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Brainstem auditory evoked responses in 200 patients with multiple sclerosis.

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Brainstem Auditory Evoked Responses
in 200 Patients with Multiple Sclerosis
Keith H. Chiappa, MD, Jane L. Harrison, BA,
Elizabeth B. Brooks, BA, and Robert R. Young, MD
Brainstem auditory evoked responses (BAERs) were recorded from 202 patients with definite, probable, or possible
multiple sclerosis (MS). Definitions of abnormality were based only on interwave separations and the wave I/wave V
amplitude ratio. Thirty-two percent of the patients had abnormal BAERs, and the presence of clinically unsuspected lesions was revealed by BAER abnormalities in 7.4% Thirty-five percent of the patients who had nystagmus
and 53% of those who had internuclear ophthalmoplegia at the time of testing had BAER abnormalities. Forty-&
percent of the abnormalities were elicited with stimulation of one ear only, stressing the importance of monaural
stimulation. Click rates faster than 10 per second did not reveal abnormalities undetected at slower rates. BAERs
were normal by these criteria in patients with labyrinthine diseases and amyotrophic lateral sclerosis. Thus, the
BAER in MS can (1)confirm the presence of central lesions in patients with suspected brainstem involvement, (2)
document the presence of clinically unsuspected lesions, and (3) be followed over time to provide possible assistance
in evaluating the effectiveness of therapeutic measures. The BAER is a useful tool in the diagnosis and management
of MS.
Chiappa KH, Harrison JL, Brooks EB, et al: Brainstem auditory evoked responses in 200 patients with
multiple sclerosis. Ann Neurol 7:135-143, 1980
In humans, click stimuli to the ears evoke 7 waves in
the submicrovolt range that appear at the scalp in the
first 10 msec after the stimulus 117, 261. These “farfield” waveforms, which are generated by activation
of brainstem auditory pathways, ate recorded at a
distance on the scalp. Depth recording and experiments with lesions in cats 11, 16, 201 suggest that the
generators of waves I through V are, respectively, the
acoustic nerve, cochlear nuclei, superior olives, lateral lemniscus (tracts and nuclei), and inferior colliculi. T h e generators of the remaining two waves are
unknown or disputed. Studies done in humans [4-8,
12-14, 27-30, 32, 34-44], some with clinicopathological correlation, are in general agreement with
the findings in cats for waves I, 11, and I11 [ 7, 14, 20,
26, 32, 35, 36, 38-40, 441. Good data are not yet
available for waves IV and V in hunian beings, however, though there is no evidence to suggest that the
origins cited above are incorrect.
Brainstem auditory evoked responses (BAERs)
have been studied in groups of normal human subjects 14-6, 12, 13,20,28-30,34, 37-40,42-441 and
in a variety of patients with neurological lesions [4 , 7,
8, 13, 14, 27-29, 32, 35-44]. Patients suspected to
have demyelinating disease often pose diagnostic
difficulties, and the finding of abnormal BAERs can
be helpful in three ways: (1) in patients who present
with a single nonbrainstem locus of central nervous
system (CNS) involvement, the abnormal BAER
provides evidence of another clinically unsuspected
site of involvement; (2) in those in whom the clinical
findings are subjective, historical, or uncertain, the
abnormal BAER can provide objective evidence of
disturbed function; and ( 3 ) by monitoring abnormal
BAERs, various modes of treatment can be followed
and objectively evaluated. Robinson and Rudge
[27-291 and Stockard et a1 [42] studied BAERs in
restricted groups of patients with multiple sclerosis
(MS), but the incidence of abnormalities reported in
those studies was markedly greater than the figures
reported by Chiappa and Norwood [7].
We present here the results of BAER studies in
202 consecutive patients with MS in which abnormality rates were essentially the same as those reported in our previous, smaller study [7]. The
waveform abnormalities occurred in typical patterns,
examples of which are shown. T h e results of a comparison of BAERs, pattern-shift visual evoked responses (PSVERs), and short-latency somatosensory
evoked responses (SERs) in these MS patients are
presented. T h e abnormalities seen in the MS patients
are contrasted to those obtained in groups of patients
From the Robert S. Schwab Computer Facility of the Clinical Neurophysiology Laboratory’ Department Of
Medical School and Massachusetts General Hospital, Boston, MA.
Accepted for publication May 27, 1979.
