Patient screening

Distinguishing Between Narcolepsy Type 1 and Type 2

Overview of The International Classification of Sleep Disorders (ICSD) – Third Edition

  • The American Academy of Sleep Medicine has subdivided the classification of narcolepsy into narcolepsy type 1 and narcolepsy type 21
  • In narcolepsy type 1:
    • Both excessive daytime sleepiness (EDS) and cataplexy are core features1
    • A diagnosis must now be confirmed with laboratory testing1
    • Laboratory testing includes sleep laboratory testing with overnight polysomnography (PSG) followed by a multiple sleep latency test (MSLT),* or cerebrospinal fluid (CSF) hypocretin-1 measurement1
  • In narcolepsy type 2:
    • Excessive daytime sleepiness is the essential feature1
    • Cataplexy is absent1
    • A diagnosis must be confirmed with laboratory testing1
      • Laboratory testing includes sleep laboratory testing with overnight PSG followed by an MSLT1*
*Sleep laboratory testing should be performed according to standard techniques, and results should be carefully interpreted in the context of the patient’s clinical history in the presence of EDS. At least 1 week of actigraphy assessment with a sleep log is strongly recommended prior to MSLT to determine factors that may bias results (eg, insufficient sleep, shift work, or other circadian rhythm disorder).1

Narcolepsy Type 1: ICSD-3 Criteria

As outlined by the American Academy of Sleep Medicine (AASM)

Diagnosing narcolepsy type 1 in adults requires identifying both1:

  1. Daily periods of the irrepressible need to sleep or daytime lapses into sleep, occurring for at least 3 months1
  2. The presence of one or both of the following1:
    1. Cataplexy and mean sleep latency of 8 minutes or less and at least 2 sleep onset rapid eye movement periods (SOREMPs) on a multiple sleep latency test (MSLT)1*
      • A SOREMP (within 15 min of sleep onset) on the preceding nocturnal polysomnogram (PSG) may replace one of the SOREMPs on the MSLT1
        • If narcolepsy type 1 is strongly suspected clinically but MSLT criteria (see B1, above) are not met, a possible strategy is to repeat the MSLT1
    2. Cerebrospinal fluid (CSF) hypocretin-1 concentration, measured by immunoreactivity, is either 110 pg/mL or less, or less than ⅓ of mean values obtained in normal subjects using the same standardized assay1
*Sleep laboratory testing should be performed according to standard techniques, and results should be carefully interpreted in the context of the patient’s clinical history in the presence of EDS. At least 1 week of actigraphy assessment with a sleep log is strongly recommended prior to MSLT to determine factors that may bias results (eg, insufficient sleep, shift work, or other circadian rhythm disorder).1

Narcolepsy Type 2: ICSD-3 Criteria

As outlined by the American Academy of Sleep Medicine (AASM)

Diagnosing narcolepsy type 2 requires identification of all of the following1:

  1. Daily periods of irrepressible need to sleep or lapses into daytime sleep, occurring for at least 3 months1
  2. Mean sleep latency of 8 minutes or less and at least 2 sleep onset rapid eye movement periods (SOREMPs) on a multiple sleep latency test (MSLT)1*
    • A SOREMP (within 15 min of sleep onset) on the preceding nocturnal polysomnogram (PSG) may replace one of the SOREMPs on the MSLT1
  3. Absence of cataplexy1
    • If cataplexy develops later, then the disorder should be reclassified as narcolepsy type 11
  4. Cerebrospinal fluid (CSF) hypocretin-1 concentration is either not measured, or found to be either greater than 110 pg/mL, or greater than ⅓ of mean values obtained in normal subjects using the same standardized assay1
    • If the CSF hypocretin-1 concentration is tested at a later stage and found to be either 110 pg/mL or less, or less than ⅓ of mean values obtained in normal subjects with the same assay, then the disorder should be reclassified as narcolepsy type 11
  5. Hypersomnolences and/or MSLT findings are not better explained by other causes such as insufficient sleep, obstructive sleep apnea, delayed sleep phase disorder, or the effect of medication or substances or their withdrawal1
* Sleep laboratory testing should be performed according to standard techniques, and results should be carefully interpreted in the context of the patient’s clinical history in the presence of EDS. At least 1 week of actigraphy assessment with a sleep log is strongly recommended prior to MSLT to determine factors that may bias results (eg, insufficient sleep, shift work, or other circadian rhythm disorder).1

Screening for Excessive Daytime Sleepiness (EDS) in Narcolepsy

Patient screening for EDS may be performed using the Epworth Sleepiness Scale (ESS)2-4

  • Patients often cannot report their own level of EDS2,5
  • Assessment tools such as the ESS are therefore helpful in quantifying the degree of sleepiness2-4
  • The ESS can also be used to monitor the progression of or improvement in EDS and has been shown to be reliable for test-retest use over a period of months2,6
  • The ESS is a subjective scale that assesses the propensity to doze or fall asleep in 8 common daytime activities3,4
    • Sitting and reading
    • Watching television
    • Sitting inactive in a public place (eg, a theater or meeting)
    • As a passenger in a car for an hour without a break
    • Lying down to rest in the afternoon when circumstances permit
    • Sitting and talking to someone
    • Sitting quietly after a lunch without alcohol
    • In a car, while stopped for a few minutes in traffic
  • Patient levels of EDS can be assessed using a simple, self-administered questionnaire3
  • Patients rate their propensity for dozing in each situation on a 4-point scale3
    • From 0, indicating they “would never doze,” to 3, indicating a “high chance of dozing”
  • A score of 0 to 10 is considered normal4
  • A score of greater than 10 is suggestive of EDS but is not diagnostic for a specific sleep disorder including narcolepsy4
  • A score of 16 or above is suggestive of a high level of EDS and is associated with significant sleep disorders including narcolepsy3

