Making the Narcolepsy Diagnosis

  • A full clinical interview assessing the presence of narcolepsy symptoms, especially a history of cataplexy, is essential for making a diagnosis of narcolepsy.1,2

  • Validated scales such as the Epworth Sleepiness Scale (ESS)1-4  and Swiss Narcolepsy Scale (SNS)5 can be used to identify narcolepsy symptoms (see Screening Tools).

  • Sleep laboratory testing, consisting of overnight polysomnogram (PSG) followed by a multiple sleep latency test (MSLT), is recommended to assess the severity of sleepiness, rule out other concomitant sleep disorders, and confirm the narcolepsy diagnosis.1

  • Cerebrospinal fluid (CSF) assessment of hypocretin-1 levels is another objective test that can confirm a narcolepsy type 1 diagnosis.1,6

Overnight Polysomnogram (PSG)

An overnight PSG* should be performed the night before multiple sleep latency test (MSLT) testing in order to rule out significant sleep disorders that may cause excessive daytime sleepiness, to assess for common coexisting conditions, such as obstructive sleep apnea (OSA), and to help confirm the narcolepsy diagnosis.1

What to look for
  • A short (within 15 min) latency to REM sleep after sleep onset (SOREMP) on the overnight PSG is a specific diagnostic marker for narcolepsy in the absence of another sleep disorder (see Diagnostic Criteria).1,7
    • A SOREMP on overnight PSG has been reported to occur in <1% of patients with other sleep disorders, such as OSA, compared with 35% to 50% of patients with narcolepsy type 1.7,8 An overnight PSG test may also identify sleep patterns that are often characteristic of narcolepsy, including: a short initial sleep latency; fragmented sleep, multiple awakenings; frequent transitions to lighter stages of sleep (eg, stage 1); and increased amount of stage 1 sleep.1,10,11 In addition, REM sleep without accompanying muscle atonia may be present.1

Multiple Sleep Latency Test (MSLT)

A daytime MSLT* should be performed in order to quantify the severity of excessive daytime sleepiness and to confirm the narcolepsy diagnosis.1

What to look for
  • An MSLT profile that meets the diagnostic criteria for narcolepsy includes mean sleep latency ≤8 minutes and ≥2 SOREMPs (REM latency within 15 minutes of sleep onset). A SOREMP on the overnight PSG can be used as one of the 2 SOREMPs.1
    • A study found the specificity of these MSLT findings to be >90%; this study compared patients with narcolepsy type 1 with population-based controls and with all patients with sleep disorders undergoing a nocturnal sleep study.7
    • Despite the high specificity of MSLT testing, the International Classification of Sleep Disorders, 3rd ed (ICSD-3) recommends that the MSLT be preceded by ≥1 week of actigraphic recording with a sleep log to rule out other causes of excessive daytime sleepiness or other factors that could bias the results of the MSLT, such as insufficient sleep, shift work, or another circadian rhythm sleep disorder.1
  • Standard Procedures
    • According to the ICSD-3, the following conditions should be met for correct interpretation of MSLT findings:
      • The patient must be free of drugs that influence sleep for ≥14 days (or ≥5 times the half-life of the drug and longer-acting metabolite), confirmed by urine drug screen. Nocturnal PSG should be performed on the night immediately preceding the MSLT to rule out other sleep disorders that could mimic the diagnostic features of narcolepsy. The sleep-wake schedule must have been standardized and, if necessary, extended to a minimum of 7 hours in bed each night for at least 7 days before PSG (preferably documented by sleep log and, whenever possible, actigraphy). Sleep time during polysomnography should be curtailed as little as possible with the goal of at least 7 hours asleep.1

CSF Hypocretin-1

A CSF hypocretin-1 level <110 pg/mL is a highly specific and sensitive finding for the diagnosis of narcolepsy type 1.1,6

What to look for
  • Hypocretin deficiency in patients with excessive daytime sleepiness is considered diagnostic for narcolepsy type 1 in the ICSD-31 and narcolepsy in the DSM-5.9 Hypocretin deficiency is generally defined as CSF hypocretin-1 levels ≤110 pg/mL or <1/3 (≤1/3 in DSM-5) of mean values obtained using the same assay in healthy subjects.1,9

Notes:

*It is important that sleep laboratory testing be performed under appropriate conditions using standardized techniques and be interpreted within the clinical context of the patient’s history and symptoms.

Sleep time during PSG should be curtailed as little as possible with the goal of at least 7 hours of sleep.1

It is strongly recommended that adequate sleep be documented by sleep log and, whenever possible, actigraphy for a period of 1-2 weeks prior to the MSLT.1

REM = rapid eye movement

+References