Although multiple sclerosis primarily affects myelin within the central nervous system, both pathologic and physiological studies suggest that mild deficits in peripheral nervous system myelin may be common. To evaluate this question further, we performed near nerve studies on sural nerves of 14 patients with multiple sclerosis. Peak-to-peak amplitude and maximum conduction velocity were normal in 9 of 14 patients, while minimum conduction velocity, or the velocity of the slowest-conducting component of the sensory action potential, was abnormally reduced in 9 patients. In addition, the supernormal period was evaluated for patients and compared with a control sample; multiple sclerosis patients showed a significant reduction in the amplitude of supernormality. Both the reduction in minimum conduction velocity and the alteration in the supernormal period are consistent with a mild defect in peripheral myelin. Key words: multiple sclerosis neuropathy sensory action potential MUSCLE & NERVE 15:73-76 1992
PERIPHERAL SENSORY ABNORMALITIES IN PATIENTS WITH MULTIPLE SCLEROSIS JEREMY M. SHEFNER, MD, PhD, JONATHAN L. CARTER, MD, and CHRISTIAN KRARUP, MD, PhD
Multiple sclerosis (MS) is generally considered to be a disease causing demyelination within the central nervous system. Conventional nerve conduction studies are usually normal in MS patients, with occasional abnormalities often attributed to a concurrent process such as an entrapment neuropathy .' Even in cases where clinical examination suggests distal muscle atrophy, EMG and nerve conduction studies have been normaL4 However, other studies have suggested that subtle peripheral nerve abnormalities may be common. Single fiber EMG studies showed mildly increased jitter in MS patients." In addition, the relative refractory period in median nerve sensory fibers was found to be prolonged in MS patients.8 In this study, w e describe 2 mild but consistent abnormalities in sensory conduction in MS pa-
From the Neurophysiology Laboratories, Brigham and Women's Hospital, and the Department of Neurology, Harvard Medical School, Boston, Massachusetts (Dr Shefner), Mayo Clinic Scottsdale, Scottsdale, Arizona (Dr Carter), and the Laboratory of Clinical Neurophysiology, Rigshospitalet, Copenhagen, Denmark (Dr. Krarup). Presented in part at the Annual Meeting of the AAEM, Chicago, Illinois, September, 1990. Address reprint requests to Dr. Shefner, Neurophysiology Laboratories, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 021 15. Accepted for publication January 17, 1991 CCC 0148-639X/92/01073-04 $04.00 0 1992 John Wiley & Sons, Inc.
Sensory Abnormalities in MS
tients. Minimum conduction velocity of the sural nerve compound sensory action potential was measured using near nerve techniques; in addition, supernormal excitability curves were studied for the sural nerve, and results compared with a control sample.
MATERIALS AND METHODS
Fourteen patients with MS were studied. All were recruited from a large MS clinic and were judged to have definite MS using the criteria of Poser et a1.'* All patients were ambulatory, with a functional disability score of less than 5.5.'' No patient had any disease likely to be associated with peripheral neuropathy. Supernormal period measurements were also obtained on a sample of 11 control subjects. Informed consent was obtained. Patients.
Stimulation and Recording Conditions. Compound sensory action potentials were recorded from the right sural nerve, using near nerve electrodes for recording and stimulation. Electrode placement was identical to that previously d e ~ c r i b e d . 'Stim~ uli were 0.2 ms rectangular wave pulses. For supernormal period measurements, a stimulus producing a supramaximal response was paired with a second stimulus of an intensity that evoked a response of approximately 1/z maximum amplitude. The supramaximal stimulus was presented first,
MUSCLE 8, NERVE
January 1992
73
and followed at a variable interstimulus interval (ISI) by the submaximal stimulus. IS1 ranged from 2 to 20 ms in increments of 2 ms. Recordings were made through DISA sensory amplifiers (15C02), and responses to 512 to 1500 supramaximal stimuli were electronically summed. For supernormal period evaluation, responses to 4 to 8 presentations of the supramaximal- submaxima1 stimulus pair were averaged for each ISI. Temperature of the limb was maintained at 34 to 36°C. For each compound sensory action potential, maximum conduction velocity (CV), peak-to-peak amplitude, and minimum CV were calculated as previously d e ~ c r i b e d . ’Maximum ~ CV and amplitude were classified as normal or reduced according to previously established age-dependent norms.’ If either value was significantly reduced, the “main component” of the sensory action potential was classified as being abnormal. Minimum CV was also compared with established norms; for sural nerve potentials, mean minimum conduction velocity in 53 normal subjects ranging in age from 16 to 79 years was 14.4 m/s, with a lower 95% confidence limit of 10.9 m/s (Behse, Buchthal, Rosenfalck, Shefner, and Krarup, unpublished data). For paired stimuli, the peak-to-peak amplitude of the second stimulus was measured for each ISI. Relative amplitude was calculated by dividing the amplitude obtained at a given IS1 by the amplitude resulting when the stimulus was presented
Data Analysis.
n=750
.