Address reprint requests to Dr Chiappa, EEG Laboratory, Massa.
chusetts General Hospital, Boston, MA o2 14,
0364-5134/80/020135-09$01.25 @ 1979 by Keith H. Chiappa 135
with diseases that are possibly related t o MS or that
have a n initial clinical presentation which is s o m e times similar to it, such as optic neuritis, cervical
transverse myelitis, trigeminal neuralgia, cerebellar
disorders, labyrinthine disorders, a n d amyotrophic
lateral sclerosis.
BAER testing was performed on a consecutive series of
614 patients referred through routine channels. After the
diagnostic evaluation was completed, the medical record of
each patient was examined by one of us (K.H.C.), usually
more than four weeks after BAER testing, and a neurological diagnosis was appended. This diagnosis was almost always the same as that given by the primary physician except
that the McAlpine MS classification criteria I231 were
applied. In brief, these are: definite MS-signs and symptoms of multiple lesions in the C N S with a clear history of
exacerbations and remissions; probable MS-multiple lesions initially followed by good recovery and then only
minor fluctuations in severity over time; possible MSsimilar to probable MS but with unusual features or paucity
of signs. Spinal Huid gamma globulin or gold sol abnormalities were taken into account if there was doubt about
the diagnosis. No evoked potential data were used for
classification. No patient in the MS group came to neurological attention because of hearing difficulties.
In addition to indisputable signs and symptoms of past o r
present brainstem involvement, such as cranial nerve abnormalities o r diplopia, the following were also taken as
evidence of (possible) brainstem involvement: a clear history of dizziness (even if it could not be further characterized), nystagmus, gait disturbance (not due to a lesion
which could be localized elsewhere by other findings),
cerebellar signs, and sensory o r motor abnormalities for
which the vertical position in the CNS could not be determined by other neurological findings. The symptoms or
signs were not necessarily present at the time the BAER
was performed.
Two anatomical diagnostic groupings were used. The
diagnosis of labyrinthine disorder included Meniere’s disease, labyrinthitis, and vestibular neuronitis. The diagnosis
of cerebellar disorder included familial (e.g., Friedreich’s
ataxia, 1 case) and nonfamilial but not alcoholic syndromes.
Of the original 614 patients, 202 were diagnosed as
having MS (81 definite, 67 probable, and 54 possible) and
18, pure optic neuritis. Other groups of interest included
labyrinthine diseases (in 2 1 patients), cerebellar disorders
(in 13), trigeminal neuralgia (in 15), cervical transverse
myelitis (in 14), amyotrophic lateral sclerosis (in 9), and
other diagnostic classifications of no interest here (226 patients). In 92 of the 614 patients, no neurological diagnosis
could be made in spite of adequate information; records
were not available o n 4 patients.
Details of the BAER test procedure have been presented
in detail previously [GI along with tables of normal values
for all determinations obtained from 50 normal subjects.
Testing was done in a quiet but no sound-shielded room.
All patients were studied i n the supine position with appropriate head propping as necessary to minimize postural
136 Annals of Neurology Vol
No 2
Februarv 1980
muscle activity in the neck and head. I n addition, chloral
hydrate and diphenhydramine were often used to induce
drowsiness and sleep in tense patients. Electrode impedances were maintained below 3,000 ohms.
Monaural, constant-polarity click stimuli were produced
by applying a square wave of 100 psec to the earphones.
All patients were tested at a rate of 10 clicks per second,
and 57 were also tested at 70 clicks per second. Click intensity was adjusted to be 60 d b above hearing threshold for
the click stimulus for the particular ear. Masking white
noise was presented to the other ear, usually at 20 d b less
than the click intensity. Occasionally, click intcnsity was
decreased 20, 30, or 40 d b to aid in recognition of wave V.
Activity was recorded in a bipolar fashion between the
earlobe ipsilateral to stimulation and the vertex, with a
forehead electrode as ground; occasionally, simultaneous
recordings were made between the earlobe contralateral to
stimulation and the vertex. If wave I was not recognizable
with the earlobe electrode, a conventional electroencephalographic (EEG) needle electrode was inserted a few
millimeters below the skin surface in the easily accessible
anterior wall of the superficial segment of the external ear
canal; this usually revealed wave I. Activity was amplified
500,000 times by a Grass P S I 1 amplifier with a filter
bandpass of 100 to 3,000 H t (6 d b down) and a 60 H z
notch filter. The amplified EEG was monitored continuously on an oscilloscope, and averaging was halted manually or automatically when excessive artifact was present.
