J Neurol (1992) 239 :277-283

Journal of

Neurology © Springer-Verlag1992

Somatosensory evoked potentials, sensory nerve potentials and sensory nerve conduction in hereditary motor and sensory neuropathy type I M. Aramideh 1, J. E. Hoogendijk 1'2, C.M. Aalfs 1, F. E. Posthumus Meyjes 1, M. De Visser 2, and B.W. Ongerboer D e Visser 1 1Department of ClinicalNeurophysiologyand 2Muscle Research Centre of the Department of Neurology, AcademicMedical Centre, Meibergdreef 9, NL-1105 AZ Amsterdam, The Netherlands Received April 11, 1991 ! Received in revised form October 24, 1991 / Accepted October 25, 1991

Summary. Thirty-nine patients from six families with hereditary motor and sensory neuropathy type I and control subjects were included in this study. A neurological deficit score (NDS) was derived from a neurological examination and compared with neurophysiological test findings. Further, sensory nerve conduction velocities (SNCV) were compared with the motor nerve conduction velocities (MNCV). Five patients whom peaks of N11/N13 complex and N20 of the median nerve sensory evoked potential (SEP) could be recorded showed normal interpeak latency. The interpeak separation P14N20 measured in six patients was normal. These findings point to the normal function of the central conductive pathways. Erb and cervical potentials of the median nerve SEP could be recorded in 10% and 12% of the patients, respectively. In contrast, about half of the patients showed a scalp N20, while in most of them no SNCV could be measured. In six patients far-field potential P14 of the median nerve SEP was the first detectable potential. Therefore, we argue in view of the anatomical structure of the thalamus, that the first generator for synchronizing and amplification of impulses is probably located in the thalamus. A third of the patients had a cortical sural nerve SEP, while no sural nerve potentials could be recorded. No association was found between the SEP findings and the NDS. There was an inverse correlation between median SNCV and the NDS, but no relationship between the former and sensory deficit alone. In 40% of the patients median SNCV and in 13% sural SNCV could be recorded and considered to be severely decreased. In contrast, the majority of the patients had mild to moderate sensory deficit. Furthermore, patients with measurable SNCVs had higher MNCVs and lower NDS than patients without measurable SNCVs. Key words: Sensory evoked potential - Sensory nerve action potential - Sensory nerve conduction velocity Hereditary motor and sensory neuropathy type I Offprint requests to: B.W. Ongerb0er De Visser

Introduction Hereditary motor and sensory neuropathy type I (HMSN I), the most common form of HMSN, is also called the hypertrophic type of Charcot-Marie-Tooth syndrome. It is an autosomal dominantly inherited disease and clinically characterized by slowly progressive distal muscle weakness and atrophy, hyporeflexia, foot deformities (pes cavus) and relatively mild sensory deficits [12, 16]. Pathological studies of peripheral nerves have shown severe degeneration with fibrosis, segmental demyelination and remyelination with onion bulb formation [6, 12, 16, 17, 27]. The electrophysiological hallmark is marked slowing of motor nerve conduction velocity (MNCV) [2, 12, 16, 27]; individuals with a median MNCV below 38 m/s are considered to be affected [16]. The majority of current publications deal with MNCVs. Conversely, there are few data available about sensory nerve conduction velocity (SNCV) [1, 16]. To our knowledge, there has been no study to show the relevance of SNCVs and sensory nerve action potentials (SNAPs) from a clinical and neurophysiological point of view and nothing has been reported about the incidence of detection of median and sural SNCVs in large groups of patients. The short latency somatosensory evoked potential (SEP) technique has been employed to evaluate the condition of the peripheral and central nervous system in patients with HMSN [21, 29, 33]. SEP has been used by some investigators to demonstrate and distinguish the variety of HMSN types [28] and to demonstrate its similarities to and differences from other neurological disorders [21, 25, 29]. It has been suggested that SEP testing may be a sensitive indicator of early involvement of afferent pathways in neurodegenerative system disorders, including HMSN [29]. In some of these studies, however, small groups of patients have been selected from larger groups with HMSN I on the basis of SEP findings. Patients with undetectable SEP potentials have been excluded from further calculations and investigations. No data, however, are available about the incidence of detection of different short-latency SEP components in patients with HMSN I, or about the

