A cross-sectional, prospective ocular motor study in 72 patients with Niemann-Pick disease type C

Eur J Neurol. 2021 Jun 7. doi: 10.1111/ene.14955. Online ahead of print.

Abstract

Objective: To characterize ocular motor function in patients with Niemann-Pick type C (NPC).

Methods: In a multicontinental, cross-sectional study we characterized ocular-motor function in 72 patients from twelve 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: 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 both downward and upward directions was similar (51°/s (68.9, [32.7-69.3]) downward vs. 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 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 in establishing a diagnosis.

Keywords: Niemann-Pick Type C; biomarkers; ocular motor function; saccades; supranuclear vertical gaze palsy; supranuclear vertical saccade palsy; video-oculography.