Most narcoleptic patients without cataplexy have normal cerebral spinal fluid (CSF) concentrations of orexin A, whereas >90% of narcoleptic subjects with cataplexy have undetectable orexin A in their CSF. 10,11 Orexin was identified as the major sleep-modulating neurotransmitter, responsible not only for sleep but also for appetite and metabolism. The discovery of hypocretin-1 and -2, also known as orexin A and B, respectively, gave rise to the hypothesis that narcolepsy is caused by a selective early hypocretin neuron loss occurring within and around the lateral area in the hypothalamus however, the exact cause of the neuronal loss in narcolepsy is still unknown. 3,8 Carrying HLA-DQB1*0602 indicates that individuals are predisposed to narcolepsy, but this factor is not enough on its own to diagnose someone with the disease, since it is found in about 12% to 38% of nonnarcoleptics. Several studies have shown a high predominance of the human leukocyte antigen (HLA)-DR2, specifically HLA-DQB1*0602, which is found in 95% of narcoleptics with cataplexy and in 41% of narcoleptics without cataplexy, indicating narcolepsy may be an autoimmune disease. 5 An additional 1.7% to 5% of relatives had narcolepsy without cataplexy.

Ohayon and Okun found that narcolepsy possibly has a genetic component, since the risks for narcolepsy with cataplexy are 2.8% to 5.6% in first-degree relatives. 6 The incidence of narcolepsy with cataplexy is estimated at 0.74 per 100,000 person-years, while narcolepsy with or without cataplexy is at 1.37 per 100,000 person-years. The prevalence of narcolepsy with cataplexy is estimated to be 25 to 50 per 100,000 people, while narcolepsy without cataplexy is estimated higher (56 per 100,000 people). 5 It is moderately more predominant in men than in women. The onset of narcolepsy typically begins in the teenage years and young adulthood, and then persists for life. Individuals with narcolepsy are often obese, with a higher than normal body mass index (BMI), probably due to low metabolic rate. Hypnopompic hallucinations are similar, but happen upon awakening. They involve abnormal visual and vivid auditory hallucinations. Hypnagogic hallucinations typically occur while falling asleep. Some patients may experience hypnagogic and hypnopompic hallucinations. 2,3 The patient’s consciousness during the episode differentiates sleep paralysis from sleep attacks. It is often a frightening experience, where patients cannot move their body or speak, although they are conscious of their surroundings. This is a brief episode involving the loss of voluntary muscle tone that usually happens immediately upon awakening or going to sleep. 1 Another symptom of narcolepsy is sleep paralysis.

It is stimulated by emotions, such as laughter, anger, or surprise. Involuntary, sudden lapses into unconsciousness are called sleep attacks.Ĭataplexy, a symptom exclusive to narcolepsy, is a strong loss of bilateral muscle tone that can last from a few seconds up to 30 minutes. Disproportionate amounts of sleepiness are also experienced during the day and can last from seconds to minutes. Narcoleptic patients often complain of sleep deprivation, constant fatigue, insomnia, and fragmented nighttime sleep. 2 Experiencing all four symptoms is not required for a narcolepsy diagnosis. 1 Four main symptoms are associated with narcolepsy: cataplexy, excessive daytime sleepiness (EDS), sleep paralysis, and hypnagogic hallucinations. Narcolepsy is an incurable neurologic sleep disorder characterized by an abnormality in onset and offset of rapid eye movement (REM) and non-REM (NREM) sleep.

Eds and cataplexy