Hypermetabolism is a deleterious prognostic factor in patients with amyotrophic lateral sclerosis

Abstract

Background and purpose: The aim of this study was to investigate patients with amyotrophic lateral sclerosis in order to determine their nutritional, neurological and respiratory parameters, and survival according to metabolic level. Methods: Nutritional assessment included resting energy expenditure (REE) measured by indirect calorimetry [hypermetabolism if REE variation (DREE) > 10%] and fat mass (FM) using impedancemetry. Neurological assessment included the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score. Survival analysis used the Kaplan-Meier method and multivariate Cox model. Results: A total of 315 patients were analysed. Median age at diagnosis was 65.9 years and 55.2% of patients were hypermetabolic. With regard to the metabolic level (DREE: < 10%, 10-20% and >20%), patients with DREE > 20% initially had a lower FM (29.7% vs. 32.1% in those with DREE ≤10%; P = 0.0054). During follow-up, the median slope of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised tended to worsen more in patients with DREE > 20% (À1.4 vs. À1.0 points/month in those with DREE ≤10%; P = 0.07). Overall median survival since diagnosis was 18.4 months. DREE > 20% tended to increase the risk of dying compared with DREE ≤10% (hazard ratio, 1.33; P = 0.055). In multivariate analysis, an increased REE:FM ratio was independently associated with death (hazard ratio, 1.005; P = 0.001). Conclusions: Hypermetabolism is present in more than half of patients with amyotrophic lateral sclerosis. It modifies the body composition at diagnosis, and patients with hypermetabolism >20% have a worse prognosis than those without hypermetabolism.

Loss of appetite is associated with a loss of weight and fat mass in patients with amyotrophic lateral sclerosis

“…In normal physiology, whole-body energy homeostasis serves to balance the supply of energy with the use of energy and is crucial for stable body weight. In ALS, several reports of hypermetabolism (18)(19)(20)(21)(22)(23)(24)(25) have suggested that increased whole-body energy expenditure is a principal cause for weight loss. However, no study has conclusively shown that weight loss in ALS is a consequence of hypermetabolism.…”

Hypermetabolism appears to be an adverse prognostic biomarker in amyotrophic lateral sclerosis: a potential for therapeutic intervention?

“…In the current issue of the journal, Jesus et al . addressed the importance of hypermetabolism as an adverse prognostic biomarker in a large ALS cohort. The study re‐affirmed that hypermetabolism was evident in approximately 50% of ALS patients, with three prognostic groups identified based on the REE variation values (<10%, 10%–20% and >20%).…”

“…In the current issue of the journal, Jesus et al [5] addressed the importance of hypermetabolism as an adverse prognostic biomarker in a large ALS cohort.…”

Accelerated trans-sulfuration metabolically defines a discrete subclass of ALS patients

“…Overall, hypermetabolism is a feature of more than half of the ALS population and was recently shown to be a deleterious prognostic factor. Patients with hypermetabolism have a 20% worse prognosis than those that do not exhibit the hypermetabolism phenotype 30,31 . Until now, hypermetabolism in ALS has mostly been considered in relation to glucose metabolism.…”