Seizures and Epilepsy: Pathophysiology and Principles of Diagnosis

Epilepsy Board Review Manual
Statement of
Editorial Purpose Seizures and Epilepsy:
The Epilepsy Board Review Manual is a study
guide for trainees and practicing physicians
Pathophysiology and
preparing for board examinations in epilepsy.
Each manual reviews a topic essential to the Principles of Diagnosis
current management of patients with epilepsy.
Contributor and Editor:

Thomas R. Henry, MD
Professor of Neurology, Director, Comprehensive Epilepsy
PUBLISHING STAFF Center, University of Minnesota Medical School,
Minneapolis, MN
PRESIDENT, Group PUBLISHER
Bruce M. White
Senior EDITOR
Robert Litchkofski
executive vice president

Barbara T. White Table of Contents
executive director
of operations
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Jean M. Gaul Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Nature of Epileptic Seizures and Epilepsies . . . . 2
Classification of Seizures. . . . . . . . . . . . . . . . . . . 4
History, Examination, and Laboratory Tests. . . . 7
Classification of Epilepsies and Epileptic
Seizures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Specific Syndromes of Epilepsy. . . . . . . . . . . . . 10
NOTE FROM THE PUBLISHER: Board Review Questions. . . . . . . . . . . . . . . . . . . 21
This publication has been developed with
out involvement of or review by the Amer References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
ican Board of Psychiatry and Neurology.
Epilepsy and Seizures: Pathophysiology and Diagnostic Principles
Epilepsy Board Review Manual
Seizures and Epilepsy:

Pathophysiology and Principles of Diagnosis
Thomas R. Henry, MD
Introduction effects, and therapeutic monitoring of antiseizure

medications. Part 6 will review both epilepsy surgery,
Epileptic seizures are among the most common including the role of neuropsychological testing in
neurologic symptoms in all human populations. planning for epilepsy surgery,2 and the application
Over 5% of Americans have at least one epileptic of neuropsychological testing in initial diagnosis and
seizure during their lifetimes.1 At any point in time, rehabilitaton of patients with epilepsy.
1% to 2% of Americans have epilepsy. Cumulative
lifetime incidence of epilepsy exceeds 3%. These definitions
statistics are similar across large human popula-
tions, although the incidence and prevalence of Seizures are defined as paroxysmal events of
epileptic seizures and epilepsies can be higher in transitory alteration in consciousness or other signs
certain smaller groups (for example, in populations or symptoms that can be due to brain dysfunction.
exposed to military combat due to high rates of trau- Epileptic seizures are seizure events that are caused
matic brain injury [TBI]). by excessive, abnormally synchronized, localized or
This article is the first of a 6-part review of epilepsy widely distributed neuronal electrical discharges3;
diagnosis and management. It provides an overview usually these electrophysiological correlates are
of the pathophysiology of epileptic seizures and clas- presumed by indirect evidence, although electro-
sification systems for seizure and epilepsy and sum- physiological recordings sometimes are performed
marizes key features of established types of epilep- during seizures. Nonepileptic seizures are seizure
sies. Subsequent articles in this series will discuss the events that are not caused by such electrocerebral
techniques, interpretation, and applications of elec- discharges. Nonepileptic seizures are sometimes
troencephalography (EEG) and video-EEG (Part 2) divided into categories of organic nonepileptic sei-
and structural and functional brain imaging (Parts 3 zures, such as atypical syncope and parasomnias,
and 4). Part 5 focuses on selection, dosing, adverse and psychogenic nonepileptic seizures, such as
Copyright2012,TurnerWhiteCommunications,Inc.,StraffordAvenue,Suite220,Wayne,PA19087-3391,www.turner-white.com.Allrightsreserved.Nopartof thispublication
may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, electronic, photocopying, recording, or otherwise, without the prior
writtenpermissionof TurnerWhiteCommunications.Thepreparationanddistributionof thispublicationaresupportedbysponsorshipsubjecttowrittenagreementsthatstipu-
late and ensure the editorial independence of Turner White Communications. Turner White Communications retains full control over the design and production of all published
materials, including selection of topics and preparation of editorial content. The authors are solely responsible for substantive content. Statements expressed reflect the views
of the authors and not necessarily the opinions or policies of Turner White Communications. Turner White Communications accepts no responsibility for statements made by
authors and will not be liable for any errors of omission or inaccuracies. Information contained within this publication should not be used as a substitute for clinical judgment.
www.turner-white.com Epilepsy Volume 1, Part 1 1

A B C
Figure 1. Paroxysmal depolarization shift (PDS). When a PDS occurs as an abnormally prolonged run of action potentials during sustained
membrane depolarization in a single neuron, as shown in the upper trace in B, the event is detectable only with microelectrodes; increased
glutamate concentration is associated with influx of cations initially, followed by increased GABA concentration with efflux of potassium.
When PDSs in a large number of neurons are synchronized for less than 200 ms, as shown in A, these electrical potentials may summate
as a spike-wave complex that is recorded with macroelectrodes, as shown in the lower trace in B. When sustained repetitive firing of PDSs
in a large number of neurons becomes synchronized for many seconds or longer, an electrographic seizure occurs, as shown in C. (Adapted
with permission from Holmes GL, Ben-Ari Y. Seizing hold of seizures. Nature Med 2003;9:9946.)
conversion symptoms and dissociative states. Many underlies all types of epileptic seizures (Figure 1)
clinicians use terms such as spell or event to and interictal epileptiform electroencephalogra-
help the patient more clearly understand that these phy (EEG) abnormalities (spikes).5,6 PDSs are
are not epileptic seizures. cellular events in which rapidly repetitive action
Epilepsy is a condition in which persisting cere- potentials are not followed by the usual refractory
bral dysfunction causes recurring epileptic seizures period, thereby generating a prolonged mem-
without the need for immediate insults to provoke brane depolarization (which is more prolonged
each seizure2; exacerbants such as sleep depriva- than typically occurs in response to normal excit-
tion can increase seizure frequency in epilepsy, atory postsynaptic potentials [EPSPs]). An inter-
however. Acute symptomatic seizures are general- ictal spike is caused by PDSs in large numbers
ized tonic-clonic seizures that occur in the absence of neurons that are synchronized such that each
of epilepsy in response to a wide range of provoking involved neuron generates one PDS at the same
insults, such as hyponatremia and other electrolyte time. An electroclinical seizure occurs when large
disorders and fever in infants and young children.3 numbers of neurons in one or more brain regions
are repeatedly generating PDSs, in sustained
Nature of epileptic seizures and repetitive firing with synchronization. Repetitive
epilepsies neuronal firing probably underlies the interictal
and ictal unit and local field recording of high-
Neurobiology of epileptic seizures frequency oscillations.7
The paroxysmal depolarization shift (PDS) is The tendency of individual neurons to enter
the pathophysiological cellular phenomenon that pathological states in which PDSs are generated
2 Hospital Physician Board Review Manual www.turner-white.com

Figure 2. Genetic channelopathies in epilepsy. (A) Genetic channelopathies can support the occurrence of paroxysmal depolar-
ization shifts (PDS) by altering the usual balance of Na+ and K+ ion conductance across neuronal membranes. Increased Na+
conductance (B, upper panel) creates a situation in which a single action potential initiates sustained depolarization as a PDS
(B, lower panel). Decreased K+ conductance (C, upper panel) also can predispose to PDS. (Adapted with permission from Chang
BS, Lowenstein DH. Epilepsy. N Engl J Med 2003;349:1261. Copyright 2003 Massachusetts Medical Society.)
can be based on intrinsic neuronal properties, In experimental models of partial epilepsies, in-
such as dysfunctional ionophores in the geneti- tracortical mechanisms of synchronization oper-
cally determined channelopathies (Figure 2), or ate during ictal discharges (Figure 4).8 There is
on extrinsic mechanisms such as inadequate evidence that in certain epilepsies specific chan-
inhibitory neurotransmitter concentrations or ex- nelopathies operate to initiate PDSs in individual
posure to excessive concentrations of excitatory neurons and produce seizures through normal
amino acids or exogenous excitotoxins. However, mechanisms of interneuronal synchronization,
large groups of neurons must generate PDSs si- while other epilepsies appear to require abnormal
multaneously to account for the episodic nature of interneuronal pathways to generate pathological
seizures. In experimental models of generalized synchronization.
epilepsies, this widespread epileptic synchroni-
zation of interictal and ictal PDSs is based on Experimental models of seizures and
intrathalamic synchronization that drives thalamo- epilepsy
cortical relay neurons to synchronize the bihemi- Experimentally induced seizures and animal
spheric cortical neuronal discharges (Figure 3).8 models of epilepsy have been used extensively to

Figure 3. Thalamocortical circuits in generalized epilepsies. Under normal conditions, brainstem monoaminergic projections synchronize
the thalamic reticular neurons into cycles of slow waves, and GABAergic projections of these neurons synchronize thalamocortical relay
neurons into cycles of slow waves, resulting in synchronized glutamatergic thalamocortical projections to widespread cortical areas that
generate the electroencephalography (EEG)-recorded slow waves of non-REM sleep and also sleep spindles. In generalized epilepsies,
repetitive paroxysmal depolarization shifts (PDSs) in thalamic reticular neurons synchronize PDSs in thalamocortical relay neurons, which
in turn synchronize PDSs in cortical neurons, thus generating EEG-recorded spike-wave discharges and sometimes absence seizures.
Presumably, a structurally normal complement of thalamic and cortical neurons and their pathways are able to generate spike-wave dis-
charges and absence seizures due to genetically based dysfunction of channels, receptors, or other neurochemical elements. (Adapted with
permission from Chang BS, Lowenstein DH. Epilepsy. N Engl J Med 2003;349:1259. Copyright 2003 Massachusetts Medical Society.)
study the nature of seizures and epilepsy and to epilepsy models, as do genetic rodent models of
develop new therapies for epilepsy.9 For much of epilepsy.
the 20th century, potential new antiseizure medi-
cations were tested in rodents with the maximal Classification of seizures
electroshock model and the pentylenetetrazole
model. Most experimental epilepsy research has Types of epileptic seizures
been performed with acute seizure and epi- The starting point in diagnosis of seizures and
lepsy preparations, although amygdala kindling epilepsy is to determine the type(s) of seizures
and post-status epilepticus models offer chronic that the individual has sustained, or at least

