Electroencephalography and Clinical Neurophysiology , 1979, 4 7 : 6 0 7 - - 6 1 0 © Elsevier/North-Holland Scientific Publishers, Ltd.

607

Clinical note BRAIN STEM AUDITORY MULTIPLE SCLEROSIS

EVOKED

POTENTIALS

AND BLINK

REFLEX

IN QUIESCENT

F. L A C Q U A N I T I , P. B E N N A , M. GILLI, W. T R O N I and B. B E R G A M A S C O 1st Neurologic Clinic, Turin University, Turin (Italy) ( A c c e p t e d for publication: April 25, 1979)

It is well k n o w n that subjects with m u l t i p l e sclerosis (MS) may have abnormal brain stem auditory evoked potentials (BAEP) and blink reflexes (BR) even in the absence of s y m p t o m s and signs of brain stem d y s f u n c t i o n ( N a m e r o w and E t e m a d i 1970; Kimura 1975; R o b i n s o n and R u d g e 1977; Stockard et al. 1977). But direct intraindividual correlations b e t w e e n these two tests, b o t h exploring the brain stem, are still missing. Moreover, in the previous reports all BAEP and BR abnormalities have been expressed as increases in latency a n d / o r decreases in amplitude o f the c o m p o n e n t s , while it seems likely that such changes must be m u c h m o r e c o m p l e x and variable in c o n s e q u e n c e o f the anatomical and functional i m p a i r m e n t of the brain stem by the disease.

Material and methods Twenty-five patients (13 males and 12 females, m e a n age 33 years, range 18--55 years) with definite MS (according to McAlpine et al. 1972) in a quiescent phase, w i t h o u t present signs of i n v o l v e m e n t of the brain stem and w i t h o u t hearing deficit, were selected f r o m the general p o p u l a t i o n of MS f o l l o w e d by our Clinic. In MS patients and in 20 normal subjects m a t c h e d for age and sex to the patient group, BAEP and B R were measured. Hearing thresholds to click stimuli were within 15 dB o f the l a b o r a t o r y standard for b o t h groups. B A E P were obtained by monaural stimulation through earphones in a s o u n d - p r o o f r o o m with clicks of 0.2 msec duration, at a rate o f 10/sec and an intensity of 75 dB SPL (sound pressure level) and recording with Ag-AgC1 disk electrodes f r o m the vertex and mastoid ipsilateral to stimulation, with the contralateral mastoid serving as ground. The nonstimulated ear was masked by white noise to prevent crosshearing. The signals were amplified by a factor of l 0 s and r e c o r d e d using a band-pass filter f r o m 32 Hz to 3.2 kHz (3 dB d o w n points); t h e y were

s u m m e d with an Amplaid-Medelec E R A MK III averager, and the c o m p u t e r average of 1,024 such responses was obtained 3 times in succession from b o t h left and right ears. In s o m e cases (see Discussion} stimulation at different intensities (95, 75, 55 dB SPL) and longer averaging (2,048 and 4,096 responses) were p e r f o r m e d . BR were o b t a i n e d (Medelec MS6) by percutaneous stimulation of the supraorbital branch of the trigemihal nerve (stimulus voltage sufficient for a maximal c o n t r a c t i o n of the ipsilateral orbicularis oculi muscle; duration 0.1 msec) and recording with coaxial needle electrodes placed in the end-plate region of the same muscle. Ten d e t e r m i n a t i o n s were p e r f o r m e d in each subject for b o t h left and right trigeminal stimulation. Habituation of the late responses (R2) was avoided by r a n d o m l y delivering the stimuli. All patients showed a normal EMG interference pattern on m a x i m a l volun-

T A B L E Ia Mean values and standard deviations of wave-peak latencies, interpeak c o n d u c t i o n t i m e and intraindividual intertrial variability of wave V of brain stem a u d i t o r y potentials in 20 normal subjects. (Monaural stimulation of 75 dB SPL intensity; left and right ear stimulations c o m b i n e d . ) All values given in msec. Wave

Mean

SD

Mean wave latencies

I II III IV V

2.0 3.0 4.1 5.4 6.0

0.1 0.2 0.2 0.3 0.2

Mean interwave latencies

I--III III--V I--V

2.1 1.9 4.0

0.2 0.2 0.2

0.1

0.1

Intertrial variability of wave V

608

F. L A C Q U A N I T I ET AL.

T A B L E Ib

tary c o n t r a c t i o n o f the orbicularis oculi muscle. Moreover the latency o f the direct response o f this muscle to s t i m u l a t i o n o f the facial nerve was always w i t h i n our n o r m a l limits. In Table Ia and b we have s u m m a r i z e d BAEP and BR latency values o b t a i n e d in the c o n t r o l group. Since BAEP and BR records did n o t s h o w significant individual d i f f e r e n c e s in l a t e n c y b e t w e e n the sides, we used as n o r m a t i v e data the c o m b i n e d averaged values for left and right stimulation.

