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Laboratory Reference for Clinical Neurophysiology$

Jay A. Liveson and Dong M. Ma

Print publication date: 1999

Print ISBN-13: 9780195129243

Published to Oxford Scholarship Online: March 2012

DOI: 10.1093/acprof:oso/9780195129243.001.0001

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Introduction

Introduction

Chapter:
(p.2) (p.3) Chapter 1 Introduction
Source:
Laboratory Reference for Clinical Neurophysiology
Author(s):

Jay A. Liveson

Dong M. Ma

Publisher:
Oxford University Press
DOI:10.1093/acprof:oso/9780195129243.003.0001

Abstract and Keywords

The study of the conduction of nerves entails depolarizing the fibers with a stimulus, followed by monitoring the evoked response. Direct recording can be made along sensory or mixed nerves. Indirect recording from a muscle is used for motor studies. Both orthodromic and antidromic studies are available as propagation occurs both proximally and distally from the point of stimulation. Sensory territories are shown in this chapter. Polyneuropathy is diagnosed electrophysiologically by abnormalities in multiple nerves. The pattern is usually diffuse and symmetrical. Less often it is patchy, with severely involved and adjacent relatively spared nerves — a distribution most appropriately described clinically as mononeuritis multiplex. Multiple nerve “entrapments” may occur, sometimes superimposed over a diffuse polyneuropathy. Because of these possibilities, multiple nerves should always be examined, including clinically normal nerves.

Keywords:   conduction, nerves, direct recording, indirect recording, polyneuropathy, mononeuritis multiplex

Pathophysiology

The study of the conduction of nerves entails depolarizing the fibers with a stimulus, followed by monitoring the evoked response. Direct recording can be made along sensory or mixed nerves (the latter consisting of both sensory and motor fibers). Indirect recording from a muscle is used for motor studies. Both orthodromic and antidromic studies are available as propagation occurs both proximally and distally from the point of stimulation. Sensory territories are shown in Figures 1 to 3.

Several processes are occurring from the onset of the stimulus to the recording of the evoked response.436 Initially, approximately 0.1 msec elapses between the threshold stimulus and the initiation of an action potential (“utilization time”). Propagation of the potential along the nerve fiber then occurs; it is this propagation time which we would optimally like to isolate for use in our calculations. The preceding processes pertain to all nerve fiber types. Additional time elapses in conduction along motor fibers because of a delay at the neuromuscular junction, and slower conduction (3 to 5 M/sec) along the muscle fiber.501,618,642,650

Clinically, nerve conduction studies can be applied: (1) to diagnose diffuse polyneuropathy, (2) to pinpoint a focal lesion, and (3) to evaluate the severity of a nerve injury.75,514

Polyneuropathy is diagnosed electrophysiologically by abnormalities in multiple nerves. The pattern is usually diffuse and symmetrical. Less often it is patchy, with severely involved and adjacent relatively spared nerves —a distribution most appropriately described clinically as mononeuritis multiplex. Multiple nerve “entrapments” may occur, sometimes superimposed over a diffuse polyneuropathy. Because of these possibilities, multiple nerves should always be examined, including clinically normal nerves.

A distinction can sometimes be made between axonal and myelin pathology on the basis of the degree of slowing of conduction velocity. Severe slowing usually implies a myelin disorder (although it also occurs in early stages of axonal regeneration). (p.4)

Introduction

Figure 1. Sensory territory (after Haymaker). Stippled areas represent autonomous innervation; white perimeters represent the maximal extent of sensory territory. Upper extremity.

Minimal slowing is nonspecific.328 A decrease in amplitude usually typifies axonal pathology, but can occur with myelin dysfunction and therefore is not specific. It occurs during degeneration or regeneration.

