title: Impairment of Smooth Pursuit as a Marker of Early Multiple Sclerosis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Monash School of Medicine, Monash University, Melbourne, VIC, Australia; School of Psychological Sciences, Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, VIC, Australia.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Lizak
authors.affiliation: Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; School of Psychological Sciences, Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, VIC, Australia.
authors.forename: Meaghan
authors.initials: M
authors.lastname: Clough
authors.affiliation: Department of Neurology, Royal Melbourne Hospital , Melbourne, VIC , Australia.
authors.forename: Lynette
authors.initials: L
authors.lastname: Millist
authors.affiliation: Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
authors.forename: Tomas
authors.initials: T
authors.lastname: Kalincik
authors.affiliation: Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; School of Psychological Sciences, Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, VIC, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
authors.forename: Owen B
authors.initials: OB
authors.lastname: White
authors.affiliation: Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; School of Psychological Sciences, Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, VIC, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Fielding
keywords: clinically isolated syndrome; multiple sclerosis; neuro-ophthalmology; ocular motor system; smooth pursuit