1
. 0.05 pV
1-1
n=1500 I
’ (
10
0
I
20
d c
Time (msec) FIGURE 1. Compound sensory action potential from a patient with multiple sclerosis. The top tracing shows the averaged response to 64 stimulus presentations; peak-to-peak amplitude is 14.6 pV, and maximum CV is 51.4 m/s (both values within normal limits). The next 2 tracings show the averaged response to 750 and 1500 stimulus presentations; the arrow denotes the position of the last component clearly growing out the background noise. Conduction velocity of this component is 9.0 mis. Right sural nerve (stim: ankle; rec: midcalf).
alone. Relative amplitude was then plotted against IS1 to yield the supernormal excitability curve. RESULTS
Table 1 shows the results of near nerve studies for the 14 MS patients. Main components of the sensory potential were within normal limits in 9 patients; in 4 patients, amplitude was reduced, while maximum CV was reduced in 2 patients. Minimum CV was reduced in 9 patients, and was the only abnormality noted in 5 patients. Patients receiving cytoxan did not show more severe abnormalities than other patients. Figure 1 shows a
Table 1. Sural nerve conduction studies in patients with MS Patient no.
74
Age
Maximum cv (mW
Amplitude (PV)
Normal ?
Minimum CV (m/s)
Normal ?
Prior cytoxan?
1 2 3 4 5 6 7 8 9 10 11 12 13 14
31 40 20 61 60 44 31 38 33 32 51 64 41 82
51 .O 43.7 55.9 44.1 40.1 55.0 54.1 59.5 46.9 56.3 41.9 55.0 60.0 51.4
23.9 12.1 49.3 27.9 9.8 20.4 12.9 36.8 38.9 21.3 84.5 4.6 13.7 14.6
Y N Y Y N Y N Y Y Y N N Y Y
8.9 13.9 16.0 5.1 6.5 9.0 8.6 7.0 15.1 13.2 8.6 9.6 13.5 9.0
N Y Y N N N N N Y Y
N Y N Y Y Y N N Y Y Y N Y N
Mean
45
51.1
26.5
Sensory Abnormalities in MS
N N Y N
10.3
MUSCLE & NERVE
January 1992
compound sensory action potential for a patient with an isolated abnormality in minimum CV. The averaged supernormal excitability curves are shown in Figure 2 for both patients and control groups. At all ISIs greater than 2 ms, relative amplitude is reduced for MS patients. In the control group, maximum supernormality is seen at a 6 ms ISI, with an increase in response amplitude of 28%. MS patients showed maximum supernormality at an 8 ms ISI, with amplitude increased 10% over baseline. A t test comparing maximum supernormality, independent of IS1 for MS patients versus controls, was significant (t = 2.65, 23 df, P < 0.02).
tients did not show more severe peripheral nerve abnormalities. This is consistent with prior studies; neuropathy has only been observed in patients treated with cytoxan when it was combined with other chemotherapeutic agents.l3~l6 Previous studies of peripheral nerve conduction in MS patients have not shown clear sensory or motor abnormalities. Gilliatt et aL5 found no differences in sensory or motor conduction between normal subjects and patients with a number of neurological diseases, including MS. Similarly, in a population of MS patients with significant hand atrophy, nerve conduction studies and EMG were within normal limits fo+ most patients4 In the present study, the most common abnormality in the sensory action potential was a reduction in minimum conduction velocity, seen in 64% of patients. This implies that a subpopulation of large myelinated fibers is conducting at a slower rate than would be expected normally. This can occur if regenerating fibers are present within a nerve bundle, usually as a consequence of chronic axonal denervation. l4 Alternatively, segmental demyelination can cause marked slowing of conduc-
DISCUSSION
In this study, we have demonstrated that most patients with MS have mild abnormalities in peripheral sensory conduction as measured using near nerve techniques. The most frequent abnormality was in minimum CV, which was often reduced in the absence of any reduction in maximum CV or amplitude. While the majority of patients received cytoxan as part of their MS treatment, these pa1.4-
-
Mean; MS
1.2-
1.o
-
0.8
-
0.6
I
0
2
.