In terms of sensitivity for early diagnosis of polyneuropathy, sensory studies may demonstrate the abnormalities earliest, especially amplitude measurements. The sural is one such sensory nerve which has been suggested as a “screening test” for polyneuropathy.82,416,417 Note, however, that sural studies can occasionally be normal at a stage where other nerves may demonstrate abnormalities.491

Late responses (F waves and H reflexes) may also be sensitive early indicators of polyneuropathy. Minimal slowing of conduction may remain undetected if only a short segment of nerve is studied. By approximately doubling the length of nerve studied by means of late responses, this slowing may become evident.3,123,380 Facial nerve latencies were found to show early changes in one study.488

Focal lesions (e.g., “entrapments”) are primarily myelin abnormalities caused by ischemia, or by myelin sheath distortion or slippage. Studies across a short nerve segment are optimal in demonstrating this type of lesion (in contrast to the polyneuropathies which may only be evident on studying a long nerve segment). If the study can be focused on the site of the lesion, the abnormality may be evident; whereas if a longer length of normal portion of nerve is included, the normal portion may compensate for and mask the small area of slowing. An abnormal nerve segment may (p.5)

Introduction

Figure 2. Sensory territory, as in Figure 1. Lower extremity, anterior, and lateral aspects.

(p.6)
Introduction

Figure 3. Sensory territory, as in Figure 1. Lower extremity, posterior, and medial aspects.

cause a change in the morphology of the evoked response (temporal dispersion), a fall in its amplitude, an increase in its latency, or a drop in conduction velocity. The segment proximal to the lesion usually conducts normally, although mild retrograde changes are known to occur (especially in carpal tunnel syndrome). The distal segment may conduct normally or abnormally, depending on the severity of the lesion.

Proximal lesions such as radiculopathies, plexus lesions, or proximal neuropathies (e.g., Guillain-Barré syndrome) are difficult to document with the routine (p.7) distal conduction studies. They may be studied electromyographically, or by using somatosensory evoked responses. Recent studies have indicated that late responses (F waves and H reflexes) may be helpful in these conditions.* In addition, root stimulation may add information.66,442

The severity of a nerve injury can be evaluated, and this information can potentially serve as the basis for subsequent comparison. Complete lesions may require surgical exploration and repair. If a response can be evoked across the site of an injury, this rules out a complete lesion. Similarly, if adequate time has elapsed for severed fibers to undergo wallerian degeneration (3 to 4 days), an intact response distal to the injury likewise argues against a complete lesion.282

The Response

The technical requirement in each conduction study is to record an evoked response. This is accomplished relatively easily with motor responses (compound muscle action potentials or CMAPs) which are large, measuring several millivolts. The difficulty here may be to determine the onset of the CMAP, which may deviate from the baseline too gradually or be obscured by the stimulus artifact (a common problem on stimulation near the recording electrode). To overcome this problem, the ground is optimally placed between the stimulating and recording electrodes, and it may be necessary to experiment with the orientation of the stimulating electrodes (from a position parallel to one perpendicular to the nerve, tuning). Occasionally, special isolation transformers are used. In addition, the shock artifact may be reduced by appropriate skin preparation (abrasion and cleaning to reduce skin resistance) or by using a needle for stimulation.

Even greater problems are encountered in recording sensory or mixed nerve action potentials which are of lower amplitude, measuring only microvolts. Because the noise level intrinsic to most amplification systems is approximately 5 μV, this may obscure a response whose amplitude is in this range. The noise level can be reduced by setting the high-frequency filter about 3000 Hz. Photographic or computer averaging may be necessary to visualize the responses.

The sensory techniques we have selected usually do not require such averaging, as the amplitudes of the responses (sensory nerve action potentials or SNAPs) substantially exceed the noise level. This is true, in general, of antidromic compared with orthodromic sensory studies (with some exceptions reported in studies of the lateral femoral cutaneous and the plantar nerves).

At times it is helpful to be able to predict the shape and polarity of the evoked response. If the electrodes are connected in a standard manner, the appropriate onset can be recognized. Sensory and motor responses can usually be distinguished by amplitude and duration. Sensory responses usually measure microvolts with a short duration. In contrast, motor responses measure several millivolts, and have several times the sensory duration. This distinction may help in some studies where both responses can be recorded, such as ulnar (Fig. 4) and lateral femoral cutaneous (Fig. 5) sensory nerve action potentials.

