Muscle Status and ALS Survival

This briefing examines whether nutritional and muscle-status measures tracked mortality and survival in adults with amyotrophic lateral sclerosis (ALS). The study focused on body composition, muscle strength, physical performance, and sarcopenia rather than on an intervention. Its results therefore describe prognostic associations within the enrolled cohort, not effects of changing nutrition, muscle mass, or clinical management. pmid:42717824

Evidence

Investigators conducted a prospective observational cohort study among 42 adults diagnosed with ALS who attended a nutrition consultation within the multidisciplinary ALS team at San Cecilio University Hospital in Granada between March 2023 and May 2025. ALS diagnoses were based on El Escorial criteria, and people with neurodegenerative diseases other than ALS were excluded. This was a clinically selected nutrition-consultation cohort, so the population was not described as all people with ALS in the surrounding community or across multiple centres. pmid:42717824

The assessment combined several nutrition- and muscle-related domains. Sarcopenia was defined with European Working Group on Sarcopenia in Older People 2 criteria, while malnutrition was assessed with Global Leadership Initiative on Malnutrition criteria. Muscle status included bioelectrical impedance vector analysis-derived parameters and muscle ultrasound, alongside handgrip strength and physical performance assessed by the Short Physical Performance Battery. The investigators compared survivors with nonsurvivors, then used logistic regression, receiver operating characteristic curve analysis, Kaplan–Meier survival analysis, and Cox proportional hazards regression to examine relationships with mortality or survival. pmid:42717824

The reported group pattern separated muscle-related measures from body mass index. Survivors had higher appendicular skeletal muscle mass index, body cellular mass index, and handgrip strength than nonsurvivors, whereas body mass index did not differ between the two groups. Sarcopenia was more prevalent among nonsurvivors than survivors. Baseline malnutrition prevalence was also described as comparable between survival groups. These comparisons show that, in this cohort, conventional body mass index did not mirror the observed survivor–nonsurvivor differences in several muscle-status measures. pmid:42717824

Appendicular skeletal muscle mass index had the highest reported discriminative ability of the three evaluated measures for predicting survival: area under the curve 0.81, 95% confidence interval 0.67–0.95, using a cut-off of 6.74 with sensitivity 0.88 and specificity 0.65. The corresponding analysis evaluated discrimination in this ALS cohort; it did not establish that the cut-off is valid in other ALS populations or that classification using it changes outcomes. pmid:42717824

In regression analyses, higher bioelectrical impedance vector analysis-derived muscle mass parameters and higher handgrip strength were associated with lower odds of mortality in univariate models, while the Short Physical Performance Battery was not associated with survival. Appendicular skeletal muscle mass index remained associated with mortality in models adjusted for age, revised Amyotrophic Lateral Sclerosis Functional Rating Scale score, and onset type. However, in the model adjusted for age, revised Amyotrophic Lateral Sclerosis Functional Rating Scale score, onset type, and disease duration, the association was not statistically significant: odds ratio 0.42, 95% confidence interval 0.13–1.10, p = 0.093. pmid:42717824

The survival analyses also reported longer survival associated with higher appendicular skeletal muscle mass index, body cellular mass index, and handgrip strength, while sarcopenia was associated with higher mortality risk. The paper characterized appendicular skeletal muscle mass index as the strongest of the tested muscle-related discriminators and described sarcopenia as identifying a higher-risk subgroup. Those statements remain specific to the measurements, definitions, follow-up, and selection process used in this single ALS nutrition-consultation cohort. pmid:42717824

Analysis — Prognostic association

The central observed pattern is that measures intended to capture muscle quantity or function distinguished survival groups more clearly than body mass index in this cohort. The multimodal approach is a strength for description: it did not treat nutrition as a single anthropometric value, and it paired bioelectrical impedance vector analysis-derived measures with ultrasound, handgrip strength, physical performance, and formal sarcopenia criteria. The comparison between survivors and nonsurvivors, followed by regression and time-to-event analyses, also provides converging association-focused analyses rather than a single unadjusted comparison. pmid:42717824

Interpretation should nevertheless center on attenuation after adjustment. Appendicular skeletal muscle mass index was associated with mortality in several adjusted models, but the fully adjusted model that included disease duration did not reach statistical significance. This pattern is consistent with a prognostic association that may overlap with disease duration, functional status, age, or onset type; the reported design cannot determine how those characteristics relate causally to muscle status and mortality. The receiver operating characteristic result describes discrimination within the observed cohort, not an established prognostic tool. Statistical significance in selected models and discrimination in this sample are not measures of clinical significance. pmid:42717824

Limitations

The retrospective design cannot establish causation. More specifically, although the study was prospective in cohort follow-up, it was observational and compared naturally occurring survivor and nonsurvivor groups rather than randomly assigning an exposure. Selection bias is plausible because enrollment was limited to adults with ALS attending nutrition consultation at one multidisciplinary unit; their disease status, referral patterns, and nutritional concerns may differ from those of people with ALS who were not seen in that setting. The measured outcomes were mortality and survival associations, not patient benefit from a nutritional or muscle-directed strategy. pmid:42717824

Muscle mass was estimated with predictive equations that were not specifically developed or validated in ALS populations, which may limit estimation accuracy in neurodegenerative disease with altered body composition. The small, single-centre cohort also constrains precision and generalizability, and the fully adjusted appendicular skeletal muscle mass index estimate included a confidence interval spanning the null. The reported receiver operating characteristic cut-off and performance characteristics consequently require external evaluation before being treated as transportable beyond the studied cohort. pmid:42717824