Supplementary Material for: Predicting Survival of Patients with Amyotrophic Lateral Sclerosis at Presentation: A 15-Year Experience

<b><i>Objective:</i></b> To describe the clinical features at first evaluation that best predict survival of the amyotrophic lateral sclerosis (ALS) population from the Salpêtrière Hospital between 1995 and 2009. <b><i>Methods:</i></b> Data are collected and entered into a clinical database from all patients seen at the Paris ALS Center. Variables analyzed were demographic and baseline information, strength testing (manual muscle testing; 1995-2009), the revised ALS Functional Rating Scale (ALSFRS-R; 2002-2009) and survival status. The χ² test and ANOVA assessed differences in variables by region and across time period. Univariate and multivariate Cox proportional hazards models determined which variables best predicted survival. Flexible modeling of continuous predictors (splines) assessed trends in survival for different variables. <b><i>Results:</i></b> 3,885 patients with ALS were seen in 1995-2009, of whom 2,037 had ALSFRS-R scores. Age, weight, strength, and site of onset varied by region of residence. The proportion of patients living outside Paris, the time to first visit, patient age, and motor function differed across time periods. In Cox models, site of onset, time to first visit greater than 18 months, strength and the year of visit after 2006 predicted survival (all p values &lt;0.0001). Compared to patients first seen between 1999 and 2002, the hazard ratio of death was 1.04 (95% CI = 0.95-1.14) for 2003-2006, and 0.76 (95% CI = 0.66-0.87) after 2006, while adjusting for other predictors of survival. The use of noninvasive ventilation increased during 2004-2008 from 16 to 51% of patients. <b><i>Conclusions:</i></b> Older age, bulbar onset, shorter delay to first visit and poor motor function at first visit predicted shorter survival rates in this large center-based sample from France, showing marked consistency across time and region of residence. Survival improved after 2006, concurrent with increasing rates of noninvasive ventilation use. Clinicopathologic correlation could better define subgroups, but identification of etiologies may be needed to elucidate individual forms of ALS with unique survival patterns.

**研究目标：** 描述1995年至2009年间来自法国萨尔皮特里耶医院的肌萎缩侧索硬化症（amyotrophic lateral sclerosis, ALS）患者队列在首次评估时的临床特征，以筛选出可最优预测患者生存结局的指标。**研究方法：** 研究对象为巴黎ALS中心接诊的全部患者，相关数据被收集并录入临床数据库。本次分析纳入的变量包括人口统计学与基线信息、肌力检测（徒手肌力检查；1995-2009年）、修订版ALS功能评定量表（revised ALS Functional Rating Scale, ALSFRS-R；2002-2009年）评分以及生存状态。采用卡方检验与方差分析，评估不同地区与不同时间段间各变量的组间差异；采用单因素及多因素Cox比例风险回归模型，筛选可最优预测患者生存结局的变量；采用连续预测变量的灵活建模方法（样条函数），分析不同变量对应的生存趋势。**研究结果：** 1995-2009年间，本中心共接诊3885例ALS患者，其中2037例拥有ALSFRS-R评分。患者的年龄、体重、肌力以及起病部位因居住地区不同而存在差异；居住在巴黎以外地区的患者占比、首次就诊延迟时间、患者年龄及运动功能均随研究时间段不同而存在显著差异。Cox回归分析结果显示，起病部位、首次就诊延迟时长超过18个月、肌力水平以及2006年后的就诊年份均可预测患者生存结局（所有P值均<0.0001）。以1999-2002年首诊的患者为参照，在校正其他生存预测变量后，2003-2006年首诊患者的死亡风险比为1.04（95%置信区间：0.95~1.14），2006年后首诊患者的死亡风险比为0.76（95%置信区间：0.66~0.87）。2004-2008年间，无创通气的临床使用率从16%上升至51%。**研究结论：** 在本项来自法国大型医学中心的队列研究中，高龄、球部起病、首次就诊延迟时长较短以及首诊时运动功能较差均为患者生存时长缩短的独立预测因素，且上述关联在不同研究时间段与不同居住地区间均保持显著一致性。2006年后患者生存结局得到改善，这与同期无创通气使用率的升高相契合。未来可通过临床病理相关性分析进一步明确ALS的亚群特征，但仍需明确具体病因以阐明具有独特生存模式的ALS亚型发病机制。