, 505t
Isovaleric aciduria, symptoms of, 265 Lesional and nonlesional focal epilepsies, dentatorubral-pallidoluysian atrophy, bipolar, 40–41, 41f, 42f, 86, 89, 98f, 222,
IV agents. See Intravenous (IV) agents indications for SEEG in, 415 276–277 374, 404
Leukodystrophy(ies), 458, 484 homocystinuria, 273–274 Cz-A1/Cz-A2, 460
metachromatic, 271 lysosomal disorders, 274 display conventions for, 86
J LGS. See Lennox-Gastaut syndrome (LGS) neuroaxonal dystrophies, 274 for displaying EEG data, 523
Jackbox, 59 LIEE. See Late infantile epileptic neuronal ceroid lipofuscinosis, type III, four-channel, for PRVEP, 450, 472
JAE. See Juvenile absence epilepsy (JAE) encephalopathy (LIEE) 274–275 MSLT, 621t, 623
JME. See Juvenile myoclonic epilepsy (JME) Light emitting diode (LED) goggles, 456 progressive myoclonus epilepsies, paired-channel, 86
Juvenile absence epilepsy (JAE), 290, 292f LKS. See Landau-Kleffner syndrome (LKS) 275–276 paired-group, 86
Juvenile myoclonic epilepsy (JME), 292–293, Loop of Meyer, 447 of early infancy PSG, 608–609, 609t
293f, 332–333, 333f LORETA. See Low-resolution tomography aminoacidurias, 270 in quantitative EEG, 551, 552–553f
(LORETA) glucose transporter 1 deficiency recording, for ventilatory monitoring in
Low-pass filter, 52–54f, 53, 82 syndrome, 269 polysomnography, 608–609, 609t
K
Low-resolution tomography (LORETA), lysosomal disorders, 268–269 referential, 41, 86, 87–88f, 374, 404
K complexes, 612
24, 358 Menkes Disease, 271 selection of, 89
in adolescence, 143
Lowered seizure threshold, 169 organic acidurias, 269–270 SEP, recording, 456, 474t, 493, 493t
in sleep, 103, 107f
Lysosomal disorders progressive encephalopathy with edema, standard neonatal, 126
and vertex transients, 196
of childhood and adolescence, 274 hypsarhythmia, and optic atrophy, 271 transverse vertex, 601
Kainate, 9
of early infancy, 268–269 vitamin metabolism, disorders of, 269 unpaired, 86
Kaplan-Meier survival curve, 206f
West syndrome, 267–268 used for BAEP, 461
Kinky hair disease, 260, 271
of late infancy voltage fields in EEG traces, display of,
Kirchhoff’s current law, 49
Kirchhoff’s voltage law, 49 M Alpers disease, 272–273 40–42, 41f
Macula, 447 congenital disorder of glycosylation, 273 Motor evoked potentials (MEPs), 501t
Krabbe disease, 268, 458
Magnetic resonance imaging (MRI), metachromatic leukodystrophy, 271 anatomy and physiology, 501–502
in BAEP, 469
coregistering EEG data with, 347, mucopolysaccharidoses, 271–272 anesthetic considerations, 505–507, 506f
349–350, 349–351f neuronal ceroid lipofuscinoses, 272 inhalational agents, 506–507
L Magnetoelectroencephalography, 369, 371 Schindler disease, 271 intravenous agents, 507
Lafora disease (EPM2), 275 Magnetoencephalography, 13, 29 Metachromatic leukodystrophy, 271 neuromuscular junction blocking
Lambda waves, 101, 115, 119f, 120 Maintenance of wakefulness test (MWT), Methylene tetrahydrofolate reductase agents, 507
Landau-Kleffner syndrome (LKS), 295, 600, 622 (MTHFR) deficiency, 262, 269 change, mechanisms of, 507–509, 508f
297, 299 interpretation, 623 Methylmalonicacidemia, 265, 266 acute trauma, 507
Laplacian montages, 44 procedure, 623 Mg2+ ions, 5 anesthetics, 507, 509
Large hemispheric brain tumors, 247 Malignant migrating focal seizures in Microelectrode arrays, 61 ischemia and blood pressure, 507
Late infantile epileptic encephalopathy infancy, 300–301, 302f lessons from, ictal discharges and ictal technical issues, 509
(LIEE), 259, 300, 306, 306–307f Maple syrup urine disease, 265, 279 penumbra, 17–19, 18f temperature, 507
DESIGN SERVICES OF
640 Index
Motor evoked potentials (MEPs) (continued ) N rhythmic temporal theta activity in, 143, Neurophysiologic intraoperative monitoring,
clinical applications, 511 N-methyl-d-aspartate (NMDA) receptors, 146, 146f 489–539
methodology, 502–505, 503t, 503f, 5, 6 sharp EEG transient in, 169, 172, brainstem auditory evoked potentials
505t, 506f NALD. See Neonatal adrenoleukodystrophy 174–178f anatomy and physiology, 512, 512t
recording techniques, 504–505 (NALD) trace alternant in, 135 anesthetic considerations, 513
stimulating techniques, 502–504 Nasal pressure transducer, for airflow trace discontinu in, 135 auditory nerve action potential, 521
safety, 509–511, 511t monitoring in polysomnography, 605– visual analysis of, 126–131, 128–133f, change, mechanisms of, 513–520, 515t,
warning criteria, 509, 510f 606, 605f 207–209 516–520f
Motor unit action potentials (MUAP), 533 NCLs. See Neuronal ceroid lipofuscinoses Neonatal epilepsy syndrome, 260 clinical applications, 521
Movement-associated arousals, effects on (NCLs) Neonatal seizures. See Seizure(s), neonatal methodology, 512–513, 514f, 515f
polysomnographic scoring, 620 NCS. See Nerve conduction studies (NCS) Neonate(s) warning criteria, 520–521
Movement(s), effects on polysomnographic NCSE. See Nonconvulsive status epilepticus with clinically diagnosed seizures, 186 electroencephalography, 521–522
scoring, 619–620 (NCSE) electrographic neonatal seizures, 177–205 anatomy and physiology, 522
MS. See Multiple sclerosis (MS) Needle electrodes, 535, 535f neonatal electroencephalographic anesthetic considerations, 523–524,
MSLT. See Multiple sleep latency test Negative centrotemporal SETs, 169 background, 205–206, 205t 524–527f
(MSLT) Neocortical anatomy, and thalamic with occult seizures, 177 change, mechanisms of, 524–526,
MTHFR deficiency. See Methylene connections, 9–11 sharp electroencephalographic transients 527–528t, 529–530f, 532t
tetrahydrofolate reductase (MTHFR) Neonatal adrenoleukodystrophy (NALD), in clinical applications, 530–531
deficiency 264–265 frontal, 165, 167–168, 167f methodology, 522–523