The average artifact level for each subject was recorded and
was usually less than 4 volts from peak to peak. The EEG
for 10.2 o r 12.8 msec after the stimulus was recorded and
processed with conventional averaging computers (Nicolet
1060 and 1070 and Grass 10 ERS). Each trial usually consisted of 1,024 or 2,048 sweeps. O n all machines, up to
four separate trials could be stored and ciisplaycd simultaneously and subsequently averaged. Photographs or X-Y
plotter graphs were taken of both the superimposed separate trials and the sum. Occasionally more than four trials
were performed, with a memory storage area keeping a
running average and the individual trials superimposed o n
the X-Y plotter paper. T h e complete test took an average
of 90 minutes to perform.
Variability between trials was used to judge the validity
of waveform characteristics, but the tracing of the sum was
used for all measurements. Latencies were measured between the positive peaks of two waves (interwave latency)
and calculated to the nearest 0.1 msec. When a peak was
not well defined, a midpoint of the waveform was estimated; this was also done when a bifid (notched) wave 111
was present. When waves IV and V were fused into a single
complex, the latency was taken to the point of final inflection before the negative limb of wave V, and this was recorded as wave V latency and amplitude only. When there
was no clear inflection point between waves IV and V, with
IV appearing as a shoulder o n V or vice versa, the midpoint
of the shoulder was estimated and latency and amplitude
measurements were made to that point. Amplitudes were
usually measured from the positive peak of the wave to the
following negative trough (vice versa for wave 1).
The upper limit of normal for each determination was
taken as the normal mean plus 3 SD derived from
50 normal subjects [6]. Only waves I, 111, and V were
measured, and interwave latency separations and amplitude
ratios were the sole factors used for determination of abnormality. No test was interpreted as abnormal o n the basis
of an abnormal inter-ear interwave latency difference
alone, though if an interwave separation was at or near the
upper limit of normal and the inter-ear interwave latency
difference was abnormal, then that segment was deemed to
have an abnormal interwave separation. The upper limits of
normal (and mean and S D for the 50 normal subjects [61)
for interwave separation were: waves 1-111, 2.6 msec (2.1 2
0.15); waves 111-V, 2.4 msec (1.9 0.18); and waves I-V,
4.7 msec (4.0 2 0.23). The upper limits of normal (with
mean and SD) for inter-ear interwave latency difference
were: waves 1-111, 0.4 msec (0.1 ? 0.09); waves 111-V, 0.4
msec (0.1 0.11); and waves I-V, 0.5 msec (0.13 2 0.1).
No test was interpreted as abnormal o n the basis of only an
abnormal IIUV amplitude ratio, although if the I/V ratio
was at o r near the upper limit of normal and the IIUV ratio
was abnormal, then the I/V ratio was deemed abnormal.
Absence of wave V was reckoned as a wave V amplitude
abnormality. The upper limits of normal (with mean and
SD) for the amplitude ratios, expressed as percentages,
were: I/V, 218% (73 % 48); and IIVV, 119% ( S O
The normal values for a rate of 7 0 clicks per second have
been published previously [6].
Wave I was present in all MS patients except for 5 in
whom it was absent unilaterally (4 of these had normal click hearing thresholds and 1 had a 50 d b deficit)
and 1 in whom it was absent bilaterally in spite of a
normal click hearing threshold. In all other MS patients, click hearing threshold was essentially normal
and wave I was present at a normal latency following
the click stimulus. Only a few patients had formal audiograms, and these were normal. Two of the patients with labyrinthine disease had no wave I bilaterally, and 1 had no wave I in one ear.
The incidence of BAER abnormalities in the 202
MS patients is shown in Table 1 and the relationships
of BAER abnormalities to clinical symptoms and
signs in Table 2. The symptoms or signs (or both)
referred to in Table 2 were not necessarily present
when the BAER was performed. However, among
the 20 patients with definite MS who had an internuclear ophthalmoplegia (INO), 13 had it at the time of
testing and 8 of these had abnormal BAERs (6
patients had recovered from the I N 0 at the time of
testing, and 5 of these had abnormal BAERs-1 patient developed the I N 0 after testing but had an abnormal BAER). Similarly, 19 of the patients with definite MS had nystagmus at the time of testing (not
related to an INO), and 11 of these had abnormal
BAERs (12 patients had recovered from nystagmus
at the time of testing, and 6 of these had abnormal
BAERs-1 patient developed the nystagmus after
testing but had an abnormal BAER).
