What are the diagnostic criteria and tests for narcolepsy?

How to Diagnose Narcolepsy

Narcolepsy diagnosis requires overnight polysomnography followed by a Multiple Sleep Latency Test (MSLT) showing mean sleep latency ≤8 minutes with ≥2 sleep-onset REM periods, or alternatively, CSF hypocretin-1 levels ≤110 pg/mL in patients with cataplexy. 1

Clinical Diagnostic Criteria

Essential Symptom

• Excessive daytime sleepiness (EDS) occurring daily for at least 3 months is required for diagnosis 1
• Patients typically experience brief involuntary sleep episodes and decreased ability to regulate sleep-wake cycles 2

Pathognomonic Feature

• Cataplexy (sudden muscle weakness triggered by emotions, particularly laughter or anger) is diagnostic for narcolepsy when present with daytime sleepiness 1, 3
• Manifests as leg/arm weakness, knee buckling, or dropping objects 1
• Consciousness remains completely preserved during episodes, with no amnesia for the event 3
• Approximately 60-90% of narcolepsy patients have cataplexy 4

Additional Supportive Symptoms

• Hypnagogic/hypnopompic hallucinations (visual hallucinations at sleep onset or upon awakening) 1
• Sleep paralysis (immobility at sleep onset or upon awakening) 1
• Only 15% of patients manifest all symptoms together 4

Comprehensive History Taking

Key Questions to Address

• Obtain history from both patient and bed partner 5
• Assess excessive daytime sleepiness, cataplexy presence, and symptom response to napping 5
• Inquire about dreaming during naps, hypnagogic hallucinations, sleep paralysis, and automatic behaviors 5
• Establish onset, frequency, duration of sleepiness, and any remission episodes 5
• Document medical, neurologic, psychiatric illnesses and medication use (prescription drugs, recreational drugs, alcohol) 5
• Screen for comorbid sleep disorders including obstructive sleep apnea and restless leg syndrome 5
• Determine duration of nighttime sleep 5

Validated Assessment Tools

• Epworth Sleepiness Scale (ESS) should be part of the evaluation 5
• Sleep diaries are useful assessment tools 5

Physical Examination

• Perform thorough physical examination including neurologic evaluation 5
• Assess cognition to help establish diagnosis and monitor treatment response 5

Diagnostic Testing Algorithm

First-Line Testing

Step 1: Overnight Polysomnography (PSG)

• Must precede MSLT to rule out other sleep disorders 1, 6
• May show short nocturnal REM sleep latency, unexplained arousals, or periodic leg movements 7
• PSG may be completely normal in narcolepsy patients 7

Step 2: Multiple Sleep Latency Test (MSLT)

• Consists of 4-5 daytime naps at 2-hourly intervals 5
• Diagnostic criteria: mean sleep latency ≤8 minutes AND ≥2 sleep-onset REM periods 1, 6
• Assesses latency to sleep onset and type of sleep that occurs 5

Alternative Confirmatory Testing

CSF Hypocretin-1 Measurement

• Diagnostic threshold: ≤110 pg/mL or <1/3 of mean normal control values 1, 6
• Can confirm narcolepsy with cataplexy in the absence of MSLT 5
• Type 1 narcolepsy shows very low or undetectable orexin levels 3
• Caused by degeneration of hypothalamic hypocretin-producing neurons 6, 4

Additional Laboratory Testing

• Brain MRI to identify neurologic causes (tumors, multiple sclerosis, intracranial bleeds, strokes) 5
• Blood work to exclude medical causes of excessive sleepiness: thyroid stimulating hormone, liver function tests, complete blood count, serum chemistry 5

Referral Criteria

Refer to sleep specialist when:

• Narcolepsy or idiopathic hypersomnia is suspected 1
• Cause of sleepiness is unknown 1
• Sleep specialists have expertise to differentiate narcolepsy from other causes and manage complex pharmacological treatment 1

Common Pitfalls and Caveats

Medication Interference

• Common medications used for chronic conditions in older adults may complicate MSLT interpretation 5
• Careful withdrawal of sedating medications is prudent before testing 5

Differential Diagnosis Challenges

• Cataplexy must be distinguished from epilepsy: patients with absence or partial complex epilepsy remain upright during attacks, while cataplexy may cause falls 3
• Distinguish from syncope: syncope involves loss of consciousness with prodromal symptoms, while cataplexy preserves consciousness 3
• In children, cataplexy presents atypically with facial hypotonia and hyperkinetic movements that may resemble seizures 3

Diagnostic Delays

• Only 15-30% of narcoleptic individuals are ever diagnosed or treated 7
• Nearly half first present for diagnosis after age 40 years due to mild disease severity or misdiagnoses 7

Special Considerations

• Do not routinely perform CSF hypocretin-1 testing in Prader-Willi syndrome despite narcolepsy-like features, as levels are typically not as low as in narcolepsy type 1 6
• Exclude sleep deprivation as a cause by ensuring adequate nighttime sleep opportunity 5
• Attention to periodic leg movements, sleep apnea, and REM sleep behavior disorder is particularly important in older patients 7