Visual Evoked Potentials and the Visuogram in Multiple Sclerosis Ivan Bodis-Wollner, M D , Charles D. Hcndley, PhD, Leland H. Mylin, AT, and John Thornton, P h D

Visual evoked potential (VEP) latency to a sinusoidal grating pattern was measured in each eye of 103 patients with multiple sclerosis (MS) and compared with results in a control group of 56 patients hospitalized for other neurological conditions. Of the 50 patients classified as having definite MS, 90% showed prolonged latency (over 131 msec) in one or both eyes. In each eye of 24 of the MS patients, psychophysical measurement of the detectability of grating patterns was obtained. This test was abnormal in 11 of 13 patients with definite MS, 3 of 4 with probable MS, and 5 of 7 with possible MS. There was no concordance between prolonged VEP latency and visual impairment as revealed by the psychophysical test. Apparently pathways determining VEP latency and spatial contrast detection may be unequally affected in MS. Bodis-Wollner 1, Hendley CD, Mylin LH, et al: Visual evoked potentials and t h e visuogram in multiple sclerosis. Ann Neurol 5:40-47, 1979

Patients with cerebral lesions involving the visual pathway may complain of blurred vision even though standard tests of visual acuity do not indicate impairment. Most such patients have impaired spatial contrast Sensitivity to grating patterns 13, 51. T h e detectability of the stimulus grating is expressed as the minimum contrast necessary to detect the presence of dark and bright bands, i.e., a pattern. A patient’s contrast threshold is compared to the normal for several patterns of different spacing (coarse to fine), and the resulting loss function is termed a “visuogram.” Most patients with cerebral lesions show loss of fine pattern detection. In many others a generalized loss of contrast sensitivity can be found, while in a smaller group, spatial contrast sensitivity losses are encountered at some pattern spacings but not at others. Testing spatial contrast sensitivity has been rewarding in patients with corneal edema [ 151, tapetoretinal degeneration [28], glaucoma [ l , 21, macular disease 1261, multiple sclerosis [ 2 4 ] , and amblyopia [ 161. Measuring spatial contrast sensitivity reveals visual deficits undetected by visual acuity measurements. Some patients with MS have changes in their visuogram, even though their visual acuity is intact [ 5 ] . Halliday and his associates [ 1 1] have shown that patterns are the appropriate stimuli for detecting abnormalities in visual evoked potentials (VEPs) in retrobulbar neuritis. Delayed VEPs arc found in about 70 to 80% of patients with MS [ 121. Among these are some who never had visual symptoms and whose vi-

sual acuity is unaffected. Nevertheless, even these patients have prolonged VEP latency to patterned stimuli. With some exceptions 17, 131, most clinical VEP studies employ checkerboard patterns as stimuli. Although some studies have shown that psychophysical tasks reveal visual impairment in patients with VEP delay and normal visual acuity 19, 10, 231, the results of the psychophysical studies cannot be directly compared to the VEP data, since stimuli for psychophysical and VEP measurements differed. In this paper we report VEP measurements with grating stimuli in 103 patients with MS. In 24 of these patients, psychophysical detection thresholds of the samc grating patterns were also determined. These latter data allow us to examine the relationship of VEP latency to the visuogram in MS.

From the Departments of Neurology and Biosraristics, Mount Sinai School of Medicine, N e w York. N Y .

Address reprint requests N e w York, N Y 10029.

Methods Spatial /requency of a grating pattcrn is expressed as the number of adjacent pairs of dark and bright bands subtended in 1 degree o f visual angle at the observer’s eye. Sparial contrajt of a steady grating is the difference of maximum luminancc (L,) and minimum luminance (L!) over their sum. Vertical gratings with sinusoidal luminance profile were generated on the cathode ray tube (CRT) of a Tektronics 561 oscilloscope (Fig 1). This screen subtended 38 degrees at t h c observer’s eyc. The CRT screen was surrounded by another screen which was back-illuminated at about the samc hue and luminance as the CRT. The space-time average luminance of the screen was constant at 10 millilam-

Accepted for publication June 12. 1078.

40 0364-5 134/79/010040-08$01.25 @ 1978 by Ivan Bodis-Wollncr

to

Dr Bodis-Wollner. 1200 Fifrh Ave.