Patients with an ESS score of greater than 10 may need to be evaluated for a potential sleep disorder including narcolepsy3,4

A narcolepsy diagnosis should be established by a sleep specialist with a nighttime polysomnogram (PSG) followed by a multiple sleep latency test (MSLT).1

Screening for Narcolepsy With Cataplexy

Initial patient screening for narcolepsy with cataplexy can be performed using the Swiss Narcolepsy Scale (SNS)7-9

  • The SNS is a subjective scale that helps screen for a symptom profile suggestive of narcolepsy with cataplexy7-9
  • Patients are assessed using a self-reporting questionnaire7
  • Patients answer 5 questions to assess the frequency of the following symptoms7
    • Q1: How often are you unable to fall asleep?
    • Q2: How often do you feel bad or not well rested in the morning?
    • Q3: How often do you take a nap during the day?
    • Q4: How often have you experienced weak knees/buckling of the knees during emotions like laughing, happiness, or anger?
    • Q5: How often have you experienced sagging of the jaw during emotions like laughing, happiness, or anger?
  • Patients rate the frequency of individual symptoms based on a 5-point scale7
    From 1, indicating "never" to 5, indicating "almost always"
  • Each answer is weighted by a positive or negative factor, according to the following equation7,9
    (6 x Q1) + (9 x Q2) – (5 x Q3) – (11 x Q4) – (13 x Q5) + 20
  • A total SNS score of less than 0 is suggestive of narcolepsy with cataplexy7,9

In a study that included patients with narcolepsy with cataplexy, an SNS score of less than 0 was found to have a sensitivity of 96% and a specificity of 98%9

In an additional study that included patients with narcolepsy with cerebrospinal fluid hypocretin-1 deficiency, an SNS score of less than 0 was reported to have a sensitivity of 93% and a specificity of 92%8

A narcolepsy diagnosis should be established by a sleep specialist with a nighttime polysomnogram (PSG) followed by a multiple sleep latency test (MSLT).1

Laboratory Testing for Narcolepsy

Polysomnography (PSG): An objective measurement of nighttime physiology

  • PSG testing is routinely indicated, together with a multiple sleep latency test, for assessing the potential presence of narcolepsy10
  • PSG testing also helps identify whether other sleep pathologies, such as obstructive sleep apnea, are present2
  • PSG testing:
    • Records normal and abnormal physiologic activity over the course of a night2,10
    • Documents the adequacy of sleep, including frequency, duration, and total amounts of different sleep stages2,10
  • In addition, PSG testing results can identify the nighttime occurrence of sleep onset rapid eye movement periods (SOREMPs)10
    • A SOREMP is defined as REM sleep within 15 minutes of sleep onset1
    • A SOREMP on an overnight PSG can be used as 1 of the 2 or more SOREMPs necessary for a narcolepsy diagnosis according to the ICSD-31
  • A SOREMP on a nocturnal PSG is a highly specific marker for narcolepsy in the absence of another sleep disorder, but with low sensitivity1,11
    • In patients who experience a SOREMP on a nocturnal PSG11:
      • Reevaluation of cataplexy should be considered11
      • Combination PSG/multiple sleep latency test (MSLT) should be considered11
  • PSG testing also measures airflow, respiratory effort, and leg activity2,10

Interpreting PSG testing results

The multiple sleep latency test (MSLT): An objective measurement of daytime physiology

  • The MSLT is indicated as part of the evaluation of patients with potential narcolepsy to confirm the diagnosis, and is performed immediately following overnight polysomnography14
    • In addition, performing an MSLT following a complete night of polysomnography is important since sleep latency is influenced by the quantity of prior sleep14
    • The MSLT also should not be performed after a split-night sleep study, as its value in supporting a narcolepsy diagnosis may be suspect if the total night sleep on the prior sleep period is less than 6 hours14
  • The MSLT assesses:
    • The ability or tendency to fall asleep (as indicated by mean sleep latency, or time to sleep onset) during normal waking hours1,14
    • The presence of sleep onset rapid eye movement periods (SOREMPs)1,14
  • Measurements are taken during four or five 20-minute nap opportunities at 2-hour intervals2,14
  • Normally, mean sleep latency is more than 10 minutes and SOREMPs (REM sleep onset less than or equal to 15 min) usually do not occur1,15
  • In narcolepsy, mean sleep latency is 8 minutes or less and a SOREMP will occur during at least 2 of the 4 or 5 daytime nap periods1,2,14,15

Interpreting MSLT results*

* At least 1 week of actigraphy assessment with a sleep log is strongly recommended prior to an MSLT to determine factors that may bias results (eg, insufficient sleep, shift work, or other circadian rhythm disorder). Patients should be free of drugs that influence sleep for at least 14 days (or at least 5 times the half-life of the drug and longer-acting metabolite) before performing an MSLT.1

Please see full Prescribing Information, including BOXED Warning.