Evoked potential study in facio-scapulo humeral muscular dystrophy

Copyright 0 Munksgaurd lW7

Acta Neurol Scand 1997: 95: 34&-?50 Printtvf in U K - all righty reservrd

ACTA NEUROLOGICA

SCANDINAVICA ISSN 0001-6314

Evoked potential study in facio-scapulohurner al-muscular dystrophy Fierro B, Daniele 0, Aloisio A, Buffa D, La Bua V, Oliveri M, Manfri: L, Brighina F. Evoked potential study in facio-scapulo-humeral muscular dystrophy. Acta Neurol Scand 1997: 95: 346-350. 0 Munksgaard 1997.

Nerve conduction velocities (NCVs), somatosensory (SEPs) and auditory evoked potentials (BAEPs) were recorded in 9 patients with facioscapulo-humeral dystrophy (FSHD) and in 20 age-matched controls. In FSHD patients a significant increase of the nerve distal sensory latencies and of the absolute SEP latencies revealed a subclinical involvement of the afferent sensory pathways, as well as the abnormal slowing of the later components of the BAEPs, pointed to a central auditory dysfunction. Moreover all patients underwent brain MRI that showed the presence of white matter hyperintense lesions in 4 of them (44%). No correlations were found between individual or total number of SEP and BAEP abnormal electrophysiological parameters and severity of WMHL, age, age at onset, duration of the disease or muscular impairment. These findings make the interpretation and pathophysiology of the nervous damage in FSHD rather uncertain. More studies are required to better define the aspects of neurogenic involvement in this type of muscular dystrophy.

Evoked potential recordings have been applied to many neurological disorders and have given valuable information about localizing the lesions in the central nervous system (CNS). Abnormalities of evoked potentials in myopathic disorders were first described by Mongia & Lundervold ( 1). Since then, abnormal visual, auditory and somatosensory evoked potentials have been reported from many authors in myotonic dystrophy (MD) (2-6) and in Duchenne muscular dystrophy (DMD) (7). However, to our knowledge, abnormalities of the evoked potentials in patients with facio-scapulo-humeraldystrophy (FSHD) have not been described. The main purpose of the present investigation was to record the frequency of electrophysiological abnormalities in patients with FSHD, and their possible correlation with age, age at onset, duration of the disease and muscular impairment. In addition patients were evaluated by magnetic resonance imaging (MRI) to determine whether impaired central conduction was associated with specific cerebral abnormalities.

346

6. Fierro, 0. Daniele, A. Aloisio, D. Buffa, V. La Bua, M. Oliveri, L. Manfre', F. Brighina Department of Neurology. 'Department of Radiology, University of Palermo

Key words. evoked potentials, MRI, muscular dystrophy Professor B. Fierro. lstituto di Neuropstchiatria. Via Gaetano La Loggia, 1, 90129 Palermo. Italy Accepted for publication February 4. 1997

Materials and methods

Nine unselected FSHD patients (7 male, 2 female) with mean age of 35.11k9.32 years were studied. Their height varied from 160 to 189 cm with a mean of 172.89f9.39. They included 5 hereditary cases (belonging to two families) and 4 apparently sporadic cases. The age of onset was difficult to establish exactly, ranging from about 16 to 36 years of age (mean: 26.44k6.09). The mean duration of the disease was 9.56k7.40 years. The diagnosis was based on clinical and electromyographic findings. The clinical muscular weakness in patients was classified as follows and arbitrarily scored for statistical analysis:

1) mild muscular weakness without functional impairment; 2) moderate muscle weakness leading to some degree of functional impairment; 3) muscle weakness with severe functional impairment and in some cases resulting in the subjects being bound to a wheelchair; 4) bedridden.

Evoked potential study in FSHD The values of fasting blood glucose of all patients were in the normal range. In all subjects clinical or laboratory investigations excluded other diseases giving rise to neuropathic disorders. There was no evidence of malignancy and no subjects were on drugs known to be toxic for the nervous system. The controls were 20 healthy subjects (14 male, 6 female) with mean age 34.82f11.70 years and mean height 171.74+1 1.69 cm. Informed consent was obtained from all subjects before testing.

Central atrophy was evaluated relative to age rather than on an absolute scale and because of this it was the most subjective of the MRI values. Atrophy was judged on the basis of the presence of enlargement of ventricles and cisterns and parenchymal atrophy with widening of sulci. The atrophy was not scored and then not considered for statistical analysis. The MRI scans were evaluated by two neuroradiologists without knowledge of clinical status. Statistical analysis

Neurophysiological examinations

Standard motor and sensory conduction velocities of the median and tibial nerves were performed. Motor (MCV) and antidromic sensory (SCV) conduction velocities, distal motor (DML) and sensory (DSL) latencies and peak to peak compound muscle (CMAPa) and sensory (SAPa) action potential amplitudes of the median and tibial nerves were calculated. Skin temperature was kept constant between 32°C and 35°C. Somatosensory evoked potentials (SEPs) were elicited by electrical stimulation of the right median and tibial nerve at the wrist and ankle respectively. EEG activity was registered at ERB point. cervical C7, C3’ and Cz, Cz’ with common reference at Fpz. Two trials of 1000 stimuli at 3 Hz frequency and 0.2 ms duration were averaged. The following absolute latencies N9, N13, N20, P40, N50, P60, and interpeak values N9-13, N13-20, P40-60 of evoked components were analyzed. Brainstem auditory evoked potentials (BAEPs) were performed in a soundproof room and each ear was stimulated using 0.1 msec condensant/ rarefaction clicks at 60 dB(SL) above the click hearing threshold at a stimulation rate of 10 Hz. The responses were recorded in two separate channels from A1-A2 referred to the vertex. Two separate sets of 1500 stimuli were run for each ear. Absolute latencies of waves I, 111, V, and the 1-111, 111-V and I-V interpeak intervals were measured. Radiological examination

