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com

NERVE CONDUCTION STUDIES:

ESSENTIALS AND PITFALLS IN PRACTICE
A Mallik, A I Weir
ii23

J Neurol Neurosurg Psychiatry 2005; 76(Suppl II):ii23–ii31. doi: 10.1136/jnnp.2005.069138

A
neurologist has sent a patient for nerve conduction studies (NCS) and has received the
report, but what does it mean? We hope to remove some of the mysteries that may
surround NCS. The techniques and how they are affected by disease are described in
general terms. These principles can be applied to specific conditions discussed elsewhere. We also
discuss the numerous pitfalls that may be encountered with NCS. Understanding these basic
concepts will allow you to get the most from your clinical neurophysiology department.
NCS are only part of a complete peripheral neurophysiological examination (PNE) and are
frequently accompanied by a needle electromyogram (EMG). The combination of both techniques
and those detailed in other articles in this issue are often required for a complete diagnostic study.
The process of choosing the appropriate tests is the responsibility of the clinical neurophysiologist
(CN) and not the referring doctor and is planned as a dynamic series of steps designed to answer
specific questions about nervous system function raised by the clinical picture.

c ABBREVIATIONS

Clinical neurophysiologists can employ a confusing number of terms and abbreviations. Box 1
lists the ones we use frequently.

WHAT DO YOU TELL THE PATIENT ABOUT THE TESTS?

NCS involve activating nerves electrically with small safe pulses over several points on the skin of
the limbs and measuring the responses obtained. Some people are frightened by the term ‘‘electric
shocks’’. The tests are at worst uncomfortable but most patients find them tolerable when they
are explained sympathetically. There are no long term side effects. Both authors have had their
own nerves tested on many occasions without difficulty and neither of us would claim
particularly high pain thresholds. A self inflicted demonstration by the CN may be helpful with
the more anxious patient as well as a simple information sheet.
There are very few contraindications to these investigations, but the most important is the
presence of some cardiac pacemakers. With most there is no risk but discussion with the patient’s
cardiologist is advised if (1) the NCS are likely to involve stimulation close to the chest wall, and
(2) if a life threatening event would be risked should the pacemaker either be triggered or
changed to a harmful default state if subject to an external voltage.

REFERRING PATIENTS FOR NERVE CONDUCTION STUDIES

NCS give data on peripheral nervous system (PNS) function which may be used to provide:
c diagnosis(es)
c description of disease state (old/new; dynamic/static pathophysiology)
c longitudinal monitoring of disease with multiple studies
c advice on prognosis and management based on tests results and disease detected.
Nerve conduction studies may be diagnostically helpful in patients suspected of having almost
any PNS disorder including disorders of nerve roots, peripheral nerves, muscle and
neuromuscular junction. Cranial nerves and spinal cord function may also be assessed. Specific
clinical indications are discussed elsewhere.
See end of article for authors’ When referring patients, it is useful to think of the specific questions you wish answered with
affiliations the PNE. In difficult cases it is helpful to discuss the referral (which should contain all relevant
_________________________ clinical information) with the CN. The PNE is an extension of the clinical history and examination
Correspondence to: and CNs will take a history and perform the relevant neurological examination but will rely on the
Dr Arup Mallik, Department of referral information to guide them. In straightforward conditions they may follow an initial
Clinical Neurophysiology,
Institute of Neurological standard protocol of tests but the investigator will be ready to modify or add to these tests on the
Sciences, Southern General basis of the initial findings. This emphasises that when NCS are performed by technical staff, the
Hospital, Glasgow G51 4TF, CN should supervise in close proximity and be available to carry out other appropriate tests. It is
UK; [email protected].
uk unnecessary (and sometimes insulting) to specify tests in the referral as long as the clinical
_________________________ question being asked is clear. For example, in a patient suspected of having right carpal tunnel

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NEUROLOGY IN PRACTICE

Box 1: List of abbreviations and terminology Box 2: Minimum basic physiological knowledge
used to understand nerve conduction studies
c ACh: acetylcholine c Membrane potential: genesis; threshold effects; effect of
c AIDP: acute inflammatory demyelinating polyneuropathy membrane damage; denervation
c AMAN: acute motor axonal neuropathy c Single axon: saltatory and non-saltatory conduction;

