脑电图技术在癫痫患者睡眠障碍、认知障碍及痫样事件识别中的应用研究

发布时间：2018-09-04 20:50

【摘要】：背景与目的：癫痫患者常常并发有睡眠障碍、认知功能减退，严重影响其生活质量；不规律用药或感染较易诱发其出现癫痫持续状态，甚至威胁其生命。神经元异常放电是癫痫发作的基础，只有借助脑电图技术方可客观判定其异常痫样放电情况，常规脑电图操作一般不记录肌电、眼动，缺乏对睡眠结构的深入了解；对痫样放电仅能定性检测、缺乏量化的标准；此外，脑电图阅图繁琐、专业性强，不易在医护工作者间普及应用。因此，我们通过将传统脑电图技术改良，增加一些睡眠参数、定量分析方法及趋势图分析方法，能进一步探讨痫样放电与睡眠-觉醒周期关系、痫样放电与认知功能的关系、及痫样放电与频繁痫样发作的关系。方法： 1.痫样放电与睡眠-觉醒周期的研究：我们将脑电图技术与眼动、肌电等睡眠参数结合，对200例癫痫患者及182例健康对照者进行24小时监测，记录结束后回放分析痫样放电出现方式、部位及睡眠结构、睡眠时相，并探讨二者之间的关系。 2.痫样放电与认知障碍的研究：我们对67例合并有认知障碍的癫痫患者进行24小时脑电图监测，并通过定量分析法对痫样放电指数进行分类，进而对不同痫样放电指数的癫痫患者进行认知相关性神经心理测试，并探讨二者之间的关系。 3.趋势图—CDSA、aEEG识别痫样发作准确性的研究：我们选择30条连续24小时记录的脑电图数据（20条包含有痫样发作、10条正常对照），3名经培训的电生理医师采用CDSA、aEEG阅图方法对30条脑电图记录进行解读，对疑似痫样发作之处进行标记，测试结束后与传统脑电图阅图法所判定的发作次数进行比较分析，明确敏感性、误诊率、漏诊率等，并统计分析不同阅图者之间的一致性。结果： 1.在探讨痫样放电与睡眠-觉醒周期的研究中：我们发现约91%的癫痫患者可通过脑电图监测发现痫样放电；清醒期、睡眠期、清醒及睡眠Ⅰ-Ⅱ期的痫样放电率分别为7.1%、19.2%、25.3%，睡眠Ⅲ-Ⅳ期的痫样放电率为1.1%；癫痫组与正常对照组的总睡眠时间、REM期睡眠时间无明显差异（P＞0.05）；癫痫组与正常组比较，，睡眠Ⅰ-Ⅱ期的睡眠时间延长(293.91±27.57min vs223.17±15.28, P=0.000)，睡眠Ⅲ-Ⅳ期时间缩短(50.11±12.12min vs133.96±10.77, P=0.000)；此外，26.7%的癫痫患者出现不对称性纺锤波，43.3%的癫痫患者发现较高睡眠时相转换率所致的睡眠结构片段化。 2.在探讨痫样放电与认知障碍的研究中：10%的痫样放电指数是对成年癫痫患者认知功能产生负性影响的最小研究截点；不同部位的痫样放电对认知功能产生不同的负性影响，如痫样放电位于额叶或颞叶者，显示较差的智商及记忆商；不同痫样放电分布，如局灶性痫样放电与多灶性、泛化性痫样放电对认知功能的负性影响无差异（WAIS-RC:86.11±11.3vs.84.04±10.8, P=0.35;WMS:84.23±9.6vs.82.31±10.23, P=0.35)；不同痫样放电持续时间，对认知功能的负性影响无差异。 3.在探讨趋势图—CDSA、aEEG识别痫样发作准确性的研究中：本研究获得较高的敏感性、较低的误诊率及漏诊率，采用CDSA阅图时，敏感性为80%，24小时的误诊率较低，约4次左右；aEEG阅图时，敏感性为81.3%，24小时的误诊率约2次；采用CDSA及aEEG阅图时，漏诊率均为每24小时，大约4次左右，且CDSA及aEEG两种阅图方法间，漏诊率无明显差异（P0.05, X2）；此外三名电生理医师采用CDSA及aEEG两种阅图方法解读敏感性、误诊率、漏诊率时，一致性较好，一致性参数分别为κ=0.52及κ=0.68。结论： 1.既往常规脑电图技术能对痫样放电进行检测分析，而睡眠结构分析需借助多导睡眠监测技术才能完成，本研究中将脑电图技术与睡眠参数相结合，同时对痫样放电与睡眠结构进行分析，建立二者之间的联系，痫样放电可以改变癫痫患者的睡眠结构，同时其睡眠结构的改变，促进痫样放电的发生，因此早期识别癫痫患者所并发的睡眠障碍、制定诊疗方案有助于更好的抑制痫样放电，控制癫痫发作，改善其生活质量。目前此类研究国内报道较少、且国内外未见大样本临床研究，而本实验临床样本量较大、且纳入的癫痫发作类型全面。 2.本研究将脑电图与定量分析法结合，在临床样本中证实痫样放电成为影响成人癫痫患者认知功能的潜在的、隐性的因素，且定量分析引起成人癫痫患者认知功能受损的最小痫样放电指数。既往癫痫常规治疗中对于临床发作次数少的癫痫患者，暂不给予药物治疗或仅给予小剂量药物治疗，不能有效抑制其痫样放电。而我们的研究可能改变传统的治疗观念，即由单纯控制癫痫的临床发作，发展为不仅控制临床发作，还需控制痫样放电，减少认知损伤，我们认为临床发作次数少，脑电图显示频繁临床下痫样放电的患者，需要早期治疗抑制痫样放电以延缓或减少对认知功能的负性影响。我们首次提出10%的痫样放电指数对成人癫痫患者认知功能存在负性影响，此类研究国内未见报道，国外有关痫样放电与认知损伤的报道较少，均在儿童癫痫患者中进行且研究阈值不同，未在成人癫痫患者中研究验证。 3.本研究证实，将脑电趋势图—CDSA及aEEG应用于痫样发作识别中，具有较高的敏感率、较低的误诊率、漏诊率，且简便快捷、可操作性强，有利于非专业医护人员应用，在成人重症病房中的推广具有应用前景。既往此种研究方法多应用于新生儿重症病房，在国内成人重症病房的应用较少，且类似研究结果不同，有一定的临床应用及推广价值。
