OBJECTIVE: To characterize ocular motor function in patients with Niemann-Pick disease type C (NPC). METHODS: In a multicontinental, cross-sectional study we characterized ocular-motor function in 72 patients from 12 countries by video-oculography. Interlinking with disease severity, we also searched for ocular motor biomarkers. Our study protocol comprised reflexive and self-paced saccades, smooth pursuit, and gaze-holding in horizontal and vertical planes. Data were compared with those of 158 healthy controls (HC). RESULTS: Some 98.2% of patients generated vertical saccades below the 95% CI of the controls' peak velocity. Only 46.9% of patients had smooth pursuit gain lower than that of 95% CI of HC. The involvement in both downward and upward directions was similar (51°/s (68.9, [32.7-69.3]) downward versus 78.8°/s (65.9, [60.8-96.8]) upward). Horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit correlated best to disease severity. Compensating strategies such as blinks to elicit saccades, and head and upper body movements to overcome the gaze palsy, were observed. Vertical reflexive saccades were more impaired and slower than self-paced ones. Gaze-holding was normal. Ocular-motor performance depended on the age of onset and disease duration. CONCLUSIONS: This is the largest cohort of NPC patients investigated for ocular-motor function. Vertical supranuclear saccade palsy is the hallmark of NPC. Vertical upward and downward saccades are equally impaired. Horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit can be used as surrogate parameters for clinical trials. Compensating strategies can contribute to establishing a diagnosis.

Actelion a Janssen company of Johnson and Johnsons Bern Switzerland

Center for Rare Diseases University Hospital Bern and University of Bern Bern Switzerland

Department of Child Neurology Comenius University Children's Hospital Bratislava Slovak Republic

Department of Neurology Hospital Universitari de Bellvitge L'Hospitalet de Llobregat Spain

Department of Neurology University Hospital Bern and University of Bern Bern Switzerland

Department of Pediatrics and Adolescence Medicine 1st Faculty of Medicine General University Hospital Prague Charles University Prague Czech Republic

German Center for Vertigo and Balance Disorders and Department of Neurology University Hospital Munich Campus Grosshadern Ludwig Maximilians University Munich Munich Germany

Melbourne Neuropsychiatry Centre University of Melbourne and NorthWestern Mental Health Parkville Victoria Australia

Neuropsychiatry Unit Royal Melbourne Hospital Parkville Victoria Australia

Optometry and Vision Science School of Medicine Deakin University Waurn Ponds Victoria Australia

Pediatric Neurology Division Children's Medical Center Pediatric Center of Excellence Myelin Disorders Clinic Tehran University of Medical Sciences Tehran Iran

SphinCS Gmbh Clinical Science for LSD Hochheim Germany

Unit of Rare Neurodegenerative and Neurometabolic Diseases Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy

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