Energy Expenditure and Brown Adipose Tissue in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder involving motor neurons of the cerebral cortex, brain stem and spinal cord. Motor neuron loss results in rapidly progressive muscle paralysis, usually leading to death from respiratory failure in 3-5 years.

Weight loss is a frequent phenomenon and an independent negative prognostic factor for survival in ALS. Involvement of bulbar muscles with dysphagia is likely to lead to decrease in energy intake resulting in negative energy balance. However, weight loss also occurs in non-dysphagic patients, and is not restricted to reduction in skeletal muscle mass but also involves fat mass reduction.

Hypermetabolism (i.e. elevation of resting energy expenditure, REE) have been reported in ALS in about 50% of ALS patients but the origin of this hypermetabolism remains unknown. Increase of REE seems paradoxical in the context of ALS because skeletal muscle mass, which accounts for a large proportion of energy consumption and heat production, is decreased in ALS patients. Brown adipose tissue (BAT) is another important organ for basal and inducible energy expenditure and thermogenesis. In humans, BAT is primarily found in infants and young children, and healthy adults has long been considered as almost devoid of functional BAT. However, a recent study using 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic (PET) scan showed that depots of functional BAT were present in about 5% of adult humans, most commonly localized in the cervical-supraclavicular region. In an autopsy series, depots of BAT in the periadrenal region were found in 19/20 ALS patients. It has been estimated that, if present, 50 g of maximally stimulated brown tissue could represent up to 20% of REE expenditure in an adult human. The presence of substantial, functional, depots of BAT could thus participate in the increase of REE observed in ALS patients.

The primary objective of this study is to identify and quantify potential depots of functional BAT in ALS patients. Secondary objectives will be to correlate amount of detectable BAT with measured REE, clinical parameters evaluating ALS progression and biological parameters.

This study will include 5 patients referred to the Paris ALS center with a diagnosis of ALS and "unexplained" (i.e. not explained by severe dysphagia) loss of 5 percent or more of normal body weight in the last 6 months. 5 ALS patients without significant weight loss will also be included in the study as controls.