Abstract
Current clinical diagnostic tools are limited in their ability to accurately differentiate idiopathic Parkinson’s disease (PD) from multiple system atrophy (MSA) and other parkinsonian disorders early in the disease course, but eye movements may stand as objective and sensitive markers of disease differentiation and progression. To assess the use of eye movement performance for uniquely characterizing PD and MSA, subjects diagnosed with PD (N = 21), MSA (N = 11), and age-matched controls (C, N = 20) were tested on the prosaccade and antisaccade tasks using an infrared eye tracker. Twenty of these subjects were retested ~7 months later. Saccade latencies, error rates, and longitudinal changes in saccade latencies were measured. Both PD and MSA patients had greater antisaccade error rates than C subjects, but MSA patients exhibited longer prosaccade latencies than both PD and C patients. With repeated testing, antisaccade latencies improved over time, with benefits in C and PD but not MSA patients. In the prosaccade task, the normal latencies of the PD group show that basic sensorimotor oculomotor function remain intact in mid-stage PD, whereas the impaired latencies of the MSA group suggest additional degeneration earlier in the disease course. Changes in antisaccade latency appeared most sensitive to differences between MSA and PD across short time intervals. Therefore, in these mid-stage patients, increased antisaccade errors combined with slowed prosaccade latencies might serve as a useful marker for early differentiation between PD and MSA, and, antisaccade performance, a measure of MSA progression. Together, our findings suggest that eye movements are promising biomarkers for early differentiation and progression of parkinsonian disorders.
Highlights
Parkinsonian disorders refer to a group of diseases linked to basal ganglia dopamine insufficiency
multiple system atrophy (MSA) participants did not make more errors than Parkinson’s disease (PD) participants [χ2(1) = 2.85, p = 0.09], and there was no significant difference between PD and control groups in prosaccade error rate [χ2(1) = 1.0, p = 0.31]
At a single time point, the study revealed two important findings: (1) error rates of MSA and PD patients in the antisaccade task were higher than controls, suggesting a behavioral biomarker for risk of a Parkinsonian disorder and (2) MSA patients show slower prosaccade latency than both controls and PD patients, suggesting a useful early behavioral marker for distinguishing MSA from PD
Summary
Parkinsonian disorders refer to a group of diseases linked to basal ganglia dopamine insufficiency. AP encompasses a less prevalent group of disorders including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), Lewy body dementia. Saccades Differentiate PD and MSA (LBD), and corticobasal degeneration (CBD), among others (2). Parkinsonian disorders share clinical features including the presence of bradykinesia plus one of the following: muscular rigidity, resting tremor, or postural instability; they differ in pathophysiology and progression rate (1, 3). Due to early overlapping symptoms, PD and MSA pose challenges in differential diagnosis, critical for early disease prognosis. No biomarkers can differentiate between the etiologies and clinical measures lack sensitivity and objectivity to uniquely characterize early stages of PD and MSA (4, 5). Biomarkers are needed to model the early differences and progression of PD and MSA
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