Chapter 6 Motor nerve conduction studies

Chapter 6 Motor nerve conduction studies

Peripheral Nerve Diseases Handbook of Clinical Neurophysiology, Vol. 7 J. Kimura (Ed.) © 2006 Elsevier B.V. All rights reserved 139 CHAPTER 6 Motor...

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Peripheral Nerve Diseases Handbook of Clinical Neurophysiology, Vol. 7 J. Kimura (Ed.) © 2006 Elsevier B.V. All rights reserved

139

CHAPTER 6

Motor nerve conduction studies Kerry H. Levin* Cleveland Clinic Foundation, OH, USA

6.1. Introduction Motor nerve conduction studies constitute a major element of the electrodiagnostic examination. They can identify features of demyelination and axon loss, they can define defects of neuromuscular junction transmission, and they can reflect severe muscle fiber loss. Stimulation is applied at distal and proximal sites along a nerve trunk. Recording of the resulting action potential occurs with surface electrodes overlying a muscle belly innervated by the stimulated nerve (Fig. 6.1). Features of a motor conduction study that can be analyzed include the amplitude, area, and configuration of the response waveform, as well as its latency and conduction velocity. 6.2. The compound muscle action potential Since the active recording electrode overlies a muscle belly, the recorded response is a compound muscle action potential (CMAP). In comparison, the sensory nerve action potential (SNAP) is recorded directly from a nerve trunk. The CMAP represents a summation in the volume conductor of all the individual muscle fiber action potentials activated by the stimulus and within the pick up territory of the active recording electrode. Normally, the CMAP is a biphasic waveform with an initial negative deflection. This configuration results from placement of the active recording electrode at the motor point of the muscle belly, where the muscle fibers are initially depolarized and their action potentials generated. In comparison, the sensory nerve action potential is normally a triphasic waveform with initial positive deflection, because the propagated

* Correspondence to: Kerry H. Levin MD, Department of Neurology, Desk S-90, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland OH 44195, USA. E-mail address: [email protected]. Tel.: +1-216-444-8370; fax: +1-216-445-4653.

depolarization along the nerve trunk approaches the recording electrode from the stimulation site. The CMAP is measured in millivolts, compared to microvolts for a sensory action potential, because the size of an action potential is proportional to the diameter of the excitable tissue from which it is derived. A number of factors contribute to the size and shape of a normal CMAP, including the geographical relationship between the active and reference recording electrodes, active recording electrode size, the effect of recording distance on CMAP size, the effect of filtering, and the effect of temperature. 6.2.1. Relationship between recording electrodes and CMAP shape Manipulating the electrode placement in a differential amplifier recording system can affect the amplitude of the recorded potential. This is especially necessary when recording sensory nerve action potentials in the microvolt range. Because the CMAP size is measured in millivolts, it is not necessary to space the active and reference recording electrodes so that the potential at the reference electrode site adds amplitude to the waveform. Rather, by minimizing the reference electrode’s contribution to the CMAP response, variability in response size due to imprecise electrode placement can be theoretically minimized, and standardization of the technique improved. This has traditionally been accomplished by applying the reference electrode over the tendon distal to the muscle belly on which the active electrode is applied. Recent work has confirmed that the reference electrode may not be electrically silent in relation to the active electrode. This is especially true for the ulnar and tibial motor nerve conduction studies, where the traditional reference electrode position can contribute a greater amount toward the main negative peak of the CMAP than does the active electrode (Kincaid et al., 1993; Brashear and Kincaid, 1996). This effect correlates with the double-peak appearance of the ulnar and

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KERRY H. LEVIN

Distance = 270 mm

7 mv

S

CV = 270 = 54 m/s 5

A 8.5 ms

Fig. 6.1 Median motor nerve conduction study, after stimulation at the elbow (A), and wrist (B). The measured distance between the two stimulation sites is 270 mm. (From Levin, 1993. Common focal mononeuropathies and their electrodiagnosis. J. Clin. Neurophysiol. 10: 181–189, reproduced with permission)

6.5 mV

S

B 3.5 ms

tibial CMAP. In comparison, the reference electrodes do not significantly contribute to the main negative component of the median and peroneal CMAPs. The large reference electrode contribution to the tibial response may result from the large amount of tibial muscle mass in the foot and its wider geographical distribution in the foot, compared to peroneal musculature. Far-field muscle potentials may also be contributing to this effect (Dumitru and King, 1991). An attempt to neutralize the effect of the reference electrode by placing it on the contralateral limb leads to further complications. With that montage, short latency components are recorded at the onset of the tibial CMAP when proximal stimulation studies are performed. These extra potentials are thought to be farfield components generated from muscle action potentials in the distal leg. They do not appear when the active and reference electrodes are ipsilateral, due to common mode rejection (Brashear and Kincaid, 1996). The size and shape of the ulnar CMAP obtained with the active electrode overlying the hypothenar region depend on the action potentials from all ulnar innervated hand muscles. Stimulating individual muscles, McGill and Lateva showed that the first peak of the negative phase of the CMAP is derived from hypothenar muscles, while the second peak is due to a volume conducted potential from interosseus muscles (McGill and Lateva, 1999). This contribution was altered by changing the relative positioning of the fingers, and could be affected by the presence of a temperature gradient in the hand. A reduction in the

