Nocturnal features and daytime characteristics in narcolepsy: reliability and diagnostic relevance for NT1 Versus NT2.

STUDY

OBJECTIVES

Assess test-retest reliability of nighttime sleep and daytime maintenance of wakefulness tests (MWTs) over a short time interval in drug-free individuals with narcolepsy; evaluate the diagnostic utility of features with good reliability.

METHODS

We analyzed the placebo arms from clinical trials in narcolepsy type 1 (NT1; n = 17; NCT05687903) and narcolepsy type 2 (NT2; n = 19; NCT05687916). Participants visited the clinic three times, four weeks apart, which included nocturnal polysomnography (nPSG) and MWT the following day. From the nPSG and daytime MWT, we derived 440 features and assessed test-retest reliability, visit effects, and NT1-NT2 differences.

RESULTS

Quantitative electroencephalography (qEEG) showed high reliability, with the top 10 features showing reliability >0.88; the 10 most reliable hypnogram features ranged from 0.68-0.78. qEEG and MWT sleep onset latencies (SOLs) were less reliable in NT2. N1 percentage, stage shift index, and wake after sleep onset were reliable and differed between diagnoses (r = 0.54-0.75; higher in NT1, p < .05). MWT SOLs at 2 p.m. and 4 p.m. demonstrated good reliability in NT1 (r = 0.89, 0.87) and differed between diagnoses (shorter in NT1; p = .037, .010). Hypnodensity Wake-REM mixtures were reliable (r = 0.83) and differed between diagnoses (higher in NT1, p = .001).

CONCLUSIONS

qEEG features showed the strongest reliability but rarely distinguished diagnoses. Measures of sleep fragmentation and wakefulness reliably differentiated NT1 from NT2 and are practical for clinical assessments and trials. Hypnodensity features, though not yet used clinically, are reliable and may offer diagnostic value. NT2 exhibited greater variability in nighttime sleep and daytime wakefulness across visits.