肌萎缩侧索硬化患者体重指数(BMI)与临床预后相关性的研究

研究背景：肌萎缩侧索硬化(Amyotrophic Lateral Sclerosis，ALS)是一种进行性的、同时累及上、下运动神经元的神经系统变性疾病，尚无特效治疗而且临床预后差。近年研究报道ALS患者常见营养不良、体重下降，并提出体重指数(Body mass index，BMI)可作为ALS患者的预后指标。关于ALS患者BMI与临床预后的关系结论不一，目前基于中国人群的ALS患者BMI评估和预后研究相对不足。
研究目的：本研究旨在通过对北京协和医院就诊的ALS患者统计分析，明确ALS患者病程早期的BMI特点、与其他临床资料的关系，并探索BMI对ALS患者生存预后的影响。
研究方法：本研究对2013年1月至2019年6月在北京协和医院神经内科就诊的ALS患者进行回顾性分析。记录所有患者的身高、起病前和基线体重，计算起病前和基线BMI，并定义ABMI=基线BMI一起病前BMI，BMI变化率(Rate ofBMI change，BMI．R)=(基线BMI一起病前BMI)÷从起病到基线时间间隔(年)。采集患者的性别、起病年龄、诊断延迟时间、诊断分级、起病部位、改良肌萎缩侧索硬化功能评分(Revised Amyotrophic Lateral Sclerosis Functional Rating Scale，ALSFRS．R)、呼吸功能评分(ALSFRS．R．respiratory function，ALSFRS．R．R)、疾病进展率(AALSFRS-R)等基线资料，每半年至一年随访，记录患者的生存状态(存活、死亡／气管切开、失访)及力如太治疗情况等信息。分别采用Kaplan．Meier分析法和Cox比例风险回归模型进行单因素和多因素生存分析。
研究结果：本研究一共纳入615例ALS患者，起病前BMI 24．11±3．05 kg／m2，基线BMI23．08±3．30埏／m2，二者存在显著性差异(P<O．001)。基线低体重患者44例(7．2％)、正常体重331例(53．8％)、超重196例(31．8％)、肥胖44例(7．2％)。231例(37．6％)患者BMI较起病前减低(ABMI S．1 kg／m2)，其中208例(33．8％)患者为快速减
低(BMI．R S．1 kg／m2／年)。BMI减低与球部起病、诊断延迟时间短、疾病快速进展相关。至最后一次随访，死亡或气管切开人数264人，占42．9％，死亡患者中位生存期29．8个月。预期中位生存期48．6(95％CI：44．2．53．0)个月，3年生存率66％，5年生存率27％。单因素生存分析中，起病年龄、诊断延迟时间、诊断分级、ABMI、BMI-R、ALSFRS—R、ALSFRS．R．R和疾病进展率对ALS患者的临床预后有显著影响(P<O．05)，进一步多因素Cox回归分析显示，BMI减低>1 kg／m2／年的患者死亡风险是BMI减低S l kg／m2／年患者的1．9倍(P<0．001)，起病年龄晚、诊断延迟时间短、诊断分级较高、疾病快速进展、基线BMI快速减低是影响ALS患者生存的独立危险因素(P<0．05)。
结论：相当一部分ALS患者在病程早期即出现BMI显著减低，这与球部起病、诊断延迟时间短、疾病快速进展相关。基线BMI变化率是ALS患者预后的独立影响因素，基线BMI快速减低提示更高的死亡风险。

Research Background: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects both upper and lower motor neurons, with no effective treatment and poor clinical prognosis. Recent studies have reported that malnutrition and weight loss are common in ALS patients, and it has been proposed that Body Mass Index (BMI) could serve as a prognostic indicator for ALS patients. However, conclusions on the association between BMI and clinical prognosis in ALS patients remain inconsistent, and studies on BMI assessment and prognosis of ALS patients in the Chinese population are relatively scarce to date.

Research Objective: This study aimed to conduct a statistical analysis of ALS patients treated at Peking Union Medical College Hospital, to clarify the characteristics of BMI in the early course of ALS, their association with other clinical data, and to explore the impact of BMI on the survival prognosis of ALS patients.

Research Methods: This study performed a retrospective analysis of ALS patients who visited the Department of Neurology of Peking Union Medical College Hospital from January 2013 to June 2019. Height, pre-onset and baseline body weight of all patients were recorded, and pre-onset and baseline BMI were calculated. We defined ΔBMI = baseline BMI − pre-onset BMI, and the rate of BMI change (BMI-R) = (baseline BMI − pre-onset BMI) ÷ time interval from onset to baseline (in years). Baseline data including gender, age at onset, diagnostic delay time, diagnostic grade, onset site, Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), respiratory function score of ALSFRS-R (ALSFRS-R-R), and disease progression rate (ΔALSFRS-R) were collected. Follow-ups were conducted every 6 months to 1 year, and information such as patient survival status (alive, dead/tracheotomy, lost to follow-up) and riluzole treatment was recorded. Univariate and multivariate survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards regression model, respectively.

Research Results: A total of 615 ALS patients were included in this study. The pre-onset BMI was 24.11±3.05 kg/m², and the baseline BMI was 23.08±3.30 kg/m², with a significant difference between the two (P<0.001). There were 44 patients (7.2%) with underweight at baseline, 331 (53.8%) with normal weight, 196 (31.8%) with overweight, and 44 (7.2%) with obesity. A total of 231 patients (37.6%) had reduced BMI compared to pre-onset levels (ΔBMI ≤ -1 kg/m²), among which 208 patients (33.8%) had rapid BMI reduction (BMI-R ≤ -1 kg/m²/year). Reduced BMI was associated with bulbar onset, shorter diagnostic delay, and rapid disease progression. As of the last follow-up, 264 patients (42.9%) died or underwent tracheotomy, with a median survival time of 29.8 months for deceased patients. The expected median survival time was 48.6 (95% CI: 44.2–53.0) months, with a 3-year survival rate of 66% and a 5-year survival rate of 27%. Univariate survival analysis showed that age at onset, diagnostic delay time, diagnostic grade, ΔBMI, BMI-R, ALSFRS-R, ALSFRS-R-R, and disease progression rate had significant effects on the clinical prognosis of ALS patients (P<0.05). Further multivariate Cox regression analysis revealed that patients with BMI reduction > -1 kg/m²/year had a 1.9-fold higher risk of death than those with BMI reduction ≤ -1 kg/m²/year (P<0.001). Older age at onset, shorter diagnostic delay, higher diagnostic grade, rapid disease progression, and rapid baseline BMI reduction were independent risk factors affecting the survival of ALS patients (P<0.05).

Conclusion: A considerable proportion of ALS patients exhibit significant BMI reduction in the early course of the disease, which is associated with bulbar onset, shorter diagnostic delay, and rapid disease progression. The rate of baseline BMI change is an independent prognostic factor for ALS patients, and rapid reduction in baseline BMI indicates a higher risk of death.