Of the 202 MS patients, 138 (68%) had normal
BAERs. The means and SDs of the interwave latency
and amplitude ratio were calculated for these patients
in their respective MS groups and as a whole. None
Table 1 . Incidence o f Abnormal BAERs in 202 Patients with Multiple Sclerosis
No. of Patientsa
Patient Status
Definite MS
With symptoms and/or signs of brainstem lesion
Without symptoms and/or signs of
brainstem lesion
All patients
34/60 (57%)
8/38 (21%)
7/33 (21%)
491131 (37%)
4/21 (19%)
6/29 (21%)
5/21 (24%)
15/71 (21%)
38/81 (47%)
14/67 (21%;)
12/54 (22%)
641202 (32%)
Probable MS
Possible MS
aThe second number for each category is the number of patients who fit the clinical criteria, irrespective of BAER results-e.g., there were
60 patients with definite MS who had symptoms or signs of brainstem lesions, and 34 of these (57%) had abnormal BAERs.
Table 2. Incidence of Abnormal BAERs i n MS with Respect t o Various Symptoms or Signs of Brainstem Lesions
No. of Patientsa
or Sign
Definite MS
Probable MS
Possible MS
Internuclear ophthalmoplegia
14/20 (70%)
16/28 (57%)
17/32 (53%)
15/31 (48%)
1/6 (17%)
2/12 (17%)
5/20 (25%)
5 / 1 5 (33%)
1/4 (25%)
2/14 (14%)
2/17 (12%)
218 (25%)
16/30 (53%)
20/54 (37%)
24/69 (35%)
22/54 (41%)
"The second number for each category is the number of patients who fit the clinical criteria, irrespective of BAER results-e.g., there were
20 patients with definite MS who had an INO, and 14 of these (70%) had abnormal BAERs. Note that the symptoms or signs were not
necessarily present when the BAER was performed, and that some patients had more than one symptom.
Chiappa et al: BAERs in Multiple Sclerosis 137
Fig I . BAERs evoked from stimulation of each ear of a single
patient, showing the marked asymmetry that can be present
with monaural stimulatinn. This also shows another type of
abnormality seen i n M S : lack of u'ave 111 arid a markedly abnormal I-V separation of 6.7 msec i n the right ear (AD); the
left ear (AS) is normul. AS superimposed trials (upper trace)
hatme 1,024 clicks each: i n AD, 2,048 clicks each. The single
trace belouj is the ai'erage of the superimposed trials. Derivation i s the earlobe ipsilateral to monaural stimulation t o the
vertex; vertex p o itii,it.y
produces an upward defection. (Calibration: 0.25
5 msec.i
of the latency determinations differed from normal
values by more than 0.1 msec, and none of those for
wave V amplitude ratio by more than 10%. There
were no significant differences in these measures
between any of the separate MS groups (definite,
probable, or possible) and the 50 normal subjects [6].
Sixty-four (32%) of the MS patients had abnormal
BAERs. There was no significant correlation between
MS classification and type of BAER abnormality.
Eight of these patients (13%) had only interwave latency abnormalities, 35 (5596) had only wave V
amplitude abnormalities, and 21 (33%) had abnormalities of both interwave latency and wave V amplitude.
The interwave latency abnormalities consisted of
abnormal 1-111 separations in 4 patients (1 of whom
also had abnormal 111-V and I-V separations while
the other 3 had no wave V), abnormal 111-V separations in 18 patients (13 of whom also had an abnormal I-V separation and 1, an abnormal 1-111 separation), and abnormal I-V separations in 17 patients (13
of whom also had abnormal 111-V separation, 3 no
wave 111, 2 normal 1-111 and 111-V separations, and 1
F i g 2 . Spectrum of IV-V complex abnormalities seen in MS. A
and B were obtained follouing stimulation of the same ear of a
single patient, B two months after A. The IV-V separation
has increasedfrom 0.5 t o 1.1 msec and the I N amplitude ratio
from 90% to 204 %; both measures i n B are at the upper limit
of normal. C and Dare from different patients, shouing furtherprogression of the abnormality. In C , icaile IV is clearly
visible but ruave V is difficult t o recognize-riote the poor yeproducibility in repeated trials. In D, wat'e V i.r abse.ut and
wave IV is not as a distinct peak. In A, B, and C the
superimposed trials (upper trace) have 1,024 clich each: in D,
2,048 clicks each. The single trace below is the average ofthe
superimposed trials. Derivation is the earlobe ipsilateral t o
monaural stimulation t o the vertex'; vertex positivity produces
an uproard deflection. (Calibratiori: 0.25 pvq5 nlsec.)