Figure 4. Epilepsy pathophysiology in mesial temporal lobe epilepsy (TLE) with hippocampal sclerosis. Epileptic reorganization of the
hippocampal formation can be caused by a variety of insults that cause loss of vulnerable neurons in experimental models, but etiologic
insults only occasionally are evident in human TLE. This epileptic reorganization includes sprouting of mossy-fiber axons of dentate
granule cells; dentate granule cells project to CA3 neurons, and increased activity in mossy-fiber projections can support excessive
excitation of CA3 neurons. Thus, according to this hypothesis, normal excitatory inputs from the entorhinal cortical neurons to these
reorganized dentate granule cells induce excessive excitation of CA3 neurons in the setting of inadequate inhibition, to initiate sustained
repetitive firing in downstream CA1 neurons as a focal seizure with the potential to propagate more widely. Several experimental models
of TLE generate the same histopathological findings in the animal hippocampus that are observed in the human hippocampal sclerosis.
(Adapted with permission from Chang BS, Lowenstein DH. Epilepsy. N Engl J Med 2003;349:1262. Copyright 2003 Massachusetts
Medical Society.)
generate a hypothesis regarding the type(s) of Types of nonepileptic seizures

seizures. Consensus by experts of the Interna- Organic nonepileptic seizures are paroxysmal
tional League Against Epilepsy (ILAE) estab- events caused by a nonepileptic condition. These
lished an electroclinical classification of seizure events are grouped as nonepileptic seizures mainly
types (Table 1) that has been widely used for because they can mimic epileptic seizures, not
over 3 decades.10 A new classification of seizures because they have a common pathophysiology.
proposed by the ILAE (Table 2) is similar to the Seizures caused by other organic conditions usu-
earlier classification with regard to generalized- ally are confused with epileptic seizures because
onset seizures, but the new classification abol- patients cannot describe their own behaviors dur-
ished the subtypes of partial-onset seizures, ing events that cause loss of consciousness, and
instead considering altered awareness and gen- because witnesses usually can provide only limited
eralized convulsive activity to be descriptors for information about behaviors during the events.11
focal seizures with evolution into generalized (In contrast, expert review of ictal behaviors on
convulsive activity. video-EEG recordings affords detailed and accurate

Table 1. ILAE 1981 Classification of Seizures described to the neurologist by the patient and
I. Partial (focal, localization-related) seizures lay observers of the seizure events.14,15 Recording
A. Simple partial seizures of habitual events on video-EEG not only shows
1. With motor signs absence of electrocerebral discharges of types ex-
2. With somatosensory or special-sensory symptoms
pected for epileptic seizures with similar behaviors,
3. With autonomic symptoms or signs
4. With psychic symptoms
but also provides an opportunity for detailed analy-
B. Complex partial seizures sis of the behaviors themselves. Specific psychiat-
1. With impairment of consciousness at onset ric syndromes do not appear to have relationships
2. Simple partial onset followed by impairment of consciousness with patterns of event behaviors. Current under-
C. Partial seizures with secondary generalization
1. With simple partial seizures evolving to generalized sei-
standings of PNES is that conversion-type reac-
zures tions and dissociative states are not under direct
2. With complex partial seizures evolving to generalized sei- conscious control, and these represent the major-
zures
3. With simple partial seizures evolving to complex partial
ity of PNES. Conversion-type PNES can occur in
seizures evolving to generalized seizures individuals with persisting somatiform disorders
II. Generalized seizures
who have evidence of other nonorganic dysfunc-
A. Absence seizures tions, but many conversion-type PNES occur in
1. With impairment of consciousness only isolation. Dissociative-state PNES often occur in
2. With mild clonic components individuals with a history of physical, sexual, or
3. With atonic components
4. With tonic components
other abuse in the setting of post-traumatic stress
5. With automatisms disorder; this group of PNES patients may be the
B. Myoclonic seizures most responsive to cognitive-behavioral forms of
C. Clonic seizures psychological therapy. While malingering with
D. Tonic seizures
consciously controlled events of unresponsive-
E. Tonic-clonic seizures
F. Atonic (astatic) seizures ness can occur, this scenario appears to be rather
uncommon as a cause of repeated PNES. Many
Adapted with permission from Proposal for revised clinical and elec-
trographic classification of epileptic seizures. From the Commission epileptologists who diagnose PNES routinely refer
on Classification and Terminology of the International League Against for psychiatric consultation first, to be certain that
Epilepsy. Epilepsia 1981;22:489501.
additional psychiatric diagnoses are not missed,
and next to a clinical psychologist for therapy.
Table 3 summarizes the commonly encountered
information regarding movements and responsive- types of nonepileptic seizures that cause loss of
ness.) For example, when syncope is not preceded consciousness or an event with unresponsiveness
by lightheadedness and postsyncopal confusion and subsequent amnesia for the event, together
occurs, other diagnoses must be entertained. Atypi- with epileptic seizure types, descriptions of motor
cal presentations of syncope and incompletely ob- behaviors at the level of detail usually achieved by
served parasomnias are among the most common nonmedical witnesses of seizures, and typical di-
organic nonepileptic seizures.12,13 agnostic tests. Transitory events without impaired
Psychogenic nonepileptic seizures (PNES) can awareness have very different diagnostic con-
mimic essentially any type of epileptic seizure, as siderations, which include simple partial epileptic

seizures, a large range of organic movements Table 2. ILAE 2010 Classification of Seizures
(including dystonias, tics, positional clonus, and I. Focal seizures
blepharospasm), a very large range of organic sub- Descriptors of focal seizures:
jective sensations and experiences (including ver- A. Without impairment of consciousness or awareness
1. With observable motor or autonomic components
tigo, tinnitus, and abdominal sensations), a large
2. Involving subjective sensory or psychic phenomena only
array of psychogenic movements, and an even B. With impairment of consciousness or awareness
larger array of psychogenic sensations-perceptions C. Evolving to a bilateral, convulsive seizure
and mental experiences. Frequently recurring move-
ments without loss of consciousness often can II. Generalized seizures
A. Tonic-clonic seizures
be video-recorded to diagnose movements that B. Absence seizures
fit established patterns of movement disorders or 1. Typical
other organic conditions; however, care must be 2. Atypical
taken not to equate bizarreness of movements with 3. Absence with special features
a. Myoclonic absence
psychogenicity, given the propensity of frontal lobe b. Eyelid myoclonia
epilepsies and REM behavior disorders to cause C. Myoclonic
peculiar movements. In general, the laboratory 1. Myoclonic
tests listed in Table 3 are more likely to provide 2. Myoclonic atonic
3. Myoclonic tonic
definitive diagnostic evidence for the nature of
D. Clonic
transitory events that are associated with impaired E. Tonic
consciousness, or at least with abnormal move- F. Atonic
ments, than they are for transitory events during G. Unknown
1. Epileptic spasms
which baseline responsiveness is maintained.
Adapted with permission from Berg AT, Berkovic SF, Brodie MJ, et al.
Revised terminology and concepts for organization of seizures and
History, examination, and laboratory epilepsies: Report of the ILAE Commission on Classification and Ter-
tests minology, 2005-2009. Epilepsia 2010;51:67685.
The common risk factors, historical associations,

and examination findings for epileptic seizures are
listed in Table 4. The risk factors for nonepileptic ing event followed by a latent period (during which
seizures generally differ from those for epileptic sei- the epileptic seizures have not yet begun to occur)
zures, including prior history of hysteriform paraly- and lastly the phase of active epilepsy. Epileptic
ses or movements and prior history of childhood seizures that occur during or within a week after
sexual abuse or other psychological trauma. An a cerebral or systemic insult are generally consid-
important exception is TBI, which is highly associ- ered provoked seizures that are not indicative of
ated with both epilepsy and psychogenic seizures. epilepsy. Among the exceptions to these patterns
Potentially epileptogenic insults usually should are conditions in which seemingly unprovoked
have occurred months or years before onset of the forms of status epilepticus occur at onset of a con-
habitually recurring epileptic seizures, giving rise to dition that later manifests as sporadically recurrent
the typical temporal pattern of an initial precipitat- seizures, such as the hemiconvulsion-hemiplegia-

Table 3. Epileptic and Nonepileptic Seizures with Impaired Awareness, Listed by Predominant Motor Activities During Seizures
Predominant Motor Phenomena as Described by Witnesses of Seizures

Convulsion Hypopostural Event Event with Automatisms Motionless Event
(Staring Spell)
Movements during period Bilateral, repetitive, rapid Sudden fall or droop, with- Staring spell, with move- Staring spell, without jerk-
of unresponsiveness flexion-extension, jerk- out jerking or shaking ments more complex ing, fall, or other move-
ing or shaking move- and localized than jerk- ments
ments ing or fall
Epileptic seizure types Generalized tonic-clonic Generalized tonic Complex partial Complex partial
Generalized clonic Generalized atonic Atypical absence Typical absence
Generalized myoclonic
Infantile spasm
Organic nonepileptic Rigors Syncope REM behavior disorder Atypical arousal
event types Vertebrobasilar TIA Somnambulism and other
Cataplexy parasomnias
Psychogenic nonepileptic Psychogenic convulsion Psychogenic swoon Psychogenic fugue state Psychogenic stare or
seizure types catatonia
Most frequently indicated EEG or video-EEG, ECG, routine or EEG or video-EEG, EEG or video-EEG,
tests routine or prolonged prolonged routine or prolonged routine or prolonged
Brain MRI Tilt-table test Brain MRI Brain MRI
(CT emergently) Brain MRI/MRA Polysomnography
CT = computed tomography; ECG = electrocardiography; EEG = electroencephalography; MRA = magnetic resonance angiography; MRI = magnetic
resonance imaging; TIA = transient ischemic attack.
Adapted with permission from Henry TR, Drury I. Non-epileptic seizures in temporal lobectomy candidates with medically refractory seizures.
Neurology 1997;48:137482
epilepsy syndrome (see Heconvulsion-Hemiplegia- EEGs are common in many epilepsies, as are inter-
Epilepsy section below). ictal focal and generalized slowing without spikes.
Brief, interictal EEG recordings with scalp elec- Video-EEG monitoring is highly valuable in diag-
trodes (routine EEGs) can record interictal epilep- nosis of paroxysmal events with impaired conscious-
tiform activities (spikes) and nonepileptiform ab- ness or with abnormal movements and behaviors.18
normalities. Interictal spikes are valuable signs of The EEG data can fully distinguish epileptic seizure
epileptic excitability.16 In most epilepsies, interictal discharges (with phenomena specific to partial-
spikes can occur intermittently, such that prolonged onset versus generalized-onset epileptic seizures),
EEG recordings often detect spikes missed with pathological generalized slowing and depression of
routine EEGs. Ambulatory EEG can detect inter- electrocerebral activities (of syncope and organic
ictal spikes and electrographic seizures that occur encephalopathies), onset of unconscious behaviors
infrequently.17 Focal interictal spikes tend to occur in during sleep (specific to REM-onset versus slow-
partial epilepsies, and generalized interictal spikes wave sleep onset), and absence of change from
often occur in generalized epilepsies, but excep- waking or drowsy baseline EEG activities (in psycho-
tions to this principle are common. Normal interictal genic events). The synchronized audio-video record-

