Ali Shoeibi1, Irene Litvan2, Eduardo Tolosa3, Teodoro Del Ser4, Euyhyun Lee5. 1. Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Parkinson and Other Movement Disorder Center, UC San Diego Department of Neurosciences, La Jolla, CA, USA. Electronic address: ilitvan@ucsd.edu. 3. Movement Disorders Unit, Neurology Service, Hospital Clínic Universitari, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain. 4. Medical Department, Noscira SA, Madrid, Spain. 5. Clinical and Translational Research Institute, UC San Diego, La Jolla, CA, USA.
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.
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 syndromepatients 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 PSPpatients with these phenotypes as a single disorder even if they have similar disease severity at screening.
Authors: Ali Shoeibi; Irene Litvan; Jorge L Juncos; Yvette Bordelon; David Riley; David Standaert; Stephen G Reich; David Shprecher; Deborah Hall; Connie Marras; Benzi Kluger; Nahid Olfati; Joseph Jankovic Journal: Parkinsonism Relat Disord Date: 2019-10-14 Impact factor: 4.891
Authors: Gabor G Kovacs; Milica Jecmenica Lukic; David J Irwin; Thomas Arzberger; Gesine Respondek; Edward B Lee; David Coughlin; Armin Giese; Murray Grossman; Carolin Kurz; Corey T McMillan; Ellen Gelpi; Yaroslau Compta; John C van Swieten; Laura Donker Laat; Claire Troakes; Safa Al-Sarraj; John L Robinson; Sigrun Roeber; Sharon X Xie; Virginia M-Y Lee; John Q Trojanowski; Günter U Höglinger Journal: Acta Neuropathol Date: 2020-05-07 Impact factor: 17.088