138 Annals of Neurology
Vol 7 N o 2
February 1980
Table 3 . Comparative Incidence of Response Abnormalities i n MS t o B A E R , PSVER, and SER Tests
No. of Patientsa
BAER without symptoms and/or signs
of brainstem lesions
PSVER overall
PSVER without history of optic
Definite MS
Probable MS
Possible MS
4/21 (19%)
6/20 (21%)
5/21 (24%)
15/71 (215%)
64/79 (81%)
26/37 (70%)
35/67 (52%)
24/50 (48%)
13/54 (24%)
11/47 (23%)
1121200 ( 5 6 % )
611134 (46%)
10/16 (63%)
4/9 (44%)
13/21 (62%)
6/11 ( 5 5 % )
5/14 (36%)
2/6 (33%)
28/51 ( 5 5 % )
12/26 (46%)
SER overall
SER without symptoms and/or signs of
sensory lesions
“The second number for each category is the number of patients who underwent the particular test and who fit the clinical criteria, irrespective of evoked response results; see explanation for Table 1.
abnormal 1-111 and 111-V separations). Figure 1 shows
an example of an abnormal I-V separation with absence of wave 111. The mean interwave latency values
for the MS patients with abnormal BAERs were:
waves 1-111, 2.8 msec; waves 111-V, 2.8 msec; and
waves I-V, 5.2 msec.
Wave V amplitude abnormalities were seen in 56
patients. In 24 of them waves IV and V were absent;
in 1 5 only wave V was absent; and in 17 there was an
abnormal I/V amplitude ratio ( 6 of these patients also
had abnormal 111-V and I-V separations). Only 11
patients were found to have abnormal BAERs on the
basis of an abnormal I/V amplitude ratio alone; the
other 6 patients with abnormal I/V amplitude ratios
also had interwave separation abnormalities. The
mean I/V amplitude ratio in the MS patients with abnormal BAERs was 323%. There was no significant
correlation in any MS or BAER abnormality group
between interwave separation and wave V amplitude.
Figure 2 shows examples of amplitude abnormalities
and absence of waves IV and V.
Of the 57 patients tested at 70 as well as 10 clicks
per second, none had normal BAERs at 10 clicks per
second and abnormal BAERs at 70 per second, although abnormalities seen at 10 per second were
sometimes proportionately worse at the faster rate.
The abnormalities in the 64 patients with abnormal
BAERs were unilateral in 29 patients (45%) and
bilateral in 35 ( 5 5 % ) .There were substantially more
bilateral abnormalities in the definite MS group
(58% of all BAER abnormalities in that group) than
in the probable MS group (25%). Forty percent of
the patients with bilateral abnormalities had different
patterns in the two ears. Figure 1 shows an example
of a purely unilateral abnormality.
The comparative incidence of response abnormalities in MS patients tested with the BAER,
PSVER, and SER modes is presented in Table 3. In
70 (35%) of the MS patients, at least one of the tests
revealed evidence of a clinically unsuspected lesion,
and in 8 patients at least two tests did so.
All 18 patients with clinically pure optic neuritis
had normal BAERs, as did all 21 patients with
labyrinthine diseases, the 15 with trigeminal neuralgia, the 14 with cervical transverse myelitis, and the 9
with amyotrophic lateral sclerosis. Five of the 13
patients with cerebellar disorders had abnormal
BAERs, and these patients were the only ones in that
group with spasticity.