ii24 c CMAP: compound muscle action potential factors which determine conduction velocity: diameter,
c CN: clinical neurophysiologist myelination, inter-nodal distance
c DRG: dorsal root ganglion c Whole nerve composition: fascicular structure; size and
c EMG: electromyogram conduction velocity distribution; afferent and efferent
c LEMS: Lambert-Eaton myasthenic syndrome modalities and their relative contribution
c MG: myasthenia gravis c Neuromuscular transmission: nerve terminal function;
c NAP: nerve action potential transmitter production, storage and release; post-synaptic
c NCS: nerve conduction studies membrane structure and function; receptor dynamics;
c NMTD: neuromuscular transmission disorders endplate potentials; propagated muscle action potentials
c PNE: peripheral neurophysiological examination c External electrical/magnetic stimulation: local depolar-
c PNS: peripheral nervous system isation; bidirectional propagation once depolarised;
c RNS: repetitive nerve stimulation effects of skin and subcutaneous tissue impedance;
c SNAP: sensory nerve action potential electrical inductive effect of applied magnetic field;
c TMS: transcranial magnetic stimulation stimulation threshold depends on: membrane proper-
c Conduction block: A reduction of proximal CMAP area/ ties(accommodation), nerve fibre location and size with
amplitude of at least 20% (usually . 50%) compared with respect to stimulator
distal CMAP area/amplitude. The duration of the c Muscle function: excitation contraction coupling; muscle
proximal CMAP should not increase by . 20% (see fibre types and function; fatigue
temporal dispersion) For an excellent interactive physiological education tool
c Temporal dispersion: A reduction in proximal CMAP see Richard Carpenter’s Neurolab at http://www.cudos.
amplitude compared with distal CMAP amplitude when ac.uk/web/copyright.htm.
the proximal CMAP duration increases by . 20%
c Orthodromic: Nerve action potentials carried in the
physiological direction of a muscle under study makes a surface recording
c Antidromic: Nerve action potentials carried in the
impossible.
direction opposite to the physiological
Nerves may be stimulated through the skin with surface
stimulators, or via a needle placed close to a nerve or a nerve
root. Spinal root and cerebral cortical stimulation may also be
syndrome it is unnecessary to ask for ‘‘NCS of the right carried out using transcutaneous magnetic stimulation
median nerve’’. (The wise CN will study both median nerves (TMS) dealt with elsewhere in this issue. Thus the full
anyway as this condition is frequently bilateral.) length of the motor pathway may be assessed from cortex to
cord, root, neuromuscular junction, and the contractile
Basic nerve and muscle physiology apparatus. Choice of the stimulation points depends both
The referring doctor needs only a minimal knowledge of basic on the desire to ‘‘bracket’’ above and below the point of a
and applied physiology to understand the test results, but all proposed focal lesion and the anatomical availability of the
PNE reports should be written in terms that do not assume appropriate structure.
specialist knowledge. A minimum knowledge set to under-
stand the principles of the techniques is shown in box 2 with The aim of the NCS
links to more detail. Our minimum knowledge set above has shown us that
peripheral nerves contain many nerve fibres of different
diameters, degrees of myelination, and afferent or efferent
The principals of nerve conduction studies
connections. The NCS studies the fastest 20% of these fibres
NCS involve the application of a depolarising square wave
and the aim of the investigation is to document focal or
electrical pulses to the skin over a peripheral nerve produ-
continuous abnormalities in the length of the mixed, motor
cing: (1) a propagated nerve action potential (NAP) recorded
or sensory nerve. Particular attention is paid to the following
at a distant point over the same nerve: and (2) a compound
questions as the test progresses:
muscle action potential (CMAP) arising from the activation c Is the fastest conduction velocity normal?
of muscle fibres in a target muscle supplied by the nerve. In c Is the velocity gradient normal. Normally nerves closer to
both cases these may be recorded with surface or needle the neuraxis and more cephalad conduct faster than more
electrodes. distal and caudal nerves.
Surface electrodes are designed to give information about c Is the CMAP normal in size and shape?
the whole of a muscle stimulated, giving data for the time c Does the CMAP alter in size, shape or duration between
taken for the fastest axons to conduct an impulse to the stimulation points?
muscle and the size of the response. – giving evidence for temporal dispersion (see terms, box 2).
Needle electrodes for NCS give very accurate conduction – giving evidence for conduction block (see terms, box 2).
time information, but because they record from only a small
area of muscle or nerve, they give poor or, in the case of the Normal values for NCS
latter, more complex information making numerical analysis Age matched ‘‘Normal’’ values for NCS parameters are either
difficult. However, needle recordings are most appropriate derived from studies of groups of neurologically normal
when severe muscle wasting has occurred, or when the depth subjects or culled from the literature. Regrettably in the view

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NEUROLOGY IN PRACTICE

ii25

Figure 1 (A, B). Median motor nerve conduction study. Active recording electrode is over the APB muscle, with stimulation at the wrist, elbow, axilla,
and brachial plexus. Panel B shows the motor response from stimulation at all four sites. Responses are of the same shape but the latency is longer with
more proximal stimulation. (C) The compound muscle action potential (CMAP) and its parameters.

