Monoaminergic Degeneration and Ocular Motor Abnormalities in De Novo Parkinson's Disease

Abstract

Background: Evaluating eye movements in Parkinson's disease (PD) provides valuable insights into the underlying pathophysiological changes.

Objective: The aim was to investigate the relationship between monoaminergic degeneration and ocular motor abnormalities in de novo PD.

Methods: Drug-naive PD patients who underwent N-(3-[¹⁸ F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane positron emission tomography scans and video-oculography at diagnosis were eligible. Measurements of saccadic accuracy, latency, and smooth pursuit gain and square wave jerk frequency were collected. Patients underwent Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and detailed cognitive tests. We investigated the associations between ocular motor measurements and specific tracer uptake ratios (SUR) in the caudate nucleus, anterior and posterior putamen, thalamus, and dorsal raphe nuclei, along with motor and cognitive symptoms.

Results: One-hundred twenty-four subjects were included in this study. Saccadic accuracy was positively associated with parkinsonian motor severity expressed as Hoehn and Yahr stages, MDS-UPDRS Part III scores, and subscores for bradykinesia and rigidity but not with tremor scores (P_FDR < 0.05). Saccadic accuracy correlated with poor performances in the Rey-Complex-Figure copy, and latency with the Digit Symbol Coding and the Montreal Cognitive Assessment scores (P_FDR < 0.05). Prolonged saccadic latency correlated with reduced thalamic SUR, whereas decreased saccadic accuracy correlated with reduced SUR in the anterior and posterior putamen (P_FDR < 0.05). Reduced smooth pursuit gain showed associations with reduced SUR in the dorsal raphe, a serotonin-predominant region, but did not correlate with parkinsonism severity scores.

Conclusion: Defective dopaminergic and nondopaminergic neural systems may discretely influence ocular motor function in de novo PD patients. © 2023 International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; dopamine transporters; eye movements; positron emission tomography; serotonin transporters.