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

Eur J Neurol 2021 Sep;28(9):3040-3050. doi: 10.1111/ene.14955. Epub 2021 Jul 12.

PMID: 34096670

Tatiana Bremova-Ertl, Larry Abel, Mark Walterfang

Highlights: In this study, ocular motor function is investigated in patients with Niemann-Pick disease type C (NPC).

Abstract

Objective: The goal of this study was to examine ocular motor function in individuals with Niemann-Pick disease type C (NPC).

Methods: We used video-oculography to assess ocular-motor function in 72 individuals from 12 countries in a multicontinental, cross-sectional study. We looked for ocular motor indicators that were linked to disease severity. Reflexive and self-paced saccades, smooth pursuit, and gaze-holding in horizontal and vertical planes were all part of our research procedure. The results were compared to 158 healthy controls (HC).

Results: The results showed that 98.2% of patients had vertical saccades that were less than the 95% confidence interval of the controls' peak velocity. Smooth pursuit gain was lower than the 95% CI of HC in only 46.9% of patients. The best correlations to disease severity were horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit. Blinks to elicit saccades and head and upper body movements to overcome the gaze palsy were identified as compensating measures. Vertical reflexive saccades were slower and more impaired than self-paced saccades. Gaze-holding was normal. The age of onset and the duration of the disease had an impact on ocular-motor performance.

Conclusions: This is the biggest cohort of NPC patients whose ocular-motor function has been studied. NPC is characterized by vertical supranuclear saccade palsy. Both vertical upward and downward saccades are equally affected. Surrogate characteristics for clinical studies include horizontal saccadic peak velocity and delay, vertical saccadic duration and amplitude, and horizontal position smooth pursuit. Compensating strategies can aid in the diagnostic process.

Keywords: Niemann-Pick type C, biomarkers, ocular motor function, supranuclear vertical gaze palsy, supranuclear vertical saccade palsy, video-oculography