of the authors the most frequent statistics used are limits of (CMAP) from surface electrodes overlying a muscle supplied
95% or less frequently 99% confidence limits of a normal by that nerve.
group to indicate abnormality of a single parameter. The recording electrodes are performed using adhesive
This approach may mislead as a crude separation between conductive pads placed onto the skin overlying the target
‘‘normal’’ and ‘‘abnormal’’ dilutes the information whereas a muscle. The active electrode is placed over the muscle belly
Z score, for example, indicating the separation between a and the reference over an electrically inactive site (usually the
single value and the group mean expressed in SD, may be muscle tendon). A ground electrode is also placed somewhere
more informative. Alternatively, (a) a number of electro- between the stimulating and recording electrodes providing a
physiological parameters may be taken together either as an zero voltage reference point. The median motor study might
‘‘index’’ or ‘‘score’’, or (b) the neurophysiologist assesses a involve stimulation at the wrist, the elbow, and less
number of parameters together to make a judgement as to frequently the axilla and the brachial plexus (fig 1A,B).
whether a clinically relevant numerical abnormality should The CMAP is a summated voltage response from the
be emphasised in the report interpretation or not. individual muscle fibre action potentials. The shortest latency
There are a number of physical parameters that require of the CMAP is the time from stimulus artefact to onset of the
correction or allowance for. The most important is tempera- response and is a biphasic response with an initial upward
ture. The fastest motor nerve conduction velocity (FMNCV) is deflection followed by a smaller downward deflection. The
reduced by approximately 1 m/s per ˚C temperature fall. CMAP amplitude is measured from baseline to negative peak
Conventionally, studies are performed as close to a surface (the neurophysiological convention is that negative voltage is
recorded temperature of 34 ˚C. If that is not achieved by demonstrated by an upward deflection) and measured in
adequate heating or the limb, rarely a temperature correction millivolts (mV) (fig 1C).
must be applied. Some measures of conduction require To record the CMAP, the stimulating current or voltage is
correction for limb length or height. Finally nerve conduction gradually increased until a point is reached where an increase
data alter with age. The motor conduction slows by 0.4– in stimulus produces no increment in CMAP amplitude. It is
1.7 m/s per decade after 20 years and the sensory by 2–4 m/s. only at this (supramaximal) point that reproducible values
for CMAP amplitude and the latency between the stimulus
SPECIFIC NERVE CONDUCTION STUDY and the onset of the CMAP can be recorded accurately.
TECHNIQUES The nerve is then stimulated at a more proximal site—in
Motor nerve conduction studies the median nerve this will be the antecubital fossa, close to
Motor studies are performed by electrical stimulation of a the biceps tendon. In the normal state stimulating the
nerve and recording the compound muscle action potential median nerve at the wrist and the elbow results in two

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NEUROLOGY IN PRACTICE

Stimulus
Cell M
body Axon F

ii26
F wave
Muscle

R M E D I A N - A P B

1 .2

1 .3

Figure 2 Median orthodromic sensory study. The index finger digital 1 .4

nerves are stimulated via ring electrodes and the response recorded 1 .5

over the median nerve at the wrist. 1 .6

1 .7

1 .8

1 .9

CMAPs of similar shape and amplitude because the same 1 .1 0

5 0 m s 5 0 0 µ V

motor axons innervate the muscle fibres making up the

response. However, the latency will be greater for elbow
stimulation compared with wrist stimulation because of the
longer distance between the stimulating and recording M F
electrodes (fig 1B). The difference in latency represents the
time taken for the fastest nerve fibres to conduct between the Figure 3 Schematic representation of the early M response from the
two stimulation points as all other factors involving distally propagated action potential and the later F wave from the
neuromuscular transmission and muscle activation are proximally propagated action potential. The latter depolarises the axon
common to both stimulation sites. If one measures the hillock causing it to backfire. Actual F wave responses are shown in the
lower trace. F waves vary in latency and shape due to different
distance between the two sites then the fastest motor nerve
populations of axons backfiring each time.
conduction velocity can be calculated as follows: FMNCV
(m/s) = distance between stimulation site 1 and site 2
(mm)/[latency site 2 – latency site 1 (ms)].
CMAP. However, an impulse also conducts proximally to the
anterior horn cell, depolarising the axon hillock and causing
Sensory conduction studies
the axon to backfire. This leads to a small additional muscle
The sensory nerve action potential (SNAP) is obtained by
depolarisation (F wave) at a longer latency. Only about 2% of
electrically stimulating sensory fibres and recording the nerve
axons backfire with each stimulus. Unlike the M response
action potential at a point further along that nerve. Once
(fig 3), F waves vary in latency and shape because different
again the stimulus must be supramaximal.
populations of neurones normally backfire with each
Recording the SNAP orthodromically refers to distal nerve
stimulus. The most reliable measure of the F wave is the
stimulation and recording more proximally (the direction in
minimum latency of 10–20 firings.
which physiological sensory conduction occurs). Antidromic
testing is the reverse. Different laboratories prefer antidromic
or orthodromic methods for testing different nerves. An Why are F waves useful?
orthodromic median sensory study is shown in fig 2. The F waves allow testing of proximal segments of nerves that
sensory latency and the peak to peak amplitude of the SNAP would otherwise be inaccessible to routine nerve conduction
are measured. The velocity correlates directly with the studies. F waves test long lengths of nerves whereas motor
sensory latency and therefore either the result may be studies test shorter segments. Therefore F wave abnormalities
expressed as a latency over a standard distance or a velocity. can be a sensitive indicator of peripheral nerve pathology,
Only the 20% largest diameter and fastest conducting particularly if sited proximally. The F wave ratio which
sensory fibres are tested using conventional sensory studies compares the conduction in the proximal half of the total
functionally supplying fine touch, vibration, and position pathway with the distal may be used to determine the site of
sense. Predominantly small fibre neuropathies affecting the conduction slowing—for example, to distinguish a root lesion
other 80% of fibres exist usually with prominent symptoms of from a patient with a distal generalised neuropathy.
pain and conventional sensory studies may be normal. In
such cases quantitative sensory testing and autonomic Errors
testing will be required, which are beyond the scope of this The main sources of non-biological error in NCS measure-
article (see Interpretation pitfalls). ments are the identification and measurement of waveform
onset and the measurement of the length of the nerve
F waves segment on the limb. Calculations have shown that in a nerve
F waves (F for foot where they were first described) are a type with a conduction velocity of 50 m/s, the 26SD experimental
of late motor response. When a motor nerve axon is error for velocity is 14 m/s over 10 cm and 4.7 m/s over
electrically stimulated at any point an action potential is 25 cm. Of the error, time measurement is 92.3% and distance
propagated in both directions away from the initial stimula- 7.7%, so the use of the measuring tape is quite adequate in
tion site. The distally propagated impulse gives rise to the conventional NCS.