[Abstract]:Background and purpose:
Epilepsy patients often have sleep disorders, cognitive impairment, seriously affecting their quality of life; irregular drugs or infections are more likely to induce their status epilepticus, or even threaten their lives. Regular EEG operation generally does not record EMG, eye movement, lack of in-depth understanding of sleep structure; epileptiform discharge can only be qualitative detection, lack of quantitative standards; in addition, EEG reading is cumbersome, professional, not easy to popularize among medical workers. Therefore, we improve the traditional EEG technology, increase some sleep parameters. The relationship between epileptiform discharges and sleep-wake cycles, between epileptiform discharges and cognitive function, and between epileptiform discharges and frequent epileptiform seizures can be further explored by quantitative analysis, trend graph analysis.
Method:
1. The study of epileptiform discharge and sleep-wake cycle: We combined EEG with sleep parameters such as eye movement and electromyography to monitor 200 epileptic patients and 182 healthy controls for 24 hours. After recording, playback analysis of epileptiform discharge, location and sleep structure, sleep phase, and explore the relationship between them.
2. Study on epileptiform discharge and cognitive impairment: We monitored the 24-hour electroencephalogram in 67 epileptic patients with cognitive impairment, classified the epileptiform discharge index by quantitative analysis, and then tested the cognitive-related neuropsychological test in epileptic patients with different epileptiform discharge index, and explored the relationship between them.
3. Trend Map-CDSA, aEEG Recognition of Epilepsy Accuracy Study: We selected 30 consecutive 24-hour recorded EEG data (20 with epilepsy, 10 normal controls), three trained electrophysiologists used CDSA, aEEG reading method to interpret 30 EEG records, marking the place of suspected epilepsy. After the test, the frequency of seizures determined by the traditional EEG reading method was compared and analyzed, and the sensitivity, misdiagnosis rate, missed diagnosis rate and so on were clarified.