F i g I. Grating pattern of sinusoidal luminance profile, produced on the cathode ray tubr oja laboratory oscilloscope.To woke cerebral potentials the pattern was reversed twice each second (the white band became black, and vice versa, every 500 mser). berts. The stimulus for VEP measurements was a grating pattern of 2 . 3 cycles per degree. This was "reversed" twice per second, i.e., dark bands abruptly turned into bright bands and bright into dark. The signal effecting this pattern reversal triggered a Nicolet 1070 signal averager. Luminance of the CRT had been calibrated for AC and DC Z-axis input. Contrast was calibrated at different spatial frequencies. Scalp electrodes were placed 2.5 cm above the patient's inion and over the temporal bone corrcsponding to the posterior temporal electrode of the international 10-20 system [ 6 ] . For several patients, an additional reference electrode was placed in the midfrontal position and measurements were compared for the temporal and midfrontal reference position (Fig 2). The ground electrode was placed on the forehead. Potentials were differentially amplified with Grass 5P5 preamplifiers and filtered with corner frequencies of 0.15 to 50 Hz. The method of constant stimuli 151 was used to determine threshold contrast as 50% detectability of the pattern. The ratio of the patient's and the normal observer's contrast threshold is expressed in decibels of sensitivity loss at a number of spatial frequencies (20 decibels corresponds to 1 log unit, or a tenfold rise in threshold). Sensitivity was tested at the following spatial frequencies: 1.15, 2 . 3 , 4.6, 9.2, 13.8, and 18.4 cycles per degree. Normal spatial contrast sensitivity values have been previously established

among normal observers and hospitalized patients IS]. Visuograrns were classified as abnormal or normal according to criteria laid down for each of the three different types of contrast sensitivity losses (level, high frequency. or notch) 151. A classification of "borderline" was used when either a level loss of more than 8 but less than 12 decibels was encountered o r when a notch or high-frequency loss was between 6 and 8 decibels' change per octave. The evoked potential waveform obtained at a stimulation rate of 1 Hz is customarily labeled for its successive negative and positive deflection according to the nomenclature of Ciganek 181. Following the method of Halliday et al [ 1 1 ] for VEPs obtained with checkerboard stimuli, the critical measurement in our studies was the latency of the major positive wave. The covariance marrix and the mean of all right eye latencies and all left cye latencies were compared between controls and patients with MS. A multivariate analysis [ 2 7 ] was used to test the null hypothesis that the mean response of the control group is equal to the mean response of the MS group. Also tested was the hypothesis that the Covariance matrices arc equal. Discriminant analysis [221 was used t o study patient data grouped under the categories definite, probable, and questionable MS. Patients were classified by the criteria of McAlpine et al 11 71 as having definite, probable, or possiblc MS. For the purpose of assessing the clinical usefulness of the VEP test, we also considered patients referred for diagnostic cvaluation. We grouped all patients as questionable MS who had the classification of possible MS or whose history was inadequate to place them according to the McAlpine criteria. Visuograms and VEPs were compared for patients with adequate information to classify them according to the McAlpine criteria.

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Fig 2. !A) V i s u a l evokedpotentials i n a controlpatient. The stimulus was a reversing grating puttern (see Fig 1 ) iiewed monocularly. Here a n d i n subrequerttfigurej OD a n d 0s refer t o stintufation of the right a d lefi eyes alotte. T i m e Jcule, 5 0 0 msec. T h e double awaw at time zero shows a n amplitude of 5 pv in this a n d subsequent figures. Latencj of the major posztii~e (downgoing) dejection is 1 1 6 msec OD a n d 1 18 msec 0s. (B) E f j k t of reference electrode location on V E P : top tracing recorded from occipital to temporal electro&. bottom tracing from 0cc:pital t o ntidfrontal electrode. hlote the someulhat larger amplitude i n the bottom tracing; the latencies ( 1 12 a n d 108 msec) do not rlrff p r s i g n i f c a n t l j , hoicwer.

