🎯 Pathology

• abnormal tendency to enter rapid eye movement (REM) sleep directly from the state of wakefulness when nearly all neurons that contain orexin (also known as hypocretin) in the posterior lateral hypothalamus are lost

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☀️ Neural projections that maintain wakefulness

1. histamine neurons in the tuberomammillary nucleus (found in the posterior hypothalamus)

   • project to all areas of the cerebral cortex promoting wakefulness

   • inhibition of these neurons triggers sleep

2. orexin neurons (found in the posterior lateral hypothalamus)

   • these neurons increase the activity of neurons that secrete wake-promoting neurotransmitters such as dopamine, noradrenaline, serotonin and histamine

     • the nuclei of these neurons are part of the reticular-activating system (RAS) in the brainstem which project to all areas of the cerebral cortex

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😴 How sleep is initiated

1. circadian rhythm

   • under the control of the suprachiasmatic nucleus in the hypothalamus which receives input fibres from the retina

   • the suprachiasmatic nucleus then projects to histaminergic neurons in the tuberomammillary nucleus and orexin neurons in the posterior lateral hypothalamus initiate sleep

2. sleep pressure

   • adenosine builds up in the brain during the day

   • high levels of adenosine in the brain increases the desire to sleep

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☕️ Effect of caffiene on sleep

• caffeine is an adenosine receptor antagonist which blocks adenosine A2A receptors in the brain

• promotes wakefulness as it combats sleep pressure

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🧪 Pathophysiology

• normally

  • orexin neurons in the lateral hypothalamus increase the activity of neurons that secrete wake-promoting neurotransmitters such as dopamine, noradrenaline, serotonin and histamine (these neurons are part of the reticular activating system in the brainstem) which project to the cerebral cortex, promoting wakefulness

  • the reticular activating system also inhibits the ventrolateral preoptic nucleus

• narcolepsy

  • less orexin means there is reduced secretion of wake-promoting neurotransmitters making it easier to fall asleep

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💡 Aetiology

• unknown, although it has been postulated it is an autoimmune process that destructs orexin-containing neurons​

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🩺 Clinical features

• typically seen in the late teens to early twenties

• day time sleepiness

• hypnogogic and hypnopompic hallucinations

• cataplexy (sudden bilateral weakness and loss of muscle tone triggered by intense emotion such as laughter)

• sleep paralysis (which may accompany hypnopompic hallucinations)

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🕵️‍♂️ Invesitigations

• actigraphy for 1-2 weeks

  • non-invasive device that monitors cycles of activity and rest

• polysomnography to rule out sleep disorders such as obstructive sleep apnoea (OSA)

• multiple sleep latency test (also known as a nap study)

  • it is a full-day test

  • this test involves giving the patient 4-5 opportunities to fall asleep every 2 hours

  • positive test:

    • rapid onset of REM sleep (< 15 mins) at least twice, or

    • a shortened mean sleep latency across all trials (< 8 minutes) is a positive result

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💆‍♂️ Management

• non-pharmacological interventions 

  • sleep hygiene

  • emotional support

  • avoid alcohol and CNS-suppressant medications

• pharmacological

  • daytime stimulants such as modafinil

  • sodium oxybate