(p.8)

Introduction

Figure 4. Ulnar sensory (S) and motor (M) responses on wrist stimulation; recording is with ring electrodes on digit V. Calibration: 20 μV, 2 msec/cm. The two types of responses can be compared and distinguished. Note: the motor response is often eliminated by separating the digits.

Introduction

Figure 5. Antidromic sensory nerve action potential, lateral femoral cutaneous nerve. Calibration: 5 μV, 2 msec/cm. Isolated sensory (S) response is seen in lower recording; at slightly higher stimulus intensity this is followed by a volume-conducted motor (M) response (upper).

(p.9) The shape of the evoked potentials using surface recording is usually fairly predictable. Antidromic SNAPs usually consist of a negative wave followed by a smaller positive deflection (Fig. 6). A small positive potential may precede this (Fig. 7), especially in certain studies (such as radial and sural nerves). Evoked CMAPs usually have a large negative component followed by a smaller positive wave (Fig. 8). This pertains if the active electrode is located over the motor point. If there is a preceding small positive wave, the electrode may not be over the motor point (especially common in tibial nerve studies), or an anomaly may be present, such as a Martin-Gruber anastomosis (see pp. 85–88 and Figs. 32, 33).

Quantitative measurement can be made of several parameters of the response (Figs. 6, 7, 8). The latency is defined as the timed elapsed between the onset of the stimulus and some portion of the response. It is usually measured to the initial deflection of the response from the baseline for motor fibers, and to the initial point of negative deflection of the sensory response. This is called the onset latency (Figs. 6, 7, 8) of the response. A more clearly defined point is the negative peak of the SNAP, which yields the peak latency of the response (Figs. 6, 7). As stated above, a SNAP is usually initially negative (Fig. 6); it may, however, be preceded by a small positive wave (Fig. 7). In this case, the onset latency is measured to the peak of the initial positive wave of the sensory response (Fig. 7).

The amplitude is another important measurement (Figs. 6, 8). It reflects the number and synchrony of the fibers being tested. Amplitude may be measured peak to peak (Figs. 6, 8), or only a portion, such as the negative peak (Fig. 8). Amplitude measurement is less reliable than latency measurement, as it is affected to a greater degree if the recording electrodes are too close. If the electrodes are less than 3 cm apart, the amplitude may be significantly attenuated, especially in sensory studies.77 The amplitude recorded by surface electrodes over the muscle or the nerve will vary significantly depending on the distance from the motor point or the nerve. This may be less critical in some studies, for example, median, ulnar, and peroneal.83,135 In others the normal amplitude values are too variable to be usefully interpreted. When needle electrodes are used, amplitude cannot be reliably measured.

The shape and duration of the response also reflect the number and synchrony of the fibers contributing to the response. With greater asynchrony, the amplitude falls, the duration increases, and the shape becomes distorted. This is termed temporal dispersion. Attempts have been made to quantitate this by measuring the duration of a defined portion of the response. This is difficult and less accurate than other measurements. During segmental studies of a nerve, sudden changes in the shape of

Introduction

Figure 6. Antidromic sensory nerve action potential, ulnar nerve. Calibration: 20 μV, 2 msec/cm. SA = stimulus artifact; A = onset latency; B = peak latency; P = peak-to-peak amplitude. This is a typical surface-recorded antidromic sensory nerve action potential recording.

(p.10)
Introduction

Figure 7. Antidromic sensory nerve action potential, sural nerve. Calibration: 20 μV, 2 msec/ cm. A = onset latency (identical to peak of the initial positive wave); B = peak latency. This is representative of sensory responses with initial positive waves.

Introduction

Figure 8. Evoked compound muscle action potential, median nerve (upper) surface recording from abductor pollicis brevis; ulnar nerve (lower) recording from abductor digiti V. Calibration: 5 mV, 2 msec/cm. A = onset latency; P = peak-to-peak amplitude; N = negative wave amplitude. These are typical surface-recorded motor responses. Note that the ulnar response commonly has a “notched” initial negative wave form.

(p.11) the response will establish the exact site of a lesion. This is especially important in compression neuropathies.