Mu rhythm, 118f Neonatal EEG, 165, 166f negative, 169, 174f, 175f quantitative analysis, 531
adult EEG, normal, 94–96, 95f anterior dysrhythmia in, 148, 149f, 150f positive sharp waves, 169, 172, 176f, warning criteria, 526–530
in neonates and children, 153–154, 154f background, classification and 177f, 178f electromyography
MUAP. See Motor unit action potentials implications of, 205–206, 205t temporal and central negative, 168–169, free running, 535–536, 535f
(MUAP) biobehavioral state in, 135 170–173f stimulated, 534–535, 535f
Mucopolysaccharidoses, 271–272 centrotemporal delta activity in, 147 Nerve action potential (NAP), auditory, motor evoked potentials, 501t
Multifocal spikes, 317–318, 317f conceptional age in, 131 513, 521 anatomy and physiology, 501–502
Multimodal brain monitoring, 587–590, 594f continuity in, 126–127, 128f Nerve conduction studies (NCS) anesthetic considerations, 505–507, 506f
Multiple fixed-dipole models, 353 delta brushes in, 144–147f, 148 anatomy and physiology, 531–533 change, mechanisms of, 507–509, 508f
Multiple sclerosis (MS) in excessive discontinuity, 157, 158f, 159 anesthetic considerations, 536 clinical applications, 511
BAEP in, 468–469 abnormal asymmetry, 161, 165 clinical applications, 538–539, 538t methodology, 502–505, 503t,
SEP in, 483 abnormal interhemispheric cranial nerve surgery, 538–539 503f, 505t, 506f
Multiple sleep latency test (MSLT), 600, 624 asynchrony, 165 peripheral nerve surgery, 538–539 safety, 509–511, 511t
interpretation of, 621–623, 622t abnormal maturation, 165, 166f spinal surgery with warning criteria, 509, 510f
procedure for, 620–621, 621t, 621f abnormal voltage, 159, 161 instrumentation, 538 nerve conduction studies
Muscle artifacts, 82, 417 for age, 159, 161t interpretation of, 536–537, 537f anatomy and physiology, 531–533
Muscle MEP recordings, 504, 505, 505t burst-suppression pattern, 159, 160f methodology, 533–534, 534f, 535f anesthetic considerations, 536
MWT. See Maintenance of wakefulness test isoelectric tracing, 161, 164f Neuroaxonal dystrophies, 274 clinical applications, 538–539, 538t
(MWT) persistent low voltage, with or without Neurointensive care unit (NICU), EEG interpretation of, 536–537, 537f
Myoclonic-astatic epilepsy, 156, 272, 287, lack of differentiation, 161, 162f, 163f monitoring in, 373 methodology, 533–534, 534f, 535f
288–289f interhemispheric synchrony in, 131, 165 Neuromuscular junction blocking agents somatosensory evoked potentials
Myoclonic-atonic seizure, 287, 306, 307f monorhythmic occipital delta activity in, (NMJBA) anatomy and physiology, 489–490, 490t
Myoclonic epilepsy in infancy (MEI), 287, 288f 143, 144f for motor evoked potentials, 507 anesthetic considerations, 494–495,
Myoclonic-tonic seizures, 306 montage selection in, 126 for somatosensory evoked potentials, 494t, 495–496f
Myoclonus, 221, 274, 293, 302 ontogeny, overview of. See Ontogeny, 494–495, 496f change, mechanisms of, 495–498, 497–501f
baltic myoclonus epilepsy, 275 overview of Neuronal ceroid lipofuscinoses (NCLs), clinical applications, 500
progressive myoclonus epilepsies, positive sharp waves, 169, 172, 176–178f 272, 272f methodology, 490–494, 490f,
275–276, 295f rhythmic occipital theta activity in, 143, type III, 274–275 491–493t, 492f
Myotome, 531 145f Neuronal specific enolase (NSE), 580 warning criteria, 498–500
DESIGN SERVICES OF
Index 641
Neurotransmitters, 5 Nonketotic hyperglycinemia, 260–261, 261f Paradoxical arousal response, 194 infancy and childhood
Newborn(s). See also under Neonate(s) Nonneuronal currents, 7 Parasomnia(s), evaluation of, 626–627, 626t alpha rhythm (alpha activity), 148
acyl-coenzyme A oxidase deficiency Nonsyndromic infantile epilepsies, 268 Parietal lobe seizures, 328 alpha variants, 151, 152f, 153
in, 265 Normal hearing level (nHL), 461 Paroxysmal depolarizing shift (PDS), 14–15 beta activity, 154–155
biotin metabolism, disorders of, 267 Normal physiological intracranial EEG, 374 Paroxysmal hypnagogic hypersynchrony, 191, distribution, 151
epileptic encephalopathies in, 262t Notch/bandstop filter, 54, 54f 191f, 192f frequency of posterior dominant
IEM causing seizures in, 262 NSE. See Neuronal specific enolase (NSE) Paroxysmal slow activity, 188, 191–192, rhythm, 148, 148f, 151
Leigh syndrome, 267 Nyquist limit, 55 192f, 193f frontal theta activity, 155–156, 156f,
maple syrup urine disease in, 265 Parvalbumin positive neurons, 8 157f
molybdenum cofactor deficiency in, Passband, 53 frontocentral theta activity, 155–156,
263–264 O Pattern reversal visual evoked potentials 156f, 157f
neonatal adrenoleukodystrophy in, Obligate wave absence, in BAEPs, 464, 464f (PRVEP), 448–456, 449–456f, 451–453t midline central theta activity, 156–157
264–265 Occipital alpha rhythm, in children, 188 abnormalities, 453–456 mu rhythm, 153–154, 154f
nonketotic hyperglycinemia in, Occipital intermittent rhythmic delta activity interpretation, 451–453 symmetry, 151
260–261, 261f (OIRDA), 242 methodology, 448 voltage of posterior dominant rhythm,
organic acidurias in, 265, 266–267 Occipital lobe seizures, 328 recording, 449–451 151
peroxisomal disorders in, 264–265 Occipital sharp waves, 103 stimulation, 448–449 introduction to, 126
pyridoxine dependency in, 262–263, Occipital slow transients, 204f, 205 Patting artifacts, 142 neonatal
263–264f Ohmic conductances, 6 PDE. See Pyridoxine-dependent epilepsy classification and implications of,
pyruvate carboxylase deficiency, 267 Ohm’s law, 5, 8 (PDE) 205–206, 205t, 206f, 207f
pyruvate dehydrogenase deficiency in, 267 Ohtahara syndrome, 259, 260 PDS. See Paroxysmal depolarizing shift composition of, 143, 144–147f, 146–
