Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Multiple system atrophy: Prognosis and treatment

Stewart A Factor, DO
Christine Doss Esper, MD
Section Editor
Howard I Hurtig, MD
Deputy Editor
John F Dashe, MD, PhD


Multiple system atrophy (MSA) is a unifying term that brings together a group of neurodegenerative disorders (olivopontocerebellar atrophy, striatonigral degeneration, and Shy-Drager) characterized by various degrees of autonomic dysfunction, cerebellar abnormalities, parkinsonism, and corticospinal degeneration.

This topic will review the prognosis and management of MSA. Other clinical aspects of MSA are reviewed separately. (See "Multiple system atrophy: Clinical features and diagnosis".)


Disease progression in MSA usually occurs over one to 18 years, and is often faster than that of idiopathic Parkinson disease [1].

In mainly retrospective studies, the median times from disease onset to disability milestones in MSA were as follows:

Development of autonomic dysfunction, 2.5 years [2]

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: May 09, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Wenning GK, Ben Shlomo Y, Magalhães M, et al. Clinical features and natural history of multiple system atrophy. An analysis of 100 cases. Brain 1994; 117 ( Pt 4):835.
  2. Tada M, Onodera O, Tada M, et al. Early development of autonomic dysfunction may predict poor prognosis in patients with multiple system atrophy. Arch Neurol 2007; 64:256.
  3. Watanabe H, Saito Y, Terao S, et al. Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients. Brain 2002; 125:1070.
  4. Schrag A, Wenning GK, Quinn N, Ben-Shlomo Y. Survival in multiple system atrophy. Mov Disord 2008; 23:294.
  5. Ben-Shlomo Y, Wenning GK, Tison F, Quinn NP. Survival of patients with pathologically proven multiple system atrophy: a meta-analysis. Neurology 1997; 48:384.
  6. Bjornsdottir A, Gudmundsson G, Blondal H, Olafsson E. Incidence and prevalence of multiple system atrophy: a nationwide study in Iceland. J Neurol Neurosurg Psychiatry 2013; 84:136.
  7. Wenning GK, Geser F, Krismer F, et al. The natural history of multiple system atrophy: a prospective European cohort study. Lancet Neurol 2013; 12:264.
  8. Low PA, Reich SG, Jankovic J, et al. Natural history of multiple system atrophy in the USA: a prospective cohort study. Lancet Neurol 2015; 14:710.
  9. Goldstein DS, Holmes C, Sharabi Y, Wu T. Survival in synucleinopathies: A prospective cohort study. Neurology 2015; 85:1554.
  10. Wenning GK, Colosimo C, Geser F, Poewe W. Multiple system atrophy. Lancet Neurol 2004; 3:93.
  11. Petrovic IN, Ling H, Asi Y, et al. Multiple system atrophy-parkinsonism with slow progression and prolonged survival: a diagnostic catch. Mov Disord 2012; 27:1186.
  12. O'Sullivan SS, Massey LA, Williams DR, et al. Clinical outcomes of progressive supranuclear palsy and multiple system atrophy. Brain 2008; 131:1362.
  13. Coon EA, Sletten DM, Suarez MD, et al. Clinical features and autonomic testing predict survival in multiple system atrophy. Brain 2015; 138:3623.
  14. Giannini G, Calandra-Buonaura G, Mastrolilli F, et al. Early stridor onset and stridor treatment predict survival in 136 patients with MSA. Neurology 2016; 87:1375.
  15. Glasmacher SA, Leigh PN, Saha RA. Predictors of survival in progressive supranuclear palsy and multiple system atrophy: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2017; 88:402.
  16. Calandra-Buonaura G, Guaraldi P, Sambati L, et al. Multiple system atrophy with prolonged survival: is late onset of dysautonomia the clue? Neurol Sci 2013; 34:1875.
  17. Stefanova N, Bücke P, Duerr S, Wenning GK. Multiple system atrophy: an update. Lancet Neurol 2009; 8:1172.
  18. Munschauer FE, Loh L, Bannister R, Newsom-Davis J. Abnormal respiration and sudden death during sleep in multiple system atrophy with autonomic failure. Neurology 1990; 40:677.
  19. Jin K, Okabe S, Chida K, et al. Tracheostomy can fatally exacerbate sleep-disordered breathing in multiple system atrophy. Neurology 2007; 68:1618.
  20. Colosimo C, Pezzella FR. The symptomatic treatment of multiple system atrophy. Eur J Neurol 2002; 9:195.
  21. Kaufmann H, Norcliffe-Kaufmann L, Palma JA. Droxidopa in neurogenic orthostatic hypotension. Expert Rev Cardiovasc Ther 2015; 13:875.
  22. Kaufmann H, Saadia D, Voustianiouk A, et al. Norepinephrine precursor therapy in neurogenic orthostatic hypotension. Circulation 2003; 108:724.
  23. Mathias CJ, Senard JM, Braune S, et al. L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure. Clin Auton Res 2001; 11:235.
  24. Iwasaki Y, Wakata N, Kinoshita M. Parkinsonism induced by pyridostigmine. Acta Neurol Scand 1988; 78:236.
  25. Kao KP, Kwan SY, Lin KP, Chang YC. Coexistence of Parkinson's disease and myasthenia gravis: a case report. Clin Neurol Neurosurg 1993; 95:137.
  26. Schenck CH, Mahowald MW. Rapid eye movement sleep parasomnias. Neurol Clin 2005; 23:1107.
  27. Panossian LA, Avidan AY. Review of sleep disorders. Med Clin North Am 2009; 93:407.
  28. Lee PH, Lee JE, Kim HS, et al. A randomized trial of mesenchymal stem cells in multiple system atrophy. Ann Neurol 2012; 72:32.
  29. Palma JA, Kaufmann H. Novel therapeutic approaches in multiple system atrophy. Clin Auton Res 2015; 25:37.
  30. Krismer F, Seppi K, Stefanova N, Wenning GK. Toward disease modification in multiple system atrophy: Pitfalls, bottlenecks, and possible remedies. Mov Disord 2016; 31:235.
  31. Study assessing safety and therapeutic activity of AFFITOPE® PD01A and PD03A in patients with early MSA (AFF009). https://clinicaltrials.gov/show/NCT02270489 (Accessed on May 09, 2017).
  32. Maab S, Levin J, Höglinger G. Current Treatment of Multiple System Atrophy. Curr Treat Options Neurol 2016; 18:51.
  33. Progression rate of MSA under EGCG supplementation as anti-aggregation-approach (PROMESA). https://clinicaltrials.gov/show/NCT02008721 (Accessed on May 09, 2017).
  34. Levin J, Maaß S, Schuberth M, et al. The PROMESA-protocol: progression rate of multiple system atrophy under EGCG supplementation as anti-aggregation-approach. J Neural Transm (Vienna) 2016; 123:439.