Brainstem and Cerebellar Volume Loss and Associated Clinical Features in Progressive Supranuclear Palsy

INTRODUCTION: Progressive Supranuclear Palsy (PSP) is a neurodegenerative 'tauopathy' with predominating pathology in the basal ganglia and midbrain. Caudal tau spread frequently implicates the cerebellum; however, the pattern of atrophy remains equivocal. We hypothesise that volume loss is appreciable in the cerebellum and brainstem regions-beyond the midbrain-in individuals with PSP and linked to motor and non-motor clinical features. 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 and support further work to understand the temporal course of cerebellar and cerebellar connectivity changes relative to other brain regions.