Hypermetabolism associated with worse prognosis of amyotrophic lateral sclerosis

Abstract

Background and objective: Exploration of hypermetabolism in amyotrophic lateral sclerosis (ALS) with different ethnicities is needed to understand its metabolic implications for clinical management. We aimed to evaluate the features of hypermetabolism and investigate its association with clinical characteristics and prognosis of ALS in a prospective Chinese cohort.

Methods: This prospective study was conducted at Peking University Third Hospital, China from 2017 to 2020. 343 participants were enrolled initially. After strict screening, 147 matched health controls and 93 patients with ALS were eligible and underwent detailed clinical assessments. Disease severity and progression were evaluated using recognized scales. Metabolic assessments included body composition and metabolic index (MI) [hypermetabolism if MI ≥ 120.0%]. Patients were followed up every 6 months for survival analysis.

Results: Compared with controls, hypermetabolism was significantly more prevalent in ALS (p = 0.009). MI was consistently higher in ALS than controls (p = 0.009). Further correlation analysis showed that MI significantly decreased with disease progression, as graded by King's College staging system (p < 0.001). MI was significantly correlated with fat-free mass and fat mass (p = 0.005 and 0.007). Survival analysis showed that hypermetabolism independently indicated a worse prognosis for ALS (HR = 1.020, CI = 1.004-1.036, p = 0.013).

Conclusion: A significant increase in the prevalence and degree of hypermetabolism was identified in ALS compared with strictly matched controls. Metabolic index, which is significantly associated with disease progression and body composition, is an independent prognostic indicator for a worse survival of ALS.

Keywords: Amyotrophic lateral sclerosis; Energy metabolism; Hypermetabolism; Prognosis.