Table 4. Summary of Risk Factors, Historical Associations, and Examination Findings for Diagnosis of Epileptic Syndromes
Risk factors and historical associations often provided by the patient or lay care givers:
Family history of epilepsy or seizures
Family history of genetic conditions that are potentially epileptogenic in family members without seizures (eg, neurofibromatosis type 1)
History of gestational or perinatal injury, febrile convulsions, developmental delay, stroke, meningitis, encephalitis, significant traumatic
brain injury, ethanol or other drug abuse, or other epileptic predispositions
Reported seizure-provoking factors: photic stimulation-flashing lights, hyperventilation, sleep deprivation, ethanol use or cessation, use of
carbamazepine or other antiseizure medications known to exacerbate specific epileptic seizure types, catamenial exacerbation, numer-
ous other possible seizure triggers and exacerbants
Risk factors and historical associations often provided by the medical chart (eg, previously diagnosed clinical-imaging conditions)
and conditions which the epileptologist will find on further evaluation:
Primary or metastatic cerebral neoplasm (glioblastoma and lower-grade glial tumors, ganglioglioma and gangliocytoma, dysembryoplastic
neuroepithelial tumor, others)
Primary or metastatic extra-axial, intracranial neoplasm (meningioma, meningeal carcinomatosis, others)
Cerebral infarction or hemorrhage, chronic (including residua of posterior reversible encephalopathy syndrome)
Cerebral infection, remote or chronic (including cysticercosis, bacterial-mycobacterial-fungal cerebritis or abscess, bacterial meningitis,
herpes or other viral encephalitis, retroviral encephalopathy, prion disease, others)
Post-traumatic encephalomalacia (particularly with retained skull or metal fragment or hemosiderin deposition)
Cerebrovascular lesion (arteriovenous malformation, cavernoma)
Malformation of cortical development (lissencephaly, schizencephaly, hemimegalencephaly, perisylvian or other polymicrogyria, band or
nodular heterotopia, focal cortical dysplasia, others)
Genetic disorders of neurocognitive development (Aicardi syndrome, fragile X syndrome, Angelman syndrome, Rett syndrome, Down
syndrome, trisomy 12p, ring 20 chromosome syndrome, Alpers disease, progressive encephalopathy with edema-hypsarrhythmia-optic
atrophy [PEHO syndrome], others)
Inherited metabolic disorders (mitochondrial diseases including pyruvate dehydrogenase deficiency and MELAS [mitochondrial encepha-
lomyopathy, lactic acidosis, and stroke-like episodes], neuronal storage disorders including Lafora disease and neuronal ceroid lipofus-
cinosis, peroxisomal disorders, cerebral calcinosis due to celiac disease, glycine encephalopathy, propionic acidemia and other organic
acidurias, pyridoxine dependency, phenylketonuria and other aminoacidopathies, urea cycle disorders, disorders of carbohydrate metab-
olism, disorders of biotin, folate, or B12 metabolism, glucose transporter protein deficiency, Menkes disease, glycogen storage disorders,
Krabbe disease, fumarase deficiency, Sanfilippo syndrome)
Neurodegenerative conditions of adult onset (Alzheimer disease, Huntington disease, others)
Neurodegenerative conditions due to neurotoxin exposure (organic solvents, lead, mercury, others)
Other cerebral conditions of adult onset (eg, multiple sclerosis, neurosarcoidosis, sequelae of lupus cerebritis, sequelae of paraneoplastic
limbic encephalitis)
Other encephalopathies of unknown etiology (eg, autism and other developmental syndromes, neuropsychiatric encephalopathies of later
onset including schizophrenia).
Neurosurgical instrumentation (eg, ventricular shunt, deep-brain stimulation electrode)
Examination findings
Cutaneous stigmata of phakomatosis or neurocutaneous syndrome (adenoma sebaceum, ash leaf spots, shagreen patches, or periungual
fibromas of tuberous sclerosis, multiple large caf-au-lait spots or axillary freckling of neurofibromatosis, facial angioma of encephalotri-
geminal angiomatosis, others)
Oculoretinal stigmata of storage disorders (cherry red spot of sialidosis, iris hamartoma of neurofibromatosis, others)
Craniofacial dysmorphism of neurodevelopemenal syndromes (Down syndrome, others)
Cranial defects suggesting unreported trauma or neurosurgical intervention
Static abnormalities of the neurological examination indicating cognitive deficits, psychosis, and cerebral motor or sensory dysfunction
Episodic abnormalities of the neurological examination including interictal spontaneous or startle-induced myoclonus and witnessed ictal
manifestations

ing of behaviors is highly informative, and even when etiology who had indirect evidence of having had
myogenic and kinesigenic artifacts obscure the EEG a causative brain insult, although the precise insult
recording, the recorded behavioral data frequently in could not be determined. Characteristically, the idio-
itself supports definitive seizure diagnosis. pathic epilepsies had no interictal evidence of brain
injury, so interictal intelligence and other functions
Classification of epilepsies and typically are normal or nearly normal. Symptomatic
epileptic syndromes partial epilepsies often feature interictal dysfunc-
tions localized to the injured area, which includes
1989 classification the ictal onset zone, with mental retardation or de-
There are many highly individual aspects of the velopmental delay in many of those with symptom-
seizures, interictal dysfunctions, and associated ce- atic generalized epilepsies (eg, delayed verbal recall
rebral and systemic conditions experienced by per- deficits in those with left-sided mesial temporal lobe
sons with epilepsy. Nonetheless, it is obvious that epilepsy-hippocampal sclerosis, a symptomatic and
some of these characteristics cluster across indi- usually cryptogenic partial epilepsy).
viduals as particular types of epilepsy. Ideally, every
person with epilepsy could be assigned to one type 2010 classification
of epilepsy, and the various types of epilepsy could Ongoing efforts to improve epilepsy classification
be classified into a neurobiologically based, clinical- were most recently summarized in 2010 (Table 6).20
ly relevant organizational schema of the epilepsies. The partial-generalized and idiopathic-cryptogenic
This ideal taxonomy of the epilepsies has yet to be dichotomies were discarded, and the epilepsy types
devised, and clinical epileptologists must use the were organized by typical developmental stage at
current epilepsy classifications to guide diagnostics seizure onset (eg, neonatal, childhood) and etiol-
and therapeutics. ogy. The established types of epilepsy are mainly
At this time, the most widely accepted clas- the same as those recognized by the 1989 clas-
sification of epilepsy types is that published by sification, although more developed and specific
the ILAE in 1989 (Table 5).19 In addition to defin- syndromes of neonatal seizure onset are included
ing accepted epilepsy types, this taxonomy used in the 2010 classification. The new epilepsy clas-
2 dichotomous principles to organize the epilepsy sification has been described as multifactorial and
types. The partial (or focal, or localization-related) flexible, with emphases on age at onset and etiol-
versus generalized dichotomy was determined by ogy, and also as a work-in-progress and incomplete.
whether the individual had partial-onset or general- Epileptologists will need to track this transitional pe-
ized-onset seizures, respectively. The idiopathic (or riod in epilepsy classification systems, but fortunate-
primary) versus symptomatic (or secondary, or ac- ly the core knowledge of classification continues to
quired) dichotomy was determined by whether the be in recognition of the individual epilepsy types.
individual had seizure intrinsic to his or her brain
structure-function in the absence of any brain insult, Specific syndromes of epilepsy
or had a brain insult that precipitated epileptogene-
sis, respectively. A special category of the symptom- A number of epilepsies are established as clini-
atic group was persons with seizures of cryptogenic cally distinguishable from epilepsy as a whole, with

Table 5. ILAE 1989 Classification of Epilepsies
1. Localization-related (focal, local, partial) epilepsies and syndromes

1.1 Idiopathic (with age-related onset)
Benign childhood epilepsy with centrotemporal spikes
Childhood epilepsy with occipital paroxysms
Primary reading epilepsy
1.2 Symptomatic
Chronic progressive epilepsia partialis continua of childhood (Kojewnikow syndrome)
Syndromes characterized by seizures with specific modes of precipitation
Temporal lobe epilepsies (amygdalo-hippocampal, lateral temporal)
Frontal lobe epilepsies (supplementary motor, cingulate, anterior frontopolar, orbitofrontal, dorsolateral, opercular, motor cortex)
Parietal lobe epilepsies
Occipital lobe epilepsies4
1.3 Cryptogenic (same syndromes as for symptomatic localization-related epilepsies, but without known etiology)
2. Generalized epilepsies and syndromes
2.1 Idiopathic (with age-related onset)
Benign neonatal familial convulsions
Benign neonatal convulsions
Benign myoclonic epilepsy in infancy
Childhood absence epilepsy (pyknolepsy)
Juvenile absence epilepsy
Juvenile myoclonic epilepsy
Epilepsy with grand mal (GTCS) seizures on awakening
Other generalized idiopathic epilepsies not defined above
Epilepsies with seizures precipitated by specific modes of activation
2.2 Cryptogenic or symptomatic
West syndrome
Lennox-Gastaut syndrome
Epilepsy with myoclonic-astatic seizures
Epilepsy with myoclonic absences
2.3 Symptomatic
2.3.1 Nonspecific etiology
Early myoclonic encephalopathy
Early infantile epileptic encephalopathy with suppression burst
Other symptomatic generalized epilepsies not defined above
2.3.2 Specific syndromes
Epileptic seizures that complicate a specific disease state
3. Epilepsies and syndromes undetermined whether focal or generalized
3.1 With both generalized and focal seizures
Neonatal seizures
Severe myoclonic epilepsy in infancy
Epilepsy with continuous spike-waves during slow wave sleep
Acquired epileptic aphasia (Landau-Kleffner syndrome)
Other undetermined epilepsies not defined above
3.2 Without unequivocal generalized or focal features. All cases with generalized tonic-clonic seizures in which clinical and EEG findings
do not permit classification as clearly generalized or localization related, such as in many cases of sleep grand mal (GTCS) are con-
sidered not to have unequivocal generalized or focal features.
4. Special syndromes
4.1 Situation-related seizures (Gelegenheitsanflle)
Febrile convulsions
Isolated seizures or isolated status epilepticus
Seizures occurring only when there is an acute metabolic or toxic event due to factors such as alcohol, drugs, eclampsia, nonketotic
hyperglycemia
Adapted with permission from Proposal for revised classification of epilepsies and epileptic syndromes. From the Commission on Classification
and Terminology of the International League Against Epilepsy. Epilepsia 1989;30:38999.

