Narcolepsy

Aka: Narcolepsy, Gelineau Syndrome, Paroxysmal Sleep, Narcoleptic Syndrome

1. Epidemiology
   1. Prevalence: 40 per 100,000 (0.02 to 0.18% of adults)
   2. Men and women affected equally
   3. Onset in teens and young adults, ages 10 to 20 years old (rarely has onset after age 50 years)
2. Pathophysiology
   1. Excessive Sleepiness
   2. Abnormal REM Sleep
3. Causes
   1. Idiopathic
      1. Hereditary related to DR-2
   2. Secondary causes
      1. Head Trauma
      2. Encephalopathy
      3. Brain Tumor
      4. Cerebrovascular insufficiency
4. Symptoms: Classic Tetrad
   1. Recurrent irresistible Daytime Sleepiness
      1. Occurs unexpectedly and at inappropriate times
   2. Cataplexy (25-30% of patients with Narcolepsy)
      1. Sudden decrease or loss of voluntary Muscle tone following emotional trigger (e.g. laughing, surprise)
      2. Episodes last seconds to minutes
         1. Localized hypotonia (e.g. jaw drop, head nod, knee sag)
         2. Generalized hypotonia (full collapse onto floor)
   3. Sleep Hallucinations
      1. Hypnagogic Hallucinations (on falling asleep)
      2. Hypnopompic Hallucinations (on awakening)
   4. Sleep Paralysis
      1. Transient, generalized inability to move or speak during sleep-wake transition
5. Differential Diagnosis
   1. See Hypersomnolence
   2. Sleep Apnea
   3. Other Primary Hypersomnia (uncommon)
      1. Idiopathic Hypersomnia
      2. Menstrual Hypersomnia
      3. Kleine-Levin Syndrome (rare syndrome of male teens)
6. Evaluation
   1. See Hypersomnolence
7. Diagnosis: Sleep Study (all patients)
   1. Sleep log or Actigraphy for 2 weeks
   2. Multiple Sleep Latency Test (daytime nap test)
      1. Polysomnogram performed for monitoring
      2. At least 2 naps with early onset REM Sleep (Rapid transition to REM)
      3. Shortened REM latency (<8 minutes compared with 15 minutes for unaffected patients)
8. Management: General Measures
   1. Schedule naps
   2. Keep a consistent sleep schedule
   3. Practice Sleep Hygiene
   4. Plan Caffeine use prior to times of needed wakefulness
9. Management: Standard Medications
   1. See Hypersomnia
   2. First-Line Stimulants for Excessive Daytime Sleepiness
      1. Modafinil (Provigil)
         1. Best safety profile and lowest abuse potential of all stimulant agents
      2. Armodafinil (Nuvigil, generic)
      3. Solriamfetol (Sunosi, expensive)
   3. Other stimulants (risk of dependence) for Excessive Daytime Sleepiness
      1. Methylphenidate (Ritalin)
      2. Dextroamphetamine (Dexedrine)
   4. Symptomatic management of Cataplexy, Sleep Paralysis or hypnagogic Hallucinations
      1. SNRI (e.g. Venlafaxine) and SSRI agents (e.g. Fluoxetine) suppress REM Sleep
      2. Clomipramine (Anafranil)
   5. Combined stimulant and Cataplexy agents
      1. Gamma hydroxybutyric acid or Sodium oxybate (Xyrem)
         1. Given twice nightly
      2. Pitolisant (Wakix)
         1. Fewer adverse effects as Sodium oxybate with similar efficacy
         2. Xu (2019) Sleep Med 64:62-70 [PubMed]
10. References
    1. Billiard (2008) Neuropsychiatr Dis Treat 4(3):557-66 [PubMed]
    2. Holder (2022) Am Fam Physician 105(4): 397-405 [PubMed]
    3. Pagel (2009) Am Fam Physician 79(5): 391-6 [PubMed]
    4. Thorpy (2006) CNS Drugs 20(1): 43-50 [PubMed]
    5. Ramar (2013) Am Fam Physician 88(4): 231-8 [PubMed]