Narcolepsy

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:

• Clinical features narcolepsy - Up.To Date