interosseus contribution was obtained with the use of a combined reference from two electrodes, one on each tendon of the hypothenar muscle group. (Fig. 6.2) Muscle fiber length and muscle position have an effect on the shape of the CMAP. Examining the thenar CMAP, Lateva and colleagues showed that changes in CMAP shape and amplitude with thumb abduction are due to changes in termination time (point at which the muscle fiber action potential reaches the muscle-tendon junction) resulting from changes in muscle fiber lengths (Lateva et al., 1996). (Fig. 6.3) 6.2.2. Relationship between electrode size and CMAP There is a complicated relationship between the recording electrode size CMAP characteristics. This topic is treated in detail in Chapter 5. One study showed an advantage to the use of a larger electrode size (comparing a standard 10 mm diameter tin disc electrode with a disposable adhesive ground electrode measuring 2.9 × 2.65 cm) in regard to inter-operator and inter-study reproducibility of results (Tjon-ATsien et al., 1996). Their study did not show a significant change in CMAP amplitude, but larger electrodes tended to produce slightly longer distal latencies and slower mean conduction velocities. However, other authors identified the opposite; over the range of round disc electrode diameter from 4 to 14 mm, there was a 10% decrease in amplitude but no change in latency,

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141

b/dt

b/dt

A

b/pt

b/pt

b/br

b/br

C

Neutral d2-d4 flexed

dt

2 ms

b/dt

b/dt

b/pt

b/pt

b/br subj KM.I

B

4 mV

b/br subj SK.r

D

b

− +

b/br

pt

E

Fig. 6.2 Cancellation of the interosseus contribution using a balanced reference. (A, C) Sums of the directly stimulated interosseus signals recorded by the b/dt and b/pt electrode configurations, and the “balanced reference” signal (b/br) formed by adding 1/3 times the signal to 2/3 times the b/pt signal, for two subjects. The interosseus contributions are almost completely canceled in the b/br signals. (B, D) The effects of length manipulation (solid line = neutral, dashed line = flexion of digits 2–4) are reduced in the b/br CMAP compared to the b/dt and b/pt CMAPs. (E) Electrode configuration for recording the balanced-reference signal. Reference electrodes are placed over both the distal and proximal tendons and are connected in parallel. The distal electrode has been cut in half to give an approximate 1 to 2 ratio between the dt and pt contributions (From McGill and Lateva, 1999, reproduced with permission from John Wiley and Sons, Inc.).

simultaneously electrically evoked components of the CMAP, due to different rates of conduction along motor nerve fibers (Schulte-Mattler et al., 2001). The lesser degree of temporal dispersion seen in CMAPs compared to SNAPs is attributed to the narrower range of conduction velocities along motor nerve fibers in a nerve trunk, and the broader duration of CMAPs (Fig. 6.5). Based on a mathematical model of the CMAP as a sum of asynchronous single nerve fiber action potentials, it has been estimated that there may be a 25-m/s difference between fastest and slowest fibers in a sensory nerve trunk, versus 11 m/s for motor fibers (Dorfman, 1984). For a SNAP, the lower

when recording over the abductor digiti minimi (Wee and Ashley, 1990). 6.2.3. Effects of distance from point of stimulation to recording site The CMAP generated at a proximal site of stimulation differs modestly from the CMAP obtained with distal simulation. (Fig. 6.4) The measurable differences include reduced amplitude and area, increased duration, and shallower initial negative slope of the proximally generated CMAP. These changes result from temporal dispersion, or desynchronization, of the

Abducted 90⬚ Abducted 45⬚ Relaxed Extended

2 mV 2 ms pt/p (x5)

tt/t(x10) b/t

A

subj FS

B

b/p subj KM

Fig. 6.3 CMAPs recorded at different thumb positions (extended, relaxed, abducted by 45˚, and abducted by 90˚) for 2 subjects (From Lateva and McGill, 1996, reproduced with permission from John Wiley and Sons, Inc.).

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Fig. 6.4 Ulnar CMAPs recording from the hypothenar eminence, resulting from stimulation at the wrist (1), below the elbow (2), above the elbow (3), at the axilla (4), and at the supraclavicular site (5). Vertical division = 5 mV; horizontal division = 5 ms.

amplitude obtained after proximal stimulation is likely related to physiological phase cancellation due to the velocity-related temporal dispersion of sensory action potentials over a nerve segment and the short duration

of sensory action potentials (Kimura et al., 1986). (Figs. 6.6 and 6.7) For motor NCS in normal subjects, most laboratories expect less than 20% decrease in the amplitude between the distal stimulation site and

Fig. 6.5 Median sensory nerve action potentials recording from digit 2, resulting from stimulation at the wrist (1), above the elbow (2), at the axilla (3), and at the supraclavicular site (4). Vertical division = 20 μV; horizontal division = 2 ms.