Result:
1. In the study of epileptiform discharges and sleep-wake cycles, we found that about 91% of epileptic patients could detect epileptiform discharges by EEG monitoring; the epileptiform discharges in waking, sleeping, waking and sleeping stages I-II were 7.1%, 19.2%, 25.3% respectively, and the epileptiform discharges in sleeping stages III-IV were 1%. There was no significant difference in total sleep time and REM sleep time between epilepsy group and normal group (P > 0.05); the sleep time of epilepsy group was prolonged (293.91 65507 In 43.3% of epileptic patients, sleep structure fragmentation caused by phase conversion rate was found.
2. In the study of epileptiform discharges and cognitive impairment, 10% of epileptiform discharges were the smallest cut-off point for the study of negative effects on cognitive function in adult epileptic patients; epileptiform discharges at different sites had different negative effects on cognitive function, such as those with epileptiform discharges in the frontal or temporal lobes, showing poor IQ and memory quotient. There was no significant difference in the negative effects of generalized epileptiform discharges on cognitive function (WAIS-RC: 86.11 + 11.3 vs. 84.04 + 10.8, P = 0.35; WMS: 84.23 + 9.6 vs. 82.31 + 10.23, P = 0.35); and there was no difference in the negative effects of different duration of epileptiform discharges on cognitive function.
3. In discussing the accuracy of trend chart-CDSA and aEEG in identifying epileptiform seizures, the sensitivity of this study was higher, the misdiagnosis rate and missed diagnosis rate were lower. When using CDSA, the sensitivity was 80%, the misdiagnosis rate of 24 hours was lower, about 4 times; when using aEEG, the sensitivity was 81.3%, the misdiagnosis rate of 24 hours was about 2 times; The missed diagnosis rate was about 4 times every 24 hours, and there was no significant difference between CDSA and aEEG (P 0.05, X2). In addition, the sensitivity, misdiagnosis rate and missed diagnosis rate of the three electrophysiologists were interpreted by CDSA and aEEG, and the consistency parameters were kappa = 0.52 and kappa = 0.68, respectively.
Conclusion:
1. Conventional EEG technology can detect and analyze epileptiform discharges in the past, and sleep structure analysis can only be accomplished by polysomnography. In this study, EEG technology is combined with sleep parameters, and epileptiform discharges and sleep structure are analyzed to establish the relationship between the two, epileptiform discharges can change epileptic patients. The changes of sleep structure and sleep structure can promote the occurrence of epileptiform discharges, so early identification of sleep disorders in patients with epilepsy and formulation of diagnosis and treatment programs can help better inhibit epileptiform discharges, control seizures and improve their quality of life. The clinical sample size is large and the seizure type is comprehensive.
2. This study combined electroencephalogram with quantitative analysis, and confirmed that epileptiform discharges were potential and recessive factors affecting cognitive function of adult epileptic patients in clinical samples, and quantitatively analyzed the minimum epileptiform discharges index of cognitive impairment in adult epileptic patients. Epilepsy patients can not effectively inhibit epileptiform discharges if they are not treated with drugs or only given small doses of drugs for the time being. However, our study may change the traditional concept of treatment, that is, to control clinical seizures only, but also to control epileptiform discharges and reduce cognitive impairment. We first proposed that 10% epileptiform discharge index had a negative effect on cognitive function in adults with epilepsy. This kind of research has not been reported in China, and there is no report about epileptiform discharge and epileptiform discharge abroad. Cognitive impairment was rarely reported in children with epilepsy and the thresholds were different, not validated in adults with epilepsy.
3. This study confirmed that the application of EEG Trend Map-CDSA and aEEG in the identification of epileptiform seizures has higher sensitivity, lower misdiagnosis rate, missed diagnosis rate, and is simple, fast and operable, which is conducive to the application of non-professional medical staff, and has a bright future in the promotion of adult intensive care units. Infantile intensive care unit is seldom used in adult intensive care unit in China, and the similar research results are different, so it has certain clinical application and popularization value.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R742.1;R741.044

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