254 Chapter 8 Sleep problems Clinically relevant sleep problems during dexamethasone treatment were reported by parents in 59% of our patients (Chapter 4). Prospectively measured sleep problems during glucocorticoid treatment were previously reported between 24% and 97% of patients with ALL.1,4,13,14 Subjective measurement of sleep in children remains challenging, especially across a wide age range, due to the limited psychometric validation of sleep questionnaires.15,16 A promising future subjective measurement tool is a (proxy-report) short PROMIS form that measures sleep disturbances, which is currently being validated in Dutch. Objective measurement of sleep problems, using actigraphy, is widely used to assess sleep-wake patterns in children.15 We used actigraphy in our RCT (Chapter 6) and found that the data was usable for 36/52 patients (69%). Especially younger children refused to wear the actigraph. Besides, even though actigraphy is excellent to detect sleep-wake pattern deviations, it is not able to identify all sleep problems, e.g. excessive somnolence, which are represented in questionnaires such as the SDSC. We therefore anticipate that combining both subjective (questionnaire) and objective (actigraphy) sleep measures would provide the most optimal insight in different sleep problems in children treated with dexamethasone. Metabolic side effects Besides neurobehavioral and sleep problems, patients report physical side effects of dexamethasone. This thesis revealed that standardized leptin values, as well as fat mass and hunger scores, increased tremendously after five days of dexamethasone treatment (Chapter 5). We did not find a correlation between these changes, which may reflect a dexamethasone-induced state of acute leptin resistance. This contributes to understanding the underlying mechanisms of metabolic adverse events in children with ALL, which in turn are risk factors for sequential cardiovascular diseases and subsequent morbidity and mortality after treatment.17 Appetite signaling and (behavioral) eating are complex processes and disruption in one or more of the pathways of satiety and weight regulation may lead to metabolic dysregulation and/or obesity. High dosages of glucocorticoids such as dexamethasone may cause or mediate such disruptions.18 We established that high dose dexamethasone treatment is associated with dysregulation of one of the players of the hormonal satiety pathway, i.e. leptin, and the feeling of hunger. Dexamethasone is known to upregulate leptin expression and release, but also leptin receptors.19-21 It is conceivable that the increase in leptin during glucocorticoid treatment has another role than solely appetite control, but to truly determine the regulating role of leptin signaling deficits during or after dexamethasone
RkJQdWJsaXNoZXIy MTk4NDMw