Summary

Narcolepsy is a chronic neurological disorder of sleep-wake regulation caused by the selective loss of Orexin (Hypocretin) producing neurons in the Lateral Hypothalamus. It is characterised by the "Tetrad of Narcolepsy": Excessive Daytime Sleepiness (EDS), Cataplexy (sudden loss of muscle tone triggered by emotion), Sleep Paralysis, and Hypnagogic Hallucinations. There are two types: Type 1 (With Cataplexy + Low Orexin) and Type 2 (Without Cataplexy + Normal Orexin). Diagnosis typically follows an overnight PSG followed by a Multiple Sleep Latency Test (MSLT) showing rapid sleep onset (<8 mins) and early REM onset (SOREMPs). Management involves stimulants (Modafinil/Pitolisant) for EDS and REM-suppressants (Venlafaxine/Sodium Oxybate) for cataplexy. [1,2]

Key Facts

• Prevalence: 1 in 2,000. Underdiagnosed (average delay 10 years).
• Mechanism: Autoimmune destruction of Hypocretin neurons (HLA-DQB1*0602 associated).
• Type 1 vs Type 2: Type 1 is defined by Orexin deficiency or Cataplexy. Type 2 is a diagnosis of exclusion.
• H1N1 Link: The 2009 Pandemrix vaccine was associated with a spike in cases (Molecular mimicry).
• Sleep Architecture: REM sleep intrudes into wakefulness (Cataplexy = REM paralysis while awake).

Clinical Pearls

"The Knees Buckle with Laughter": Cataplexy is almost exclusively triggered by POSITIVE emotion (laughter, joking). If it happens with stress or fear, question the diagnosis.

"Sleeping at the Wheel": EDS is not just tiredness; it is an irresistible "Sleep Attack". Patients may fall asleep while talking or eating.

"Micro-sleeps": Automatic behaviour can continue during sleep attacks (e.g., writing nonsense while asleep in class).

"Sodium Oxybate (GHB)": A powerful sedative used to consolidate night-time sleep. It is highly regulated but transforms quality of life for severe Type 1 patients.

1. Excessive Daytime Sleepiness (EDS)

• The primary symptom. Usually first to appear.
• Sleep Attacks: Irresistible urge to sleep. Refreshing short naps (15-20 mins).
• Epworth Sleepiness Scale: Usually >15/24.

2. Cataplexy (Type 1 Specific)

• Sudden, transient loss of muscle tone.
• Trigger: Emotion (Laughter, Surprise, Anger).
• Severity: Range from simply jaw dropping/knees buckling to full collapse.
• Consciousness: Preserved. The patient can hear everything but cannot move.
• Duration: Seconds to minutes.

3. Sleep Paralysis

• Inability to move upon falling asleep or waking up.
• Often accompanied by terrifying sensation of a "presence" in the room.

4. Hypnagogic Hallucinations

• Hypnagogic: Upon falling asleep.
• Hypnopompic: Upon waking.
• Vivid, often frightening visual/auditory hallucinations (e.g. intruder, fire).

5. Disrupted Nocturnal Sleep

• Paradoxically, despite EDS, night sleep is fragmented.

• Obstructive Sleep Apnoea (OSA): Commonest cause of EDS.
• Idiopathic Hypersomnia: EDS without SOREMPs/Cataplexy. Difficult to treat.
• Sleep Deprivation: By far the most common cause in society.

• AASM Guidelines: Treatment of Narcolepsy.
• EFNS Guidelines.

What is Narcolepsy?

It is not just "being tired". Your brain has lost the chemical (Orexin) that keeps you awake and regulates your dreams.

What is Cataplexy?

It is like a "short circuit" where strong emotion triggers the paralysis that usually happens when you are dreaming. So when you laugh, your muscles relax and you might fall.

Can I drive?

Not until your symptoms are fully controlled. Most patients can return to driving once stable on medication, but you must inform the DVLA/DMV.

Common Exam Questions

1. Physiology:

• Q: What is the defining feature of Narcolepsy on MSLT?
• A: SOREMPs (Sleep Onset REM Periods). Entering REM sleep almost immediately.

2. Pharmacology:

• Q: What is the mechanism of Pitolisant?
• A: H3 Receptor Inverse Agonist (increases Histamine release).

3. Signs:

• Q: Does cataplexy involve loss of consciousness?
• A: No. It is pure loss of tone. Consciousness is preserved.

Multiple Sleep Latency Test (MSLT)

• Preparation:
  • Stop REM suppressants (SSRI/TCA) 2 weeks prior. (Rebound REM can cause false positives).
  • Urine Drug Screen (exclude stimulants/cannabis).
  • Adequate prior sleep (PSG showing >6h sleep the night before).
• Protocol: 4 or 5 nap opportunities at 2-hour intervals. 20 minutes allowed to fall asleep.
• Results:
  • Narcolepsy: Mean Sleep Latency <8 min AND ≥2 SOREMPs.
  • Idiopathic Hypersomnia: Mean Sleep Latency <8 min but <2 SOREMPs.
  • Normal: Mean Sleep Latency >10-15 min. No SOREMPs.

"The Invisible Disability."

• Education: Children with narcolepsy are often labelled as "lazy" or "bored". Teachers need education (allow scheduled naps).
• Employment: Unpredictable sleep attacks limit career choices (e.g. Pilot, HGV Driver, shift work).
• Driving:
  • UK (DVLA): Must cease driving on diagnosis. Can return if symptoms controlled for 3 months.
  • Cataplexy: If triggered by laughter, is driving safe? (Usually yes, unless triggered by road rage).

Advanced Viva Questions

1. Pharmacology:

• Q: What is the risk of Sodium Oxybate?
• A: Respiratory Depression (especially with alcohol). Abuse potential (GHB). It has a very narrow therapeutic inded.

2. Physiology:

• Q: How does Orexin affect appetite?
• A: Orexin is "Orexigenic" (stimulates appetite). Paradoxically, Narcolepsy patients (who lack it) are often obese. This is likely due to metabolic dysregulation and inactivity.

3. Genetics:

• Q: What is the utility of HLA testing?
• A: High Negative Predictive Value. If you are HLA-DQB10602 Negative, you almost certainly do NOT have Type 1 Narcolepsy.*

16. Patient and Layperson Explanation (Expanded)

• What is Narcolepsy?: It is a biological condition where the brain lacks the chemical "Orexin" which keeps you awake. It is like a car with a faulty ignition switch - the engine cuts out unexpectedly.
• Sleep Hygiene: Regular naps. Avoid heavy meals. No alcohol close to bedtime.
• Safety: If you feel sleepy, stop driving immediately. It is illegal and dangerous to continue.

17. Deep Dive: Sodium Oxybate (Xyrem)

"The Paradoxical Sedative."

• What is it?: Sodium salt of Gamma-Hydroxybutyrate (GHB).
• Mechanism: GABA-B agonist. It is a powerful neurological depressant.
• Role in Narcolepsy:
  • It is taken at night (liquid dose at bedtime + second dose 4 hours later).
  • It forces the brain into deep Slow Wave Sleep (SWS), which Narcoleptics lack.
  • By consolidating night sleep, it reduces daytime sleepiness AND cataplexy (by suppressing REM pressure).
• Safety:
  • Respiratory depression risk.
  • Strict "Risk Evaluation and Mitigation Strategy" (REMS) program.
  • Patient must not drink alcohol.

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.