Evidence map›Paper›PMID 26025783›Full record

ArticleThe Lancet. Neurology2015

Natural history of multiple system atrophy in the USA: a prospective cohort study.

Phillip A Low, Stephen G Reich, Joseph Jankovic, Clifford W Shults, Matthew B Stern, Peter Novak, Caroline M Tanner, Sid Gilman, Frederick J Marshall, Frederick Wooten and 6 more

Registry-linked trialOpen access · greenAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04431713 (An Open Label, Single Site, 48 Week, Randomised Controlled Trial Evaluating the Safety and Efficacy of Exenatide Once-weekly in the Treatment of Patients With Multiple System Atrophy), which is not on this map. Cited by 199 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
199citing papers in PubMed, 7 pooled it
16.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04431713 phase2completednot on this mapstarted 2020, after this paper: background citation

An Open Label, Single Site, 48 Week, Randomised Controlled Trial Evaluating the Safety and Efficacy of Exenatide Once-weekly in the Treatment of Patients With Multiple System Atrophy

TypeinterventionalSponsorUniversity College, LondonRan2020 to 2024Enrolled50ConditionsMultiple System AtrophyArmsExenatide Pen Injector [Bydureon]
3 · Its place in the literature

Who cites it

199 citing papers in PubMed, 7 syntheses or guidelines pooled it, 323 citations in OpenAlex.

  1. Tremor in multiple system atrophy: a systematic literature review.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy.Movement disorders : official journal of the Movement Disorder Society · 2022
    Pooled it
  6. Pooled it
  7. Pooled it
  8. Trial
  9. Trial
  10. Trial
  11. Article
  12. Article
  13. Article
  14. Multiple system atrophy: cure and care.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  15. Observational
  16. Article
  17. The role of neuro-imaging in multiple system atrophy.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  18. Types of Pain in Multiple System Atrophy.Movement disorders : official journal of the Movement Disorder Society · 2026
    Article
  19. Review
  20. Article

139 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 13 institutions in 2 countries.

Phillip A LowDepartment of Neurology, Mayo Clinic, Rochester, MN, USA. Electronic address: low@mayo.edu.
Stephen G ReichDepartment of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA.
Joseph JankovicDepartment of Neurology, Baylor College of Medicine, Houston, TX, USA.
Clifford W ShultsDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Matthew B SternParkinson's Disease and Movement Disorders Center, Pennsylvania Hospital, Philadelphia, PA, USA.
Peter NovakDepartment of Neurology, University of Massachusetts, Worcester, MA, USA.
Caroline M TannerDepartment of Neurology, University of California, San Francisco, CA, USA.
Sid GilmanDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.
Frederick J MarshallDepartment of Neurology, University of Rochester, Rochester, NY, USA.
Frederick WootenDepartment of Neurology, University of Virginia Health System, Charlottesville, VA, USA.
Brad RacetteDepartment of Neurology, Washington University School of Medicine, St Louis, MO, USA; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa.
Thomas ChelimskyDepartment of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA.
Wolfgang SingerDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
David M SlettenDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Paola SandroniDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Jay MandrekarDivision of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
Mayo Clinic in Arizona · USBaylor College of Medicine · USMayo Clinic · USMedical College of Wisconsin · USPennsylvania Hospital · USUniversity of California, San Diego · USUniversity of California, San Francisco · USUniversity of Maryland, Baltimore · USUniversity of Massachusetts Chan Medical School · USUniversity of Michigan–Ann Arbor · USUniversity of Rochester · USUniversity of the Witwatersrand · ZAUniversity of Virginia Health System · US

Funding

Mayo Clinic Center for Translational Science ActivitiesUL1TR000135 · NCATS · MAYO CLINIC ROCHESTER · PI KHOSLA, SUNDEEP · 2012 to 2015
$41.2M
Studies on Diagnosis, Pathophysiology, and Treatment of Autonomic Failure in MSAP01NS044233 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MASLIAH, ELIEZER · 2003 to 2014
$12.4M
Training CoreU54NS065736 · NINDS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI FREEMAN, ROY · 2009 to 2018
$11.6M
Epidemiology and Biomarkers of Parkinsonism in WeldersK24ES017765 · NIEHS · WASHINGTON UNIVERSITY · PI RACETTE, BRAD A · 2009 to 2018
$1.5M
Differential Approach to the Postural Tachycardia SyndromeK23NS075141 · NINDS · MAYO CLINIC ROCHESTER · PI SINGER, WOLFGANG · 2012 to 2016
$872k
NCATS NIH HHS UL1 TR000135NIEHS NIH HHS K24 ES017765NINDS NIH HHS K23 NS075141NINDS NIH HHS K23NS075141NINDS NIH HHS P01 NS044233NINDS NIH HHS U54 NS065736
6 · The paper itself

Abstract

backgroundMultiple 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.

methodsWe 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.

findingsWe 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.

interpretationProbable 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.

fundingUS National Institutes of Health, Mayo Clinic, and Kathy Shih Memorial Foundation.

Indexed as

Disease ProgressionActivities of Daily LivingAdultAgedAged, 80 and overCerebellar AtaxiaCohort StudiesFemaleFollow-Up StudiesHumansMaleMiddle AgedMultiple System AtrophyParkinsonian DisordersProspective StudiesRetrospective Studies

Identifiers

PMID26025783
PMCPMC4472464
OpenAlexW2166522195

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.