Conduction velocity along a nerve segment is a calculated value expressed as distance divided by time (meters per second). In sensory or mixed nerve conduction studies, one latency and the distance are adequate to calculate the conduction velocity. Podivinsky547 has concluded that the conduction velocity calculated using the latency to the onset of the negative deflection is more representative than using peak latency values.

In the case of motor studies, conduction velocity cannot be calculated directly from one latency because this includes the neuromuscular junction delay and the slower conduction along the muscle fibers. Instead, the procedure is to find the latency difference between responses from two stimulation points. This eliminates all but the propagation time along the intervening length of nerve and can be used to calculate the conduction velocity of this segment.

Nerve conduction studies are technical procedures with many variables. In order to increase the reliability of the procedures these variables must be standardized as much as possible. The following is a discussion of biologic and technical variables that have to be taken into consideration.

Biologic Variables

Age

Saltatory conduction depends on mature myelination of peripheral nerve fibers. Because myelination occurs during the first years of life, the age of the subject must be taken into account.

Studies have shown that conduction velocity of premature babies reflects gestational age, suggesting that nerve development occurs in utero. As a result, conduction determination may be useful in estimating gestational age of low-birth-weight infants. A summary of the published data is included in Appendix 2.

In newborns, conduction velocity is approximately half of the adult values; it increases until normal adult values are attained by 3 to 5 years of age. Another maturational change is disappearance of median and ulnar H reflexes by 7 to 12 months of age. A summary of published data on infant maturation is included in Appendix 3.

In adults, the conduction values vary slightly from decade to decade, but this is usually of little significance until over age 60. Older subjects usually have slower conduction and lower amplitude responses, and these are especially evident in sensory studies. This may be a sign of myelin or axonal degeneration.

Temperature

Many studies have demonstrated the effect of temperature on human conduction velocity (Table 1). Velocity changes with the temperature at a rate of 0.7 to 2.4 M/sec for each degree centigrade. This effect decreases at higher temperatures, becoming less significant above approximately 30°C skin temperature.

(p.12)

Table 1. Temperature Effect

Change (M/sec per °C)

Nerves Studied

Reference

0.2*

Ulnar motor latency

Carpendale (1956)90

2.4

Ulnar motor

Henriksen (1958)274

0.7–1.5

Ulnar motor

Kato (1960)336

1.7–1.9

Sciatic motor

Gassel and Trojaborg (1964)227

2.0

Median SNAP

Buchthal and Rosenfalck (1966)77

1.0–1.3

Median and ulnar motor

Abramson et al. (1970)1

0.9–1.1

Median SNAP

Abramson et al. (1970)2

1.51–1.96

Median SNAP

Ludin and Beyeler (1977)435

1.3–1.4

Ulnar SNAP

Lowitsch et al. (1977)432

Median motor and SNAP

Dejesus et al. (1973)142

1.1–1.7

Tibial motor, sural SNAP

Halar et al. (1980)258

2.0

Peroneal motor

Halar et al. (1981)259

(*) msec per °C.

The shape of the response is also affected. Its latency, duration, and amplitude all increase as temperature falls.60 Ludin and Beyeler435 found a similar puzzling amplitude increase with temperature drop between 26° and 22°C.

In many laboratories the temperature of the skin is monitored and correction is made by heating the extremity, or by recalculating the conduction velocity for abnormally low temperature. In other laboratories only the ambient room temperature is controlled.

Gender

The difference between male and female subjects was found to be significant in a few studies. This included sensory studies of median, ulnar, radial, sural, and superficial peroneal nerves59,408 and in motor study of the ulnar nerve.401 Bolton and Carter59 found that amplitude correlated with finger circumference. Occasionally, the effect of aging was apparent in one gender only.344,405

Handedness

Hand dominance was found to correlate with slightly faster conduction velocity in some studies. This included median and ulnar conduction.51,129,626 In other studies no clear correlation was seen.401

Diurnal Variation

There have been several studies of possible diurnal variation.58,125 A circadian rhythm was found by Ferrario, Tredici, and Crespi.211 Others, however, have found (p.13) that any effect measured less than the standard deviation and therefore did not decrease reliability.700,734

