The multifocal visual evoked potential (mfVEP) as a clinical tool in detecting visual pathway abnormalities in multiple sclerosis

Abstract

Purpose. The mfVEP is an objective non-invasive electrodiagnostic test that provides local (typically 60) visual evoked responses across over 40 deg field of vision. In addition to response amplitudes, the mfVEP also provides time response (latency) information. Latency measurements are of great importance when evaluating the visual pathway of multiple sclerosis (MS) patients because one of the hallmarks of the disease is demyelination of nerve fibers which slows signal conduction. The aims of this dissertation were (1) to evaluate the sensitivity and specificity of the mfVEP in detecting visual pathway abnormalities in MS patients, (2) to describe the mfVEP characteristics in MS patients with or without a history of optic neuritis (ON), (3) to compare the sensitivity of the mfVEP with Humphrey visual field (HVF) and optical coherence tomography (OCT) in detecting visual pathway abnormality in MS, and (4) to investigate the effect of reduction in stimulus contrast on mfVEP results.

Methods. mfVEPs were recorded monocularly using a 60-sector cortically scaled pattern-reversal dartboard stimulus (VERIS). Customized software was used to compare amplitude and latency for each sector to built-in normative data, and to construct probability plots (analogous to HVF total deviation plots). Experiment 1: Size and location of clusters of adjacent abnormal sectors on probability plots were analyzed for three groups: MS patients with a history of ON (MS-ON, n=74 eyes), or without (MS-no-ON, n=71 eyes), and control subjects (n=100 eyes). Receiver operating characteristic (ROC) curves were constructed for cluster criteria and percent of abnormal sectors. Experiment 2: Results from mfVEP, HVF and OCT (retinal nerve fiber layer) were compared for MS-ON (n=47 eyes, last ON episode was ≥6 months prior to the study) and MS-no-ON (n=65 eyes). Percent of observed agreement among the tests was examined and linear regression analysis was done. Topographic comparisons were made based on OCT quadrants. Experiment 3: Stimulus contrast was varied over 6 levels (10, 25, 35, 50, 75, 95%) for 7 control subjects. Contrast response functions (CRFs) were described for the entire field, and at different eccentricities (1, 2.5, 5.6, 9.8, 15.0, 22.2 deg).

Results. (1) Cluster criteria based on amplitude and latency probability plots showed the greatest area under the ROC curve yielding a criterion with high sensitivity and specificity. (2) Response amplitudes were reduced and latencies were longer in the MS-ON group, with significant differences between all groups: MS-ON, MS-no-ON, and controls. Abnormal sectors were diffusely distributed. (3) MfVEP identified more abnormal MS-ON eyes than HVF and OCT. MfVEP and HVF identified more abnormal MS-no-ON eyes than OCT did. Linear regression showed stronger correlation between the functional tests (mfVEP vs. HVF) than between structural and functional tests (OCT vs. mfVEP or HVF). Topographic agreement among tests was weak. (4) CRFs based on response amplitude were adequately described by a simple hyperbolic function. The mfVEP contrast response function in the central visual field saturated at a substantially higher contrast level compared to those from eccentric regions. Mean latency increased slightly with reduction in contrast and did not vary significantly with eccentricity.

Conclusions. The mfVEP provides high sensitivity and specificity in detecting abnormalities in visual function in MS patients. MfVEP provides information on visual abnormalities not revealed by HVF or OCT. Combining results of all three tests is beneficial in detecting vision-related defects in MS patients. The effect of reduction in stimulus contrast on the mfVEP amplitude is most apparent in central visual field. The effect of contrast and eccentricity on latency is relatively small.