Documenta OphthalmoloNca 46,2: 345-351, 1979 VALUE OF PATTERN EVOKED CORTICAL POTENTIALS F O R THE DIAGNOSIS OF MULTIPLE SCLEROSIS G.H.M. VAN LITH, A.G.M. VAN VLIET & G.T.M. VAN DOK-MAK

(Rotterdam,)

INTRODUCTION In the preceding paper, it was stated that for the diagnosis of multiple sclerosis (MS) objective evidence of separate lesions is important (van Vliet & van Lith, 1978). Especially in patients with symptoms of a focal lesion in the spinal cord, the detection of lesions in the brainstem or the visual pathways may be decisive. The aim of the present investigation was to elucidate the value of the visually evoked cortical potentials (VECPs), recorded with a slow pattern reversal stimulus according to Halliday's method (Halliday et al., 1973). Special attention was paid to the reliability, the sensitivity and the specificity of the test. As to the sensitivity of the test, Halliday et al. (1973) found a delay in the pattern VECPs in all but 2 of 51 patients with MS. 16 patients had no history of an optic neuritis. Asselman et al. (1975), using the same method, reported 51 patients with definite or suspected MS. In the group of definite or probable MS (grouping of McAlpine et al., 1972), the VECPs were delayed in 84% and 83% respectively, in the group of possible MS only in 21%. Recently, Matthews et al. (1977) published the results of 186 patients. The percentage of delayed responses was 75% in the group of definite MS, 58% in the group of probable MS and 38% in that of possible MS. Concerning the specificity of delayed VECPs, Halliday et al. wrote in 1973 that an increase in latency times may also be found in spinocerebellar degeneration with optic atrophy, in dominantly inherited optic atrophy and in compressive lesions of the optic nerve. In our experience, especially compressive lesions around the chiasm lead to delayed VECPs. In dominantly inherited optic atrophies we measured latencies in two early cases and in one advanced case; they were normal. Though usually one-sided, also important for the differential diagnosis is the observation of Asselman et al. (1975) that delayed VECPs occur in ischaemic opticoneuropathy. Other ophthalmological lesions in which we noticed delayed responses, are glaucoma, retinal circulatory disturbances and other diseases causing retinal oedema.

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The significance of the examination of the pattern VECPs for the diagnosis MS is the detection of a second lesion. This is especially important in suspect cases with brainstem symptoms, such as vertigo, diplopia and dysarthria, or with single signs, such as nystagmus and sensory defects in the trigeminal area. Therefore we also investigated, apart from patients with established or suspected MS, a group of patients who almost certainly did not have MS, but had a cryptogenic neuropathy of a cranial nerve other than the optic nerve. MATERIAL The material included 43 patients (27 female and 16 male). On the basis of the clinical history and the neurological signs, the multiple sclerosis patients were grouped as described by McAlpine et al. ( 1 9 7 2 ) i n definite multiple sclerosis (8 patients), probable multiple sclerosis (10 patients) and possible multiple sclerosis (16 patients). F o r a more detailed description of the patient material the reader is referred to the preceding article (van Vliet & van Lith, 1978). The group with neuropathy of a cranial nerve other than the optic nerve consisted of 5 patients with Bell's palsy (1 bilateral), 1 patient with herpes zoster oticus, 2 patients with bilateral neuropathy of the 8th nerve and 1 patient with vestibular neuronitis. Pattern stimulation was carried out according to Halliday's method, using a projector system, a TV system being less suitable for measuring latency times (van Lith et al., 1978). The field size was 30 ~ subtended visual angle, the check size 1~ Two luminances were applied: 400 apostilb (asb) for the light checks and 40 asb for the dark checks or 40 asb and 4 asb respectively. The reversal frequency of the checks was 2 movements per second, each movement being accomplished in 5 msec. The registering electrode was placed in the midline 15% of the nasion-inion distance above the inion, i.e. approximately 5 cm. For the referential electrode an earlobe was used. Bandwidth of the amplifier was 0 . 1 6 - 7 5 Hz, 125 responses were averaged. The peak latency time to the first large positive wave was measured. According to the latency time, normal subjects and patients are groiaped in classes of 10 msec. RESULTS Figure 1 represents the results of 20 eyes of 20 normal subjects (open columns) and of 16 eyes of patients with definite MS (closed columns). In the normal group the mean value of the latency time at the higher

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Fig. 1. Latency times of pattern VECPs in 20 normal eyes (open columns) and in 16 eyes of patients with definite MS (closed columns). Upper part: luminance level of 400 asb for the light checks and 40 asb for the dark checks, lower part; 40 and 4 asb respectively. At the low luminance level the VECPs in 2 eyes were too low to be measured.