Results V E P Latency The mean VEP latency of the right eye in the 56 control subjects was 116 2 8 (SD) mscc and that of the left eyc, 116 2 8 msec. The mean interocular difference was 4 2 5 msec. The 95% confidence limit of the normal interocular difference was 10 mscc, while the upper 95% limit of the normal latency was 131 msec. T h e mean VEP latency of the right eye i n all 50 patients with definite MS was 151 36 msec, and that of the left eye, 15 1 36 msec. The mean interocular difference was 26 25 msec in this group. A multivariate test clearly @ < 0.0001) disproved the hypothesis that control and definite MS patients belong to the same population. This hypothesis was rejected based on the mean responses of the two groups as well as on the covariance matrices. Each observer in the control group exhibited a stronger correlation than patients did between VEP latency in the left eye with that in the right eye. Figure 3 shows

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a plot of VEP latency in the left versus the right eye for the control and definite MS groups. The control group data were used to estimate the mean response and covariance matrix for a bivariate normal distribution. Using these estimates, an ellipse containing 95% of the total probability for the control group was determined as shown in Figure 3. Using a discriminant function [22 J developed from the data of the control and definite MS groups, 1 of the 5 6 controls would have been misclassified as abnormal because her data point fell below the normal range. Of the 50 MS patients, 45, or 90%, were correctly classified; 5 patients (10%) would have been misclassified as normal. T w o of these misclassified patients had several episodes of blurred vision in addition to other symptoms. Their VEP latencies were 115 msec OD and 119 msec 0s and 136 msec OD and 136 msec 0s. T h e latter patient was above the 95% confidence limit for each eye separately, yct was Classified normal based o n the small, symmetrical increase in latency. The 3 other patients had several attacks of brainstem and cerebellar symptoms but n o visual symptoms. O n e of them had nystagmus at the time of the VEP measurement. H e r latency was 126 msec OD and 134 mscc 0s. T h c discriminant function was applied to a group of patients with probable and a group with questionable diagnoses of MS. Of 2 1 i n the probable group, 7 patients were classified as normal, while of 32 with questionable MS, 27 were classified as normal. The last result is influenced by the inclusion in this group of patients referred t o us for diagnostic evaluation, many of whom did not meet the McAlpine criteria of possible MS. Seven of 10 patients with spinal but no visual symptoms had abnormal VEPs. One of these could not be included in the statistical evaluation because his VEPs were so poor that no reliable latency measurements could be done. T h e 3 patients with normal VEP latency were 40, 48, and 50 years old, n o t very different in age from the mean age of this group (47 years).

V zsuograms Visuograms were obtained in 24 patients (13 with definite, 4 with probable, and 7 with possible MS). Twenty of these patients had visual acuity of 20/25 o r better. In 2 patients, visual acuity was 20/50 OD and 20/30 OS, while 1 patient’s acuity was 20/40 OD and 20/20 0s. None o f the patients had central scotoma. T h e visuogram was normal in both cyes of 5 patients (2 definite, 1 probable, and 2 possible MS) and borderline in both eyes of 2 patients ( 1 probable and 1 possible MS). T h e visuogram was abnormal in seventeen eyes, borderline in seven, and normal in ten

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F i g 3 . IAteni');ofthe major positive VEP dejeition in I0 patients uith definite MS (stars) and 56 control patients (filled circles; numerulc indicate two or three measurements at that locus).Valuafor the riKht and left q e s are .rhoum o n the ordinate and abscissa, respectively. An ellipse bas been druuin within which 95 % of the normal population u'ould be expected t o fall bused on the statistics ofthe controlgroup. The data of the MS group scatter iuidelj~,and the lack of interoculur concordunce for many of these patients i s evident.

eyes of thc remaining 1 7 patients. T h u s the visuogram classified 5 patients (21%) as normal, 2 patients as borderline, and 17 patients (71%) as abnormal, since eithcr o n e eye alone o r both eyes had abnormal visuograms. Sixteen eyes showed a high-frequency, ten eyes a levcl, and two a shallow, borderline notch type visuogram.

Comparison of V E P Latencies with Visuogrum Only a few patients showed concordance between VEP latency and visuogram abnormality (Fig 4 A ) . Some patients w h o had very prolongcd latencies in both eyes had normal visuograms (Fig 4B), o r the latency might be increased in the left eye while thc visuograrn was depresscd for the right eye, o r vice versa (Fig 4C, I)). T h e following null hypothesis was tested: Assumc that the average V E P latency for each separate eye for cach visuogram classification group (normal, borderline, o r abnormal) is identical. This null hypothesis could not be rejccted based o n an analysis of variance: the mean V E P latency was identical (14 1 msec) iri each visuogram g r o u p and for each eye. In addition a Wilcoxon rank test was consistent