sulfite oxidase deficiency in, 263–264 OIRDA. See Occipital intermittent rhythmic (PDS) 148, 149f, 150f
urea cycle disorders in, 265 delta activity (OIRDA) Peak latency. See Absolute latency ontogeny, 134f
Zellweger syndrome in, 264 Ontogeny, pediatric EEG. See Pediatric Pediatric acute encephalopathy, 161 adolescence, 143
nHL. See Normal hearing level (nHL) EEG, ontogeny Pediatric EEG, 125–209 childhood, 2 to 10 years, 142
NICU, EEG monitoring in. See Optic nerve fibers, anatomy and waveform electrographic neonatal seizures and conceptional age
Neurointensive care unit (NICU), EEG generators, 447 clinical correlations 24 to 29 weeks, 131, 134
monitoring in Optic neuritis, for visual evoked potentials, arousal, activity of, 193–194 30 to 32 weeks, 134–135, 136f
NMDA receptors. See N-methyl-d-aspartate 458, 459f characteristics 33 to 34 weeks, 135
(NMDA) receptors Organic acidurias, 265–267, 269–270 amplitude, 182, 185f, 186 35 to 36 weeks, 135, 137f, 138
NMJBA. See Neuromuscular junction Ornithine transcarbamylase deficiency, duration, 177, 181–182f, 182 37 to 40 weeks, 138, 139f, 140f
blocking agents 265, 266f location, 177, 179–180f 41 to 44 weeks, 138
Nocturnal behavioral events, evaluation of, Oscillation(s), 11 morphological appearance, 182, 45 to 46 weeks, 138, 141f
626–627, 626t and cellular activity, relationship between, 183–184f early infancy, 46 weeks to 1 year, 138,
Non-Ohmic conductances, 6 13–14 drowsiness, activity of 140, 142
Noncerebral artifacts, 40 hierarchical phase-amplitude coupling, 12f, 14 monorhythmic slow activity, late infancy, 1 to 2 years, 142
Nonconvulsive seizures, continuous EEG in, high-frequency, EEG markers of ictal 187–188, 189–190f types and significance of abnormal, in
572t, 578–581 territories, 19–24, 20f, 23f paroxysmal slow activity, 188, neonates and children
Nonconvulsive status epilepticus (NCSE) structure of EEG, 12–13, 12f 191–192, 192f, 193f excessive discontinuity, 157, 158f, 159,
algorithm for diagnosis of, 231f postarousal hypersynchrony, 194–195, 160f, 161, 161t, 162f, 163f, 164f,
clinical signs associated with, 227, 228t 194–195f 165, 166f
controversy topics, 228 P sharp waves and spikes in older infant sharp electroencephalographic
duration of monitoring, 230 P100 waveform latency, 447, 448, 452 and child transients, 165, 167–169, 167f, 168f,
generalized nonconvulsive ictal activity, 229f Paired-channel montages, 86 hyperventilation response, 170–178f, 172
interictal-ictal continuum, 228 Paired-group montages, 86 186–187, 187f visual analysis, in neonates and children
prevalence range of, 227 Panayiotopoulos syndrome (PS), 296, photic stimulation, 187 abnormalities in, 131, 208–209
proposed criteria for, 228–230 296–297f sleep, activity of, 195–196, 196–204f, continuity, 126–127, 128f, 207–208
seizure termination in patients with, 230f Paradoxical alpha, 94 198, 200, 202, 205 gradient and principal components, 208
DESIGN SERVICES OF
642 Index
Pediatric EEG (continued ) benign childhood epilepsy with esophageal pressure monitors in, 606–607 respiratory monitoring with, 604–609,
interhemispheric symmetry, 129, 129f, centrotemporal spikes, 295, inductive plethysmography, 606, 607f, 608f 605–608f, 609t
130f, 131 296–297, 298f intercostal EMG, 607 thermistors in, 604–605
interhemispheric synchrony, 129, 131, conditions masquerading, 299 piezoelectric belts in, 607 thermocouples in, 604–605
132f, 133f, 208 late-onset occipital lobe epilepsy, 297, recording montage in, 608–609, 609t Positive occipital sharp transients of sleep
organization and principal 299f ventilatory effort monitoring, 606 (POSTs), 103, 105f, 202, 202f, 203f
components, 128 panayiotopoulos syndrome, 296, 296–297f PNPO. See Pyridoxine 5′-phosphate oxidase Positive rolandic sharp waves (PRS), 169,
organized approach to, 207–209 Periodic lateralized epileptiform discharges (PNPO) 172, 176f
special features in, 131, 208 (PLEDs), 244–245, 247f, 248f, 249 PNS. See Peripheral nervous system (PNS) Positive sharp waves, neonatal, 169, 172,
state, 126–127, 128f, 207–208 in focal interictal epileptiform discharges, Point source dipole model, 346 176f, 177f, 178f
symmetry, 208 318–319, 318f Polarity convention Positive temporal sharp waves (PTS), 169,
Pediatric epilepsy syndromes, 283–312 Periodic leg movements (PLMs), effects on for BAEPs, 461 172, 178f
diagnosis of epilepsy, based on EEG polysomnographic scoring, 619–620 in recording techniques, 81 Positive vertex sharp wave (PVS), 169,
features, 284, 284t Periodic pattern, 220 Poliodystrophy, progressive infantile, 172, 177f
epilepsies with encephalopathies, 299–308, Peripheral nerve surgery, 538–539 272–273, 273f Positron emission tomography (PET), 363, 371
301–308f Peripheral nervous system (PNS), 480 Polymorphic delta activity, 279 Postarousal hypersynchrony, 194–195, 194–195f
epileptic encephalopathies, 301–308 Peripheral waveforms, 444 Polyphasic waves, 151 Posterior dominant rhythm, 96
epileptogenic encephalopathies, 300–301 Peroxisomal disorders, 264–265 Polysomnography, 600–610, 601–608f, 609t, frequency of, 148, 148f, 151
late infantile epileptic encephalopathy, Persistent low voltage, with or without lack 611f, 612t, 613–615f, 618f voltage of, 151
306, 306–307f of differentiation, 161, 162f, 163f airflow monitoring by, 604–609, Posterior quadrant seizures, 412–413, 413f
Lennox-Gastaut syndrome (LGS), PET. See Positron emission tomography (PET) 605–608f, 609t Posterior slow-wave transients, associated
307, 308f Phantom spike-and-wave, 108 alternatives to, 606 with eye movements, 153
West syndrome, 304–306, 305f Phase progression, 11 anterior tibialis EMG in, 603, 604f Posterior slow waves of youth (PSWY),
