Survival in synucleinopathies: A prospective cohort study.

Abstract

OBJECTIVES:

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: David S Goldstein, Courtney Holmes, Yehonatan Sharabi, Tianxia Wu
• Journal: Neurology (Neurology) Vol. 85 Issue 18 Pg. 1554-61 (Nov 03 2015) ISSN: 1526-632X [Electronic] United States
• PMID: 26432848 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: © 2015 American Academy of Neurology.

Chemical References

• Fluorine Radioisotopes
• alpha-Synuclein
• Dihydroxyphenylalanine

Topics

• Aged
• Brain (diagnostic imaging)
• Cerebellar Diseases (diagnostic imaging, mortality)
• Cohort Studies
• Dihydroxyphenylalanine
• Female
• Fluorine Radioisotopes
• Humans
• Longitudinal Studies
• Male
• Middle Aged
• Multiple System Atrophy (classification, diagnostic imaging, mortality)
• Parkinson Disease (diagnostic imaging, mortality)
• Parkinsonian Disorders (diagnostic imaging, mortality)
• Proportional Hazards Models
• Prospective Studies
• Pure Autonomic Failure (diagnostic imaging, mortality)
• Radionuclide Imaging
• alpha-Synuclein