Clinical Research Of The Prognostic Role Of Body Mass Index (BMI) In Amyotrophic Lateral Sclerosis Patients

Background:Amyotrophic lateral sclerosis(ALS)is a progressive degenerative disorder of the nervous system that mainly involves the upper and lower motor neurons.Patients with ALS suffer from the poor clinical prognosis without specific treatment so far.In recent years,studies have reported common malnutrition and weight loss in ALS patients,which are regarded as the result of decreased intake due to dysphagia,loss of appetite and depression together with hypermetabolism.It is proposed that body mass index(BMI)could be used as a prognostic factor for ALS patients,but the prognostic role of BMI in ALS patients remains controversial.The domestic research on the relationship between BMI and survival prognosis of ALS patients is relatively limited.Objective:The study aimed to clarify the characteristics of ALS patients’ BMI in the early stage and the association between BMI and other clinical features,and explore the impact of BMI on patients’ survival prognosis.Method:We conducted a retrospective analysis of the clinical data of ALS patients in Peking Union Medical College Hospital from January 2013 to June 2019.Height,premorbid and baseline weight of all patients were recorded at the first visit,premorbid and baseline BMI were calculated(weigh/height2).We focused on the BMI change(△BMI)from onset to the first visit using the formula:baseline BMI-premorbid BMI,and the rate of BMI change(BMI-R)using the formula:(baseline BMI-premorbid BMI)/(Interval period from onset to first visit(y)).The collection of clinical data at baseline included gender,onset age,diagnostic delay,diagnostic categories,onset site,the Revised ALS Functional Rating Scale(ALSFRS-R),ALSFRS-R-respiratory function(ALSFRS-R-R),disease progression rate(△ALSFRS-R),etc.The endpoint was defined as death or tracheotomy,all patients were followed up every half to one year for outcomes and medication of Riruzole.Kaplan-Meier survival curve and Cox proportional hazards regression model were applied to perform univariate and multivariate survival analysis.Results:A total of 615 ALS patients were enrolled in the study,premorbid BMI and baseline BMI were 24.11±3.05 kg/m2 and 23.08±3.30 kg/m2,respectively,showing a significant difference between both values(P<0.001).44 patients(7.2%)with underweight at baseline,331 patients(53.8%)with normal weight,196 patients(31.8%)with overweight,and 44 patients(7.2%)were obese.231 patients(37.6%)had a lower baseline BMI than premorbid one(△BMI≤-1 kg/m2),and 208 patients(33.8%)showed a sharp reduction(BMI-R ≤-1 kg/m2/year).The reduction of BMI was related to bulbar-onset,shorter diagnostic delay,and the rapid progression of disease.264 patients(42.9%)reached the endpoint till last follow-up with a median survival time of 29.8 months.The overall median survival length was estimated as 48.6(95%CI:44.2-53.0)months.Estimated three-year and five-year survival rate with K-M curve were 66%and 27%,respectively.In univariate survival analysis,onset age,diagnostic delay,diagnostic categories,△BMI,BMI-R,ALSFRS-R,ALSFRS-R-R and disease progression rate had a significant influence on the survival of ALS patients(P<0.05).Further Cox regression analysis showed that mortality rate in patients with a BMI reduction>1 kg/m2/year was 1.9 times of that in patients with a BMI reduction≤1 kg/m2/year(P<0.001).Late onset age,shorter diagnostic delay,higher diagnostic category,rapid disease progression and sharp reduction of BMI at baseline were independent risk factors for mortality in ALS patients(P<0.05).Conclusion:A considerable number of ALS patients had a significant decrease of BMI in the early stage,which was associated with bulbar-onset,shorter diagnostic delay,and rapid progression of disease.The rate of BMI change at baseline had a significant influence on the survival of ALS patients,sharp reduction of BMI in the early stage predicted higher risk for mortality.