癫痫与睡眠障碍相关机制研究进展

睡眠在癫痫疾病管理中具有非常重要的作用,睡眠的昼夜节律可以影响癫痫的发作频率及发作时间。睡眠质量下降是癫痫发作的常见诱因,提高睡眠效率和控制癫痫发作对所有癫痫患者的生活质量都有显著积极影响。癫痫发作过程机制复杂,目前研究表明癫痫发作时细胞兴奋性及一系列的神经递质、激素、离子通道发生变化,这些变化可能会作用于睡眠-觉醒周期,引发睡眠结构及昼夜节律发生变化。而这些关联可能为针对癫痫控制及癫痫患者睡眠障碍和昼夜节律紊乱提供新的治疗途径,从而达到既能良好的控制癫痫发作,又能改善患者的睡眠,从而改善患者生活质量。     

睡眠与癫痫的研究进展

癫痫与睡眠障碍并存，常导致诊断错误和癫痫发作恶化。同时睡眠障碍、抗惊厥药物及癫痫发作均对癫痫患者有影响，睡眠与癫痫发作相互作用，形成恶性循环。本文综述了睡眠及睡眠障碍对癫痫患者的各种影响。     

癫痫与睡眠

癫痫和睡眠之间相互作用、密切相关。癫痫发作和癫痫样放电对于睡眠结构、睡眠效率等具有显著的影响,同样睡眠觉醒周期也影响癫痫样活动的分布和频率,且纠正睡眠障碍有助于癫痫的治疗。本文简要综述了癫痫和睡眠之间的相互关系和机理。     

癫痫患者全夜自然睡眠结构的研究

目的　观察癫痫患者发作间期全夜自然睡眠结构特点 ,并评价其与正常对照组睡眠结构的差异 ;评价发作类型、用药情况及是否记录到发作间电发放对睡眠结构的影响。方法　对 2 0名癫痫患者及 11名对照进行全夜自然睡眠多导监测 ,并结合患者的发作类型、是否记录到发作间电发放 (IIDs)及服用 AEDs的情况进行分组统计分析 ,评价各组患者与正常对照间各睡眠参数的差异。结果　癫痫患者组 ,记录到 IIDs组 ,及该组患者中部分性发作者和未服 AEDs者均较正常对照 TRT、RL 显著延长 (P<0 .0 5)。记录到 IIDs的患者睡眠效率显著下降 (P≤0 .0 5) ,其中部分性发作者入睡后觉醒次数较全身性发作者显著增多 (P<0 .0 5)。部分性发作者较全身性发作者NREM睡眠期转换次数有增高的趋势。不同用药癫痫患者睡眠脑电图较正常对照组睡眠破碎性增加。结论　癫痫患者与正常对照比较 RL延长 ;睡眠破碎性增加 ;记录到 IIDs的患者睡眠效率降低 ;部分性发作患者较全身性发作患者有 NREM期转换次数频繁的趋势 ;记录到 IIDs患者中服用 AEDs的情况对其睡眠结构无显著影响。     

剥夺睡眠与睡眠诱发试验脑电图对不同类型癫痫的作用

目的：探讨诱发试验脑电图与不同类型癫痫的关系及临床意义。方法：对９８例临床确诊的癫痫患者分别进行常规脑电图检查和剥压睡眠诱发及睡眠诱发脑电图试验,比较三次结果的异常率和棘波出现率。结果：睡眠与剥夺睡眠诱发试验均可提高脑电图的异常率和棘波出现率,均可提高全身性强直阵挛发作、复杂部分性发作和失神发作等类型癫痫的棘波出现率,录夺睡眠诱发还可提高简单部分发作棘波的出现率,而对多种类并存者和不能分类者均无意义。结论：诱发试验提高棘波出现率不仅与诱发方法有关,而且与癫痫的发作类型有关。     

