TY - JOUR

T1 - Disease Progression in Multiple System Atrophy—Novel Modeling Framework and Predictive Factors

AU - Kühnel, Line

AU - Raket, Lars Lau

AU - Åström, Daniel Oudin

AU - Berger, Anna Karin

AU - Hansen, Ingeborg Helbech

AU - Krismer, Florian

AU - Wenning, Gregor K.

AU - Seppi, Klaus

AU - Poewe, Werner

AU - Molinuevo, JoséLuis

AU - the EMSA-SG Natural History Study Investigators

N1 - Publisher Copyright: © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - disease progression

KW - motor subtype

KW - multiple system atrophy

KW - multivariate nonlinear mixed-effects models

KW - neurodegenerative disease

UR - http://www.scopus.com/inward/record.url?scp=85135999966&partnerID=8YFLogxK

U2 - 10.1002/mds.29077

DO - 10.1002/mds.29077

M3 - Journal article

C2 - 35668573

AN - SCOPUS:85135999966

VL - 37

SP - 1719

EP - 1727

JO - Movement Disorders

JF - Movement Disorders

SN - 0885-3185

IS - 8

ER -