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143

Individual responses

Summated responses

F

S

F

F

S

Fig. 6.6 A model for phase cancellation between fast (F) and slow (S) conducting sensory fibers. With distal stimulation, two unit discharges summate in phase to produce a sensory action potential twice as large. With proximal stimulation, a delay of the fiber causes phase cancellation between the negative peak of the fast fiber and positive peak of the slow fiber, resulting in a 50% reduction in size of the summated response (From Kimura et al., 1986, with permission.).

elbow or knee, with the exception of the tibial study, where there can be up to 50% decrease in amplitude with proximal stimulation. The degree of temporal dispersion in a CMAP is related to the length of the conducted segment and the range of conduction velocities in the nerve trunk. Therefore, the impact will be greater along nerves in the leg, especially the tibial nerve. Using clinical measurements and Fourier analysis from 86 subjects, Schulte-Mattler et al., found that amplitude loss was most marked for the tibial (36%) and ulnar (21%) nerves, area loss for the median (12%) and ulnar (18%) nerves, and duration prolongation for the tibial (32%) and ulnar (17%) nerves (Schulte-Mattler et al., 2001). None of these findings was age dependent. Their data showed that the dependence of these variables on length was approximately linear. In a disease

state, the range between fastest and slowest motor fibers increases, and phase cancellation becomes more prominent along motor nerves (Lee et al., 1975). 6.2.4. Effects of filtering on the compound muscle action potential Electrophysiological recordings obtained from a differential amplifier can be altered by manipulating the bandwidth of frequencies allowed to contribute to the recording. Filter settings are chosen to maximize the contribution of frequencies close to the recording electrodes and minimize contamination of the recording by remote generators. Because amplitude, latency, and waveform configuration change as filter settings are altered, standard settings are required.

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KERRY H. LEVIN Individual responses

Summated response

F

S

F S

Fig. 6.7 Same arrangement as in Fig. 6.6 to show the relationship between fast (F) and slow (S) conduction motor fibers. With distal stimulation, two unit discharges representing motor unit potentials summate to produce a muscle action potential twice as large. With proximal stimulation, long-duration motor unit potentials still superimpose nearly in phase despite the same latency shift of the slow motor fiber as the sensory fiber shown in Fig. 6.6. Thus, a physiological temporal dispersion alters the size of the muscle action potential only minimally, if at all (From Kimura et al., 1986, with permission.)

Increasing the low frequency filter setting tends to reduce CMAP amplitude, peak latency, and total waveform duration (Fig. 6.8). These effects are related to the filtering out of important low frequency components contributing to the overall size of the CMAP waveform. There is no effect on the onset latency of the CMAP (Dumitru and Walsh, 1988). Decreasing the high frequency filter tends to increase peak and onset latencies, and increase the negative spike component of the CMAP (Fig. 6.9). Onset latency becomes delayed because highfrequency components over a short duration at the onset of the waveform are filtered out, causing a “drop out” of the first part of the potential. There is little effect on the amplitude down to a frequency of 500 Hz. 6.2.5. Effects of temperature on the compound muscle action potential A decrease in muscle temperature corresponds with increased CMAP amplitude, duration, rise time, and area. Local cooling leads to increased voltage of muscle fiber action potentials (Ricker et al., 1977). This is the result of delayed voltage-gated sodium channel inactivation, leading to excess depolarization of the muscle fiber membrane and, subsequently, increased propagated action potential duration, spike height, and area (Scheopfle and Erlanger, 1941).

6.2.6. Sources of error in compound muscle action potential recordings Of all the motor NCS parameters, CMAP amplitude appears to have the least reproducibility (Bleasel and Tuck, 1991; Claus et al., 1993; van Dijk et al., 1994, Kohara et al., 2000). While mean motor nerve conduction velocities are highly reproducible, the coefficient of variation for CMAP amplitude and latency has ranged from 8.5–46% (Tjon-A-Tsien et al., 1996). Inability to reproducibly localize the optimum recording site appears to be the main cause of variability. Van Dijk et al. showed that a variability of 5–10 mm in the recording site could have a profound effect on CMAP amplitude (van Dijk et al., 1994). Variability in CMAP amplitude and latency recordings is even higher in patients with diabetic neuropathy (Tjon-A-Tsien et al., 1996). Other sources of error can be identified in the routine laboratory on a daily basis, although their contributions have not been studied scientifically. Submaximal stimulus intensity, imprecise stimulator placement, stimulus spread to adjoining nerve trunks, and temperature fluctuations all contribute to CMAP recording variability and error. The normal CMAP amplitude, configuration, or both may be altered in the presence of anomalous innervation. In the case of the median-to-ulnar