录像脑电图监测对发作性疾病的诊断价值

目的研究录像脑电图（VEEG）在癫痫的诊断、鉴别诊断和临床发作分型中的价值,探讨癫痫患者自然睡眠时相与样放电之间的关系。方法使用录像脑电图对93例发作性疾病患者进行长程脑电监测,记录清醒和睡眠时的脑电图,并作诱发试验,明确发作性质,确定癫痫的临床发作类型,并分析发作间期癫痫样放电的睡眠-觉醒时相分布。结果93例发作性疾病患者中有临床发作者51例,样放电者72例,结合病史、临床表现和EEG结果而诊断为癫痫71例,其中69例患者确定了临床发作类型,20例修正了临床发作类型;71例确诊为癫痫患者中有完整睡眠-觉醒周期者65例,觉醒期有样放电者49例,睡眠期有样放电者61例,其中NREMⅠ-Ⅱ期52例（85.2%）,NREMⅠ-Ⅳ期3例（4.9%）,NREWⅢ-Ⅳ期6例（9.9%）,REM期未见。结论VEEG检测有利于癫痫的诊断和确定临床发作分型,睡眠监测有助于样波的检出,睡眠期样放电主要出现于NREMⅠ-Ⅱ期。     

剥夺睡眠脑电图对儿童精神运动性癫痫的诊断价值及其影响因素

目的 研究剥夺睡眠脑电图(EEG)对儿童精神运动性癫痫的诊断价值及其影响因素.方法 对110例常规EEG检查阴性的精神运动性癫痫患儿进行剥夺睡眠EEG检查;比较剥夺睡眠EEG检查阳性与阴性患儿的有关临床资料;并对有关指标作多因素Logistic回归分析.结果 睡眠剥夺EEG检查阳性62例(56.4％)、阴性48例(43.6％).与睡眠剥夺EEG阴性组相比,阳性组有缺氧窒息史的比率显著增高,有发作诱因的比率和癫痫的发作频率明显降低,发作时间明显延长(P ＜0.05 ～0.01).多因素Logistic回归分析显示,发作诱因、发作频率和发作时间是影响睡眠剥夺EEG阳性率的相关因素(P ＜0.05～0.001).结论 剥夺睡眠EEG可提高儿童精神运动性癫痫的诊断率,癫痫的发作诱因、发作频率和发作时间均为影响其阳性率的因素.     

女性癫痫患者生物标记物的研究进展

<正>癫痫是女性常见的神经系统疾病，全球大约有50万癫痫女性处于育龄期。女性癫痫患者一生面临诸多挑战，约1/3的女性癫痫患者会出现月经期癫痫^[1]。此外，女性癫痫患者在妊娠前需要关注癫痫和妊娠的相关问题，如控制癫痫发作、抗癫痫药物致畸性和补充叶酸等问题。睡眠和癫痫是一种双向关系，有1/3的癫痫患者在睡眠期间出现癫痫发作，24%～55%的癫痫患者报告有睡眠障碍^[2]。本综述介绍了细胞色素P4501A1 (CYP1A1)、亚甲基四氢叶酸还原酶(MTHFR)、微粒体环氧化物水解酶(EPHX1)、快速动眼睡眠百分比(REM%)等与女性癫痫患者相关的生物标记物，为女性癫痫患者的靶向治疗提供思路和手段。     

成人癫痫共患抑郁患者睡眠障碍的临床特点及其影响因素

目的探讨成人癫痫共患抑郁患者睡眠障碍的临床特点及其影响因素。方法采取横断面研究方法,对100例癫痫患者应用贝克抑郁量表Ⅱ(BDI-Ⅱ)进行评估。癫痫患者与年龄、性别等严格匹配的50名健康成人均完成匹兹堡睡眠质量量表(PSQI)和Epworth嗜睡量表(ESS)评定。结果 100例成人癫痫患者中30例共患抑郁,共患率为30%。癫痫共患抑郁患者PSQI总分和ESS总分分别为(5.93±1.41)分和(6.57±4.48)分,均高于非抑郁癫痫组分别为(2.09±1.38)分和(3.79±1.98)分及对照组分别为(0.94±0.91)分和(2.30±1.53)分,P0.05。多元回归分析显示癫痫共患抑郁组的PSQI总分与病程和发作控制相关(t=4.279,2.406;P0.05);癫痫共患抑郁组的ESS总分与病程和发作类型相关(t=6.662,2.645;P0.05)。结论成人癫痫共患抑郁患者白天嗜睡程度增加、睡眠质量下降,其损害的严重程度与患者的病程、发作控制和发作类型密切相关。     

