Narcolepsy

Narcolepsy

SYMPTOMS
1. EXTREME DAYTIME SLEEPINESS
2. CATAPLEXY - sudden unexpected loss of muscle tone whilst awake which can lead to immediate collapse
3. HYPNAGOGIC HALLUCINATIONS - Dream like experiences that occur during wakefulness
4. SLEEP PARALYSIS - inability to move occurring when falling asleep or waking up
NEURAL ABNORMALITIES
1. Cells in hypothalamus secrete a NT Hypocretin (orexin). Orexin regulates sleep wake states, feeding behaviour and reward processes
  1. Orexin system interacts with systems controlling emotion, reward & energy levels.
  2. Hypothalamus damage leads to reduced orexin
    1. analysing CSF in narco, 90% had low orexin levels almost undetectable.
2. DEMENT - disabled orexin production in mice. Mice that couldn't make Hcrt developed narco like symptoms like cataplexy
3. SCAMMELL ET AL - 23 yr old male, narco after hyp damage. Low orexin levels in CSF
  1. ARII ET AL - 16 yr old female, hyp damage after surgery to remove tumour. Developed narco & had reduced orexin levels in CSF
  2. Methodological Issues - CASE STUDIES, rare brain damage. Not all narco have hyp damage. Not generalisable to all narco.
4. ANIMAL RESEARCH - humans neural mechanisms more complex, narco more likely to be effected by stress and increased REM sleep.
GENETIC ABNORMALITIES
1. Suggested result of mutated gene called HYPOCRETIN RECEPTOR 2. Dogs bred to inherit gene develop disorder. Failed to show same in humans.
2. HLA GENE: 90% of narco sufferers inherit defective version of HLA gene know as DQB1*05. The HLA gene is found on surface of WBC & has a role in recognising and destroying foreign antigens.
  1. Narco occurs when DQB1*05 destroys body's own Hcrt cells as an autoimmune response.
3. GORDON ET AL - injected mice with antibodies from blood of 9 narcos resulting in narco - like symptoms. When injected with antibodies of normal blood, no effect.
4. MIGNOT - twin study, 16 pairs of MZ twins, 4 pairs concordant for disorder (25%). MZ genetically identical so expect higher concordance rate.
5. REDUCTIONIST - interactionist approach more valid. HLADQB1*05 inherited but then triggered into action by external event causing narco such as infection, brain injury, diet & stress.

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