Table 6. ILAE 2010 Proposal for Classification of Epilepsies
Organizational Group Electroclinical Syndrome

Neonatal onset group Benign familial neonatal epilepsy (BFNE)
Early myoclonic encephalopathy (EME)
Early myoclonic encephalopathy (EME)
Infancy onset group Epilepsy of infancy with migrating focal seizures
West syndrome
Myoclonic epilepsy in infancy (MEI)
Benign infantile epilepsy
Benign familial infantile epilepsy
Dravet syndrome
Myoclonic encephalopathy in nonprogressive disorders
Childhood onset group Febrile seizures plus (FS+) (can start in infancy)
Panayiotopoulos syndrome
Epilepsy with myoclonic atonic (previously astatic) seizures
Benign epilepsy with centrotemporal spikes (BECTS)
Autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE)
Late onset childhood occipital epilepsy (Gastaut type)
Epilepsy with myoclonic absences
Lennox-Gastaut syndrome
Epileptic encephalopathy with continuous spike-and-wave during
sleep (CSWS)
Landau-Kleffner syndrome (LKS)
Childhood absence epilepsy (CAE)
Adolescence Adult Juvenile absence epilepsy (JAE)
Juvenile myoclonic epilepsy (JME)
Epilepsy with generalized tonicclonic seizures alone
Progressive myoclonus epilepsies (PME)
Autosomal dominant epilepsy with auditory features (ADEAF)
Other familial temporal lobe epilepsies
Less specific age relationship Familial focal epilepsy with variable foci (childhood to adult)
Reflex epilepsies
Distinctive constellations Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE with HS)
Rasmussen syndrome
Gelastic seizures with hypothalamic hamartoma
Hemiconvulsionhemiplegiaepilepsy
Epilepsies that do not fit into any of these diagnostic categories
Epilepsies attributed to and organized by structural-metabolic causes
Epilepsies of unknown cause
Conditions with epileptic seizures that are traditionally not diagnosed Benign neonatal seizures (BNS)
as a form of epilepsy per se Febrile seizures (FS)
Adapted with permission from Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilep-
sies: Report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 2010;51:67685.
diagnostic criteria by (1) seizure types, (2) age regarding (4) associated cerebral and systemic
at onset, and (3) EEG and imaging findings, and conditions, (5) interictal cerebral dysfunctions, and
in many instances supplemented by information (6) typical responses to specific medications or

other therapies that had been used before the cur- Lennox-Gastaut syndrome, and is most often as-
rent attempt to diagnose the individuals epilepsy sociated with brain structural abnormalities includ-
type. Successful classification of epilepsy type ing unilateral or bilateral cerebral hypoplasia and
usually supports the physician's efforts to estab- other developmental malformations. The prognosis
lish a prognosis regarding remission of active epi- for neurocognitive development is grim.
lepsy. Many individual patients have epilepsy with
specific seizure types but lack other information Infancy
that permits diagnosis of an established epilepsy Epilepsy of infancy with migrating focal
syndrome. When seizure types can be diagnosed seizures is a rare, severe, and progressive focal
but the overall epilepsy cannot be classified, the epilepsy in which focal seizures arise in multiple
physician's ability to make an accurate prognosis bihemispheric regions and are refractory to medi-
is limited. The following list of epileptic syndromes cations.31,32 Brain magnetic resonance imaging
is derived from the current ILAE consensus on (MRI) studies initially are normal but show progres-
classification,20 grouped by age at seizure onset. sive atrophy. Many of these children die in the first
year, and most continue to have refractory seizures
Neonatal period throughout childhood, with severe developmental
Benign familial neonatal epilepsy (BFNE) delay and microcephaly.
is an autosomal dominant condition in which West syndrome is an uncommon electroclini-
brief (12 sec) generalized events include tonic, cal syndrome of multiple etiologies characterized
apneic, and other features.2124 Seizures usually by the triad of infantile spasms, hypsarrhythmia on
begin within the first days after birth and remit in EEG, and developmental regression.3340 Tuberous
over 80% within the first 6 weeks. Those whose sclerosis is the single most common cause; other
seizures do not remit may have a few seizures in causes include focal cortical dysplasias, other mal-
adulthood. Several potassium channelopathies ap- formations of cortical development such as lissen-
pear to be responsible for BFNE. The prognosis for cephaly, perinatal asphyxia and infarction, prenatal
neurocognitive development is good. and postnatal brain infections, and various other ce-
Early myoclonic encephalopathy (EME) is rebral structural lesions and metabolic syndromes.
a neonatal syndrome with frequent myoclonia A small number of these patients have no identifi-
and focal motor seizures and is associated with able cause; this idiopathic West syndrome has a
a burstsuppression pattern on EEG.2527 Various more favorable prognosis for cessation of seizures
metabolic syndromes are the most common etiolo- and normal development. Many West syndrome pa-
gies. Some children with EME recover with normal tients evolve into the Lennox-Gastaut syndrome and
or nearly normal neurocognitive development. other generalized epilepsies with mental retardation.
Ohtahara syndrome, or early infantile epileptic The spasms are difficult to treat with medications,
encephalopathy with burst-suppression (EIEE), is including adrenocorticotropic hormone (ACTH) and
a neonatal syndrome with frequent tonic seizures vigabatrin, and multilobar resections have been
and is associated with burstsuppression on the used when one hemisphere predominates in mal-
interictal EEG.2830 This syndrome often evolves formation or epileptiform activity, in some cases with
into the West syndrome and subsequently into the reportedly good functional outcomes.

Myoclonic epilepsy in infancy (MEI) is a rare developmental delays that will constitute severe
syndrome in which subtle or massive myoclonic mental retardation and as refractory myoclonic ab-
jerks occur in clusters of a few seconds duration sences.5457 Irregular and fragmented spike-wave
or somewhat longer.4143 The interictal EEG is nor- discharges and low-amplitude multifocal spikes
mal, while during jerks there are generalized fast occur with generalized slowing of the waking EEG.
spike-/polyspike-wave discharges. No other types Most of these patients have a genetic develop-
of seizures occur; the myoclonic seizures usually mental disorder, with Angelman syndrome pre-
are controlled with valproate, and most patients dominating over the 4p-deletion syndrome (Wolf
with MEI have no seizures later in life. Hirschhorn syndrome) and Rett syndrome, but
Benign infantile epilepsy and benign familial perinatal anoxia also can cause this electroclinical
infantile epilepsy feature partial seizures with or syndrome.
without secondary generalization that most often
begin between 6 months and 2 years of age.4448 Childhood
The interictal EEG usually is normal, although Childhood absence epilepsy (CAE) or pyk-
some have midline spikes during slow-wave sleep. nolepsy is the most widely recognized form of
Ictal EEG recordings show clear focal onsets, most epilepsy in childhood, but not the most common,
often with either temporal or centroparietal maxima with a prevalence of less than 10% in children
across this population (but a single ictal onset with epilepsy.5867 Seizure onset is usually at 3 to 8
pattern in an individual patient). Brian imaging is years of age in children with normal development.
normal. Often patients have an associated viral Most have only absence (petit mal) seizures, often
gastroenteritis, without encephalitis. Acute therapy occurring multiple times daily before treatment, but
with antiseizure agents may be unnecessary. Sei- some also rarely experience generalized tonic-
zure recurrence later in life is rare and normal intel- clonic (GTC) seizures. The interictal EEG is usu-
lectual development is expected. ally normal except for brief bursts of generalized
Dravet syndrome is a rare and progressive 3-per-second spike-wave discharges, which are
epileptic encephalopathy that usually begins with provoked with photic stimulation and hyperven-
febrile and afebrile generalized and unilateral clonic tilation; often there is also occipital intermittent
or tonic-clonic seizures in infancy, when the EEG rhythmic delta slowing. Generalized 3-per-second
is normal interictally.4953 Ongoing seizures and de- spike-wave discharges usually last 10 to 20 sec-
velopmental delay are associated with findings of onds during the seizures. Brain imaging is gener-
generalized spike- and polyspike-wave and diffuse ally considered unnecessary, as no lesional or
theta slowing on the waking EEG by 2 years. This acquired epilepsies cause these types of seizures
syndrome can occur with GEFS+, but in these in- with these EEG findings. Ethosuximide is usually
stances is rarely familial, as new mutations account effective for absences, and valproate for both ab-
for most cases of GEFS+ with Dravet syndrome. sences and GTC seizures. Seizures cease by the
Myoclonic encephalopathy in nonprogres- teens in over 90% of patients, and those whose
sive disorders (also termed myoclonic status in seizures persist most often evolve into the juvenile
nonprogressive encephalopathy) is usually evident myoclonic epilepsy syndrome.
by the end of the first year of life, manifesting as Lennox-Gastaut syndrome (LGS) begins at

age 3 to 8 years or rarely later, but in perhaps 20% nosed as focal seizures with sensory and motor
of cases is preceded by the West syndrome.68-73 facial or glossopharyngeal seizures, often with
This archetypal symptomatic or cryptogenic gener- grunting or drooling. Diagnosis often occurs after
alized epilepsy is defined by mixed seizure types, a first nocturnal GTC seizure. The interictal EEG
generalized slow spike-wave discharges and gen- most often shows single and repetitive unilateral
eralized slowing on waking-drowsy interictal EEG, or bilateral independent spike-wave complexes
generalized paroxysmal fast activity on sleeping of centrotemporal maximum, without focal delta
interictal EEG, and developmental delay. The typi- slowing at the spike site(s), but sometimes with
cal seizure is a medically refractory drop attack as generalized 3-per-second spike-wave discharges.
a generalized tonic seizure. Atypical absences and Atypical clinical or EEG features may indicate the
GTC seizures are very common. Generalized aton- need for brain imaging. When therapy is needed,
ic, generalized clonic, generalized myoclonic, and carbamazepine or other agents usually control the
focal seizures often occur. Later age of onset and seizures at modest doses. Epilepsy almost always
relatively normal intellect sometimes are observed. remits within several years of onset.
Etiologies include the phakomatoses, various mal- Benign epilepsy with occipital spikes (Pan-
formations of cortical development, early diffuse ayiotopoulos syndrome) is the second most com-
anoxic and focal ischemic injuries, and others as mon benign partial epilepsy of childhood.8487
for the West syndrome. Cryptogenic LGS with Focal seizure onset is usually at 3 to 6 years of
normal brain MRI accounts for perhaps one-third age in children with normal development, although
of cases. Valproate, zonisamide, and other agents a large minority has a preceding history of febrile
are typical of the polytherapy needed to avoid sta- convulsions. Most have focal seizures with gaze
tus epilepticus, but only infrequently is full seizure deviation, emesis and other autonomic signs, and
control achieved in childhood. By adulthood, the impaired consciousness, with nocturnal predilec-
interictal EEG often evolves away from general- tion. Hemiconvulsions and GTC seizures are com-
ized slow spike-wave, so technically the individual mon. Interictal EEGs show normal background
no longer has LGS, but often has the same types activities with high-amplitude occipital spike-wave
of seizures under improved control. Focal seizures complexes on eye closure, and spike activation
occur in some patients with LGS, and the interictal by sleep with unilateral or bisynchronous occipital
EEG may show more focal spike elements. Intel- spikes; some also have other foci of spikes or gen-
lectual prognosis is poor, and psychosis, episodic eralized spike-wave bursts. Most have only a few
dyscontrol, and other disabling behavioral disor- seizures, but paradoxically these few seizures fre-
ders are common. quently generate status epilepticus. Carbamaze-
Benign epilepsy with centrotemporal spikes pine and valproate are usually effective, although
(BECTS) is the most common benign partial epi- many do not require medication. Focal seizures
lepsy of childhood, and the single most common consistently cease within 2 years of onset.
form of epilepsy in childhood.7483 Seizure onset Late onset childhood occipital epilepsy
is usually at 3 to 13 years of age in children with (Gastaut type) is a rare condition that features focal
normal development. Most patients with BECTS seizures beginning at age 6 to 12 years, with visual
have nocturnal events that eventually are diag- hallucinations or blindness, often with gaze devia-

