P-106 Spontaneous pupil fluctuations differentiate progressive supranuclear palsy patients from healthy controls

Abstract

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative, atypical, debilitating Parkinsonian syndrome with rapid disease progression and mostly poor prognosis. The lack of early disease biomarkers and hence delayed clinical diagnosis has so far impeded clinical research and treatment options. The pathophysiology of PSP comprises the aggregation of phosphorylated tau-proteins in the form of neurofibrillary tangles particularly in the basal ganglia and the brainstem. Spontaneous fluctuations of pupil diameter under constant luminance have been shown to reflect activity in neuromodulatory arousal networks located in the brainstem and pupillometry is being increasingly used as a non-invasive proxy measure for activity in these networks. Alterations in spontaneous pupil fluctuations as a potential disease biomarker for progressive supranuclear palsy remain yet untested.

Objective: The present study aims to assess differences in the pattern of spontaneous pupil fluctuations between PSP patients and healthy controls to establish a possible non-invasive neurophysiological biomarker for PSP.

Methods: We measured pupil diameter of 19 PSP patients (age 72,3 years mean ±8,3 STD, 11 males, disease duration 3,4±1,9 years) as well as 12 healthy participants (age 66.1 years mean ± 6.4 STD, 11 males) and assessed the pattern of spontaneous fluctuations in resting conditions under constant luminance in three repeated blocks of 3min. We used spectral density estimation to asses power spectra of spontaneous fluctuation of pupil diameter, computed the area under the curve (AUC within frequencies of 1/12-1/4 Hz) and slope of the resulting power spectra functions and used t-tests to assess significance of differences between the two groups.

Results: We found a significant difference in the pattern of spontaneous pupil fluctuations between PSP patients and healthy controls. There was a significant reduction of the AUC of spontaneous fluctuations around 0.25 Hz, a frequency at which the pupil diameter has been described to fluctuate in healthy participants at rest.

Conclusion: Our results suggest that spontaneous pupil diameter fluctuations at rest might serve as a viable, non-invasive biomarker to differentiate PSP patients and healthy, age-matched controls. Activity changes of brainstem arousal networks, reflected by the spontaneous pupil fluctuations in PSP, constitutes a plausible explanation for this finding, as brainstem structures are primary brain region affected by neurodegeneration in PSP.