Page 121 - The autoimmune hypothesis of narcolepsy and its unexplored clinical features M.S. Schinkelshoek

unique in terms of the short interval between a normal hypocretin-1 value in the cerebrospinal fluid and the first clinical signs of the disease. A second lumbar puncture confirmed the diagnosis of NT1 showing a complete disappearance of hypocretin-1 from the cerebrospinal fluid. In this chapter, we describe the pentad of core symptoms of NT1, but we also highlight the weight gain that the patient experienced.
The weight increase that frequently emerges early in the disease, as in the patient described in Chapter 1 (Daniels, 1934, Wang et al., 2016, Nordstrand et al., 2019b), is one of the most debilitating symptoms. Especially in children who develop NT1 this symptom plays a central role in the burden of the disease (Ponziani et al., 2016).
In Chapter 5, we describe a retrospective study on NT1 patients who start using sodium oxybate. Weight loss has been described as a side effect of this medication in one of the hallmark clinical trials on the effect of sodium oxybate in NT1 (The U.S. Xyrem® Multicenter Study Group, 2003) and in our outpatient clinic, patients using sodium oxybate frequently report a decrease in weight when they start using this compound. We compared NT1 patients that started using modafinil with those who started using sodium oxybate and found that sodium oxybate was associated with a mean BMI decrease of 0.84 kg/m2 in men and 2.56 kg/m2 in women. NT1 patients that started using modafinil did not significantly lose weight.
Several explanations for both the weight increase when developing NT1 and the subsequent weight loss when initiating sodium oxybate treatment have been proposed. Inactivity (Middelkoop et al., 1995), medication use (Black SW, 2015) and different eating habits (Lammers et al., 1996) as a cause for obesity in NT1 have not been confirmed, even though several symptoms of eating disorders, such as food craving and binge eating were reported in a majority of NT1 patients (Fortuyn et al., 2008). One study reported a lower basal metabolic rate (BMR) close after disease onset in children with NT1, which restored to normal levels in the following months (Wang et al., 2016). Therefore, the effect of NT1 on the individual body mass index (BMI) set point is regarded as the most important cause of the observed obesity. Recent observations suggest that also food-related responses in the cortex are enhanced in NT1 and could potentially contribute to increased food intake leading to obesity, even though this effect on intake has not been shown (van Holst et al., 2018).
Summary, discussion and future perspectives
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