Sleep-stage transitions during polysomnographic recordings as diagnostic features of type 1 narcolepsy

Abstract

Objective: Type 1 narcolepsy/hypocretin deficiency is characterized by excessive daytime sleepiness, sleep fragmentation, and cataplexy. Short rapid eye movement (REM) latency (≤15 min) during nocturnal polysomnography (PSG) or during naps of the multiple sleep latency test (MSLT) defines a sleep-onset REM sleep period (SOREMP), a diagnostic hallmark. We hypothesized that abnormal sleep transitions other than SOREMPs can be identified in type 1 narcolepsy.

Methods: Sleep-stage transitions (one to 10 epochs to one to five epochs of any other stage) and bout length features (one to 10 epochs) were extracted from PSGs. The first 15 min of sleep were excluded when a nocturnal SOREMP was recorded. F(0.1) measures and receiver operating characteristic curves were used to identify specific (≥98%) features. A data set of 136 patients and 510 sex- and age-matched controls was used for the training. A data set of 19 cases and 708 sleep-clinic patients was used for the validation.

Results: (1) ≥5 transitions from ≥5 epochs of stage N1 or W to ≥2 epochs of REM sleep, (2) ≥22 transitions from ≥3 epochs of stage N2 or N3 to ≥2 epochs of N1 or W, and (3) ≥16 bouts of ≥6 epochs of N1 or W were found to be highly specific (≥98%). Sensitivity ranged from 16% to 30%, and it did not vary substantially with and without medication or a nocturnal SOREMP. In patients taking antidepressants, nocturnal SOREMPs occurred much less frequently (16% vs. 36%, p < 0.001).

Conclusions: Increased sleep-stage transitions notably from ≥2.5 min of W/N1 into REM are specifically diagnostic for narcolepsy independent of a nocturnal SOREMP.

Keywords: Diagnostic features; Narcolepsy; Polysomnography; Sleep-stage transitions.

Fig. 1.

Illustration of the transition feature groups. A total of eight feature groups were computed whereof seven of them hold the transition feature groups “To REM sleep,” “To N3 sleep,” “To N2 sleep,” “To N1 sleep,” “To wakefulness,” “To N2/N3 sleep,” and “To W/N1 sleep.” Every transition from one to 10 epochs before the transition to one to five epochs after the transition was identified and summed. The first feature in the “To N3 sleep” feature group thus holds the total number of transitions defined as one epoch of REM sleep to one epoch of N3 sleep; the second feature holds the total number of transitions defined as two epochs of REM sleep to one epoch of N3 sleep, etc.

Fig. 2.

ROC curves for the final chosen features, where the sleep-stage transition counts are for the entire night. The red dots indicate the performance measures where sensitivity and specificity are equally rated, and the black dots indicate the chosen thresholds for which the specificity measure yielded a minimum of 98% on the training data set. The blue curves represent the training data set and the green curves represent the validation data set.