Metabolic Alterations in Patients with Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurological condition which affects motor neurons are. These are present in the central and the peripheral nervous systems. In ALS, both systems are affected. When only the peripheral nervous system is affected, we refer to the condition, progressive spinal muscular atrophy (PMA). When only the central nervous system is affected, we refer to the disease, primary lateral sclerosis (PLS). The three conditions together are called the motor neuron diseases (MND). As motor neurons control the muscles, their degeneration results in weakness in bulbar and/or spinal muscles. Eventually, the respiratory muscles become affected, causing patients to develop progressive respiratory symptoms which, in turn, result in death. ALS would appear to be caused by a variety of pathophysiological mechanisms. There is evidence of a disturbed metabolic state in patients with ALS, giving rise to the metabolic hypothesis. Previous researches have shown that metabolic changes may result in different disease courses. The metabolism may be disrupted due to 1) an altered and insufficient intake of a patient, for example due to swallowing difficulties, and/or 2) changes in the metabolic state. Changes in the metabolic state have been found on a cellular level – including motor neurons – in some patients with ALS; in turn, these may result in a general disruption of metabolism. Whether this is a cause or consequence of the disease is not known. However, in either situation, the metabolic state might function as a biomarker for disease progression. An altered metabolism can result in various disturbed processes, for which there are a variety of biomarkers, including cholesterol, body weight and the individual components of body weight: fat-free mass and fat mass. In addition, the measurement of the metabolic state itself might serve as a potential biomarker. Although determining the metabolic state may be challenging, previous studies have demonstrated its importance; A subgroup of patients with ALS do have an increased metabolic state – also known as hypermetabolism – which has proved to result in a shorter survival. Therefore, it is important to apply a uniform method when determining the metabolic state and the metabolic biomarkers in the attempts to predict the disease course and prognosis. This could inform better counselling of patients and their relatives regarding disease course and survival. This dissertation focusses on metabolic changes in ALS, the prognostic value of various metabolic biomarkers and, moreover, on fat-free mass. We 1) compare different techniques for measuring fat-free mass and 2) assess the effect of several formulae on the determining resting energy expenditure. These results were used to investigate the metabolic state of the patients by determining the metabolic index. We found that hypermetabolism is not a specific phenomenon in ALS. This dissertation supports the need for further (longitudinal) studies to gain clarity on changes in fat-free mass and metabolic state during the disease course. Moreover, the effect of specific therapies on maintaining fat-free mass and/or altering the metabolic index and, subsequently, determine their prognostic value is worthwhile, as shown in this dissertation.