familial epilepsies, 284–287, 286f Phase reversal, 37, 40, 86, 89 axial EMG in, 603 97–98, 142, 151
autosomal dominant nocturnal frontal Phenylketonuria, 270–271 basic sleep scoring with, 611–612, POSTs. See Positive occipital sharp transients
lobe epilepsy, 285–286, 286f Phosphomannomutase-2 deficiency, type Ia, 273 611f, 612t of sleep (POSTs)
benign familial infantile epilepsy, 285 Photic driving response, 100 carbon dioxide detectors in, 606 Posttetanic stimulation, 504
benign familial neonatal epilepsy, 285 Photic stimulation, in normal pediatric EEG, and computer-assisted scoring, 610 Potential(s), sources of, 28–30, 29–30f
familial lateral temporal lobe 187 and EEG sleep recording, 601–603, Power, 565–566
epilepsy, 286 Photo-epileptiform discharges, 323, 324f 601f, 603f PPR. See Photoparoxysmal response (PPR)
familial mesial temporal lobe epilepsy, Photomyoclonic response, 101 electro-oculogram in, 602–603, 602f Preamplifiers, 61
286–287 Photoparoxysmal response (PPR), 100–101, inductive plethysmography, 606, 607f, 608f Precision, 56
focal structural epilepsies, 308–310 323, 324f interpretation of, 610–620, 611f, 612t, Primary current, 29
genetic generalized spike-wave epilepsies, Piezoelectric belts, for ventilator monitoring 613–615f, 618f Prion diseases, 250
287–293, 288–293f in polysomnography, 607 arousals and, 612–613, 613–615f Progressive childhood encephalopathy, 258–280
childhood absence epilepsy, 290, Place cells, 11 awakenings and, 612–613, 613–615f age categorization, 260
290f, 291f PLEDs. See Periodic lateralized epileptiform EEG-related variables in, 611–613, early myoclonic encephalopathy,
epilepsy with myoclonic absences, 290 discharges (PLEDs) 611f, 612t, 613–615f 260–261, 260f
juvenile absence epilepsy, 290, 292f Plethysmography, inductive, for ventilatory movement-related variables in, 619–620 EEG hallmark of, 259
juvenile myoclonic epilepsy, monitoring in polysomnography, 606, in pediatric sleep-disordered breathing, inborn error of metabolism, 259
292–293, 293f 607f, 608f 618–619 causing seizure in newborn, 262–267,
masquerading conditions, 293 PLP-DE. See Pyridoxal respiration-related variables in, 263–264f, 266f
myoclonic-astatic epilepsy, 287, 5′-phosphatedependent epilepsy 616–619, 618f limited repertoire of immature EEG, 259
288–289f (PLP-DE) in sleep apnea diagnosis, 617–618 metabolic disorders, 267–279
myoclonic epilepsy in infancy, 287, 288f Pneumotachography, for airflow monitoring nasal pressure transducer in, 605–606, 605f of childhood and adolescence, 273–279,
by interictal EEG characteristics, 311t in polysomnography, 606, 607f, 608f, 609t pneumotachography in, 606, 607f, 275f, 276f
self-limited epilepsies with focal spikes, arterial oxygen assessment in, 607–608 608f, 609t of early infancy, 267–271, 270f
293–299, 296–299f ECG in, 608 recording, ambulatory, 609–610 of late infancy, 271–273, 271f, 273f
DESIGN SERVICES OF
Index 643
role of EEG in child with suspected, R electrode placement in, 79–80, 80f Scalp cup electrodes, 59, 60f
279–280 Rarefaction, 461, 513 filters in, 82, 82–85f, 85 Scalp EEG pattern, 37, 376
spectrum of epileptic encephalopathies, 259 Reactance, 52 issues related to digital, 80–81 artifacts for, 417
Progressive Encephalopathy with Edema, Reactivity montages in, 85–86, 87–88f, 89 in assessment of normal EEG, 90
Hypsarhythmia, and Optic Atrophy of alpha rhythm, 92, 251 for motor evoked potentials, 504–505 factors in determination of, 30, 32–35f
(PEHO Syndrome), 271 EEG, in encephalopathic patients, 215– polarity conventions in, 81 amplitude, of cortical activity, 32–33
Progressive infantile poliodystrophy, 272– 217, 216f for PRVEP, 449–451 source area, 31, 32–33f
273, 273f of mu rhythm, 95 sensitivity in, 81–82 source location, 31
Progressive myoclonus epilepsies (PME), Recording(s) for somatosensory evoked potentials, source orientation, 31–32, 34f
275–276, 295f auditory nerve action potential, 521 491–494, 492f synchrony, of cortical activity,
Progressive neurological syndrome, in cerebral death, technical standards for Referential montages, 41, 86, 87–88f 33–34, 35f
infancy, 269 EEG, 235t Referential recordings, 86, 374 ictal, 335–336
Propagation, EEG source characterization, derivation, in visual evoked potentials, 448 Reformatting, 40 potentials, 339–341, 340f, 341f
36f, 37 differential amplifier, 444 REM sleep (R sleep), in sleep architecture, recordings, 335
Propionic acidemia, 265 digital, issues related to, 80–81 104, 108f, 109f Scalp electrodes, 59, 78, 335, 473
PRS. See Positive rolandic sharp waves EEG Resistor(s), 46t, 47, 47f, 48, 48f Schindler disease, 271
(PRS) clinical indications of subdural Respiration(s), effects on polysomnographic SEEG. See Stereo-electro-encephalography
PRVEP. See Pattern reversal visual evoked electrode, 373 interpretation, 616–619, 618f (SEEG)
potentials (PRVEP) sleep, 601–603, 601f, 602f Respiratory artifact, 235t SEF. See Spectral edge frequency (SEF)
PS. See Panayiotopoulos syndrome (PS) electrodes Respiratory monitoring, polysomnography Seizure(s). See also Epilepsy
Pseudo petit mal, 191, 192 for motor evoked potentials, 504–505 in, 604–609, 605–608f, 609t absence, 331
Pseudo-temporal epilepsy, 409, 410f for somatosensory evoked potentials, Retina, anatomy and waveform generators, atonic, 334, 335f
PTS. See Positive temporal sharp waves 491–492, 492f 447–448 atypical absence, 334
(PTS) in evoked potentials, 444–445 Rett syndrome, 278, 279f bilateral independent temporal lobe, 408
Pulsation artifacts, 417 intracranial, in EEG, 374–377, 375f, 376f, Reye syndrome, 270 central cortex, 411–412, 412f
