Identifying Markers to Discern Narcolepsy From Other Sleep Problems

Atonia index during wakefulness (WAI) might represent a promising electrophysiological marker of narcolepsy, as it suggests higher susceptibility to dissociative wake/sleep irregularity missing in other forms of hypersomnias, according to study findings published in Clinical Neurophysiology.¹ The investigators note that it could assist in distinguishing between narcolepsy and other hypersomnias.

The atonia index during REM sleep was significantly lower in narcolepsy type 1 (NT1) than in narcolepsy type 2 (NT2), validating that NT1 tends to present as REM sleep without atonia.

Narcolepsy is a sleep disorder represented by excessive daytime sleepiness, unexpected onsets of REM sleep periods, and fragmented night sleep, and it can be separated into NT1, which is classified by low levels of hypocretin, the patient reports bouts of cataplexy, or meets sleep study requirements, and NT2, which is diagnosed via reports of daytime sleepiness without patients showing symptoms of cataplexy, and patients usually have less severe symptoms with normal levels of hypocretin.² NT2 outnumbers NT1 significantly.²

This study was conducted because arriving at a diagnosis of narcolepsy calls for several diagnostic tests and invasive procedures that are complex and can cause delay. The investigators intended to discover the changes in muscle tone at different levels of vigilance during the complete MSLT and each nap in patients with NTI and NT2 compared with other hypersomnias and its potential diagnostic value.

Study participants were 29 patients with NT1 (mean [SD] age, 34.9 [16.8] years), 16 patients with NT2 (mean [SD] age, 39 [11.8] years), and 20 control patients with other hypersomnias (mean [SD] age, 45.1 [15.1]). There were 11 patients who were male and 18 patients who were female in the NT1 group, 10 patients who were male and 6 patients who were female in the NT2 group, and 10 patients who were male and 10 patients who were female in the control group.

Next, atonia index was assessed at different levels of vigilance (wake and REM sleep) in each nap and the entirety of the MSLT of each group. The validity of atonia index in classifying patients with narcolepsy (NT1 and NT2) was evaluated using receiver operating characteristic (ROC) curves.

The investigators found that WAI was significantly higher in narcolepsy groups (NT1 and NT2, P < .001) compared with the hypersomniac group. Atonia index during REM sleep (RAI) (P = .03) and WAI in nap with sudden onsets of REM sleep periods (SOREMP) (P = .001) were lower in NT1 than in NT2. The ROC curves showed high area under the curve (AUC) values for WAI in distinguishing participants experiencing other hypersomnias. RAI and WAI in nap with SOREMP showed a poor AUC value differentiating NT1 and NT2.

Good sensitivity and specificity values were especially obvious in NT2 and could be useful because of the poor test-retest reliability of MSLT in NT2 compared to NT1. RAI gave a less accurate AUC to discern NT1 from NT2, which did not surprise the authors, considering that prior studies have found REM sleep without atonia and REM sleep behavior disorder to have similar prevalence rates in NT1 and NT2.

“Therefore, the presence of RBD or RSWA both in NT1 and NT2 suggests the potential role of other than orexin-related intrinsic factors causing REM sleep instability,” the authors noted.

However, localized loss of hypocretin neurons was detailed in the posterior hypothalamus of patients with NT2, implying possible orexinergic dysfunction in NT2 as well. WAI was found to be similar in participants with NT1 and NT2, suggesting the role of other disease-related factors that cause REM sleep instability.

The authors said that WAI might be a promising electrophysiological biomarker of narcolepsy based on the traditional diagnostic MSLT. To their knowledge, this is the first study to focus on atonia index at different vigilance levels during MSLT in people with narcolepsy.

They also wrote that future larger and multicenter studies using multiple compound indices should confirm the data; these studies should use patients with idiopathic hypersomnia as a comparison group, and idiopathic hypersomnia with or without long duration of sleep should be distinguished. Lastly, atonia index changes should be analyzed during different sleep stages in night polysomnography as described for RBD to improve its clinical interpretation.

References

1. Romigi A, Caccamo M, Testa F, et al. Muscle atonia index during multiple sleep latency test: a possible marker to differentiate narcolepsy from other hypersomnias. Clin Neurophysiol. 2023;149:25-31. doi:10.1016/j.clinph.2023.01.019

2. Sleep Center of Middle Tennessee. What is narcolepsy? causes, symptoms, diagnosis & treatment. Sleep Center of Middle Tennessee. August 31, 2020. Accessed March 17, 2023. https://sleepcenterinfo.com/blog/what-is-narcolepsy-causes-symptoms-diagnosis-treatment/