Saccade, pupil, and blink abnormalities in prodromal and manifest alpha-synucleinopathies.

Abstract

Background: Saccade, pupil, and blink control are impaired in patients with α-synucleinopathies (αSYN): Parkinson's disease (PD) and multiple system atrophy (MSA). Isolated REM (rapid eye movement) Sleep Behavior Disorder (iRBD) is a prodromal stage of PD and MSA and a prime candidate for investigating early oculo-pupillo-motor abnormalities that may precede or predict conversion to clinically manifest αSYN.

Objective: Determine whether saccade, pupil, and blink responses in iRBD are normal or similar to those identified in PD and MSA.

Methods: Video-based eye-tracking was conducted with 68 patients with iRBD, 49 with PD, 17 with MSA, and 95 healthy controls (CTRL) performing an interleaved pro-/anti-saccade task that probed sensory, motor, and cognitive processes involved in eye movement control.

Results: Horizontal saccade and blink behavior was intact in iRBD, but abnormal in PD and MSA. iRBD patients, however, demonstrated reduced pupil dilation size, which closely resembled the changes found in PD and MSA. In the iRBD group, the extent of these pupillary changes appeared to correlate with the degree of hyposmia and reduction in dopamine transporter imaging signal.

Conclusions: Pupil abnormalities were present in iRBD, but blink and horizontal saccade responses were intact. Future longitudinal studies are required to determine which prodromal pupil abnormalities predict conversion from iRBD to PD or MSA and to identify the time window, in relation to conversion, when horizontal saccade responses become abnormal.