癫痫患者睡眠感知误差与睡眠结构的关系

目的 探讨癫痫患者睡眠感知误差与睡眠结构的关系。方法 收集102例癫痫患者,比较 低估睡眠时间组、评估基本准确组、高估睡眠时间组间睡眠结构的差异。结果 78%的癫痫患者存在睡 眠感知误差,低估者占35%,高估者占43%。与评估基本准确组比较,低估组伴有强直-阵挛发作的比例 更高。在高估组、评估基本准确组、低估组间,N1+2期脑电醒觉指数依次趋于增大;与评估基本准确组比较, 高估组N3 期觉醒比例增大。结论 大多数癫痫患者存在睡眠感知误差,伴有强直-阵挛发作者趋于低估 睡眠时间。癫痫患者的睡眠感知误差与睡眠不稳定性有关;其中,低估睡眠时间与N1+2 期睡眠不稳定性 增加有关,高估睡眠时间与N3期睡眠不稳定性增加有关。     

Correlations Between Night Sleep Duration and Seizure Frequency in Temporal Lobe Epilepsy

Summary: Correlations between occurrence of complex partial seizures and altered sleep duration were analyzed in a small but strongly homogeneous population of temporal lobe epilepsy patients. Sleep deprivation and oversleep were determined individually; 682 epileptic seizures occurring on 4,995 days were related to occasional alterations of night sleep duration. The seizure-inducing effect of an actual relative sleep deprivation was 67-100% in four cases and 49-64% in four cases. Oversleep had no consistent seizure-provoking effect. Relative sleep deprivation may have a seizure-provoking effect, especially in temporal lobe epilepsy. This information may be used to instruct epileptic patients concerning sleep hygiene which might improve the efficacy of antiepileptic drug (AED) treatment, even if no change is made in medication.     

Increased sleep fragmentation in experimental autoimmune encephalomyelitis

Sleep disturbance in patients with multiple sclerosis is prevalent and has multifactorial causes. In mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, we determined the dynamic changes of sleep architecture and the interactions between sleep changes and EAE symptoms. The changes of sleep patterns were mainly reflected by altered sleep stage distribution and increased sleep fragmentation. Increased waking and decreased non-rapid eye movement sleep occurred after EAE onset and persisted through the symptomatic phase. There also was increased sleep state transition, indicating a reduction of sleep cohesiveness. Furthermore, the extent of sleep fragmentation correlated with the severity of disease. This is the first study of sleep characteristics in EAE mice demarcating specific changes related to the autoimmune disorder without confounding factors such as psychosocial impact and treatment effects. The reduction of sleep efficiency and cohesiveness supports the notion that enhancing sleep might facilitate the recovery of mice from EAE, pertinent to the multimodality treatment of multiple sclerosis.     

Cancer-related problems,sleep quality,and sleep disturbance among long-term cancer survivors at 9-years post diagnosis

ObjectiveTo estimate the prevalence of sleep difficulties in a large cohort of long-term cancer survivors (>5 years) and examine associations with four domains of cancer-related problems.MethodsThis study analyzed a nationwide sample (N = 1903) of cancer survivors (31% Breast; 20% prostate) at nine years (m = 8.9 sd = 0.6) post-diagnosis with a mean age of 64.5 years. Sleep quality and sleep disturbance were assessed by the Pittsburgh Sleep Quality Index. Multivariable logistic regression models examined associations between cancer-related problems (physical distress, emotional distress, economic distress, and fear of recurrence) and sleep difficulty (poor vs. low sleep quality and high vs. low sleep disturbance). Odds ratios (OR) and 95% confidence intervals (CI) were estimated, adjusting for medico-demographics, behavioral factors, and sleep medication use.ResultsIn sum, 20% percent of the sample reported poor sleep quality, 51% reported high sleep disturbance and 17% reported both. Sleep medication use was reported by 28% of the total sample. All four domains of cancer-related problems were significantly associated with poor sleep quality and high sleep disturbance. Above median cancer-related physical distress had the strongest association with both poor sleep quality (OR = 3.42; 95% CI = 2.44–4.79) and high sleep disturbance (OR = 4.06; 95% CI = 3.09–5.34).ConclusionsAmong nine-year cancer survivors, multiple domains of cancer-related health problems were associated with sleep difficulties. Knowledge of the relationship between cancer-related problems and sleep may aid clinicians during the evaluation and treatment of sleep problems in long-term cancer survivors. Future research should utilize prospective data to better understand the causal nature of the associations.     