with the interpretation that the normal group, as determined from the visuogram, does not, o n thc average, exhibit a shorter latency than the abnormal or borderline group. T h c latency was 141 msec in each group. W e then considered spatial contrast sensitivity in each eye of each patient for only the 2.3 cycles per degree pattern that was used as the stimulus for VEP latency measurements. T h e association was n o better between the contrast sensitivity calculated for this pattern alone and latency changcs with the identical pattern. For patients w h o had abnormal VEP latency in the right cye, the average contrast sensitivity loss was 3.6 decibels in the same eyc, while for patients with left eye abnormality, it was 5.7 decibels. For patients with normal latcncies, the corresponding losses were 1.1 and 2.5 decibels. These diffcrenccs did not reach statistical significance. Furthcrmore, VEP latency versus sensitivity loss to thc same pattern showed wide scatter (Fig 5 ) .

Discussion Reversing chcckerboard patterns are commonly used for clinical evoked potential studies. W e havc been using grating patterns with sinusoidal luminance profile for several reasons [41. Grating patterns are easy to generate o n oscilloscope screens in a broad range of luminance profiles, contrasts, spatial frequencies, and rcversal rates. A grating stimulus with sinusoidal luminance profile contains only a single spatial frequency and has n o cdge. Suboptimal correction in patients with rcfractivc errors causes no change in the luminance waveform o n thc retina, only a reduction in contrast.

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F i g 4. Detection threshold measurements were taken for several gratings of different coarseness (spatialfrequency). Thepatient's contrast threshold was compared to the rzormal observer's and chartedas a visuogram. (A)Normal VEP latency (122 msec) and normal visuogram OD, prolonged VEP latency 1146 nzsec) and borderline visuogram OS, i n a patient with probable MS. Visual acuit-y was 20120 OD and 20125 0s. ( B ) Normal visuogram i n a 54-year-old woman with the spinalform of MS. Visual acuity was 20120 O U . The VEPs have increased latencies ( 158 and 162 msec) i n both eyes. (C) Visuograms of a patient with definite MS who had cerebellar symptoms and blurred vision in either eye alone occurring episodically. The visuogram shows a high-frequency loss i n the right eye only. Visualacuity was 20120 OU. The evokedpotentiallatency, on the other hand, is moreprolonged in the left eye (144 nisec, as opposed to 134 msec i n the right eye). (0)Bilaterally increased latency (140 OD, 150 0s)i n apatient with probable MS. Visualacuity was 20120 O U . The visuogram is very abnormal OD but only borderline 0s.

44 Annals of Neurology Vol 5 No 1 January 1979

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F i g 5 . sensitivity loss to a 2.3 cycles per degree grating i s plotted as a function ofwokedpotential latency. D a t a from 48 eyes of 24 patients are shown. The vertical line at I 3 1 msec shows the upper limit of normal latency for allpatients. Stars Jymbolize data from patients with a ckassificafion of deJrnite MS, sqaares, probable MS, and rirchr, porsibh MS.

The compelling reason for selecting gratings, however, was that from many physiological studies, detailed knowledge has been gained concerning the processing of these grating stimuli by the visual systems of cats, monkeys, and humans. Using these stimuli provides a powerful tool in the exploration of the physiology and pathophysiology of the visual system. Visuograms can demonstrate visual impairment not revealed by conventional acuity measurements [Sl. Our data show that grating stimuli are useful in the clinical evaluation of the MS patient. Ninety percent of patients with definite MS had abnormal VEP latency to grating stimuli. As with checkerboard stimuli, both interocular delay and binocular increase were noted in patients with MS, even among those who never had visual symptoms. Among other patients who had prolonged VEP latency to the grating stimulus, we noted many with diseases of the extrapyramidal system. This was so conspicuous that we excluded these patients' data from the control group and considcred them in a separate report [7]. Nevertheless, abnormal VEPs in Parkinson disease hardly weaken the diagnostic valuc of the VEP test in MS, as the two patient groups are easy to differentiate clinicalIy. Visuograms showed losses in about 70% of all MS patients. Losses could be shown in comparison to the norm, not just by a differcnce of the contrast sensitivity in the two eyes. Losses were not confined to fine o r coarse pattcrns; rather, different patients, or often the two eyes of the same patient, showed a different type of visuogram. A wealth of physiolog-