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Table 1 Typical nerve conduction study abnormalities seen with axon loss or demyelination
Axon loss Demyelination

Sensory responses Small or absent Small or absent

Distal motor latency Normal or slightly prolonged Prolonged
CMAP amplitude Small Normal (reduced if conduction block or temporal dispersion)
Conduction block/temporal dispersion Not present (responses may disperse slightly) Present
Motor conduction velocity Normal or slightly reduced Notably reduced ii27
F waves minimum latency Normal or slightly prolonged Significantly prolonged

It is not necessary to have all the features of axon loss or demyelination to come to a conclusion. Some conditions only affect motor or sensory nerves, and some
processes are length dependent and others universal. It can sometimes be quite difficult to decide whether a process is primarily demyelinating or demyelinating
with secondary axonal changes as features of both may coexist.

NERVE CONDUCTION STUDIES IN DISEASE axons conduct normally and one would expect latencies and
General conduction velocities to remain normal. However, with
NCS provides information to locate lesions in the length of a increasing motor axon loss some of the largest fastest
nerve, and pathophysiological information. Peripheral nerve conducting fibres will be lost. Therefore distal motor latency
pathology primarily affects axons or myelin. In reality, the may be slightly prolonged (, 120% of normal limit) and
two pathologies often co-exist but usually one predominates conduction velocity slightly slowed (. 80% of normal limit).
(table 1). The dynamics and timing of an axonal insult can affect the
In focal lesions characterisation of the pathophysiological abnormalities seen. Immediately after a traumatic complete
process can be important for determining prognosis. A transection of the nerve, the portion of the nerve distal to the
patient with a radial nerve palsy at the spiral groove causing lesion will be normal as there has not been time for axonal
wrist drop is more likely to make a complete and speedier degeneration to occur. The CMAP amplitude will only start to
recovery (6–12 weeks) if this is mainly due to focal fall a few days later. Conversely, if there is a very slow loss of
demyelination and/or conduction block (neuropraxia) com- axons in a generalised neuropathy, the remaining unaffected
pared with when significant axonal injury has also occurred axons may have time to sprout new connections to muscle
(6–12 months). fibres that have lost their innervation (collateral reinnerva-
In generalised processes it is also important to determine tion) and the CMAP may remain within the normal
whether a peripheral neuropathy is demyelinating or axonal amplitude range even though the total number of nerve
as this will affect further investigation and management. For axons is smaller. However, the immature regenerating fibres
example, acute inflammatory demyelinating polyneuropathy have slower velocities due to the effect of the short internodal
(AIDP or Guillain-Barré syndrome) results in a characteristic distances and this produces a more dispersed CMAP.
pattern of segmental nerve demyelination and may be treated
with human immunoglobulin or plasma exchange. In demyelination
Conversely a length dependent axonal neuropathy develop-
With loss of myelin thickness nerve conduction is slowed
ing in a patient on chemotherapy requires reassessment of
and, if severe enough, saltatory conduction fails (conduction
the chemotherapy or addition of a protective agent.
block). NCS shows severely prolonged motor latencies and
Neuropathies may be classified pathologically in this notably slowed conduction velocities. The precise changes
fashion, anatomically or electrophysiologically.
seen depend on the site and extent of demyelination. If
demyelination is very proximal then distal motor latency and
Motor NCS conduction velocity may be normal in which case only F
In axonal loss
waves may show abnormalities.
The most striking abnormality is a reduction in CMAP
amplitude as fewer functioning motor axons are connected to
muscle fibres. Since myelin is unaffected, the remaining
Normal nerve