Technical Variables

Electrodes

Surface or needle electrodes are available for recording and stimulating. Attention should be paid to the size, shape, and particularly the interelectrode distance of the active and reference electrodes. The amplitude, especially, is influenced by recording electrode placement (see p. 9). Because of the major changes caused by minimal needle movement, many consider needle recording electrodes unreliable for measuring amplitude. Even latency measurement requires repeated needle repositioning until a minimal value is measured. In spite of these difficulties, needle electrodes may be useful in cases where the response is small, such as in orthodromic sensory studies, or motor recording from an atrophic muscle. Needle recording electrodes may also yield a response relatively uncontaminated by volume conduction (e.g., in radial motor studies).

Stimulation

Usually supramaximal stimulation is delivered in order to fire all of the nerve fibers. In some sensory studies this may be impossible because the smaller sensory response may be obscured by the larger motor response (Figs. 4, 5). Occasionally, using a low voltage, short duration stimulation overcomes this difficulty. Supramaximal stimulation may also be difficult in areas where an adjacent nerve may be depolarized. Stimulation using needle electrodes may permit accurate localization of the stimulus to a specific nerve. Furthermore, a lower voltage stimulation can be used than with surface stimulation; the result may be a more comfortable procedure.

Ground

Placement of the ground is less critical. If convenient, it is positioned between the stimulating and recording electrodes.

Distance Measurement

The procedure for measuring distance between the stimulating cathode and the active recording electrode must be standardized. This distance may be kept constant, or identical anatomic landmarks may be used to determine electrode placement. Measurement should always be performed in one standard position. Change of degree of flexion across each joint may affect the distance, which in turn will affect the calculated velocity.105,496 Use of a tape measure which follows the skin’s surface contours will yield a different value than use of obstetric calipers, which bypass (p.14) the surface contour variations. This may play a more significant role in some studies (e.g., ulnar, radial, and axillary nerves) than in others (e.g., peroneal nerve).104,105,134,293,427

Machine Settings

Amplifier and filter settings have an effect and should be maintained constant during a study requiring multiple measurements. Latency values will decrease as increased amplification makes an earlier deviation from the baseline apparent. Filter settings have an effect on amplitude. This is especially prominent in sensory studies where the high-frequency filter setting can dramatically alter the thickness of the oscilloscope sweep. A low-frequency filter setting can also contribute to the amplitude. Because of this, it is best to adopt standard filter settings.

Error

The precision or reliability of a procedure is the degree to which the same results can be duplicated on repetition. Conduction studies have limited precision because of inherent technical errors. Honet, Jebsen, and Perrin283 found that measurement of a single photographed response by one individual on two separate occasions yielded an error of 2.0 to 3.0 M/sec; this represents an error of 4% to 5% of the measured value. This error can be increased by merely removing and replacing the electrodes, doubling the error (to 4.0 to 6.0 M/sec, or a 7% to 10% error) if a week is allowed to elapse between examinations. In other studies, the error ranged from 5% to 12.5%.48,229,471 Thus, even under optimal circumstances a sizable error will persist. The reported value should reflect this by being expressed no more accurately than to the nearest 5 M/sec. Most published values are expressed to fractions of these units, implying a greater precision than is realistic. We have reproduced the published values unchanged, leaving it to the reader to reinterpret them.

Although Simpson621 considered the distance measurement as the greatest source of error, Maynard and Stolov464 attributed only 11% of the total error to this measurement. They attributed the other 89% to the time measurement. This error was especially prominent in studies of a short nerve segment. It was especially significant when the conduction velocity was slowed.

Although it is impossible to eliminate error, it may be minimized with meticulous attention to the technical details discussed above. Attention must be paid to electrode selection and placement, to careful stimulation, to ground placement, to measurement of distances, and to machine settings. In two studies, merely using a different but identical machine resulted in different values.21,156 Henriksen274 emphasized temperature regulation. Time scale linearity and accuracy must be checked.

Practice is required for each examiner to gain precision in measuring latencies and distances. Care must be taken to mark the skin carefully only under the cathode and without distorting the skin.

