Impairment of Smooth Pursuit as a Marker of Early Multiple Sclerosis

Nathaniel Lizak, Meaghan Clough, Lynette Millist, Tomas Kalincik, Owen B. White, Joanne Fielding

Multiple sclerosis (MS) is a diffuse disease that disrupts wide-ranging cerebral networks. The control of saccades and smooth pursuit are similarly dependent upon widespread networks, with the assessment of pursuit offering an opportunity to examine feedback regulation. We sought to characterize pursuit deficits in MS and to examine their relationship with disease duration. Twenty healthy controls, 20 patients with a clinically isolated syndrome (CIS), and 40 patients with clinically definite MS (CDMS) participated. Thirty-six trials of Rashbass' step-ramp paradigm of smooth pursuit, evenly split by velocity (8.65°, 17.1°, and 25.9°/s) and ramp direction (left/right), were performed. Four parameters were measured: latency of pursuit onset, closed-loop pursuit gain, number of saccades, and summed saccade amplitudes during pursuit. For CDMS patients, these were correlated with disease duration and Expanded Disability Status Scale (EDSS) score. Closed-loop pursuit gain was significantly lower in CIS than controls at all speeds. CDMS gain was lower than controls at medium pursuit velocity. CDMS patients also displayed longer pursuit latency than controls at all velocities. All patients accumulated increased summed saccade amplitudes at slow and medium pursuit speeds, and infrequent high-amplitude saccades at the fast speed. No pursuit variable significantly correlated with EDSS or disease duration in CDMS patients. Smooth pursuit is significantly compromised in MS from onset. Low pursuit gain and increased saccadic amplitudes may be robust markers of disseminated pathology in CIS and in more advanced MS. Pursuit may be useful in measuring early disease.