Assessment of glymphatic function in narcolepsy using DTI-ALPS index

Sleep is a modulator of glymphatic activity which is altered in various sleep disorders. Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness (EDS), rapid onset of rapid eye movement (REM) sleep, cataplexy, disturbed night sleep with fragmentation. It is categorized into two types, type 1 (NT1) and type 2 (NT2) depending on the presence of cataplexy and/or absence of orexin. We sought for alterations in glymphatic activity in narcoleptic patients using diffusion tensor imaging (DTI) along perivascular space (ALPS) index on magnetic resonance imaging (MRI).

Adult patients diagnosed with NT1 or NT2 who had polysomnography (PSG) and MRI with DTI were included in the study. Sleep recording included Epworth Sleepiness Scale (ESS) score, sleep latency during multiple sleep latency test (MSLT), sleep efficiency during night PSG, wake after sleep onset (WASO), REM sleep latency during PSG, percentage of non-REM (NREM), REM sleep and wakefulness during night PSG. DTI-ALPS index was calculated for each patient and age-sex matched healthy control(HC)s.

The study group was composed of 25 patients [F/M = 15/10, median age = 34 (29.5-44.5)], 14 with NT1 and 11 with NT2 disease. ESS, WASO and percentage of wakefulness were significantly higher in NT1 patients (p < 0.05). Mean DTI-ALPS was not significantly different neither between narcoleptic patients and HCs, nor between NT1 and NT2 patients (all, p > 0.05). However, DTI-ALPS was negatively correlated with WASO (r = -0.745, p = 0.013) and percentage of wakefulness (r = -0.837, p = 0.005) in NT1 patients. DTI-ALPS correlated negatively with percentage of N1 sleep (r = -0.781, p = 0.005) but positively with REM percentage (r = 0.618, p = 0.043) in NT2 patients.

In this study, DTI-ALPS was not significantly different in narcoleptic patients than the HCs. However, the glymphatic index as assessed by DTI-ALPS correlated with PSG parameters; negatively with WASO, percentage of wakefulness in NT1, percentage of N1 sleep in NT2, and positively with REM sleep in NT2. A tendency for a reduction in DTI-ALPS in NT1 patients compared to both NT2 patients and HCs was also found. These findings might show the first evidence of an alteration of glymphatic activity, especially in NT1 patients, thus warrant further prospective studies in larger size of narcoleptic patient cohorts.