Natural history of multiple system atrophy in the USA

A prospective cohort study

Phillip Anson Low, Stephen G. Reich, Joseph Jankovic, Clifford W. Shults, Matthew B. Stern, Peter Novak, Caroline M. Tanner, Sid Gilman, Frederick J. Marshall, Frederick Wooten, Brad Racette, Thomas Chelimsky, Wolfgang Singer, David M. Sletten, Paola Sandroni, Jayawant Mandrekar

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Background: Multiple system atrophy is a rare, fatal neurodegenerative disorder with symptoms of autonomic failure plus parkinsonism, cerebellar ataxia, or both. We report results of the first prospective natural history study of multiple system atrophy in the USA, and the effects of phenotype and autonomic failure on prognosis. Methods: We recruited participants with probable multiple system atrophy-of either the parkinsonism subtype (MSA-P) or the cerebellar ataxia subtype (MSA-C)-at 12 neurology centres in the USA specialising in movement or autonomic disorders. We followed up patients every 6 months for 5 years and assessed them with the Unified Multiple System Atrophy Rating Scale part I (UMSARS I; a functional score of symptoms and ability to undertake activities of daily living), UMSARS II (neurological motor evaluation), and the Composite Autonomic Symptoms Scale (COMPASS)-select (a measure of autonomic symptoms and autonomic functional status). We assessed potential predictors of outcome. We used Cox proportional hazards models to calculate univariate hazard ratios for shorter survival using age at disease onset as a continuous variable and sex, clinical phenotype, and early development of neurological and autonomic manifestations as categorical variables. Findings: We recruited 175 participants. Mean age at study entry was 63·4 years (SD 8·6). Median survival from symptom onset was 9·8 years (95% CI 8·8-10·7) and median survival from enrolment was 1·8 years (0·9-2·7). Participants with severe symptomatic autonomic failure (symptomatic orthostatic hypotension, urinary incontinence, or both) at diagnosis (n=62) had a worse prognosis than those without severe disease (n=113; median survival 8·0 years, 95% CI 6·5-9·5 vs 10·3 years, 9·3-11·4; p=0·021). At baseline, patients with MSA-P (n=126) and MSA-C (n=49) had much the same symptoms and functional status: mean UMSARS I 25·2 (SD 8·08) versus 24·6 (8·34; p=0·835); mean UMSARS II 26·4 (8·8) versus 25·4 (10·5; p=0·764); COMPASS-select 43·5 (18·7) versus 42·8 (19·6; p=0·835). Progression over 5 years, assessed by change in UMSARS I, UMSARS II, and COMPASS-select, was modest. Interpretation: Probable multiple system atrophy is a late-stage disease with short survival. The natural histories of MSA-P and MSA-C are similar and severe symptomatic autonomic failure at diagnosis is associated with worse prognosis. Funding: US National Institutes of Health, Mayo Clinic, and Kathy Shih Memorial Foundation.

Original languageEnglish (US)
Pages (from-to)710-719
Number of pages10
JournalThe Lancet Neurology
Volume14
Issue number7
DOIs
StatePublished - Jul 1 2015

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Multiple System Atrophy
Cohort Studies
Prospective Studies
Parkinsonian Disorders
Survival
Cerebellar Ataxia
Natural History
Phenotype
Orthostatic Hypotension
National Institutes of Health (U.S.)
Urinary Incontinence
Neurology
Activities of Daily Living
Neurologic Manifestations
Age of Onset
Proportional Hazards Models
Neurodegenerative Diseases

ASJC Scopus subject areas

  • Clinical Neurology

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Natural history of multiple system atrophy in the USA : A prospective cohort study. / Low, Phillip Anson; Reich, Stephen G.; Jankovic, Joseph; Shults, Clifford W.; Stern, Matthew B.; Novak, Peter; Tanner, Caroline M.; Gilman, Sid; Marshall, Frederick J.; Wooten, Frederick; Racette, Brad; Chelimsky, Thomas; Singer, Wolfgang; Sletten, David M.; Sandroni, Paola; Mandrekar, Jayawant.

In: The Lancet Neurology, Vol. 14, No. 7, 01.07.2015, p. 710-719.

Research output: Contribution to journalArticle

Low, PA, Reich, SG, Jankovic, J, Shults, CW, Stern, MB, Novak, P, Tanner, CM, Gilman, S, Marshall, FJ, Wooten, F, Racette, B, Chelimsky, T, Singer, W, Sletten, DM, Sandroni, P & Mandrekar, J 2015, 'Natural history of multiple system atrophy in the USA: A prospective cohort study', The Lancet Neurology, vol. 14, no. 7, pp. 710-719. https://doi.org/10.1016/S1474-4422(15)00058-7
Low, Phillip Anson ; Reich, Stephen G. ; Jankovic, Joseph ; Shults, Clifford W. ; Stern, Matthew B. ; Novak, Peter ; Tanner, Caroline M. ; Gilman, Sid ; Marshall, Frederick J. ; Wooten, Frederick ; Racette, Brad ; Chelimsky, Thomas ; Singer, Wolfgang ; Sletten, David M. ; Sandroni, Paola ; Mandrekar, Jayawant. / Natural history of multiple system atrophy in the USA : A prospective cohort study. In: The Lancet Neurology. 2015 ; Vol. 14, No. 7. pp. 710-719.
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T1 - Natural history of multiple system atrophy in the USA

T2 - A prospective cohort study

AU - Low, Phillip Anson

AU - Reich, Stephen G.

