The role of the SenseWear device and ghrelin for metabolism in amyotrophic lateral sclerosis

Initially, pathological abnormalities in amyotrophic lateral sclerosis (ALS) were thought to be restricted to motor neurons, but in the past few years it has become apparent that also the nutritional state, energy intake and energy expenditure are altered (1–3). Metabolism and nutritional status are very important prognostic factors for survival in patients with ALS (4). However, to date it has been challenging to reliably predict energy expenditure during the disease course (5,6). The SenseWear Armband is a bracelet device to accurately measure resting energy expenditure (REE) in healthy subjects (7–9). It has been validated against the double labelled water method (dLW) (10). Ghrelin and leptin, which regulate appetite and metabolism, were recently found to have a neuroprotective effect in neurodegenerative diseases (11,12). In this study we evaluated the SenseWear armband for measuring REE, measured ghrelin, leptin and determined caloric intake and nutritional status in patients with amyotrophic lateral sclerosis (ALS). First energy expenditure (EE) and caloric intake were measured over three days in 10 healthy controls. EE over 24 h was very stable in all subjects, not exceeding 3% day-to-day variability. The main problem of this study was recruitment of patients; that patients had to move to a different building for ghrelin and leptin measurements after a regular 2-h consultation was too burdensome for most of the patients. However, in two patients (P1, P2) and their spouses (C1, C2) EE and caloric intake could be measured over 48 h twice with an interval of six months. Total ghrelin was 30% lower in ALS patients (P1, P2) compared to spouses (C1, C2) and normal values. Comparing EE between consecutive days revealed reliable measurements (P1: 2064 and 2124 kcal/day, P2: 2020 and 1969 kcal/day, C1: 1740 and 1599 kcal/day, C2: 1569 and 1422 kcal/day). Despite balanced EE and caloric intake both patients had profound weight loss over time (P1 74.5 kg vs. 68.4 kg, P2 76 kg vs. 71 kg). Both patients also had a higher EE at night six months after the first measurement (P1 744 vs. 1186, P2 854 vs. 1029). This suggests an increasing resting expenditure as the disease progresses, which is in line with other studies demonstrating hypermetabolism of the order of about 10% in ALS patients compared to a healthy population (13,14). Interestingly, ghrelin levels were lower in patients compared to control subjects and published normal values (15). Ghrelin is a hormone that leads to hunger and stimulates appetite (16). Weight loss causes a higher release of ghrelin, yet the appetite in both patients was reduced as described in other studies (17). Low ghrelin levels may also have an influence on the protection of the motor neurons. A possible effect of ghrelin on glutamate excitotoxicity has been reported earlier (12). Despite all its limitations this study supports the hypothesis that ghrelin plays a key role in the metabolism of patients with ALS (12). The study shows that the SenseWear Armband is easy to use, not only for healthy subjects as in previous studies (7–9), but also for ALS patients with neurological problems and focal neurological deficits. Novel tubes are now available that allow blood to be taken on site without further immediate processing. This may help to recruit patients into such studies.