278 clinical c o n d i t i o n a n d S N C V a n d S N A P studies in patients with d e t e c t a b l e S E P p o t e n t i a l s c o m p a r e d with patients with u n d e t e c t a b l e S E P p o t e n t i a l s . By c o n s i d e r i n g the a n a t o m i c a l structure of the c e n t r a l n e r v o u s system p a t h w a y s , the p r e s e n t study i n v e s t i g a t e d the origin of far-field S E P potentials. F u r t h e r m o r e , it analysed the findings of S N C V in c o m p a r i s o n with M N C V , S E P findings a n d clinical c o n d i t i o n , to find o u t w h e t h e r they give a n y a d d i t i o n a l i n f o r m a t i o n a b o u t the p a t i e n t s with H M S N type I.

Materials and methods

Controls Different control groups were used to obtain the normative data of the several measurements. Median nerve SEPs were recorded in 16 control subjects, 9 females and 7 males, aged 15-65 years (mean 28 years) and sural nerve SEPs in 39 control subjects, 28 females and 11 males, aged 11-60 years (mean 33 years). The height of each control subject was measured. Recording of the SEPs was carried out with the subject in a supine position in a quiet and dimly lit room. The subjects were encouraged to relax completely with eyes closed. The constant current stimuli were wave electrical pulses of 0.2ms duration at 5.1 s intervals delivered to the median nerve at the wrist and to the sural nerve at the ankle. Stimulus intensity was adjusted to produce a small muscle twitch for median nerve stimulation, while for sural nerve stimulation the voltage was adjusted to three times subjective (sensory) threshold. Median nerve SEPs were recorded with surface electrodes from Erb's point (N9 potential), the spinous process of the third cervical vertebra (Cv-3) (N11/N13 complex) and the ipsi- and contralateral scalp 15 mm posterior to C3 (C3') and C4 (C4') (10-20 system), referred to linked earlobes (N20 potential). Sural nerve SEPs were recorded over Cz, 3 cm posterior to Cz and referred to Fpz, C3 and C4. Electrode impedances were less than 5 kfL The overall bandpass was 0.8 Hz to 3.3 kHz, analysis time 50 ms. The binwidth was 100 s with 511 points/channel. For both SEPs, two series of 400 potentials were recorded, averaged and superimposed with a Nicolet averager Pathfinder I and checked for reproducibility. For the central conduction time (CCT) measured from the cervical complex to the cortical N20 potential, the signal-noise ratio was poor and, therefore, in patients with detectable cervical and scalp potentials, the peak CCT, and not the onset CCT, were measured. Standard procedures for median nerve stimulation and MNCV measurement have been reported previously [31]. The antidromic SNCV of median nerve from elbow to wrist was measured by recording potentials from the digital nerves at the base of the index finger by means of ring electrodes. The formulae of the normal MNCV and of the normal SNCV of the distal segment of the median nerve used in our laboratory are: 61.51 0.1020 x age (years) + 4.00 (SD) and 65.71 - 0.0760 × age (years) + 4.76 (SD), respectively [31]. In 19 control subjects, 10 females and nine males, aged 15-79 years (mean 35 years) SNAPs of the median nerve after proximal stimulation (at the elbow) and distal (at the wrist) were recorded. The amplitude was measured from the baseline to the negative peak. Antidromic SNCVs of the sural nerve were investigated in 46 control subjects, 20 females and 26 males, between the ages of 14 and 86 years (mean 50 years) by means of stimulating electrodes over the nerve at the lower edge of the lateral belly of the gastrocnemius and recording by surface electrodes over the lateral ankle. Our data, obtained from control subjects, by means of SEP and SNCV of the median and sural nerve, were comparable with the results of previous investigators [9, 36, 39].

