To assess whether quantitative eye movement measures correlate with disease severity in X-linked dystonia parkinsonism (XDP).

XDP is a neurogenetic movement disorder found in individuals with Filipino ancestry, involving a combination of parkinsonism and dystonia caused by a hexameric repeat expansion within the TAF1 gene. Eye movements are abnormal in XDP and other causes of parkinsonism, are frequently asymptomatic and may represent subtle and early markers of motor dysfunction, particularly in cerebellar disorders. Quantitative video oculography has been proposed as a potential clinical biomarker in other movement disorders.

We enrolled 17 patients with symptomatic XDP. Each participant underwent video oculography assessing spontaneous gaze, pursuits and saccades and were compared to normative control data. Given severe cervical dystonia and blepharospasm, there was no usable data in 3 patients, due to inability to fix on a target. Disease severity was assessed with the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Burke-Fahn-Marsden scale (BFM) and a novel disease-specific XDP Rating Scale (XDP-MDSP).

All patients had clinical oculomotor abnormalities (two with only reduced upgaze/convergence), generally involving saccadic pursuits and hypometric saccades, with square wave jerks (SWJs) in 2/17. On quantitative analysis (n=14), 9/14 (64.3%) had SWJs, even in early/mild disease and there were abnormalities in horizontal (12/14) more than vertical (9/14) pursuit gain and abnormal saccades in 8/14. Horizontal saccade gain strongly correlated with worsening dystonia severity, as measured by the BFM (r=-0.57, p=0.035) and XDP-MDSP (r=-0.65, p=0.012), remaining highly significant after controlling for age.

Oculomotor abnormalities are widespread in XDP and the frequent presence of SWJs could suggest involvement of cerebellar pathways. Quantitative oculomotor measures correlated with worsening clinical dystonia and overall disease severity in XDP, suggesting video oculography may represent a quantitative measure of disease severity. Further study will inform its potential use as an outcome measure in future clinical trials.