Clinical features and autonomic testing predict survival in multiple system atrophy
Clinical features and autonomic testing predict survival in multiple system atrophy
复制标题
DOI：
10.1093/brain/awv274
复制
发表时间：
2015-12-01
期刊：
影响因子：
14.5
通讯作者：
Singer, Wolfgang
中科院分区：
文献类型：
--
作者：
Coon, Elizabeth A.;Sletten, David M.;Singer, Wolfgang
多系统萎缩的特征是自主神经功能衰竭沿着帕金森综合征和/或小脑共济失调的运动症状。关于某些临床特征的影响，包括运动亚型（多系统萎缩-帕金森综合征与多系统萎缩-小脑共济失调）、发病年龄、性别和早期自主神经症状对多系统萎缩患者生存率的影响，有不同的报告。我们试图评估一个大型多系统萎缩患者队列的总生存率和生存预测因素，这些患者来自一个转诊中心，该中心常规进行客观自主神经测试。对1998年1月至2012年12月期间在罗切斯特的马约诊所评价并使用自主神经反射屏幕评估的所有多系统萎缩病例进行了回顾性审查。共确定了685例患者; 594例符合可能的多系统萎缩标准，91例符合可能的多系统萎缩标准。多系统萎缩-帕金森综合征是430例患者（63%）的主要亚型。多系统萎缩-小脑性共济失调的平均发病年龄（58.4岁）早于多系统萎缩-帕金森综合征（62.3岁; P < 0.001）。从症状发作到死亡的中位病程为7.51年（95%置信区间7.18-7.78），而从诊断到死亡的时间为3.33年（95%置信区间2.92-3.59）。多系统萎缩的运动亚型之间的生存率没有差异（P = 0.232）。最初的运动症状是最常见的（61%），其次是自主神经发作（28%）和运动和自主神经症状的组合（11%）。运动或自主神经症状的初始发作不影响生存时间。然而，一些临床和自主实验室功能预测不利的生存在一个单变量分析。多变量模型保留了以下不利的生存预测因素：（i）发病3年内的福尔斯（风险比2.31，P < 0.0001）;（ii）膀胱症状（危险比1.96，P < 0.0001）;（iii）症状发作3年内进行过导尿（风险比1.67，P < 0.003）;（iv）症状发作1年内的立位不耐受（风险比1.28，P < 0.014）;（v）发病年龄较大（危险比1.02，P = 0.001）;和（vi）通过有效的复合自主神经严重性评分测量的自主神经衰竭程度（危险比1.07，P < 0.0023）。我们的结论是，仔细选择的临床特征可以用来预测多系统萎缩患者的生存率。自主神经功能测试增加了一个额外的，独立的生存预测因子，证明其价值不仅在多系统萎缩的诊断，而且作为预后指标。
Multiple system atrophy is characterized by autonomic failure along with motor symptoms of parkinsonism and/or cerebellar ataxia. There are differing reports on the influence of certain clinical features, including motor subtype (multiple system atrophy-parkinsonism versus multiple system atrophy-cerebellar ataxia), age of onset, gender, and early autonomic symptoms, on the survival in patients with multiple system atrophy. We sought to evaluate overall survival and predictors of survival in a large cohort of patients with multiple system atrophy seen at a single referral centre where objective autonomic testing is routinely performed for this indication. All cases of multiple system atrophy evaluated at Mayo Clinic, Rochester and assessed with an autonomic reflex screen between January 1998 and December 2012 were retrospectively reviewed. A total of 685 patients were identified; 594 met criteria for probable multiple system atrophy, and 91 for possible multiple system atrophy. Multiple system atrophy-parkinsonism was the predominant subtype in 430 patients (63%). Average age of onset was earlier in multiple system atrophy-cerebellar ataxia (58.4 years) compared to multiple system atrophy-parkinsonism (62.3 years; P < 0.001). Median disease duration from symptom onset to death was 7.51 years (95% confidence interval 7.18-7.78) while time from diagnosis to death was 3.33 years (95% confidence interval 2.92-3.59). There was no difference in survival between motor subtypes of multiple system atrophy (P = 0.232). An initial motor symptom was most common (61%) followed by autonomic onset (28%) and combined motor and autonomic symptoms (11%). The initial onset of either motor or autonomic symptoms did not influence length of survival. However, a number of clinical and autonomic laboratory features predicted unfavourable survival in a univariate analysis. A multivariate model retained the following unfavourable predictors of survival: (i) falls within 3 years of onset (hazard ratio 2.31, P < 0.0001); (ii) bladder symptoms (hazard ratio 1.96, P < 0.0001); (iii) urinary catheterization within 3 years of symptom onset (hazard ratio 1.67, P < 0.003); (iv) orthostatic intolerance within 1 year of symptom onset (hazard ratio 1.28, P < 0.014); (v) older age of onset (hazard ratio 1.02, P = 0.001); and (vi) degree of autonomic failure as measured by a validated composite autonomic severity score (hazard ratio 1.07, P < 0.0023). We conclude that carefully selected clinical features can be used to predict survival in patients with multiple system atrophy. Autonomic testing adds an additional, independent predictor of survival, demonstrating its value not only in the diagnosis of multiple system atrophy but also as prognostic marker.