I
4
-
I
6
.
I
8
-
10
I
-
12
I
-
14
I
-
16
~
-
18
I I
.
20
FIGURE 2. Averaged relative supernormality as a function of interstimulus interval. Open symbols represent data from normal subjects, while closed symbols represent data from patients with multiple sclerosis. Error bars are 1 standard error of the mean.
Sensory Abnormalities in MS
MUSCLE & NERVE
January 1992
75
tion in a minority of fibers even when the main component of the compound sensory action potential is conducted normally. Consistent with this possibility, a quantitative study of sural nerves from MS patients showed abnormal fibers with sporadic internodes of reduced myelin thickness in 8 of 10 patients." Studies of the recovery cycle of peripheral nerve offer extremely sensitive, albeit nonspecific, measures of peripheral nerve function. The supernormal period is the phase of the activity cycle just after the relative refractory period, when sensory axons have a lower threshold to electrical stimulation than at Maximum supernormality occurred at ISIs of 4 to 8 ms in both patients and controls, similar to results obtained in other mammalian m0de1s.I~ The supernormal period has been found to correlate closely with a voltagesensitive depolarizing after potential. Manipulations that change the amplitude of this after potential also affect the magnitude of supernormality. Convincing evidence has been presented by Barrett and Barrett' that the depolarizing after potential is due to a passive capacitative current
','
leaking either through or underneath the myelin sheath in the region of the axon internode. Thus, any abnormality that promotes the leakage of current through the myelin sheath should increase the depolarizing after potential and, therefore, the amount of supernormality. The present study documents a consistent reduction in the amplitude of supernormality in the peripheral nerve of MS patients as compared with controls, similar to a prior study of MS patients, in which 40% of patients failed to demonstrate significant supernoramlity at single IS1 of 6 ms.3 However, the mechanism underlying this reduction in supernormality is unclear. As noted above, increased internodal current leakage through the myelin sheath should increase supernormality rather than decrease it; the mild segmental demyelination shown to be present in MS peripheral nerve might, therefore, be expected to have an effect opposite to that observed in this study. These considerations suggest that other abnormalities, in addition to demyelination, may contribute to the reduced supernormality seen in MS patients.
REFERENCES 1. Barrett EF, Barrett JN: Intracellular recording from vertebrate myelinated axons: mechanism of the depolarizing after potentia1.J Physiol 1982;323:117- 144. 2. Bowe CV, Kocsis JD, Waxman SG: The association of the supernormal period and the depolarizing afterpotential in myelinated frog and rat sciatic nerve. Neuroscience 1987;21:585-593. 3. Eisen A, Paty D, Hoirch M: Altered supernormality in multiple sclerosis peripheral nerve. Muscle Nerue 1982;5:411-414. 4. Fisher M, Long R, Drachman D: Hand muscle atrophy in multiple sclerosis. Arch Neurol 1983;40:811-815. 5. Gilliatt RW, Goodman HV, Willison RG: T h e recording of lateral popliteal nerve action potentials in man. J Neurol Neurosurg Psychiatry 1961;24:305-318. 6. Gilliatt RW, Willison RG: T h e refractory and supernormal periods of the human median nerve. J Neurol Neurosurg Psychiatry 1963;26:136- 147. 7. Hasson J, Terry R, Zimmerman H: Peripheral neuropathy in multiple sclerosis. Neurology 1958;8:503-510. 8. Hopf HC, Eysholdt M: Impaired refractory periods of peripheral sensory nerves in multiple sclerosis. A n n Neurol 1978;4:499-501. 9. Horowitz S, Krarup C: Conduction studies in 139 normal sural nerves. Electroenceph Clin Neurophysiol 1987;66:S47.