Intracerebral hemorrhage and sleep-disordered breathing

Objective/BackgroundLimited data are available on sleep-disordered breathing (SDB) following intracerebral hemorrhage (ICH). Our aim was to characterize the objective measures of post-ICH SDB and questionnaire-reported pre-ICH sleep characteristics, overall and by ethnicity.Patients/MethodsParticipants with ICH who were enrolled in the population-based Brain Attack Surveillance in Corpus Christi project (2010–2016) reported their pre-ICH sleep duration and completed the Berlin Questionnaire to characterize pre-ICH risk of SDB. A subsample was screened for SDB (respiratory event index ≥10) using ApneaLink Plus portable monitoring. Ethnic differences in post-ICH SDB or questionnaire-reported pre-ICH sleep characteristics were assessed using a log binomial model or a linear regression model or a Fisher's exact test.ResultsICH cases (n = 298) were enrolled (median age = 68 years, 67% Mexican American). Among 62 cases with complete ApneaLink data, median time to post-ICH SDB screening was 11 days (IQR: 6, 19). Post-ICH SDB prevalence was 46.8% (95% CI: 34.4–59.2), and this rate did not differ by ethnicity (p = 1.0). Berlin Questionnaires for 109 of the 298 ICH cases (36.6% (95% CI: 31.1–42.0)) suggested a high risk for pre-ICH SDB, and the median pre-ICH sleep duration was eight hours (IQR: 6, 8). After adjusting for confounders, there was no difference in ethnicity in high risk for pre-ICH SDB or pre-ICH sleep duration.ConclusionsNearly half of the patients had objective confirmation of SDB after ICH, and more than one-third had questionnaire evidence of high risk for pre-ICH SDB. Opportunities to address SDB may be common both before and after ICH.     

Maternal and paternal sleep during pregnancy in the Child-sleep birth cohort

Study objectivesMaternal and paternal sleep insufficiency during pregnancy appears to be a risk factor for health and wellbeing in young families. Here, we evaluated the prevalence of sleep insufficiency and symptoms of insomnia during pregnancy (at 32nd pregnancy week) and their relationship to depression, anxiety and environmental stress.MethodsThe study is based on a population based sample from Finland consisting of 1667 mothers and 1498 fathers from the Child-sleep birth cohort. We evaluated both the core symptoms of insomnia (sleep onset problems, nocturnal awakenings, too-early awakenings, and poor sleep quality) and the presence of insufficient sleep. Insufficient sleep was defined as a two-hour difference between self-assessed sleep need and reported sleep duration, or sleep duration shorter than six hours per night.ResultsWe found that symptoms of insomnia were more prevalent among women than among men (9.8% vs. 6.2%), whereas sleep debt was less prevalent among women than among men (4.5% vs. 9.6%). Overall, 11.8% of the women and 14.9% of the men reported either significant insomnia or short sleep. Symptoms of insomnia were related to symptoms of depression both among women and men (AOR 3.8, 95% CI 2.6–5.6 vs. AOR 1.9, 95% CI 1.1–3.2), while short sleep was related to depression among women (AOR 3.3, 95% CI 1.8–5.8), and to low education, poor health and a larger number of children among men.ConclusionsThe study showed that insomnia and sleep insufficiency are prevalent among women and men during pregnancy. The findings underline the impact of insomnia to both maternal and paternal health during pregnancy as well as to the implementation of effective interventions to prevent negative consequences of sleep disturbances.     

