Progression in ALS is not linear but is curvilinear
Progression in ALS is not linear but is curvilinear
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DOI：
10.1007/s00415-010-5609-1
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发表时间：
2010-10-01
影响因子：
6
通讯作者：
Meininger, Vincent
中科院分区：
文献类型：
--
作者：
Gordon, Paul H.;Cheng, Bin;Meininger, Vincent
该研究的目的是确定 ALS 进展曲线的形状，评估临床变量对进展率的影响，并评估功能衰退与生存之间的关联。前瞻性地收集了 2002 年至 2008 年在巴黎 Hpital de la SalptriSre SLA 中心就诊的所有患者的数据，并将其输入临床数据库。分析的变量包括人口统计和基线信息、ALS 功能评定量表 (ALSFRS-R)、力量测试 (MMT) 和生存率。广义加性混合模型描述了 ALSFRS-R 和 MMT 分数随时间的变化。线性混合效应评估了人口统计和临床指标对进展率的影响，Cox 模型检查了它们对生存的影响。在 2,452 名已确诊的 ALS 患者中，1,884 名有足够的数据可供分析。 ALSFRS-R和MMT呈曲线下降；二次拟合描述了趋势，但线性拟合则没有。 ALSFRS-R 总评分与发病年龄呈负相关 (p < 0.001)，与基线 ALSFRS-R (p < 0.001) 以及更严重的延髓特征 (p < 0.001) 呈正相关。 ALSFRS-R 和 MMT 下降率较高、发病年龄和延髓发病年龄较大预示生存期较短。 ALS 的恶化是非线性的。疾病的早期和晚期阶段显示出最快的下降速度。年龄较大和延髓体征与更急剧的衰退有关，并且随着初始衰退速度更快，但与当前的功能状态无关，也可以预测生存。
The aim of the study is to determine the shape of the progression curve in ALS, assess the impact of clinical variables on the rate of progression, and evaluate the association between functional decline and survival. Data were prospectively collected and entered into a clinical database from all patients seen in 2002-2008 at the Centre SLA, Hpital de la SalptriSre, Paris. Variables analyzed were demographic and baseline information, the ALS functional rating scale (ALSFRS-R), strength testing (MMT), and survival. Generalized additive mixed models characterized changes in ALSFRS-R and MMT scores over time. Linear mixed effects assessed the impact of demographic and clinical measures on rate of progression and Cox models examined their effect on survival. Of 2,452 patients with ALS identified, 1,884 had adequate data for analysis. The ALSFRS-R and MMT declined in a curvilinear way; a quadratic fit described the trends but a linear fit did not. The total ALSFRS-R score was negatively associated with age-of-onset (p < 0.001), and positively associated with baseline ALSFRS-R (p < 0.001) as well as more severe bulbar features (p < 0.001). Higher rate of decline in ALSFRS-R and MMT, older age-at-onset and bulbar-onset predicted shorter survival. Deterioration in ALS is non-linear. The early and late phases of the illness show the most rapid rates of decline. Older age and bulbar signs are associated with a steeper decline, and along with more rapid initial rate of decline, but not current functional status, also predict survival.