Responses arrive at
recording electrode
Conduction block Temporal dispersion almost together =
Distal
stimulation
Demyelination
Temporal dispersion
Responses arrive at
Proximal different times
stimulation phase cancellation =

Figure 4 Both these traces show demyelination in median motor

studies. The trace on the left shows almost complete conduction block Figure 5 Schematic representation of phase cancellation and
with an absent response with proximal stimulation. The trace on the temporal dispersion in demyelination. In the normal nerve, the
right shows temporal dispersion where the CMAP duration increases by responses are synchronised in time and therefore summate (amplitude
almost 40% with proximal stimulation. In both situations the CMAP is higher that that of the individual components). Temporal dispersion
amplitude with proximal stimulation is smaller. results in an increased duration and reduced amplitude of CMAP.

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No lesion Pre-ganglionic lesion Post-ganglionic lesion Figure 6 Sensory responses are

normal in pre-ganglionic lesions even
though sensation may be abnormal
DRG clinically. Post-ganglionic lesions result
in abnormal sensory responses. DRG,
dorsal root ganglion.

ii28
Spinal
cord

Normal Abnormal Abnormal

sensation sensation sensation

RULNAR- Ort ho -V RULNAR- Ort ho -V

2 2

1 4 1 4
3 V1 3 V1
10ms 10 µV 10ms 10 µV
10 10

Normal SNAP Normal SNAP Abnormal SNAP

Conduction block or temporal dispersion both result in a Focal lesions

reduction in CMAP amplitude. The CMAP area is used to Multiple sensory NCS allow the investigator to locate sensory
assess the contribution of these two processes. In conduction neuropathies that involve single or multiple digital nerves
block there is complete failure of conduction in some or all of distally (for example, vasculitis or hand arm vibration
the motor axons studied. Therefore the CMAP area with syndrome) right up to the major trunks, cords, and divisions
stimulation proximal to site of conduction block is smaller of the brachial plexus proximally.
(. 20% reduction) compared with distal stimulation (fig 4). In proximal nerve trauma, maintenance of the sensory
For true conduction block to be detected, the proximal CMAP potential depends on the intact cell bodies in the dorsal root
duration must not increase by . 20%. In temporal dispersion ganglia. Thus sensory NCS are extremely useful in localising
(fig 4) there is a loss of synchrony in the nerve action a PNS lesion as either pre- and/or post-ganglionic. In a
potentials resulting in a loss of CMAP amplitude because the patient with a clinically suspected C8, T1 root lesion and with
positive part of one muscle fibre action potential cancels out appropriate anaesthesia in that dermatome, the absence of
the negative part of another (phase cancellation) (fig 5). the ulnar and medial antebrachial cutaneous sensory
potential places the lesion distal to the dorsal root ganglion
Clinical correlates of motor conduction velocity slowing and (DRG) in the lower trunk of the brachial plexus and not at
conduction block root level (fig 6). Needle EMG can then be used to define this
It is important to realise that slowing of conduction velocity further.
alone without conduction block does not result in weakness
as the impulses are still conducted from nerve to muscle. A F waves
good example of this is the presence of profound slowing of Generalised disorders
motor nerve conduction in totally asymptomatic primary F waves are sensitive to all forms of generalised peripheral
relatives of patients with demyelinating hereditary motor and neuropathy with their absence or a prolonged minimum
sensory neuropathy. latency occurring early. For example, in AIDP where
demyelination may be segmental, proximal and patchy,
Sensory NCS F wave abnormalities may be the earliest and (in mild cases)
In generalised disorders the only electrophysiological abnormality seen.
In both axonal and demyelinating pathologies the SNAP In axonal pathology F wave latencies may also be mildly
amplitude is reduced for different reasons. Sensory axonal delayed in keeping with the motor conduction velocity
loss will result in a smaller SNAP. Demyelination also slowing secondary to the loss of the fastest conducting motor
produces small SNAPs but with prolonged durations. As axons.
they are of much shorter duration than CMAPs they are more In motor neuronopathies such as the motor neurone
susceptible to phase cancellation (fig 5). diseases, prolongation of any F wave latency is strong
The distribution of sensory NCS abnormalities may be evidence either that this is the incorrect diagnosis (such as
helpful in determining aetiology. For example, the loss of in multifocal motor neuropathy) or that a second patholo-
SNAPS in the lower limbs is common in an axonal dying back gical process is present.
neuropathy related to drugs like vincristine, whereas equal
involvement of upper and lower limb SNAPS raise the Focal lesions
possibility of a sensory ganglionopathy such as that related to F waves may be absent in focal peripheral nerve or anterior
thalidomide treatment. spinal disorders. They were initially also thought to be very