Only waves I, 111, and V were used in the evaluation
of BAERs in these patients. The lower frequency of
recognizability of waves 11, IV, and especially VI and
VII in normal subjects [GI renders them less useful;
these waves also tend to disappear earlier with lowering of effective stimulus intensities [38].If wave VI
could be more reliably recognized, it would permit
investigation of another section of white matterthat between the presumed generator of wave V (the
inferior colliculus) and the suggested generator of
wave VI, the medial geniculate nucleus. The use of a
noncephalic reference electrode [ 6 ] did not increase
the amplitude of wave VI, and except for binaural
stimulation-which induces other complications-no
maneuver was found to increase the amplitude of that
The reliability of our technique is demonstrated by
the fact that in the MS patients with BAERs interpreted as normal (the BAER-normal MS group), no
measurement made was statistically different from
normal values [6].Those MS patients with abnormal
interwave separations in the BAER had latency values a mean of 4.9 SDs above the normal mean, and
those MS patients who were found to have abnormal
BAERs on the basis of an abnormal I/V amplitude
ratio (17% of the BAER-abnormal MS group) had
amplitude percentages a mean of 5.5 SDs above the
Chiappa et al: BAERs in Multiple Sclerosis 139
normal mean. These facts, and the higher incidence
of abnormalities in the definite MS group, suggest
that the BAER is a reliable test for clinical use.
Although 3 SDs above the normal mean was used
as the upper limit of normal, the BAER-normal MS
patients (including those in the definite MS group)
had values for both interwave latency and amplitude
which were identical to those obtained in a group of
50 normal subjects [ 6 ] .The fact that the values for
the MS patients had a bimodal distribution (also
noted for absolute wave V latency by Robinson and
Rudge [28]), being either completely normal or
markedly abnormal, suggests that the smallest MS
plaques in this part of the auditory system are
sufficient to produce a marked conduction abnormality.
Robinson and Rudge [28] did not distinguish between latency and amplitude abnormalities, but
Stockard et a1 [42]found that the majority of BAER
abnormalities in their MS patients involved interwave latency. A majority of the BAER abnormalities
in our MS patients were wave V amplitude abnormalities, although both types of anomalies were present in many cases. Specifically, the most common
BAER abnormalities in our MS patients were absence or abnormally low amplitude of wave V (in
87% of the BAER-abnormal MS patients) and increased 111-V separation (in 28% of the BAERabnormal MS patients). The presumed generators of
waves I11 and V are the superior olivary complex and
inferior colliculus, respectively. Thus, the majority of
the conduction abnormalities lie between them, as
might be expected since that is the longest segment
of white matter in the tracts being tested. However,
in those patients who had recognizable wave Vs,
there was no significant correlation between 111-V
separation and the wave I/V amplitude ratio, despite
our expectations to the contrary. In fact, in 17% of
the BAER-abnormal MS patients, the 111-V separation was normal and the I/V amplitude ratio abnormal.
In addition, 3 patients had the unusual combination of no wave 111, a recognizable wave V of normal amplitude, and an abnormal I-V separation (see
Fig 1).The disparity between these different kinds of
abnormalities is not easily resolved merely by considering the known conduction deficits in demyelinated axons, such as slow conduction across the demyelinated segment and increased refractory period
[24].Multiplicity of lesions, possible contributions to
the BAER waveforms from conduction in separate
but parallel tracts, and possible synchronous activation of different auditory tract structures need to be
The importance of monaural stimulation, suggested by previous studies [4-7, 32,40,42], was evident here since 4596 of the BAER abnormalities
140 Annals of Neurology Vol 7 No 2 February 1980
were elicited with stimulation of one ear only (see Fig
I). The prevalence of monaural abnormalities suggests that, with respect to the BAER waveform
generators, there is relatively little bilateral conduition, although the anatomy had suggested otherwise.
Furthermore, our experience with clinicopathological correlations in BAERs [4, 71 suggests that the
actively conducting part of the system tested by the
BAER is primarily ipsilateral to the ear being stimulated. This is a very important consideration in the
clinical interpretation of BAERs, and more clinicopathological correlations will be available shortly to
prove or disprove this point.