76
Sensory Abnormalities in MS
10. Kurtzke JF: Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (DSS). Neurulugy 1983;33:1444- 1452. 11. Pollock M, Calder C, Allpress S: Peripheral nerve abnormality in multiple sclerosis. A n n Neurol 1977;2:41-48. 12. Poser CM, Paty DW, Scheinberg L, et al: New diagnostic criteria for multiple sclerosis. A n n Neurol 1983;13:227231. 13. Rosenfeld CS, Broder LE: Cisplatin-induced autonomic neuropathy. Cancer Treat Rep 1984;68:659-660. 14. Shefner JM, Buchthal F, Krarup C: Slowly conducting rnyelinated fibers in peripheral neuropathy. Muscle Nerve 1991; 14:534-542. 15. Swadlow HA, Waxman SG: Activity-dependent variations in the conduction properties of central axons, in Waxman SG (ed): Physiology and Pathobiolo
PERIPHERAL SENSORY ABNORMALITIES IN PATIENTS WITH MULTIPLE SCLEROSIS JEREMY M. SHEFNER, MD, PhD, JONATHAN L. CARTER, MD, and CHRISTIAN KRARUP, MD, PhD
Multiple sclerosis (MS) is generally considered to be a disease causing demyelination within the central nervous system. Conventional nerve conduction studies are usually normal in MS patients, with occasional abnormalities often attributed to a concurrent process such as an entrapment neuropathy .' Even in cases where clinical examination suggests distal muscle atrophy, EMG and nerve conduction studies have been normaL4 However, other studies have suggested that subtle peripheral nerve abnormalities may be common. Single fiber EMG studies showed mildly increased jitter in MS patients." In addition, the relative refractory period in median nerve sensory fibers was found to be prolonged in MS patients.8 In this study, w e describe 2 mild but consistent abnormalities in sensory conduction in MS pa-
From the Neurophysiology Laboratories, Brigham and Women's Hospital, and the Department of Neurology, Harvard Medical School, Boston, Massachusetts (Dr Shefner), Mayo Clinic Scottsdale, Scottsdale, Arizona (Dr Carter), and the Laboratory of Clinical Neurophysiology, Rigshospitalet, Copenhagen, Denmark (Dr. Krarup). Presented in part at the Annual Meeting of the AAEM, Chicago, Illinois, September, 1990. Address reprint requests to Dr. Shefner, Neurophysiology Laboratories, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 021 15. Accepted for publication January 17, 1991 CCC 0148-639X/92/01073-04 $04.00 0 1992 John Wiley & Sons, Inc.
Sensory Abnormalities in MS
tients. Minimum conduction velocity of the sural nerve compound sensory action potential was measured using near nerve techniques; in addition, supernormal excitability curves were studied for the sural nerve, and results compared with a control sample.
MATERIALS AND METHODS
Fourteen patients with MS were studied. All were recruited from a large MS clinic and were judged to have definite MS using the criteria of Poser et a1.'* All patients were ambulatory, with a functional disability score of less than 5.5.'' No patient had any disease likely to be associated with peripheral neuropathy. Supernormal period measurements were also obtained on a sample of 11 control subjects. Informed consent was obtained. Patients.
Stimulation and Recording Conditions. Compound sensory action potentials were recorded from the right sural nerve, using near nerve electrodes for recording and stimulation. Electrode placement was identical to that previously d e ~ c r i b e d . 'Stim~ uli were 0.2 ms rectangular wave pulses. For supernormal period measurements, a stimulus producing a supramaximal response was paired with a second stimulus of an intensity that evoked a response of approximately 1/z maximum amplitude. The supramaximal stimulus was presented first,
MUSCLE 8, NERVE
January 1992
73
and followed at a variable interstimulus interval (ISI) by the submaximal stimulus. IS1 ranged from 2 to 20 ms in increments of 2 ms. Recordings were made through DISA sensory amplifiers (15C02), and responses to 512 to 1500 supramaximal stimuli were electronically summed. For supernormal period evaluation, responses to 4 to 8 presentations of the supramaximal- submaxima1 stimulus pair were averaged for each ISI. Temperature of the limb was maintained at 34 to 36°C. For each compound sensory action potential, maximum conduction velocity (CV), peak-to-peak amplitude, and minimum CV were calculated as previously d e ~ c r i b e d . ’Maximum ~ CV and amplitude were classified as normal or reduced according to previously established age-dependent norms.’ If either value was significantly reduced, the “main component” of the sensory action potential was classified as being abnormal. Minimum CV was also compared with established norms; for sural nerve potentials, mean minimum conduction velocity in 53 normal subjects ranging in age from 16 to 79 years was 14.4 m/s, with a lower 95% confidence limit of 10.9 m/s (Behse, Buchthal, Rosenfalck, Shefner, and Krarup, unpublished data). For paired stimuli, the peak-to-peak amplitude of the second stimulus was measured for each ISI. Relative amplitude was calculated by dividing the amplitude obtained at a given IS1 by the amplitude resulting when the stimulus was presented
Data Analysis.
n=750
.