PVS. See Positive vertex sharp wave (PVS) 377–380f Rhythmic bursting (Ih), 10 clonic, 334
Pyknolepsy, 290 MEP Rhythmic delta activity, 219–220, 219f clonic-tonic-clonic, 334
Pyramidal cells, 6, 8, 29 muscle, 505, 505t Rhythmic midtemporal theta bursts of complex focal, 325–326
Pyramidal neurons, 29, 522 spinal cord, 505, 505t drowsiness (RMTD), 106, 111f diffuse tonic-focal clonic, 310
Pyramidal somata, 7 montage, 608–609, 609t bilateral independent, 110f dipole source modeling of, 350,
Pyridoxal 5′-phosphatedependent epilepsy parameters of, normal adult EEG, 91–92 Rhythmic occipital theta activity, in neonatal 352f, 353, 354f
(PLP-DE), 263 pattern reversal visual evoked potentials, EEG interpretation, 143, 145f EEG-confirmed neonatal, 186
Pyridoxine 5′-phosphate oxidase (PNPO), 263 449–451 Rhythmic temporal theta activity, in neonatal for EEG voltage topography, 339
Pyridoxine dependency, 261t, 262–263, procedure for intracerebral depth EEG interpretation, 143, 146, 146f electrographic neonatal, 177–205
263–264f electrodes encephalography. See Ripples, 21 extratemporal complex focal, 328–330,
Pyridoxine-dependent epilepsy (PDE), 263 Intracerebral depth electrodes of prematurity. See Delta brushes, in 329–332f
Pyruvate carboxylase deficiency, 267 encephalography, recording procedure neonatal EEG interpretation focal clonic, 310
Pyruvate dehydrogenase deficiency, 267 referential, 86, 374 RMTD. See Rhythmic midtemporal theta focal tonic, 310
spinal cord MEP, 505, 505t bursts of drowsiness (RMTD) focal tonic-clonic, 310
techniques, 78–89 Rolandic epilepsy (RE). See Benign frontal lobe, 409, 410–411, 410f
Q for brainstem auditory evoked childhood epilepsy with centrotemporal generalized, 330
QEEG. See Quantitative EEG (qEEG) potentials, 459–460, 513 spikes generalized tonic-clonic, 333–334
Quantitative EEG (qEEG), 95, 252 calibration in, 81–82 generalized tonic-closure, 333–334
in intensive care unit, 562–563, 565–569, cerebral generators of EEG potentials hypermotor focal, 310
574–578f in, 78–79, 79f S infantile focus, 309–310
neurophysiologic intraoperative conventions and sensitivity/filter Safety, electrical. See Electrical safety insular lobe, 413, 414f, 415
monitoring, 531 settings, 80–85 Sampling rate, in digitization, 55 malignant migrating focal, in infancy,
Queen Square method, 449–450 EEG derivations in, 78 Sandhoff disease, 268 300–301, 302f
DESIGN SERVICES OF
644 Index
Seizure(s) (continued) temporal and central negative, 168–169, Sleep architecture, 101–104, 103–109f anesthetic considerations, 494–495, 494t,
mesial vs. neocortical temporal lobe, 408, 170–173f in late infancy, 142 495–496f
408f Sharp waves in older infants, 131 inhalational agents, 494
myoclonic-atonic, 287 in SETs, 165 Sleep-disordered breathing, pediatric, intravenous agents, 494
myoclonic-tonic, 306 and spikes in older infant and child, 186–187 polysomnographic scoring of, 618–619 neuromuscular junction blocking
neonatal vertex transients, 195–196, 196–201f, 198, Sleep disorders, 599–627 agents, 494–495
disorders associated with, ambulatory 200, 202 ambulatory PSG recording in, 609–610 change, mechanisms of, 495–498,
EEG monitoring in, 628 Shunting inhibition, 8 clinical evaluation of, 623–624, 625f, 626t 497–501f
EEG-related, 177–186, 181–185f, 186t Sialidosis excessive daytime sleepiness, evaluation of, acute trauma, 495–496
amplitude of, 182, 185f, 186 type I, 274 624–626, 625f ischemia and anoxia/blood
duration of, 177, 181–182f, 182 type II, 274 insomnia, evaluation of, 627 pressure, 495
location in, 177, 179–180f Sigma-delta converter, 57, 58f laboratory evaluation of, 599–627. See also technical issues, 496–498
morphological appearance of, 182, Signal analysis, 92 specific test, e.g., Polysomnography temperature, 496
183–184f Signal resolution, 56–57, 57f maintenance of wakefulness test, 623–627 in Charcot-Marie-Tooth disease, 484
in newborns and, 262–267 Silver chloride electrodes, 58 multiple sleep latency test in, 620–623, clinical applications, 500
occipital lobe, 328 Simple filters, 52–54, 52f, 53f, 54f 621t, 621f, 622t clinical correlations, 483–484
parietal lobe, 328 Simple focal seizures, 325 parasomnias, evaluation of, 626–627, 626t in Friedreich ataxia, 483
posterior quadrant, 412–413, 413f Single-moving dipole model, 342, 343f, 344f polysomnography in, technical aspects, interpretation, 474–476, 475f, 476t
sensorimotor, 411–412, 412f Single-photon emission computed 600–610, 601–608f, 609t, 611f, Krabbe disease, 484
simple focal, 325 tomography (SPECT), 371 612t, 613–615f, 618f. See also maturational issues of, 481
symptomatic generalized tonic-clonic, 334 Sinusoidal alpha rhythm, 14 Polysomnography median nerve, 473f, 475f, 477f, 480, 481
tonic, 334 SIRPIDs. See Stimulus-induced rhythmic, Sleep Disorders Task Force of the American dorsal column pathway, 483, 489, 501
unilateral mesial temporal lobe, 407 periodic or ictal discharges Sleep Disorders Association, 613 short-latency cortical potentials
Seizure-onset rhythms, 377, 381 6-Hz generalized spike-and-wave discharges Sleep patterns, 227, 241 and, 470
Seizure-onset zone (SOZ), 425–433, 427–433f (GSW), 108, 112f Sleep scoring, with polysomnography, 611– metachromatic leukodystrophy, 484
definition, 425 Sleep 612, 611f, 612t methodology, 472t, 473f, 474t, 490–494,
epileptogenicity index, 430 active, in newborn, 127, 128f Sleep spindles, 10, 103, 131, 165 490f, 491–493t, 492f
epileptogenicity maps, 433, 433f activity of Sleepiness, daytime, excessive, evaluation of, recording techniques, 472–474, 491–494
intracerebral ictal-onset patterns, 427, occipital slow transients, 204f, 205 624–626, 625f stimulating techniques, 471–472,
