Progression of two Progressive Supranuclear Palsy phenotypes with comparable initial disability

Abstract

IntroductionTo avoid bias and optimize statistical power of disease-modifying therapeutic trials, it is critical to include homogeneous populations with similar rate of progression over time. Patients with Progressive Supranuclear Palsy (PSP)-Parkinsonism phenotype have overall slower disease progression than those with PSP-Richardson syndrome phenotype. However, it is unclear if the progression rate of PSP-Parkinsonism is the same when the PSP-Parkinsonism converts to PSP Richardson syndrome. We aimed to determine and compare disease progression rate of patients with the two most common PSP phenotypes: PSP-Parkinsonism and PSP Richardson syndrome, participating in the TAUROS trial. Methods138 patients, 56 with PSP-Parkinsonism and 82 with PSP-Richardson syndrome, with similar clinical severity at baseline, were followed up to 60 weeks. PSP-Parkinsonism allocation was based on experts’ judgement and PSP-Richardson on probable NINDS-PSP criteria. Global disease progression was measured by the PSP Rating Scale as primary outcome measure and several secondary outcome measures. ResultsPSP-Richardson syndrome patients had significantly faster progression based on the primary and three secondary outcome measures: the Dementia Rating Scale-2, Frontal Assessment Battery, and lexical fluency scale. Analyses including only patients with a baseline symptom duration under five years showed similar results. PSP phenotype was the strongest predictor for disease progression. ConclusionThis research showed that even when disease severity and clinical features at baseline are similar, patients with PSP- Richardson syndrome progressed significantly faster than those with PSP-Parkinsonism. Therefore, unless stratified by phenotype, future therapeutic clinical trials should not lump PSP patients with these phenotypes as a single disorder even if they have similar disease severity at screening.