Faster rates of stimulation alter all aspects of the
BAER, including interwave separations [b, 12, 30,
431. Stockard et a1 [40,421 and Robinson and Rudge
[28] had reported that increased click repetition rate
(Robinson and Rudge used paired clicks) revealed a
higher incidence of abnormalities in the BAERs of
MS patients. Previously we had not found this [7],
nor was a greater incidence of abnormality detected
with a testing rate of 70 clicks per second in the present group of MS patients, although abnormalities
seen at 10 clicks per second were sometimes proportionately worse at 70 per second. The relative
difficulty of waveform recognition at 70 clicks per
second, with increased waveform duration and indistinct peaks, restricted the clinical utility of that stimulus rate. In a few patients with disease other than
MS, we have noted the reverse situation: the I-V separation was abnormal at 10 clicks per second and
normal at 70 per second. This “normalization” may
be due to failure of conduction altogether in the abnormal fibers at the faster rate, possibly because of an
increased refractory period. With the abnormal contribution of these fibers removed from the resultant
waveforms, the activity manifested is only that from
the normally conducting fibers; hence the normal appearance. Although this effect was sought in the MS
patients, it was not found.
Conductive hearing losses d o not affect BAER I-V
latency separations, and cochlear losses tend to
shorten the I-V separation slightly at lower click intensities [9, 101; therefore, it is unlikely that either
condition would have led to false-positive findings in
this study. In spite of obvious abnormalities in the
BAER, none of the MS patients studied here had
clinical complaints of hearing difficulties, and click
thresholds were essentially normal (formal audiograms were rarely obtained, but those done were
normal). This picture is consistent with the findings
of routine audiological testing in MS patients [211,
but detailed auditory and vestibular [25] as well as
auditory localization testing [20a] may reveal funct i o n d abnormalities in MS patients. In the study by
Hausler and Levine, almost all MS patients with ab-
normal BAERs had abnormal interaural time discrimination as well. Occasionally MS patients d o have
symptomatic hearing difficulties that are apparently
related to the disease [ 191, but none were seen in this
group. Subjectively normal hearing in the presence
of gross abnormalities in the BAER is probably partly
explained by the BAER abnormalities being produced by temporal dispersion of the click-induced
volley as it ascends the affected tracts. These asynchronous potentials d o not sum to generate a discrete
peak of activity discernible at the scalp, but the integrity of conduction, albeit deranged, is sufficient to
sustain functionally normal hearing. However, this
does not explain those cases in which the amplitude
and waveform shape are essentially normal but there
is an abnormally large interwave separation. Perhaps
in these cases the demyelination involves a majority of the fibers equally. Also, of course, BAER
waveform generation might have little to d o with
functional hearing.
The incidence of abnormalities found in MS patients in this study agrees well with results obtained
in our previous group of 75 patients [71 but differs
widely from the results of others [27-29,423. Robinson and Rudge [27-29] studied 88 patients with
definite MS only and used absolute wave V latency
and amplitude measurements for test interpretations.
They reported 79% and 51% abnormality rates, respectively, in patients with and without signs of
brainstem lesions; also, they used binaural stimulation, which has been shown to mask abnormalities [4,
6, 431. Stockard et a1 [42] reported on 100 patients
with MS, using monaural stimulation and the preferred interwave latency and amplitude ratio criteria.
However, their definite MS group was selected to
contain only patients with clinical evidence of brainstem involvement and their probable and possible
MS groups to include only patients without past or
present clinical evidence of brainstem involvement.
Their abnormality rates were 93%, 7796, and 35% in
the MS groups, respectively, and 65% overall.
A comparison between the figures from these two
studies and our Table 1 reveals that our values are
markedly lower in all areas. Since our techniques and
normal values closely resemble those of Stockard et
a1 [42] and yet our abnormality rates were so much
lower, we compared some of the clinical data from
our group of MS patients with Kurtzke’s Army series
[ 181, which included approximately 2,000 patients.
Seventy-three percent of those patients had no optic
signs, 62% had no sensory symptoms in limbs, and
19% had diplopia, as compared with 6796, 5 1 9 6 , and
14% in our MS group. O n the basis of these clinical
findings, our group seems to consist of a reasonably
typical cross-section of MS patients with respect to
these elements of the disease. Fifty-eight percent of
Kurtzke’s patients had no brainstem symptoms, as
contrasted to 35% in our group; this difference appears to be due to our more liberal definition of
which symptoms or signs might constitute evidence
of a brainstem lesion (see Methods). W e believe that
our definition most clearly defines that group of patients in whom an abnormal BAER would be useful
to the clinician. However, it is recognized that a large
part of the clinical utility of the BAER lies in its ability to document an abnormality when the history,
neurological examination, or both are equivocal; that
some of these symptoms and signs are frequently
produced by lesions outside the brainstem; and that
these factors possibly produce convervative figures
concerning the clinical utility of BAERs in MS.