MOTOR NERVE CONDUCTION STUDIES

145 Fig. 6.8 Ulnar CMAPs recording from the hypothenar eminence, after stimulation at the wrist. Low filter setting is 2 Hz (1), 10 Hz (2), 20 Hz (3), 50 Hz (4), and 500 Hz (5). The high filter setting remains constant at 10 KHz. Vertical division = 10 mV; horizontal division = 5 ms.

crossover in the forearm (estimated to occur in 5–30% of arms), ulnar motor nerve fibers reside in the median nerve at the elbow, but switch back into the ulnar nerve trunk somewhere in the forearm. This leads to co-stimulation of median and ulnar motor fibers at the elbow but not at the wrist, giving rise to disparity between the CMAP waveforms at the two sites of stimulation (Chapter 14). 6.3. Motor conduction latency and velocity The speed with which an electrical impulse passes along a motor nerve trunk is a composite of the speeds of individual motor nerve fiber action potential propagations to the recorded muscle motor point. These are, in turn, related to the diameter of nerve fibers, temperature, stimulation intensity, and age.

6.3.1. Effects of temperature on motor conduction velocity Temperature has a marked effect on nerve conduction (see above). Nerve conduction velocity decreases in proportion to the decrease in temperature, without a significant influence from nerve fiber size. Conduction velocity can be measured to decline to as low as 1–2% of normal velocity, before conduction fails entirely at 7–8˚C (Paintal, 1965). The degree of change in conduction velocity with progressive change in temperature for upper extremity nerve trunks has been defined (Halar et al., 1980, 1983). For the median motor conduction velocity, there is a 1.5 m/s decline for every 1˚ C temperature decrease. The median motor distal latency increases by 0.2 m/s for each 1˚ C decrease in temperature. The

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Fig. 6.9 Ulnar CMAPs recording from the hypothenar eminence, after stimulation at the wrist. The response with a latency of 2.8 ms corresponds to a high filter setting of 10 KHz, 2.9 ms corresponds to 2 KHz, 3.0 ms corresponds to 1 KHz, and 3.2 ms corresponds to 500 Hz. The low filter setting remains constant at 2 Hz. Vertical division = 5 mV; horizontal division = 2 ms.

ulnar motor conduction velocity decreases by 2.1 m/s for every 1˚ C temperature decrease, and the ulnar motor distal latency increases by 0.2 m/s for each 1˚C decrease in temperature. 6.3.2. Effects of age on motor conduction velocity Peripheral nerves at birth are not fully myelinated. Motor nerve conduction velocities in the neonate are about one half the adult values. The developmental process of myelination continues until the age of 3 to 5 years, when conduction velocities approach adult values (Wagner and Buchthal, 1972). Over the age of 50 years, conduction velocity declines by 1–2 m/s per decade. There is an associated progressive increase in distal latency. 6.3.3. Sources of error in obtaining motor conduction velocity A number of sources of error exist in the performance of NCS that can lead to spurious conduction velocities. Foremost among these is measurement of the dis-

tance over which the conduction is occurring. Landmarks easily shift on extremities, giving rise to significant variation in the same patient and among patients. These errors tend to be amplified over shortconduction distances (since the error is a larger proportion of the whole distance), and when conduction velocities are higher (Maynard and Stolov, 1972). Anatomy and nerve trunk position issues also predispose to a lack of reliability. When analyzing nerve conduction around a joint (classically the ulnar nerve as it courses around the elbow), the conduction distance varies according to whether the joint is flexed (the nerve is stretched to its fullest extent and lengthened) or extended (the nerve is kinked on itself and shortened). However, the latency of conduction remains the same, so that in the flexed elbow position, the calculated conduction velocity will be slower than in the extended elbow position. Stimulus spread can introduce error in the conduction velocity measurement. When the stimulus intensity is increased beyond the ideal supramaximal level, a shift in the location of nerve trunk depolarization can