tion or eyelid fluttering, and often followed by post- alternating, and axial or appendicular. Untreated,
ictal migraine headaches.8893 The focal seizures these seizures often occur repeatedly on many
often evolve into hemiconvulsions or GTC seizures. nights. Most patients have no other type of seizure,
The interictal EEG typically shows unilateral or bi- a normal interictal EEG, normal intelligence and
synchronous occipital spikes of high amplitude with neurologic examination, and normal brain MRI.
fields extending over adjacent parietal and temporal Even the ictal EEG may be difficult to interpret,
areas, and with attenuation on eye opening. Brain often with anterior or diffuse attenuations or rhyth-
MRI is normal. Seizures often are medially refrac- mic slow waves rather than sharply construed or
tory, but tend to remit by the late teens. high-amplitude focal discharges. Known causative
Epilepsy with myoclonic atonic (astatic) sei- mutations code for subunits of neuronal nicotinic
zures (Doose syndrome) is a rare syndrome with receptors. Most patients with ADNFLE attain sei-
onset at 2 to 5 years of age, usually in develop- zure control with carbamazepine or other agents,
mentally normal children.9497 The initial seizures but a sizeable minority do not attain seizure control
typically are repetitive GTC seizures, with only and may have increased risk of chronic neurobe-
isolated GTC seizures thereafter, but followed by havioral sequelae.
persisting epileptic drop attacks. The drop attacks Epilepsy with myoclonic absences is a rare,
are generalized myoclonic-atonic (or myoclonic idiopathic generalized epilepsy with onset at age
astatic) seizures with components both of in- 1 to 12 years of myoclonic absences as the sole
creased and decreased muscle tone. The interictal seizure type, or as myoclonic absences with other
EEG is abnormal due to generalized slowing in seizure, particularly GTCs.101103 Myoclonic absenc-
waking with high-amplitude atypical generalized es briefly impair awareness, with proximal arm and
spike-wave complexes at sleep onset. The ictal other jerks during transitory increases in tone that
EEG may be similar but with more and higher am- cause the arms to elevate for a few seconds, rarely
plitude slowing and spiking, and often with greater with falling. The interictal and ictal EEG shows
rhythmicity of slow waves and spikes. Brain MRI generalized 3-per-second spike-wave discharges.
is normal. Valproate can reduce seizures, which Prognosis for medication control and later remis-
usually remit after several months. Some of these sion is generally good.
patients have persisting cognitive deficits. Epileptic encephalopathy with continuous
Autosomal-dominant nocturnal frontal lobe spike-and-waveduring sleep (CSWS), also
epilepsy (ADNFLE) is a rare syndrome with sei- known as electrical status epilepticus in sleep
zure onset in middle childhood and adolescence in (ESES), is a rare cryptogenic syndrome in which
the majority of affected patients.98100 The disorder various focal or generalized (including absence)
was once considered to be paroxysmal noctur- seizures can occur in early-middle childhood.104,105
nal dystonia, but with the advent of video-EEG, The requisite EEG feature is occurrence of gener-
ictal recordings established the epileptic nature alized spike-wave discharge during greater than
of the events. These focal seizures have been 85% of the non-REM sleep recording. Global cog-
termed hypermotor because of their vigorous but nitive decline occurs and usually leaves permanent
rather variable movements, which can be low- and deficits, despite relative ease of medication control
high-amplitude, synchronous or asynchronous or of seizures and later remission of epilepsy.

Landau-Kleffner syndrome (LKS) is a rare absence and GTC seizures, but concerns with
cryptogenic syndrome that is highly associated teratogenicity in young women often favor use of
with CSWS, as the same non-REM spike-wave lamotrigine or other agents. Seizures cease in the
discharges occur, with similar types of seizures late teens in over 80% of patients, with more than
and medication responsiveness as in CSWS.106,107 10 lifetime GTC seizures being a negative prog-
A progressive loss of previously acquired language nostic sign. As with CAE, most nonremitters evolve
function defines LKS, and after epilepsy remits per- into JME.
manent auditory agnosia and aphasia are common. Juvenile myoclonic epilepsy (JME) probably
Febrile seizures plus (FS+) (more often termed is the second most common epileptic syndrome
generalized, or genetic, epilepsy with febrile sei- across all ages, after mesial TLE, and accounts
zures plus, or GEFS+) is an electroclinical-genetic for perhaps one-sixth of adult epilepsies.110114
syndrome with a starting point of febrile convul- Seizure onset is usually at ages 12 to 18 years
sions of early childhood or infancy, but a wide in individuals with normal development, and may
range of subsequent epilepsy manifestations that follow on CAE or JAE. Myoclonus in early waking
have considerable overlap with other electroclinical states is positive or negative, and segmental or
syndromes.108,109 These syndromes include myo- massive; massive negative myoclonus can cause
clonic-astatic epilepsy, Dravet syndrome, various an injurious fall without loss of consciousness.
generalized epilepsies, and familial temporal lobe Occurrence of at least 1 GTC seizure has been
epilepsy TLE with or without hippocampal scle- a formal requirement for this diagnosis, but GTC
rosis. Some affected individuals have only febrile seizures should be rare after medication initiation
seizures. Early publications reported genes whose with good compliance and avoidance of the prin-
products disrupted neuronal sodium channel func- cipal precipitants (sleep deprivation and ethanol).
tion at the ionophores alpha subunit (SCN1A mu- Approximately one-third of those with JME have
tations), but other sodium channel components, absence seizures. The interictal EEG typically is
and in some cases GABAA receptor subunits, normal except for brief, generalized, fast (46-per-
are affected by more recently reported genes that second) spike-/polyspike-wave discharges, often
cause GEFS+. increased with photic stimulation and hyperventila-
tion, or sometimes with generalized 3-per-second
AdolescenceAdult spike-wave discharges. Jerks often coincide with
Juvenile absence epilepsy (JAE) is somewhat polyspikes, but ictal recordings are rarely if ever
more common that CAE.5867 Many authorities needed for diagnosis. Valproate (in those without
consider CAE and JAE to be a continuum. Seizure child-bearing potential), zonisamide, lamotrigine,
onset is usually at 8 to 12 years of age in children and other agents usually can control seizures fully
with normal development. In addition to absence in patients with good medication and lifestyle com-
seizures, which tend to occur less frequently pliance. Unlike other idiopathic generalized epi-
before treatment in JAE than in CAE, most also lepsies, prognosis for remission is very poor, with
occasionally experience GTC seizures. Interictal reports of GTC seizure recurrence in elderly JME
and ictal EEGs in JAE are highly similar to those patients on medication withdrawal after decades of
of CAE. Valproate may be most effective for both seizure freedom.

Epilepsy with generalized tonic-clonic sei- cystatin B, a cysteine protease inhibitor, with some
zures alone is clearly a common situation. As mutations developed for clinical tests. Baltic familial
an epileptic syndrome, it suffers from a paucity myoclonus epilepsy features cognitive decline that
of published research, with no defined age-range can be stabilized if seizures are controlled, which
of onset and no established diagnostic criteria to also prolongs survival. Valproate and zonisamide
fully distinguish the syndrome from recurrent GTC are the medications most frequently used for sei-
seizures of other causes.115,116 Seizure frequency zure control in PME.
and relationship to seizure-provoking factors is Autosomal dominant epilepsy with audi-
poorly defined. Interictal EEG sometimes shows tory features (ADEAF) is a rare TLE of teenage
generalized 3-per-second spike-wave discharges. or early adult onset, characterized by auras with
Brain MRI presumably is normal in this idiopathic unformed auditory hallucinations and frequent
epilepsy. Medications are chosen for seizure type GTC seizures.122,123 The interictal EEG is normal or
rather than epilepsy type, and prognosis for remis- shows interictal spikes of posterior temporal maxi-
sion is unclear. mum. Brain MRI is normal or may show subtle en-
Progressive myoclonus epilepsies (PME) are largement of lateral temporal cortex without clearly
a well-defined set of etiologies with a common clin- dysplastic features. Seizures generally are easily
ical syndrome, which unfortunately is most often controlled with medications.
untreatable and progressive to early death.117121 Other familial TLEs are uncommon, and are
The syndrome consists of myoclonus, mixed GTC often associated with febrile convulsions before
and other seizures, dementia, and usually other onset of auras, focal seizures with impaired aware-
progressive neurologic deficits, including ataxia. ness, and GTC seizures similar to those of mesial
Onset is usually in late childhood or adolescence, TLE with hippocampal sclerosis.124127 Interictal and
depending on the etiology. The interictal EEG ictal EEGs are similar to those of mesial TLE with
shows generalized and multifocal slowing, multi- hippocampal sclerosis, and some individuals have
focal spikes often with posterior predominance, hippocampal atrophy on MRI. Clear distinction of
and atypical generalized spike-/polyspike-wave familial from sporadic mesial TLE probably will
discharges. Depending on the age of degenera- require genetic tests that are yet to be developed.
tion, cerebral atrophy is present on MRI. Causes
include Lafora disease, neuronal ceroid lipofusci- Less specific age relationship
nosis, myoclonus epilepsy and ragged red fibers Familial focal epilepsy with variable foci is
(MERRF), sialidosis, and other neurodegenerative a rare syndrome with variable onset in childhood
storage diseases, each with specific biochemi- or adulthood. In this syndrome, each affected in-
cal or tissue studies allowing diagnosis. Seizures dividual has focal epilepsy limited to one invariant
are refractory and decline is inexorable, except in focus, but the family has individuals with different
Baltic familial myoclonus epilepsy (Unverricht-Lun- foci in frontal, temporal, and occipital lobes.127,128
dborg disease), an autosomal recessive condition Focal seizures are defined by semiology and EEG
that probably occurs in most human populations, abnormalities, as brain MRI is consistently normal.
although somewhat less rarely near the Baltic Sea. Reflex epilepsies must be differentiated from
Most cases involve mutations in genes encoding reflex seizures.129131 Many forms of epilepsy feature