ical data suggests that there is increasing size specificity of individual neurons of the primate's primary visual pathways as the cortcx is approached: a cortical neuron that responds best to a certain grating pattern may not be responding at all to a pattern containing bars half as wide o r twice as wide [20]. Based on this physiological cvidencc, it would appear that in MS the diseasc process randomly affects these size-specific pathways of the visual system. In some patients, VEP latency was abnormal in one eye alone while the visuogram was abnormal only in the other, or two eyes with equal latency changes might have very unequal visuograms o r vice versa. The lack of concordance between the threshold for detection of the 2.3 cycles per degree pattern and the VEP is surprising. Identical stimuli are used in both tests, except that a high-contrast grating is used for the VEP while low contrast is used to determinc threshold. From the no better than chance coincidcnce of the two measures of abnormality, i t appears that we are dealing with independent tests of visual function and that the psychophysical correlate of delayed optic nerve conduction to a suprathreshold grating stimulus is not a loss of contrast sensitivity. I t is possible that detection may be impaired by a lesion of optic nerve axons while VEP latency may be delayed by demyclination, but i t is most unlikely that in MS axons could be attacked before the myelin sheaths. Yet we found paticnts with abnormal visuograms whose VEP latencies were normal. It is worth briefly reviewing some of the explanations proposed concerning VEP delay in multiple sclerosis. The most plausible theory for VEP latency changes has emerged from McDonald's work on conduction properties of demyelinated fibers [ 181. McDonald pointed out, however, that a local nerve conduction defect cannot explain large VEP latency changes [ 191, and several investigators [ 1 1, 141 have speculated that these changes in optic neuritis may be caused by intraretinal, preganglionic abnormalities. O u r data on discordant psychophysics and &c-

Bodis-Wollner et al: Visual Evoked Potentials in MS 45

trophysiology d o not favor this hypothesis in MS. As the same stimulus was used for both tests, it seems likely chat the same retinal circuitry responded regardless of the type of measurement. Retinal disease would have affected both of them. Another hypothesis explaining the pathophysiology of VEP changes is that MS selectively affects only o n e type o f optic nerve fiber [ 9 ] As . in the cat, monkey retinal ganglion cells subserving macular vision have been subdivided i n t o two categories 1251. “X”type cells have optimal response to fine patterns steadily presented. and have axons of smaller diametcr and slower conduccion velocity. “Y” type cells respond best to coarser stimuli presented intermittently. Their axons are of larger diameter and have more rapid conduction velocity. Perhaps VEP responses rely predominantly o n the Y fiber system, while psychophysical responses depend on the X system. T h e fact that w e used the same grating stimulus for both measurements and found abnormal but discordant responses with both methods is n o t easily reconciled with the notion that o n e of the two systems is selectively involved in MS. Furthermore, the complete visuogram pattern varied markedly among patients and showed different types of losses. Thus, considering all the psychophysical evidence concerning low versus high spatial frequency dominance of the X and Y neurons, a loss of only o n e type is unlikely to account for our data. We concur with Cook and Arden [91 that there is n o selective involvement of X o r Y cells in MS. O u r data suggest that pathways determining thc latency of VEPs may be different from those responsible for spatial contrast detection and that MS does not prefcrentially affect o n e pathway but strikes haphazardly at any. Recently, McDonald [ 191 and Cook and Ardcn 191 considereJ the possibility that cortical processing delays underlie increased VEP latency. Sincc some patients have uniocular latency changes, suggesting a prechiasmal abnormality, this hypothesis would seem to be ruled out. However, in the striate cortex of the rhesus monkey, the first neurons receive geniculate fibers from o n e eye only. Perhaps monocular latency changes are caused by lesions involving the eyccortex pathway as far u p as the first cortical relay neuron. We as well as others 1241 have found differe n t visuogram patterns in the two eyes of thc same patient. In view of the spatial frequency selectivity o f cortical neurons in the cat [201, we suggest (at least partial) cortical disorder as an explanation for our findings. H o w MS could selectively involvc pathways subserving one eye alone remains an enigma, however. T h e proposed role of viral uveitis in the origin of MS [2 11 raises the interesting thought that neurotropic migration from o n e eye to t h e coctcx could cause monocular changes. For the moment this

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remains a purcly conjectural explanation of asymmetries in the visual system of patients with MS. Supported in part by N I H Grant EY 01708. rhe Clinical Center for Parkinson’s Disease and Allied Disorders, Grant NS 11631-5. and Grant-in-Aid G-601 of Fight-for-Sight, Inc. Special thanks are due t o M r Louis Dickhardr and Mrs E. Heinrichs of the M.S. Association of Queens, N e w York. W e thank all referring physicians, in particular D r G . Lehrer.