MOTOR NERVE CONDUCTION STUDIES

change by 3–5 millimeters (Buchthal and Rosenfalck, 1966). If the stimulus spread occurs in the direction of the recording electrode, the true conduction distance is shorter than the measured distance, leading to a falsely increased conduction velocity. A theoretical consideration is the effect of passive lengthening or shortening of muscle fibers on latency and velocity of conduction. Measuring over a segment of a muscle fiber, Trontelj used single fiber recordings to show that stretching a muscle fiber could reduce its conduction velocity by 22%, while shortening the muscle fiber could increase the velocity by up to 33% (Trontelj, 1993). In another study, intramuscular stimulation of nerve fibers in the biceps brachii showed no significant change in impulse conduction velocity with muscle fiber length change when recording over the center fiber length, but a decrease in latency by as much as 24% occurred with muscle fiber shortening (Brown et al., 1996). In shortened muscle, the plasmalemma of a muscle fiber is folded and there are inpouchings of membrane known as caveolae (Dulhunty and Franzini-Armstrong, 1975). This may explain why the time taken for impulses to travel between individual sarcomeres, and to reach the end of a muscle is least in the shortened position. 6.4. Performing routine motor nerve conduction studies 6.4.1. Overview Nerve conduction studies and the needle electrode examination constitute the major components of the electrodiagnostic examination. In most clinical laboratories, the NCS are performed first, and guide the physician in the approach to the needle electrode examination. NCS require no active participation from the patient. Although the electrical stimulations are uncomfortable, they are tolerable to all but the most sensitive patients. They are indispensable for the electrodiagnosis of focal nerve lesions in the extremities and are the only way to gain physiological confirmation of the presence of demyelination. There are a number of limitations regarding the use and interpretation of motor NCS. First, very proximal portions of nerve trunks cannot be reliably accessed for stimulation. Second, because of unavoidable technical imprecision in performing motor NCS and because of a wide range of normal for CMAP amplitudes, detection of motor axon loss by NCS is relatively insensitive, unless over 50% of

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nerve fibers have been lost. Comparison with the contralateral limb can improve the sensitivity, if the condition is unilateral. Third, motor NCS are also relatively insensitive to the presence of muscle fiber loss in myopathy. Individual clinical EMG laboratories differ in the technical aspects of performing motor nerve conduction studies. However, the basic approaches are similar in most laboratories. The following descriptions are considered standard techniques. 6.4.2. Setting up the electrodiagnostic machine Machine settings must be adjusted for proper motor nerve conduction study results. Settings to be adjusted include the filters, sweep speed, and gain. Filter settings for motor NCS should allow a wide recording bandwidth. The low filter setting is usually set at 2 Hz, and the high filter setting is 10 KHz. Because the CMAP response is large (measured in millivolts), the effect of contamination from CMAPs of neighboring muscle bellies is less important. Thus, the objective is to include as many of muscle fiber action potentials as possible in the summated CMAP of the recorded muscle. For each nerve trunk stimulation, the sweep speed needs to be adequate in order to capture the produced CMAP. Reliable measurement of the latency depends on a precise waveform offset from baseline. The visual characteristics of that take-off point change with changes in the sweep speed. Thus, in order to optimize reproducibility of technique, the sweep speed should be fast enough to capture CMAPs at all planned points of stimulation. Normal distal motor latencies recorded after stimulation at the wrist or ankle range from 3 to 6 ms in normal adults. In the arm, latencies measured at the hand muscles after stimulation at the elbow and supraclavicular sites of stimulation range from 6 to 10 ms, and 13 to 15 ms, respectively. In the leg, latencies measured at the foot muscles after stimulation at the knee range from 8 to 10 ms in normal adults. These values correlate directly with the length of the arm and leg. In disease states, latencies may increase by a factor of two or more. When no motor response is recorded after nerve stimulation, it is important to increase the sweep speed to identify the presence of a pathologically slowed response. The gain setting should also be chosen to maximize CMAP visibility and accuracy of measurement of amplitude and latency. Like the sweep speed, the gain

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setting should be the same for all stimulation points of a given nerve trunk. This will avoid inaccuracies in the measurement of latency. Increasing the gain tends to increase onset latency (Dumitru and Walsh, 1988) (Table 6.1). 6.4.3. Stimulus guidelines and pitfalls For motor NCS, stimulus duration should be 0.2 ms initially. The stimulus voltage should be increased gradually until there is no further increase in CMAP amplitude. At that point, the stimulus voltage should be increased by another 10–20%, the so-called supramaximal stimulus intensity. If a maximum CMAP is not achieved, the duration should be increased, and the process repeated. Failure to use a supramaximal stimulus will result in the possibility of a less than maximal CMAP amplitude. On the other hand, excessive stimulation increases the possibility that nearby nerve trunks will be co-stimulated, leading to a falsely increased CMAP amplitude or a spurious waveform configuration. Co-stimulation is likely to occur between the median and ulnar nerve trunks at the wrist and above the elbow; among the median, ulnar, and radial nerve trunks at the axilla; and between the peroneal and tibial nerve trunks in the popliteal fossa. Excessive stimulation can also lead to stimulus jump beyond the region immediately under the stimulating electrodes. In general both the cathode and anode of the stimulator should be placed on the nerve trunk, with the cathode distal (and closest) to the recorded muscle. The anode may be swiveled off the nerve trunk when there is excessive shock artifact and when the usual placement causes direct muscle belly stimulation, as is the case when stimulating the facial nerve and recording over the nasalis muscle. Table 6.1 Effect of gain setting on the CMAP latency after median nerve stimulation at the wrist, recording over the abductor pollicis brevis muscle* Gain setting (mV/division)

Onset latency (m/s)

Amplitude (mV)

500 1000 5000 10 000

3.4 3.5 3.7 3.8

23 23

*The high and low frequency filters remained constant at 10 000 Hz and 10 Hz, respectively (Dumitru and Walsh, 1988).

