Objective: To test the hypothesis that patients with multiple sclerosis (MS) with intereye asymmetry on low contrast letter acuity, and thickness of the retinal nerve fiber layer (RNFL), would exhibit corresponding changes in cortical timing and amplitude responses on pattern reversal multifocal visual evoked potentials (mfVEP), contingent upon variable stimulus contrast. Methods:In a cross-sectional study, we investigated a cohort of 11 normal subjects and 40 patients with MS, 21 of whom had a history of acute optic neuritis (MS-AON) with an intereye asymmetry with respect to RNFL thickness, and on low contrast letter acuity performance. Pattern reversal mfVEP was performed at high (100%), low (33.3%), and very low (14.2%) Michelson-contrast levels.Results: Compared to baseline measures at 100% contrast, the mean amplitude of the mfVEP was reduced in MS-AON eyes, upon pattern-reversal stimulation at the 2 lower contrast levels (p Ͻ 0.0001). With respect to changes in timing responses, the intereye asymmetry was increased in the MS-AON patients upon lower contrast pattern-reversal stimulation (p Ͻ 0.0001 for 33.3% compared to 100%, and p Ͻ 0.001 for 14.2% compared to 100%). The fellow eye in 12 (57%; p Ͻ 0.001) of the patients with an abnormal eye, and a history of AON, revealed abnormal amplitude and timing responses upon low contrast stimulation (signifying unmasking of occult damage). Conventional visual evoked potential (VEP) studies can reveal the cardinal features of inflammatory demyelination within the anterior visual system, such as prolongation in the P-100 latency. Conclusions: 1This finding represents the pathophysiologic signature of conduction slowing, and represents one of the earliest demonstrable and objective features of acute optic neuritis (AON). 2-4The recent assessment of conventional VEP measures, with the application of a low contrast pattern-reversal method, represents a potentially practical refinement in the sensitivity and specificity of detecting demyelinating optic neuropathy.5 Nonetheless, conventional VEP testing yields a single summed potential from the entire visual field of stimulation, rendering this *These authors contributed equally to this work.From the

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