TY - JOUR
T1 - Natural history of multiple system atrophy in the USA
T2 - A prospective cohort study
AU - Low, Phillip A.
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, Jay
N1 - Funding Information:
The work was supported by the US National Institutes of Health (P01 NS044233 to PAL, K23NS075141 to WS), Mayo Clinic's Center for Clinical and Translational Science (UL1 TR000135), the Kathy Shih Memorial Foundation, and the Mayo Clinic. We thank all patients, their families, and referring physicians for their support.
Funding Information:
JJ has received grants during the study from Allergan, Ceregene, CHDI Foundation, GE Healthcare, Huntington's Disease Society of America, Huntington Study Group, Ipsen, Lundbeck, Michael J Fox Foundation for Parkinson Research, Medtronic, Merz Pharmaceuticals, National Institutes of Health, National Parkinson Foundation, St Jude Medical, Teva Pharmaceutical Industries, UCB, University of Rochester, Parkinson Study Group; personal fees from Allergan, Auspex Pharmaceuticals, Ipsen Biopharmaceuticals, Lundbeck, Merz Pharmaceuticals, Teva Pharmaceutical Industries, UCB, US World Meds; and grants outside the submitted work from Allergan, Ceregene, CHDI Foundation, GE Healthcare, Huntington's Disease Society of America, Huntington Study Group, Ipsen, Lundbeck, Michael J Fox Foundation for Parkinson Research, Medtronic, Merz Pharmaceuticals, National Institutes of Health, National Parkinson Foundation, St Jude Medical, Teva Pharmaceutical Industries, UCB, University of Rochester, Parkinson Study Group, and Cambridge University Press, Elsevier, Future Science Group, Hodder Arnold, Lippincott Williams and Wilkins, and Wiley-Blackwell. MBS has been a consultant for Teva, Merz, Adamas, and Civitas; has received equity from Civitas and Adamas; and has been an officer for the International Parkinson and Movement Disorder Society. CMT has received personal fees from Adamas Pharmaceuticals and Pfizer Pharmaceuticals. FJM has received grants from Teva Pharmaceuticals, Medivation, St Jude/ANS Microsystems, and Batten Disease Support and Research Association. TC has received grants from National Institutes of Health-National Institute of Diabetes and Digestive and Kidney Diseases and Ironwood Pharmaceuticals. PAL, SGR, PN, SG, FW, BR, WS, DMS, PS, and JM declare no competing interests. CWS is deceased.
Publisher Copyright:
© 2015 Elsevier Ltd.
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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U2 - 10.1016/S1474-4422(15)00058-7
DO - 10.1016/S1474-4422(15)00058-7
M3 - Article
C2 - 26025783
AN - SCOPUS:84930541886
VL - 14
SP - 710
EP - 719
JO - The Lancet Neurology
JF - The Lancet Neurology
SN - 1474-4422
IS - 7
ER -