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Natural history of multiple system atrophy in the USA: a prospective cohort study
Open accessAbstract
Background Multiple system atrophy (MSA) is a rare, fatal neurodegenerative disorder exhibiting a combination of parkinsonism and/or cerebellar ataxia with autonomic failure. We report the first North American prospective natural history study of MSA, and the effects of phenotype and autonomic failure on prognosis. Methods 175 subjects with probable MSA, both MSA-P and MSA-C, were recruited and prospectively followed for 5 years with evaluations every 6 months in 12 centers. Natural history was evaluated by Kaplan-Meier survival analysis. We compared MSA-P with MSA-C and evaluated predictors of outcome. These subjects were evaluated with 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. Findings Mean age of symptom onset was 63.4 (SD 8.57) years. Median survival from symptom onset by Kaplan-Meier analysis was 9.8 years (95% CI 8.8-10.7). Subjects with severe symptomatic autonomic failure (symptomatic orthostatic hypotension, urinary incontinence) at diagnosis had a worse prognosis, surviving 8.0 years (95% CI, 6.5-9.5, n=62) while remaining subjects survived a median of 10.3 years (95% CI, 9.3-11.4, n=113). At baseline MSA-P (n=126) and MSA-C (n=49) were not different in symptoms and function, UMSARS I, 25.2 (8.08) vs 24.6 (8.34), p=0.835; UMSARS II, 26.4 (8.77) vs 25.4 (10.51), p=0.7635; COMPASS_select), 43.5 (18.66) vs 42.8 (19.56), p=0.835. Progression, evaluated by change in UMSARS I, UMSARS II, COMPASS_select over the next 5 years, was not significantly different between MSA-P and MSA-C. Median time to death from enrollment baseline was 1.8 (95% CI, 0.9-2.7) years. Interpretation Probable MSA represents late-stage disease with short survival. Natural history of MSA-P and MSA-C are similar. Severe symptomatic autonomic failure at diagnosis is associated with worse prognosis. Funding National Institutes of Health (P01 NS044233), Mayo CTSA (UL1 TR000135), the Kathy Shih Memorial Foundation, and Mayo funds.
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Second consensus statement on the diagnosis of multiple system atrophy
Gilman, S., Wenning, G. K., Low, P. A., Brooks, D. J., Mathias, C. J., Trojanowski, J. Q., Wood, N. W., Colosimo, C., Dürr, A., Fowler, C. J., et al. (2008) · Neurology · doi:10.1212/01.wnl.0000324625.00404.15 · Cited by 3,140
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The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy
Wenning, G. K., Stankovic, I., Vignatelli, L., Fanciulli, A., Calandra‐Buonaura, G., Seppi, K., Palma, J., Meissner, W. G., Krismer, F., Berg, D., et al. (2022) · Movement Disorders · doi:10.1002/mds.29005 · Cited by 833
Self-citationPoewe, W., Stankovic, I., Halliday, G., Meissner, W. G., Wenning, G. K., Pellecchia, M. T., Seppi, K., Palma, J.-A., & Kaufmann, H. (2022) · Nature Reviews Disease Primers · doi:10.1038/s41572-022-00382-6 · Cited by 279
(2019) · International Review of Neurobiology · doi:10.1016/bs.irn.2019.10.004 · Cited by 253
Mesenchymal Stromal Cell Therapies for Neurodegenerative Diseases
Staff, N. P., Jones, D. T., & Singer, W. (2019) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2019.01.001 · Cited by 150
Self-citationT cell infiltration in both human multiple system atrophy and a novel mouse model of the disease
Williams, G. P., Marmion, D. J., Schonhoff, A. M., Jurkuvenaite, A., Won, W.-J., Standaert, D. G., Kordower, J. H., & Harms, A. S. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02126-w · Cited by 102
Metadata
- Authors
- Low, P. A., Reich, S. G., Jankovic, J., Shults, C. W., Stern, M. B., Novak, P., Tanner, C. M., Gilman, S., Marshall, F. J., Wooten, F., Racette, B., Chelimsky, T., Singer, W., Sletten, D. M., Sandroni, P., & Mandrekar, J.
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 14
- Issue
- 7
- Pages
- 710-719
- ISSN
- 1474-4422 (ISSN-L)
- OpenAlex
- W2166522195
- Cited by
- 336
- References
- 1
- FWCI
- 15.39
- Type
- journal article
- Language
- en
- Open access
- green
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- Low, P. A., Reich, S. G., Jankovic, J., Shults, C. W., Stern, M. B., Novak, P., Tanner, C. M., Gilman, S., Marshall, F. J., Wooten, F., Racette, B., Chelimsky, T., Singer, W., Sletten, D. M., Sandroni, P., & Mandrekar, J. (2015). Natural history of multiple system atrophy in the USA: a prospective cohort study. The Lancet Neurology. https://doi.org/10.1016/s1474-4422(15)00058-7
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