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REPETITIVE NERVE STIMULATION

Repetitive nerve stimulation (RNS) is used in the evaluation
Pre-exercise of patients with suspected neuromuscular transmission
disorders (NMTD) such as myasthenia gravis (MG) or
Lambert-Eaton myasthenic syndrome (LEMS). RNS is a
Immediately post-exercise
modified motor NCS where instead of recording CMAPs with
single supramaximal electrical stimuli, a train of 8–10 stimuli ii29
1 min post-exercise is applied and the sequential response amplitudes and/or
areas measured. This may be carried out at low (3–4 Hz) or
2 min post-exercise high frequency stimulation (20–50 Hz). In the latter case the
train is prolonged to allow 2–10 seconds of continuous data
to be measured. Both distal and proximal muscles/nerves
should be studied in every patient suspected of an NMTD as
the sensitivity of the test is greatly increased by this means.
With low frequency stimulation in normal subjects, the
CMAP amplitude and/or area falls over the first 4–5 stimuli
by a maximum of 10–12%. The maximum fall should be
between potentials 1 and 2 (see RNS pitfalls). A number of
department specific protocols have been published to study
the RNS over time both before and after a period of
maximum voluntary contraction of the muscle to pick up
early or late NMT failure (fig 7).
High frequency stimulation may be used to discover
evidence of a post-synaptic transmitter release disorder like
LEMS. It is painful and requires considerable patient
tolerance. There is evidence that recording low frequency
RNS immediately before and after a 20–30 second period of
Figure 7 (A) Normal repetitive nerve stimulation from abductor digiti
minimi muscle in the hand. The amplitude of the CMAPs within each maximum voluntary contraction by the patient is equally
train does not decrement nor is there any significant increment in CMAP sensitive and is more humane (fig 8).
amplitude after exercise. (B) Repetitive nerve stimulation in myasthenia There are many pitfalls in the RNS test and artefact almost
gravis from the nasalis muscle. Four stimulus trains are given—all at always gives rise to an abnormal test. Thus adherence to a
baseline with no exercise. A reproducible decrement of 55% is seen strict protocol and heightened suspicion on the part of the CN
(train 3 is technically unsatisfactory because of movement artefact).
to an abnormal result is essential as are repeated studies for
reproducibility of abnormalities (see RNS pitfalls).

useful in identifying individual root distribution abnormal- Physiological basis for the RNS
ities. However, particularly in the upper limbs, the substantial The neuromuscular junction consists of the motor axon
overlap of segmental innervation in the distally available terminal, the synaptic cleft, and the post-synaptic muscle
peripheral nerves makes this test on its own of low sensitivity membrane. As the motor axon potential depolarises the nerve
and anatomical specificity. In addition, the effect of terminal, voltage gated calcium channels open increasing the
demyelination is diluted by the length of the path over concentration of calcium in the pre-synaptic nerve terminal.
which the F wave passes. In distinguishing the presence of a This in turn facilitates the release of quanta of acetylcholine
distal or proximal lesion, the use of the F wave ratio which (ACh) from the nerve terminal into the synaptic cleft. ACh
compares the F wave latency in the upper and lower halves of binds to receptors on the post-synaptic membrane causing
the limb (conventionally using knee and elbow as the depolarisation (end plate potential). The size of the end plate
dividing line) may be useful. potential is dependent on the amount of ACh released and its

Figure 8 These traces show typical

electrophysiological features of a pre-
synaptic neuromuscular transmission
Ulnar CMAP
1 Pre-exercise disorder in a patient with LEMS. The
traces on the left show a small amplitude
ulnar CMAP that after exercise increases
Pre-exercise
2 0 secs post-exercise fourfold in amplitude. The traces on the
right show repetitive nerve stimulation
studies. The amplitude increases post-
3 30 secs post-exercise exercise. Trains 1, 3, and 4 show a
Post-exercise decrement of 30% which repairs with
1 min post-exercise exercise (train 2).
4

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Table 2 Performance of tests

