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Narcolepsy:
A Sleeping Disorder
Debbie Lee, Peter Tran
Kenneth Yu, Aziz Bellarbi-Salah
Presentation Outline
 History and Background Information on
Narcolepsy (Debbie)
 Narcolepsy Effects on Sleep (Peter)
 Canine Model of Narcolepsy (Aziz)
 Neural Correlates of Narcolepsy (Ken)
 Questions (Everyone)
History of Narcolepsy
 In 1880, Jean Bapiste Gelineau first
described Narcolepsy as
 a rare neurosis...characterized by an urgent
necessity to sleep, sudden and of short
duration which recurred at intervals more or
less long
 William Dement and his colony of
narcoleptic dogs
Definition
Narcolepsy (n.): A disorder due to a
malfunction of the sleep/wake cycle
regulating system in the brain, caused by the
lack of an important chemical in the part of
the brain responsible for controlling sleep
narcolepsy sleep disorders in adults patients.ppt
Narcolepsy in the Movies
From Deuce Bigalow, Male Gigolo (1999)
Characteristics of
Narcolepsy
 Daytime sleepiness
 Cataplexy
 Sleep Paralysis
 Instantaneous REM sleep
 Hypnagogic Hallucinations
1 in 2000 (or 250,000)
Americans have Narcolepsy
While less than 50,000 are aware of their
own disease!
Normal Sleep/Wake Cycle
 Sleep is not merely passive
 Normal sleep occurs with a distinct cycle of
stages:
1. Waking state
2. 4 stages of non-REM (Slow Wave)
3. REM sleep
REM Sleep
 Rapid Eye Movements
 Neocortex activation similar to the waking
state
 Makes up 20% of sleep duration
 Occurs 70-90 minutes into sleep
 Muscular paralysis
Narcoleptic Sleep Cycles
 Onset of sleep = less than 10 minutes
 Poor nocturnal sleep contributes to feelings of
sleepiness in the morning
 REM sleep = less than 20 minutes
 Quick onset of REM sleep causes inadequate
rest, other mental problems
 Hallucinations and nightmares
REM Sleep and Narcolepsy
 Loss of muscle control resembles a
neurological protective of REM sleep
 Hypnagogic hallucinations, illusions
similar to dreams
 Sleep paralysis where after falling to or
waking from sleep, a person finds that
they cannot move
Canine-Human Correlation
 Canines and Humans share similar
phenotypical, and physiological characteristics
for narcolepsy.
 2 Hypotheses for Human Narcolepsy
 1. Disease occurs at immediate onset
 2. Disease occurs at a delayed onset
Canine Model for Narcolepsy
 Found Axonal Degeneration in:
 Amygdala
 Basal Forebrain
 Entopenucular Nucleus
 Medial Septal Region
Canine Model
 Found that Narcolepsy was caused by a
mutation in:
 Orexin Peptide Gene
 Involved with sleep and wake cycles
 Hypocretin Receptor 2 Gene (Hctr2)
 Involved with excitatory system
Hypocretins and Narcoleptics
Figure 1. Number of Hcrt Cells Decreased in Narcoleptics
 85-90% of Narcoleptics possess a
reduction in Hypocretin Neurons
Role of Hypocretins
 Modulate neurons involved with REM sleep
 Help the interaction between the aminergic
and cholinergic systems
 May produce wakefulness and depress REM
sleep
 Stimulation of hypocretin receptor 2 gene
Neurological Correlates
 Dorsolateral Pons and Medial Medulla
 Normal: suppresses muscle tone during REM
 Narcoleptics: causes cataplexy
 Amygdala
 Normal: aids perception of emotional responses
 Narcoleptics: activates of Brain stems motor inhibitory system
causing cataplexy through strong emotional triggers
 Hypothamalus
 Normal: regulates the excitatory system
 Narcoleptic: possesses a reduction Hypocretins and thus causes a
decrease in Hcrt activation, which results in sleepiness
Narcoleptic Cures
 There is no cure for narcolepsy
 However, some drugs help with the
many of the symptoms
 Amphetamines- help with day time sleepiness
 Antidepressants-help with suppressing REM,
cataplexy, paralysis, and hallucination
 Hypocretin- helped cure dogs of cataplexy
Narcolepsy and Consciousness
 One theory proposes that the lack of
brainstem activation may be related to the
preservation of consciousness of the outside
world that occurs during cataplectic states but
not during REM sleep periods
Questions
 Whats a Narcoleptics Favorite band?