Points of stimulation along a nerve trunk are limited to sites close to the skin surface. Routinely, these sites are at the wrist, elbow, ankle, and popliteal fossa. Nerve trunks can also be stimulated in the axilla and in the supraclavicular fossa. Specific nerve trunks are also accessible, such as the phrenic and spinal accessory nerves in the neck, and the facial and trigeminal nerves face. Needle electrodes used for stimulation may be able to reach some deep nerves, such as extra-spinal nerve roots. 6.4.4. Electrode placement and pitfalls Electrodiagnostic standard practice requires that the active recording electrode be placed over the motor point of the muscle belly innervated by the nerve trunk being stimulated. This location is identified by moving the electrode with each stimulus until a CMAP of maximal amplitude and initial negative deflection occurs. This task is relatively straightforward in the distal hand and foot muscles. The reference electrode is traditionally placed distal to the active recording electrode, on a relatively electrically silent structure such as a muscle tendon. As noted above, in actuality there is no electrically inactive site. The reference electrode is especially likely to contribute to the ulnar and tibial CMAP waveform appearance (Brashear and Kincaid, 1996). The task is more difficult when recording proximally (such as the forearm), where there are layers of overlapping muscles, either innervated by the same nerve trunk, or innervated by a nerve trunk that may be co-stimulated with the nerve trunk under investigation. In either case, there is a potential for generation of a spurious CMAP waveform that has an initial volume-conducted positive deflection, a falsely enlarged amplitude, or an altered configuration. A spurious CMAP may also be generated from hand muscles, such as the thenar group, when stimulating proximally at the axilla and supraclavicular site, where co-stimulation of the ulnar nerve is sometimes unavoidable. In this setting, volume-conducted components from closely positioned ulnar innervated muscles contaminate the thenar (median-derived) CMAP. Contamination of the thenar recording may be reduced by selectively recording from the thenar muscle group with an intramuscular needle electrode, thus decreasing the recording distance and minimizing the distant volume–conducted contributions. When stimulating the ulnar nerve proximally and recording from the hypothenar group in the hand, there is less chance of contamination from median nerve costimulation, since there are no large median innervated muscles in close proximity to the hypothenar group.

MOTOR NERVE CONDUCTION STUDIES

6.4.5. Calculating the conduction velocity Conduction velocity can be calculated easily after stimulating at two sites along a nerve trunk. The distal latency is the time elapsed from the point of distal (wrist or ankle) stimulus to the time of initial CMAP onset. This value is subtracted from the latency obtained when stimulating at the proximal site and recording from the muscle belly. After measuring the distance between the proximal and distal stimulation sites, it is simply a matter of completing the equation v = distance/time. The resulting value represents the conduction velocity in the forearm and foreleg, since the distal conduction has been subtracted out (Fig. 6.1). When a nerve trunk remains superficial over a whole segment of its length, it is possible to sequentially stimulate at short intervals. Examples include the median nerve at the wrist and palm, and the ulnar nerve across the elbow. Segmental conduction studies can be performed along short segments, as the stimulator is moved at 1 cm increments along the nerve, a technique described as inching. Inching has the potential to localize a focal nerve lesion (site of compression, entrapment, or focal demyelination) by demonstrating slowing or amplitude drop over a short nerve segment (Chapter 8). In general, a distal conduction velocity (from the distal-most site of stimulation to the muscle belly recording electrode site) is not calculated, because the latency of conduction over that segment includes conduction time along the small-diameter terminal axon branches, the neuromuscular junction transmission time, the time to depolarize the muscle membrane, and the time to generate a muscle fiber action potential. The distal latency is, therefore, longer than the latency over the same distance along a more proximal segment of the nerve. The difference between the distal latency and a more proximal latency over the same distance is described as the residual latency, and reflects the conduction time through terminal axons and the neuromuscular junction transmission time. Representative normal limits of some motor nerve conduction studies are displayed in Table 6.2. 6.4.6. Practical guidelines A number of practical guidelines will improve the reliability and sensitivity of motor NCS. At the hand the skin temperature should be maintained at 35˚C or above; at the foot the temperature should be at least 32˚C. When applying stimulation, it is critical to

149 Table 6.2 Normal limits of motor nerve conduction studies in a 40-year-old

Median Ulnar Peroneal Tibial

Amplitude Distal (mV) Latency (ms)

Conduction velocity (m/s)

