Progression of two Progressive Supranuclear Palsy phenotypes with comparable initial disability. (September 2019)

• Record Type: Journal Article
• Authors: Shoeibi, Ali; Litvan, Irene; Tolosa, Eduardo; Ser, Teodoro del; Lee, Euyhyun
• Is Part Of: Parkinsonism & related disorders. Volume 66(2019)
• Page Start: 87
• Page End: 93
• Publication Date: 2019-09
• Subjects: Progression -- Progressive supranuclear palsy -- Progressive supranuclear palsy-Parkinsonism -- Progressive supranuclear palsy-Richardson syndrome; Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2019.07.010
• Languages: English
• ISSNs: 1353-8020

Abstract

Abstract: Introduction: To 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. Methods: 138 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. Results: PSP-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. Conclusion: This 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. Highlights: Patients with PSP-Richardson progressed faster than those with PSP-Parkinsonism despite similar disease severity at baseline. PSP phenotype was the strongest predictor of disease progression. To avoid bias, future PSP trials would benefit from stratifying PSP patients with PSP-Richardson and PSP-P by phenotype.