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Brainstem and cerebellar volume loss and the associated clinical features in Progressive Supranuclear Palsy

Year: 2025

Type: preprint

Abstract: INTRODUCTION Progressive Supranuclear Palsy (PSP) is a neurodegenerative tauopathy. Tau pathology predominates in the basal ganglia and midbrain, with spread to other brain regions. Involvement of the cerebellum remains equivocal, but is increasingly recognized in the pathophysiology of neurological diseases. We hypothesize that volume loss is appreciable in cerebellum alongside brainstem regions. METHODS In this cross-sectional observational study volumetric brainstem and cerebellar subsegmentation of T1-weighted magnetic resonance imaging (MRI) was performed in 37 adults with PSP. Group-level comparisons were made with 38 adults with Parkinson’s disease (PD) and 35 healthy control (HC) subjects. Regional volumes in the PSP cohort were correlated against disease severity and cognition. RESULTS Compared with HC, the midbrain, corpus medullare and flocculonodular lobe were smaller in PSP (d=0.90-1.2). Compared with PD, the midbrain, pons and superior cerebellar peduncle (SCP) were smaller in PSP (d=0.82-1.9). There was a positive correlation between the frontal assessment battery (FAB) and volume of the superior (r=0.50) and inferior (r=0.48) cerebellar posterior lobes. The PSP rating scale also correlated with SCP (r=-0.58) and midbrain (r=-0.52) volume. CONCLUSION Additional regions of brainstem and cerebellar volume loss, alongside midbrain atrophy, were observed in PSP. The reported clinico-radiologic correlations suggest a role of the cerebellum in cognitive dysfunction. These findings indicate that the cerebellum is not spared in PSP, and support further work to understand the temporal course of cerebellar and cerebellar connectivity changes relative to other brain regions.

Source: medRxiv

DOI: 10.1101/2025.07.06.25330975