 REM
References
http://med.stanford.edu/school/Psychiatry/narcolepsy/narcolepsyhistory.html
Narcolepsy Genes Wake Up the Sleep Field (in Science's Compass; Perspectives)
Joseph S. Takahashi. Science, New Series, Vol. 285, No. 5436. (Sep. 24, 1999), pp. 2076-2077.
Genetic Linkage of Autosomal Recessive Canine Narcolepsy with a 亮 Immunoglobulin Heavy-
Chain Switch-Like Segment
E. Mignot et al. Proceedings of the National Academy of Sciences of the United States of
America, Vol.88, No. 8. (Apr. 15, 1991), pp. 3475-3478.
Neuronal Activity in Narcolepsy: Identification of Cataplexy-Related Cells in the Medial
Medulla (in Reports) Jerome M. Siegel; Robert Nienhuis; Heidi M. Fahringer; Richard
Paul; Priyattam Shiromani; William C. Dement; Emmanuel Mignot; Charles Chiu Science,
New Series, Vol. 252, No. 5010. (May 31, 1991), pp. 1315-1318.
Prostaglandin E 2 and Its Methyl Ester Reduce Cataplexy in Canine Narcolepsy
Seiji Nishino; Emmanuel Mignot; Beate Fruhstorfer; William C. Dement; Osamu
Hayaishi Proceedings of the National Academy of Sciences of the United States of
America, Vol. 86, No. 7. (Apr. 1, 1989), pp. 2483-2487.

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narcolepsy sleep disorders in adults patients.ppt

  • 1. Narcolepsy: A Sleeping Disorder Debbie Lee, Peter Tran Kenneth Yu, Aziz Bellarbi-Salah
  • 2. Presentation Outline History and Background Information on Narcolepsy (Debbie) Narcolepsy Effects on Sleep (Peter) Canine Model of Narcolepsy (Aziz) Neural Correlates of Narcolepsy (Ken) Questions (Everyone)
  • 3. History of Narcolepsy In 1880, Jean Bapiste Gelineau first described Narcolepsy as a rare neurosis...characterized by an urgent necessity to sleep, sudden and of short duration which recurred at intervals more or less long William Dement and his colony of narcoleptic dogs
  • 4. Definition Narcolepsy (n.): A disorder due to a malfunction of the sleep/wake cycle regulating system in the brain, caused by the lack of an important chemical in the part of the brain responsible for controlling sleep
  • 6. Narcolepsy in the Movies From Deuce Bigalow, Male Gigolo (1999)
  • 7. Characteristics of Narcolepsy Daytime sleepiness Cataplexy Sleep Paralysis Instantaneous REM sleep Hypnagogic Hallucinations
  • 8. 1 in 2000 (or 250,000) Americans have Narcolepsy While less than 50,000 are aware of their own disease!
