Hypocretin-1/orexin-A, sleep and excessive daytime sleepiness in patients with nonconvulsive status epilepticus: A cross-sectional cohort study.

Background and Objectives: Nonconvulsive status epilepticus (NCSE) manifests as a change in mental status without a coma (NCSE proper) or comatose NCSE. Hypocretin-1/orexin-A (H/O) is involved in alertness and sleep maintenance. Sleep impairment and excessive daytime sleepiness (EDS) have a negative impact on cognitive functions and activities of daily living (ADL).
Methods: Patients meeting the NCSE criteria underwent cerebrospinal fluid and brain magnetic resonance imaging examinations, polysomnographies (PSG), multiple latency sleep tests (MSLT), and completed Epworth Sleepiness Scale (ESS). Montreal Cognitive Assessment was used to evaluate cognitive functions, and the Barthel Index was used to assess ADL in the acute phase (V1) and three months follow-up (V2).
Results: From May 2020 to May 2023, we enrolled 15 patients, eight (53.3 %) women, with a median age of 69 (14) years. The median H/O CSF concentration was 250 (63.6) pg/ml; however, only three CSF samples (20 %) decreased below the borderline concentration of 200 pg/ml. Fourteen out of 15 patients (93.3 %) completed the PSG study. The median of wakefulness after sleep onset was 167 (173.5) min, sleep efficiency (SE) was 62.9 (63) %, sleep latency (SL) was 6 (32) min, REM sleep was 2.85 (7.2) %, and REM first episode latency was 210.5 (196.5) minutes. The medians of the stages N1 NREM were 4.65 (15) %, N2 NREM 68.4 (29.9) %, and N3 NREM 21.8 (35.5) %. MSLT mean latency was 7.7 (12.6) minutes. A significant negative correlation exists between H/O CSF concentrations and the stage N1 NREM (r _s  = -0.612, p = 0.02), and the proportion of cumulative sleep time with oxygen saturation below 90 % in total sleep time (TST) t90 (r _s  = -0.57, p = 0.03). MSLT had significant negative correlation with TST (r _s  = -0.5369, p = 0.0478), with SE (r _s  = -0.5897, p = 0.0265), with apnea-hypopnea index (r _s  = -0.7631, p = 0.0002) and with deoxygenation index (r _s  = -0.8009, p = 0.0006). A positive correlation exists between MSLT and SL (r _s  = 0.6284, p = 0.0161) and between ESS and t90 (r _s  = 0.9014, p = 0.0004). The correlation between H/O CSF concentrations and EDS, cognitive performance, and ADL was not proved.
Conclusions: Patients after NCSE exhibited sleep impairment and excessive daytime sleepiness. Hypocretin-1/orexin-A concentrations decreased only in 20 % of these cases.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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