The natural history of multiple system atrophy: a prospective European cohort study.
The natural history of multiple system atrophy: a prospective European cohort study.
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DOI：
10.1016/s1474-4422(12)70327-7
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发表时间：
2013-03
期刊：
影响因子：
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通讯作者：
European Multiple System Atrophy Study Group
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文献类型：
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作者：
Wenning GK;Geser F;Krismer F;Seppi K;Duerr S;Boesch S;Köllensperger M;Goebel G;Pfeiffer KP;Barone P;Pellecchia MT;Quinn NP;Koukouni V;Fowler CJ;Schrag A;Mathias CJ;Giladi N;Gurevich T;Dupont E;Ostergaard K;Nilsson CF;Widner H;Oertel W;Eggert KM;Albanese A;del Sorbo F;Tolosa E;Cardozo A;Deuschl G;Hellriegel H;Klockgether T;Dodel R;Sampaio C;Coelho M;Djaldetti R;Melamed E;Gasser T;Kamm C;Meco G;Colosimo C;Rascol O;Meissner WG;Tison F;Poewe W;European Multiple System Atrophy Study Group
多系统萎缩(MSA)是一种致命性的退行性运动障碍，其特征是自主神经功能衰竭、小脑性共济失调和各种组合的帕金森症。在这里，我们提出了由欧洲MSA研究小组进行的一项前瞻性多中心研究的最终分析，以调查MSA的自然历史。对临床诊断为MSA的患者进行2年的临床随访。在研究完成2年后确定生命状态。使用统一的MSA评分表(UMSARS)评估疾病进展，这是一种针对疾病的调查问卷，能够对MSA患者的自主神经和运动障碍进行半定量评分。采用其他评分方法对全球疾病严重程度、自主神经症状和生活质量进行评分。用Kaplan-Meier分析计算生存率，用Cox回归模型确定预测因素。分组差异通过适当的参数检验和非参数检验进行分析。样本量估计使用配对两组t检验来计算。141名中重度疾病患者符合MSA的共识标准。平均发病年龄56·2岁(SD8·4)。经Kaplan-Meier分析，症状出现的中位生存期为9.8年(95%可信区间为8.1~11.4)。帕金森病患者MSA(危险比[HR]2·08，95%CI 1·09-3·97；p=0·026)和膀胱排空不全(HR 2·10，1·02-4·30；p=0·044)预示着较短的生存期。24个月UMSARS日常生活活动、运动检查和总分的进展率分别为49%(9·4[SD 5·9])、74%(12·9[8·5])和57%(21·9[11·9])。在整个随访过程中，自主神经症状评分一直在进步。基线症状持续时间较短(OR0·68，0·5~0·9；P=0·006)和无左旋多巴反应(OR3·4，1·1~10·2；P=0·03)预示UMSARS进展迅速。样本量估计表明，一项有258名患者(每组129人)的干预试验将能够在80%功率下检测到一年UMSARS运动检查下降率30%的有效大小。我们的前瞻性数据集为基于超过先前研究的随访期的MSA的演变提供了新的见解。它也是患者咨询和规划多中心试验的有用资源。欧洲联盟第五框架方案、奥地利国家银行和奥地利科学基金。
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. 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. 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. 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. Fifth Framework Programme of the European Union, the Oesterreichische Nationalbank, and the Austrian Science Fund.