Objective: The objective of this study was investigate whether multiscale entropy, a measure of complexity, when applied to the path of unconstrained eye movements could be used to differentiate people with Parkinson’s disease (PD) and Progressive Supranuclear Palsy (PSP).

Background: PD and PSP are complex conditions often misdiagnosed due to overlapping symptoms. Eye movements are often assessed at the bedside as saccadic abnormalities provide a clue to PSP¹. Saccades in PSP have been shown to be irregular in trajectory² but direct comparison of this irregularity with PSP has not been undertaken. Entropy analysis, a method for quantifying the complexity or irregularity of biological signals, has shown promise in evaluating neurological disorders (REF) and may offer insights into the oculomotor function of people with PD and PSP. This study explores the application of entropy analysis in potentially providing a novel, non-invasive approach to distinguish parkinsonian conditions, allowing for more accurate diagnoses at early disease stages.

Method: Twenty-four people with PSP, 38 PD, and 9 matched controls completed a free-viewing eye-tracking task. Participants viewed clips of scenery and faces, while eye movements were recorded using the Eyelink 1000+. Multiscale Entropy Analysis was carried out on 40s of uninterrupted data, to calculate the complexity index (CI) of the eye movements’ path in both horizontal and vertical planes. The PSP cohort also completed the PSP rating scale (PSPRS).

Results: Horizontal CI was significantly different between groups with the control group exhibiting greater CI than both PD and PSP (p<0.01). Those with PSP also exhibited greater horizontal complexity than those with PD (p<0.01). In the vertical plane however, those with PSP exhibited the greatest CI, significantly greater than the PD cohort (p>0.01). Neither horizontal nor vertical CI was correlated with clinical scales or subscales.

Conclusion: Differences in eye movement complexity between PD and PSP may be due to distinct neuropathology or pattern of disease progression. The lack of correlation with clinical scales and specific oculomotor subscales suggests changes in eye movement complexity may reflect subtle disease-specific differences which could act as a potential non-invasive, subclinical biomarker to distinguish PSP from PD at earlier stages of disease progression before these changes are visible to the naked eye.

References: 1. Pinkhardt EH, Jürgens R, Becker W, Valdarno F, Ludolph AC, Kassubek J. Differential diagnostic value of eye movement recording in PSP-parkinsonism, Richardson’s syndrome, and idiopathic Parkinson’s disease. J Neurol. 2008 Dec;255(12):1916-25. doi: 10.1007/s00415-009-0027-y. Epub 2009 Jan 14. PMID: 19224319.
2. Shaikh AG, Factor SA, Juncos J. Saccades in progressive supranuclear palsy – maladapted, irregular, curved, and slow. Mov Disord Clin Pract. 2017;4(5):671-681. doi:10.1002/mdc3.12491

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MDS Abstracts - https://www.mdsabstracts.org/abstract/multiscale-entropy-a-new-oculomotor-measure-of-psp/