luminance is 100 msec, that at the lower luminance 110 msec, the standard error for both groups being 5 msec. Apart from this difference in l a t e n c y time, it can be clearly seen in the figure that the distinction between the normal group and the MS group is much clearer at the lower luminance than at the higher luminance level. Therefore, the numerical evaluation has been carried out with the results obtained at the lower luminance level. In this group the latencies of 1 patient could not be measured, because the amplitudes were too low. If a latency of more than 120 msec is considered to be pathological, all other patients had delayed VECPs. In the group of 10 patients with propable MS (fig. 2), VECPs of 2 patients were too low to be evaluated, while 4 other patients had delayed VECPs. 16 patients with possible MS, all with measurable VECPs, were examined (fig. 3): VECPs were delayed in 11 cases. In the group of 9 patients with Bell's palsy or octavus VIIIth nerve neuropathy, delayed VECPs were seen in 4 patients, in two of them on one

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eye only. It appeared that there was no significant difference in abnormal VECPs between this group and the MS group (X 2 = 2.55; p > 0.10).

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Fig. 2: Results of 20 normal eyes compared to those of 20 eyes of patients with probable MS. At the low luminance level (lower part of the figure) the VECPs in 4 eyes were too low to be measured. See further legend figure 1.

DISCUSSION All authors agree that in definite MS a high incidence of delayed VECPs occur. In our group of patients this is also the case. Striking, especially in figure 1 and 3, is that the distinction between the normal and the pathological group is less pronounced at the higher luminance level than at the lower luminance level. At the latter, therefore, sensitivity and reliability are better. The difference in latency times between the two luminance levels in the normal group as well as in, the pathological groups makes it highly important to check the luminance level of the screen of the apparatus and the distance between the screen and the patient regularly and carefully. Furthermore, the pupil size, on which the illumination of the retina depends also, has to be measured at the luminance level present during the examination. Pupil

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Fig. 3. Results of 20 normal eyes compared to those of 32 eyes of patients with possible MS. See further legend figure 1. sizes larger than 6 mm or smaller than 4 mm have to be taken into account, since then retinal illumination deviates more than 0.5 log unit (Le Grand, 1968). The answer to the question, whether the pattern VECPs may contribute to the diagnosis of MS, has to be negative for the group of definite MS since the diagnosis was already established. The delayed VECPs in the 6 patients with probable MS will very probably point to the diagnosis, but the normal VECPs in the other 4 patients will not exclude it. How far the VECPs, whether normal or abnormal, are decisive in the group of possible MS, can only be evaluated when a definite diagnosis based on other symptoms can be made. Some reservation has to be made concerning the specificity of the delayed VECPs. From literature and from our experience, it is clear that this symptom is not specific for MS. First of all, some ophthalmological diseases have to be excluded, most of which can usually be detected by determination of the visual acuity, although chronic glaucoma can be treacherous. More problems may be encountered in the differentiation of delayed VECPs in the various neurological disorders which may cause them. Compression on optic fibres and heredo-ataxias were already mentioned. Bell's palsy and octavus VIllth nerve neuropathy have to be added. As far as we know the latter two have not been described previously.

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Fig. 4. Results of 20 normal eyes compared to 18 eyes of patients with neuropathies of other cranial uerves. See further legend figure 1.

SUMMARY Delayed pattern evoked electrical cortical potentials provide a very sensitive index of clinically silent optic nerve lesions, but are not specific for multiple sclerosis. Apart from the influence of retinal illumination and of some ophthalmological diseases, delayed responses may also occur when optic nerve fibres are compressed. We observed them in Bell's palsy and octavus VUlth nerve neuropathy.

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REFERENCES Asselman, P., Chadwick, D.W. & Marsden, C.D. Visual evoked responses in the diagnosis and management of patients suspected of multiple sclerosis. Brain 98: 261-282 (1975). Grand, Y. Le. Light, colour and vision; 2nd ed. London, Chapman & Hall, 1968. Halliday, A.M., McDonald, W.I. & Mushin, J. Visual evoked response in diagnosis of multiple sclerosis. B~it_ med. J. 4 : 6 6 1 - 6 6 4 (1973). Lith, G.H.M. van, Marle, G.W. van & Dok-Mak, G.T.W. van. Variation in latency times of visually evoked cortical potentials. Brit. J. OphthaL 6 2 : 2 2 0 - 2 2 2 (1978). Matthews, W.B. et al. Pattern reversal evoked visual potential in the diagnosis of multiple sclerosis. J. Neurol. Neurosurg. Psyehiat. 40:1009-1014 (1977). MeAlpine, D., Lumsden, C.E. & Acheson, E.D. Multiple sclerosis. A reappraisal. London, Churchill, 1972. Vliet, A.G.M. van & Lith. G.H.M. van. Nystagmography as a diagnostic tool in multiple sclerosis. To be published in this volume. Author's address: Eye Department Erasmus University Eye Hospital Schiedamse Vest 180 3000 LM Rotterdam The Netherlands

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