Page 123 - The autoimmune hypothesis of narcolepsy and its unexplored clinical features M.S. Schinkelshoek
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Future perspectives
Scientific data on the pentad of NT1 core symptoms is gathered in almost every clinical trial or cohort study that is performed in NT1. Even though the primary endpoint in most studies is either cataplexy frequency or excessive daytime sleepiness, the effect of interventions on hypnagogic hallucinations, sleep paralysis and disturbed night sleep is frequently reported as a secondary endpoint. However, the burden of the disease is only partly dictated by these symptoms. Other symptoms, or neglected expression of core symptoms, such as weight gain, disturbed vigilance, depressive symptoms and sleep state misperception, are adding to the social disability, educational difficulties and mental problems that NT1 patients experience in everyday life. Clinical trials and studies using information derived from prospective clinical databases, that describe the effect of interventions on these other symptoms, are much needed. It will greatly support NT1 patients’ futures to be able to treat their symptoms that are not part of the core pentad, based on clinical evidence.
Based on Chapter 5, it is clear that weight gain can be influenced by medication, but also that future research should focus on the mechanisms that underlie weight gain in NT1. Investigating the role of brown adipose tissue in both weight gain and subsequent weight loss upon initiation of sodium oxybate treatment seems promising. Many preclinical studies suggest a role for the hypocretin system in brown adipose tissue activation (Madden et al., 2012, Sellayah et al., 2011), but also in the differentiation and development of this tissue (Rogers et al., 2012, Sellayah and Sikder, 2014). However, the first study to assess brown adipose tissue in NT1 patients did not find any differences when its activation was compared to that of healthy controls, but the sample size was small and the protocol did not allow for adequate maximal brown adipose tissue activation measurements (Enevoldsen et al., 2018). Prospective larger studies are needed to evaluate the role of brown adipose tissue in the weight gain accompanying the development of NT1.
Summary, discussion and future perspectives
 • A long sleep latency and the occurrence of only NREM stage 1 sleep both predict daytime sleep state misperception
• Patients and physicians should take the presence of daytime sleep state misperception into account when making treatment decisions
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