Page 124 - The autoimmune hypothesis of narcolepsy and its unexplored clinical features M.S. Schinkelshoek

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The mechanism that leads to the weight loss that follows the initiation of sodium oxybate treatment in NT1 might also involve brown adipose tissue activation, since the main metabolite of sodium oxybate, succinate, was recently shown to strongly induce brown adipose tissue thermogenesis (Mills et al., 2018).
Chapter 6 on the other hand, shows that symptoms that are not easily recognized, such as sleep state misperception, might influence a patient’s ability to assess daytime function adequately and might therefore influence treatment decisions. Being aware of the presence of these symptoms is important for sleep physicians and should always be taken into account when assessing treatment effect. Gathering information on daily functioning from relatives or other people that are close to the patient seems pivotal in adequately assessing the burden of the disease for that patient. This is also highly relevant when performing clinical research, since excessive daytime sleepiness as a primary endpoint is often measured by questionnaires. Developing tools that enable researchers to include symptoms such as sleep state misperception and disturbed vigilance in the outcome parameters of clinical trials could be a first step to acknowledging the diversity of symptoms that make up the burden of NT1.
Overall conclusion
Both basic and clinical research on NT1 have increased rapidly over the past two decades, sparked by the discovery of hypocretin in the late 1990s. However, many questions remain unanswered. A clear understanding on what mechanisms drive the presumed autoimmune response leading to the development of NT1 is pivotal to eventually develop a causal treatment for or prevention of the disorder. This thesis describes several factors that might play a role in the pathophysiological process. At the same time, interest in invalidating consequences beyond the core clinical symptoms slowly but steadily increases, as Chapter 5 and 6 show. For NT1 patients this is arguably even more important than small improvements in preventing daytime sleep and the occurrence of cataplexy.