generalized or focal seizures that sometimes occur Evolution into a GTC seizure may be immedi-
immediately on photic stimulation, startle, or other ately preceded by oculocephalic version. Typical
particular stimuli, but these seizures also occur interictal EEG findings include unilateral or bilat-
spontaneously in the absence of the potentially eral anterior temporal spikes or runs of intermittent
ictogenic stimulus. In reflex epilepsy, the seizures rhythmic delta activity (specific TLE discharges),
should occur only in response to a specific set of nonspecific focal temporal or generalized slow-
stimuli. The prototypical example of reflex epilepsy ing, or a persistently normal interictal EEG. Typical
is primary reading epilepsy. In this very rare and ictal discharges are focal frontotemporal rhythmic
quite remarkable syndrome, the patient can pre- discharges that can be sinusoidal or sharply con-
dictably induce focal seizures by reading complex toured and evolve in field, frequency, and morphol-
material for prolonged periods of time, after which ogy, or similar discharges that are nonlocalizing
mandibular myoclonus or orofacial sensations or at onset and sometimes develop later temporal
movements occur. If the individual persists in read- maximum. Brian MRI can be normal or nonspecifi-
ing, a GTC seizure consistently ensues. Interictal cally abnormal (with subcortical white matter signal
EEG and brain MRI are normal, but bilateral or alterations, for example), but the classic signs are
unilateral EEG spikes of left temporoparietal pre- unilateral or rarely bilateral hippocampal atrophy
dominance occur during the focal seizures. and T2 signal increase. This syndrome is medi-
cally refractory in perhaps 50% of individuals, but
Distinctive constellations and less is more likely to be amenable to surgical resection
specific age relationship than are most other epilepsies.
Mesial temporal lobe epilepsy with hippo- Rasmussen syndrome is an electroclinical syn-
campalsclerosis (MTLE-HS) is probably the drome of epilepsia partialis continua with progres-
single most common form of epilepsy, if one al- sive atrophy of the affected cerebral hemisphere
lows for limitations in detection of very mild hip- and profound medication refractoriness.140144 Char-
pocampal sclerosis by current clinical MRI tech- acteristic onset is in early to middle childhood,
niques.125,132139 Habitual seizure types often are but considerably later onset is recognized, as are
preceded by febrile convulsions. The typical auras, variants with aphasic or other focal seizures rather
focal seizures with impaired awareness and with than focal motor seizures. The clinical and EEG ab-
or without automatisms, and afebrile GTC seizures normalities are highly lateralized, with EEG slowing,
can begin by 2 or 3 years of age, but more often spikes and seizures continuing over months and
begin in middle childhood or well into adulthood. years, usually with limited response to tolerable or
Psychic and autonomic auras can include dreamy intoxicating polypharmacy. Serial brain MRI shows
states with perceived unreality or dj vu or jamais progressive atrophy of the affected hemisphere,
vu phenomena, gustatory or olfactory hallucina- correlating with progressive hemiparesis. Brian tis-
tions, epigastric rising sensations, and a variety sue shows characteristic microglial proliferation
of other symptoms. With more widespread ictal and nodularization, perivascular lymphocytic cuff-
discharges, an initial motionless staring spell often ing, and neuronal loss and gliosis in the affected
is followed by chewing, swallowing, nonspecific hemisphere. T-cell dysfunction and other lines of
hand movements, and various other automatisms. evidence support various anti-inflammatory and

immune-modulating therapies, which possibly blunt 2. Henry TR, Roman DD. Presurgical epilepsy localiz-
tion with interictal cerebral dysfunction. Epilepsy Behav
the severity of cerebral degeneration over the years 2011;20:194208.
of ongoing seizures. Functional hemispherectomy 3. Fisher RS, Boas WVE, Blume W, et al. Epileptic seizures
may allow the other hemisphere to develop more and epilepsy: definitions proposed by the International
League Against Epilepsy (ILAE) and the International Bu-
normally, with seizure control, in selected children. reau for Epilepsy (IBE). Epilepsia 2005;46:4702.
Gelastic seizures with hypothalamic ham- 4. Beghi E, Carpio A, Forsgren L, et al. Recommendation
artoma is a rare syndrome of focal seizures with for a definition of acute symptomatic seizure. Epilepsia
2010;51:6715.
mirthless laughter and GTC seizures that is specifi- 5. Matsumoto H, Ajmone Marsan C. Cellular mechanisms in
cally associated with a neuronal-glial hamartoma of experimental epileptic seizures. Science 1964;144:1934.
the hypothalamus.145147 Precocious puberty, ictal 6. Holmes GL, Ben-Ari Y. Seizing hold of seizures. Nature
semiology, and brain MRI findings are diagnostic. Med 2003;9:9946.
7. Bragin A, Engel J Jr, Wilson CL, et al. Hippocampal and
Interictal and ictal EEG epileptiform findings are vari- entorhinal cortex high-frequency oscillations (100--500 Hz)
able. Seizures often are intractable, but resective or in human epileptic brain and in kainic acid--treated rats
radiosurgical procedures have significant efficacy. with chronic seizures. Epilepsia 1999;40:12737.
8. Chang BS, Lowenstein DH. Epilepsy. N Engl J Med
Hemiconvulsion-hemiplegia-epilepsy (HHE) 2003;349:125766.
is a rare syndrome most often of early childhood 9. Fisher RS. Animal models of the epilepsies. Brain Res
onset.148150 The first manifestation usually is hemi- Brain Res Rev 1989;14:24578.
10. Proposal for revised clinical and electrographic classifica-
convulsive status epilepticus lasting one to several tion of epileptic seizures. From the Commission on Clas-
hours, or longer if untreated. After status ends, a sification and Terminology of the International League
new postictal hemiplegia persists. After a latent Against Epilepsy. Epilepsia 1981;22:489501.
11. Syed TU, LaFrance EC, Kahriman ES, et al. Can semiol-
period of 1 to 4 years, focal seizures begin to ogy predict psychogenic nonepileptic seizures? a prospec-
occur as complex partial seizures (focal seizures tive study. Ann Neurol 2011;69:9971004.
with impaired awareness), focal clonic seizures, or 12. Derry CP, Duncan JS, Berkovic SF. Paroxysmal motor dis-
other types of focal seizures. These seizures may orders of sleep: The clinical spectrum and differentiation
from epilepsy. Epilepsia 2006;47:177591.
be controlled with medications, or sometimes with 13. Parry SW, Tan MP. An approach to the evaluation and
resective surgery. The optimal therapy is aggres- management of syncope in adults. BMJ 2010;340:c880.
sive management of all childhood status epilepti- 14. Devinsky O, Gazzola D, LaFrance WC. Differentiating
between nonepileptic and epileptic seizures. Nature Rev
cus, and with improving health care delivery the Neurosci 2011;7:21020.
incidence of HHE appears to have declined. 15. Henry TR, Drury I. Non-epileptic seizures in temporal
lobectomy candidates with medically refractory seizures.
Neurology 1997;48:137482.
BOARD REVIEW QUESTIONS 16. Pillai J, Sperling MR. Interictal EEG and the diagnosis of
Test your knowledge of this topic. epilepsy. Epilepsia 2006;47(suppl 1):1422.
Go to www.turner-white.com and select Epilepsy 17. Gilliam F, Kuzniecky R, Faught E. Ambulatory EEG moni-
from the drop-down menu of specialties. toring. J Clin Neurophysiol 1999;16:111115.
18. Cascino GD. Video-EEG monitoring in adults. Epilepsia
2002;43(suppl 3):8093.
References 19. Proposal for revised classification of epilepsies and epilep-
tic syndromes. From the Commission on Classification and
1. Hesdorffer DC, Logroscino G, Benn EK, et al. Estimating Terminology of the International League Against Epilepsy.
risk for developing epilepsy: a population-based study in Epilepsia 1989;30:38999.
Rochester, Minnesota. Neurology. 2011;76:237. 20. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminol-

ogy and concepts for organization of seizures and epilep- 1997;26:38995.

sies: Report of the ILAE Commission on Classification and 37. Chugani HT, Shields WD, Shewmon DA, et al. Infantile
Terminology, 2005-2009. Epilepsia 2010;51:67685. spasms: I. PET identifies focal cortical dysgenesis in
21. Berkovic SF, Heron SE, Giordano L, et al. Benign familial cryptogenic cases for surgical treatment. Ann Neurol
neonatal-infantile seizures: characterization of a new so- 1990;27:40613.
dium channelopathy. Ann Neurol 2004;55:5507. 38. Dulac O, Plouin P, Jambaque I. Predicting favorable out-
22. Hirsch E, Velez A, Sellal F, et al. Electroclinical signs come in idiopathic West syndrome. Epilepsia 1993;34:747
of benign neonatal familial convulsions. Ann Neurol 56.
1993;34:83541. 39. Kuzniecky R, Andermann F, Guerrini R. Infantile spasms:
23. Leppert M, Anderson VE, Quattlebaum T, et al. Benign an early epileptic manifestation in some patients with the
familial neonatal convulsions linked to genetic markers on congenital bilateral perisylvian syndrome. J Child Neurol
chromosome 20. Nature 1989;337:6478. 1994;9:4203.
24. Shevell MI, Sinclair DB, Metrakos K. Benign familial neo- 40. Lombroso CT. A prospective study of infantile spasms: clin-
natal seizures: clinical and electroencephalographic char- ical and therapeutic correlations. Epilepsia 1983;24:135
acteristics. Pediatr Neurol 1986;2:2725. 58.
25. Dalla Bernardina B, Zullini E, Fontana E. Electroclinical 41. Auvin S, Pandit F, De Bellecize J, et al. Benign myoclonic
longitudinal study of ten cases of Angelmans syndrome. epilepsy in infants: electroclinical features and long-term
Epilepsia 1993;34(Suppl 2):71. follow-up of 34 patients. Epilepsia 2006;47:38793.
26. Lombroso CT. Early myoclonic encephalopathy, early in- 42. Darra F, Fiorini E, Zoccante L, et al Benign myoclonic epi-
fantile epileptic encephalopathy, and benign and severe in- lepsy in infancy (BMEI): a longitudinal electroclinical study
fantile myoclonic epilepsies: a critical review and personal of 22 cases. Epilepsia 2006;47 Suppl 5:3135.
contributions. J Clin Neurophysiol 1990;7:380408. 43. Lombroso CT, Fejerman N. Benign myoclonus of early
27. Ohtahara S, Yamatogi Y. Epileptic encephalopathies in infancy. Ann Neurol 1977;1:13843.
early infancy with suppression-burst. J Clin Neurophysiol 44. Capovilla G, Beccaria F. Benign partial epilepsy in infancy
2003;20:398407. and early childhood with vertex spikes and waves during
28. Fusco L, Pachatz C, Di Capua M, Vigevano F. Video/ sleep: a new epileptic form. Brain Dev 2000;22:9398.
EEG aspects of early-infantile epileptic encephalopathy 45. Dulac O, Cusmai R, de Oliveira K. Is there a partial benign
with suppression-bursts (Ohtahara syndrome). Brain Dev epilepsy in infancy? Epilepsia 1989;30:798801.
2001;23:70814. 46. Nelson GB, Olson DM, Hahn JS. Short duration of benign
29. Mizrahi EM, Clancy RR. Neonatal seizures: early-onset partial epilepsy in infancy. J Child Neurol 2002;17:4405.
seizure syndromes and their consequences for develop- 47. Okumura A, Watanabe K, Negoro T, et al. Long-term
ment. Ment Retard Dev Disabil Res Rev 2000;6:22941. follow-up of patients with benign partial epilepsy in infancy.
30. Ohtahara S, Ohtsuka Y, Yamatogi Y, Oka E. The early- Epilepsia 2006;47:1815.
infantile epileptic encephalopathy with suppression-burst: 48. Watanabe K, Yamamoto N, Negoro T, et al. Benign complex
developmental aspects. Brain Dev 1987;9:3716. partial epilepsies in infancy. Pediatr Neurol 1987;3:20811.
31. Coppola G, Plouin P, Chiron C, et al. Migrating partial sei- 49. Dravet C, Bureau M, Oguni H, et al. Severe myoclonic epi-
zures in infancy: a malignant disorder with developmental lepsy in infancy (Dravet syndrome). In: Roger J, Bureau M,
arrest. Epilepsia 1995;36:101724. Dravet C, et al, eds. Epileptic syndromes in infancy, child-
32. Wilmshurst JM, Appleton DB, Grattan-Smith PJ. Migrating hood and adolescence. 4th ed. London: John Libbey: 2005.
partial seizures in infancy: two new cases. J Child Neurol 50. Fukuma G, Oguni H, Shirasaka Y, et al. Mutations of
2000;15:71722. neuronal voltage-gated Na+ channel alpha 1 subunit
33. Alvarez LA, Shinnar S, and Moshe SL. Infantile spasms due gene SCN1A in core severe myoclonic epilepsy in in-
to unilateral cerebral infarcts. Pediatrics 1987;79:10246. fancy (SMEI) and in borderline SMEI (SMEB). Epilepsia
34. Asano E, Juhasz C, Shah A, et al. Origin and propagation 2004;45:1408.
of epileptic spasms delineated on electrocorticography. 51. Siegler Z, Barsi P, Neuwirth M, et al. Hippocampal sclero-
Epilepsia 2005;46:108697. sis in severe myoclonic epilepsy in infancy: a retrospective
35. Bachman DS. Spontaneous remission of infantile spasms MRI study. Epilepsia 2005;46:7048.
with hypsarrhythmia. Arch Neurol 1981;38: 785. 52. Singh R, Andermann E, Whitehouse WP, et al. Severe
36. Chiron C, Dumas C, Jambaque I, et al. Randomized myoclonic epilepsy of infancy: extended spectrum of
trial comparing vigabatrin and hydrocortisone in infan- GEFS+? Epilepsia 2001;42:83744.
tile spasms due to tuberous sclerosis. Epilepsy Res 53. Yakoub M, Dulac O, Jambaque I, et al. Early diagno-

