Multiple system atrophy: Prognostic indicators of survival

Authors


  • Funding agencies: This study was supported in part by National Institutes of Health (NS 32352 Autonomic Disorders Program Project, NS 44233 Pathogenesis and Diagnosis of Multiple System Atrophy, U54 NS065736 Autonomic Rare Disease Clinical Consortium and K23NS075141 Differential Approach to the Postural Tachycardia Syndrome), Mayo CTSA (UL1 TR000135), NIH Research Training Grant under Ruth L. Kirschstein National Research Service Award T32 HD07447, Shih Memorial, and Mayo Funds. The Autonomic Diseases Consortium is a part of the NIH Rare Diseases Clinical Research Network (RDCRN). Funding and/or programmatic support for this project has been provided by U54 NS065736 from the National Institute of Neurological Diseases and Stroke (NINDS) and the NIH Office of Rare Diseases Research (ORDR).

  • Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Neurological and autonomic presentation in multiple system atrophy (MSA) may predict early mortality. Quantification of early autonomic failure as a mortality predictor is lacking. Early neurological and autonomic clinical features were retrospectively reviewed in 49 MSA cases (median age at onset, 56.1 years; 16 women) confirmed by autopsy at Mayo Clinic. When available, the 10-point composite autonomic severity score derived from the autonomic reflex screen provided quantification of the degree of autonomic failure and thermoregulatory sweat test quantitated body surface anhidrosis. Symptoms at onset were autonomic in 50%, parkinsonian in 30%, and cerebellar in 20% of cases. Survival (median [95% confidence interval]) was 8.6 [6.7-10.2] years. Survival was shorter in patients with early laboratory evidence of generalized (composite autonomic severity score ≥ 6) autonomic failure (7.0 [3.9-9.8] vs. 9.8 [4.6-13.8] years; P = 0.036), and early requirement of bladder catheterization (7.3 [3.1-10.2] vs. 13.7 [8.5-14.9] years; P = 0.003) compared with those without these clinical features. On Cox proportional analysis, prognostic indicators of shorter survival were older age at onset (hazard ratio [95% confidence interval], 1.04 [1.01-1.08]; P = 0.03), early requirement of bladder catheterization (7.9 [1.88-38.63]; P = 0.004), and early generalized (composite autonomic severity score ≥ 6) autonomic failure (2.8 [1.01-9.26]; P = 0.047). Gender, phenotype, and early development of gait instability, aid-requiring ambulation, orthostatic symptoms, neurogenic bladder, or significant anhidrosis (thermoregulatory sweat test ≥ 40%) were not indicators of shorter survival. Our data suggest that early development of severe generalized autonomic failure more than triples the risk of shorter survival in patients with MSA. © 2014 International Parkinson and Movement Disorder Society

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