1
. 0.05 pV
1-1
n=1500 I
’ (
10
0
I
20
d c
Time (msec) FIGURE 1. Compound sensory action potential from a patient with multiple sclerosis. The top tracing shows the averaged response to 64 stimulus presentations; peak-to-peak amplitude is 14.6 pV, and maximum CV is 51.4 m/s (both values within normal limits). The next 2 tracings show the averaged response to 750 and 1500 stimulus presentations; the arrow denotes the position of the last component clearly growing out the background noise. Conduction velocity of this component is 9.0 mis. Right sural nerve (stim: ankle; rec: midcalf).
alone. Relative amplitude was then plotted against IS1 to yield the supernormal excitability curve. RESULTS
Table 1 shows the results of near nerve studies for the 14 MS patients. Main components of the sensory potential were within normal limits in 9 patients; in 4 patients, amplitude was reduced, while maximum CV was reduced in 2 patients. Minimum CV was reduced in 9 patients, and was the only abnormality noted in 5 patients. Patients receiving cytoxan did not show more severe abnormalities than other patients. Figure 1 shows a
Table 1. Sural nerve conduction studies in patients with MS Patient no.
74
Age
Maximum cv (mW
Amplitude (PV)
Normal ?
Minimum CV (m/s)
Normal ?
Prior cytoxan?
1 2 3 4 5 6 7 8 9 10 11 12 13 14
31 40 20 61 60 44 31 38 33 32 51 64 41 82
51 .O 43.7 55.9 44.1 40.1 55.0 54.1 59.5 46.9 56.3 41.9 55.0 60.0 51.4
23.9 12.1 49.3 27.9 9.8 20.4 12.9 36.8 38.9 21.3 84.5 4.6 13.7 14.6
Y N Y Y N Y N Y Y Y N N Y Y
8.9 13.9 16.0 5.1 6.5 9.0 8.6 7.0 15.1 13.2 8.6 9.6 13.5 9.0
N Y Y N N N N N Y Y
N Y N Y Y Y N N Y Y Y N Y N
Mean
45
51.1
26.5
Sensory Abnormalities in MS
N N Y N
10.3
MUSCLE & NERVE
January 1992
compound sensory action potential for a patient with an isolated abnormality in minimum CV. The averaged supernormal excitability curves are shown in Figure 2 for both patients and control groups. At all ISIs greater than 2 ms, relative amplitude is reduced for MS patients. In the control group, maximum supernormality is seen at a 6 ms ISI, with an increase in response amplitude of 28%. MS patients showed maximum supernormality at an 8 ms ISI, with amplitude increased 10% over baseline. A t test comparing maximum supernormality, independent of IS1 for MS patients versus controls, was significant (t = 2.65, 23 df, P < 0.02).
tients did not show more severe peripheral nerve abnormalities. This is consistent with prior studies; neuropathy has only been observed in patients treated with cytoxan when it was combined with other chemotherapeutic agents.l3~l6 Previous studies of peripheral nerve conduction in MS patients have not shown clear sensory or motor abnormalities. Gilliatt et aL5 found no differences in sensory or motor conduction between normal subjects and patients with a number of neurological diseases, including MS. Similarly, in a population of MS patients with significant hand atrophy, nerve conduction studies and EMG were within normal limits fo+ most patients4 In the present study, the most common abnormality in the sensory action potential was a reduction in minimum conduction velocity, seen in 64% of patients. This implies that a subpopulation of large myelinated fibers is conducting at a slower rate than would be expected normally. This can occur if regenerating fibers are present within a nerve bundle, usually as a consequence of chronic axonal denervation. l4 Alternatively, segmental demyelination can cause marked slowing of conduc-
DISCUSSION
In this study, we have demonstrated that most patients with MS have mild abnormalities in peripheral sensory conduction as measured using near nerve techniques. The most frequent abnormality was in minimum CV, which was often reduced in the absence of any reduction in maximum CV or amplitude. While the majority of patients received cytoxan as part of their MS treatment, these pa1.4-
-
Mean; MS
1.2-
1.o
-
0.8
-
0.6
I
0
2
.
I
4
-
I
6
.
I
8
-
10
I
-
12
I
-
14
I
-
16
~
-
18
I I
.
