Page 85 - The autoimmune hypothesis of narcolepsy and its unexplored clinical features M.S. Schinkelshoek

Introduction
Narcolepsy type 1 (NT1) is a chronic neurological disorder characterised by excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep (Black et al., 2017). In addition to the classical symptoms, other symptoms have been reported. These include autonomic abnormalities and obesity (Fronczek et al., 2008). Narcolepsy type 1 is caused by a loss of hypothalamic hypocretin (orexin)-producing neurons (Nishino et al., 2001). Hypocretin neurons project throughout the central nervous system to areas known to be important in the control of sleep-wakefulness, but also to areas important in neuroendocrine homeostasis, autonomic regulation and the control of feeding (Willie et al., 2001).
From as early as the 1930s it has been reported that obesity is more prevalent in narcolepsy patients than in healthy controls (Daniels 1934; Wang et al., 2016). Abdominal fat deposition and waist circumference were found to be significantly increased in narcolepsy patients (Kok et al., 2003). who also have a higher prevalence of the metabolic syndrome compared to idiopathic hypersomnia patients (Poli et al., 2009). Also in children NT1 onset was associated with rapid weight gain (Ponziani et al., 2016). Cause for the observed obesity in NT1 has not been elucidated. It is probably not secondary to inactivity or to medication use (Black et al., 2017). Studies of eating habits showed conflicting results regarding caloric intake, the prevalence of eating disorders in NT1 (Fortuyn et al., 2008) and basal metabolic rate. A recent study in children with NT1 showed a lower basal metabolic rate (BMR) closely after disease onset, which restored to normal levels in the following months (Wang et al., 2016). Therefore, it is hypothesized that NT1 induces a change in the individual body mass index (BMI) set point (Dahmen et al., 2009), but the exact mechanism causing this hypothesized change in NT1 patients remains unclear. Management of BMI in NT1 is important, as a higher BMI seems a risk factor for diseases, such as diabetes type 2 and cardiovascular disease (Kok et al., 2003) and predisposes to psychosocial and professional disability (World Health Organization, 2000; Narbro et al., 1996).
Recent observations suggest that pediatric and adult narcolepsy patients lose weight when using sodium oxybate (SXB; Boscolo-Berto et al., 2012; Ponziani et al., 2016). Weight loss in narcolepsy patients with (mean loss of 5.1kg) and without cataplexy (mean loss of 2kg) treated with SXB has been reported (Husain
Medication and BMI change
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