AU - Jankovic, Joseph

AU - Shults, Clifford W.

AU - Stern, Matthew B.

AU - Novak, Peter

AU - Tanner, Caroline M.

AU - Gilman, Sid

AU - Marshall, Frederick J.

AU - Wooten, Frederick

AU - Racette, Brad

AU - Chelimsky, Thomas

AU - Singer, Wolfgang

AU - Sletten, David M.

AU - Sandroni, Paola

AU - Mandrekar, Jayawant

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Background: Multiple system atrophy is a rare, fatal neurodegenerative disorder with symptoms of autonomic failure plus parkinsonism, cerebellar ataxia, or both. We report results of the first prospective natural history study of multiple system atrophy in the USA, and the effects of phenotype and autonomic failure on prognosis. Methods: We recruited participants with probable multiple system atrophy-of either the parkinsonism subtype (MSA-P) or the cerebellar ataxia subtype (MSA-C)-at 12 neurology centres in the USA specialising in movement or autonomic disorders. We followed up patients every 6 months for 5 years and assessed them with the Unified Multiple System Atrophy Rating Scale part I (UMSARS I; a functional score of symptoms and ability to undertake activities of daily living), UMSARS II (neurological motor evaluation), and the Composite Autonomic Symptoms Scale (COMPASS)-select (a measure of autonomic symptoms and autonomic functional status). We assessed potential predictors of outcome. We used Cox proportional hazards models to calculate univariate hazard ratios for shorter survival using age at disease onset as a continuous variable and sex, clinical phenotype, and early development of neurological and autonomic manifestations as categorical variables. Findings: We recruited 175 participants. Mean age at study entry was 63·4 years (SD 8·6). Median survival from symptom onset was 9·8 years (95% CI 8·8-10·7) and median survival from enrolment was 1·8 years (0·9-2·7). Participants with severe symptomatic autonomic failure (symptomatic orthostatic hypotension, urinary incontinence, or both) at diagnosis (n=62) had a worse prognosis than those without severe disease (n=113; median survival 8·0 years, 95% CI 6·5-9·5 vs 10·3 years, 9·3-11·4; p=0·021). At baseline, patients with MSA-P (n=126) and MSA-C (n=49) had much the same symptoms and functional status: mean UMSARS I 25·2 (SD 8·08) versus 24·6 (8·34; p=0·835); mean UMSARS II 26·4 (8·8) versus 25·4 (10·5; p=0·764); COMPASS-select 43·5 (18·7) versus 42·8 (19·6; p=0·835). Progression over 5 years, assessed by change in UMSARS I, UMSARS II, and COMPASS-select, was modest. Interpretation: Probable multiple system atrophy is a late-stage disease with short survival. The natural histories of MSA-P and MSA-C are similar and severe symptomatic autonomic failure at diagnosis is associated with worse prognosis. Funding: US National Institutes of Health, Mayo Clinic, and Kathy Shih Memorial Foundation.

AB - Background: Multiple system atrophy is a rare, fatal neurodegenerative disorder with symptoms of autonomic failure plus parkinsonism, cerebellar ataxia, or both. We report results of the first prospective natural history study of multiple system atrophy in the USA, and the effects of phenotype and autonomic failure on prognosis. Methods: We recruited participants with probable multiple system atrophy-of either the parkinsonism subtype (MSA-P) or the cerebellar ataxia subtype (MSA-C)-at 12 neurology centres in the USA specialising in movement or autonomic disorders. We followed up patients every 6 months for 5 years and assessed them with the Unified Multiple System Atrophy Rating Scale part I (UMSARS I; a functional score of symptoms and ability to undertake activities of daily living), UMSARS II (neurological motor evaluation), and the Composite Autonomic Symptoms Scale (COMPASS)-select (a measure of autonomic symptoms and autonomic functional status). We assessed potential predictors of outcome. We used Cox proportional hazards models to calculate univariate hazard ratios for shorter survival using age at disease onset as a continuous variable and sex, clinical phenotype, and early development of neurological and autonomic manifestations as categorical variables. Findings: We recruited 175 participants. Mean age at study entry was 63·4 years (SD 8·6). Median survival from symptom onset was 9·8 years (95% CI 8·8-10·7) and median survival from enrolment was 1·8 years (0·9-2·7). Participants with severe symptomatic autonomic failure (symptomatic orthostatic hypotension, urinary incontinence, or both) at diagnosis (n=62) had a worse prognosis than those without severe disease (n=113; median survival 8·0 years, 95% CI 6·5-9·5 vs 10·3 years, 9·3-11·4; p=0·021). At baseline, patients with MSA-P (n=126) and MSA-C (n=49) had much the same symptoms and functional status: mean UMSARS I 25·2 (SD 8·08) versus 24·6 (8·34; p=0·835); mean UMSARS II 26·4 (8·8) versus 25·4 (10·5; p=0·764); COMPASS-select 43·5 (18·7) versus 42·8 (19·6; p=0·835). Progression over 5 years, assessed by change in UMSARS I, UMSARS II, and COMPASS-select, was modest. Interpretation: Probable multiple system atrophy is a late-stage disease with short survival. The natural histories of MSA-P and MSA-C are similar and severe symptomatic autonomic failure at diagnosis is associated with worse prognosis. Funding: US National Institutes of Health, Mayo Clinic, and Kathy Shih Memorial Foundation.

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