Page 25 - The autoimmune hypothesis of narcolepsy and its unexplored clinical features M.S. Schinkelshoek

assay has a detection limit of 50 pg/mL and an intra-assay variability of <5%. To adjust for inter-assay variability to previously reported values, Stanford reference CSF samples were included in the assay (Ripley et al., 2001).
Because of this finding, a second lumbar puncture was performed in March 2018, after informed consent, that showed an undetectable hypocretin-1 level in the CSF, which confirmed the diagnosis of NT1. Hypocretin-1 measurements in both CSF samples of this patient were repeated in duplicate in one assay, to rule out inter-assay variability as an explanation for the observed difference between both samples. In line with the earlier measurements, hypocretin-1 levels before and after symptom onset were 272 and 0 pg/mL, respectively.
Discussion
The disease phenotype and sleep laboratory findings in this patient are characteristic of sporadic pediatric NT1 (Postiglione et al., 2018). Interestingly, the first NT1 symptoms arose shortly after a normal hypocretin-1 level was measured in the CSF of this patient. This adds to the knowledge from previous case reports that hypocretin-1 deficiency could already be measured within weeks after symptom onset (Kubota et al., 2003, Kanbayashi et al., 2002). Another case report also shows both a hypocretin-1 measurement prior to and several months after symptom onset (Savvidou et al., 2013). Since the first measurement was more than a year before symptom onset, it remained largely unclear how long it took for the hypocretin-producing neurons to disappear in that case. The short interval between hypocretin-1 measurement and symptom onset in this case suggests that the decrease in hypocretin-1 concentration from normal to undetectable levels may be a process lasting only a few weeks or even less.
The onset of symptoms can be gradually in NT1, but also subacute, as in this case. The latter course of symptom onset is described particularly in pediatric (Postiglione et al., 2018) and post-H1N1 influenza narcolepsy cases (Sarkanen et al., 2016). This pediatric patient was not vaccinated in the 2009 H1N1 vaccination campaign. There was also no indication that other environmental triggers presumed to be linked to NT1 symptom onset (such as Streptococcus pyogenes (Ambati et al., 2015)) were present in this patient. However, the enteroviral infection that led to the patient’s admission to a hospital for several days might constitute an environmental trigger, that has not been described
Hypocretin deficiency in CSF
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