sis of severe myoclonic epilepsy in infancy. Brain Dev 70. Gastraut H, Roger J, Soulayrol R, et al. Childhood epileptic
1992;14:299303. encephalopathy with diffuse slow spike-waves (otherwise
54. Aicardi J, Chevrie JJ. Myoclonic epilepsies of childhood. known as petit mal variant) or Lennox syndrome. Epilep-
Neuropadiatrie 1971;3:17790. sia 1966;7:13979.
55. Dalla Bernardina B, Dulac O, Fejerman N, et al. Early myo- 71. Lennox WG, Davis JP. Clinical correlates of the fast and
clonic epileptic encephalopathy (E.M.E.E.). Eur J Pediatr the slow spike-wave electroencephalogram. Pediatrics
1983;140:24852. 1950;5:62644.
56. Erba G, Lombroso CT. Angelmans (Happy Puppet) syn- 72. Ohtahara S, Yamatogi Y, Ohtsuka Y. Prognosis of the Len-
drome: Clinical, CT scan and serial electroencephalo- nox syndrome-long-term clinical and electroencephalo-
graphic study. Clin Electroencephalogr 1973;20: 12840. graphic follow-up study, especially with special reference
57. Dalla Bernardina B, Fontana E, Darra F. Myoclonic to relationship with the West syndrome. Folia Psychiatr
status in nonprogressive encephalopathies. Adv Neurol Neurol Jpn 1976;30:27587.
2005;95:5970. 73. Tassinari CA, Dravet C, Roger J, et al. Tonic status
58. Aarts JH, Binnie CD, Smit AM, Wilkins AJ. Selective cogni- epilepticus precipitated by intravenous benzodiazepine
tive impairment during focal and generalized epileptiform in five patients with Lennox-Gastaut syndrome. Epilepsia
EEG activity. Brain 1984;107( Pt 1):293308. 1972;13:42135.
59. Berkovic SF, Andermann F, Andermann E, Gloor P. Con- 74. Aicardi J, Chevrie JJ. Atypical benign partial epilepsy of
cepts of absence epilepsies: discrete syndromes or bio- childhood. Dev Med Child Neurol 1982;24:28192.
logical continuum? Neurology 1987;37:9931000. 75. Beydoun A, Garofalo EA, Drury I. Generalized spike-
60. Browne TR, Dreifuss FE, Penry JK, et al. Clinical and waves, multiple loci, and clinical course in children with
EEG estimates of absence seizure frequency. Arch Neurol EEG features of benign epilepsy of childhood with centro-
1983;40:46972. temporal spikes. Epilepsia 1992;33:10916.
61. Cobb WA, Gordon N, Matthews SC, et al. The occipital 76. Blom S, Heijbel J. Benign epilepsy of children with centro-
delta rhythm in petit mal. Electroencephalogr Clin Neuro- temporal EEG foci: a follow-up study in adulthood of pa-
physiol 1961;13:1423. tients initially studied as children. Epilepsia 1982;23:629
62. Holmes GL, McKeever M, Adamson M. Absence seizures 32.
in children: clinical and electroencephalographic features. 77. Caraballo R, Cersosimo R, Fejerman N. Idiopathic partial
Ann Neurol 1987;21:26873. epilepsies with rolandic and occipital spikes appearing in
63. Lennox WG. The petit mal epilepsies; their treatment with the same children. J Epilepsy 1998;11:26164.
tridione. J Am Med Assoc 1945;129:106974. 78. Bernardina BD, Beghini G. Rolandic spikes in children with
64. Meencke HJ, Janz D. Neuropathological findings in prima- and without epilepsy. (20 subjects polygraphically studied
ry generalized epilepsy: a study of eight cases. Epilepsia during sleep). Epilepsia 1976;17:1617.
1984;25:821. 79. Gelisse P, Corda D, Raybaud C, et al. Abnormal neuroim-
65. Penry JK, Porter RJ, Dreifuss RE. Simultaneous recording aging in patients with benign epilepsy with centrotemporal
of absence seizures with video tape and electroencepha- spikes. Epilepsia 2003;44:3728.
lography. A study of 374 seizures in 48 patients. Brain 80. Kramer U, Zelnik N, Lerman-Sagie T, Shahar E. Benign
1975;98:42740. childhood epilepsy with centrotemporal spikes: clinical
66. Wirrell EC, Camfield CS, Camfield PR, et al. Long-term characteristics and identification of patients at risk for mul-
prognosis of typical childhood absence epilepsy: remission tiple seizures. J Child Neurol 2002;17:1719.
or progression to juvenile myoclonic epilepsy. Neurology 81. Lerman P, Kivity S. Benign focal epilepsy of childhood. A
1996;47:91218. follow-up study of 100 recovered patients. Arch Neurol
67. Wolf P, Goosses R. Relation of photosensitivity to epileptic 1975;32:2614.
syndromes. J Neurol Neurosurg Psychiatry 1986;49:1386 82. Lombroso CT. Sylvian seizures and midtemporal spike foci
91. in children. Arch Neurol 1967;17:5259.
68. Bauer G, Aichner F, Saltuari L. Epilepsies with diffuse slow 83. Wirrell EC, Camfield PR, Gordon KE, et al. Benign rolandic
spikes and waves of late onset. Eur Neurol 1983;22:344 epilepsy: atypical features are very common. J Child Neu-
50. rol 1995;10:4558.
69. Chugani HT, Mazziotta JC, Engel J Jr. Phelps ME. The 84. Caraballo RH, Sologuestua A, Granana N, et al. Idiopathic
Lennox-Gastaut syndrome: metabolic subtypes deter- occipital and absence epilepsies appearing in the same
mined by 2-deoxy-2[18F]fluoro-D-glucose positron emis- children. Pediatr Neurol 2004;30:2428.
sion tomography. Ann Neurol 1987;21: 413. 85. Kuzniecky R, Rosenblatt B. Benign occipital epilepsy: a

family study. Epilepsia 1987;28:34650. 102. Guerrini R, Bureau M, Mattei MG, et al. Trisomy 12p
86. Panayiotopoulos CP. Benign childhood epilepsy with oc- syndrome: a chromosomal disorder associated with
cipital paroxysms: a 15-year prospective study. Ann Neurol generalized 3-Hz spike and wave discharges. Epilepsia
1989;26:5156. 1990;31:55766.
87. Panayiotopoulos CP. Elementary visual hallucinations, 103. Manonmani V, Wallace SJ. Epilepsy with myoclonic ab-
blindness, and headache in idiopathic occipital epilepsy: sences. Arch Dis Child 1994;70:28890.
differentiation from migraine. J Neurol Neurosurg Psychia- 104. Patry G, Lyagoubi S, Tassinari CA. Subclinical electrical
try 1999;66:53640. status epilepticus induced by sleep in children. A clinical
88. Blume WT, Wiebe S, Tapsell LM. Occipital epilepsy: lateral and electroencephalographic study of six cases. Arch Neu-
versus mesial. Brain 2005;128:120925. rol 1971;24:24252.
89. Fejerman N. [Atypical evolution of benign partial epilepsy 105. Praline J, Hommet C, Barthez MA, et al. Outcome at adult-
in children]. Rev Neurol 1996;24:141520. hood of the continuous spike-waves during slow sleep and
90. Gastaut H. A new type of epilepsy: benign partial epilepsy Landau-Kleffner syndromes. Epilepsia 2003;44:143440.
of childhood with occipital spike-waves. Clin Electroen- 106. Hirsch E, Marescaux C, Maquet P, et al. Landau-Kleffner
cephalogr 1982;13:1322. syndrome: a clinical and EEG study of five cases. Epilepsia
91. Kivity S, Ephraim T, Weitz R, Tamir A. Childhood epilepsy 1990;31:75667.
with occipital paroxysms: clinical variants in 134 patients. 107. Landau WM, Kleffner FR. Syndrome of acquired aphasia
Epilepsia 2000;41:152233. with convulsive disorder in children. Neurology 1957;7:523
92. Ludwig BI, Marsan CA. Clinical ictal patterns in epileptic 30.
patients with occipital electroencephalographic foci. Neu- 108. Escayg A, Heils A, MacDonald BT, et al. A novel SCN1A
rology 1975;25:46371. mutation associated with generalized epilepsy with febrile
93. Talwar D, Rask CA, Torres F. Clinical manifestations in seizures plus--and prevalence of variants in patients with
children with occipital spike-wave paroxysms. Epilepsia epilepsy. Am J Hum Genet 2001;68:86673.
1992;33:66774. 109. Scheffer IE, Berkovic SF. Generalized epilepsy with febrile
94. Doose H. Myoclonic astatic epilepsy of early childhood. seizures plus. A genetic disorder with heterogeneous clini-
In: Roger J, Bureau M, Dravet C, et al, eds. Epileptic syn- cal phenotypes. Brain 1997;120 (Pt 3):47990.
dromes in infancy, childhood and adolescence. London: 110. Aliberti V, Grunewald RA, Panayiotopoulos CP, Chroni E.
John Libbey: 2005. Focal electroencephalographic abnormalities in juvenile
95. Dulac O, Plouin P, Shewmon A. Myoclonus and epilepsy myoclonic epilepsy. Epilepsia 1994;35:297301.
in childhood: 1996 Royaumont meeting. Epilepsy Res 111. Asconape J, Penry JK. Some clinical and EEG as-
1998;30:91106. pects of benign juvenile myoclonic epilepsy. Epilepsia
96. Nabbout R, Kozlovski A, Gennaro E, et al. Absence of 1984;25:10814.
mutations in major GEFS+ genes in myoclonic astatic epi- 112. Delgado-Escueta AV, Enrile-Bacsal F. Juvenile myoclonic
lepsy. Epilepsy Res 2003;56:12733. epilepsy of Janz. Neurology 1984;34:28594.
97. Oguni H, Fukuyama Y, Imaizumi Y, Uehara T. Video- 113. Janz D, Christian W. Impulsiv-Petit mal. Dtsch Z Nerven-
EEG analysis of drop seizures in myoclonic astatic heilkd 1957;176:34886.
epilepsy of early childhood (Doose syndrome). Epilepsia 114. Zifkin B, Andermann E, Andermann F. Mechanisms, ge-
1992;33:80513. netics, and pathogenesis of juvenile myoclonic epilepsy.
98. Hirsch E, Sellal F, Maton B, et al. Nocturnal paroxysmal Curr Opin Neurol 2005;18:14753.
dystonia: a clinical form of focal epilepsy. Neurophysiol Clin 115. Berg AT, Shinnar S. The risk of seizure recurrence follow-
1994;24:20717. ing a first unprovoked seizure: a quantitative review. Neu-
99. Meierkord H, Fish DR, Smith SJ, et al. Is nocturnal parox- rology 1991;41:96572.
ysmal dystonia a form of frontal lobe epilepsy? Mov Disord 116. Hauser WA, Anderson VE, Loewenson RB, McRoberts
1992;7:3842. SM. Seizure recurrence after a first unprovoked seizure. N
100. Scheffer IE, Bhatia KP, Lopes-Cendes I, et al. Autosomal Engl J Med 1982;307:5228.
dominant nocturnal frontal lobe epilepsy. A distinctive clini- 117. Berkovic SF, Andermann F, Carpenter S, Wolfe LS. Pro-
cal disorder. Brain 1995;118 ( Pt 1):6173. gressive myoclonus epilepsies: specific causes and diag-
101. Capovilla G, Rubboli G, Beccaria F, et al. A clinical spec- nosis. N Engl J Med 1986;315:296305.
trum of the myoclonic manifestations associated with 118. Koskiniemi M, Toivakka E, Donner M. Progressive myoc-
typical absences in childhood absence epilepsy. A video- lonus epilepsy. Electroencephalographical findings. Acta
polygraphic study. Epileptic Disord 2001;3:5762. Neurol Scand 1974;50:33359.

