Low muscle mass may help predict survival in people with ALS

Low muscle mass in the arms and legs, as well as sarcopenia (low muscle mass and strength), were each linked to poorer survival in people with amyotrophic lateral sclerosis (ALS), a small prospective study in Spain found.

“These findings suggest that muscle mass may provide prognostic information complementary to conventional clinical markers,” the researchers wrote.

The study, “Appendicular Skeletal Muscle Mass and Sarcopenia as Prognostic Markers in Amyotrophic Lateral Sclerosis,” was published in the Journal of Cachexia, Sarcopenia and Muscle.

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ALS is caused by the loss of motor neurons — the nerve cells that control movement — leading to muscle wasting and weakness that gradually worsens. Disease progression and survival vary widely, and established factors such as age at onset, symptom location, breathing problems, and functional status only partly explain this variability.

Previous ALS studies have associated muscle wasting and weight loss with faster disease progression and shorter survival. Muscle mass, muscle strength, and function can provide complementary information about muscle health, but their combined value for predicting survival in people with ALS has not been well established.

“Although previous studies support the prognostic relevance of muscle loss in ALS, the clinical utility of an integrated and feasible … assessment combining muscle mass, muscle strength, and sarcopenia has not been sufficiently explored,” the researchers wrote. In this study, sarcopenia was defined as both low muscle strength and low muscle mass.

To learn more, a team of researchers prospectively followed 42 adults with ALS who attended a nutrition consultation at the ALS multidisciplinary unit of San Cecilio University Hospital in Granada, Spain, between 2023 and 2025.

Participants had a mean age of 66.1 years, and most were men (64%). More than half (54%) had bulbar-onset ALS, when weakness first affects the muscles needed for swallowing, chewing, and speaking.

Survivors had more muscle mass and strength at baseline

A total of 19 people (45%) died during the study period. Mean survival from symptom onset to death or last follow-up was 21.1 months (nearly two years).

At baseline, participants who survived had lost significantly less weight over the previous six months than those who died (3.54% vs. 9.13%) and had greater muscle mass and strength.

Specifically, survivors had significantly higher appendicular skeletal muscle mass index (ASMI), which reflects muscle mass in the arms and legs relative to height, and significantly greater handgrip strength.

Body cell mass index (BCMI), an estimate of metabolically active body tissue relative to height, was also significantly higher among survivors.

The survivor group was also significantly less likely to have sarcopenia at baseline than the nonsurvivor group (4.8% vs. 27.8%). Body mass index, a measure of nutritional status based on weight and height, and the proportion of malnourished participants were not significantly different between the groups.

“Muscle depletion may occur before substantial weight loss or overt malnutrition becomes clinically evident, suggesting that traditional nutritional markers alone may underestimate early nutritional and muscular deterioration,” the researchers wrote.

In initial statistical analyses, higher values for several measures of muscle mass, including ASMI, and greater handgrip strength were significantly associated with lower odds of death.

ASMI showed the strongest association, being linked to 71% lower odds of death. However, when the analysis was adjusted for several established ALS prognostic factors, including functional status, age, disease duration, and site of symptom onset, this association was no longer statistically significant.

ASMI showed the strongest ability to distinguish survival outcomes

The researchers also assessed how well several muscle measures could distinguish patients with different survival outcomes using the area under the curve (AUC), a statistical measure of how well a test distinguishes between two groups. AUC scores range from zero to one, with higher scores indicating better discrimination.

ASMI had the highest AUC, at 0.81, compared with 0.70 for BCMI and 0.71 for handgrip strength, suggesting ASMI had the best ability of the three measures to distinguish patients with different survival outcomes.

The team also identified cut-off values for several muscle measures that could help predict survival. After adjusting for age and functional status, ASMI below the cut-off was associated with about five times the risk of death, while BCMI below the cut-off was associated with more than three times the risk. Sarcopenia was associated with about 17 times the risk of death.

“ASMI appears to be a relevant prognostic factor in patients with ALS, while sarcopenia identifies a subgroup at higher risk of mortality,” the researchers wrote. These factors may “also have value as enrichment or stratification tools in future ALS clinical trials by helping to identify patients with distinct prognostic profiles.”

Among the study’s limitations, the researchers noted its small sample size and single-center design, which limit the precision and generalizability of the findings. Also, information on nutritional interventions and ALS treatments was not systematically available and could have affected muscle preservation and survival.

Finally, the team called for larger prospective studies to confirm these findings, noting that the observational design does not allow conclusions about whether muscle-related factors cause poorer survival.