Improved characterization of visual evoked potentials in multiple sclerosis by topographic analysis

Abstract

In multiple sclerosis (MS), the combination of visual, somatosensory and motor evoked potentials (EP) has been shown to be highly correlated with the Expanded Disability Severity Scale (EDSS) and to predict the disease course. In the present study, we explored whether the significance of the visual EP (VEP) can be improved with multichannel recordings (204 electrodes) and topographic analysis (tVEP). VEPs were analyzed in 83 MS patients (median EDSS 2.0; 52 % with history of optic neuritis; hON) and 47 healthy controls (HC). TVEP components were automatically defined on the basis of spatial similarity between the scalp potential fields (topographic maps) of single subjects' VEPs and reference maps generated from HC. Non-ambiguous measures of latency, amplitude and configuration were derived from the maps reflecting the P100 component. TVEP was compared to conventional analysis (cVEP) with respect to reliability in HC, validity using descriptors of logistic regression models, and sensitivity derived from receiver operating characteristics curves. In tVEP, reliability tended to be higher for measurement of amplitude (p = 0.06). Regression models on diagnosis (MS vs. HC) and hON were more favorable using tVEP- versus cVEP-predictors. Sensitivity was increased in tVEP versus cVEP: 72 % versus 60 % for diagnosis, and 88 % versus 77 % for hON. The advantage of tVEP was most pronounced in pathological VEPs, in which cVEPs were often ambiguous. TVEP is a reliable, valid, and sensitive method of objectively quantifying pathological VEP in particular. In combination with other EP modalities, tVEP may improve the monitoring of disease course in MS.

Fig. 1

Topographic analysis I: generation of reference maps from healthy controls. a Conventional VEP (Oz–Fpz-electrode pair) from the grand mean VEP of all healthy controls. b Butterfly plot of the grand mean VEP of all healthy controls derived from 204 electrodes (average reference). c Grand mean VEP represented as a time series of topographic maps derived from the butterfly plot: time periods of quasi-stable topographies (“functional microstate”) are flagged by parentheses (for display, each five single topographic maps (=5 ms) are averaged). d Reference maps of single EP-components; from left to right, the “N75/N145”-, “P100”- and “P240”-maps are displayed and color-coded. Reference maps are the average of a group of topographic maps with high spatial similarity; N75 and N145 are represented as one reference map because of their overlapping spatial distribution of the electric potential on the scalp. e Butterfly plot as in (b) with additional color-coding according to the presence of a component during the time course of the EP, determined by the magnitude of spatial similarity of single topographic maps with one of the reference maps (fitting procedure, see text) (Color figure online)

Fig. 2

Topographic analysis II: automatic definition of EP components in an individual VEP. a Conventional VEP (Oz–Fpz-electrode pair) in a healthy control. b Butterfly plot of same subject derived from 204 electrodes (average reference). c VEP represented as a time series of topographic maps derived from the butterfly plot. (For display, five single topographic maps (=5 ms) are averaged). Marked asymmetry is seen despite monocular full-field stimulation. d Reference maps of single EP components derived from all healthy controls (see Fig. 1d). e Butterfly plot as in (b) with additional color-coding according to the presence of a component during the time course of the EP, determined by the magnitude of spatial similarity of single topographic maps with one of the reference maps (fitting procedure, see text) (Color figure online)

Fig. 3

Examples of single VEPs in a healthy subject (a) and two patients (b, c); upper panel: conventional VEP; middle panel: butterfly plots with topographically defined, color-coded EP components; lower panel: corresponding time course of GFP with respective color-coding. (GFP global field power, uV microVolt; red lines: time window for quantitative analysis). a Same healthy subjects as in Fig. 2: in addition to conventional waveform and butterfly plot with color-coded EP-components (see Fig. 2), the time course of the GFP and the time window for analysis is shown (lower panel). A wider time window would have falsely given the late peak as the latency of the P100 component. b MS patient with positive history of ON, visual acuity 0.5, EDSS 4.0: conventional waveform shows a small and a high positive peak at 95 and 160 ms, latency and amplitude measurement is ambiguous; the color-coding of the butterfly plot and the time course of GFP reflect the fact that spatial similarity of topographic maps (see Fig. S1) is highest to the “P100”-reference; for analysis, the latency at the end of the time window is used (tLat = 150 ms; replacement procedure 3). c MS patient with positive history of ON, visual acuity 0.5, EDSS 2.0: conventional waveform shows a shallow peak at 103 ms; the color-coding of the butterfly plot and the time course of GFP reflect the fact that spatial similarity of topographic maps (see Fig. S2) is highest to the “N75”-reference; for analysis, the most pathological values of latency, amplitude and configuration (tLat, tAmp, tAUC and tFit) measured in the sample are used (replacement procedure 2) (Color figure online)