Page 12 - The autoimmune hypothesis of narcolepsy and its unexplored clinical features M.S. Schinkelshoek

General introduction
Narcolepsy is a sleep-wake disorder that can be subdivided in two types, diagnosed according to the criteria outlined in the Third Version of the International Classification of Sleep Disorders (ICSD, 2014). The distinction between type 1 and 2 is made based on the presence of cataplexy and/or hypocretin deficiency. This thesis will focus mainly on narcolepsy type 1 (NT1), since this disease entity is clearly distinct from other hypersomnolence disorders because of the presence of cataplexy and the absence of hypocretin in the cerebrospinal fluid (Table 1). NT1 is characterized by five core symptoms: excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and disturbed night sleep. It is a rare disorder with a prevalence of around 1 in 3000 individuals (Wijnans et al., 2013).
Until the 1980s, not much was known about the cause of narcolepsy. During the 1980s the identification of a strong association of a human leukocyte antigen (HLA) molecule with narcolepsy gave researchers a direction where to look for the cause of the disease. This marked the starting point of the interest in the autoimmune hypothesis of narcolepsy.
Table 1. Diagnostic criteria for narcolepsy type 1 according to the Third Version of the International Classification of Sleep Disorders.
Criteria A and B must be met for making the diagnosis of narcolepsy type 1
• A.The patient has daily periods of irrepressible need to sleep or daytime lapses into
sleep occurring for at least 3 months.
• B.The presence of one or both of the following:
• 1. Cataplexy and a mean sleep latency of ≤8 minutes and two or more sleep-onset
REM periods (SOREMPs) on an multiple sleep latency test (MSLT) performed according to standard techniques. A SOREMP (within 15 minutes of sleep onset) on the preceding nocturnal polysomnogram may replace one of the SOREMPs on the MSLT.
• 2. CSF hypocretin-1 concentration, measured by immunoreactivity, is either ≤110 pg/ mL or <1/3 of mean values obtained in normal subjects with the same standardized assay.
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