Patients Thirty-nine subjects, 11 females and 28 males, aged 15-67 years (mean 34 years), from six families, with clinical and electrophysiological evidence of HMSN I were included in the study. They were examined both clinically and electrophysiologically. The diagnosis was established in the propositus of each family by the presence of distal muscle weakness and wasting, areflexia, distal sensory disturbances, pes cavus and on having a median MNCV of less than 25 m/s. Each family showed an autosomal dominantly inheritance pattern. In three families sural nerve biopsy was performed in the propositus and the findings were in accordance with HMSN I [14, 35]. None of the affected subjects was suffering from diabetes mellitus or was taking neurotoxic drugs or excessive amounts of alcohol. The height of each patient was recorded and a mean value of 170cm, SD 11.7 calculated. A neurological deficit score (NDS), as the reflection of the clinical condition, was derived from a neurological examination in which a set of evaluations was performed and scored as follows; reflexes: 0 = normal, 1 = absence of 1-2 reflexes (unilateral), 2 = absence of 3-4 reflexes (unilateral); atrophy: 0 = absent, 1 = mild to moderate, 2 = severe; foot and hand deformities: 0 = absent, 1 = mild, 2 = moderate, 3 = severe; paresis [considering the most affected muscle and using the Medical Research Council (MRC) scale]: 0 = absent, 1 = MRC grade 4, 2 = MRC grade 3, 3 = MRC grade 2-0 in only one muscle, 4 = MRC grade 2-0 in two or more muscles; sensory deficit (consisting of vibration, joint position, pain and touch sensation): 0 = absent, 1 = mild, 2 = moderate, 3 = severe. The sum of scores for reflexes, atrophy, foot and hand deformities, paresis and sensory deficit was used to obtain the NDS, which was used for correlation with the neurophysiological findings.

Statistical analyses All data obtained from the control and patient groups were computerized by means of a BMDP computer program and analysed by using the follwing statistical tests: paired t-test, regression analysis test, chi-square test, Kendall's coefficient of concordance and Kruskal-Wallis one-way analysis of variance. For the correlations, P values smaller than 0.05 were considered to be significant.

Results T a b l e 1 shows a s u m m a r y of the n e u r o l o g i c a l findings in 39 p a t i e n t s with H M S N I. Most of the p a t i e n t s h a d mild to m o d e r a t e n e u r o l o g i c a l deficits a n d 20% of all p a t i e n t s h a d severe h a n d a n d foot deformities, paresis or s e n s o r y deficits. T h e m a j o r i t y of t h e m h a d only o n e of these t h r e e s y m p t o m s or a c o m b i n a t i o n of two s y m p t o m s a n d o n l y some of t h e m s h o w e d all three s y m p t o m s . F r o m the clinical a n d electrophysiological data, n o significant corr e l a t i o n s could be f o u n d b e t w e e n the different m e m b e r s of a single family or b e t w e e n families. T h e results of S E P a n d S N C V studies of the m e d i a n a n d sural n e r v e in the c o n t r o l subjects a n d the p a t i e n t s are s u m m a r i z e d in T a b l e 2. C o n c e r n i n g the m e d i a n n e r v e SEPs t h e r e were 4 ( 1 0 % ) o u t of 39 p a t i e n t s with a det e c t a b l e E r b N9 p o t e n t i a l , 5 ( 1 2 % ) with a d e t e c t a b l e N l l / N 1 3 complex, 9 ( 2 3 % ) with d e t e c t a b l e P14 a n d 18 ( 4 6 % ) with a d e t e c t a b l e cortical N20 p o t e n t i a l (Fig. 1). A l l p e a k l a t e n c y times of the N9, N l l / N 1 3 c o m p l e x a n d P14 p o t e n t i a l s w e r e delayed. F o u r of the 18 p a t i e n t s with cortical N20 p o t e n t i a l s ( 2 2 % ) h a d a n o r m a l l a t e n c y time (Fig. 1, 2 A ) a n d the r e m a i n i n g 14 a d e l a y e d N 2 0 l a t e n c y (Fig. 2B). I n 5 p a t i e n t s p e a k C C T could b e calculated

