Two peaks of onset are suggested, at ages 15—25 years and ages 30—35 years. Onset can be abrupt or progressive (over years). Severity is highest when onset is abrupt in children, and then decreases with age or with treatment, so that symptoms such as cataplexy can oc- casionally disappear. Abrupt onset in young, prepubescent children can be associated with obesity and premature puberty, a phenotype more frequently observed since 2009. In adolescents, onset is more difficult to pinpoint. Onset in adults is often unclear, with some individuals reporting having had excessive sleepiness since birth. Once the disorder has manifested, the course is persistent and lifelong.
In 90% of cases, the first symptom to manifest is sleepiness or increased sleep, followed by cataplexy (within 1 year in 50% of cases, within 3 years in 85%). Sleepiness, hypnagogic hallucinations, vivid dreaming, and REM sleep behavior disorder (excessive movements during REM sleep) are early symptoms. Excessive sleep rapidly progresses to an inability to stay awake during the day, and to maintain good sleep at night, without a clear increase in total 24—hour sleep needs. In the first months, cataplexy may be atypical, especially in children. Sleep paralysis usually develops around puberty in children with prepubertal onset. Exacerbations of symptoms suggest lack of compliance with medications or devel- opment of a concurrent sleep disorder, notably sleep apnea.
Young children and adolescents with narcolepsy often develop aggression or behav- ioral problems secondary to sleepiness and / or nighttime sleep disruption. Workload and social pressure increase through high school and college, reducing available sleep time at night. Pregnancy does not seem to modify symptoms consistently. After retirement, indi- viduals typically have more opportunity for napping, reducing the need for stimulants.
Maintaining a regular schedule benefits individuals at all ages.
Temperamental. Parasomnias, such as sleepwalking, bruxism, REM sleep behavior dis- order, and enuresis, may be more common in individuals who develop narcolepsy. Indi- viduals commonly report that they need more sleep than other family members.
Environmental. Group A streptococcal throat infection, inﬂuenza (notably pandemic
HINI 2009), or other winter infections are likely triggers of the autoimmune process, pro- ducing narcolepsy a few months later. Head trauma and abrupt changes in sleep-wake patterns (e.g., job changes, stress) may be additional triggers.
Genetic and physiological. Monozygotic twins are 25%—32% concordant for narcolepsy.
The prevalence of narcolepsy is 1%—2% in first-degree relatives (a 10- to 40-fold increase overall). Narcolepsy is strongly associated with DQBI‘06202 (99% vs. 12%—38% in control subjects of various ethnic groups; 25% in the general US. population). DQB1*03:01 in- creases, while DQB1‘O5:01, DQBI‘06:01, and DQB1*06:03 reduce risk in the presence of
DQBI‘06202, but the effect is small. Polymorphisms within the T-cell receptor alpha gene and other immune modulating genes also modulate risk slightly.
Narcolepsy has been described in all ethnic groups and in many cultures. Among African
Americans, more cases present without cataplexy or with atypical cataplexy, complicating diagnosis, especially in the presence of obesity and obstructive sleep apnea.
Functional imaging suggests impaired hypothalamic responses to humorous stimuli.