【摘要】：背景與目的： 癲癇患者常常并發(fā)有睡眠障礙、認知功能減退，嚴重影響其生活質量；不規(guī)律用藥或感染較易誘發(fā)其出現癲癇持續(xù)狀態(tài)，甚至威脅其生命。神經元異常放電是癲癇發(fā)作的基礎，只有借助腦電圖技術方可客觀判定其異常癇樣放電情況，常規(guī)腦電圖操作一般不記錄肌電、眼動，缺乏對睡眠結構的深入了解；對癇樣放電僅能定性檢測、缺乏量化的標準；此外，腦電圖閱圖繁瑣、專業(yè)性強，不易在醫(yī)護工作者間普及應用。因此，我們通過將傳統腦電圖技術改良，增加一些睡眠參數、定量分析方法及趨勢圖分析方法，能進一步探討癇樣放電與睡眠-覺醒周期關系、癇樣放電與認知功能的關系、及癇樣放電與頻繁癇樣發(fā)作的關系。 方法： 1.癇樣放電與睡眠-覺醒周期的研究：我們將腦電圖技術與眼動、肌電等睡眠參數結合，對200例癲癇患者及182例健康對照者進行24小時監(jiān)測，記錄結束后回放分析癇樣放電出現方式、部位及睡眠結構、睡眠時相，并探討二者之間的關系。 2.癇樣放電與認知障礙的研究：我們對67例合并有認知障礙的癲癇患者進行24小時腦電圖監(jiān)測，并通過定量分析法對癇樣放電指數進行分類，進而對不同癇樣放電指數的癲癇患者進行認知相關性神經心理測試，并探討二者之間的關系。 3.趨勢圖—CDSA、aEEG識別癇樣發(fā)作準確性的研究：我們選擇30條連續(xù)24小時記錄的腦電圖數據（20條包含有癇樣發(fā)作、10條正常對照），3名經培訓的電生理醫(yī)師采用CDSA、aEEG閱圖方法對30條腦電圖記錄進行解讀，對疑似癇樣發(fā)作之處進行標記，測試結束后與傳統腦電圖閱圖法所判定的發(fā)作次數進行比較分析，明確敏感性、誤診率、漏診率等，并統計分析不同閱圖者之間的一致性。 結果： 1.在探討癇樣放電與睡眠-覺醒周期的研究中：我們發(fā)現約91%的癲癇患者可通過腦電圖監(jiān)測發(fā)現癇樣放電；清醒期、睡眠期、清醒及睡眠Ⅰ-Ⅱ期的癇樣放電率分別為7.1%、19.2%、25.3%，睡眠Ⅲ-Ⅳ期的癇樣放電率為1.1%；癲癇組與正常對照組的總睡眠時間、REM期睡眠時間無明顯差異（P＞0.05）；癲癇組與正常組比較，，睡眠Ⅰ-Ⅱ期的睡眠時間延長(293.91±27.57min vs223.17±15.28, P=0.000)，睡眠Ⅲ-Ⅳ期時間縮短(50.11±12.12min vs133.96±10.77, P=0.000)；此外，26.7%的癲癇患者出現不對稱性紡錘波，43.3%的癲癇患者發(fā)現較高睡眠時相轉換率所致的睡眠結構片段化。 2.在探討癇樣放電與認知障礙的研究中：10%的癇樣放電指數是對成年癲癇患者認知功能產生負性影響的最小研究截點；不同部位的癇樣放電對認知功能產生不同的負性影響，如癇樣放電位于額葉或顳葉者，顯示較差的智商及記憶商；不同癇樣放電分布，如局灶性癇樣放電與多灶性、泛化性癇樣放電對認知功能的負性影響無差異（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)；不同癇樣放電持續(xù)時間，對認知功能的負性影響無差異。 3.在探討趨勢圖—CDSA、aEEG識別癇樣發(fā)作準確性的研究中：本研究獲得較高的敏感性、較低的誤診率及漏診率，采用CDSA閱圖時，敏感性為80%，24小時的誤診率較低，約4次左右；aEEG閱圖時，敏感性為81.3%，24小時的誤診率約2次；采用CDSA及aEEG閱圖時，漏診率均為每24小時，大約4次左右，且CDSA及aEEG兩種閱圖方法間，漏診率無明顯差異（P0.05, X2）；此外三名電生理醫(yī)師采用CDSA及aEEG兩種閱圖方法解讀敏感性、誤診率、漏診率時，一致性較好，一致性參數分別為κ=0.52及κ=0.68。 結論： 1.既往常規(guī)腦電圖技術能對癇樣放電進行檢測分析，而睡眠結構分析需借助多導睡眠監(jiān)測技術才能完成，本研究中將腦電圖技術與睡眠參數相結合，同時對癇樣放電與睡眠結構進行分析，建立二者之間的聯系，癇樣放電可以改變癲癇患者的睡眠結構，同時其睡眠結構的改變，促進癇樣放電的發(fā)生，因此早期識別癲癇患者所并發(fā)的睡眠障礙、制定診療方案有助于更好的抑制癇樣放電，控制癲癇發(fā)作，改善其生活質量。目前此類研究國內報道較少、且國內外未見大樣本臨床研究，而本實驗臨床樣本量較大、且納入的癲癇發(fā)作類型全面。 2.本研究將腦電圖與定量分析法結合，在臨床樣本中證實癇樣放電成為影響成人癲癇患者認知功能的潛在的、隱性的因素，且定量分析引起成人癲癇患者認知功能受損的最小癇樣放電指數。既往癲癇常規(guī)治療中對于臨床發(fā)作次數少的癲癇患者，暫不給予藥物治療或僅給予小劑量藥物治療，不能有效抑制其癇樣放電。而我們的研究可能改變傳統的治療觀念，即由單純控制癲癇的臨床發(fā)作，發(fā)展為不僅控制臨床發(fā)作，還需控制癇樣放電，減少認知損傷，我們認為臨床發(fā)作次數少，腦電圖顯示頻繁臨床下癇樣放電的患者，需要早期治療抑制癇樣放電以延緩或減少對認知功能的負性影響。我們首次提出10%的癇樣放電指數對成人癲癇患者認知功能存在負性影響，此類研究國內未見報道，國外有關癇樣放電與認知損傷的報道較少，均在兒童癲癇患者中進行且研究閾值不同，未在成人癲癇患者中研究驗證。 3.本研究證實，將腦電趨勢圖—CDSA及aEEG應用于癇樣發(fā)作識別中，具有較高的敏感率、較低的誤診率、漏診率，且簡便快捷、可操作性強，有利于非專業(yè)醫(yī)護人員應用，在成人重癥病房中的推廣具有應用前景。既往此種研究方法多應用于新生兒重癥病房，在國內成人重癥病房的應用較少，且類似研究結果不同，有一定的臨床應用及推廣價值。
[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.
【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R742.1;R741.044

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