Technique Pitfall Explanation

Motor NCS Temperature A low FMNCV or long DL may relate to low skin temperature. It should always be recorded and cool
limbs heated
F waves No pathway length allowance Because of the long pathway, normal values have to be related to limb length, pathway
measurement or body height
ii30 Motor NCS Waveform measurements If the onset of the CMAP is positive—that is, a downward deflection—the active recording electrode
is misplaced away from the motor point and spurious latency and amplitude values will occur
If an initially positive going waveform is only seen in proximal median nerve stimulation there is a
likelihood of an anatomic anomaly in the forearm
Motor and sensory Inadequate numbers of nerves In order to determine whether abnormalities are focal, generalised, length dependent, a sample of
NCS studied nerves in upper and lower limbs usually need to be studied
Even in simple entrapment neuropathies, studies should be bilateral and include at least one other
nerve not under suspicion to exclude an underlying generalised process
Motor and sensory Inadequate range of stimulus sites Dependent on the clinical picture stimulation may be required proximally to detect focal proximal
NCS abnormality. However, particularly with root and plexus stimulation, care in ensuring supramaximal
stimulation is vital
Motor NCS Electrode positioning If optimal positioning not used, the indifferent electrode may contribute significantly to amplitude
measurements
Motor NCS Nerve length measurement A flexible ruler/tape is necessary to follow the nerve path accurately
Some measurements around joints are affected by flexion/extension of the joint. For example, the
least errors are found in ulnar NCS if the elbow is flexed to .100˚
Motor NCS Not supramaximal If the CMAP is not recorded supramaximally at all sites, the measured FMNCV will be in error.
Spurious conduction block may be seen if proximal nerve stimulation is not supramaximal
Motor NCS Over stimulation If a nerve is stimulated with too high a current/voltage, adjacent nerves may be recruited and
produce spurious results
Sensory NCS Stimulus artefacts Particularly in the lower limb nerves the stimulus may cause an artefact which alters the NAP shape.
This must be allowed for in calculation if it cannot be abolished
Sensory NCS Absent potentials In some nerves, using the orthodromic technique, the 95% confidence limits may include zero
microvolts. Thus an absent potential may not be ‘‘abnormal’’
Motor and sensory NCS Normal values Failure to use age specific normal values in the very young and very old may lead to error
RNS Inadequate positioning and If the recording electrodes do not lie right over the motor point, a spurious decrement may be
movement restriction created as the muscle contracts repeatedly. Care over positioning and ideally splintage of the
muscle so that it remains isometric helps
Inadequate facilitation Patients may need continuous encouragement to obtain 30–30 second maximal voluntary
contraction
Too short an analysis period RNS trains should be followed for at least 3 minutes (preferably 5) to pick up the occasional post-
facilitation exhaustion
Limited sites The sensitivity of RNS in NMT disorders is greatly increased by studying both proximal (nasalis,
trapezius) muscles as well as distal (abductor digiti minimi).
Wrong test As a rule of thumb, a patient who has an unequivocally normal edrophonium test will frequently also
have a normal distal and proximal RNS test. In these circumstances the authors go straight to single
fibre electromyography of an intermediate and proximal muscle as a more sensitive test.

CMAP, compound muscle action potential; DL, distal latency; FMNCV, fastest motor nerve conduction velocity; NAP, nerve action potential; NCS, nerve
conduction studies; NMT, neuromuscular transmission; RNS, repetitive nerve stimulation.

Table 3 Interpretation
Pitfall Explanation

Overinterpretation of results c A limited numerical abnormality must be reported but placed in the context of the clinical problem—for example, the
finding of a subclinical carpal tunnel abnormality on NCS does not make the diagnosis of carpal tunnel syndrome
c An NCS abnormality may relate to a previous and currently irrelevant injury or operation
Over simplification of results c All studies should be interpreted together in case multiple diagnoses are present. Occum’s razor may be too sharp. For
example, in a patient with obvious polymyositis, NCS should ideally be performed to delineate any additional
coexisting neuropathy
Misinterpretation of NCS results c If the FMNCV is normal, the patient may still have slowing of conduction of other nerve fibres related to a neuropathy
c If the SNAPS are normal in all respects the patient may still have a small fibre sensory neuropathy producing symptoms
and signs
c If a nerve is reported unstimulatable, think of anomalous innervation or anatomical variation of nerve position before
concluding pathology
Misinterpretation of RNS results c If a decrement continues throughout the RNS train, this is probably artefact
c If a decrement is found in RNS, it is not pathognomic of myasthenia gravis. It has been found to be abnormal in a
number of conditions with abnormal nerve terminal function (motor neurone disease, active axonal neuropathy) or
muscle membrane instability (polymyositis)
c While MG and LEMS are the most common NMT disorders, the unwary will miss correctly diagnosing congenital
myasthenic syndromes, botulism, drug and toxins (for example, organophosphates), all of which have characteristic
PNE patterns when all tests are interpreted together with the clinical picture
For the referrer c If the referring doctor has not asked a specific question of the CN investigator, they should not be surprised if
occasionally their request for a PNE is misunderstood
c A PNE request should never be couched in ‘‘please exclude’’ terms. While probabilities may be discussed, total
exclusion of a diagnosis depends on non-biological errors such as sampling
c In the UK, CN are a scarce resource, often struggling with large waiting lists. Thus all referrals should be considered in
terms of: (a) what knowledge will I gain about my patient from this investigation? (b) Will the result change my
management? (c) How urgent should the request be?

