ABSTRACT
Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations (HH), and sleep paralysis (SP) (i.e., narcolepsy tetrad) (1,2). A major break through in narcolepsy research was recently made through the identification of hypocretin deficiency in narcolepsy-cataplexy (2-9). Hypocretins are hypothalamic neuropeptides involved in various fundamental hypothalamic functions including, sleep-wake control, energy homeostasis, autonomic and neuroendocrine functions (10-12). Hypocretin containing neurons are located exclusively in the lateral hypothalamic area (LHA). Since hypocretin deficiency in narcolepsy is also tightly associated with human leukocyto antigen (HLA) DR2/DQ6 (DQB10602) positivity, an acquired cell loss of hypocretin containing neurons with autoimmune process are suggested in “so-called” idiopathic cases of narcolepsy (2,6). “Idiopathic narcolepsy” has been used for the cases with narcolepsy unassociated with apparent radiographical or clinical evidence of brain pathology apart from sleeprelated abnormalities. Hypocretin deficiency in the brain can be determined clinically via cerebrospinal fluid (CSF) hypocretin-1 measures with CSF hypocretin-1 levels in healthy subjects above 200 pg/ml regardless of gender, age (from neonatal to 70s), and time of the CSF collections (1,4,6). Due to the specificity and sensitivity of low CSF hypocretin-1 levels (less than 110 pg/mL or 30% of the mean normal levels) narcolepsy-cataplexy is high among various sleep disorders (2,13,14), CSF hypocretin measures will be included in the diagnostic criteria for narcolepsy-cataplexy in the 2nd revision of international classification of sleep disorders (ICSD).
