93 Potential Immunological Triggers for Central Disorders of Hypersomnolence Introduction Central disorders of hypersomnolence are primary neurological disorders characterized by excessive daytime sleepiness (EDS) [4]. These diagnostic entities are currently identified, narcolepsy type 1 and 2, and idiopathic hypersomnia [8]. Narcolepsy type 1 arises from a complex interaction of predisposing genetic and environmental factors leading to autoimmunemediated hypocretin-1 deficiency, which instigates the development of cataplexy [4]. In narcolepsy type 2 and idiopathic hypersomnia, hypocretin-1 levels are normal, and cataplexy is absent. Narcolepsy type 1 and type 2 present rapid onset of rapid eye movement sleep during the polysomnography (PSG) and/or multiple sleep latency test (MSLT), which is not recurrently seen in idiopathic hypersomnia [8]. Long-lasting non-refreshing naps with sleep inertia and substantially prolonged nocturnal sleep are often associated with idiopathic hypersomnia [179]. Investigations following the surge in narcolepsy type 1 incidence rates after the H1N1 pandemic in 2009–2010 provided insights into potential environmental triggers for developing narcolepsy [56-60, 134, 136, 137, 159]. The H1N1 influenza vaccine Pandemrix (GlaxoSmithKline Biologicals, Wavre, Belgium) has been linked to narcolepsy type 1 [56, 57, 134, 159] in several European countries. No other vaccines have been implicated to contribute to the pathophysiology of narcolepsy type 1. A similar increase in incidence was noted in Asian countries and the United States, where Pandemrix was not in use, so a putative viral infection was assumed responsible [58-61, 136, 137, 162]. The relative absence of H1N1 infections between the 1918 Spanish flu and the 2009-2010-H1N1 pandemics suggests that other triggers may be involved in developing narcolepsy [62]. Multiple studies have proposed streptococcus pyogenes infections, as recent infections, elevated antibody levels and streptococcusassociated Sydenham chorea have been reported close to narcolepsy type 1 onset [10, 33, 63-67, 180]. Traumatic brain injuries have also been associated with EDS and low hypocretin-1 levels without cataplexy, but this phenotype often disappeared within six months with normalizing hypocretin-1 levels [181]. Case reports and series have reported Guillain-Barre syndrome [182], Wernicke’s encephalopathy [183], tumours affecting the hypothalamus [184], and multiple sclerosis [185] lesions sporadically triggering secondary narcolepsy. There is limited evidence on the common latency between infection and the development of narcolepsy. Case reports suggested this could be days [56, 64]. In contrast, recent studies investigating the prevalence of H1N1 vaccination in people with narcolepsy indicated that this latency could be several months 4
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