Challenges in diagnosing narcolepsy without cataplexy: a consensus statement

Abstract

Background: Diagnosing narcolepsy without cataplexy is often a challenge as the symptoms are nonspecific, current diagnostic tests are limited, and there are no useful biomarkers. In this report, we review the clinical and physiological aspects of narcolepsy without cataplexy, the limitations of available diagnostic procedures, and the differential diagnoses, and we propose an approach for more accurate diagnosis of narcolepsy without cataplexy.

Methods: A group of clinician-scientists experienced in narcolepsy reviewed the literature and convened to discuss current diagnostic tools, and to map out directions for research that should lead to a better understanding and more accurate diagnosis of narcolepsy without cataplexy.

Recommendations: To aid in the identification of narcolepsy without cataplexy, we review key indicators of narcolepsy and present a diagnostic algorithm. A detailed clinical history is mainly helpful to rule out other possible causes of chronic sleepiness. The multiple sleep latency test remains the most important measure, and prior sleep deprivation, shift work, or circadian disorders should be excluded by actigraphy or sleep logs. A short REM sleep latency (≤ 15 minutes) on polysomnography can aid in the diagnosis of narcolepsy without cataplexy, although sensitivity is low. Finally, measurement of hypocretin levels can helpful, as levels are low to intermediate in 10% to 30% of narcolepsy without cataplexy patients.

Keywords: insomnia; multiple sleep latency test; narcolepsy; polysomnography.

Figure 1

Proposed algorithm for the diagnosis of narcolepsy without cataplexy and its differential diagnoses. ISS, insufficient sleep syndrome (chronic sleep deprivation); CSF, cerebrospinal fluid; EDS, excessive daytime sleepiness; ESS, Epworth Sleepiness Scale; MSL, mean sleep latency; MSLT, multiple sleep latency test; SOREMP, sleep onset rapid eye movement sleep. ⁽¹⁾ In patients with an atypical history or neurological deficits, other causes of narcolepsy-like findings should be considered, and a brain MRI should be performed. Suggested laboratory parameters include a full iron panel, complete blood count, vitamin B12, and thyroid markers (TSH, T4). Children with Na-2 should receive a more extensive workup for unusual causes of sleepiness (e.g., tumors, metabolic disorders, seizures). ⁽²⁾ Sleep logs or preferably actigraphy over 14 days should be performed before the PSG and MSLT to exclude ISS or shift work. If the habitual sleep schedule is a concern, it may be helpful to schedule the MSLT just after 1-2 weeks' vacation to provide an opportunity for adequate sleep on a regular schedule. ⁽³⁾ During the nocturnal PSG, the patient should be permitted their habitual amount of sleep, which will usually be more than 6 hours of sleep. Long sleepers should be allowed to sleep up to 10 hours. ⁽⁴⁾ MSLT should be performed according to AASM guidelines, and medications that might alter sleep pressure or REM sleep should be discontinued well in advance. For example, antidepressants should be discontinued at least 3 weeks prior to the sleep studies. ⁽⁵⁾ According to ICSD-3 criteria, one SOREMP within 15 minutes of sleep onset on the preceding nocturnal PSG can be included in the total SOREMP count. ⁽⁶⁾ In patients without cataplexy, we recommend measuring CSF hypocretin to distinguish Na-1 from Na-2. ⁽⁷⁾ A clinical history of frequent hypnagogic/hypnopompic hallucinations, frequent sleep paralysis, fragmented nocturnal sleep, or positive HLA DQB1*06:02 typing may increase the likelihood of Na-2. ⁽⁸⁾ Sleep inertia, the need for multiple alarm clocks, and long but unrefreshing daytime naps are more indicative of idiopathic hypersomnia. ⁽⁹⁾ In patients with multiple SOREMPs but normal mean sleep latency or normal hypocretin levels, the MSLT should be repeated, preferably after a period of documented sleep extension.