What is the workup for narcolepsy?

Diagnostic Workup of Narcolepsy

The diagnostic workup for narcolepsy must include polysomnography (PSG) followed by a multiple sleep latency test (MSLT), which are essential for confirming the diagnosis and ruling out other sleep disorders. 1

Clinical Evaluation

Key Symptoms to Assess

• Excessive daytime sleepiness (EDS) - cardinal symptom present in all cases
• Cataplexy (sudden loss of muscle tone triggered by emotions) - highly specific for narcolepsy type 1
• Sleep paralysis (inability to move while falling asleep or waking up)
• Hypnagogic/hypnopompic hallucinations (vivid dream-like experiences)
• Disrupted nighttime sleep
• Automatic behaviors (performing routine activities with no later recall)

Important Clinical Features

• Age of onset (typically second or third decade, but can occur at any age)
• Presence of frequent short naps that feel refreshing
• Emotional triggers for cataplexy (especially laughter)
• Family history of sleep disorders
• Recent infections or vaccinations (potential triggers)

Diagnostic Testing

First-Line Testing

1. Overnight Polysomnography (PSG)

   • Rules out other sleep disorders (OSA, PLMD)
   • May show:
     • Short sleep latency
     • Short REM sleep latency (<20 minutes)
     • Fragmented sleep architecture
     • Unexplained arousals

2. Multiple Sleep Latency Test (MSLT) - performed the day after PSG

   • Diagnostic criteria for narcolepsy:
     • Mean sleep latency <8 minutes
     • ≥2 sleep-onset REM periods (SOREMPs)
   • Must be performed after adequate nocturnal sleep documented by PSG
   • Patient should be free of medications that affect sleep for 2 weeks prior

Additional Testing to Consider

• HLA typing (HLA-DQB1*06:02) - supportive but not diagnostic
• Hypocretin-1 (orexin) levels in cerebrospinal fluid (CSF)
  • Low or undetectable levels (<110 pg/mL) are diagnostic for narcolepsy type 1
  • Requires lumbar puncture
  • Particularly useful when MSLT results are equivocal or when medication withdrawal is not possible

Differential Diagnosis Evaluation

• Obstructive sleep apnea (OSA)
• Insufficient sleep syndrome
• Idiopathic hypersomnia
• Delayed sleep phase disorder
• Depression
• Medication effects
• Seizure disorders

Pitfalls and Caveats

1. MSLT Reliability Issues

   • False positives and false negatives can occur
   • Ensure patient has adequate sleep prior to testing (confirmed by sleep diary or actigraphy)
   • Withdraw REM-suppressing medications (antidepressants) at least 2 weeks before testing

2. Pediatric Considerations

   • Cataplexy in children may present differently (facial hypotonia, motor tics)
   • Children may not report sleepiness but show behavioral problems or poor school performance
   • Obesity is common in children with narcolepsy (>50%)

3. Common Misdiagnoses

   • Epilepsy (cataplexy mistaken for seizures)
   • Psychiatric disorders (hallucinations mistaken for psychosis)
   • ADHD (inattention due to sleepiness)

4. Testing Timing

   • Consider delaying testing in cases of recent infection or vaccination
   • Repeat testing may be necessary if initial results are equivocal

Treatment Considerations

After diagnosis, treatment should focus on improving excessive daytime sleepiness and cataplexy:

1. First-line medications for EDS:

   • Modafinil (200-400mg daily) - FDA approved, strong recommendation 1, 2
   • Pitolisant - strong recommendation for adults 1

2. For cataplexy:

   • Sodium oxybate - effective for both EDS and cataplexy 1
   • Antidepressants (SNRIs, SSRIs) for cataplexy management

3. For pediatric patients:

   • Modafinil (conditional recommendation) 1
   • Sodium oxybate (conditional recommendation) 1

4. Non-pharmacologic approaches:

   • Scheduled daytime naps
   • Regular sleep schedule
   • Sleep hygiene education

The diagnostic process requires careful attention to clinical history, proper testing protocols, and consideration of age-specific presentations to ensure accurate diagnosis and appropriate treatment of this chronic neurological disorder.