The natural history of multiple system atrophy: a prospective European cohort study - 14/02/13

Doi : 10.1016/S1474-4422(12)70327-7

Gregor K Wenning, ProfMD ^a,^⁎ , Felix Geser, MD ^a,^b, Florian Krismer, MD ^a, Klaus Seppi, MD ^a, Susanne Duerr, MD ^a, Sylvia Boesch, MD ^a, Martin Köllensperger, MD ^a, Georg Goebel, PhD ^c, Karl P Pfeiffer, PhD ^c,^d, Paolo Barone, MD ^e, Maria Teresa Pellecchia, MD ^e, Niall P Quinn, MD ^f, Vasiliki Koukouni, MD ^f, Clare J Fowler, MD ^g, Anette Schrag, MD ^h, Christopher J Mathias, MD ^f, Nir Giladi, MD ⁱ, Tanya Gurevich, MD ⁱ, Erik Dupont, MD ^j, Karen Ostergaard, MD ^j, Christer F Nilsson, MD ^k, Håkan Widner, MD ^k, Wolfgang Oertel, MD ^l, Karla Maria Eggert, MD ^l, Alberto Albanese, MD ^m, Francesca del Sorbo, MD ^m, Eduardo Tolosa, MD ⁿ, Adriana Cardozo, MD ⁿ, Günther Deuschl, MD ^o, Helge Hellriegel, MD ^o, Thomas Klockgether, MD ^p, Richard Dodel, MD ^l, Cristina Sampaio, MD ^q, Miguel Coelho, MD ^q, Ruth Djaldetti, MD ^r, Eldad Melamed, MD ^r, Thomas Gasser, MD ^s, Christoph Kamm, MD ^s,^t, Giuseppe Meco, MD ^u, Carlo Colosimo, MD ^u, Olivier Rascol, MD ^v, Wassilios G Meissner, MD ^w, François Tison, MD ^w, Werner Poewe, MD ^a
for The European Multiple System Atrophy Study Group
^a Department of Neurology, Innsbruck Medical University, Innsbruck, Austria
^b Department of Neurology, University of Ulm, Ulm, Germany
^c Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck
^d FH Joanneum, Graz, Austria
^e Neurodegenerative Diseases Centre, University of Salerno, Italy
^f Institute of Neurology, Queen Square, London, UK
^g Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, London
^h Department of Clinical Neurosciences, Royal Free and University College Medical School, University College London, London, UK
ⁱ Department of Neurology, Movement Disorders Unit, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
^j Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
^k Division of Neurology, Department of Clinical Sciences, University of Lund, Lund, Sweden
^l Department of Neurology, Philipps-University Marburg, Germany
^m Istituto Neurologico Carlo Besta, Università Cattolica del Sacro Cuore, Milano, Italy
ⁿ Neurology Service, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic, IDIBAPS, Universitat de Barcelona, Spain
^o Department of Neurology, Christian-Albrechts University of Kiel, Germany
^p Department of Neurology, University of Bonn, and DZNE, German Center for Neurodegenerative Diseases, Bonn, Germany
^q Faculdade de Medicina de Lisboa, Hopital Santa Maria, Centro de Neurosciencias de Lisboa, Portugal
^r Department of Neurology, Rabin Medical Center, Petach-Tiqva, Israel
^s Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tuebingen, and DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany
^t Department of Neurology, University of Rostock, Rostock, Germany
^u Department of Neurology and Psychiatry, Sapienza University, Rome, Italy
^v Departments of Clinical Pharmacology and Neurosciences, French Reference Centre for MSA, Faculty of Medicine Purpan, University UPS of Toulouse III, Toulouse, France
^w Department of Neurology and French Reference Centre for MSA, University Hospital Bordeaux and Institute for Neurodegenerative Diseases, University Bordeaux 2, Bordeaux, France

^*Correspondence to: Prof Gregor K Wenning, Division of Neurobiology, Department of Neurology, Anichstraße 35, A-6020 Innsbruck, Austria

Summary

Background

Multiple system atrophy (MSA) is a fatal and still poorly understood degenerative movement disorder that is characterised by autonomic failure, cerebellar ataxia, and parkinsonism in various combinations. Here we present the final analysis of a prospective multicentre study by the European MSA Study Group to investigate the natural history of MSA.

Methods

Patients with a clinical diagnosis of MSA were recruited and followed up clinically for 2 years. Vital status was ascertained 2 years after study completion. Disease progression was assessed using the unified MSA rating scale (UMSARS), a disease-specific questionnaire that enables the semiquantitative rating of autonomic and motor impairment in patients with MSA. Additional rating methods were applied to grade global disease severity, autonomic symptoms, and quality of life. Survival was calculated using a Kaplan-Meier analysis and predictors were identified in a Cox regression model. Group differences were analysed by parametric tests and non-parametric tests as appropriate. Sample size estimates were calculated using a paired two-group t test.

Findings

141 patients with moderately severe disease fulfilled the consensus criteria for MSA. Mean age at symptom onset was 56·2 (SD 8·4) years. Median survival from symptom onset as determined by Kaplan-Meier analysis was 9·8 years (95% CI 8·1–11·4). The parkinsonian variant of MSA (hazard ratio [HR] 2·08, 95% CI 1·09–3·97; p=0·026) and incomplete bladder emptying (HR 2·10, 1·02–4·30; p=0·044) predicted shorter survival. 24-month progression rates of UMSARS activities of daily living, motor examination, and total scores were 49% (9·4 [SD 5·9]), 74% (12·9 [8·5]), and 57% (21·9 [11·9]), respectively, relative to baseline scores. Autonomic symptom scores progressed throughout the follow-up. Shorter symptom duration at baseline (OR 0·68, 0·5–0·9; p=0·006) and absent levodopa response (OR 3·4, 1·1–10·2; p=0·03) predicted rapid UMSARS progression. Sample size estimation showed that an interventional trial with 258 patients (129 per group) would be able to detect a 30% effect size in 1-year UMSARS motor examination decline rates at 80% power.

Interpretation

Our prospective dataset provides new insights into the evolution of MSA based on a follow-up period that exceeds that of previous studies. It also represents a useful resource for patient counselling and planning of multicentre trials.

Funding

Fifth Framework Programme of the European Union, the Oesterreichische Nationalbank, and the Austrian Science Fund.

Le texte complet de cet article est disponible en PDF.

Plan

Introduction

Methods

Study design and patients

Rating scales

Statistical analysis

Role of the funding source

Results

Discussion

Export

Vol 12 - N° 3

P. 264-274 - mars 2013 Retour au numéro

Article précédent

Prevalence of active convulsive epilepsy in sub-Saharan Africa and associated risk factors: cross-sectional and case-control studies
Anthony K Ngugi, Christian Bottomley, Immo Kleinschmidt, Ryan G Wagner, Angelina Kakooza-Mwesige, Kenneth Ae-Ngibise, Seth Owusu-Agyei, Honorati Masanja, Gathoni Kamuyu, Rachael Odhiambo, Eddie Chengo, Josemir W Sander, Charles R Newton, for the SEEDS group

| Article suivant

Hypothermia for acute ischaemic stroke
Tzu-Ching Wu, James C Grotta

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

connectez-vous ou créez un compte

The natural history of multiple system atrophy: a prospective European cohort study - 14/02/13

Summary

Background

Methods

Findings

Interpretation

Funding

Plan

Export citations

Fichier

Contenu

Accès rapides

Mon compte

Aide & support

Plateformes Elsevier Masson

Déclaration CNIL