Malady Wise

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Narcolepsy

Maladywise

Overview

  • 1 in 2000

  • Starts teens and early 20s (range 5 to 40)

Types

  • Type 1 = Narcolepsy with cataplexy

  • Type 2 = Narcolepsy without cataplexy

Cause

  • Loss of orexin signalling

  • Genetic factors

  • Rarely brain lesions

Pathophysiology

  • Orexin-A and B

  • Made in lateral hypothalamus

  • Release during wakefulness and increase activity to promote wakefulness

  • Orexins stabilise wakefulness and prevent transition in REM or non-REM sleep

  • Loss of orexin also REM sleep phenomena (cataplexy, hypnagogic hallucinations, sleep paralysis)

Genetics

  • 95% of patients have DQB1*0602 haplotype

Autoimmune

  • Theory is orexin neurons are selectively killed by an autommune process

  • Onset appears highest in spring ? triggered by winter infection

  • ASOT and anti-DNase B titres are sometimes elevated in the first year after narcolepsy ? strep

  • Some Europeans developed narcolepsy after receiving Pandemrix, an H1N1 flu vaccine in 2009

Secondary Narcolepsy

  • Rarely occurs with brain lesions

  • Occurs in Parder-Willi syndrome

Clinical

  • Disorder of sleep-wake control

  • Elements of sleep intrude into waking and waking into sleep

  • Chronic daytime sleepiness with or without cataplexy, hallucinations, sleep paralysis

  • 1 in 3 patients have all these symptoms

  • Type 1 = Transient facial weakness or falls triggered by joking or laughing or the inability to move for one to two minutes after awakening or just before falling asleep

  • All patients have chronic sleepiness

    • Prone to nap, often inappropriately

    • Sleep attacks = rapidly dozing off

    • Narcolepsy improves after a quick nap

  • Cataplexy is emotionally trigger transient muscle weakness

    • Usually positive emotions (laugh, excitement) but sometimes anger, frustration

    • Develops within 3 to 5 years in 60% of people with narcolepsy

    • Muscle weakness is partial in face, neck, knees

    • Ptosis, smile interruption, collapse

  • Hypnagogic hallucinations

    • Vivid, frightening, tactile, or auditory hallucinations as the patient is falling asleep

  • Sleep Paralysis

    • Inability to move for 1 to 2 minutes when awakening or falling asleep

  • Other features

    • Fragmented sleep

      • Usually fall asleep quickly

      • Spontaneously awaken several times overnight and difficulty returning to sleep

    • Higher incidence of comorbid sleep disorders

      • Insomina = 28%

      • OSA = 21%

      • non-REM sleep parasomnias = 10%

      • RLS = 24%

    • Neuropsychiatric comorbidities

      • Depression, Anxiety, ADHD, Psychosis

Diagnosis

Questions

  • Are you sleepy most of the day?

  • Do you feel rested on waking in the morning?

  • Are your naps refreshing?

  • Do you ever see, feel, or hear things that you know aren’t there as you are falling asleep?

  • Are you ever unable to move when you first awake or as you are falling asleep?

  • Do you have muscle weakness when you laugh or tell a joke?

  • Over the last two weeks, how often have you fallen asleep when you did not intend to?

If answer = yes consider

  • Polysomnography and multiple sleep latency test

Tests

  • Orexin-A in CSF

Resources: