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Oxford Textbook of

Clinical
Neurophysiology
Oxford Textbooks in Clinical Neurology

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Oxford Textbook of
Clinical
Neurophysiology
Edited by
Kerry R. Mills
Department of Basic and Clinical Neuroscience, King’s College London, UK

Series Editor
Christopher Kennard

1
1
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 Preface
Clinical Neurophysiology provides a wide range of techniques for
investigating patients with neurological conditions and is crucial in
some, such as entrapment neuropathies and epilepsy. The discipline
has advanced in recent years and can now provide information in
the clinic on such diverse aspects as the function of single ion chan-
nels in peripheral nerve disease to the degree of degeneration of
the corticospinal tract in patients with, say, motor neurone disease.
We also have techniques to investigate brain function on a milli-
second timescale with EEG and MEG and are able to co-​register
this activity with brain structure using MRI and fMRI. Clinical
Neurophysiologists, therefore, need not only to have an in-​depth
knowledge of the neurological conditions that they will encounter,
but also to understand the technical aspects of their techniques and
to appreciate how signals are recorded and dealt with in the digital
domain by our modern computer systems. They should be particu-
larly aware of the pitfalls that can befall them. One might say that
the modern clinical neurophysiologist is a cross between a clinician
and a digital signal processor.
One must never lose sight, however, of the fact that the patient is
the prime concern for diagnosis and prognosis. It is a much quoted
aphorism that clinical neurophysiology is an extension of the neu-
rological examination and this is still true. Despite the welcome
development of test protocols, algorithms, flow charts, minimal
standards, and so on, they come to naught unless they provide an
answer for the patient in front of you. Only the well-​trained clinical
neurophysiologist will be able to assess both the clinical informa-
tion and then put the neurophysiological data in context.
Successful practice of neurophysiology also demands a knowl-
edge of the basic science underlying the investigations performed,
in order to reach a conclusion with regard to the pathology likely
to be involved. This volume provides sections giving a summary of
the basic science underlying the techniques, a description of the
techniques themselves and a section describing the use of the tech-
niques in clinical situations. The subject has traditionally been sub-
divided into EEG, the recording of brain electrical activity through
electrodes placed on the scalp, nerve conduction studies, and EMG,
the electrical activity deriving from nerve and muscle, and evoked
potentials where brain activity locked in time to a peripheral nerve,
visual or auditory stimulus is averaged to give information on affer-
ent pathways. However, many basic principles are common to all
techniques and these are emphasized in the first section.
I hope this will prove a useful textbook and reference source for
trainees in neurophysiology, neurology, and neurosurgery but also
that it will appeal to general neurologists, paediatricians and tech-
nologists undertaking neurophysiology. This venture would not
have been possible without the willingness of authors to provide
their excellent contributions for which I thank them. I would also
like to thank Oxford University Press for continual encouragement.
Kerry R. Mills
 Contents

Abbreviations ix 10 Reflex studies 107

Josep Valls-​Solé
Contributors xiii
11 Electroencephalography 119
SECTION 1 Michalis Koutroumanidis,
Dimitrios Sakellariou, and Vasiliki Tsirka
Scientific basis of clinical
neurophysiology 1 12 Intracranial electroencephalographic
recordings 131
1 Nerve, muscle, and neuromuscular Gonzalo Alarcón and Antonio Valentín
junction 3
Machiel J. Zwarts
13 Magnetoencephalography 149
Paul L. Furlong, Elaine Foley,
2 The motor unit 9 Caroline Witton, and Stefano Seri
David Burke and James Howells
14 Transcranial magnetic stimulation 163
3 Motor control: spinal and Kerry R. Mills
cortical mechanisms 19
15 Evoked potentials 175
David Burke
Helmut Buchner
4 Cortical activity: single cell, cell
16 Polysomnography and other
assemblages, and networks 31
investigations for sleep disorders 187
John G. R. Jefferys
Zenobia Zaiwalla and Roo Killick
5 Recording of neural signals, neural
17 Clinical neurophysiology of the pelvic floor 195
activation, and signal processing 37
Adrian J. Fowle
Dick F. Stegeman and Michel J. A. M. Van Putten

SECTION 2 SECTION 3
Techniques of clinical neurophysiology 47 Clinical aspects: peripheral
nervous system 207
6 Nerve conduction studies 49
Jun Kimura 18 The clinical approach to neurophysiology 209
Kerry R. Mills
7 Electromyography 67
Erik Stålberg 19 Focal neuropathies 213
Jeremy D. P. Bland
8 Quantitative electromyography 81
Anders Fuglsang-​Frederiksen, 20 Generalized peripheral neuropathies 223
Kirsten Pugdahl, and Hatice Tankisi Hessel Franssen
9 Axonal excitability: molecular basis 21 Disorders of single nerves,
and assessment in the clinic 97 roots, and plexuses 235
Susanna B. Park, Cindy S-​Y. Lin, and Matthew C. Kiernan Kerry R. Mills
viii  contents

22 Neurophysiology in amyotrophic lateral 29 Syncope 337

sclerosis and other motor degenerations 243 Shane Delamont
Mamede de Carvalho and Michael Swash
30 Convulsive and non-​convulsive
23 Clinical aspects of neuromuscular status epilepticus 345
junction disorders 257 Matthew C. Walker
Donald B. Sanders
31 Presurgical evaluation for epilepsy surgery 355
24 Primary muscle diseases 267 Robert Elwes
Robin P. Kennett and Sidra Aurangzeb
32 Encephalopathy, central nervous
25 Paediatric conditions 277 system infections, and coma 379
Matthew Pitt Michalis Koutroumanidis and Robin Howard
26 EMG-​guided botulinum toxin therapy 291 33 Migraine, stroke, and cerebral ischaemia 399
V. Peter Misra and Santiago Catania Gonzalo Alarcón, Marian Lazaro, and Antonio Valentín
34 Electroclinical features of
SECTION 4 paediatric conditions 411
Clinical aspects: central Sushma Goyal
nervous system 299 35 Sleep disorders 425
Zenobia Zaiwalla and Roo Killick
27 Genetic generalized epilepsy 301
Friederike Moeller, Ronit M. Pressler, and J. Helen Cross 36 Intraoperative monitoring 437
Marc R. Nuwer
28 Focal epilepsy 313
Tim Wehner, Kanjana Unnwongse, and Beate Diehl Index 451
 Abbreviations

3,4-​DAP 3,4-​diaminopyridine CIPN chemotherapy-​induced peripheral neuropathy

AASM American Academy of Sleep Medicine CMAP compound muscle action potential
AC alpha coma CMCT central motor conduction time
Ach acetylcholine CMRR common mode rejection ratio
AChR acetylcholine receptor CMS congenital (genetic) myasthenic syndromes
ADC analogue-​to-​digital converter CMT Charcot–​Marie–​Tooth neuropathy
ADHD attention deficit hyperactivity disorder CNE concentric needle electrode
ADM abductor digiti minimi CNS central nervous system
ADP adenosine diphosphate CPAP continuous positive airways pressure
AED anti-​epileptic drug CPSE complex partial status epilepticus
AEP auditory evoked potential CPT carnitine palmityl transferase
AFP acute flaccid paralysis CRD complex repetitive discharges
AHI apnoea–​hypopnoea index CSA central sleep apnoea
AHP after-​hyperpolarization CSAP compound sensory action potentials
AIDP acute inflammatory demyelinating polyneuropathy CSR common system reference
ALS amyotrophic lateral sclerosis CTS carpal tunnel syndrome
AMAN acute motor axonal neuropathy CV conduction velocity
AMSAN acute motor and sensory axonal neuropathy cVEMP cervical vestibular evoked myogenic potential
APB abductor pollicis brevis DHPR dihydropyridine receptor
ASFAP apparent single fibre action potential DICS dynamic imaging of coherent sources
ASPS advanced sleep phase syndrome DM dermatomyositis
ATC alpha-​theta coma DML distal motor latency
ATP adenosine triphosphate DNET dysembryoplastic neuroepithelial tumour
BAEP brain stem auditory evoked potential dSPM dynamic statistical parametric mapping
BCR bulbocavernosus reflex DSPS delayed sleep phase syndrome
BECTS benign epilepsy with centrotemporal spikes EAS external anal sphincter
BF body floating ECD equivalent-​current dipole
BFNC benign familial neonatal seizures ECG electrocardiograph
BiPED bilateral periodic epileptiform discharges ECoG electrocorticography
BIS bispectral index ED emergency departments
BMI body mass index EDS excessive daytime sleepiness
BOLD blood oxygenation level dependent EEG electroencephalograph
BP blood pressure EEG-​fMRI EEG and functional MRI
BRE benign Rolandic epilepsy EGTCSA epilepsy with generalized tonic–​clonic seizures
CAE childhood absence epilepsy on awakening
CAP cyclical alternating pattern EIEE early infantile epileptic encephalopathy
CB conduction block EIM electrical impedance myography
CBF cerebral blood flow ELMA eyelid myoclonia with absences
CCEP corticocortical-​evoked responses EM epileptic myoclonus
cEEG continuous EEG monitoring EMA epilepsy with myoclonic absences
CF cardiac floating EME early (neonatal) myoclonic encephalopathy
CGA corrected gestational age EMG electromyograph
CHEP cold and hot evoked potential ENM epileptic negative myoclonus
CIDP chronic inflammatory demyelinating EOG electro-​oculogram
polyneuropathy EP evoked potential
x  abbreviations

EPP endplate potential IP interference pattern

EPSP excitatory post-​synaptic potential IPA interference pattern analysis
ER event-​related IPS intermittent photic stimulation
ESES electrical status epilepticus in slow wave sleep IPSP inhibitory post-​synaptic potentials
ESS Epworth Sleepiness Scale IS infantile spasms
EUS external urethral sphincter iv intravenous
FARR Friedreich’s ataxia with retained reflexes IVIg intravenous immunoglobulin
FCD focal cortical dysplasia JAE juvenile absence epilepsy
FCR flexor carpi radialis JME juvenile myoclonic epilepsy
FD fibre density JMG juvenile MG
FDI first dorsal interosseous KCC2 K+–​Cl–​ cotransporter
FFT Fast Fourier Transform LE limbic encephalitis
FIRDA frontal intermittent delta activity LEMS Lambert Eaton myasthenic syndrome
FLE frontal lobe epilepsy LFF low frequency filters
fMRI functional magnetic resonance imaging LICI long interval intracortical inhibition
FO foramen ovale LMN lower motor neuron
FOG fibres containing oxidative and glycolytic enzymes LOC loss of consciousness
FOLD female, occipital, low amplitude, drowsy LSB least-​significant-​bit
FOS fixation-​off sensitivity M1 primary motor cortex
FP Fasciculation Potential MADSAM multifocal acquired demyelinating sensory
FR fatigue-​resistant muscle fibres and motor neuropathy
FS febrile seizures MAE myoclonic astatic epilepsy
FS+ febrile seizures plus MAG myelin associated glycoprotein
FWCV F wave conduction velocity MCS minimally conscious state
GA gestational age MCV motor conduction velocity
GABA gamma amino butyric acid ME myoclonic encephalopathy
GBS Guillain–​Barré syndrome MEG magnetoencephalography
GEFS genetic epilepsy with febrile seizures plus MEP motor evoked potential
GGE genetic generalised epilepsy MEPP miniature endplate potentials
GN geniculate nucleus MG myasthenia gravis
GPED generalized periodic epileptiform discharge MLAEPs middle latency auditory evoked potentials
GPPR generalized photoparoxysmal response MMN multifocal motor neuropathy
GSWD generalized spike-​wave discharge MMNCB multifocal motor neuropathy with conduction block
GTCS generalized tonic-​clonic seizures MN motoneuron
HCN hyperpolarisation-​activated cyclic nucleotide-​gated MND motor neurone disease
HCP half-​cell potentials MNE minimum norm estimate
HFF high frequency filter MRI magnetic resonance imaging
HFO high frequency oscillations MS multiple sclerosis
HIBI hypoxic–​ischaemic brain injury MSA multiple system atrophy
HIE hypoxic ischaemic encephalopathy MSLT multiple sleep latency test
HLA human leucocyte antigen MTLE mesial temporal lobe epilepsy
HNA hereditary neuralgic amyotrophy MTS mesial temporal sclerosis
HNPP hereditary neuropathy with pressure palsies MU motor unit
HR heart rate MUAP motor unit action potential
HSE herpes simplex encephalitis MUNE motor unit number estimation
HUT head-​up tilting MUNIX motor unit number index
IBM inclusion body myositis MUP motor unit potential
IC intracranial MuSK muscle specific kinase
ICC intra-​class correlation coefficiency MVC maximum voluntary contraction
ICEEG intracranial EEG MWT maintenance of wakefulness test
ICSD International Classification of Sleep Disorders NCS nerve conduction study
IED inter-​electrode distance NCSE non-​convulsive status epilepticus
IEE infantile epileptic encephalopathies NCSz non-​convulsive seizures
IGE idiopathic generalized epilepsy NFLE nocturnal frontal lobe epilepsy
IIED interictal epileptiform discharges NMJ Neuromuscular Junction
ILAE International League Against Epilepsy NM negative myoclonus
IoC impairment of cognition NMDA N-​methyl D-​aspartate
IONM intraoperative neurophysiological monitoring NREM non-​rapid eye movement sleep
IOZ ictal onset zone NRGC nucleus reticularis gigantocellularis
  abbreviations xi

NTLE neocortical temporal lobe epilepsy SE status epilepticus

OBPP obstetric brachial plexus palsy sEMG surface EMG
ODI Oxygen Desaturation Index SEP somatosensory evoked potential
OM ocular myasthenia SEPT9 septin gene
ORIDA occipital intermittent rhythmic delta activity SFAP single fibre action potentials
OS Ohtahara’s syndrome SFEMG single fibre electromyography
OSA obstructive sleep apnoea SFN small fibre neuropathy
PAD primary afferent depolarization SICF short interval intracortical facilitation
PC periodic complex SICI short-​interval intracortical inhibition
PCA principle component analysis SIRPID stimulus-​induced rhythmic, periodic, or ictal
pCO2 partial pressure of CO2 discharge
PED periodic epileptiform discharge SMA supplementary motor areas
PET positron emission tomography SMEI severe myoclonic epilepsy of infancy
Pi inorganic phosphate SNAP sensory nerve action potential
PIC persistent inward current SNR signal-​to-​noise ratio
PLED periodic lateralized epileptiform discharge SNRI serotonin–​norepinephrine reuptake inhibitors
PLM periodic limb movement SOL sleep onset latency
PLMD periodic limb movement disorder SOREMP sleep onset REM period
PLMS periodic leg movements in sleep SOZ seizure onset zone
PLMW periodic limb movements during resting SP silent period
wakefulness SPECT single photon emission computed tomography
PM polymyositis SPES single pulse electrical stimulation
PME progressive myoclonic encephalopathies SQUIDS superconducting quantum interference devices
PMEI partial migrating epilepsy in infancy SREDA subclinical rhythmical electrographic discharges
PMP22 peripheral myelin protein 22 in adults
PNTML pudendal nerve terminal motor latency SSEPs short-​latency somatosensory evoked potentials
PoTS postural orthostatic tachycardia syndrome SSMA supplementary sensorimotor area
PPR photo paroxysmal response SSR sympathetic skin response
PROMM proximal myotonic myopathy SSRI serotonin-​specific reuptake inhibitors
PSG polysomnography TA tibialis anterior
PSP progressive supranuclear palsy TC theta coma
PSTH peri-​stimulus time histogram tcACS transcranial alternating current stimulation
ipsw positive sharp waves tcCO2 transcutaneous carbon dioxide monitoring
PTT pulse transit time tcDCS transcranial direct current stimulation
PVS persistent vegetative state tce transcranial electrical
R&K Rechtschaffen and Kales TD temporal dispersion
RDI respiratory disturbance index TES transcranial electrical stimulation
REM rapid eye movement TH therapeutic hypothermia
RERA respiratory effort related arousal TIA transient ischaemic attack
RIP respiratory inductance plethysmography TILDA the Irish Longitudinal Study on Aging
RIV relative intertrial variation TIVA total intravenous anaesthesia
RL residual latency TLE temporal lobe epilepsy
RLS restless leg syndrome TLI terminal latency index
RMTD rhythmic mid-​temporal theta bursts of drowsiness TLOC transient loss of consciousness
RNS repetitive nerve stimulation TMS transcranial magnetic stimulation
RSBD REM sleep behaviour disorder TNMG transient neonatal myasthenia gravis
RSN resting-​state networks TOF train of four
rTMS repetitive TMS TPE therapeutic plasma exchange
RyR ryanodine receptor TRP transient receptor potential
SAE sepsis-​associated encephalopathy UARS upper airway resistance syndrome
SAM synthetic-​aperture magnetometry UMN upper motor neuron
SAP sensory action potential UW unresponsive wakefulness
SBS secondary bilateral synchrony VC vital capacity
sCJD Creutzfeldt–​Jacob disease vEEG video EEG
SCLC small cell lung cancer VEP visual evoked potential
SCV sensory conduction velocity VGCC voltage-​gated calcium channels
SDB sleep disordered breathing VGKC voltage gated potassium channel
SDTC strength duration time-​constant WHAM wakefulness, high amplitude, anterior, male
 Contributors

Gonzalo Alarcón, Comprehensive Epilepsy Center Neuroscience
Institute, Academic Health Systems, Hamad Medical
Corporation, Doha, Qatar; Department of Basic and Clinical
Neuroscience, Institute of Psychiatry, Psychology and
Neuroscience, King’s College London, UK; Department
of Clinical Neurophysiology, King’s College Hospital NHS
Trust, London, UK; Departamento de Fisiología, Facultad de
Medicina, Universidad Complutense, Madrid, Spain
Sidra Aurangzeb, Specialty Registrar in Neurology and Clinical
Neurophysiology, Oxford University Hospitals NHS Trust, UK
Jeremy D. P. Bland, Consultant in Clinical Neurophysiology, East
Kent Hospitals University NHS Foundation Trust, UK
Helmut Buchner, Department of Neurology and Clinical
Neurophysiology, Klinikum Vest Hospital, Recklinghausen,
Germany
David Burke, Department of Neurology, Royal Prince Alfred
Hospital and University of Sydney, Australia
Mamede de Carvalho, Professor of Physiology, Institute of
Physiology, Faculty of Medicine, Instituto de Medicina
Molecular, University of Lisbon, Portugal; Department of
Neurosciences, Hospital de Santa Maria-​CHLN, Lisbon,
Portugal
Santiago Catania, Consultant Clinical Neurophysiologist,
Department of Clinical Neurophysiology, The National Hospital
for Neurology and Neurosurgery, London, UK
J. Helen Cross, Clinical Neurosciences Section, UCL Institute of
Child Health, Great Ormond Street Hospital for Children,
London, UK
R. Shane Delamont, Consultant Neurologist, Departments of
Neurology and Neurophysiology, King’s College Hospital,
London, UK
Beate Diehl, Department of Clinical and Experimental Epilepsy,
Institute of Neurology, University College London, UK;
Department of Clinical Neurophysiology, National Hospital for
Neurology and Neurosurgery, Queen Square, London, UK
Robert Elwes, Consultant Neurologist and Clinical
Neurophysiologist, King’s College Hospital, London, UK
Elaine Foley, Aston Brain Centre, School of Life and Health
Sciences, Aston University, Birmingham, UK
Adrian J. Fowle, West Surrey Clinical Neurophysiology, Ashford
and St Peter’s Hospitals NHS Foundation Trust, Chertsey, UK
Hessel Franssen, Associate Professor of Neurology and Clinical
Neurophysiology, Department of Neuromuscular Disorders,
Brain Center Rudolf Magnus, University Medical Center
Utrecht, the Netherlands
Anders Fuglsang-​Frederiksen, Department of Clinical
Neurophysiology, Aarhus University Hospital, Denmark
Paul L. Furlong, Aston Brain Centre, School of Life and Health
Sciences, Aston University, Birmingham, UK
Sushma Goyal, Consultant Paediatric Clinical Neurophysiologist,
Evelina London Children’s Hospital, Puffin EEG Department, St
Thomas’ Hospital, London, UK
Robin Howard, Department of Neurology, The National Hospital
for Neurology, Neurosurgery and Psychiatry, London, UK
James Howells, Bill Gole MND Fellow, Brain and Mind Centre,
and Sydney Medical School, University of Sydney, Australia
John G. R. Jefferys, Professor of Neuroscience and Senior
Research Fellow, Department of Pharmacology, University of
Oxford, UK
Robin P. Kennett, Consultant in Clinical Neurophysiology, Oxford
University Hospitals NHS Trust, UK
Matthew C. Kiernan, Brain and Mind Centre, Sydney Medical
School, University of Sydney, Australia
Roo Killick, Sleep Physician & Postdoctoral Research Fellow,
Woolcock Institute of Medical Research and Sydney Medical
School, University of Sydney, NSW, Australia
Jun Kimura, Department of Neurology, University of Iowa Health
Care, Iowa City, USA
Michalis Koutroumanidis, Department of Neurology and
Department of Clinical Neurophysiology and Epilepsy, Guy’s
and St Thomas’ NHS Foundation Trust, London, UK
xiv  contributors
Marian Lazaro, Nerve and Brain Studies Department, Guy’s
and St Thomas NHS Foundation Trust, London, UK;
Neurophysiology Department, Evelina London Children’s
Hospital, St Thomas’ Hospital, London, UK
Cindy S-​Y Lin, Translational Neuroscience Facility, School of
Medical Sciences, University of New South Wales, Australia
Kerry R. Mills, Emeritus Professor of Clinical Neurophysiology,
Department of Basic and Clinical Neuroscience, King’s College
London, UK
V. Peter Misra, Consultant Clinical Neurophysiologist, Imperial
College Heathcare NHS Trust, Hammersmith Hospital,
London, UK
Friederike Moeller, Department of Neurophysiology, Great
Ormond Street Hospital for Children, London, UK
Marc R. Nuwer, Professor and Vice Chair, Department of
Neurology, David Geffen School of Medicine, Department
Head, Clinical Neurophysiology, Ronald Reagan UCLA Medical
Center, University of California, Los Angeles, USA
Susanna B. Park, Brain and Mind Centre, Sydney Medical School,
University of Sydney, Australia
Matthew Pitt, Consultant Clinical Neurophysiologist, Department
of Clinical Neurophysiology, Great Ormond Street Hospital for
Children, London, UK
Ronit M. Pressler, Clinical Neurosciences Section, UCL Institute
of Child Health, Great Ormond Street Hospital for Children,
London, UK
Kirsten Pugdahl, Department of Clinical Neurophysiology, Aarhus
University Hospital, Denmark
Michel J. A. M van Putten, Neurologist/​Clinical neurophysiologist,
Professor of Clinical Neurophysiology, Hospital Medisch
Spectrum Twente, Department of Clinical Neurophysiology
and Clinical Neurophysiology (CNPH), MIRA-​Institute for
Biomedical Technology and Technical Medicine, Faculty of
Science and Technology, University of Twente, Enschede, the
Netherlands
Dimitrios Sakellariou, Department of Clinical Neurophysiology
and Epilepsy, Guy’s and St Thomas’ NHS Foundation Trust,
London, UK; Department of Academic Neurosciences, King’s
College London, UK; Neurophysiology Unit, Department of
Physiology, School of Medicine, University of Patras, Greece
Donald B. Sanders, Professor of Neurology, Duke University
Medical Center, Durham, NC, USA
Stefano Seri, Aston Brain Centre, School of Life and Health
Sciences, Aston University, Birmingham, UK
Erik Stålberg, Department of Clinical Neurophysiology, Section of
Neuroscience, Uppsala University, Sweden
Dick F. Stegeman, Medical Physicist, Radboud University
Medical Center Nijmegen, Department of Neurology/​Clinical
Neurophysiology, Donders Institute for Brain, Cognition and
Behaviour, Nijmegen, the Netherlands
Michael Swash, Emeritus Professor of Neurology, Barts & the
London School of Medicine, Queen Mary University of
London, UK; Consultant Neurologist, Royal London Hospital,
UK; Professor of Neurology, University of Lisbon, Portugal
Hatice Tankisi, Department of Clinical Neurophysiology, Aarhus
University Hospital, Denmark
Vasiliki Tsirka, Department of Clinical Neurophysiology and
Epilepsy, Guy’s and St Thomas’ NHS Foundation Trust, London,
UK; Department of Academic Neurosciences, King’s College
London, UK
Kanjana Unnwongse, Section of Adult Epilepsy, Department of
Neurology, Prasat Neurological Institute, Bangkok, Thailand
Antonio Valentín, Department of Basic and Clinical
Neuroscience, Institute of Psychiatry, Psychology and
Neuroscience, King’s College London, UK; Department
of Clinical Neurophysiology, King’s College Hospital NHS
Trust, London, UK; Departamento de Fisiología, Facultad de
Medicina, Universidad Complutense, Madrid, Spain
Josep Valls-​Solé, EMG Unit, Neurology Department, University of
Barcelona, Hospital Clinic, Barcelona, Spain
Matthew C. Walker, Professor of Neurology, UCL Institute
of Neurology and National Hospital for Neurology and
Neurosurgery, Queen Square, London, UK
Tim Wehner, Department of Clinical and Experimental Epilepsy,
Institute of Neurology, University College London, UK;
Department of Clinical Neurophysiology, National Hospital
for Neurology and Neurosurgery, Queen Square, London, UK
Caroline Witton, Aston Brain Centre, School of Life and Health
Sciences, Aston University, Birmingham, UK
Zenobia Zaiwalla, Consultant in Clinical Neurophysiology and
Non Respiratory Paediatric and Adult, Sleep Disorders Lead,
John Radcliffe Hospital, Oxford, UK
Machiel J. Zwarts, Kempenhaeghe, Academic Centre for Epilepsy,
Heeze, The Netherlands
1

SECTION 1

Scientific basis of clinical

neurophysiology
2
3
CHAPTER 1
Nerve, muscle, and
neuromuscular junction
Machiel J. Zwarts
Introduction
A thorough understanding of anatomy and physiology is essen-
tial for every clinical neurophysiologist. In this chapter, the basics
of the physiology of nerve and muscle function with respect to
signal transduction are presented. Although this information is
also essential for the workings of the brain, the measurements of
the electromyographer have a more direct relevance with these
basics. For example, with single fibre electromyograph (EMG) the
transmission at a single neuromuscular junction can be studied
in detail. The same applies to pathology. Many peripheral nerve
disorders and abnormalities, for example, conduction block, can
be directly understood from the physiology of nerve action poten-
tial generation and conduction. Therefore, some emphasis is made
upon the peripheral nervous system.
The membrane potential
Every cell is surrounded by a membrane, typically a lipid bilayer.
In this membrane numerous special proteins and receptors reside.
They all have different functions related to transport, either active
or passive. The inner part of the cell is usually electro-​negative
with respect to the outer part. Using a micropipette one can
measure this potential difference of about 60–​100 mV (negative
inside). This is known as the resting membrane potential or trans-
membrane potential. A large part of this potential difference is
explained by the different concentrations of ions between extra-
cellular and intracellular compartments (1–​3).
The classic example to explain this is taken from a large con-
tainer filled with water and divided by a semipermeable mem-
brane (Fig. 1.1). On one side of the membrane, a salt is added to
the water, which dissolves into positively and negatively charged
ions. Consequently, depending on the permeability of the mem-
brane for the ion, some of the ions move through the membrane
because of the concentration gradient. However, this is immedi-
ately accompanied by an opposing force due to the developing
electrical gradient (if the ions are positively charged, the diffu-
sion of ions will result in a negatively charge in the compartment
from which they leave). A new equilibrium will arise between the
forces due to concentration gradient and the electrochemical gra-
dient. This equilibrium is described by the Nernst equation:
E1 = RT ln [I]O / ZF [I ]i
where E is the transmembrane potential, R the gas constant, F the
Faraday constant, T the absolute temperature, Z the charge of the
ions, and [I]‌o and [I]i the outer and inner concentrations of the ion,
respectively.
Using physiological concentrations of potassium, the calculated
transmembrane potential inside the cell is –​84 mV with respect to
the outside, which is close the normal resting value of the mem-
brane potential.
Indeed, the resting membrane potential of nerve cells, includ-
ing axons is usually governed mainly by the concentration gradi-
ent of potassium, with low extracellular concentrations and high
intracellular concentrations. For muscles, the situation is slightly
different (vide infra).
The concentrations gradients for different ions are usually
rather high. Another example is sodium, being high extracellu-
lar (~140 mM) and low intracellular (~12 mM). These gradients
high low
– + +
+ –
– +
+
– –
+
+
+ –
– + +
+ +
–
Fig. 1.1 Schematic presentation of a container with fluid divided by a
semipermeable membrane. The membrane does not permit diffusion of the
anions. The positively charged cations follow the concentration gradient, moving
to the right, but thereby create an electrochemical gradient. The left part of the
container becomes negative with respect to the right side. The two opposing
forces reach an equilibrium described by the Nernst equation.
4
4 Section 1 scientific basis of clinical neurophysiology
are maintained by active and thus energy dependent-​pumping
processes. The most important is the Na–​K pump that transports
3 Na+ ions from inside to outside, for 2 K+ ions from outside to
inside the cell. This is an energy-​dependent process consuming
adenosine triphosphate (ATP).
It should be realized that we speak here of bio-​electricity. In
fact, the currents and voltage differences in the body are based
on the concentration and diffusion of charged ions. This is com-
pletely different from the electricity as we know it in our world of
toasters and television sets. Here, the electricity is based on the
flow of electrons. The transition of bio-​electricity to the electricity,
as we know it, occurs at the electrode-​skin interface.
Ion channels
Specialized proteins in the cell membrane make it possible to
use the transmembrane potential as the driving force to gener-
ate action potentials that conduct along the neurons, dendrites
and axons, as well as along the muscle membrane (4–​8). These
proteins span the axon, neuron, or muscle membrane, and con-
sist of different subunits that allow conformational changes—​ion
channels. Nowadays, for every ion, whole families of channels are
known (9). The channel usually consists of subunits, and one or
more smaller subunits. Each subunit is formed of multiple (often
six) transmembrane-​spanning elements (see Fig. 1.2). The central
part of the channel (the pore) is water filled and allows passage
of ions. Usually, the channel is ion specific to a greater or lesser
degree. If the inner pore is open, the ion can enter or leave the cell
without hindrance (following its electrochemical gradient) and, if
closed, the permeability for the ion is very low. The opening and
closing of the channel is called gating. Depending on the channel,
the state can be closed as default, e.g. Na+ channels, these open
Nav channel
I II
– –
+ – + –
1 2 34 5 6 12 345
+ +
Pore
Voltage
sensing
Amino
terminus
Fig. 1.2 Schematic presentation of the voltage gated Na+ channel with subunits. Voltage sensing is accomplished by subunit I, the fourth segment, indicated on
the left.
Adapted from Nature, 409, Sato C, Ueno Y, Asai K, Takahashi K, Sato M, Engel A, and Fujiyoshi Y, The voltage-​sensitive sodium channel is a bell-​shaped molecule with several cavities,
pp. 1047–​51, copyright (2001), with permission from Nature Publishing Group; Science STKE, 2004(253), Yu FH and Catterall WA, The VGL chanome: a protein superfamily specialized for
electrical signaling and ionic homeostasis, pp. re15, Copyright (2004), with permission from American Association for the Advancement of Science.
on a change in membrane potential, so-​called voltage-​dependent
channels. Some K+ channels are not voltage dependent, but they
open and close in a random matter. Other channels are ligand
specific and respond to opening when in contact with a certain
neurotransmitter.
The voltage-​dependent Na+ channel consists of one principal
subunit, the alpha subunit with four homologous repeats. In addi-
tion, one beta subunit is present. The fourth segment of the alpha
subunit is the voltage sensing part (Fig. 1.2). This voltage sensing
part consists of charged amino acids that are displaced by the
transmembrane voltage field. As a result, the pore of the channel
undergoes a conformational change and the net result is a large
increase in Na+ conductance. Following this activation, the Na+
channel inactivates, probably by another part of the alpha subunit
(repeats III–​IV). Both a fast and slow inactivation of the channel
has been described.
The action potential
The Na+ and K+ channels play key roles in the generation of action
potentials (2,3,6).
Following a local depolarization of the membrane of around –​
20 mV to a threshold value of –​70 mV, the Na+ channel undergoes
a conformational change accompanied by a considerable increase
in Na+ permeability. Consequently, the membrane potential
approaches the resting state potential of Na+ (about +40 mV;
Fig. 1.3). Within 1 ms following the above described events, the
Na+ channels are inactivated; at the same time, K+ channels start
to open allowing K+ to leave the cell. These processes permit the
membrane potential to be restored. In the period of inactivation
of the Na channels, the membrane is completely refractory to a
new depolarization (absolute refractory period) and afterwards
III IV
– –
+ + +
6 12 345 6 12 345 6
+ +
h
Inactivation
Carboxy
terminus
5

Chapter 1 nerve, muscle, and neuromuscular junction 5

50 ENa a positive potential, at the place of the depolarization itself this

Squid axon reverses to negative and in the trailing phase of the potential, a
action potential positive deflection occurs again (see also Chapter 6 and ref. (2)).

Open channels per µm2 of membrane

18.5° C Essentially, this triphasic form is the basic form of all extracellu-
EM
lar measurements near an axon or muscle fibre. Another impor-
0
tant point is that the display of action potentials and the resulting
measurements are usually provided as voltage changes against
Membrane potential (mV)

40 time (see Fig. 1.3), based upon a point measurement at a certain

Na channels
–50
Ek
0 1
Time ms
0 25
Distance (mm)
Fig. 1.3 Action potential of a giant squid axon. Note the increase of open Na
channels, producing the rise of the membrane potential and the subsequent rise
in K channels responsible for the repolarization and overshoot of the membrane
potential.
Adapted from Hille B, Introduction to physiology of excitable cells. In: Patton HD, Fuchs AF,
Hille B, et al. (Eds), Textbook of physiology, 21st edn. copyright (1989), with permission from
Elsevier.
is partially refractory. Following an overshoot of the mem-
brane potential (after-​hyperpolarization), the initial equilibrium
emerges again (Fig. 1.4). Intracellularly, the action potential is
a monophasic, positive potential. Extracellularly, however, the
situation is more complicated. The current is spread in a large
volume conductor and in addition travels along the nerve. The
result is basically a triphasic waveform. The leading part of the
action potential approaching a recording electrode first generates
Action potential
+30
zation
potential (mV)
position. In space, the action potential has a considerable physi-
cal spread. For example, an action potential of 1.5 ms duration
20
K channels and a conduction velocity of 50 m/​s has a physical spread along
the nerve of 75 mm (50 m/​s = 50 mm/​ms, in 1.5 ms a distance of
0 1.5 × 50 mm = 75 mm is travelled). Since extracellular action
potentials are always measured as the difference between two
electrodes, this large spatial spread can easily make both record-
ing electrodes active with respect to the action potential and
Local circuit currents
thereby influence the recorded amplitude.
The conduction of the action potential is generated by the pas-
sive spread of current that induces a depolarization further ahead
in the membrane. This process generates the same changes in
nearby voltage-​dependent Na channels, thereby producing a
regenerative potential travelling along the axon.
2 3 4
50 75
Saltatory conduction and conduction
velocity
The above described processes of conduction hold for the unmyeli-
nated axon. However, many axons are myelinated. Schwann cells
(in the peripheral nervous system) lying near the axon are wrapped
around the axon, thereby creating an electrical insulation of the
axon. In the brain, the oligodendrocyte fulfils the same purpose
(5,7). The resistance of the membrane at the insulated parts is up to
300 times higher. Between the covered parts of the axon, small bare
parts of axon exist at regular intervals that are called the nodes of
Ranvier. Due to this configuration, the action potential leaps from
node to node, the insulated parts of the axon cannot be depolar-
ized. This way of conduction is less energy consuming. Secondly,
the conduction velocity rises enormously, typically from 2–​4 ms
to 40–​60 m/​s in the human peripheral nervous system. The axon
membrane at the nodes of Ranvier is highly specialized to make
this possible, with a very high concentration of voltage-​gated Na
channels, which facilitates uninterrupted conduction.
The conduction velocity depends on a large number of fac-
tors, an important factor being the temperature. Since all these
processes are dependent on metabolism, a low temperature will
slow the conduction. Furthermore, the resistance of the axon is
important; this depends largely on the internal resistance, which
is related in a square root manner to the diameter. In myelinated

0
Menbrane

Repolari

axons, the conduction velocity is linearly related to the diameter

Depolari

of the axon. The capacitance of the membrane is also important—​

a large capacitance implies that more charge is needed to depolar-
zation

Resting ize the membrane at a certain point.