427t, 428–430f positive occipital sharp transients, 202, Slow activity 490–491
symptomatogenic zone, 425 202f, 203f evaluating amount and duration of, 153 pediatric considerations, 480–483
Self-limited epilepsies with focal spikes, 293–299 sharp-wave, vertex transients, 195–196, monorhythmic, 187–188, 188f, 189f, 190f Pelizaeus-Merzbacher disease, 484
benign childhood epilepsy with centro 196–201f, 198, 200, 202 paroxysmal, 188, 191–192, 191f, 192f, 196f physiology, 489–490, 490t
temporal spikes, 295, 296–297, 298f fast activity, 200, 201f, 202 Slow alpha variant pattern, 142 as predictors of outcome in coma, 483
conditions masquerading, 299 K complexes and vertex transients, Slow spike-and-wave discharge pattern, recording
late-onset occipital lobe epilepsy, 297, 299f 196, 198f 322, 322f montage for, 493, 493t
panayiotopoulos syndrome, 296, 296–297f spindles, 198, 198f, 199f, 200, 200–201f Slow-wave activity, 241–243 parameters for, 493–494
Sensitivity, recording conventions and, apnea, diagnosis of, 617–618 Slow-wave sleep, in sleep architecture, stimulation
80–85 continuous slow-wave, in newborns, 138 103–104, 107f for eliciting, 471
Sensorimotor seizures, 411–412, 412f deprivation of, activation by, 102, 622 Small sharp spikes, 109, 165 of peripheral nerves by, 480
Sensory-evoked potentials, 30 EEG during, 196 Somatosensory alpha rhythm. See Mu warning criteria, 498–500
SEPs. See Somatosensory evoked potentials effects on BAEPs, 460 rhythm waveform generators, 470–471, 471t
(SEPs) effects on EEG in juvenile myoclonic Somatosensory evoked potentials (SEPs) Sound intensity methods, for BAEPs, 461
Sharp-and-slow-wave complexes, 322 epilepsy, 293 abnormalities, 476–480, 477–482f Source analysis, EEG, 249
Sharp EEG transients (SETs) vertex sharp-wave transients during, in adrenoleukodystrophy, 484 SOZ. See Seizure-onset zone (SOZ)
frontal, in neonates, 165, 167–168, 167f 195–196, 196–201f, 198, 200, 202 amplifier setting for, 474 Spasm(s)
negative, 169, 174f, 175f vertex transients during, 196, 197f in amyotrophic lateral sclerosis, 483 with focal features, 310
positive sharp waves, 169, 172, 176f, 177f, 178f video-EEG monitoring during, 609 anatomy, 470–471, 471t, 489–490, 490t infantile, video-EEG monitoring in, 227
DESIGN SERVICES OF
Index 645
Spatial sampling, coregistering EEG data in extratemporal lobe epilepsy, vs. depth electrodes, 369 Temperature
with, 347, 349–350, 349f, 350f, 351f indications for in intracranial EEG, 367–389, 370–372f, effects on BAEPs, 516, 517f
Spatiotemporal multiple dipole model, central cortex seizures, 411–412, 412f 375–380f, 382–388f effects on MEP, 507
342–343, 345f, 346 frontal lobe seizures, 409, 410–411, 410f risks and complications of placement, effects on nerve conduction and SEP, 496
Spectral edge frequency (SEF), 566 insular lobe seizures, 413, 414f, 415 371–373 Temporal intermittent rhythmic delta activity
Sphenoidal electrodes, 80, 328f posterior quadrant seizures, 412–413, 413f Subdural hematoma, 372 (TIRDA), 242, 244f
Spherical head models, 349 guided radiofrequency thermocoagulation, focal encephalopathies in, 239t, 251 in focal interictal epileptiform discharges,
Spielmeyer-Vogt disease, 274–275 435–436, 436f PLEDS in, 251 319–320, 319f
Spike-and-slow-waves, generalized in lesional and nonlesional focal epilepsies, Subdural strips electrodes, 60 Temporal lobe
atypical, 321 indications for, 415 Successive-approximation converter, complex focal seizures, 326–328, 327–329f
Spike and wave discharges (SWDs), 10 in temporal lobe epilepsy, indications for 57, 58f seizures, 353
Spike sources, for EEG voltage topography, bilateral independent temporal lobe Sucking artifact, in infant, 142 sources, dipole source modeling of, 353,
339, 340, 363 seizures, 408, 408f Sulfite oxidase deficiency, 263–264 355–358f
Spikelets, 7 pseudo-temporal seizures, 409, 410f “Supernormal” EEG, for age, 152f, 153 spikes, 349
Spikes temporal plus epilepsy, 408–409, 409f Superposition principle, 52, 342 Temporal lobe epilepsy (TLE), 368, 377
in basal temporal cortex, 363 unilateral mesial temporal lobe Surface electrodes, 504, 534–535, 535f familial lateral, 286
intracranial interictal, role of, 376 seizures, 407 Surface ground electrode, 472 familial mesial, 286–287
in SETs, 165 Stereo-encephalography. See Intracerebral Surface-positive sharp transients, 202 focal onset in, 381
sharp waves and, 316, 316f depth electrodes encephalography Surround inhibition, epileptiform activity, ictal EEG changes in, 326
in older infant and child, 186–187 Stereotactic radiofrequency cellular basis of, 19, 20f, 21f indications for SEEG in, 407–415, 409f,
-sorting algorithms, 4 thermocoagulation (RFTC), 435–436, 436f SWDs. See Spike and wave discharges 411–413f
-wave discharges, triphasic waves vs., 222 Stimulated electromyography, 534–535 (SWDs) Temporal plus epilepsy, 408–409
Spinal cord function, intraoperative Stimulation, procedure of, 434, 435 Sylvian fissure, 340 TES. See Transcranial electrical stimulation
monitoring of Stimulus(i), acoustic, for BAEPs. See Symmetry, in neonatal EEG interpretation, (TES)
MEP monitoring in, 505, 505t Acoustic stimulation, for BAEPs 208, 215f, 562f Thalamic connections, neocortical anatomy
SEP monitoring in, 489 Stimulus-induced rhythmic, periodic or ictal Symptomatic generalized epilepsies and, 9–11
Spinal surgery, with instrumentation, 538, discharges, 216, 217f, 561 atonic and akinetic seizures, 334, 335f Thalamic hemorrhage/stroke, focal
538t Stimulus polarity, for BAEPs, 461 atypical absence seizures, 334 encephalopathies in, 239t, 254
