Atrophy in Midbrain & Cerebral/Cerebellar Pedunculi is Specific for Progressive Supranuclear Palsy - A Cross-Validation Whole-Brain Meta-Analysis

Objective: Progressive supranuclear palsy (PSP) is an atypical parkinsonian syndrome characterized by vertical gaze palsy and postural instability. Midbrain atrophy is suggested as a hallmark, but it has not been validated systematically in whole-brain imaging. Methods: We conducted whole-brain meta-analyses identifying disease-specific atrophy in structural MRI. Eighteen studies were identified (N=315 PSP, 393 controls) and separated into gray or white matter analyses (15/12). With overlay analyses, we cross-validated two meta-analytical algorithms: anatomical likelihood estimation and seed-based D mapping. Results: Whole brain meta-analyses revealed consistent gray matter atrophy in bilateral thalamus, anterior insulae, midbrain, and left caudate nucleus. White matter alterations were consistently detected in bilateral superior/middle cerebellar pedunculi, cerebral pedunculi, and midbrain atrophy. Conclusions: Our meta-analyses identify gray matter atrophy of the midbrain and white matter atrophy of the cerebral/cerebellar pedunculi and midbrain as specific to PSP. We support the incorporation of structural MRI data, and particularly these structures, into the revised PSP diagnostic criteria.