Page 23 - The autoimmune hypothesis of narcolepsy and its unexplored clinical features M.S. Schinkelshoek

Introduction
Narcolepsy type 1 (NT1) is associated with a selective and irreversible loss of >90% of neurons in the lateral hypothalamus that produce the sleep- wake regulating neuropeptides hypocretin-1 and -2 (Thannickal et al., 2000, Peyron et al., 2000). The hypocretin-1 concentration in the cerebrospinal fluid (CSF) serves as a biomarker for the presence or absence of these hypocretin- producing neurons (Nishino et al., 2000b). Therefore, this measurement is part of the diagnostic criteria for NT1 and can be performed as an alternative to the frequently used polysomnography with multiple sleep latency test when there is a clinical suspicion of NT1.
Several case reports show that shortly after narcoleptic symptoms arise the hypocretin-producing neuronal loss is severe enough to lead to very low or undetectable CSF hypocretin-1 concentrations (Kubota et al., 2003, Kanbayashi et al., 2002). However, there is hardly any information about how long it may take before the critical number of cells is lost or how long it takes before severe hypocretin-1 deficiency leads to clinical symptoms. We describe a case that may shed (more) light on this lack of knowledge.
Report of case
In May 2017, we diagnosed a 17-year old Dutch girl with NT1 at the outpatient clinic of the Sleep-Wake Centre SEIN in Heemstede, the Netherlands. She had previously been healthy except for a hospital admission in September 2016 because of high fever, and a suspicion of a viral meningitis. Because of this suspicion, a lumbar puncture was performed. Analysis of the CSF showed a normal cell count and normal protein and glucose levels, excluding a viral meningitis. According to the hospital routine procedures, excess CSF was stored for later use, if necessary. Eventually the fever was attributed to a PCR-confirmed enteroviral gastroenteritis. Since there were no respiratory or dermatologic symptoms, the clinical suspicion of an infection with Streptococcus pyogenes was low and further diagnostic testing was not performed.
Within weeks after her dismissal from the hospital in September 2016 she developed severe excessive daytime sleepiness. In December 2016 typical cataplectic attacks (knee-buckling and later general atonia with falls triggered
Hypocretin deficiency in CSF
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