Brain MRI examination was performed using a middle-field MR unit and conventional T, weighted spin echo scans (200O/25- 110/2). White matter signal abnormalities was judged by both the size and total number of high signal lesions. The total number of lesions was identified and placed into three categories on the basis of size (0.5 - 1.5 - 2.5 cm). Total score used for crosscorrelation analysis was a product of the number and size of the lesions, that were rated as mild ( l ) , moderate (2) or severe (3).

Statistical analysis of the results was carried out by the Student’s t-test, Chi-square test and Pearson’s correlation coefficient. Significance levels of PcO.05 were considered significant. Individual values were regarded as abnormal when 2 SD above or below the normal mean. Results

Table 1 shows the mean values of motor and sensory conduction velocities for median and tibial nerves in patients and in controls. Mean distal sensory latencies were significantly prolonged in both nerves in patients with respect to the controls. There were no other appreciable differences between patients and controls except for median MCV and median and tibial CMAPa, even if the lower values in patients did not reach statistical significance. The CMAPa of the median nerve was only marginally significant (P=0.06). Peripheral conduction values were impaired in 3 patients for the median nerve and in 5 for the tibial nerve (Table 3); median and tibial involvement

Table 1 Median and tibial nerve conduction values in patients and controls (rneankSD) FSHD

Controls

Median MCV DML CMAPa

546i-40 347+07 137+39

scv

601122

OSL

3 33kO 5” 37 3 i- 15 6

58.4+ 5.6 3.10k0.4 16.9 k 4 . l 60.4 k 5.6 2.97k03 38 5k13.2

45 1 1 3 7 65021 0 952244 469~73 943+15’ 240+44

467+51 573+18 11 5 + 3 8 46.6&48 7 17+2 3 242k62

SAPa Tibia1 MCV DML CMAPa

scv DSL SAPa ~~

~~

MCV SCV (m/sec). DML, DSL (msecl CMAPa (mV], SAPa (pVJ

Pi005

347

Fierro et al. Table 2 Median and tibial SEP values in patients and in controls (meanFSD1

FSHD

Controls

SEPs Median N9 N13 N20 N9-13 N13-20

1007iO75"" 13 73 +O 97"" 19 72 + O 90"" 3 67 & 0 53 569i045

919+071 12 67+0 91 1 8 2 5 1 1 11 3 48 +O 36 5 58 +O 46

Tibia1 P40 N50 P60 P40-60

40 09 i 2 24' 50 09+3 01'" 61 7 6 i 2 0 1 " " 21 6 7 i 2 22

3 7 8 9 + l 88 4753+1 34 58725260 21 05+324

167i015 3 83&0 16 5 73 +O 20 2 12+022 189iO99 406+0 13"

17+021 3 8 1 0 30 55i030 21+010 171020 38i025

166i011 384+0 13 579+0 16' 2 18+0 14"" 196+0 14 4 11 k0 10""

171020 37+020 55+030 19+020 192+045 38i025

BAEPs Right

I 111 V 1-111 Ill-v

I -v Left I Ill

v /-Ill Ill-v

I-v P< 0 05; ** P< 0 01

coexisted in 2 and only 1 patient had exclusively sensory nerve anomalies. Table 2 shows the mean values of SEP latencies in patients and in controls. The mean absolute latencies from the median and tibial nerves were significantly prolonged in patients with respect to the controls, while the mean interpeak intervals did not differ between groups. When analyzed individually, prolonged N9, N13, P40 and N50 absolute

latencies were the most frequent abnormalities; 1 patient only showed abnormal N9-13 and N13-20 intervals. No patients showed abnormal P40-60 values nor absent responses. Seven FSHD patients (77%) had at least one abnormal SEP parameter without significant differences in median and tibial involvement, the total number of SEP abnormalities being the same for both nerves (Table 3). The BAEP data from patients and controls are shown in Table 2. A significant increasing of V wave mean latency and 1-111 and I-V mean intervals was present in patients compared to the controls. No differences between patients and controls were observed about the latency of the I wave that also showed a normal shape. Individual analysis revealed the presence of abnormal BAEP values in 5 patients (5.5%). Bilateral abnormalities (with both right- or left-sided stimulation) predominated, with only 2 patients showing unilateral abnormalities at the left side. In FSHD group, 1-111 interval was the only abnormal parameter in 4 patients, one of which presented also absent V wave on the left side. In the other patient right V wave latency and both I-V intervals were abnormal. Coexisting abnormalities of SEP and BAEP were present in 4 patients (Table 3). Pearson's correlation showed significant relationships between individual values of the motor and sensory conduction velocities and the latencies of the SEP components. In particular median SCV was negatively related to N9 (r=-0.72, P