Narcolepsy

DESCRIPTION

Lifelong disabling autoimmune neurologic disorder primarily characterized by excessive daytime sleepiness (EDS) (cardinal symptom) and inappropriate transitions from wakefulness into rapid eye movement (REM) sleep. It can be conceptualized as condition in which the transitions between the awake and sleep states are unstable.
Main symptoms follow the mnemonic CHESS: cataplexy, hypnagogic hallucinations, EDS, sleep paralysis, sleep disruption.
Subdivided into type 1 (previously termed narcolepsy with cataplexy) and type 2 (previously termed narcolepsy without cataplexy)

Prevalence in North America and Europe is reported to range from 20 to 50 per 100,000; prevalence may be higher in the Japanese population.
An estimated 135,000 to 200,000 people in the United States have narcolepsy, although number may be higher due to underdiagnosis.
More than half of patients with narcolepsy have symptoms before age of 18 years, and 10–15% have symptoms before age of 10 years.
Diagnosis may lag 10 to 15 years after onset of symptoms.

1st-degree relatives of patients with narcolepsy type 1 have a 1–2% risk (which is 10- to 40-fold more than the general population) of developing narcolepsy.
Both genetic and environmental factors (such as infections and possibly the H1N1 vaccination) may be involved in the development of narcolepsy.
There is an association between narcolepsy type 1 and human leukocyte antigens (HLAs) subtypes, specifically DQB1*0602 and DR2 antigens. 86–98% of patients with narcolepsy type 1 are positive for DQB1*0602, compared to 40–50% of patients with narcolepsy type 2.

Narcolepsy is not preventable.
Delays in diagnosis of narcolepsy are common, especially in children.
Physicians should screen for sleep dysfunction and excessive sleepiness as part of anticipatory guidance and serve as advocates for the patients regarding academic and work accommodations.

Hypocretin (also known as orexin) is a neuropeptide produced by neurons in the lateral hypothalamus that promotes wakefulness and suppresses REM sleep.
To better reflect pathophysiology, the American Academy of Sleep Medicine has categorized narcolepsy into type 1 and type 2.
- Type 1 involves hypocretin deficiency, such as would be detected in cerebrospinal fluid (CSF) via lumbar puncture or manifested clinically by the presence of cataplexy.
- Type 2 does not involve hypocretin deficiency, and in the absence of CSF testing would be the presumptive diagnosis for a patient who had not manifested cataplexy.
- Onset of cataplexy or detection of hypocretin deficiency in a patient without cataplexy would indicate a change in diagnosis from type 2 to type 1.
Narcolepsy type 1 is most likely caused by selective loss of hypothalamic hypocretin-producing neurons.
The association between narcolepsy and specific HLA antigens supports an autoimmune pathogenesis.

Comorbid sleep disorders, such as obstructive sleep apnea, restless legs syndrome, and insomnia may be present.
Secondary narcolepsy may be seen with CNS trauma, strokes, brain tumors, and demyelinating diseases, particularly involving the hypothalamic region.
Genetic syndromes associated with secondary narcolepsy
- Prader-Willi syndrome
- Myotonic dystrophy
- Niemann-Pick type C