Neurofilament Light Chain Levels, Skeletal Muscle Loss, and Nutritional Decline: Key Prognostic Factors in Amyotrophic Lateral Sclerosis

Abstract

Introduction/aims: Hypermetabolism and weight loss are established negative prognostic factors in amyotrophic lateral sclerosis (ALS). However, the role of individualized body composition parameters in predicting ALS progression has been underexplored. This study aimed to investigate the correlation between nutritional parameters, neurofilament light chain (NfL) levels, and disease progression in ALS patients.

Methods: The Global Leadership Initiative on Malnutrition criteria were used to define malnutrition in this study. Nutritional status was assessed using body mass index and bioelectrical impedance analysis. The rate of disease progression was defined by the change in the Revised ALS Functional Rating Scale score (ΔFRS). NfL was quantified using single molecule array technology. Spearman's analyses were used to assess correlations.

Results: Sixty of 110 ALS patients were classified as malnourished. There was a strong positive correlation between NfL and ΔFRS (r = 0.71), and a moderate negative correlation with disease duration (r = -0.55). The correlations between NfL and body composition parameters were statistically significant, although weak. NfL levels were significantly higher in fast progressors (p < 0.0001 compared to slow progressors) and in malnourished patients (p = 0.0001). Of the 34 fast progressor patients, 28 (82%) exhibited some degree of malnutrition.

Discussion: Our findings indicate that poor nutritional status, particularly reduced skeletal muscle mass-both independently and in combination with fat mass loss-is associated with elevated NfL levels and faster ALS progression. NfL, combined with nutritional parameters, could serve as a valuable biomarker for disease severity. Further research is warranted to clarify the role of skeletal muscle abnormalities in ALS progression.

Keywords: amyotrophic lateral sclerosis; malnutrition; neurofilament light chain; rehabilitation; sarcopenia.

FIGURE 1

(A) ALS patients were stratified according to the rate of disease progression as explained in the Section 2. Median values and interquartile ranges are shown in the violin plots. The nonparametric Kruskal–Wallis test was performed to compare NfL data. (B) ALS patients were stratified based on nutritional status according to GLIM criteria: No malnutrition vs. any degree of malnutrition. Median values and interquartile ranges are shown in the violin plots. The nonparametric Mann–Whitney test was used to compare NfL data.

FIGURE 2

A scatter graph shows the positive association between the rate of disease progression (ΔFRS) and the levels of NfL. Red squares represent the patients with malnutrition while green circles represent the not malnourished patients. A discontinuous line intercepting y‐axis at y = 1 marks the fast progressors patients (ΔFRS ≥ 1 points/month).