An 11-year-old female with a recent diagnosis of narcolepsy came to our institution for a second opinion. She was experiencing daytime sleepiness, had moderate snoring at night, and an Epworth Sleepiness Scale score (modified scale for children) of 13. She had experienced no instances of falling asleep at unintended times (i.e., no sleeping during meals or class). She additionally had no prior instances of sleep paralysis, hypnagogic or hypnopompic hallucinations, or cataplexy. Her normal major sleep time was from 23:00 to 07:00 and she took no medications. On physical examination BMI was 21 (85th percentile), Mallampati score was 3, neck circumference was 14.25 inches, and tonsils were grade 2.
Reports from outside polysomnogram (PSG) and multiple sleep latency test (MSLT) were obtained, and the pertinent results are shown in Table 1.
The patient was given a diagnosis of narcolepsy as her mean sleep latency (MSL) was ≤ 8 minutes and she had 2 sleep onset REM periods (SOREMPs).
QUESTION: Does this patient have narcolepsy?
ANSWER: The diagnosis of narcolepsy cannot be made based on the initial PSG and MSLT due to deviations from the recommended protocol that reduce the validity of testing.
Narcolepsy is a diagnosis made with careful clinical consideration and attention to established protocols for PSG and MSLT. The PSG preceding the MSLT should occur during a patient's normal major sleeping time, with a minimum total sleep time (TST) of 360 minutes. Given that other sleep disorders (e.g., OSA) can result in an MSLT meeting narcolepsy diagnostic criteria, the PSG should be negative for alternate causes of sleepiness. The MSLT should begin with an initial nap 1.5–3 hours after the end of nocturnal PSG, with subsequent naps every 2 hours. The established MSLT criteria for narcolepsy are MSL ≤ 8 min and ≥ 2 SOREMPs. A SOREMP on the PSG may count as one of the 2 SOREMPs.1,2 One should note that SOREMPs are not specific to narcolepsy and can occur in other sleep disorders, including untreated OSA and insufficient sleep. For these reasons, before pursuing MSLT to diagnose narcolepsy, full treatment of OSA should take place. If narcolepsy is still suspected despite adequate treatment of OSA with CPAP, MSLT can then be pursued. To address the potential confounding effects of inadequate sleep, the PSG preceding the MSLT must have a TST ≥ 360 minutes. Ideally the patient should have regular and sufficient sleep during the 2 weeks preceding testing.3–5
In our case, the results of our patient's outside MSLT are confounded for multiple reasons. First, PSG did not take place during the patient's normal major sleep time. Although the initial nap started more than 1.5 h after the lights-on time, the fact that the lights-on time and the initial nap were at 04:17 and 06:13, respectively, hardly replicates the patient's normal sleeping time. The patient typically woke up at 07:00 daily and thus had to wake up nearly 3 hours earlier than her regular wake time for this study. Second, subsequent naps were all less than 2 hours apart—a clear variation in protocol.1,3,5 Additionally, the study was terminated after 4 naps and SOREMPs were identified in the first and third naps. Although stopping the study after 4 naps is acceptable protocol if 2 SOREMPs have already occurred,4 if the physician disagrees with the technologist's scoring of REM on the MSLT, the opportunity to identify an additional SOREMP on the fifth nap is missed. SOREMPs in this patient may have been related to the first nap occurring during her usual sleep period and decreased opportunity in the PSG for REM sleep due to early awakening. It is important to note that in adolescents without narcoleptic symptoms, early rise time (earlier school start), delayed circadian phase, and insufficient sleep can all lead to pressure to have REM on MSLT. Indeed, Carskadon et al. showed that in 10th graders without symptoms of narcolepsy or immediate family history, REM occurred once on MSLT in 48% (12/25), and twice in 16% (4/25).6 REM on MSLT must therefore be carefully interpreted in adolescents who are forced to wake up early, even if it is their typical schedule. Finally, it should also be noted that mild sleep apnea was present on the initial PSG as her AHI was 2.6 (an AHI ≥ 1 is diagnostic in pediatric patients), and full treatment should have occurred prior to MSLT.1,3,5
After evaluating the patient and review of prior studies, we ordered repeat PSG followed by MSLT. PSG was repeated, as there was concern that the prior study may have underestimated the severity of sleep apnea given the termination of the study prior to the time the patient likely had a significant amount of REM sleep. Repeat MSLT was indicated, as appropriate study conditions were not present during initial testing4 and the patient's parents were hesitant to proceed with treatment of sleep apnea if the cause of sleepiness was narcolepsy. A PSG was performed with lights out at 21:07 and lights on at 06:25. The findings included a TST of 522 minutes, an AHI of 3.2, and no SOREMP. An MSLT followed PSG with first nap at 08:10 and subsequent naps spaced 2 hours apart according to the established protocol. The patient slept in 4 of 5 naps. The MSL was 10.7 minutes and no SOREMPs occurred. The MSLT did not support a diagnosis of narcolepsy, and the patient's sleepiness was attributed to mild OSA given an AHI of 3.2. Referral was made to ENT and the patient underwent tonsillectomy and adenoidectomy with resolution of symptoms.
SLEEP MEDICINE PEARLS
When evaluating a patient with a prior diagnosis of narcolepsy, one should carefully review the previous MSLT for errors in protocol and confounding variables or medications.
It is important to question the patient (or parent) concerning the pattern of typical sleep before testing.
MSLT must be preceded by a PSG with an adequate sleep time (360 minutes) during the patient's normal major sleep time. “Adequate” sleep time must be considered based on the age of the patient with children requiring more sleep than adults. The initial nap should be 1.5 to 3 hours after the end of nocturnal PSG, and subsequent naps spaced 2 hours apart.1,3,4,5
Underlying causes of sleepiness (such as OSA, inadequate sleep, or poor sleep hygiene) should be fully treated prior to any future MSLT, if it is still indicated.1,3,4
A repeat MSLT is indicated if the previous MSLT was not done according to protocol or if initial MSLT is negative in a patient where narcolepsy is strongly suspected.
This was not an industry supported study. The authors have indicated no financial conflicts of interest.
continuous positive airway pressure
mean sleep latency
multiple sleep latency test
obstructive sleep apnea
sleep onset REM period
total sleep time
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