NARCOLEPSY What is it?

DIAGNOSIS Irresistible need to rest, lapsing into sleep, napping all in the same day Over the course of three months at least three times a week

DIAGNOSIS(CONT.) Cataplexy Long Standing: (Seconds to Minutes) Bilateral loss of muscle tone Maintained consciousness Precipitated by laughter or joking Children/Others within first six months Spontaneous grimace Jaw opening episodes where they would thrust their tongue No signs of emotional triggers Hypocretin Deficiency Produced from the brain stem and hypothalamic neurons Initially found in narcoleptic dogs and mice Polysomnography Showing REM (Rapid Eye Movement) Latency less than or equal to 15 Min.

LEVELS OF NARCOLEPSY Mild Infrequent Cataplexy Urge to nap about 2 times a day Less disturbed nocturnal sleep Moderate Cataplexy once daily or every other day Disturbed sleep, Restless nights Requirement of napping multiple times a day Severe Multiple attacks of drug- resistant Cataplexy Always being sleepy or physically asleep Disturbed sleep, Restless nights

NORMAL SLEEP To understand narcolepsy we need to understand normal sleep Two stages: REM (Rapid Eye Movement) and NREM (Non-Rapid Eye Movement) EEG shows that NREM is broken up into four stages Human sleep cycle approximately 90 minutes and occur 4-5 times a night Goes between four stages of NREM followed by REM Sleep and wake states must be sustained within certain lengths to be effective

EFFECT ON SLEEP Narcolepsy is a major neurological disorder Narcoleptic patients go into REM sleep quicker Known as reduced REM sleep latency or sleep onset REM period (SOREMP) Some cases NREM is completely bypassed Cataplexy, Sleep Paralysis, and Hypnogogic Hallucinations may stem from this jump or even from the REM intruding on the NREM sleep

SLEEP PARALYSIS Transient, Conscious state of involuntary immobility most likely arising from REM sleep 59 year old man studied to better understand Sleep Paralysis Has narcolepsy and cataplexy Experienced sleep paralysis during sleep MSLT (Multiple Sleep Latency Test) Neurologist questions man during episode Able to answer simple questions about self but unable to move Awakes 17 min. later Able to remember the entire event but unable to determine whether the event truly happened or if he dreamed it.

TESTS Narcoleptic Dogs Gene mutation Mice Hypocretin Deficiency Lack of Hypocretin in both dogs and mice found Led to check of Hypocretin in Humans Gene mutation has little to nothing to do with narcolepsy Low levels of Hypocretin-1 in humans

HYPOCRETIN Hypocretin production or Hypocretin neurons are selectively damaged in narcoleptic pateints Gives a better more efficient way of diagnosing someone with narcolepsy Normal levels of hypocretin-1 should be well over 200pg mL -1 Narcoleptic patients have under 110pg mL -1 94% accurate MSLT (Multiple Sleep Latency Test) Polygraphic measure of daytime sleepiness Still do not know why Hypocretin is targeted

TREATEMENTS Amphetamines and amphetamine-like compounds, recently modafinil Only symptomatic does nothing for the pathophysiology of narcolepsy No way of treating Catapexy Hypocretin replacement therapy may be new therapeutic option May be effective for the sleepiness and the cataplexy Animals are currently being tested on to see if the replacement will hold or has a chance of holding