279 Table 1. Neurological findings in the 39 patients with hereditary motor and sensory neuropathy type I (HMSN I)

Paresis

Patients n

Atrophy

%

Hand and Patients foot deformities n %

Patients n

%

Sensory deficit

Patients n

Reflexes

Patients

n

%

%

6

15

Absent

4

10

Absent

12

30

Absent

5

13

Normal

5

13

M R C grade 4

16

42

Mild

12

30

Mild to moderate

14

36

Mild

10

25

Absent in 1-2 reflexes

l0

25

MRCgrade3

3

8

Moderate

15

40

Severe

13

34

Moderate

16

42

Absent in 3-4 reflexes

24

62

8

20

8

20

Absent

M R C 2-0 in one muscle

6

15

M R C 2-0 in > one muscle

8

20

Severe

Severe

Table 2. Summary of sensory evoked potential (SEP), sensory nerve action potential (SNAP) and sensory nerve conduction velocity

(SNCV) studies of the median and sural nerve in control subjects and in 39 patients with HMSN I. CCT, Central conduction time Median nerve

Sural nerve

N9

N11/N13

P14

N20

Peak CCT

SNAP ~

SNCV b

N35/P40

SNCV

10.1 (1.1) ms

11.1 (1.3) ms

14.6 (1.2) ms

19.5 (1.7) ms

6.1 (0.4) ms

40.0 (18.3) gg

-

44.3 (3.0) ms

42.4 (2.5) m/s

4 (10%)

5 (12%)

9 (23%)

18 (46%)

5 (12%)

16 (41%)

16 (41%)

18 (46%)

5 (12%)

14.7 (2.2) ms

18.7 (1.5) ms

22.7 (4.2) ms

27.8 (5.7) ms

5.5 (0.37) ms

7.7 (8.4) ~V

26.3(9.3)

6s.9(11.0)

20(5.0)

m/s

ms

m/s

Control subjects Mean values (SD)

Patients No. of patients with detectable values (%) Mean values (SD)

SNAP recorded after distal stimulation at the wrist b See the text for the formula 3O n. SEP

Median

E

Median

40 i

N9

Nll/N13

n. SEP

• 25 E

3o

20 25-

15

P

P

p p

~

10

I

[

i

i

i

i

i

i

120

130

140

150

160

170

180

n. SEP

Median

35

P

E

30

~

~

100~-

i 130

I 140

i 150

NiP

"~

J 160

I 170

I I 180

/

I I / 190 2 0 0 height (cm)

- 40

P

P P

! --

~

Sural n. SEP

~

P ~

[ ~

~

B

E

P~ p

~

I

; I E ~ = 80~-

P P

~

p P

- Y = 0.07824 + 0.07027 x'height

0 ~ 120

190 2 0 0 height (cm)

P P

P p

25

/

I

~

p ~

R = 0.833

-

P

P

N20 •

.~

1

A

40

P P 2SO

- R = 0.932 Y = - 1 . 2 5 5 9 + 0 . 6 6 9 7 x height

0

-

20

15 -

p

p Pp

60 t-

p p

pp

pP

p

~

20 15 10

20 ~- R = 0 . 7 9 6

R = 0.909 Y = 3.1041 + 0 . 0 9 6 6 0 x height

120

I

i

I

i

i

i

t

130

140

150

160

170

180

I

i

190 2 0 0 height (cm)

0 I

Y - - - 4 . 0 1 9 7 + 0 . 2 8 3 3 1 x height I

120 D

I

130

i

i

i

i

140

150

160

170

l

i

i

180 190 2 0 0 height (cm)

Fig. 1 A - D . Relationships of the height of control subjects to peak latency time (latency time) of Erb (N9), spinal (N11/N13 complex) at Cv-4 level, cortical (N20) sensory evoked potentials, following median nerve stimulation, and N35/P40 of the sural nerve. The mean values and standard deviations (diagonal lines), correlation coefficients (R) and the regression equations, calculated by using the data from control subjects, are shown. P represents the value found in each patient

280

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