119. Lafreniere RG, Rochefort DL, Chretien N, et al. Unstable 134. Engel J Jr, Wiebe S, French J, et al. Practice parameter:
insertion in the 5 flanking region of the cystatin B gene temporal lobe and localized neocortical resections for epi-
is the most common mutation in progressive myoclonus lepsy: report of the Quality Standards Subcommittee of the
epilepsy type 1, EPM1. Nat Genet 1997;15:298302. American Academy of Neurology, in association with the
120. Magaudda A, Ferlazzo E, Nguyen VH, Genton P. Un- American Epilepsy Society and the American Association
verricht-Lundborg disease, a condition with self-limited of Neurological Surgeons. Neurology 2003;60:53847.
progression: long-term follow-up of 20 patients. Epilepsia 135. French JA, Williamson PD, Thadani VM, et al. Characteris-
2006;47:8606. tics of medial temporal lobe epilepsy: I. Results of history
121. Shibasaki H, Yamashita Y, Neshige R, et al. Pathogenesis and physical examination. Ann Neurol 1993;34:77480.
of giant somatosensory evoked potentials in progressive 136. Risinger MW, Engel J Jr, Van Ness PC, Henry TR, Cran-
myoclonic epilepsy. Brain 1985;108(Pt 1):22540. dall PH. Ictal localization of temporal lobe seizures with
122. Michelucci R, Poza JJ, Sofia V, et al. Autosomal dominant scalp/sphenoidal recordings. Neurology 1989;39:128893.
lateral temporal epilepsy: clinical spectrum, new epitempin 137. So N, Gloor P, Quesney LF, et al. Depth electrode investi-
mutations, and genetic heterogeneity in seven European gations in patients with bitemporal epileptiform abnormali-
families. Epilepsia 2003;44:128997. ties. Ann Neurol 1989;25:42331.
123. Winawer MR, Martinelli Boneschi F, Barker-Cummings C, 138. Sperling MR, OConnor MJ. Auras and subclinical sei-
et al. Four new families with autosomal dominant partial zures: characteristics and prognostic significance. Ann
epilepsy with auditory features: clinical description and Neurol 1990;28:3208.
linkage to chromosome 10q24. Epilepsia 2002;43:6067. 139. Williamson PD, French JA, Thadani VM, et al. Characteris-
124. Andermann E, Abou-Khalil B, Berkovic SF, et al. Deja-vu tics of medial temporal lobe epilepsy: II. Interictal and ictal
is the characteristic aura in benign familial temporal lobe scalp electroencephalography, neuropsychological testing,
epilepsy. Epilepsia 1997;38:200. neuroimaging, surgical results, and pathology. Ann Neurol
125. Cendes F, Lopes-Cendes I, Andermann E, Andermann F. 1993;34:7817.
Familial temporal lobe epilepsy: a clinically heterogeneous 140. Bien CG, Urbach H, Deckert M, et al. Diagnosis and stag-
syndrome. Neurology 1998;50:5547. ing of Rasmussens encephalitis by serial MRI and histo-
126. Kobayashi E, Lopes-Cendes I, Guerreiro CA, et al. Seizure pathology. Neurology 2002;58:2507.
outcome and hippocampal atrophy in familial mesial tem- 141. Li Y, Uccelli A, Laxer KD, et al. Local-clonal expansion of
poral lobe epilepsy. Neurology 2001;56:16672. infiltrating T lymphocytes in chronic encephalitis of Ras-
127. Scheffer IE, Phillips HA, OBrien CE, et al. Familial partial mussen. J Immunol 1997;158:142837.
epilepsy with variable foci: a new partial epilepsy syn- 142. McLachlan RS, Girvin JP, Blume WT, Reichman H. Ras-
drome with suggestion of linkage to chromosome 2. Ann mussens chronic encephalitis in adults. Arch Neurol
Neurol 1998;44:8909. 1993;50:26974.
128. Berkovic SF, Serratosa JM, Phillips HA, et al. Familial par- 143. Rasmussen T, Olszewski J, Lloydsmith D. Focal sei-
tial epilepsy with variable foci: clinical features and linkage zures due to chronic localized encephalitis. Neurology
to chromosome 22q12. Epilepsia 2004;45:105460. 1958;8:43545.
129. Bickford RG, Whelan JL, Klass DW, Corbin KB. Reading 144. Pardo CA, Vining EP, Guo L, et al. The pathology of Ras-
epilepsy: clinical and electroencephalographic studies of a mussen syndrome: stages of cortical involvement and neu-
new syndrome. Trans Am Neurol Assoc 1956(81st meet- ropathological studies in 45 hemispherectomies. Epilepsia
ing);100102. 2003;45:51626.
130. Koutroumanidis M, Koepp MJ, Richardson MP, et al. The 145. Breningstall GN. Gelastic seizures, precocious puberty,
variants of reading epilepsy. A clinical and video-EEG and hypothalamic hamartoma. Neurology 1985;35:1180
study of 17 patients with reading-induced seizures. Brain 3.
1998;121(Pt 8):140927. 146. Kahane P, Ryvlin P, Hoffmann D, et al. From hypothalamic
131. Matthews WB, Wright FK. Hereditary primary reading epi- hamartoma to cortex: what can be learnt from depth re-
lepsy. Neurology 1967;17:91921. cordings and stimulation? Epileptic Disord 2003;5:20517.
132. Cascino GD, Jack CR, Jr, Parisi JE, et al. Magnetic reso- 147. Kuzniecky R, Guthrie B, Mountz J, et al. Intrinsic epilepto-
nance imaging-based volume studies in temporal lobe epi- genesis of hypothalamic hamartomas in gelastic epilepsy.
lepsy: pathological correlations. Ann Neurol 1991;30:31 Ann Neurol 1997;42:6067.
36. 148. Chauvel P, Dravet C. The HHE syndrome. In: Roger J, Bu-
133. Engel JJ. Current concepts: surgery for seizures. N Engl J reau M, Dravet C, et al, eds. Epileptic syndromes in infancy,
Med 1996;334:64752. childhood, and adolescence. London: John Libbey: 2005.

149. Freeman JL, Coleman LT, Smith LJ, Shield LK. Hemi- 150. Roger J, Dravet C, Bureau M. Unilateral seizures: hemicon-
convulsion-hemiplegia-epilepsy syndrome: characteristic vulsions-hemiplegia syndrome (HH) and hemiconvulsions-
early magnetic resonance imaging findings. J Child Neurol hemiplegia-epilepsy syndrome (HHE). Electroencephalogr
2002;17:1016. Clin Neurophysiol Suppl 1982;21121.
Copyright 2012 by Turner White Communications Inc., Wayne, PA. All rights reserved.

Seizures and Epilepsy: Pathophysiology and Principles of Diagnosis

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Seizures and Epilepsy: Pathophysiology and Principles of Diagnosis

Uploaded by

Copyright:

Available Formats

Epilepsy Board Review Manual

Contributor and Editor:

executive vice president

Seizures and Epilepsy:

Introduction effects, and therapeutic monitoring of antiseizure

www.turner-white.com Epilepsy Volume 1, Part 1 1

2 Hospital Physician Board Review Manual www.turner-white.com

www.turner-white.com Epilepsy Volume 1, Part 1 3

4 Hospital Physician Board Review Manual www.turner-white.com

generate a hypothesis regarding the type(s) of Types of nonepileptic seizures

www.turner-white.com Epilepsy Volume 1, Part 1 5

6 Hospital Physician Board Review Manual www.turner-white.com

The common risk factors, historical associations,

www.turner-white.com Epilepsy Volume 1, Part 1 7

Predominant Motor Phenomena as Described by Witnesses of Seizures

8 Hospital Physician Board Review Manual www.turner-white.com

www.turner-white.com Epilepsy Volume 1, Part 1 9

10 Hospital Physician Board Review Manual www.turner-white.com

Table 5. ILAE 1989 Classification of Epilepsies

1. Localization-related (focal, local, partial) epilepsies and syndromes

www.turner-white.com Epilepsy Volume 1, Part 1 11

Table 6. ILAE 2010 Proposal for Classification of Epilepsies

Organizational Group Electroclinical Syndrome

12 Hospital Physician Board Review Manual www.turner-white.com

www.turner-white.com Epilepsy Volume 1, Part 1 13

www.turner-white.com Epilepsy Volume 1, Part 1 15

16 Hospital Physician Board Review Manual www.turner-white.com

www.turner-white.com Epilepsy Volume 1, Part 1 17

18 Hospital Physician Board Review Manual www.turner-white.com

www.turner-white.com Epilepsy Volume 1, Part 1 19

20 Hospital Physician Board Review Manual www.turner-white.com

www.turner-white.com Epilepsy Volume 1, Part 1 21

ogy and concepts for organization of seizures and epilep- 1997;26:38995.

22 Hospital Physician Board Review Manual www.turner-white.com

www.turner-white.com Epilepsy Volume 1, Part 1 23

24 Hospital Physician Board Review Manual www.turner-white.com

www.turner-white.com Epilepsy Volume 1, Part 1 25

26 Hospital Physician Board Review Manual www.turner-white.com

You might also like