>6 >7 >4 >6

>50 >50 >40 >40

<3.9 (8 cm distance) <3.0 (8 cm distance) <5.5 (5 cm distance) <5.8 (8 cm distance)

observe the degree and distribution of muscle contraction. This assures that adequate stimulation is being applied and that the expected muscle contraction is occurring. Co-stimulation of neighboring nerve trunks will be observable by visual inspection of the muscle groups contracting. The failure to achieve a normal response requires a careful search for technical causes. These include over or under stimulation, off-nerve stimulation, improper recording electrode placements, and improper set up of the voltage and/or duration of stimulus. Any response obtained that is considered abnormal must be compared with the response on the opposite side when the symptoms are unilateral. When a response is at the lower end of the normal range, it is appropriate to study the opposite side, looking for subtle pathology that may not constitute an abnormality based its absolute value. 6.4.7. Advanced techniques Several uncommonly used techniques may be useful in special situations. With motor NCS a needle electrode can at times be useful, both for stimulation and recording. A needle electrode can be used to penetrate deep to the skin surface to stimulate a nerve trunk not accessible with percutaneous stimulation. Use of a needle electrode to stimulate the median or ulnar nerve branches in the forearm can provide an additional distal or proximal site of stimulation to confirm the precise location of a conduction block. A needle electrode can also be used for recording purposes. In the setting of severe nerve trauma, a CMAP from an involved muscle may not be obtainable using disc electrodes applied to the overlying skin. A needle electrode within the muscle may be able to record small CMAP responses otherwise not obtainable. CMAPs can be obtained after stimulation from sites proximal to the peripheral nervous system.

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Trans-cranial magnetic stimulation produces recordable muscle potentials with latencies that reflect transmission along central and peripheral motor pathways (see Chapter 19). Intra-operatively electric motor evoked potentials provide similar information when used for cortical and spinal cord stimulation. 6.5. Basic patterns of pathology 6.5.1. Electrodiagnostic correlates of weakness Although a number of symptoms bring patients to the electrodiagnostic laboratory, weakness is the primary symptom being explored with motor NCS. Among all the motor parameters examined, CMAP amplitude is the only one that correlates closely with weakness. While changes in conduction velocity and latency may be seen in patients who are weak, weakness is directly related to interruption of impulses along motor nerves, leading to failure to depolarize muscle fibers. Established axon loss of motor nerve fibers produces CMAPs of reduced amplitude at all points of stimulation along the nerve, irrespective of the location of initial injury to the nerve fibers. Conduction block is the result of demyelination along motor nerve fibers to the extent that essentially all action potential propagation across the demyelinated

segment ceases, even though the underlying motor axons remain intact. The result of either axon loss or conduction block along a nerve fiber is the failure of action potential arrival at the nerve terminal and, ultimately, failure of muscle fiber contraction. Less complete demyelination along a nerve fiber may cause disruption of saltatory conduction without complete interruption of action potential transmission. The result is slowing of conduction, but the action potential reaches the nerve terminal, and ultimately its muscle fiber contracts. Thus, slowing of conduction velocity and prolongation of latency do not by themselves cause weakness. 6.5.2. Evolution of CMAP loss in an acute axon loss process After nerve transection, a series of pathological events takes place culminating in Wallerian degeneration of the nerve fibers. In spite of complete disconnection of the distal nerve fibers from their proximal portions and their anterior horn cells, and also in spite of cessation of axonal transport, the distal nerve fiber membranes can still be depolarized and action potential propagation continues for some days. Progressively, nerve fiber disintegration and neuromuscular junction transmission failure result in loss of nerve excitability and muscle fiber depolarization.

Injury 100

80

60 NCS amp. (%)

40

20

0

0

1

2

3

Motor and sensory, stimulating proximal to lesion

6 4 5 Days post-injury

7

8

Motor, stimulating distal to lesion

9

10

11

12

Sensory, stimulating distal to lesion

Fig. 6.10 The time course of changes in the CMAP and sensory nerve action potential amplitudes following a severe axon loss lesion (From Wilbourn, AJ, 1986 AAEE Case Report #12: Common peroneal mononeuropathy at the fibular head. Muscle Nerve 9: 825–836, reproduced with permission from John Wiley and Sons, Inc.)

