Sex-associated differences in routine inflammatory markers and neuromuscular ultrasound measurements in amyotrophic lateral sclerosis: a retrospective cross-sectional study

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with substantial clinical heterogeneity. Systemic inflammatory markers and neuromuscular ultrasound measurements have both been studied in ALS, but their sex-associated differences within ALS cohorts remain incompletely characterized. OBJECTIVE: To examine sex-associated differences in routine inflammatory markers and neuromuscular ultrasound measurements in patients with ALS, and to determine whether these differences persisted after adjustment for available clinical and anthropometric variables. METHODS: In this retrospective cross-sectional study, 135 patients with ALS were included. Routine inflammatory markers, including neutrophils, monocytes, lymphocytes, platelets, and erythrocyte sedimentation rate (ESR), were analyzed alongside quantitative neuromuscular ultrasound measurements. Between-sex comparisons were performed, and false discovery rate correction was applied to account for multiple testing. Multivariable linear regression analyses were performed with adjustment for age, disease duration, body mass index (BMI), ALSFRS-R total score, FVC% predicted, smoking status, hypertension, and diabetes. RESULTS: Female patients showed lower ALSFRS-R total scores and higher estimated progression rates in unadjusted comparisons, whereas pulmonary function variables did not differ significantly between sexes. After FDR correction, estimated progression rate, neutrophil count, monocyte count, ESR, and masseter muscle thickness remained significantly different between sexes, while the ALSFRS-R difference was borderline significant. In fully adjusted models, female sex was associated with lower neutrophil count, monocyte count, and median nerve cross-sectional area; biceps brachii thickness showed a less stable association after sensitivity analysis. An exploratory secondary analysis showed lower rectus femoris cross-sectional area during thigh-lift in female patients after full adjustment. In the spline sensitivity analysis, this association remained statistically significant but was interpreted cautiously because it was not present in the earlier adjustment models. CONCLUSIONS: Selected routine inflammatory markers and neuromuscular ultrasound measurements differed between male and female patients within this ALS cohort. These findings support consideration of sex and anthropometric context, including body size, when interpreting inflammatory markers and ultrasound-based structural measurements. In the absence of healthy controls, the observed ultrasound differences cannot be attributed specifically to ALS-related biology. Studies with healthy controls, longitudinal functional outcomes, body-composition assessment, and independent multicenter cohorts are needed to clarify the disease-specific and prognostic relevance of these observations.