Our data show no significant differences between
the three MS groups in the number of clinically unsuspected lesions revealed by the BAER (see Table
l), with the overall rate of detection being 2 1% for
those without symptoms or signs of brainstem lesions
(7.4% of the entire MS group). The BAER abnormality rates, regardless of clinical findings, were
47%, 21%, and 22% in the three MS groups, respectively. This compares favorably with abnormality
rates of 49%, 11%, and 0% detected by computerized tomography (CT) [ 151; data on the number
of clinically silent lesions revealed was not available
in the C T study. The C T and the BAER may to some
extent be complementary, since the latter tests a section of white matter not well defined by the former.
These data indicate that the BAER is a useful clinical
diagnostic test in the evaluation of patients suspected
of having MS, even if judged only on the number of
clinically silent lesions revealed.
Almost all the MS patients had PSVERs tested (79,
67, and 54 in the three MS groups, respectively),
and some had median nerve SERs evaluated as well
(16, 21, and 14). Detailed methods and normal
ranges have been published elsewhere for the
PSVER [33]and median nerve SER [ 3 ] .Table 3 presents the comparative incidence of abnormalities
shown by the three evoked response tests in this
group of MS patients. Note that not all patients
underwent all three tests. The PSVER showed the
highest abnormality rate overall and also demonstrated proportionately the highest incidence of clinically unsuspected lesions; these results are consistent
with the high frequency of lesions found in the optic
nerves of MS patients at autopsy [223. As might be
expected because of the length of white matter tracts
involved in the median nerve SER, that test had results almost as significant as those of the PSVER,
while the BAER ranked third.
It should be reiterated here that a large part of the
clinical utility of the BAER lies not only in its ability
to reveal unsuspected, and thus multiple, lesions, but
Chiappa et al: BAERs in Multiple Sclerosis
also in its capability of documenting clinically
equivocal findings. For example, some patients with
MS initially presented with symptoms or signs that
could have been produced by disease in the
labyrinths. Other than absence of wave I in 3 of the
patients with Meniere’s disease, no abnormalities of
interwave separations or amplitude ratios in the
BAER were seen in the 2 1 patients with labyrinthine
diseases. Thirty-five percent of the MS patients
who presented with nystagmus at the time of testing
had BAER abnormalities. Thus the BAER can be
helpful in this setting: if it is abnormal, the lesion is
probably centrally rather than peripherally located.
Conversely, 53‘;; of the patients with an I N 0 at the
time of testing had abnormal BAERs, so the BAER
does not help to distinguish MS from the other
causes o f I N 0 (infarction and tumor [ll]), which
might also affect both the medial longitudinal fasciculus and auditory tracts. The BAER is abnormal in
some patients with system disorders affecting cerebellar function, particularly those who have spasticity, and thus is not helpful in differentiating possible
MS in that setting. Amyotrophic lateral sclerosis
sometimes appears initially with symptoms or signs
that might be suggestive of MS; in our 9 patients with
amyotrophic lateral sclerosis, none had abnormal
BAERs. Thus, the presence or absence of BAER abnormalities can be helpful during the initial presentation of patients with these diseases when MS is part
o f the differential diagnosis.
Optic neuritis and cervical transverse myelitis may
have closely related or identical causes to MS; all the
patients with those diseases had normal BAERs, and
the patients with optic neuritis who were tested also
had normal SERs (all the patients with cervical transverse myelitis had abnormal SERs). Trigeminal
neuralgia has been associated with MS, 8% [ 2 ] and
274 [ 3 I ] of patients with trigeminal neuralgia having
been found to have MS; of our 15 patients with
trigeminal neuralgia, none had abnormal BAERs.
Thus, as is the case clinically, at the time of onset of
optic neuritis, cervical transverse myelitis, or
trigeminal neuralgia, there may be no evidence from
evoked response testing of lesions elsewhere in the
The consistency of the BAER when followed over
time in normal subjects [b]suggests that it could be
used to follow the activity of lesions affecting these
tracts and might provide assistance in evaluating the
effectiveness of therapeutic measures, as suggested
by Stockard and Rossiter [40].
Supported in part by the Edwin Minot Fund for Research in Electroencephalograph> and a student stipend award from the Boston
Mental Health Foundation
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