MOTOR NERVE CONDUCTION STUDIES

After a severe proximal motor nerve trunk transection, with stimulation of the nerve distal to the point of transection, the CMAP amplitude remains normal until day 3 after transection. From that point, until day 5–8, there is a nearly linear decline in the evoked CMAP amplitude until the lowest amplitude is obtained, determined by the proportion of motor nerve fibers transected (Wilbourn, 1986) (Fig. 6.10). During this process, there is no significant change in the motor latencies or conduction velocities. In studies of progressive motor neuron disease of the ALS type (amyotrophic lateral sclerosis), Lambert demonstrated that the mean ulnar motor conduction velocity of 322 patients did not fall below 50 m/s until >75% of CMAP amplitude had been lost, corresponding to loss of the last fastest-conducting motor nerve fibers. (Lambert, 1962) In comparison, the sensory nerve action potential amplitude falls at a different rate after nerve fiber transection. With stimulation and recording distal to the point of nerve transection, the sensory nerve action potential amplitude remains normal until day 5. From that point, until day 8–10, there is a nearly linear decline in the evoked sensory nerve action potential amplitude until the lowest amplitude is obtained, determined by the proportion of sensory nerve fibers

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transected (Wilbourn, 1986) (Fig. 6.10). Decline of the sensory nerve action potential amplitude reflects failure of nerve fiber action potential propagation alone, since the response is recorded from the nerve fibers themselves. The faster failure of motor conduction as measured from the CMAP likely reflects earlier failure of neuromuscular junction transmission. 6.5.3. Patterns of abnormality on routine nerve conduction studies Disorders affecting peripheral nerves may be primarily axon loss in etiology, primarily demyelinating, or mixed. Motor NCS are a critical component of the assessment of nerve pathophysiology. With axon loss processes, the NCS pattern differs for acute and subacute/chronic lesions. With an acute complete transection of the median nerve trunk in the forearm of 3 days’ duration or less, stimulation of the median nerve at the elbow, recording over the thenar eminence will yield no CMAP response. With stimulation anywhere below the site of transection, the CMAP will have normal amplitude. After 8 days from the time of transection, stimulation of the nerve anywhere along its course will yield no CMAP response (Fig. 6.11).

Axon loss

Distal stimulation site

Proximal stimulation site

Normal

Acute discontinuity conduction block between proximal and distal stimulation sites

Axon loss anywhere along nerve, >8 days

Fig. 6.11 CMAPs with various axon loss lesions. The first waveform in each line results from distal motor nerve trunk stimulation, and the second waveform results from proximal nerve trunk stimulation.

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KERRY H. LEVIN

Demyelination Distal stimulation site

Proximal stimulation site

Normal or conduction block proximal to stimulation sites

Generalized, synchronized slowing

Segmental slowing between sites of stimulation

Focal conduction block distal to distal stimulation site

Focal conduction block between sites of stimulation

Fig. 6.12 CMAPs with various demyelinating lesions. The first waveform in each line results from distal motor nerve trunk stimulation, and the second waveform results from proximal nerve trunk stimulation.

With predominantly demyelinating processes, the NCS pattern varies according to the nature and severity of the demyelinating lesion. A focal conduction block (such as is seen with compressive radial neuropathy at the spiral groove) will resemble the pattern noted above in the acute stage of a partial or complete nerve trunk transection. A diffusely and homogeneously demyelinating process (such as Charcot–Marie–Tooth Disease Type 1a) will demonstrate relatively preserved CMAP configurations with prolonged latencies and slowed conduction velocities. A non-uniform, segmental demyelinating process (such as acute inflammatory demyelinating polyneuropathy; i.e., Guillain–Barré syndrome) may demonstrate conduction block and variable slowing within the same nerve trunk, resulting in CMAPs with reduced amplitude and dispersed configuration at proximal sites of stimulation (Fig. 6.12). Focal or generalized slowing of conduction as the sole manifestation of a peripheral nerve disorder is uncommon. Median neuropathy at or distal to the wrist (carpal tunnel syndrome) of mild-moderate severity may be the only common example of this pattern. Mixed patterns of demyelination and axon loss are common. This is because: (1) progressive demyelination is often associated with damage to the underlying axons; and (2) axon loss processes develop electrophysiological features of demyelination as a reflection of nerve regeneration. Some axon loss disorders, such as diabetic polyneuropathy, have an electrophysiological signature which includes mild features of demyelination. Focal entrapment of the peroneal nerve at the fibular head is an example of a focal nerve disorder that is characterized most commonly by the

Mixed axon loss and conduction block

Distal stimulation site

Proximal stimulation site

Normal

Axon loss with focal conduction block between sites of stimulation

Fig. 6.13 CMAPs with mixed axon loss and demyelinating lesions. The first waveform in each line results from distal motor nerve trunk stimulation, and the second waveform results from proximal nerve trunk stimulation.

MOTOR NERVE CONDUCTION STUDIES

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Wagner, AL and Buchthal, F (1972) Motor and Sensory conduction in infancy and childhood: reappraisal. Dev. Med. Child Neurol., 14: 189–216. Wee, AS and Ashley, RA (1990) Relationship between the size of the recording electrodes and morphology of the CMAPs. Electromyogr. Clin. Neurophysiol., 30: 156–168. Wilbourn, AJ (1986) AAEM Case Report #12: common peroneal mononeuropathy at the fibular head. Muscle Nerve, 9: 825–836.