Disease Progression in Multiple System Atrophy-Novel Modeling Framework and Predictive Factors.

disease progression motor subtype multiple system atrophy multivariate nonlinear mixed-effects models neurodegenerative disease

Journal

Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688

Informations de publication

Date de publication:
08 2022
Historique:
revised: 21 04 2022
received: 13 01 2022
accepted: 02 05 2022
pubmed: 8 6 2022
medline: 20 8 2022
entrez: 7 6 2022
Statut: ppublish

Résumé

Multiple system atrophy (MSA) is a rare and aggressive neurodegenerative disease that typically leads to death 6 to 10 years after symptom onset. The rapid evolution renders it crucial to understand the general disease progression and factors affecting the disease course. The aims of this study were to develop a novel disease-progression model to estimate a population-level MSA progression trajectory and predict patient-specific continuous disease stages describing the degree of progress into the disease. The disease-progression model estimated a population-level progression trajectory of subscales of the Unified MSA Rating Scale and the Unified Parkinson's Disease Rating Scale using patients in the European MSA natural history study. The predicted disease continuum was validated via multiple analyses based on reported anchor points, and the effect of MSA subtype on the rate of disease progression was evaluated. The predicted disease continuum spanned approximately 6 years, with an estimated average duration of 51 months for a patient with global disability score 0 to reach the highest level of 4. The predicted continuous disease stages were shown to be correlated with time of symptom onset and predictive of survival time. MSA motor subtype was found to significantly affect disease progression, with MSA-parkinsonian (MSA-P) type patients having an accelerated rate of progression. The proposed modeling framework introduces a new method of analyzing and interpreting the progression of MSA. It can provide new insights and opportunities for investigating covariate effects on the rate of progression and provide well-founded predictions of patient-level future progressions. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Sections du résumé

BACKGROUND
Multiple system atrophy (MSA) is a rare and aggressive neurodegenerative disease that typically leads to death 6 to 10 years after symptom onset. The rapid evolution renders it crucial to understand the general disease progression and factors affecting the disease course.
OBJECTIVES
The aims of this study were to develop a novel disease-progression model to estimate a population-level MSA progression trajectory and predict patient-specific continuous disease stages describing the degree of progress into the disease.
METHODS
The disease-progression model estimated a population-level progression trajectory of subscales of the Unified MSA Rating Scale and the Unified Parkinson's Disease Rating Scale using patients in the European MSA natural history study. The predicted disease continuum was validated via multiple analyses based on reported anchor points, and the effect of MSA subtype on the rate of disease progression was evaluated.
RESULTS
The predicted disease continuum spanned approximately 6 years, with an estimated average duration of 51 months for a patient with global disability score 0 to reach the highest level of 4. The predicted continuous disease stages were shown to be correlated with time of symptom onset and predictive of survival time. MSA motor subtype was found to significantly affect disease progression, with MSA-parkinsonian (MSA-P) type patients having an accelerated rate of progression.
CONCLUSIONS
The proposed modeling framework introduces a new method of analyzing and interpreting the progression of MSA. It can provide new insights and opportunities for investigating covariate effects on the rate of progression and provide well-founded predictions of patient-level future progressions. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Identifiants

pubmed: 35668573
doi: 10.1002/mds.29077
pmc: PMC9540561
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1719-1727

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Références

Ann Gen Psychiatry. 2012 May 17;11(1):14
pubmed: 22594786
Mov Disord. 2012 Aug;27(9):1186-90
pubmed: 22806758
J Neurol Neurosurg Psychiatry. 1994 Sep;57(9):1047-56
pubmed: 8089667
Brain. 2015 Dec;138(Pt 12):3623-31
pubmed: 26369944
Lancet Neurol. 2015 Jul;14(7):710-9
pubmed: 26025783
N Engl J Med. 2015 Jan 15;372(3):249-63
pubmed: 25587949
Transl Neurodegener. 2020 Feb 17;9:7
pubmed: 32095235
Stat Med. 2021 Jun 30;40(14):3251-3266
pubmed: 33853199
Mov Disord. 2004 Sep;19(9):1020-8
pubmed: 15372591
Lancet Neurol. 2004 Feb;3(2):93-103
pubmed: 14747001
J Neural Transm (Vienna). 2021 Oct;128(10):1529-1543
pubmed: 34398313
Brain. 2002 May;125(Pt 5):1070-83
pubmed: 11960896
Brain. 2008 May;131(Pt 5):1362-72
pubmed: 18385183
Neurology. 1967 May;17(5):427-42
pubmed: 6067254
J Neurol Neurosurg Psychiatry. 1989 Jun;Suppl:78-89
pubmed: 2666581
Biometrics. 2017 Dec;73(4):1343-1354
pubmed: 28182831
Mov Disord. 2004 Dec;19(12):1391-402
pubmed: 15452868
J Clin Pharmacol. 2012 May;52(5):629-44
pubmed: 21659625
Front Big Data. 2020 Aug 12;3:24
pubmed: 33693397
Neurology. 1999 Feb;52(3):523-8
pubmed: 10025781
Alzheimers Dement. 2021 Dec;17(12):1938-1949
pubmed: 34581496
Lancet Neurol. 2013 Mar;12(3):264-74
pubmed: 23391524
Lancet Neurol. 2009 Dec;8(12):1172-8
pubmed: 19909915
J Neural Transm (Vienna). 2005 Dec;112(12):1677-86
pubmed: 16049636
Mov Disord. 2007 Jan;22(1):41-7
pubmed: 17115387
Int Rev Neurobiol. 2019;149:137-192
pubmed: 31779811
Mov Disord. 2014 Aug;29(9):1151-7
pubmed: 24909319
Neurobiol Dis. 2020 Jun;139:104813
pubmed: 32087288
Nat Rev Neurol. 2017 Apr;13(4):232-243
pubmed: 28303913

Auteurs

Line Kühnel (L)

H. Lundbeck A/S, Copenhagen, Denmark.
Department of Mathematical Sciences, University of Copenhagen, Copenhagen, Denmark.

Lars Lau Raket (LL)

H. Lundbeck A/S, Copenhagen, Denmark.
Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.

Daniel Oudin Åström (DO)

H. Lundbeck A/S, Copenhagen, Denmark.

Anna-Karin Berger (AK)

H. Lundbeck A/S, Copenhagen, Denmark.

Ingeborg Helbech Hansen (IH)

H. Lundbeck A/S, Copenhagen, Denmark.

Florian Krismer (F)

Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.

Gregor K Wenning (GK)

Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.

Klaus Seppi (K)

Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.

Werner Poewe (W)

Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.

JoséLuis Molinuevo (J)

H. Lundbeck A/S, Copenhagen, Denmark.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH