Narcolepsy-cataplexy nearly always results from the loss of hypothalamic hypocretin (orexin)—producing cells, causing hypocretin deficiency (less than or equal to one-third of control values, or 110 pg/mL in most laboratories). Cell loss is likely autoimmune, and ap- proximately 99% of affected individuals carry HLA-DQB1*06:02 (vs. 12%—38% of control subjects). Thus, checking for the presence of DQB1*06:02 prior to a lumbar puncture for eval- uation of CSF hypocretin-l immunoreactivity may be useful. Rarely, low CSF levels of hypo- cretin-I occur without cataplexy, notably in youths who may develop cataplexy later. CSF hypocretin-l measurement represents the gold standard, excepting associated severe con- ditions (neurological, inﬂammatory, infectious, trauma) that can interfere with the assay.
confirm the diagnosis (Criterion B3). These tests must be performed after the individual has stopped all psychotropic medications, following 2 weeks of adequate sleep time (as documented with sleep diaries, actigraphy). Short rapid eye movement (REM) latency (sleep-onset REM period, REM latency less than or equal to 15 minutes) during polysom- nography is sufficient to confirm the diagnosis and meets Criterion B3. Alternatively, the
MSLT result must be positive, showing a mean sleep latency of less than or equal to 8 min- utes and two or more sleep-onset REM periods in four to five naps.
When sleepiness is severe, automatic behaviors may occur, with the individual continuing his or her activities in a semi-automatic, hazelike fashion without memory or conscious- ness. Approximately 20%—60% of individuals experience vivid hypnagogic hallucinations before or upon falling asleep or hypnopompic hallucinations just after awakening. These hallucinations are distinct from the less Vivid, nonhallucinatory dreamlike mentation at sleep onset that 6ccurs in normal sleepers. Nightmares and vivid dreaming are also fre- quent in narcolepsy, as is REM sleep behavior disorder. Approximately 20%—60% of indi- viduals experience sleep paralysis upon falling asleep or awakening, leaving them awake but unable to move or speak. However, many normal sleepers also report sleep paralysis, especially with stress or sleep deprivation. Nocturnal eating may occur. Obesity is com- mon. Nocturnal sleep disruption with frequent long or short awakenings is common and can be disabling.
Individuals may appear sleepy or fall asleep in the waiting area or during clinical ex- amination. During cataplexy, individuals may slump in a chair and have slurred speech or drooping eyelids. If the clinician has time to check reﬂexes during cataplexy (most attacks are less than 10 seconds), reﬂexes are abolished—an important finding distinguishing gen— uine cataplexy from conversion disorder.
Narcolepsy-cataplexy affects 0.02%—0.04% of the general population in most countries.
Narcolepsy affects both genders, with possibly a slight male preponderance.
Onset is typically in children and adolescents/young adults but rarely in older adults.