OBJECTIVE The lack of prognostic biomarkers in patients with amyotrophic lateral sclerosis (ALS) induced researchers to develop clinical evaluation tools for stratification and survival prediction. We assessed the correlation between patterns of functional involvement, considered as a cumulative number of body regions involved, and overall survival in a population-based series of patients with ALS (PARALS). METHODS We derived the functional involvement of four body regions at diagnosis using ALSFRS-R subscores for bulbar, upper limbs, lower limbs and respiratory/thoracic regions. We analysed the effect of number of body regions involved (NBRI) at diagnosis on overall survival, adjusting for age at onset, sex, site of onset, diagnostic delay, forced vital capacity, body mass index, mutational status, cognition and comparing it with King's staging system. RESULTS The NBRI was strongly related to survival, with a progressive increase of death/tracheostomy risk among groups (two body regions HR=1.24, 95% CI 1.06 to 1.45, p=0007; three body regions HR=1.65, 95% CI 1.38 to 1.98, p<0.001; four body regions HR=2.68, 95% CI 2.11 to 3.39, p<0.001). Using ALSFRS-R score, the consistency between the number of regions involved and King's clinical stage at diagnosis was very high (81%). The evaluation of respiratory/thoracic region and cognition allowed to subdivide patients into different prognostic categories. Regional spreading of the disease is associated with survival, independently from the initial region involved. CONCLUSIONS The evaluation of NBRI, with the inclusion of initial respiratory/thoracic involvement and cognition, can be useful in many research fields, improving the stratification of patients. Our findings highlight the importance of the spatial spreading of functional impairment in the prediction of ALS outcome.

中文翻译：

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诊断时症状的局部扩散是肌萎缩性侧索硬化症的一种预后指标：一项基于人群的研究。

目的肌萎缩性侧索硬化症（ALS）患者缺乏预后生物标志物，促使研究人员开发出用于分层和生存预测的临床评估工具。我们评估了功能性参与模式（被视为涉及的身体区域的累积数量）与以人群为基础的一系列ALS（PARALS）患者总体生存率之间的相关性。方法我们使用ALSFRS-R分数对延髓，上肢，下肢和呼吸/胸部区域进行诊断时得出了四个身体部位的功能参与。我们分析了诊断时涉及的身体部位数量（NBRI）对总体存活率的影响，调整了发病年龄，性别，发病部位，诊断延迟，强迫肺活量，体重指数，突变状态，认知水平，并与之进行了比较。国王' 的登台系统。结果NBRI与生存密切相关，组间死亡/气管切开术风险逐渐增加（两个身体区域HR = 1.24，95％CI 1.06至1.45，p = 0007；三个身体区域HR = 1.65，95％CI 1.38至1.98，p <0.001；四个身体区域HR = 2.68，95％CI 2.11至3.39，p <0.001）。使用ALSFRS-R评分，涉及的区域数与King的临床分期之间的一致性非常高（81％）。对呼吸/胸腔区域和认知的评估可以将患者分为不同的预后类别。疾病的区域传播与生存相关，而与所涉及的初始区域无关。结论NBRI的评估，包括最初的呼吸/胸腔受累和认知，​​在许多研究领域中可能是有用的，改善患者分层。我们的发现突出了功能障碍的空间扩散在预测ALS结果中的重要性。