Spinal waveforms, 444 Stopband, 53 clonic seizures, 334 Thalamocortical circuit, 10
Spindle coma, 198 Stray capacitance, 66 symptomatic generalized tonic-clonic Therapeutic hypothermia (TH), 582
frequency pattern, 225–226, 226f Stray inductances, 66 seizures, 334 Thermistor(s), for airflow monitoring in
Spindle-like fast rhythms. See Delta brushes, Stroke, role of EEG in, 254–255 tonic-clonic seizures, 334 polysomnography, 604–605
in neonatal EEG interpretation Subacute necrotizing encephalomyelopathy. tonic seizures, 334 Thermocouple(s), for airflow monitoring in
Spindles, sleep, 198, 198f, 199f, 200, See Leigh syndrome Synaptic activity, as source of extracellular polysomnography, 604–605
200–201f Subacute sclerosing panencephalitis (SSPE), current flow, 79, 79f Theta activity
Spontaneous arousal, 195 220, 250–251 Synaptic currents, 5 frontal, 155–156, 156f, 157f
Spontaneous modulation, 14 Subarachnoid hemorrhage, 239t, 254, 563 Synchrony, 165 frontocentral, 155–156, 156f, 157f
Stage 1 sleep (N1 sleep), in sleep architecture, Subclinical rhythmic electrographic discharge of cortical activity, 33–34, 35f midline central, 156–157
102, 104f in adults (SREDA), pattern in EEG, interhemispheric, in neonatal EEG Theta frequency(ies), 97, 98f
Stage 2 sleep (N2 sleep), in sleep architecture, 111–112, 115f interpretation, 129, 130f, 131 Third rhythm, 94
103, 105f, 106f Subcortical waveforms, 444 3D CT/MRI co-registration technique, 371
Stage 3 sleep (N3 sleep), in sleep architecture, Subdermal electrodes, 535, 535f 3-Hz spike-and-wave discharges,
103–104, 107f Subdural electrode corticography. See T 320–321, 320f
Stage W (wakefulness), in sleep architecture, Intracranial EEG Tay-Sachs disease, 268 Threshold intensity, 472
102, 103f Subdural electrodes TBI. See Traumatic brain injury (TBI) Time constant, 51
Status epilepticus, continuous EEG in, characteristics of, 369, 370f TCAs, effects on EEG activity. See Tricyclic Time discretization, 55–56, 55–56f
575–578 clinical indications of, in EEG antidepressants (TCAs), effects on EEG Time domain analysis, 563, 565
Stereo-electro-encephalography (SEEG), 395 recording, 373 activity Time-frequency analysis, 566
DESIGN SERVICES OF
646 Index
Time-varying circuits, 51–52, 51f cerebellopontine angle, BAEPs in, 469 Vertex transients Visual sleep scoring, 610
TIRDA. See Temporal intermittent rhythmic in median and tibial SEP, 483 K complexes and, 196 Visual system, 443
delta activity (TIRDA) of optic nerve, VEPs in, 458 sharp-wave, 195–196, 196–201f, 198, Vitamin metabolism, disorders of, 269
TLE. See Temporal lobe epilepsy (TLE) Two-point moving average, 62 200, 202 Voltage. See also Cortical generators and
Tonic seizures, 334 Type I glutaric acidemia, 270 Vertex waves (V-waves), 131, 165 EEG voltage fields
Total conductance, 2 Tyrosinemia type III, 271 in sleep architecture, 102, 104f discretization (signal resolution),
Total throughput, for digitizer, 57 Video-EEG monitoring 56–57, 57f
Toxic encephalopathies, 238 absence seizures with JME, 333 of posterior dominant rhythm, 151
Trace alternant pattern, 135, 137f U for recording seizures, 609 sources, in electrical circuit theory, 48
Trace deflection, 40 UIEA. See Utah Intracortical Electrode role of, 177 Voltage-dependent Ca2+ channels, 6
Trace discontinu (discontinuous tracing) Array (UIEA) Viral encephalitis, in EEG abnormalities, 251
EEG pattern, 135, 136f Unilateral mesial temporal lobe seizures, 407 Visual analysis (VA), of pediatric EEG
Transcranial electrical stimulation (TES), 502 Unilateral P100 waveform latency, 453 abnormalities in, 131, 208–209 W
Transfer function, 4 Unpaired montages, 86 continuity, 126–127, 128f, 207–208 Wakefulness test, maintenance of. See
Transient evoked otoacoustic emissions, 470 Unverricht-Lundborg progressive familial gradient and principal components, 208 Maintenance of wakefulness test (MWT)
Transient ischemic attacks (TIAs), focal myoclonic epilepsy. See Baltic myoclonus interhemispheric symmetry, 129, 129f, Waking EEG, in newborns, 138
encephalopathies in, 239t, 251 epilepsy 130f, 131, 208 WAR pattern, 523, 524f
Transmembrane current, 5 Urea cycle disorders, 265 interhemispheric synchrony, 129, 131, Waveform composition symmetry, 129
Trauma Utah Intracortical Electrode Array (UIEA), 132f, 133f, 208 Waveforms, definition of, 443–444
acute, 495–496, 507 60–61, 61f organization and principal West syndrome, 259
brachial plexus, 539 components, 128 in epileptic encephalopathies,
head. See Head trauma organized approach to, 207 304–306, 305f
nerve, 521 V special features in, 131, 208 metabolic disorders of early infancy,
Traumatic brain injury (TBI), 226, 580 VA. See Visual analysis (VA), of pediatric state, 126–127, 128f, 207–208 267–268
Tricyclic antidepressants (TCAs), effects on EEG Visual cortex, primary, 447 Wicket spike (wickets) waveforms, 110,
EEG activity, 622 VARETA technique, 358 Visual evoked potentials (VEPs) 111f, 114f
Triphasic waves, 222–224 Vascular diseases, BAEPs in, 469 anatomy and waveform generators,
in hepatic encephalopathy, 223f Vasospasm, 214, 515 447–448
spike-wave discharges vs., 222 Ventilatory efforts, 604 clinical correlations, 458–459, 459f X
Tumor(s) monitoring of, 606 flash, 456–457, 457f X-linked adrenoleukodystrophy, 264
brain, 245–247 VEPs. See Visual evoked potentials (VEPs) luminance and, 448
epileptiform abnormalities in, 243–244 Vertebrobasilar ischemia, 252–253, 255f pattern reversal, 448–456, 449–456f,
infratentorial, 247, 249 Vertebrobasilar stroke, focal 451–453t Z
large hemispheric, 247 encephalopathies in, 239t, 252–253 pediatric considerations, 457–458 Zellweger syndrome, 264
DESIGN SERVICES OF

