Cataplexy can also be brought on by excitement, anger, grief, or any intense emotion. Ĭataplexy is a sudden, often bilateral muscle weakness lasting a few seconds to a couple of minutes in response to increased emotion (typically laughter) during which patients remain conscious. , The only required symptom for the diagnosis of narcolepsy is daily, irrepressible, rapid lapses into REM sleep known as “sleep attacks” that are present for at least three months. The average time from onset of symptoms to diagnosis is about 15 years. The typical patient with narcolepsy will begin experiencing symptoms in either their mid-teens or mid-thirties with a progressive increase of symptoms. Patients present with moderate to severe daytime sleepiness. Unfortunately, many other neurotransmitters play a role in the sleep-wake cycle, and making a correlation with any one of them is difficult. The deficiency in hypocretin is believed to produce intermittent wake and sleep states. Many patients with narcolepsy have no or little hypocretin in the CSF. The hypocretin system now appears to play a vital role in narcolepsy. The cataplexy seems to have its origin in the pons and the mesocorticolimbic dopaminergic system. The pathophysiology of narcolepsy type 2 is not well understood. The RAS no longer consistently causes the release of wake-promoting neurotransmitters to the cortex and inconsistently inhibits the VLPO. This results in rapid transitions between sleep and wake and allows the intrusion of REM-related phenomena into wakefulness. In narcolepsy type 1, the mechanism that separates wake from sleep becomes unstable without sufficient levels of orexin. ĭuring normal REM sleep, orexin decreases, which decreases RAS activity and promotes atonia.

The wake-promoting and the sleep-promoting systems are usually mutually inhibitory to ensure complete transitions. Heightened emotions increase activity in the amygdala and subsequently the orexin-containing neurons, which suppresses REM. The RAS also inhibits the sleep-promoting ventrolateral preoptic area (VLPO), suppressing GABA, which in turn increases the activity of motor neurons and muscle tone. Narcolepsy is classified as follows based on clinical features:ĭuring normal wakefulness, orexin-containing neurons in the lateral hypothalamus increase the activity of the nuclei of the Reticular Activating System (RAS), which increases wake-promoting neurotransmitters in the cortex dopamine, norepinephrine, serotonin, and histamine inhibit REM and acetylcholine is increased in both wakefulness and REM. The mechanism of narcolepsy type 2 is less clear, but it is thought that it may be due to a similar but less severe loss of orexin neurons. Although a specific autoantibody that correlates with disease mechanism in narcolepsy has not yet been identified, this does strongly suggest that narcolepsy type 1 may be an autoimmune disease.

Antibodies against streptococcal infections have also been associated with the onset of narcolepsy type 1. Additionally, there was an increase in the number of reported cases of narcolepsy in non-vaccinated patients after wild A(H1N1) pandemic influenza infection. The same adjuvant was, however, also used in Canada but the corresponding increase in reported cases did not occur there. In 2009 there was an increase in the number of cases of narcolepsy type 1 reported in Europe after receiving the European AS03-adjuvanted A(H1N1) pandemic influenza vaccine (Pandemrix) and it was initially thought that the immune response to the adjuvant might have been the cause of the disease. Some patients initially diagnosed with narcolepsy type 2 will develop cataplexy, indicating disease progression. Less commonly, trauma and tumors may result in narcolepsy. Current hypotheses include less destruction of orexin cells, impaired orexin receptor signaling, or an unknown mechanism. The cause of narcolepsy type 2 is not entirely clear. HLA haplotype DQB1*0602 is present in 95% of narcolepsy type 1 patients, but this is also present in about 20% of the general population without narcolepsy.

The reason for this is not fully understood, but it is thought to be an autoimmune process possibly triggered by an infection. Narcolepsy type 1 occurs when nearly all of the neurons that contain orexin (also called hypocretin) are lost.

Narcolepsy and cataplexy symptoms