Sleep Reactivity and Sleep Efforts in Shift Workers

ObjectiveThe current study aimed to investigate the differences in sleep reactivity and sleep effort differs among late night shift workers (LSWs) and non-late night shift workers (non-LSWs), and non-shift workers (non-SWs). MethodsIn total, 6,023 participants (1,613 non-SWs, 3,339 LSWs, and 1,071 non-LSWs) were recruited. Non-SWs was defined as those who works at fixed schedules during standard daylight. LSWs was defined as who work late night hours (10 _PM–6 _AM), while non-LSWs was SWs who did not work during late night. All completed the Ford Insomnia Response to Stress Test (FIRST), the Glasgow Sleep Effort Scale (GSES), the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Insomnia Severity Index (ISI), and the short-term Center for Epidemiologic Studies-Depression scale (CES-D) through online survey. ResultsLSWs and non-LSWs reported higher FIRST, GSES scores than non-SWs. In addition, LSWs reported higher FIRST, GSES scores than non-LSWs. FIRST scores were correlated with CES-D, PSQI, ISI, and ESS for LSWs, non-LSWs, and non-SWs alike. GSES scores were also correlated with CES-D, PSQI, ISI, and ESS for LSWs, non-LSWs, and non-SWs alike. ConclusionSWs showed higher sleep reactivity and sleep effort than non-SWs. LSWs had higher sleep reactivity and sleep effort than non-LSWs, and these variables are associated with insomnia, daytime sleepiness, and depressive symptoms. Our findings suggests that late night schedule, may increase sleep reactivity and sleep effort, which are associated with sleep and mood disturbances.     

Intranasal oxytocin increases respiratory rate and reduces obstructive event duration and oxygen desaturation in obstructive sleep apnea patients: a randomized double blinded placebo controlled study

BackgroundActivation of the oxytocin network has shown benefits in animal models of Obstructive Sleep Apnea (OSA) as well as other cardiorespiratory diseases. We sought to determine if nocturnal intranasal oxytocin administration could have beneficial effects in reducing the duration and/or frequency of obstructive events in obstructive sleep apnea subjects.MethodsTwo sequential standard “in-lab” polysomnogram (PSG) sleep studies were performed in patients diagnosed with OSA that were randomly assigned to initially receive either placebo or oxytocin (40 i.u.) administered intranasally in this double blinded randomized placebo controlled study. Changes in cardiorespiratory events during sleep, including apnea and hypopnea durations and frequency, risk of event-associated bradycardias, arterial oxygen desaturation and respiratory rate were assessed in 2 h epochs following sleep onset. Oxytocin significantly decreased the duration of obstructive events, as well as the oxygen desaturations and incidence of bradycardia that were associated with these events. Notably, oxytocin increased respiratory rate during non-obstructive periods. There were no significant changes in sleep architecture and no adverse effects were reported.ConclusionsOxytocin administration can benefit OSA subjects by reducing the duration and adverse consequences of obstructive events. Oxytocin could also be beneficial in situations involving respiratory depression as oxytocin increased respiratory rate. Additional studies are needed to further understand the mechanisms by which oxytocin promotes these changes in cardiorespiratory function. The long-term efficacy and optimal dose of intranasal oxytocin treatment should also be determined in OSA subjects.ClinicalTrials.gov NCT03148899.     

Sleep homeostasis in the rat in the light and dark period

Sleep is regulated by the interaction of a homeostatic (Process S) and a circadian component. The duration of prior wakefulness is the main factor influencing subsequent sleep duration and its intensity. We investigated in the rat whether the sleep-wake history before sleep deprivation (SD) contributes to the effects of sleep loss incurred during the SD. A 24-h baseline recording was followed by 6 h SD at light onset (SD-Light, n=7), or at dark onset (SD-Dark, n=8) and 18 h recovery. Both SDs led to a pronounced increase in slow wave activity (SWA, EEG power between 0.75 and 4.0 Hz) in NREM sleep and increased sleep consolidation. The prolongation of sleep episodes was associated with increased intra-episode SWA. The amount of waking before the SD correlated positively with the SWA increase during recovery, and SWA levels before SD were negatively correlated with their subsequent increase. The time-course of SWA (Process S) as well as of single frequency bins within the SWA band was successfully simulated based on vigilance-state distribution. The time constant of the exponential monotonic decay (Td) was higher for the 0.75-1.0 Hz bin compared to all remaining frequency bins of the SWA band, reflecting a slower process determining the slow EEG component during sleep. The data show that the homeostatic response after SD, consisting of increased sleep intensity and sleep consolidation is determined by a combination of SD and the preceding vigilance-state history. The slower dynamics of low frequency delta power compared to fast delta frequencies point to heterogeneity within the traditionally defined SWA band.