  • 9. Normal Sleep/Wake Cycle Sleep is not merely passive Normal sleep occurs with a distinct cycle of stages: 1. Waking state 2. 4 stages of non-REM (Slow Wave) 3. REM sleep
  • 10. REM Sleep Rapid Eye Movements Neocortex activation similar to the waking state Makes up 20% of sleep duration Occurs 70-90 minutes into sleep Muscular paralysis
  • 11. Narcoleptic Sleep Cycles Onset of sleep = less than 10 minutes Poor nocturnal sleep contributes to feelings of sleepiness in the morning REM sleep = less than 20 minutes Quick onset of REM sleep causes inadequate rest, other mental problems Hallucinations and nightmares
  • 12. REM Sleep and Narcolepsy Loss of muscle control resembles a neurological protective of REM sleep Hypnagogic hallucinations, illusions similar to dreams Sleep paralysis where after falling to or waking from sleep, a person finds that they cannot move
  • 13. Canine-Human Correlation Canines and Humans share similar phenotypical, and physiological characteristics for narcolepsy. 2 Hypotheses for Human Narcolepsy 1. Disease occurs at immediate onset 2. Disease occurs at a delayed onset
  • 14. Canine Model for Narcolepsy Found Axonal Degeneration in: Amygdala Basal Forebrain Entopenucular Nucleus Medial Septal Region
  • 15. Canine Model Found that Narcolepsy was caused by a mutation in: Orexin Peptide Gene Involved with sleep and wake cycles Hypocretin Receptor 2 Gene (Hctr2) Involved with excitatory system
  • 16. Hypocretins and Narcoleptics Figure 1. Number of Hcrt Cells Decreased in Narcoleptics 85-90% of Narcoleptics possess a reduction in Hypocretin Neurons
  • 17. Role of Hypocretins Modulate neurons involved with REM sleep Help the interaction between the aminergic and cholinergic systems May produce wakefulness and depress REM sleep Stimulation of hypocretin receptor 2 gene
  • 18. Neurological Correlates Dorsolateral Pons and Medial Medulla Normal: suppresses muscle tone during REM Narcoleptics: causes cataplexy Amygdala Normal: aids perception of emotional responses Narcoleptics: activates of Brain stems motor inhibitory system causing cataplexy through strong emotional triggers Hypothamalus Normal: regulates the excitatory system Narcoleptic: possesses a reduction Hypocretins and thus causes a decrease in Hcrt activation, which results in sleepiness
  • 19. Narcoleptic Cures There is no cure for narcolepsy However, some drugs help with the many of the symptoms Amphetamines- help with day time sleepiness Antidepressants-help with suppressing REM, cataplexy, paralysis, and hallucination Hypocretin- helped cure dogs of cataplexy
  • 20. Narcolepsy and Consciousness One theory proposes that the lack of brainstem activation may be related to the preservation of consciousness of the outside world that occurs during cataplectic states but not during REM sleep periods
  • 21. Questions Whats a Narcoleptics Favorite band? REM
  • 22. References http://med.stanford.edu/school/Psychiatry/narcolepsy/narcolepsyhistory.html Narcolepsy Genes Wake Up the Sleep Field (in Science's Compass; Perspectives) Joseph S. Takahashi. Science, New Series, Vol. 285, No. 5436. (Sep. 24, 1999), pp. 2076-2077. Genetic Linkage of Autosomal Recessive Canine Narcolepsy with a 亮 Immunoglobulin Heavy- Chain Switch-Like Segment E. Mignot et al. Proceedings of the National Academy of Sciences of the United States of America, Vol.88, No. 8. (Apr. 15, 1991), pp. 3475-3478. Neuronal Activity in Narcolepsy: Identification of Cataplexy-Related Cells in the Medial Medulla (in Reports) Jerome M. Siegel; Robert Nienhuis; Heidi M. Fahringer; Richard Paul; Priyattam Shiromani; William C. Dement; Emmanuel Mignot; Charles Chiu Science, New Series, Vol. 252, No. 5010. (May 31, 1991), pp. 1315-1318. Prostaglandin E 2 and Its Methyl Ester Reduce Cataplexy in Canine Narcolepsy Seiji Nishino; Emmanuel Mignot; Beate Fruhstorfer; William C. Dement; Osamu Hayaishi Proceedings of the National Academy of Sciences of the United States of America, Vol. 86, No. 7. (Apr. 1, 1989), pp. 2483-2487.