–70 potential From a clinical perspective, it is important to understand the
important influence of temperature on the conduction velocity.
1 2 3 4 5 6
Temperature at the feet can easily reach 20–​25°C in countries with
Time (ms)
temperate or more harsh climates. This not only influences the
Fig. 1.4 Change in membrane potential during an action potential. The duration conduction, but also the amplitude of the recorded potentials. In
of the action potential is roughly 1–​1.5 ms. pathology, demyelination is an important factor causing reduced
https://​psychlopedia.wikispaces.com/​action+potential velocities or even conduction block.
6
6 Section 1 scientific basis of clinical neurophysiology
In addition specialized areas of the nodes of Ranvier and on
the axon cell body have membrane domains with specialized
function. One of them is the initial axon segment. It contains
clusters of ion channels, such that the segment has the lowest
threshold for firing, thus serving to integrate synaptic input to
the nerve cell.
Neuromuscular junction
and other synapses
Another highly specialized region of the motor axon is its termi-
nal part where it connects to the muscle (10,11). Here, the action
potential is transferred to the muscle by means of chemical neu-
rotransmission. The motor nerve branches into many small twigs,
each innervating a single muscle fibre. The end of the nerve twig is
called a bouton. It contains many mitochondria and microtubules
on one side, and vesicles clustered about membrane thickenings
at the other (Fig. 1.5). The muscle membrane underlying this bou-
ton is also specialized, it contains many folds, thereby increasing
its surface area to about eight times the axon terminal side. At
the summit of the junctional folds, a very high number of acetyl-
choline receptors (Ach) receptors are present. The synaptic cleft
between muscle and axon is about 20–​30 nm wide.
The action potentials arriving at the neuromuscular junction
give rise to a strong influx of calcium through voltage-​gated
Ca channels. This, in turn, triggers the release of ACh through
a cascade of intracellular signalling events terminating in the
induction of exocytosis of small vesicles which contain about
Myelin
Schwann
cell
Basement
membrane
Synaptic
space
Muscle
Fig. 1.5 The neuromuscular junction with above the ending of the motor axon in a specialized region, where Ca2+ influx following an action potential is the trigger
for Ach-​containing vesicles to be released. The released ACh crosses the synaptic cleft and reaches the specialized area of the muscle with many folds containing ACh
receptors responsible for a local depolarization of the muscle membrane, which is the trigger of a propagated action potential along the muscle fibre.
Reproduced from Anaesthesia, 64(Suppl. 1), Martyn JAJ, Jonsson Fagerlund M, Eriksson LI, Basic principles of neuromuscular transmission, pp. 1–​9, copyright (2009), with permission from
John Wiley and Sons.
5000–​10,000 ACh molecules each. About 100 vesicles are released
by every action potential. Every neuromuscular junction (NMJ)
contains about 200,000–​400,000 vesicles of which 1000–​30,000
lie in the immediate surroundings of the so-​called active zones.
These active zones contain the vesicles that are released by an
action potential. The much larger pool of vesicles lying further
away from the membrane, serve as a reserve pool. Following
the release of ACh containing vesicles, ACh crosses the synap-
tic cleft in a fraction of a millisecond and binds to ligand gated
ACh receptors in the muscle membrane resulting in a depolariza-
tion of about 90 mV. This is called the endplate potential (EPP).
Usually, a depolarization of about 10–​15 mV is enough to gener-
ate an action potential in the extrasynaptic muscle membrane.
This 90 mV depolarization is more than enough to trigger voltage
gated Na channels in the extrasynaptic muscle membrane lead-
ing to a propagated action potential along the muscle fibre in both
directions. In the depth of the folds of the NMJ a very high con-
centration of Na channels is present to facilitate this process. The
propagated muscle action potential halts at the tendon. Similar
to nerve conduction, the conduction along the muscle membrane
also depends on temperature and diameter of the muscle fibre
(12,13). It is comparable with the conduction of unmyelinated
nerve axons (~4 m/​s).
It should be noted that the magnitude of the EPP is not fixed.
It is dependent on factors related to presynaptic (number of vesi-
cles released and vesicle content), post-​synaptic (number of Ach
receptors), and synaptic cleft factors, such as the acetylcholinest-
erase (AChase) activity. Furthermore, the EPP amplitude is also
Mitochondrion
Nerve
Mitocrotubules
Nerve
terminal Active zone or
release site
Acetylcholinesterase
Acetylcholine receptors
Primary Secondary
cleft cleft
Na+
channels
Actin-myosin
complex
7
Chapter 1
dependent on the firing history of the axon. Following repetitive
stimulation several phases of potentiation are recognized with dif-
ferent time courses.
After its release, the ACh is hydrolysed by AChase in a rapid
and effective way. The resulting choline is used by the nerve ter-
minal again to form ACh after its uptake. Except for the release
of a large number of ACh containing vesicles following an action
potential, single vesicles are also released spontaneously in a ran-
dom manner. This results in small depolarizations of the muscle
membrane of about 1 mV; these are called miniature endplate
potentials (MEPP). They result in a small depolarization of the
muscle membrane, insufficient to produce a self-​sustaining action
potential, but only giving electrotonic spread of the current.
However, with needle EMG these depolarizations can be recorded
as endplate noise.
The NMJ is just an example of a specialized synapse. In the
brain, the connection between neurons consists of a multitude
of different synapses. However, the basic layout is the same as
for the NMJ. Many different neurotransmitters are known,
either excitatory or inhibitory. Examples are glutamate, sero-
tonin, acetylcholine, etc. Glutamate is by far the most impor-
tant excitatory neurotransmitter in the brain. Every neuron in
the brain receives many thousands of excitatory and inhibitory
inputs via these synapses on the dendritic tree, cell body, but
also the axon hillock. The net result of all these influences deter-
mines the membrane potential and thus the firing behaviour of
the cell.
Muscle membrane, t-​tubules,
and excitation-​contraction coupling
As stated above, the action potential originating at the NMJ travels
in both directions along the muscle membrane with a conduction
velocity of about 4 m/​s (12,13). Since most NMJs are placed more
(A)
Z-disk
I-band
Sarcomere
A-band
M-line
Z-disk
T-tubule SR TC
Sarcolemma
Fig. 1.6 (A) The propagated action potential along the sarcolemma (on the left) is conducted into the T tubule, which leads to extrusion of Ca2+ from the
sarcoplasmatic reticulum and triggers the actin myosine proteins to contract by sliding of the filaments and shortening the sarcomere. (B) The DHPR receptors are
shown, which are voltage sensitive and activate the release of Ca2+ via the RyR1 receptors.
Adapted from Prog Biophys Mol Biol, 108(3), Hernandez-​Ochoa EO and Schneider MF, Voltage clamp methods for the study of membrane currents and SR Ca release in adult skeletal muscle
fibers, pp. 98–​118, copyright (2012), with permission from Elsevier.
nerve, muscle, and neuromuscular junction 7
or less at the centre of the muscle fibre, an even contraction of the
muscle is assured. Since the motor axons divide into many twigs
each innervating one muscle fibre, both during voluntary activa-
tion and as a result of stimulating the motor nerve, a summation
of hundreds of more or less synchronously activated muscle fibre
action potentials can be recorded by the clinical neurophysiolo-
gist. This amplification effect is very helpful, since in this way it
is easy to record (for example, with needle EMG), the firings of a
single motor neuron.
The action potential of the sarcolemma is generated in a similar
manner as the nerve action potential. An important difference,
however, is the conductance of the chloride channels, which is high
in muscle (as opposed to axons) and important in determining
the resting membrane potential and in the repolarization phase
of the muscle membrane (14–​16). Therefore, the afterdepolariza-
tion of the muscle action potential is slow. The propagated action
potential along the sarcolemma also enters the t-​tubule system,
specialized invaginations of the sarcolemma (Fig. 1.6A). Here, we
encounter a special situation where the extracellular space is con-
fined to a small tubule. As a consequence, the concentration of
extracellular ions that accumulate after action potentials can rise
to high levels, especially during rapid firing of the motor unit. The
high conductance of the muscle membrane for chloride assures
that this will not happen, as it passively follows the Na+, thereby
restoring the membrane depolarization quickly (14).
Depolarization of the transverse tubules is detected by voltage-​
sensitive Ca 2+ channels (Cav), also known as dihydropyridine
receptors (DHPRs), and these communicate directly with Ca 2+
channels, also known as ryanodine receptors (RyRs), which can
deliver far more calcium than can enter through the Ca 2+ chan-
nels themselves (17,18) (Fig. 1.6B).
The consequent increased concentration of intracellular Ca 2+
is bound by troponin C (TnC), which triggers contraction.
Consequently, a segment of actin becomes available to myosin as
(B)
T-tubule
+ +
DHPR – –
(Cav1.1) + + + +
– –
C
II-III loop
N
C
SR
RyR1
8
8 Section 1 scientific basis of clinical neurophysiology
one tropomyosin is moved away from the myosin-​binding site on
actin. The subsequent binding of myosin to actin generates force
and shortening of sarcomeres. At low intracellular Ca2+ concen-
trations, tropomyosin blocks the myosin-​binding site on actin.
The contraction of the muscle itself is realized by supramolecu-
lar structures, the sarcomeres (19,20). These consist of thick and
thin filaments composed of myosin and actin, respectively. These
are positioned intertwined with each other, partly overlapping.
The molecular motor is myosin, which is attached at the thin
filaments and is an elongated molecule with a tail and a head.
The head is the moving part of the molecule and responsible for
force generation. It is attached at actin (cross-​bridge). After bind-
ing to ATP actin and myosin dissociate, ATP hydrolysis occurs
(producing inorganic phosphate (Pi) and adenosine diphosphate
(ADP)), which is followed by a conformational change of the
head and binding of actin to myosin again. The release of Pi is
followed by another conformational change in the head of the
myosin molecule and transmitted to the actin molecule resulting
in a power stroke. As long as Ca is freely bound within the thin
filaments and ATP is available this cross-​bridge cycling contin-
ues. However, Ca 2+ is taken up again swiftly following an action
potential by the sarcoplasmatic reticulum and the force produc-
tion ceases.
As described above, a single action potential along a motor
axon gives rise to the simultaneous contractions of a few hundred
muscle fibres, which are all governed by this motor neuron (the
motor unit) resulting in a twitch. The peak force of a single twitch
is about 10–​20% of the maximal force of the motor unit. At high
frequencies a fused tetanic contraction can be obtained resulting
in maximal force, this occurs at frequencies around 40 Hz.
In conclusion, a survey is provided of the essential workings of
the excitable cell, the way membrane potentials originates, and the
depolarization of the membrane through voltage-​dependent ion
channels. The consequent transmission of action potentials and
conveying of information to other neurons is described. Finally,
neuromuscular transmission and the activation of the muscle
membrane are discussed, resulting in contraction. At all levels,
neurological diseases can affect proper functioning of these sys-
tems resulting in abnormalities the clinical neurophysiologist
encounters in his daily practice. These are discussed in subsequent
chapters.
References
1. Di Resta, C. and Becchetti, A. (2010). Introduction to ion channels.
Advances in Experimental Medicine and Biology, 674, 9–​21.
2. Dumitru, D., Stegeman, D.F., and Zwarts, M.J. (2002). Electric
sources and volume conduction; Appendix: the leading/​trailing
dipole model and near-​field/​far-​field waveforms. In: Electrodiagnostic
medicine (Eds D. Dumitru, A. M. Amato, and M. J. Zwarts), 2nd edn,
pp. 27–​67. Philadelphia, PA: Hanley and Belfus, Inc.
3. Putten, van M.J.A.M. (2009). Essentials of neurophysiology.
Berlin: Springer.
4. Ashcroft, F.M. (2000). How channels work. In: Ion channels and
disease (Eds F. M. Ashcroft), pp. 21–​158. London: Academic Press.
5. Rasband, M.N. (2011). Composition, assembly, and maintenance of
excitable membrane domains in myelinated axons. Seminars in Cell
& Developmental Biology, 22(2), 178–​84.
6. Debanne, D., Campanac, E., Bialowas, A., Carlier, E., and Alcaraz, G.
(2011). Axon physiology. Physiological Review, 91, 555–​602.
7. Rasband, M.N. (2011). Composition, assembly, and maintenance of
excitable membrane domains in myelinated axons. Seminars in Cell
& Developmental Biology, 22(2), 178–​84.
8. Hille, B. (1989). Introduction to physiology of excitable cells.
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et al., 21st edn, pp. 1–​80. Philadelphia, PA: WB Saunders.
9. Yu, F.H., Yarov-​Yarovoy, V., Gutman, G.A., and Catterall, W.A.
(2005). Overview of molecular relationships in the voltage-​gated ion
channel superfamily. Pharmacological Reviews, 57, 387–​9510
10. Martyn, J.A.J., Jonsson Fagerlund, M., and Eriksson, L.I. (2009).
Basic principles of neuromuscular transmission. Anaesthesia,
64(Suppl. 1), 1–​9.
11. Nishimune, H. (2012). Active zones of mammalian neuromuscular
junctions: formation, density, and aging. Annals of the New York
Academy of Sciences, 1274(1), 24–​32.
12. Blijham, P.J., ter Laak, H.J., Schelhaas, H.J., van Engelen, B.G.M.,
Stegeman, D.F., and Zwarts, M.J. (2006). Relation between muscle
fiber conduction velocity and fiber size in neuromuscular disorders.
Journal of Applied Physiology, 100, 1837–​41.
13. Arendt-​Nielsen, L. and Zwarts, M.J. (1989). Measurement of muscle
fiber conduction velocity in human—​techniques and applications.
Journal of Clinical Neurophysiology, 6, 173–​90.
14. Bretag, A.H. (1987). Muscle chloride channels. Physiological Reviews,
67, 618–​724.
15. Jurkat-​Rott, K., Fauler, M., and Lehmann-​Horn, F. (2006). Ion
channels and ion transporters of the transverse tubular system
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275–​90.
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extracellular chloride concentration in mammalian skeletal muscle
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methods for the study of membrane currents and SR Ca release
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9
CHAPTER 2
The motor unit
David Burke and James Howells
What is a motor unit?
The term ‘motor unit’ refers to the lower motor neuron (or ‘moto-
neuron’), its axon, and the few hundred muscle fibres that it inner-
vates. The term is generally reserved for α motoneurons, which
innervate the force-​producing muscle fibres of skeletal muscle
(termed ‘extrafusal’ muscle fibres, as distinct from the ‘intrafusal’
muscle fibres of muscle spindles, which are innervated by γ moto-
neurons). So-​called β motoneurons branch to innervate both
extrafusal and intrafusal muscle. The properties of the motoneu-
ron, its axon, and the muscle fibres that it innervates are matched.
This chapter will consider the motor units of skeletal muscle and
will focus on those innervating the limbs.
The α motoneurons recruited first in a voluntary contraction, by
transcranial stimulation of the motor cortex or by reflex action are
of small size, in accordance with the so-​called ‘size principle’ (1).
They have axons of relatively small diameter (and consequently
slow conduction velocity) and innervate a relatively small number
of ‘red’ muscle fibres, which produce small twitch contractions
that are resistant to fatigue (Fig. 2.1). On the other hand, the first
axons activated by weak electrical stimulation of motor axons in
the peripheral nerve tend to be of large diameter and conduction
velocity. The parent motoneurons are larger, and the twitch con-
tractions produced by their ‘white’ muscle fibres produce greater
force, with a greater tendency to fatigue.
The term ‘motor unit’ is often used to refer to the motor unit
action potential (MUAP), which is the electromyograph (EMG)
signature of the motor unit, due to the summed activity of the
muscle fibres (or single fibre action potentials (SFAPs); see
Chapter 7) innervated by the single motor axon. The size and
shape of individual MUAPs vary with the distribution of muscle
fibres within the muscle, their proximity to the recording elec-
trodes, and their depth within the muscle, whether one uses sur-
face electrodes or intramuscular needles or wires. High-​density
recording techniques have been developed that allow the activ-
ity of multiple single units to be identified in surface recordings,
using multiple closely spaced electrodes fixed to the skin over
the contracting muscle (2–​4). In routine diagnostic studies using
intramuscular needle electrodes, commercial EMG machines now
allow the activity of different motor units to be identified during
voluntary contractions using spike identification and interference
pattern decomposition.
EMG activity can be used to measure the activity of α moto-
neurons, termed the ‘final common path’ by Sherrington (5), thus
allowing insight into the descending and reflex influences that
play on the motoneuron pool. EMG potentials are the usual output
measured in motor control studies, whether the EMG activity is
part of a voluntary contraction, due to a reflex process or due to
transcranial stimulation. As mentioned above, the activity of a
single motor unit can often be recorded, and this provides infor-
mation about the behaviour of a single α motoneuron. Unless
selective recording techniques are used, this will be a low-​
threshold motor unit because it is difficult to distinguish indi-
vidual MUAPs when many are active. Studying the behaviour of
single units can be important because conclusions based on the
behaviour of the whole motoneuron pool rely on the assump-
tion that it behaves in a homogeneous way to inputs and that it
does so with a linear input/​output relationship (6). This does not
always occur, the best example being that cutaneous inputs can
alter motor unit recruitment threshold by raising the threshold
for voluntary activation of small motor units and lowering it for
larger motor units (7).
Motoneuron
Motoneurons have been considered passive responders to the net
sum of the excitatory and inhibitory inputs acting on them, but it
is clear that they can respond to neuromodulators and intracel-
lular messengers by changing the intrinsic properties of the cell
membrane and their responsiveness to inputs. The motoneurons
considered in this Chapter are located in the grey matter of the
anterior horn of the spinal cord, predominantly in Rexed’s lamina
IX (8), in columns extending over a number of segments overlap-
ping with those for adjacent muscles. In early development, there
are more motoneurons than in adulthood, the excess being lost
by apoptosis, in part because they do not receive neurotrophic
factor support from the innervated muscle. As mentioned above,
motoneurons fall into two groups, correlated with their size. α
motoneurons are larger and innervate skeletal muscle (the so-​
called ‘extrafusal’ muscle). Small γ motoneurons innervate the
intrafusal muscle of the muscle spindle and will not be consid-
ered further in this chapter. [The so-​called β motoneurons, which
innervate both extra-​and intrafusal muscle, are of size similar to
that of α motoneurons.]
Morphology
The motoneuron has an extensive pattern of dendrites, which
increase the extent and surface area over which excitatory and
inhibitory inputs to the motoneuron form synapses that regulate its
excitability and discharge. Each motoneuron has one axon, which
arises from the cell body at a specialized region, the axon hillock,
and which extends from the anterior horn through the anterior
root into the peripheral nerve to innervate the relevant muscle—​a
length of as much as 1 m or more (Fig. 2.1). Acetylcholine is the
10