Mean values and s t a n d a r d deviations o f reflex response latencies and intraindividual intertrial variability o f Rl o f blink reflex in the same c o n t r o l g r o u p (left and right trigeminal s t i m u l a t i o n s combined). All values given in msec.

Minimal lateneies

Intertrial variability o f R1

Reflex response

Mean

SD

R1 R2 R2 contralat.

10.2 28.7 27.1

0.7 2.8 3.4

1.0

0.6

Results The responses o b t a i n e d f r o m MS p a t i e n t s were c o n s i d e r e d a b n o r m a l if either left or right or b o t h responses s h o w e d a b n o r m a l latencies (see below). The a m p l i t u d e s o f the various c o m p o n e n t s , w h i c h are also quite variable in n o r m a l subjects, were n o t c o n s i d e r e d to be a reliable i n d e x o f a b n o r m a l i t y .

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Fig. 1. L e f t side: brain s t e m a u d i t o r y p o t e n t i a l s evoked by 10 c/sec m o n a u r a l click s t i m u l a t i o n at 75 dB SPL in a normal subject (a), and in t h r e e d i f f e r e n t MS p a t i e n t s ( b - - d ) ; t w o separate, c o n s e c u t i v e averages o f 1,024 responses o b t a i n e d during the same session and u n d e r the same b a c k g r o u n d c o n d i t i o n s are s u p e r i m p o s e d in all records. Right side: blink reflexes o b t a i n e d by trigeminal s u p r a m a x i m a l s t i m u l a t i o n and r e c o r d i n g f r o m ipsilateral orbicularis oculi muscle; traces are f r o m a n o r m a l subject (e), and successive records (f--h) o b t a i n e d in one MS p a t i e n t during the same session and u n d e r the same c o n d i t i o n s .

B R A I N S T E M R E S P O N S E S IN MS

609

B A E P abnormalities

In 6 patients (24%), there was prolongation of one or m o r e of the interwave latencies (I--III, III--V, I--V) by m o r e than the upper 95% confidence limit, while all BAEP tracings o b t a i n e d during consecutive trials overlapped exactly (Fig. l b ) . In 3 patients (12%) the tracings overlapped exactly e x c e p t for wave V, which peaked at significantly different latencies during consecutive trials (Fig. l c ) . In 7 patients ( 2 8 % ) w e obtained tracings with p o o r superimposition of all waves e x c e p t wave I (Fig. l d ) . As a whole, the prevalence of B A E P abnormalities in our MS group was 64% (16 of 25 patients). B R abnormalities

Correlation b e t w e e n B A E P and B R

In Fig. 2 we have summarized the prevalences of B A E P and BR abnormalities and the correlation b e t w e e n the two tests in the MS group: 13 patients (52%) had b o t h BAEP and BR abnormalities; 7 patients (28%) had neither B A E P nor BR abnormalities; 5 patients (20%) had either B A E P or BR abnormalities.

Discussion

Eleven patients (44%) had prolongation o f the minimal latency of one or m o r e of the reflex responses (R1, R2, R2 contralateral) outside the upper 95% c o n f i d e n c e limit. F o u r patients (16%), on the contrary, had normal minimal latencies but abnormally large differences b e t w e e n the minimal and the maximal latencies of R1 obtained in consecutive d e t e r m i n a t i o n s (Fig. l f , g, h). However, the total n u m b e r of patients with significantly high intertrial variability o f R] was 11 (44%), since s o m e of t h e m

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(7) had prolongation of the minimal latency as well. As a whole, the prevalence of BR abnormalities in our MS group was 60% (15 of 25 patients).

B R

abnormalities

BAEPendBR abnormalities

Fig. 2. Prevalences in the MS group (from left to right): brain stem a u d i t o r y evoked potential (BAEP) abnormalities (64%); blink reflex (BR) abnormalities (60%); abnormalities of b o t h B A E P and BR (52%).

