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- Koellensperger, Martin, et al.
(author)
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Presentation, Diagnosis, and Management of Multiple System Atrophy in Europe: Final Analysis of the European Multiple System Atrophy Registry
- 2010
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In: Movement Disorders. - : Wiley. - 0885-3185. ; 25:15, s. 2604-2612
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Journal article (peer-reviewed)abstract
- Multiple system atrophy (MSA) is a Parkinson's Disease (PD)-like alpha-synucleinopathy clinically characterized by dysautonomia, parkinsonism, cerebellar ataxia, and pyramidal signs in any combination. We aimed to determine whether the clinical presentation of MSA as well as diagnostic and therapeutic strategies differ across Europe and Israel. In 19 European MSA Study Group centres all consecutive patients with a clinical diagnosis of MSA were recruited from 2001 to 2005. A standardized minimal data set was obtained from all patients. Four-hundred thirty-seven MSA patients from 19 centres in 10 countries were included. Mean age at onset was 57.8 years; mean disease duration at inclusion was 5.8 years. According to the consensus criteria 68% were classified as parkinsonian type (MSA-P) and 32% as cerebellar type (MSA-C) (probable MSA: 72%, possible MSA: 28%). Symptomatic dysautonomia was present in almost all patients, and urinary dysfunction (83%) more common than symptomatic orthostatic hypotension (75%). Cerebellar ataxia was present in 64%, and parkinsonism in 87%, of all cases. No significant differences in the clinical presentation were observed between the participating countries. In contrast, diagnostic work up and therapeutic strategies were heterogeneous. Less than a third of patients with documented orthostatic hypotension or neurogenic bladder disturbance were receiving treatment. This largest clinical series of MSA patients reported so far shows that the disease presents uniformly across Europe. The observed differences in diagnostic and therapeutic management including lack of therapy for dysautonomia emphasize the need for future guidelines in these areas. (C) 2010 Movement Disorder Society
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| 2. |
- Koellensperger, Martin, et al.
(author)
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Red flags for multiple system atrophy
- 2008
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In: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 23:8, s. 1093-1099
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Journal article (peer-reviewed)abstract
- The clinical diagnosis Of Multiple system atrophy (MSA) is fraught with difficulty and there are no pathognomonic features to discriminate the parkinsonian variant (MSA-P) from Parkinson's disease (PD). Besides the poor response to levodopa, and the additional presence of pyramidal or cerebellar signs (ataxia) or autonomic failure as major diagnostic criteria, certain other clinical features known as "red flags" or warning signs may raise the clinical suspicion of MSA. To study the diagnostic role of these features in MSA-P versus PD patients, a standardized red flag check list (RFCL) developed by the European MSA Study Group (EMSA-SG) was administered to 57 patients with probable MSA-P and 116 patients with probable PD diagnosed according to established criteria. Those red flags with a specifity over 95% were selected for further analysis. Factor analysis was applied to reduce the number of red flags. The resulting set was then applied to 17 patients with possible MSA-P who on follow-up fulfilled criteria of probable MSA-P. Red flags were grouped into related categories. With two or more of six red flag categories present specificity was 98.3% and sensitivity was 84.2% in our cohort. When applying these criteria to patients with possible MSA-P, 76.5% of them would have been correctly diagnosed as probable MSA-P 15.9 (+/- 7.0) months earlier than with the Consensus criteria alone. We propose a combination of two out of six red flag categories as additional diagnostic criteria for probable MSA-P. (C) 2008 Movement Disorder Society.
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| 3. |
- Wenning, Gregor K., et al.
(author)
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The natural history of multiple system atrophy: a prospective European cohort study
- 2013
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In: Lancet Neurology. - 1474-4465. ; 12:3, s. 264-274
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Journal article (peer-reviewed)abstract
- 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.
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