10 Section 1 scientific basis of clinical neurophysiology

ce

s
an

re
fib
ist

nt
cv
y

d
es

a
od

cle
l

ist
ol

na
tr

h
ll b

sh

us

s
itc
xo
pu

re
re

Im
ce

tw
ra

ue
in

th
all

we

pe

tig
gh

w
w
Sm

Slo
Ty
Lo

Lo
Hi

Fa
Twitch contraction Tetanic contraction

ACh
ct ½rt

ACh

Graded
depolarization Then saltatory ct ½rt 100 ms 10 s
at axon hillock conduction
La
rg
Lo

Hi

Fa

Ty

Fa

Fa
ec
ste

st
gh
w

pe

tig
ell

tw
in

ra
th

ua
II m
bo
p

itc
re

xo

bl
ut

dy

us
s

e
h
n
ho
r

al

cle
es

dl

cv
ist

fib
anc

re
s
e

Fig. 2.1 The motor unit. Cell body, axon, innervated muscle fibres, twitch contraction, and force of tetanic contraction for a small and for a large motoneuron.
The muscle fibres are ‘red’ (type I) for the small motoneuron and ‘white’ (type II) for the large motoneuron. ‘Threshold’ refers to the threshold for recruitment of
the motoneuron in voluntary and reflex contractions, not the threshold of the axon to electrical stimulation (which tends to be lower the larger the axon).
ct = contraction time; ½rt = half relaxation time; cv = conduction velocity; ACh = acetylcholine, the transmitter released at the neuromuscular junction. Force profiles are illustrative and
uncalibrated.