John S. Ebersole, Aatif M. Husain, Douglas R. Nordli Jr.-Current Practice of Clinical Electroencephalography-Wolters Kluwer (2014) PDF

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Current Practice of Clinical

Editor Associate Editor Associate Editor

© 2014 by Wolters Kluwer Health

Library of Congress Cataloging-in-Publication Data

A.G. Christina Bergqvist, MD François Dubeau, MD Mohamad Z. Koubeissi, MD

Rodney A. Radtke, MD Joseph I. Sirven, MD William O. Tatum IV, DO

Chapter 1 The Cellular Basis of EEG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Chapter 2 Cortical Generators and EEG Voltage Fields . . . . . . . . . . . . . . . . . . 28

Chapter 3 Engineering Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

Chapter 4 Recording Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78

Chapter 5 Normal Adult EEG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

Chapter 6 Normal Pediatric EEG: Neonates and Children . . . . . . . . . . . . . . . . 125

Chapter 8 EEG in Focal Encephalopathies: Cerebrovascular Disease,

Chapter 9 Progressive Childhood Encephalopathy . . . . . . . . . . . . . . . . . . . . . 258

Chapter 10 Pediatric Epilepsy Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283

Chapter 11 EEG in Adult Epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315

Chapter 12 EEG Voltage Topography and Dipole Source Modeling

Chapter 13 Subdural Electrode Corticography . . . . . . . . . . . . . . . . . . . . . . . . . 367

Chapter 14 Intracerebral Depth Electrode Electroencephalography

Chapter 15 Evoked Potentials Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442

Chapter 16 Neurophysiologic Intraoperative Monitoring . . . . . . . . . . . . . . . . . 488

Chapter 17 Continuous EEG Monitoring in the Intensive Care Unit . . . . . . . . . 543

Chapter 18 Sleep Disorders: Laboratory Evaluation . . . . . . . . . . . . . . . . . . . . . 599

Introduction The Relationship between Oscillations

Figure 1.1: Local circuits induced by transmembrane currents. A: Changes in intra-

recorded spike bursts. C: Human in vivo microelectrode recording of interictal epileptiform

Figure 1.6: Microelectrode recordings of animal and human

FIGURE 1.8: Activity patterns in the ictal penumbra, and fol-

Figure 2.3: A: Surface-negative interictal spikes in temporal convexity cortex

Figure 2.4: Simultaneous intracranial

Figure 2.5: Simultaneous intracranial (A)

Figure 2.6: Schematic of a brain cross section illustrating four rep-

Figure 2.8: EEG traces depicting a left

Figure 2.9: EEG voltage fields from specific cortical

Figure 2.10: EEG voltage fields from specific cortical

Figure 2.11: EEG voltage fields from specific cortical

Figure 2.12: Left: Head sche-

EEG machines, wires from electrodes were physically connected to ampli-

Figure 2.16: Bottom: The magnitude and polarity of

As discussed earlier, however, maximal information about source char- Conclusions

Electrical Basics New Electrodes

engineering, where three-dimensional geometry can be further idealized

Fundamental Electrical Components Capacitor

cept of conductance. Conductance (G) is defined as the inverse of resistance,

(The factor of 20 is because in engineering the convention is to consider the R

Figure 3.17: Example of digitizer resolution. In this example, the bit-depth is 5,

5,000 2 (25,000)m V 10,000m V Vin 2N comparators Encoder N bits

by viscous gels, by mechanical restrictions (bands or rubber caps), or by

Common Types of Electrodes

FIR versus IIR 0.1 Hz

calib (50 µV, 0.5 s)

Figure 3.24: Effect of digital highpass filters of different cutoffs on the

misleadingly reduced. The wise electroencephalographer should always be Electrical Safety

Fp1 - F7 a few microamperes. Nevertheless, if applied directly to the heart, 0.1 mA

“Cut” (high frequencies)

INTRODUCTION montage. Different types of montages and different arrangements of chan-

Figure 4.2: A: Electrode nomenclature of

Figure 4.3: A: Ictal pattern for a left hemisphere

Figure 4.3: (continued)

Figure 4.4: A: EEG with prominent L temporal

Figure 4.6: A: A bifrontal discharge, likely a

Figure 4.6: (contiuned)

Introduction Activating Procedures

Figure 6.23: Monomorphic, rhythmic 6- to 7-Hz moderate-

Figure 6.67: Positive occipital sharp transients of sleep (POSTs) during

ociety Guidelines for Minimal Technical Standards for EEG Recording in