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Narcolepsy

Associated with 4 symptoms:excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis.

A chronic neurological sleep disorder in which the brain’s natural sleep-wake cycle is disrupted.

A central disorder of hypersomnolence, with daytime sleepiness not caused by disturbed nocturnal sleep or misaligned circadian rhythms.

Patients experience episodes of excessive sleepiness throughout the day.

Approximately 1 in every 2000 to 3000 people are affected.

Risk factors:

Typically begins in people between 10 and 30 years old.

Family history, risk of narcolepsy is 20 to 40 times higher if there is a family member who has narcolepsy.

Family risk of narcolepsy is low, only about 1 percent.

Prevalence equal in men and women.

Under recognized and under diagnosed.

No cure exists.

Symptoms include:

Excessive daytime sleepiness.

Patients can fall asleep without warning, anywhere, anytime.

Impaired concentration.

Severity of sleepiness equivocal to that if an individual sleep deprived for 48-72 hours.

Patients cannot stay up for long periods of time.

Refers to a chronic sleep disorder characterized by overwhelming daytime drowsiness and sudden attacks of sleep.

Can cause serious disruptions in daily routine, and activities.

Sometimes, it is accompanied by a sudden loss of muscle tone, known as cataplexy.

Cataplexy can be triggered by strong emotion.

Orexins are peptides produced by neurons in the lateral hypothalamus that innervate the cortex brings them in other regions where it promotes wakefulness and regulates REM sleep.

Cataplexy can cause sudden onset of slurred speech, weakness of most muscles and last a few minutes.

Cataplexy is uncontrollable.

Cataplexy is triggered by intense emotions.

Some with narcolepsy experience only one or two episodes of cataplexy a year.

People with type 1 narcolepsy have low levels of hypocretin, and this is particularly low in those who experience cataplexy.

Hypocretin is a neurochemical that helps regulate wakefulness and REM sleep.

Hypocretin (orexin) produced by the hypothalamus cells, keeps people awake and alert: low or absent hypocretin is associated with narcolepsy type 1.

The classic form of narcolepsy is called narcolepsy type 1.

Patients with narcolepsy usually also have visual dream like hallucinations and sleep paralysis, the presence of HLA-DQB1 06:02 variant and disturbed nocturnal sleep.

Narcolepsy is associated with a specific variant of the human leukocyte antigen (HLA) complex.

Genome-wide analysis shows that, in addition to the HLA variant, individuals  with narcolepsy also exhibit a specific genetic mutation in the T-cell receptor alpha locus.

Narcolepsy type 1 is caused by severe loss or lack of brain orexin neuropeptides.

Type 2 narcolepsy is not associated with the lack of hypocretin.

Narcolepsy type 2 is characterized by sleepiness, aberrant REM periods at the onset of sleep, and no cataplexy.

Other patients with narcolepsy experience numerous episodes daily.

Narcolepsy patients often experience a temporary inability to move or speak while falling asleep or upon waking.

Such episode of sleep paralysis last a few seconds or minutes.

Not everyone with sleep paralysis has narcolepsy, and any people without narcolepsy experience some episodes of sleep paralysis.

Precipitating emotions are usually positive, such as laughter or excitement, but sometimes fear, surprise or anger is responsible.

Narcolepsy that occurs with cataplexy is called type 1 narcolepsy.

Narcolepsy that occurs without cataplexy is known as type 2 narcolepsy.

Associated with extreme exhaustion.

People with narcolepsy do not sleep more than average, but their sleep is disrupted multiple times at night.

Patients with narcolepsy may suffer with other sleep disorders such as periodic leg movement disorder, sleep apnea or insomnia.

Hypnagogic hallucinations can occur as one falls asleep and hypnopompic hallucinations can occur upon waking.

Some patients with narcolepsy experience automatic behavior during brief episodes of narcolepsy performing tasks normally performed.

Uniquely associated with cataplexy, which refers to sudden loss of skeletal muscle tone without the loss of consciousness.

REM sleep is typically when most dreaming happens.

REM sleep can occur at any time of the day in people with narcolepsy.

Individuals with narcolepsy may suddenly enter into REM sleep without first experiencing NREM sleep.

Cataplexy, sleep paralysis and hallucinations are similar to changes that occur in REM sleep, but occur during wakefulness or drowsiness with narcolepsy.

People with narcolepsy often transition quickly to REM sleep, usually within 15 minutes of falling asleep.

Sleep begins with a phase called non-rapid eye movement (NREM) sleep.

During NREM sleep, brain waves slow considerably.

After an hour or so of NREM sleep, brain activity changes, and REM sleep begins.

Symptoms typically present in adolescence or early adulthood with peak onset ages 15-3.

Diagnosis usually delayed about 10 years, particularly in women.

Cataplexy often triggered by strong emotional experienced.

Cataplexy can vary in intensity, and be devastating.

Cataplexy may last seconds to minutes and be confined to arms, legs, and facial muscles.

Cataplexy lasting for hours may occur following withdrawal of antidepressants.

Solriamfetol (Sunosi) to improve wakefulness in adults with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea.

The CNS stimulant modafinil and its R- enantiomer  armodafinil have been used his first line treatments for excessive daytime sleepiness due to narcolepsy.
Alternative treatments include mixed amphetamine salts Adderall and methylphenidate and others.
Histamine-H3 receptor agonist/inverse agonist pitolisant is more effective than placebo in treating excessive daytime sleepiness and cataplexy in patients with narcolepsy, but is not more affective than other drugs.
In patients with narcolepsy type I, orexin receptor 2 agonist results in greater improvement on measures of sleepiness and cataplexy than placebo, but is associated with hepatotoxic effects.
Orexin-deficient people with narcolepsy have increased obesity rather than decreased BMI, as would be expected if orexin were primarily an appetite stimulating peptide.

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