Narcolepsy in Adult Patients: Clinical Insights

The International Classification of Sleep Disorders, third edition, text revision (ICSD-3-TR) diagnostic criteria require results from objective sleep laboratory testing to support a narcolepsy diagnosis.¹ An MSLT, which measures the patient’s physiologic tendency to fall asleep under standardized conditions, is the primary objective measure.^1,2

A mean MSLT sleep latency of ≤8 minutes defines pathological sleepiness for the purposes of a narcolepsy diagnosis, but it is not diagnostic unless there is also objective evidence of REM sleep dissociation, the occurrence of sleep-onset REM periods (SOREMPs).¹

Multiple SOREMPs during an MSLT are more specific to narcolepsy than short sleep latency. However, SOREMPs may also be observed with insufficient sleep, circadian rhythm sleep-wake disorders, sleep-related breathing disorders, using or withdrawing from certain substances/medications, or in individuals without narcolepsy. Therefore, a patient’s MSLT results should be considered alongside the patient’s medical history and clinical history, rather than being solely relied upon for diagnosis.¹

MSLTs should be conducted based on standardized procedures that are defined in the American Academy of Sleep Medicine (AASM) recommended protocol.^1,2 Patients should be encouraged to obtain adequate sleep during the preceding week and especially during the night prior to the MSLT.¹ It is recommended that adequate sleep is documented by sleep log and actigraphy, whenever possible, for 1 to 2 weeks prior to conducting the MSLT.²

Adequate sleep on the night prior to the MSLT should be documented on overnight PSG. The average amount of sleep required for healthy adults is ≥7 hours; the nighttime PSG should allow for a minimum of 7 hours of time in bed and a minimum of 6 hours of sleep, with timing that corresponds to the patient’s major sleep period. This may require delaying the start of the MSLT to accommodate a later termination of the PSG.²

The occurrence of ≥1 SOREMP on the overnight PSG in the presence of cataplexy is diagnostic for narcolepsy type 1, and can replace one of the 2 SOREMPs on the MSLT required for a diagnosis of narcolepsy type 2.¹

Narcolepsy is divided into narcolepsy type 1 and narcolepsy type 2 based on the concept that the presence of orexin (hypocretin) deficiency is a fundamental marker of narcolepsy type 1; however, CSF hypocretin-1 testing is not required for a narcolepsy diagnosis. If CSF hypocretin-1 is measured, the threshold for diagnosis of narcolepsy type 1 is ≤110 pg/mL or less than one-third of mean values obtained in normal subjects using the same standardized assay. Low CSF hypocretin-1 is diagnostic of narcolepsy in the presence of EDS that is not better explained by another sleep disorder, mental disorder, or medication/substance use or withdrawal.¹

Objective sleep testing is essential for making a differential diagnosis of narcolepsy.¹