excitatory transmitter at its terminals at the neuromuscular junc-
tion and is also the transmitter on the recurrent axon collaterals
that project to Renshaw cells.
Synaptic actions
Excitatory post-​synaptic potentials (EPSPs) and inhibitory post-​
synaptic potentials (IPSPs) are summed at the axon hillock. The axon
hillock terminates with the first myelin segment, at a ‘heminode’
(Fig. 2.1). An action potential is triggered if the membrane potential
threshold is exceeded. It then propagates in an ‘all-​or-​none’ manner
along the motor axon ‘jumping’ from node of Ranvier to node of
Ranvier (saltatory conduction), ultimately invading the motor nerve
terminals innervating the muscle fibres of the motor unit. EPSPs are
brief depolarizing potentials, resulting from the opening of ligand-​
gated channels by the excitatory transmitter, glutamate, which is
released from the presynaptic terminals. The reaction of glutamate
with its receptors on the post-​synaptic membrane opens the channel
and allows an inward flow of positive ions (Na+, K+, Ca2+) into the
post-​synaptic cell. EPSPs may be graded in size, dependent on the
number of active boutons that the presynaptic axon has on the cell.
They have a slow decay, allowing temporal summation of the excita-
tory effects of closely spaced inputs in different axons. Not all synap-
tic boutons are necessarily invaded every time there is an impulse in
the parent axon and its branches. The phenomenon of post-​tetanic
potentiation is probably due to the activation of a greater percentage
of the synapses from an afferent on the motoneuron, i.e. to the acti-
vation of previously ‘silent’ synapses.
Similarly, IPSPs are brief hyperpolarizing potentials, resulting from
the opening of ligand-​gated channels by the inhibitory transmitter,
glycine, which is released from the presynaptic terminals and trig-
gers a Cl–​ current that causes transient hyperpolarization. The action
of glycine is antagonized by strychnine. A major contribution to the
IPSP is the conductance change in the motoneuron, independent of
the change in membrane potential that it produces (9).
Gamma amino butyric acid (GABA) is the neurotransmitter
responsible for ‘presynaptic inhibition’ of group Ia terminals on
motoneurons. The anatomical substrate is an axo-​a xonal synapse
in which the axons from a presynaptic inhibitory interneuron
synapse with the presynaptic terminals of the incoming afferent
fibres. Activity at this synapse produces a depolarization of the
afferent terminals (so-​called ‘primary afferent depolarization’).
This reduces the amount of excitatory transmitter released at the
synapse and thereby decreases transmission at that synapse, and
does so without altering the excitability of the motoneuron. At
the Ia-​motoneuron synapse, presynaptic inhibition is mediated
primarily through the activation of GABA A receptors, and can
be blocked by bicuculline (10). Baclofen blocks GABA B receptors,
and its effects on spinal cord function in patients with spasticity
are not effects on presynaptic inhibition (as was once thought).
It is of interest that the synapses of corticospinal axons on the
motoneuron are not affected by presynaptic inhibition (6).
Motoneuron recruitment
The recruitment of α motoneurons by voluntary effort, corticospi-
nal volleys, and reflex action proceeds in an orderly sequence from
small to large as the excitatory input grows. This is largely because
the smaller the motoneuron the greater the input resistance. In
accordance with Ohm’s law, the potential produced by a given
current is greater in small motoneurons because of their higher
input resistance (Fig. 2.1). In addition to a slower conduction
velocity and a higher input resistance, small low-​t hreshold moto-
neurons have a longer membrane time constant, lower rheobase,
and longer after-​hyperpolarization (AHP). These properties can
change after exercise and in diseases, such as stroke or spinal cord
11
injury. Inhibitory actions are also generally matched to the size
of the motoneuron, unless the distribution of synapses is non-​
uniform (see ‘What is a motor unit?’ and (7)).
When the force of a voluntary contraction is increased, new pre-
viously silent motoneurons are recruited and the discharge rate of
active motoneurons increases. The extent to which these strate-
gies are used varies for different muscles. The discharge rates of
motoneurons are also related to size, with higher rates achievable
by large motoneurons (which produce large twitch contractions
with a greater tendency to fatigue; Fig. 2.1). This is so whether the
contraction is a steady submaximal effort or a brief intense effort,
and is not surprising because the shorter contraction times for
these motor units would require a higher rate to produce ‘fusion’
(see ‘Muscle twitches, tetanic contractions, and voluntary force’).
Input–​output relationship
The gain of the input–​output relationship for the motoneuron pool
can be altered, and this has major implications for motor control
studies because the same volley would then produce a different
output, not necessarily related to the experimental condition or
manipulation. The best documented mechanism for changing
the gain of a motoneuron is the development of persistent inward
currents (PICs) in motoneurons (Fig. 2.2; for reviews, see (11,12).
PICs are due to dendritic persistent Na+ currents and L-​t ype Ca 2+
currents, and can result in ‘plateau potentials’, which long outlast
the stimulus that triggered them. They can result in an apparently
self-​sustained motoneuron discharge, and have been implicated
in the spasms of spinal spasticity in rats (13) and humans (14).
Intact descending monoaminergic drives are necessary for PICs
to develop in motoneurons (11), but these pathways are transected
in complete spinal lesions. The PICs then occur because of plastic
changes in spinal circuitry. Over time there is greater ‘expression
of 5-​HT2C receptor isoforms that are spontaneously active (consti-
tutively active) without 5-​HT. Such constitutive receptor activity
restores large persistent calcium currents in motoneurons in the
absence of 5-​HT’ (15).
Repolarization and the after-​hyperpolarization
Repolarization of the motoneuron following an action potential
involves fast K+ currents, but is followed by an AHP, the dura-
tion of which is a major determinant of the neuron’s firing rate.
In different neurons, the AHP can last tens to some hundreds
of milliseconds, and has two components, both dependent on
the Ca 2+-​activated K+ channel family, which has a slow action.
The AHP is longest in small motoneurons, and shortens with
increasing discharge rate, the speed of recovery dependent on
the decay of the currents driving the hyperpolarization, and
particularly the speed of buffering of internal calcium. Recovery
from the AHP may also be facilitated by the hyperpolarization-​
activated current, I h, although its role in motoneurons is largely
related to their resonant properties (12). I h is more active in
larger motoneurons and, not surprisingly, is more active on the
axons of low threshold to electrical stimulation (see ‘Biophysical
properties and their implications”). As discussed further under
‘Motor axon’, I h is a depolarizing current that is activated by
hyperpolarization and operates to oppose that hyperpolariza-
tion. The hyperpolarisation-​activated cyclic nucleotide-​gated
(HCN) channels underlying this current are among the most
sensitive to metabolic demands, and contribute to the plasticity
Chapter 2 the motor unit 11
(A) Synaptic input
Green –90 mV
Current
Red –55 mV
Depolarized holding potential
5 nA
(B)
PIC sustained current
Current
PIC amplification
5 nA
Net persistent inward current
(red minus green traces)
(C)
10 mV
Self-sustained firing
Voltage
1 sec
Fig. 2.2 Persistent inward currents, plateau potentials, and self-​sustained firing.
The dendritic persistent inward current (PIC) amplified and prolonged synaptic
input in a low-​threshold, type S motoneuron. (A) At a hyperpolarized holding
potential (−90 mV; green trace), synaptic input produced a steady current with a
sharp onset and offset. At a depolarized holding potential (~−55 mV; red trace),
the PIC is activated, and amplifies and prolongs the same input. Baseline holding
currents are removed to allow the traces to be superimposed. (B) The difference
between the currents in A reflects the net PIC contribution. (C) Under current
clamp conditions, the same input produces a steady excitatory post-​synaptic
potential (EPSP) when the cell is hyperpolarized (~−90 mV; green trace). At a
more depolarized level (−70 mV; red trace, offset removed), the input evokes
repetitive firing and then slower self-​sustained firing when the input is removed.
Reproduced from Clin Neurophysiol, 121(10), ElBasiouny SM, Schuster JE, Heckman CJ,
Persistent inward currents in spinal motoneurons: important for normal function but
potentially harmful after spinal cord injury and in amyotrophic lateral sclerosis, pp. 1669–​79,
copyright (2010), with permission from Elsevier.
of neural connections. In an analogous way, the HCN isoform
present in the heart, HCN4, is highly expressed in the pace-
maker region of the heart and is responsible for normal cardiac
rhythmicity.
Motor axon
In human studies with skin and subcutaneous tissue between
the surface stimulation and the nerve trunk, the activation of
motor axons in descending order of size is not as reliable as in
experiments in animals where the nerve can be exposed. The
sequence of activation with electrical stimulation is still broadly
in order of descending conduction velocity (16), and presum-
ably therefore axonal diameter. The stimulus–​response curve
is sigmoidal or ‘S-​shaped’, and relatively steep when compared
with the stimulus-​response curve for cutaneous afferent axons
[(17,18); see Fig. 2.3]. The stimulus–​response curve is not rou-
tinely measured in routine diagnostic studies, but in chronic
demyelinating diseases, an increase in threshold and a decrease
in the slope of the stimulus–​response curve can be valuable diag-
nostic findings (19).
12
12 Section 1 scientific basis of clinical neurophysiology
(A) 50
CSAP
10
40
CMAP
CSAP (µV)
30
5 axons in the nerve. The range of conduction velocities for motor
20
10
0 0
0 2 4 6 8 of the fastest. This range has not been confirmed in later stud-
Stimulus (mA)
(B) 100 CMAP
Peak response (% max)
CSAP
0 Biophysical properties and their implications
0 100
Stimulus (% mean threshold)
Fig. 2.3 Activation of motor units and cutaneous afferents by graded electrical
stimulation. (A) Amplitudes of compound sensory action potentials (CSAP;
shown in red) and compound muscle action potentials (CMAP; shown in green)
in response to graded stimuli. The filled circles mark the half-​maximal compound
response. Note the earlier, but more gradual CSAP response to increasing
stimulus intensity than motor. (B) Normalized stimulus–​response relationships
for the data in (A) with the peak response normalized to the maximal compound
response. The stimulus is normalized as a percentage of the mean threshold
(marked as filled circles in (A)).
The function, growth, and survival of an axon depends on axo-
plasmic transport to and from the cell body of nutrients, proteins,
lipids, and other essential factors. Orthograde (anterograde) trans-
port from the cell body for vesicles is relatively fast, 200–​400 mm/​
day, but that of proteins, such as channels and cytoskeletal neurofil-
aments is relatively slow, at an overall rate of <10 mm/​day, because
of frequent pauses in the transport. Retrograde axoplasmic trans-
port returns debris, such as used vesicles to the cell body, and this
pathway provides a route for certain neurotropic viruses, such as
herpes simplex, rabies, and poliomyelitis, to invade the cell body.
Conduction velocity of the fastest axons
In human nerves, the fastest motor axons innervating upper-​
limb muscles have conduction velocities of 50–​6 0 m/​s in the
distal upper limb and 40–​50 m/​s in the distal lower limb. These
velocities are 5–​10 m/​s slower over the same nerve segment than
the fastest cutaneous and muscle afferents (which have similar
maximal velocities in humans (20)). However, the threshold for
afferents is much lower than that of motor axons—​for example,
human group Ia afferents can be activated using stimuli 0.5–​0.6
times that required for the lowest-​threshold motor axons (6).
While differences in size contribute, the axons have different bio-
physical properties (see ‘Biophysical properties and their implica-
tions’), and these are major reasons for the higher threshold for
motor axons.
Conduction velocity distribution
Routine motor conduction studies rely on measuring the latencies
for the onset of the compound muscle action potential (CMAP),
CMAP (mV)
and the conduction velocities are therefore those for the fastest
axons innervating a muscle has been determined using colli-
sion techniques, often referred to as the Hopf technique (21), but
preceded by the report of Thomas et al. (22). In the latter study,
velocities for the slowest motor axons were 30–​50% less than those
ies, e.g. a 12% spread of conduction velocities, from the fastest 5%
to the slowest 5% was reported using a computer-​based collision
technique (23). The range of conduction velocities for a motor
nerve has also been estimated using decomposition techniques,
the spread of velocities being 12–​24 m/​s for the thenar muscles
(24), with the fastest motor axons slower than the fastest cutane-
