title: Survival in synucleinopathies: A prospective cohort study.
abstract: OBJECTIVE
  Parkinson disease (PD), multiple system atrophy (MSA), and pure autonomic failure (PAF) involve cytoplasmic deposition of α-synuclein and are considered to be synucleinopathies. Approximately 40% of patients with PD, most patients with MSA, and all patients with PAF have neurogenic orthostatic hypotension (OH). This study compared long-term survival in these synucleinopathies.
  
  
  METHODS
  In this prospective cohort study, survival data were obtained for 97.6% of 206 referred patients evaluated between 1994 and 2014 (47 PD + OH, 54 PD no OH, 15 cerebellar MSA [MSA-C], 57 parkinsonian MSA [MSA-P], 28 PAF). Individual diagnoses were confirmed by clinical criteria and results of pharmacologic, neurochemical, and neuroimaging tests of sympathetic noradrenergic innervation. The Cox proportional hazard model was used to calculate hazard ratios (HRs) from symptom onset and from time of evaluation to death.
  
  
  RESULTS
  Patients with MSA-C or MSA-P had shorter survival from symptom onset than did patients with PD + OH (age- and sex-adjusted HR = 6.1, 5.6; p < 0.0001 each), PAF (HR = 10.8, 9.9; p < 0.0001 each) or PD no OH (HR = 14.9, 13.6; p < 0.0001 each). Among parkinsonian patients who died, median times from motor onset to death were 7.5 years in MSA-P, 11.6 years in PD + OH, and 15.8 years in PD no OH. Probabilities of survival for 10 years from onset of relevant symptoms were 0.39 in MSA-C, 0.33 in MSA-P, 0.74 in PD + OH, 0.87 in PAF, and 0.93 in PD no OH.
  
  
  CONCLUSIONS
  In synucleinopathies, survival depends on the particular disease, with the risk of death greater in MSA-P than in PD + OH and in PD + OH than in PD no OH.
authors.affiliation: From the Clinical Neurocardiology Section (D.S.G., C.H.) and Office of the Clinical Director (T.W.), Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Hypertension Unit (Y.S.), Chaim Sheba Medical Center and Tel Aviv University, Tel HaShomer, Israel. goldsteind@ninds.nih.gov.
authors.forename: David S
authors.initials: DS
authors.lastname: Goldstein
authors.affiliation: From the Clinical Neurocardiology Section (D.S.G., C.H.) and Office of the Clinical Director (T.W.), Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Hypertension Unit (Y.S.), Chaim Sheba Medical Center and Tel Aviv University, Tel HaShomer, Israel.
authors.forename: Courtney
authors.initials: C
authors.lastname: Holmes
authors.affiliation: From the Clinical Neurocardiology Section (D.S.G., C.H.) and Office of the Clinical Director (T.W.), Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Hypertension Unit (Y.S.), Chaim Sheba Medical Center and Tel Aviv University, Tel HaShomer, Israel.
authors.forename: Yehonatan
authors.initials: Y
authors.lastname: Sharabi
authors.affiliation: From the Clinical Neurocardiology Section (D.S.G., C.H.) and Office of the Clinical Director (T.W.), Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Hypertension Unit (Y.S.), Chaim Sheba Medical Center and Tel Aviv University, Tel HaShomer, Israel.
authors.forename: Tianxia
authors.initials: T
authors.lastname: Wu
mesh_terms: D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging; D002526:Cerebellar Diseases / Q000000981:diagnostic imaging / Q000401:mortality; D015331:Cohort Studies; D004295:Dihydroxyphenylalanine; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000145:classification / Q000000981:diagnostic imaging / Q000401:mortality*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000401:mortality*; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000401:mortality; D016016:Proportional Hazards Models; D011446:Prospective Studies; D054970:Pure Autonomic Failure / Q000000981:diagnostic imaging / Q000401:mortality*; D011877:Radionuclide Imaging; D051844:alpha-Synuclein
chemical_list: D005462:Fluorine Radioisotopes; D051844:alpha-Synuclein; D004295:Dihydroxyphenylalanine