A l t h o u g h calculated according to criteria different from those usually a d o p t e d , our percentages of BAEP and B R abnormalities are n o t dissimilar to those separately r e p o r t e d in the literature for groups of MS patients w i t h o u t signs of brain stem involvement ( N a m e r o w and E t e m a d i 1970; Kimura 1975; Robinson and Rudge 1977; Stockard et al. 1977). A positive correlation b e t w e e n B A E P and B R abnormalities was f o u n d by us in m o s t of our MS patients. This good correlation is n o t surprising if we consider the close p r o x i m i t y of the brain stem areas respectively e x p l o r e d by these two tests. A major p o i n t seems to be the finding of B A E P and BR changes o t h e r than the simple increase in the latencies of the c o m p o n e n t s . Many patients had BAEPs which showed little superimposition on consecutive repetition. It m u s t be n o t e d that this great variability did n o t d e p e n d on either stimulus intensity (it was observed at 95, 75 and 55 dB SPL stimulus intensity) or n u m b e r of averaged responses (it could be seen at 1,024, 2,048 and 4,096 response averaging). This leads to the conclusion that n o t only can brain stem d e m y e l i n a t i o n slow the c o n d u c t i o n velocity along its nervous p a t h w a y s (so causing a latency increase of B A E P central c o m p o n e n t s ) but it can also give rise to a more serious d y s f u n c t i o n of the ascending chain of electrical generators which sequentially produce the individual c o m p o n e n t s of BAEP. The variable deflections of B A E P obtained in m a n y of our MS patients are n o t at all comparable to the well recognized, c o n s t a n t waves shown by normal subjects and basing the latency m e a s u r e m e n t s on t h e m could actually jeopardize the results. It must be noted, incidentally, that such abnormal, variable deflections appear t o o large to be the result o f a mere c o n d u c t i o n desynchronization along brain stem a u d i t o r y pathways. On the contrary, such d e s y n c h r o n i z a t i o n w o u l d give rise, on averaging, to signals less distinguishable or totally indistinguishable from background noise. The intraindividual intertrial variability o f B R

610 component latencies is probably not caused by a single factor (Troni et al., in preparation). We only wish to point out here the possibility of abnormal quantitative fluctuations in the pool of reflexly activated units which give rise to BR responses. A support for this hypothesis is provided by the frequent finding of parallel latency and amplitude fluctuations of such variable reflex responses. In conclusion, it emerges from our results that several different criteria have to be used in order to recognize BAEP and BR abnormalities reliably in MS patients.

Summary Brain stem auditory evoked potentials (BAEP) and blink reflexes (BR) were studied in 25 patients with multiple sclerosis (MS), the diagnosis being definite according to McAlpine's criteria, in the quiescent phase, without signs of brain stem involvement. BAEP abnormalities were found in 64% of the cases and BR abnormalities in 60%. A good correlation between the two tests was found in most patients. The abnormalities consisted of delayed latencies and/ or high intraindividual variability in shape and latency of BAEP and BR components. It seems that demyelination of brain stem pathways results not only in conduction slowing but also in more serious dysfunction of the generators of the evoked components.

R6sum6 P o t e n t i e l s dvoquds auditifs d u tronc cdrdbral et rdflexe de c l i g n e m e n t chez des sujets avec scldrose en plaques en phase silencieuse

Les potentiels 6voqu6s auditifs du t r o n c c6r6bral (PEAT) et le r6flexe de clignement (RC) ont 6t6

F. LACQUANITI ET AL. etudi6s chez 25 patients atteints de scl6rose en plaques (SEP) de diagnostic certain (selon les crit4res de McAlpine), en phase silencieuse et sans signes de tocalisation au niveau du tronc c4r6bral. Des anomalies des PEAT ont 6t6 trouv6es dans 64% des cas et des anomalies d u RC, dans 60%. Une bonne corr61ation entre les deux examens a 6t~ obtenue chez la plupart des malades. Les anomalies consistaient en augmentations de latences et/ou en une grande variabitit6 intraindividuelle de la forme et de la latence des composantes des PEAT et RC. I1 semble que la d6my61inisation des voies du tronc c6r6bral produise non seulement un ralentissement de la conduction nerveuse mais aussi un mauvais fonctionnement des g~ndrateurs des composantes des potentiels 6voqu6s.

References Kimura, J. Electrically elicited blink reflex in diagnosis of multiple sclerosis. Brain, 1975, 98: 413-426. McAlpine, D., Lumsden, C.E. and Acheson, E.D. Multiple Sclerosis: a Reappraisal. Churchill-Livingstone, Edinburgh, 1972. Namerow, N.S. and Etemadi, A. The orbicularis oculi reflex in multiple sclerosis. Neurology (Minneap.), 1970, 20: 1200--1203. Robinson, K. and Rudge, P. Abnormalities of the auditory evoked potentials in patients with multiple sclerosis. Brain, 1977, 100: 19--40. Stockard, J.J., Stockard, J.E. and Sharbrough, F.W. Detection and localization of occult lesions with brain stem auditory responses. Mayo Clin. Proc., 1977, 52: 761--769.