伴中央颞区棘波良性儿童癫痫睡眠期痫样放电对听觉前注意加工的影响

Effects of sleep epileptiform discharge on aural pre-attentive processing of children with benign childhood epilepsy with central-temporal spikes

目的探讨伴中央颞区棘波良性儿童癫痫（benign childhood epilepsy with central-temporal spikes，BECTS）患儿听觉信息的前注意加工及其与非快速眼动（NREM）睡眠期的发作间期痫样放电（interictal epileptiform discharge，IED）的关系，为BECTS患儿认知功能损害的早期评估及干预提供较为客观的电生理依据。方法选取2012年2月至2015年11月在新乡医学院第二附属医院诊断为BECTS患儿29例，男17例，女12例；年龄（9.17±2.42）岁（4～14岁）；病程0.5～4.0年。另选取在本院行常规体检的健康儿童20例作为健康对照组，男14例，女6例；年龄（8.55±3.09）岁（5～13岁）。对2组儿童进行失匹配负波（mismatch negativity，MMN）测试，分析MMN波幅、潜伏期，并对BECTS组患儿进行视频脑电图（VEEG）长程监测，分析放电发生时段（清醒、睡眠）、位置、IED指数，比较2组MMN指标及BECTS组MMN与VEEG的相关性。结果VEEG显示BECTS患儿睡眠结构未见明显异常改变。所有患儿痫样放电均位于Rolandic区，其中左侧11例，右侧8例，双侧10例。痫样放电时段：仅在睡眠期发放者17例，清醒期和睡眠期均有发放者12例，此12例患儿均表现为睡眠期痫样放电[（40.24±25.15）次/min]较清醒期[（1.92±1.38）次/min]显著增多，差异有统计学意义（t＝5.270，P＝0.000）。NREM睡眠1、2期IED指数为（40.73±10.69）次/min，其中〈5次/min者2例，〉80次/min者3例，此3例患儿基本达到睡眠中癫痫性电持续状态，余为17.2～64.6次/min。本组患儿仅监测到4例睡眠期临床发作，与睡眠期大量的IED呈电-临床分离现象。BECTS组MMN波幅[（6.06±1.89） μV]较健康对照组[（7.28±1.64）μV]降低，差异有统计学意义（t＝2.346，P＝0.025）；潜伏期[（191.37±40.13） ms]较健康对照组[（179.35±39.80） ms]延长，但差异无统计学意义（t＝1.037，P＝0.355）。相关分析显示，BECTS患儿MMN波幅与睡眠期放电（r＝－0.407，P〈0.05）与NREM睡眠1、2期IED指数（r＝－0.644，P〈0.01）均呈负相关；MMN潜伏期与NREM睡眠1、2期IED指数呈正相关（r＝0.386，P〈0.05）；余VEEG指标与MMN无相关性。结论BECTS患儿存在听觉信息的前注意加工障碍，特别是无意识参与的自动加工能力受损，使自动加工转向集中注意加工的＂注意开关＂作用减弱，不能有效过滤无关信息。睡眠期IED损害听觉分辨力和记忆痕迹的形成与强化，干扰新信息的获取、加工、存储及匹配，是导致患儿前注意加工障碍的重要因素，MMN可早期发现患儿前注意加工障碍的电生理改变。

ObjectiveTo explore the relationship between aural pre-attentive processing and non-rapid eye movement（NREM） sleep interictal epileptiform discharge （IED） in children with benign childhood epilepsy with central-temporal spikes （BECTS）, in order to provide objective electrophysiological basis for early assessment of cognitive function lesion of BECTS children and intervention.MethodsTwenty-nine children diagnosed as BECTS in the Second Affiliated Hospital of Xinxiang Medical University from February 2012 to November 2015 were selected, including 17 males and 12 females, and they were 4-14 years old with average age of （9.17±2.42） years, and the course of disease was 0.5-4.0 years.Twenty healthy children who had hospital routine check-up were selected as healthy control group, containing 14 males and 6 females, and they were 5-13 years old with average age of （8.55±3.09） years.Mismatch negativity （MMN） test was carried out in both groups, and the MMN amplitudes and latencies were analyzed.The long-term video electroencephalogram （VEEG） monitoring was conducted in the BECTS group to analyze the discharge phases （waking, sleep）, locations and the IED indexes.The intergroup MMN indexes and the correlation between MMN and VEEG in the BECTS group were compared.ResultsThe VEEG showed that the sleep structure of BECTS children did not change obviously.All children′s epileptiform discharges were located in the Rolandic area, including 11 cases on the left side, 8 cases on the right side, and 10 cases on both sides.Epilepsy discharge time： 17 patients showed epileptiform discharges in sleep stages only and 12 patients showed epileptiform discharge in both sleep and waking stages.Epileptiform discharges of the 12 patients increased more significantly in sleep stage than that in waking stage [（40.24±25.15） times/min vs.（1.92±1.38） times/min], and the difference was statistically significant（t=5.270, P=0.000）. The sample IED index in stage 1 and 2 of NREM was （40.73±10.69） times/min, in which 2 cases had IED indexes 〈 5 times/min, the IED indexes of 3 cases 〉80 times/min who reached electrical status epilepticus during sleep, and others were 17.2-64.6 times /min.Clinical seizures in sleep stages were monitored in only 4 cases, which showed an electro-clinical segregation phenomenon from large quantities of sleep IED.The MMN amplitude was lower in the BECTS group than that in the healthy control group [（6.06±1.89） μV vs.（7.28±1.64） μV], and the difference was statistically significant（t=2.346, P=0.025）. Latency of BECTS group was longer than that in the healthy control group [（191.37±40.13） ms vs.（179.35±39.80） ms], but the difference was not statistically significant（t=1.037, P=0.355）. Correlation analysis showed that the MMN amplitude was negatively related to discharge phases （r=-0.407, P〈0.05） and the IED indexes （r=-0.644, P〈0.01）, and latency was positively related to the IED indexes （r=0.386, P〈0.05）, while the other VEEG indexes were not correlated with MMN.ConclusionsThe BECTS children have aural pre-attentive processing disturbance, especially unconscious automatic processing ability impairment, which weaken ＂ attention switch＂ action of automatic processing switching to focused attention processing and fail to filter irrelevant information effectively.Sleep IED is an important factor in impairing the formation and reinforcement of acoustic discrimination and memory trace, interfering the acquisition, proce-ssing, storage and matching of new information, which induces children pre-attentive processing disturbance.The MMN may discover the electrophysiological changes of children pre-attentive processing disturbance in early stage.