Objective: Rapid-eye movement (REM) sleep behavior disorder (RBD) has been identified as the most specific and common prodromal stages of α-synucleinopathies (αSYN) such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and the sporadic disease multiple system atrophy (MSA). Within 10 to 20 years, patients with RBD convert up to 85% of cases to a neurodegenerative disease of the type of αSYN. Therefore, the identification of RBD patients who are more likely to phenoconvert needs highly sensitive and specific prodromal biomarkers.

Background: Previous studies on the manifest aSYN have shown that patients with PD and MSA have oculomotor and pupillomotor abnormalities. Therefore, we systematically investigated saccade, pupil, and blink behavior in the PD and MSA and their prodrome RBD compared to healthy age and gender-matched controls(CTRL).

Method: We recruited 134 CTRL, 39 RBD, 37 early diagnosed PD, and 15 MSA, and they sat in front of a monitor in a dark room. We performed an Interleaved pro-/anti- saccade task (IPAST: pro instruction: subjects instructed to look towards stimulus; anti instruction: subjects instructed to look away from the stimulus). Task instruction was conveyed by the color of a central fixation point that initiated each trial. This was followed by a 200ms gap of no stimuli before the peripheral stimulus appeared 10° to the left or right of the fixation point. A video-based monocular eye tracker was used to monitor gaze location, pupil size, and blink rate.

Results: Our results showed that PD and MSA had more anti-saccade direction errors than CTRL and RBD, and more of these errors occurred at express saccade latencies. Saccade amplitude was reduced in PD and MSA compared to CTRL. Pupil dilation response was smaller in RBD, PD, and MSA compared to CTRL. In anti-saccade trials, MSA showed a smaller dilation size than both RBD and PD. In the fixation period, RBD and MSA showed a reduced blink rate but not PD.

Conclusion: We identified potential prodromal markers in RBD and differences between αSYN. The RBD group showed altered blink and pupil behavior compared to the CTRL group. PD and MSA saccadic deficits were more severe than the RBD deficits. Future longitudinal studies are needed to determine the robustness of these oculomotor measures to identify prodromal aSYN.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/eye-tracking-paradigm-to-identify-disease-specific-behavioral-biomarkers-in-neurodegeneration/