CN, clinical neurophysiologist; LEMS, Lambert Eaton myasthenic syndrome; MG, myasthenia gravis; PNE, peripheral neurophysiological examination; SNAPS,
sensory nerve action potentials.

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NEUROLOGY IN PRACTICE

binding to receptors. In the healthy state, the end plate this case we are just comparing the amplitude of the first
potential reaches a threshold level and causes an action CMAP in the train before and after exercise (fig 8). Despite
potential to be propagated along a muscle fibre resulting in this increment, within each low frequency train a further
muscle contraction. Normally there is a large safety factor for decrement may occur due to ACh depletion.
neuromuscular transmission with the amount of ACh
released per impulse several times that required to generate PITFALLS
a threshold level end plate potential. There are many pitfalls that can trap the unwary both in the ii31
In low frequency RNS, the rate of stimulation is such that performance and the interpretation of the NCS and RNS. For
the end plate physiology is stressed, but not to the level that convenience these are separated in tables 2 and 3. The
produces the natural facilitation of NMT at greater stimula- technical pitfalls more appropriately addressed to the reader
tion frequencies. Thus an abnormal fall (decrement) in who is an expert or training in CN are not included.
CMAP amplitude and/or area at low stimulation rates
indicates a drop in the safety factor for transmission whether CONCLUSIONS
from a pre- or post-synaptic cause. Nerve conduction studies as part of the PNE are an extension
In high frequency stimulation natural facilitation is of the clinical history and examination and are important in
enhanced by pre-synaptic Ca++ influx and this may counter- the management of cranial and peripheral neuromuscular
act a process such as LEMS where quantal release is disease as well as contributing to diagnosis of spinal cord
depressed. lesions. NCS can be extremely useful both in localising
lesions and determining the pathological processes respon-
RNS in disease
sible. We have listed many of the pitfalls both for the CN
NMT disorders may be congenital or acquired and in broad
carrying out and interpreting the tests as well as for the
terms can be thought of as pre-synaptic or post-synaptic
referring doctor. For the former it is vital both to carry out
depending on where the defect lies.
tests accurately and reproducibly and to develop an investi-
Post-synaptic disorders of neuromuscular junction gation strategy based on the patient’s symptoms and signs
transmission rather than a fixed protocol. The investigator should then
The archetypal post-synaptic disorder is myasthenia gravis report the results clearly and then place them in the context
(MG) where antibodies to acetylcholine receptors (AChR) of the clinical situation.
cause degradation and increased turnover of receptor as well For the neurologist or other referring doctor, it is equally
as macrophage initiated post-synaptic membrane simplifica- vital that the clinical questions asked are explicit and
tion. In MG the safety factor is lost because as AChRs are answerable for the most to be gained from what can be a
depleted, less post-synaptic depolarisation occurs and some considerable investment in time and skills for the investi-
end plate potentials do not reach threshold for genesis of a gator and tolerance of discomfort in the patient. For the best
propagated muscle membrane potential producing neuro- use of scarce resources therefore training and awareness of
muscular block. If this process affects a significant proportion all the techniques detailed in this monograph are essential as
of the tested muscle end plates, the RNS baseline train will part of general neurological training.
show a significant decrement (greater than 10%). The ..................
decrement is usually measured by comparing the amplitude Authors’ affiliations
of the third or fourth CMAP in the train to the first (fig 7B). A Mallik, A I Weir, Department of Clinical Neurophysiology, Institute of
Very often some slight facilitation reduces the decrement Neurological Sciences, Southern General Hospital, Glasgow, UK
over potentials 7–10 of the train.
An abnormal decrementing RNS test is non-specific and
can be seen in a number of circumstances where muscle REFERENCES
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(see RNS pitfalls). Lippincott Williams & Wilkins, 1998.
c An extremely readable book with excellent explanatory sections on
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In LEMS there are antibodies to voltage gated calcium Elsevier, 2004.
c A reference text covering all aspects of clinical neurophysiology
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Lecture. Muscle & Nerve 1997;20:777–87.
a small initial CMAP amplitude. Here calcium influx into the c Reviews basic techniques, principles and pitfalls of nerve conduction
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4 DeLisa JA, Lee HJ, Baran EM, et al. Manual of nerve conduction velocity and
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sub-threshold. c Line drawings illustrate how to actually perform most nerve conduction
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However, the diagnostic abnormality is of a significant 5 BSCN website. www.bscn.org.uk/education.
. 100% increment in the CMAP amplitude after exercise or c Contains part of the Glasgow interactive EMG course with examples of
all the abnormalities discussed as well as self assessment cases.
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Nerve conduction studies: essentials and

pitfalls in practice
A Mallik and A I Weir

J Neurol Neurosurg Psychiatry 2005 76: ii23-ii31

doi: 10.1136/jnnp.2005.069138

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