Appendicular Skeletal Muscle Mass and Sarcopenia as Prognostic Markers in Amyotrophic Lateral Sclerosis

ABSTRACT Background Amyotrophic lateral sclerosis (ALS) is characterized by progressive muscle wasting and functional decline. Prognostic assessment in clinical practice relies largely on functional scales and traditional anthropometric measures. The prognostic relevance of muscle mass, muscle strength and sarcopenia in ALS remains incompletely defined. This study evaluated the prognostic value of muscle mass, muscle function and sarcopenia in relation to mortality in patients with ALS. Methods A prospective observational cohort study was conducted at the ALS Multidisciplinary Unit (UMELA), San Cecilio University Hospital in Granada. Sarcopenia was defined according to the European Working Group of Sarcopenia in Older People 2 (EWGSOP2) and malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Muscle status was assessed using bioelectrical impedance vector analysis (BIVA)‐derived parameters, muscle ultrasound, handgrip strength (HGS) and physical performance (SPPB). Differences between survivors and nonsurvivors were analysed and logistic regression explored potential predictors of mortality. Receiver operating characteristic (ROC) curves were constructed for significant predictors. Survival was analysed using the Kaplan–Meier and Cox proportional hazards regression. Results A total of 42 patients with ALS were included (mean age 66.1 ± 10.3 years, and 15 (36%) were female). During follow‐up (mean survival 21.1 ± 10.5 months), 45% died. Survivors showed higher appendicular skeletal muscle mass index (ASMI) (6.94 ± 0.91 vs. 5.80 ± 0.98 kg/m 2 , p = 0.001), body cellular mass index (BCMI) (8.92 ± 1.59 vs. 7.64 ± 1.87 kg/m 2 , p = 0.034) and HGS (25.45 ± 11.11 vs. 17.67 ± 8.83 kg, p = 0.032), while BMI did not differ ( p = 0.540). Sarcopenia was more prevalent in nonsurvivors (27.8% vs. 4.8%, p = 0.047). In multivariable analysis, ASMI remained associated with mortality after adjustment for age, onset type and ALSFRS‐R (OR 0.33, 95% CI 0.11–0.81, p = 0.026), but this association was not statistically significant in the fully adjusted model including disease duration ( p = 0.093). ASMI showed the highest discriminative ability (AUC 0.81), compared to BCMI (AUC 0.70) and HGS (AUC 0.71). ROC‐derived cut‐offs (ASMI 6.74 kg/m 2 ; BCMI 7.2 kg/m 2 ; HGS 21 kg) stratified survival. Higher ASMI (HR 7.53, p = 0.008), BCMI (HR 4.18, p = 0.005) and HGS (HR 4.02, p = 0.019) were associated with longer survival, whereas sarcopenia increased mortality risk (HR 15.53, p < 0.001). Conclusions Beyond BMI, skeletal muscle mass—particularly ASMI—was associated with survival in ALS. Sarcopenia identifies a subgroup of patients at particularly high risk of death. Sarcopenia assessment may improve prognostic stratification and support clinical management in ALS.