Other sources of error include reversal of the stimulating electrodes, which can add an error as high as 0.5 msec. The stimulation must be supramaximal,546 but care must be taken not to depolarize an adjacent nerve to prevent contamination of the response.

(p.15) It is crucial that identically shaped responses are obtained in a study with multiple measurements. This will prevent erroneously using a volume conducted response from an adjacent muscle. Such a response can be obtained if a nearby nerve is stimulated or if anomalous communication exists between nerves (see pp. 85–88).

Several devices have been developed to minimize the error introduced during time measurement. Time markers coordinated with the stimulus onset eliminate the need to estimate this point. Similarly, the onset of the response is determined automatically in other machines.383,470 These features have been combined with distance measuring devices in specially automated meters.376,384 These devices did reduce the error.

Another approach has been to superimpose the responses from two stimulation points with delayed stimulation or a delay line.255,257 Bjorkqvist and associates54 increased the reliability for sequential studies by studying multiple nerves and obtaining an average of the pooled values.

Statistics

It is important to keep in perspective the goals and limitations of performing conduction studies. The objective is to establish clinically relevant diagnoses. A patient’s signs and symptoms serve as springboards to a differential diagnosis leading to an appropriate battery of tests. Occasionally, these include evoked neurophysiological responses. The latter are recorded and transformed into numerical values. It is these numbers that have to be interpreted.

In order to translate the numbers into evidence of normal or abnormal function, we sample an asymptomatic population and take these values to represent the population of “normal” values. The limits of these values are expressed in terms of their mean values and the variation from this value [standard deviation (SD)], and the range of values is noted. If we assume a normal distribution, deviation from the mean in a normal population is substantial. Approximately 16% will have values 1 SD from the mean (using one-tail tests); 2.3% of their values will deviate 2 SDs. Even 3 SDs will be exceeded by 0.1% of the normal population. Thus there is always a possibility that a value substantially removed from the mean will belong to a normal subject. By defining 3 SDs as a sign of pathology, we can minimize such “false-positive” interpretations. Of course this will lead to “false-negative” interpretation of possibly significant values in other cases. The examiner must select realistic objectives, aware that false-positive and false-negative interpretations are unavoidable a finite percentage of the time.

The standard deviation can be kept to a minimum (increasing the sensitivity of the tests) by careful attention to all technical details.

(p.16) Format of the Book

an = 40

bs = 22c(19–48 y.o.,dm = 31)

e Latency (msec)

f Amplitude (μV)

h1.9 ± i0.3j(1.5–2.4)k[10.0–14.0 cm]

h8.6 ±i3.9j(5.0–20.0)

g Cond. Velocity (M/sec)

h64.0 ±i7.4j(51.3–73.7)

(a) n = number of nerve studies

(b) s = number of subjects

(c) age range of subjects (y.o. = years old)

(d) m = mean age of subjects

(e) latency of response in milliseconds

(f) amplitude of response in microvolts (μV) or millivolts (mV)

(g) conduction velocity in meters per second (M/sec)

(h) mean value

(i) standard deviation

(j) range of values

(k) range of distances

Information summarized in the paragraph under the data:

  • Type of study (orthodromic, antidromic, mixed nerve)

  • Stimulation type and sites (cathodes indicated by S1, S2, etc.)

  • Recording type and site (Ra indicating active electrode; Rr indicating reference electrode)

  • Ground site (Gd)

  • Latency measurement (onset, peak, onset of negative wave)

  • Amplitude measurement (peak-to-peak, negative peak)

  • Limb position

  • Distance measurement (tape, obstetrical calipers)

  • Special considerations

  • Temperature monitoring and control

  • Gender considerations

  • Age considerations

Abbreviations used in the diagrams:

  • S1, S2, etc.: stimulating cathode sites (The anode site is proximal to this in all but the H reflex and F wave studies; its site is omitted from the diagrams.)

  • Ra: active recording electrode site

  • Rr: reference recording electrode site

  • Gd: ground site

Notes:

(*) References 38, 64, 65, 148, 149, 164, 213, 329, 351, 370, 374, 421, 484, 665, 687.