ous afferents and the slowest motor axons faster than the slowest
cutaneous afferents. This is consistent with the steeper stimulus-​
response curve of motor axons in Fig. 2.3.
200
Axons have only one function, the secure transmission of impulses
for minimal expenditure of energy and, to do this, their biophysi-
cal properties are adapted to the pattern and rate of discharge that
they are normally required to maintain. Motor axons have prop-
erties that differ from those of cutaneous afferent axons (25,26)
and group I muscle afferents (27). Specifically, motor axons are
less excitable (i.e. they require stronger stimuli), and this is largely
because they have less activity of two depolarizing conduct-
ances: Ih (the hyperpolarization-​activated current, due to activity
of hyperpolarization-​activated cyclic-​nucleotide gated channels)
and INaP (the persistent Na+ current). The latter is more active on
sensory axons because they are ~4 mV more depolarized than
motor axons (26). The greater INaP underlies the longer strength-​
duration time constant and lower rheobase of sensory axons (28).
These differences dictate that sensory axons can be activated at
lower threshold than motor axons, and this reason is arguably
more important than any size difference. One implication of the
lesser excitability of motor axons is that diseased or damaged
motor axons would be more likely to undergo conduction block
than sensory axons for the same impulse load (25,29).
There are differences in the properties of motor axons innervat-
ing different muscles (30), presumably because they discharge at
different rates and in different patterns. In addition, as discussed
above, high-​and low-​t hreshold motoneurons innervating a sin-
gle muscle maintain different discharge rates and patterns and,
not surprisingly, the biophysical properties of their axons are
graded with the threshold for stimulation (31,32). In particular,
there is greater activity of HCN channels on the motor axons of
lowest threshold to electrical stimulation (i.e. the larger, faster-​
conducting motor axons). If these differences extend throughout
the axon and its terminals, fasciculation would be more likely to
arise in the more excitable larger motor units. The graded differ-
ences in biophysical properties also have implications for some
motor unit number estimation (MUNE) techniques, particularly
those that rely on the assumption that the properties of a select
group of motor units are representative of the pool. Not only does
motor unit size (and CMAP amplitude) vary systematically with
13
(A) (B)
M waves
F waves
50 µV 200 µV
100 ms 100 ms
Fig. 2.4 F-​waves. F waves of the thenar muscles. (A) Superimposition of 20
consecutive responses. (B) Raster display of the same 20 responses. Note the
variability of waveform and latency, and in particular the potential for phase
cancellation if the raw traces were averaged. High-​pass filter 100 Hz.
Reproduced from Pierrot-​Deseilligny E and Burke D, The Circuitry of the Human Spinal Cord.
Its Role in Motor Control and Movement Disorders, copyright (2005), with permission from
Cambridge University Press.
motoneuron size and axonal conduction velocity, but the proper-
ties of the axons differ.
F waves
When an axon is stimulated electrically, impulses are conducted
in both directions from the stimulation site, orthodromically to
the muscle, producing the MUAP (also known as the M wave), and
antidromically back to the motoneuron. On 2–​5% of occasions,
the antidromic impulse produces a ‘backfiring’ of the motoneu-
ron and this results in an orthodromic impulse being conducted
in that axon back to the muscle. This produces a late discharge,
at ~30 ms for the intrinsic muscle of the hand, due to antidromic
conduction to the motoneuron, the ‘turn-​around’ time, and then
orthodromic conduction from motoneuron to muscle.
F waves produced by a sequence of 10–​20 stimuli vary in latency,
onset polarity, and morphology for most muscles (Fig. 2.4), and
this indicates that there is no simple summation of motor unit
action potentials into the CMAP. This is relevant for some MUNE
techniques. It also implies that overall F-​wave activity cannot be
measured by averaging raw EMG traces to a sequence of stimuli—​
the traces need to be full-​wave rectified before averaging and,
before rectification, it is essential that the EMG trace has returned
to baseline after the M wave (33).
While many different measures of F wave activity have been
advocated, the best validated is the shortest latency of a sequence
of F waves. Given a representative sample, this measure reflects the
conduction time for the fastest (largest) motor axons in the pool,
the motor axons that are responsible for conventional conduction
velocity measurements. The spread of F wave latencies (‘chrono-
dispersion’) is also often reported (as are mean and maximal F
wave latencies), justified because all motoneurons can generate F
waves (34). However, motoneurons will do so only if they do not
discharge reflexly in response to the intense afferent volley and, in
practice, F waves are generated mainly by motoneurons with rap-
idly conducting axons (33,35). This is presumably because reflex
discharges in low-​t hreshold motoneurons will prevent the anti-
dromic motor volleys from generating the F wave discharges (see
Chapter 2 the motor unit 13
Fig. 3.7, Chapter 3). Either way, F wave studies are an important
component of diagnostic testing because they provide informa-
tion about the whole length of fast motor axons, from motoneuron
to muscle. Such studies complement routine motor nerve conduc-
tion studies, which are commonly performed only on the more
accessible distal segments.
F waves are often used in motor control studies to control for the
excitability of the motoneuron pool. This practice is flawed (36), as
discussed in Chapter 3.
Motor unit number estimates
Most techniques used to estimate the number of surviving motor
units in a given muscle rely on EMG recordings and dividing the
maximal CMAP by the ‘mean’ MUAP (Fig. 2.5). It is rare for a
distal nerve to innervate only one muscle and, for example, for
the median-​innervated thenar muscles, some median-​innervated
motor units may be relatively deep or relatively remote from
recording electrodes over abductor pollicis brevis. There will be
significant phase cancellation when single MUAPs are summed
(Fig. 2.3) and, given the issues raised in the previous section, it can
be concluded that incremental stimulation methods of MUNE are
intrinsically flawed. It is also possible to perform similar measure-
ments using the force produced by the twitch contraction of the
muscle, but again the twitch forces for the different motor units in
a pool vary greatly from small to large, and the transducer needs
to be able to resolve the forces produced in different axes by the
various muscles innervated by the stimulated nerve.
A number of MUNE techniques have been advocated: the incre-
mental stimulation method in Fig. 2.5, multiple point stimulation,
spike-​triggered averaging, and versions of the statistical method
introduced by Daube (37). These techniques are reviewed else-
where (38,39). Other techniques with various advantages have
been reported or are under development (4, 40–​42). In myopathic
diseases, the decrease in size of the single motor unit means that
small MUAPs may be close to the noise level for detection, and
incremental techniques cannot be recommended. However, in
neuropathic diseases, such as motor neuron disease/​amyotrophic
lateral sclerosis (ALS), the loss of motor units is accompanied by
enlargement of the surviving MUAPs, improving the signal-​to-​
noise ratio. However, this is partially offset by the greater instabil-
ity of individual MUAPs in ALS.
Clinical utility does not require that a measure be accurate
in absolute terms—​merely that changes in the measure mirror
changes in clinical status, and that the technical limitations are
recognized by clinicians. In ALS, changes in MUNE can provide
good evidence of progression of disease (40,41), even if the abso-
lute values are debatable. ‘MUNE values were the most sensitive
index for documenting changes in disease progression over time’,
more sensitive than other measures, including clinical assessment
and handgrip dynamometry (43).
Muscle
In mammals, each muscle fibre is innervated by a single motor
axon, any polyneuronal innervation being eliminated during the
neonatal period (44). The number of muscle fibres innervated by
a motor axon (the ‘innervation ratio’) varies with the muscle: <20
for extraocular muscles, 100–​200 for the intrinsic muscles of the
hand and >1000 for medial gastrocnemius. The number of motor
14
14 Section 1 scientific basis of clinical neurophysiology
(A) (B)
5
5
CMAP (mV)
Peak (mV)
0
–5
0 –.4
300 310 320 330
ms
Fig. 2.5 CMAP to incremental stimulation. (A) Compound muscle action potentials recorded over the thenar eminence in response to graded stimuli to the median
nerve at the wrist. (B) Baseline-​to-​peak measurements of the CMAP shown in (A). (C) Fine detail of the recruitment of low-​electrical threshold motor units into the
compound response. Note that with this scaling the antidromic volley in sensory axons in the digital nerve can be seen in recordings over abductor pollicis brevis (APB),
and is indicated by the red arrow.
axons innervating any one muscle also varies, from a hundred or
more for individual intrinsic muscles of the hand to 500–​600 for
medial gastrocnemius.
Fibre types
Muscle fibres are classified as type I or II by their histochemical
profile in muscle biopsy tissue, but in diagnostic biopsies it is not
possible to distinguish between fibres belonging to different motor
units of the same type. In rat muscle, tetanisation of single motor
axons allowed Edström and Kugelberg (45) to demonstrate glyco-
gen depletion in muscle fibres innervated by a single motor axon,
and thereby to identify the cross-​sectional area of muscle occu-
pied by the glycogen-​depleted fibres. These pioneering studies
demonstrated that the muscle fibres belonging to a single motor
unit were scattered over a substantial cross-​section of the muscle,
15–​20%, with fibres from different motor units intermixed, so that
a gradually rising ‘ramp’ contraction of the muscle would have a
smooth force profile. It is unusual for more than two muscle fibres
from the same motor unit to be immediately adjacent one another.
These findings in animals have been confirmed for human muscle
using single fibre EMG and scanning EMG techniques by Stålberg
and colleagues (46).
Physiological properties
Motor units can also be classified by the physiological properties
of the innervated muscle fibres. Physiological and histochemical
properties are causally matched, but the two approaches involve
different terminologies, dependent on the approach used to clas-
sify the muscle fibres. For example, large motoneurons have large,
fast-​conducting motor axons and tend to innervate ‘white’ muscle
fibres, which produce twitch contractions that are fast and of high
amplitude (Fig. 2.1, lower unit). However, these twitch contrac-
tions are more susceptible to fatigue when activity is sustained
(hence type FF [fast-​twitch fatiguable] motor units.) The fibres
(C)
.2
CMAP (mV)
0
–.2
2 3 4 5 300 310 320 330
Stim (mA) ms
in the motor unit are rich in glycolytic enzymes (and the unit is
therefore also termed FG [fast-​t witch glycolytic], with histochemi-
cally type II muscle fibres). Small motoneurons have smaller, more
slowly conducting motor axons that innervate relatively few ‘red’
muscle fibres (Fig. 2.1, upper unit). Together, they produce twitch
contractions that are slow and of low amplitude, but are resistant
to fatigue (hence type S [slow] motor units). These muscle fibres
are rich in oxidative enzymes (and are therefore also termed SO
[slow oxidative] motor units, and the muscle fibres are histochem-
ically referred to as type I). In between these two extremes there
are large motoneurons that innervate fast-​twitch, but fatigue-​
resistant muscle fibres (FR), containing oxidative and glycolytic
enzymes (FOG units). In most studies on human subjects, the
physiological properties are continuously graded, rather than fall-
ing into two or three distinct entities.
The slowly contracting ‘red’ muscle fibres of the first recruited
type S motor units underlie steady sustained contractions, such
as those involved in maintaining a posture. They are red because
of their myoglobin content and blood supply, and they have more
mitochondria than ‘white’ muscle fibres. The fast ‘white’ muscle
fibres of later recruited type F motor units have more sarcoplas-
mic reticulum and this allows them to take up and release Ca 2+
more rapidly. Accordingly, these fibres are designed more for
rapid movement and brief bursts of strength. However, lactic acid
builds up more in these fibres and they are more prone to fatigue.
Muscle twitches, tetanic contractions,
and voluntary force
The twitch contractions of the first voluntarily recruited motor
units have a slow contraction time (~100 ms in human muscles,
measured from the EMG potential to the peak of the evoked force)
and a slow half-​relaxation time (~150 ms, measured from the force
peak to the time when force has decreased by 50% from its peak)
and produce relatively small forces. Later recruited motor units
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Title: Modern cookery for private families