References 1. Arden G B , Jacobsen JJ: A simple grating test for contrast sensitivity: preliminary results indicate value in screening for glaucoma. Invesr Ophthalmol Visual Sci 17.23-32, 1078 2. Arkin A, Bodis-Wollner I. Wolkstcin M. et al: Spariotemporal contrast sensitivities in glaucoma. Invesr Ophthalmol Visual Sri [Suppl] 1:1.45. 1978 3. Bodis-Wollner I: Visual acuity and contrast sensitivity in patients with cerebral lesions. Science 178:769-771. 10?2 4. Bodis-Wollner 1. Bender MB: Ncuroophthalmology: elcctrophysiology and psychophysics of acuity and contrast derection. Prog Neurol Psychiatry 3 8 9 3 - 1 15, 1973 5. Bodis-Wollncr I, Diamond SP: T h e measurement of spatial contrast sensitiviry in cascs of blurreti vision associated with cerebral lesions. Brain 99:695-7 10, 1976 6. Bodis-Wollner 1. Hendley CD. Kulikowski JJ: Electrophysiological and psychophysical responses to modulation of contrast of a grating pattern. Perception 1:341-340. 1972 7. Bodis-Wollner 1, Yahr M D : Measurements of visual evoked potentials in Parkinson’s disease. Brain 101:661-67 1, 1378 8. Ciganek L: The EEG response (evokecl potcnrial) to light stimulus in man. Illectroencephalogr Clin Neurophysiol 13:165-172. 1961 9. Cook JH. Arden G B : Unilateral retrobulbar neuritis. il comparison of evoked potentials an11 psychological measuremenrs. in Desnicdt J I (cd): Visual Evoked Potentials in Man. OxforJ. Englan‘l. Clarcndon. 1977 1 0 Ellenberger C. Ziegler S: Visual cvokcd potentials anJ quantitative perimctry i n multiple sclerosis. Ann Neurol 1 :56l5 6 4 , 1977 1. Hallijay A M . McDonald W1. Mushin J: DelaycJ visual evoked response in optic neuritis. Lancet 1.082-985, 1972 2. H a l l i h y AM, McDonald WI. Mushin J: Visual evoked porentials in patients with demyelinaring disease, in Desniedt JE (ed): Visual Evoked Potentials in Man. Oxford. England. < : l a r e n ~ h ,1977 3. liennerici M. Wenzel D, Freuncl H-J: T h e comparison o f small-size rectangle and checkerboard stiniulation for the evaluation of delayed visual evoke11 rcsponscs in patients suspccred of multiple sclerosis. Brain 100.119-1 36. 1077 14. H e r o n JR. Regan D, Milner BA: Delay in visual perception in unilateral optic atrophy after retrobulbar neuritis. Brain 97:69-78. 1974 15. €less RF. Garner LF: T h e effect of corneal edema on visual function. Invest Ophthalmol Visual SCI 16:5- I ? . l 9 7 ? 16 Levi DM. Harwcrth RS: Spatio-remporal interactions i r i anisomctropic and strabismic amblyopia. Invcsr 0phrhalmi)l Visual Sci 16:90-95, 1977 I ? . McAlpine D. Lumsden CE. Acheson ED: Mulriple Sclerosis: A Reappraisal. Edinburgh and London. Churchill/Livingstonc, I972 18. McDonald WI: Pathophysiology in mulriplc sclerosis. Brain 07:179-196. 1974 19. McDonald WI: Pathophysiology of conduction in central

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26. Sjostrand J , FrisGn L: Contrast sensitivity in niacular disease. Acta Ophthalmol 55:507-5 14. 1977 27. Timm NH: Multivariate Analysis. Belmont, CA, Wadsworth, 1 9 7 5 , p 261 28. Wolkstrin M, Atkin A, Bodis-Wollner 1: Grating acuity in two sisters with tapetoretinal degeneration. Doc Ophrhalmol 12:45-50.

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Visual evoked potentials and the visuogram in multiple sclerosis.

Visual Evoked Potentials and the Visuogram in Multiple Sclerosis Ivan Bodis-Wollner, M D , Charles D. Hcndley, PhD, Leland H. Mylin, AT, and John Thor...
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