What are the diagnostic criteria and tests for narcolepsy?

How to Diagnose Narcolepsy

Diagnose narcolepsy through overnight polysomnography followed by a Multiple Sleep Latency Test (MSLT), with mean sleep latency ≤8 minutes and ≥2 sleep-onset REM periods confirming the diagnosis. 1

Clinical Presentation Required for Diagnosis

The diagnosis begins with identifying excessive daytime sleepiness occurring daily for at least 3 months as the core symptom. 1 When obtaining the history, interview both the patient and bed partner to capture the full clinical picture. 2

Key Symptoms to Assess

Primary symptoms:

• Excessive daytime sleepiness lasting ≥3 months is mandatory for diagnosis 1
• Cataplexy (sudden muscle weakness triggered by emotions, particularly laughter or anger) is pathognomonic when present with daytime sleepiness—patients remain conscious throughout episodes, have no amnesia, and can recall everything that happened 1, 3

Auxiliary symptoms:

• Hypnagogic/hypnopompic hallucinations (visual hallucinations at sleep onset or upon awakening) 1
• Sleep paralysis (immobility at sleep onset or upon awakening) 1
• Automatic behaviors during wakefulness 2
• Dreaming during brief naps 2

Critical History Elements

Document the following specific details:

• Onset, frequency, and duration of sleepiness and any remission periods 2
• Response to napping and whether dreaming occurs during naps 2
• Medical, neurologic, and psychiatric comorbidities 2
• Current and recently discontinued medications, alcohol, and recreational drugs 2
• Symptoms of obstructive sleep apnea or restless leg syndrome 2
• Duration of nighttime sleep to exclude sleep deprivation 2

Use the Epworth Sleepiness Scale (ESS) as a standardized assessment tool, along with sleep diaries. 2

Physical Examination

Perform a thorough physical examination including detailed neurologic evaluation. 2 Assess cognition both for diagnostic purposes and to establish a baseline for monitoring treatment response. 2

Diagnostic Testing Algorithm

Step 1: Overnight Polysomnography (PSG)

The MSLT must be preceded by overnight PSG to rule out other sleep disorders. 1 The PSG may show:

• Short nocturnal REM sleep latency 4
• Unexplained arousals 4
• Periodic leg movements 4
• Evidence of sleep apnea (which is more common in narcolepsy) 4

Note that the PSG may be completely normal in narcolepsy patients. 4

Step 2: Multiple Sleep Latency Test (MSLT)

The MSLT involves 4-5 daytime nap opportunities at 2-hour intervals, measuring latency to sleep onset and sleep type. 2

Diagnostic criteria:

• Mean sleep latency ≤8 minutes across all nap opportunities 1
• Presence of REM sleep on ≥2 naps 2, 1

Both criteria must be met for MSLT confirmation of narcolepsy. 1

Step 3: CSF Hypocretin-1 Testing (When Indicated)

CSF hypocretin-1 levels can confirm Type 1 narcolepsy (narcolepsy with cataplexy) when:

• Levels are ≤110 pg/mL or <1/3 of mean normal control values 1
• MSLT is unavailable or contraindicated 2
• Type 1 narcolepsy shows very low or undetectable orexin levels 3

Important caveat: CSF testing is not routinely recommended in Prader-Willi syndrome despite narcolepsy-like features, as levels are typically not as low as in narcolepsy type 1. 5

Additional Laboratory Testing

Order the following to identify alternative causes of hypersomnia:

• Brain MRI to identify neurologic causes (tumors, multiple sclerosis, intracranial bleeds, strokes) 2
• Thyroid stimulating hormone 2
• Liver function tests 2
• Complete blood count 2
• Serum chemistry 2

When to Refer to Sleep Specialist

Refer to a sleep specialist when narcolepsy or idiopathic hypersomnia is suspected or when the cause of sleepiness is unknown. 1 Sleep specialists have the expertise to differentiate narcolepsy from other causes of excessive sleepiness and manage complex pharmacological treatment. 1

Common Diagnostic Pitfalls

Misdiagnosis as psychiatric disorders or epilepsy is common because only 15% of patients manifest all symptoms together. 6 Cataplexy can be mistaken for seizures, but key distinguishing features include:

• Preserved consciousness during cataplexy (vs. altered consciousness in epilepsy) 3
• Emotional triggers, especially laughter 3
• No post-ictal confusion 3
• Episodes typically shorter than the ~1 minute duration of epileptic movements 3

Delayed diagnosis occurs frequently—only 15-30% of narcoleptic individuals are ever diagnosed, and nearly half first present after age 40. 4 Be aware that medications commonly used in older adults may complicate MSLT interpretation. 2

In children, cataplexy presents differently with profound facial hypotonia, active tongue/perioral movements, and may occur without clear emotional triggers, resembling seizures but without loss of consciousness. 3