Author: Eliza Acton

Release date: December 23, 2023 [eBook #72482]

Language: English

Original publication: London: Longmans, Green, Reader, and

Dyer, 1882

Credits: Aaron Adrignola and the Online Distributed

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*** START OF THE PROJECT GUTENBERG EBOOK MODERN

COOKERY FOR PRIVATE FAMILIES ***
 MODERN COOKERY

F O R P R I VAT E FA M I L I E S

BY ELIZA ACTON

NEW EDITION

LONDON
LONGMANS, GREEN, READER, AND DYER
1882.
 PREFACE.

It cannot be denied that an improved system of practical domestic

cookery, and a better knowledge of its first principles, are still much
needed in this country; where, from ignorance, or from
mismanagement in their preparation, the daily waste of excellent
provisions almost exceeds belief. This waste is in itself a very
serious evil where so large a portion of the community often procure
—as they do in England—with painful difficulty, and with the heaviest
labour, even sufficient bread to sustain existence; but the amount of
positive disease which is caused amongst us by improper food, or by
food rendered unwholesome by a bad mode of cooking it, seems a
greater evil still. The influence of diet upon health is indeed a subject
of far deeper importance than it would usually appear to be
considered, if we may judge by the profound indifference with which
it is commonly treated. It has occupied, it is true, the earnest
attention of many eminent men of science, several of whom have
recently investigated it with the most patient and laborious research,
the results of which they have made known to the world in their
writings, accompanied, in some instances, by information of the
highest value as to the most profitable and nutritious modes of
preparing various kinds of viands. In arranging the present enlarged
edition of this volume for publication, I have gladly taken advantage
of such of their instructions (those of Baron Liebig especially) as
have seemed to me adapted to its character, and likely to increase
its real utility. These, I feel assured, if carefully followed out, will
much assist our progress in culinary art, and diminish the
unnecessary degree of expenditure which has hitherto attended its
operations; for it may safely be averred that good cookery is the best
and truest economy, turning to full account every wholesome article
of food, and converting into palatable meals, what the ignorant either
render uneatable, or throw away in disdain. It is a popular error to
imagine that what is called good cookery is adapted only to the
establishments of the wealthy, and that it is beyond the reach of
those who are not affluent. On the contrary, it matters comparatively
little whether some few dishes, amidst an abundant variety, be
prepared in their perfection or not; but it is of the utmost
consequence that the food which is served at the more simply
supplied tables of the middle classes should all be well and skilfully
prepared, particularly as it is from these classes that the men
principally emanate to whose indefatigable industry, high
intelligence, and active genius, we are mainly indebted for our
advancement in science, in art, in literature, and in general
civilisation.
When both the mind and body are exhausted by the toils of the
day, heavy or unsuitable food, so far from recruiting their enfeebled
powers, prostrates their energies more completely, and acts in every
way injuriously upon the system; and it is no exaggeration to add,
that many a valuable life has been shortened by disregard of this
fact, or by the impossibility of obtaining such diet as nature
imperatively required. It may be urged, that I speak of rare and
extreme cases; but indeed it is not so; and the impression produced
on me by the discomfort and the suffering which have fallen under
my own observation, has rendered me extremely anxious to aid in
discovering an efficient remedy for them. With this object always in
view, I have zealously endeavoured to ascertain, and to place clearly
before my readers, the most rational and healthful methods of
preparing those simple and essential kinds of nourishment which
form the staple of our common daily fare; and have occupied myself
but little with the elegant superfluities or luxurious novelties with
which I might perhaps more attractively, though not more usefully,
have filled my pages. Should some persons feel disappointed at the
plan I have pursued, and regret the omissions which they may
discover, I would remind them, that the fashionable dishes of the day
may at all times be procured from an able confectioner; and that part
of the space which I might have allotted to them is, I hope and
believe, better occupied by the subjects, homely as they are, to
which I have devoted it—that is to say, to ample directions for
dressing vegetables, and for making what cannot be purchased in
this country—unadulterated bread of the most undeniably
wholesome quality; and those refreshing and finely-flavoured
varieties of preserved fruit which are so conducive to health when
judiciously taken, and for which in illness there is often such a vain
and feverish craving when no household stores of them can be
commanded.[1]
1. Many of those made up for sale are absolutely dangerous eating; those
which are not adulterated are generally so oversweetened as to be
distasteful to invalids.

Merely to please the eye by such fanciful and elaborate

decorations as distinguish many modern dinners, or to flatter the
palate by the production of new and enticing dainties, ought not to be
the principal aim, at least, of any work on cookery. “Eat,—to live”
should be the motto, by the spirit of which all writers upon it should
be guided. I must here obtrude a few words of personal interest to
myself. At the risk of appearing extremely egotistic, I have appended
“Author’s Receipt” and “Author’s Original Receipt” to many of the
contents of the following pages; but I have done it solely in self-
defence, in consequence of the unscrupulous manner in which large
portions of my volume have been appropriated by contemporary
authors, without the slightest acknowledgment of the source from
which they have been derived. I have allowed this unfairness, and
much beside, to pass entirely unnoticed until now; but I am suffering
at present too severe a penalty for the over-exertion entailed on me
by the plan which I adopted for the work, longer to see with perfect
composure strangers coolly taking the credit and the profits of my
toil. The subjoined passage from the preface of my first edition will
explain in what this toil—so completely at variance with all the
previous habits of my life, and, therefore, so injurious in its effects—
consisted; and prevent the necessity of recapitulating here, in
another form, what I have already stated in it. “Amongst the large
number of works on cookery which we have carefully perused, we
have never yet met with one which appeared to us either quite
intended for, or entirely suited to the need of the totally
inexperienced! none, in fact, which contained the first rudiments of
the art, with directions so practical, clear, and simple, as to be at
once understood, and easily followed, by those who had no previous
knowledge of the subject. This deficiency, we have endeavoured in
the present volume to supply, by such thoroughly explicit and minute
instructions as may, we trust, be readily comprehended and carried
out by any class of learners; our receipts, moreover, with a few
trifling exceptions which are scrupulously specified, are confined to
such as may be perfectly depended on, from having been proved
beneath our own roof and under our own personal inspection. We
have trusted nothing to others; but having desired sincerely to render
the work one of general usefulness, we have spared neither cost nor
labour to make it so, as the very plan on which it has been written
must of itself, we think, evidently prove. It contains some novel
features, calculated, we hope, not only to facilitate the labours of the
kitchen, but to be of service likewise to those by whom they are
directed. The principal of these is the summary appended to the
receipts, of the different ingredients which they contain, with the
exact proportion of each, and the precise time required to dress the
whole. This shows at a glance what articles have to be prepared
beforehand, and the hour at which they must be ready; while it
affords great facility as well, for an estimate of the expense attending
them. The additional space occupied by this closeness of detail has
necessarily prevented the admission of so great a variety of receipts
as the book might otherwise have comprised; but a limited number,
thus completely explained, may perhaps be more acceptable to the
reader than a larger mass of materials vaguely given.
“Our directions for boning poultry, game, &c., are also, we venture
to say, entirely new, no author that is known to us having hitherto
afforded the slightest information on the subject; but while we have
done our utmost to simplify and to render intelligible this, and several
other processes not generally well understood by ordinary cooks, our
first and best attention has been bestowed on those articles of food
of which the consumption is the most general, and which are
therefore of the greatest consequence; and on what are usually
termed plain English dishes. With these we have intermingled many
others which we know to be excellent of their kind, and which now so
far belong to our national cookery, as to be met with commonly at all
refined modern tables.”
Since this extract was written, a rather formidable array of works
on the same subject has issued from the press, part of them from the
pens of celebrated professional gastronomers; others are constantly
appearing; yet we make, nevertheless, but slight perceptible
progress in this branch of our domestic economy. Still, in our
cottages, as well as in homes of a better order, goes on the “waste”
of which I have already spoken. It is not, in fact, cookery-books that
we need half so much as cooks really trained to a knowledge of their
duties, and suited, by their acquirements, to families of different
grades. At present, those who thoroughly understand their business
are so few in number, that they can always command wages which
place their services beyond the reach of persons of moderate
fortune. Why should not all classes participate in the benefit to be
derived from nourishment calculated to sustain healthfully the
powers of life? And why should the English, as a people, remain
more ignorant than their continental neighbours of so simple a matter
as that of preparing it for themselves? Without adopting blindly
foreign modes in anything merely because they are foreign, surely
we should be wise to learn from other nations, who excel us in aught
good or useful, all that we can which may tend to remedy our own
defects; and the great frugality, combined with almost universal
culinary skill, or culinary knowledge, at the least—which prevails
amongst many of them—is well worthy of our imitation. Suggestions
of this nature are not, however, sufficient for our purpose. Something
definite, practical, and easy of application, must open the way to our
general improvement. Efforts in the right direction are already being
made, I am told, by the establishment of well-conducted schools for
the early and efficient training of our female domestic servants.
These will materially assist our progress; and if experienced cooks
will put aside the jealous spirit of exclusiveness by which they are
too often actuated, and will impart freely the knowledge they have
acquired, they also may be infinitely helpful to us, and have a claim
upon our gratitude which ought to afford them purer satisfaction than
the sole possession of any secrets—genuine or imaginary—
connected with their craft.
The limits of a slight preface do not permit me to pursue this or
any other topic at much length, and I must in consequence leave my
deficiencies to be supplied by some of the thoughtful, and, in every
way, more competent writers, who, happily for us, abound at the
present day; and make here my adieu to the reader.
ELIZA ACTON
London, May, 1855.
 VOCABULARY OF TERMS,
PRINCIPALLY FRENCH, USED IN MODERN COOKERY.

Aspic—fine transparent savoury jelly, in which cold game, poultry,

fish, &c., are moulded; and which serves also to decorate or
garnish them.
Assiette Volante—a dish which is handed round the table without
ever being placed upon it. Small fondus in paper cases are
often served thus; and various other preparations, which require
to be eaten very hot.

Blanquette—a kind of fricassee.

Boudin—a somewhat expensive dish, formed of the French
forcemeat called quenelles, composed either of game, poultry,
butcher’s meat, or fish, moulded frequently into the form of a
rouleau, and gently poached until it is firm; then sometimes
broiled or fried, but as frequently served plain.
Bouilli—boiled beef, or other meat, beef being more generally
understood by the term.
Bouillie—a sort of hasty pudding.
Bouillon—broth.
Casserole—a stewpan; and the name also given to a rice-crust,
when moulded in the form of a pie, then baked and filled with a
mince or purée of game, or with a blanquette of white meat.
Court Bouillon—a preparation of vegetables and wine, in which (in
expensive cookery) fish is boiled.
Consommé—very strong rich stock or gravy.
Croustade—a case or crust formed of bread, in which minces,
purées of game, and other preparations are served.
Crouton—a sippet of bread.

Entrée—a first-course side or corner dish.[2]

2. Neither the roasts nor the removes come under the denomination of
entrées; and the same remark applies equally to the entremets in the
second course. Large standing dishes at the sides, such as raised pies,
timbales, &c., served usually in grand repasts, are called flanks; but in
an ordinary service all the intermediate dishes between the joints and
roasts are distinguished by the name of entrées, or entremets.

Entremets—a second-course side or corner dish.

Espagnole, or Spanish sauce—a brown gravy of high savour.

Farce—forcemeat.
Fondu—a cheese soufflé.

Gâteau—a cake, also a pudding, as Gâteau de Riz; sometimes

also a kind of tart, as Gâteau de Pithiviers.

Hors d’œuvres—small dishes of anchovies, sardines, and other

relishes of the kind, served in the first course.

Macaroncini—a small kind of maccaroni.

Maigre—made without meat.
Matelote—a rich and expensive stew of fish with wine, generally of
carp, eels, or trout.
Meringue—a cake, or icing, made of sugar and whites of egg
beaten to snow.
Meringué—covered or iced with a meringue-mixture.

Nouilles—a paste made of yolks of egg and flour, then cut small like
vermicelli.

Purée—meat, or vegetables, reduced to a smooth pulp, and then

mixed with sufficient liquid to form a thick sauce or soup.

Quenelles—French forcemeat, for which see page 163.

Rissoles—small fried pastry, either sweet or savoury.

Sparghetti—Naples vermicelli.
Stock—the unthickened broth or gravy which forms the basis of
soups and sauces.

Tammy—a strainer of fine thin woollen canvas.

Timbale—a sort of pie made in a mould.
Tourte—a delicate kind of tart, baked generally in a shallow tin pan,
or without any: see page 574.

Vol-au-vent—for this, see page 357.

Zita—Naples maccaroni.
TABLE OF CONTENTS.
 CHAPTER I.

SOUPS.
Page

Ingredients which may all be 1

used for making Soup of
various kinds
A few directions to the Cook 2
The time required for boiling 4
down Soup or Stock
To thicken Soups 4
To fry Bread to serve with Soup 5
Sippets à la Reine 5
To make Nouilles (an elegant 5
substitute for Vermicelli)
Vegetable Vermicelli 5
(Vegetables cut very fine for
Soups)
Extract of Beef, or very strong 6
Beef Gravy-Soup (Baron
Liebig’s receipt)
Bouillon (the common Soup of 7
France), cheap and very
wholesome
Clear pale Gravy Soup, or 10
Consommé
Another receipt for Gravy Soup 10
Cheap clear Gravy Soup 11
Glaze (Note) 11