Multifocal visual evoked potentials are influenced by variable contrast stimulation in MS

Abstract

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

Retinal architecture and mfERG

“…[1][2][3][4] Whereas spectral-domain optical coherence tomography (OCT) has been of great utility in precisely characterizing the topography of retinal architecture, multifocal electroretinography (mfERG) is a technique that can yield information on discrete functional responses within the retina, following a stimulus with precisely defined characteristics. [5][6][7][8][9][10][11][12][13][14][15] The retinal ganglion cell (RGC) contribution to the global retinal response is small, thereby limiting the utility of this technique for the purpose of examining retinal mechanisms of axonal and neuronal degeneration. …”

“…Multifocal patternreversal visual-evoked potentials were performed monocularly as previously described (6.3 software, VERIS; EDI, Redwood City, CA) to assess changes in timing and magnitude (i.e., amplitude) of visual cortical responses. 13,21 We analyzed mean amplitude and timing response asymmetry across 60 sectors of cortical responses. To interrogate the intereye differences spanning the 60 sectors (organized as rings) of cortical responses, waveform metrics were transformed into pseudocolor 2-dimensional representations through the VERIS software, which utilized both root-meansquare and goodness-of-fit computations.…”

“…In figure 2F, to interrogate the intereye differences spanning the 60 sectors (organized as rings) of mfVEP-induced cortical responses, waveform metrics were transformed into pseudocolor 2-dimensional representations, as previously reported. 13,21 Gray coloring of the rings indicate that both eyes are in the noise level of the device, and therefore no analytical conclusions can be rendered. White represents visual cortical response waveforms that are strong and equally balanced between the 2 eyes (expected in normal subjects).…”

“…Specifically, we assessed for response dominance by analyzing intereye differences across the 60 sectors containing spatially discrete visual cortical responses (organized as rings), and then used the VERIS software to convert them into pseudocolor 2-dimensional map representations as previously reported. 13,21 We then assessed for the relationship between cortical response dominance by mfVEP pseudocolor maps and abnormalities in mfERG-generated ONHC responses, as previously described by our group. 13 As such, there was dominance in the cortical responses generated from the unaffected (or at least less-affected) eye, which corresponded to a greater number of abnormal ONHC responses on the same side in 12 of the 13 patients (92% concordance, with a CI for one proportion with continuity correction at 62%-100%) (figure 2).…”

Low-contrast multifocal visual evoked potentials

“…Consequently, the full-field VEP is of limited value in detecting optic neuropathy in patients with small or more peripheral visual field defects. 6 Furthermore, the finding of multifocal VEP latency delays in patients with a history of optic neuritis predicts progression to MS. 7 In this issue of Neurology ® , Frohman et al 8 describe a further refinement of the VEP paradigm, wherein multifocal VEPs were evaluated at 3 contrast levels: high contrast (100%), low contrast (33.3%), and very low contrast (14.2%). 6 The central 24°-32°o f the visual field is divided into 58 -60 segments, each of which contains a 4 ϫ 4 grid of black-andwhite checks that reverse according to a pseudorandom sequence (figure).…”