20
FIGURE 2. Averaged relative supernormality as a function of interstimulus interval. Open symbols represent data from normal subjects, while closed symbols represent data from patients with multiple sclerosis. Error bars are 1 standard error of the mean.
Sensory Abnormalities in MS
MUSCLE & NERVE
January 1992
75
tion in a minority of fibers even when the main component of the compound sensory action potential is conducted normally. Consistent with this possibility, a quantitative study of sural nerves from MS patients showed abnormal fibers with sporadic internodes of reduced myelin thickness in 8 of 10 patients." Studies of the recovery cycle of peripheral nerve offer extremely sensitive, albeit nonspecific, measures of peripheral nerve function. The supernormal period is the phase of the activity cycle just after the relative refractory period, when sensory axons have a lower threshold to electrical stimulation than at Maximum supernormality occurred at ISIs of 4 to 8 ms in both patients and controls, similar to results obtained in other mammalian m0de1s.I~ The supernormal period has been found to correlate closely with a voltagesensitive depolarizing after potential. Manipulations that change the amplitude of this after potential also affect the magnitude of supernormality. Convincing evidence has been presented by Barrett and Barrett' that the depolarizing after potential is due to a passive capacitative current
','
leaking either through or underneath the myelin sheath in the region of the axon internode. Thus, any abnormality that promotes the leakage of current through the myelin sheath should increase the depolarizing after potential and, therefore, the amount of supernormality. The present study documents a consistent reduction in the amplitude of supernormality in the peripheral nerve of MS patients as compared with controls, similar to a prior study of MS patients, in which 40% of patients failed to demonstrate significant supernoramlity at single IS1 of 6 ms.3 However, the mechanism underlying this reduction in supernormality is unclear. As noted above, increased internodal current leakage through the myelin sheath should increase supernormality rather than decrease it; the mild segmental demyelination shown to be present in MS peripheral nerve might, therefore, be expected to have an effect opposite to that observed in this study. These considerations suggest that other abnormalities, in addition to demyelination, may contribute to the reduced supernormality seen in MS patients.
REFERENCES 1. Barrett EF, Barrett JN: Intracellular recording from vertebrate myelinated axons: mechanism of the depolarizing after potentia1.J Physiol 1982;323:117- 144. 2. Bowe CV, Kocsis JD, Waxman SG: The association of the supernormal period and the depolarizing afterpotential in myelinated frog and rat sciatic nerve. Neuroscience 1987;21:585-593. 3. Eisen A, Paty D, Hoirch M: Altered supernormality in multiple sclerosis peripheral nerve. Muscle Nerue 1982;5:411-414. 4. Fisher M, Long R, Drachman D: Hand muscle atrophy in multiple sclerosis. Arch Neurol 1983;40:811-815. 5. Gilliatt RW, Goodman HV, Willison RG: T h e recording of lateral popliteal nerve action potentials in man. J Neurol Neurosurg Psychiatry 1961;24:305-318. 6. Gilliatt RW, Willison RG: T h e refractory and supernormal periods of the human median nerve. J Neurol Neurosurg Psychiatry 1963;26:136- 147. 7. Hasson J, Terry R, Zimmerman H: Peripheral neuropathy in multiple sclerosis. Neurology 1958;8:503-510. 8. Hopf HC, Eysholdt M: Impaired refractory periods of peripheral sensory nerves in multiple sclerosis. A n n Neurol 1978;4:499-501. 9. Horowitz S, Krarup C: Conduction studies in 139 normal sural nerves. Electroenceph Clin Neurophysiol 1987;66:S47.
76
Sensory Abnormalities in MS
10. Kurtzke JF: Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (DSS). Neurulugy 1983;33:1444- 1452. 11. Pollock M, Calder C, Allpress S: Peripheral nerve abnormality in multiple sclerosis. A n n Neurol 1977;2:41-48. 12. Poser CM, Paty DW, Scheinberg L, et al: New diagnostic criteria for multiple sclerosis. A n n Neurol 1983;13:227231. 13. Rosenfeld CS, Broder LE: Cisplatin-induced autonomic neuropathy. Cancer Treat Rep 1984;68:659-660. 14. Shefner JM, Buchthal F, Krarup C: Slowly conducting rnyelinated fibers in peripheral neuropathy. Muscle Nerve 1991; 14:534-542. 15. Swadlow HA, Waxman SG: Activity-dependent variations in the conduction properties of central axons, in Waxman SG (ed): Physiology and Pathobiolo
