【作者】 青浩渺；

【导师】 李方； 崔瑞雪； 霍力；

【作者基本信息】 北京协和医学院 ， 临床医学， 2012， 博士

【摘要】 研究背景和目的：癫痫是一种慢性中枢神经系统疾病,目前我国的患病率约5%0。大部分患者可以通过抗癫痫药物治疗得到缓解,但是仍有约20%的患者经过正规的抗癫痫药物治疗无法缓解。外科手术是目前对药物难治性癫痫的主要治疗手段。对于存在明确致痫灶的癫痫,多数患者在手术切除致痫灶后可以取得无发作或减少发作。所以准确的术前定位对癫痫外科手术至关重要。通常大多数患者都会行多种无创的术前检查以明确定位,并考虑是否适于手术。有部分患者仅通过无创手段难以定位,则需要行有创神经电生理检查。由于有创神经电生理检查花费昂贵,且存在多种并发症风险,其应用也需要充分的证据支持。自20世纪80年代以来,18-氟脱氧葡萄糖正电子发射断层扫描(18-fluorodeoxyglucose positron emission tomography, FDG-PET)在癫痫致痫灶的定位中已得到广泛应用,其定位敏感性和准确性已经得到大量研究的证实,为癫痫外科治疗的有创检查和手术决策提供了充分的依据。本课题拟通过回顾分析2006~2011年期间于北京协和医院就诊的药物难治性癫痫患者临床诊疗过程,来研究FDG-PET在药物难治性癫痫外科治疗临床决策中的作用。材料和方法：164例于2006年1月～2011年4月期间于北京协和医院就诊,并行FDG-PET检查的药物难治性癫痫患者,其中男性91例,女性73例,就诊年龄分布于3～57岁,平均就诊年龄26.1岁。临床病程1-44年,平均病程12.8年。收集所有患者FDG-PET、头皮视频监测脑电图(scalp video electroencephalogram, SVEEG)、头颅磁共振成像(magnetic resonance imaging, MRI)、颅内电极脑电图(intracranial electroencephalogram, ICEEG)、术中皮层脑电图(electrocorticogram, ECoG)等检查结果及手术方式等资料,并通过电话随访及门诊病案资料,按照国际抗癫痫联盟(International League Against Epilepsy, ILAE)2001年标准判断手术疗效。以术后疗效为金标准,评价FDG-PET、SVEEG、MRI三种检查方法的致痫灶定位率,分析FDG-PET图像表现与手术预后间的关系,并讨论FDG-PET对有创检查的应用决策和电极铺设范围的影响。结果和讨论：1.共104例患者术后疗效分级为OC1-3,其中101例FDG-PET定位结果与术区一致,FDG-PET对致痫灶的定位敏感性为97.1%,高于MRI (83.7%, P=0.002)及SVEEG (85.6%, P=0.002)。 FDG-PET对其中5例额叶癫痫及13例MRI无异常表现的颞叶癫痫均准确定位,具有良好的检出能力。对于12例致痫灶位于颞叶后部、顶叶、枕叶的后皮质癫痫,FDG-PET成功定位其中10例。FDG-PET对颞叶癫痫及部分颞叶外癫痫具有良好的敏感性,可以为手术决策提供依据。2.8例FDG-PET表现为明显多发低代谢灶的患者均疗效不佳,另18例多灶表现的患者未行手术。在无明显多灶性表现的颞叶癫痫中,邻近脑叶受累和显著功能失联络表现亦是前颞叶切除术疗效不佳的危险因素,其比值比(odds ratio,OR)分别为32.54(P<0.001,95%CI:6.40,165.44),7.73(P=0.003,95%CI:1.96,30.52)。 FDG-PET可以排除部分不适合手术的病例,其图像表现可用于预测手术疗效,改变手术决策。3.25例ICEEG取得结果的患者中,有19例(76%)所定位致痫灶位于FDG-PET的低代谢灶皮层区域。11例额叶癫痫及后皮质癫痫中,有10例FDG-PET定位与ICEEG相符。5例FDG-PET提示为单侧颞叶病灶且存在MRI异常的患者,其定位均与ICEEG结果相符。FDG-PET对颅内电极脑电图的应用决策及电极铺设范围具有重要指导价值,尤其对额叶癫痫及后皮质癫痫具有较高的提示意义。对于部分MRI和FDG-PET结果一致的颞叶癫痫患者,FDG-PET可以减少ICEEG的应用。4.74例ECoG监测到放电的患者其定位均与FDG-PET一致。对于无明显定位分歧、FDG-PET表现为单一局限低代谢灶的颞叶癫痫,可减少术中皮层脑电图的应用,降低经济负担。而在非颞叶癫痫中,FDG-PET表现与术中皮层脑电图高度一致,对皮层电极铺设范围具有良好的提示性。结论：FDG-PET对致痫灶具有较高的定位敏感性,可以筛选适合手术的患者。其图像表现对手术疗效有一定预测价值,可以排除部分不宜手术的患者,为手术决策及术区规划提供支持。FDG-PET还可以指导术前及术中有创脑电图的应用决策,辅助规划电极铺设位置和范围。所以FDG-PET对药物难治性癫痫外科治疗的临床决策具有指导价值。更多还原

【Abstract】 Background and Objectives:Epilepsy is a chronic central nervous system disease, the prevalence is about5‰in China. Most of the patients can get remission through antiepileptic drug thrapy, but still20%of the patients are intractable. For many of these patients epilepsy surgery offers the only opportunity to become free of seizures. If definite epileptogenic zone can be located, most patients will get seizure free or reduction after resection. So accurate preoperative locating is very important for epilepsy surgery. Most of the patients undergo a variety of noninvasive preoperative examinations in order to locate the epileptic zone, and evaluate the eligibility for operation. Advances in technology to localize focal epileptogenic zone, such as high resolution magnetic resonance imaging (MRI), have substantially improved the success of surgical treatment. As some patients are difficult to locate with non-invasive methods, invasive electrophysiological examinations are needed. As invasive electrophysiological examinations are expensive, also have risk of complications, the application needs sufficient supporting evidences.18-fluorodeoxyglucose positron emission tomography (FDG-PET) has been widely used in epilepsy epileptogenic zone localization since the1980s. The sensitivity and accuracy has been confirmed by lots of researches. FDG-PET can be used to judge whether the patient be appropriate for surgery, and forecast the surgical outcome. For some patients hard to locate epileptic zones, FDG-PET images can also be used to support the application of invasive electrophysiological examinations, provide information directing the planting of intracranial electrodes. We discussed the directive value of FDG-PET in the surgical decision making of refractory epilepsy.Methods and Materials:We retrospectively reviewed164refractory epilepsy cases(91M,73F) of Peking Union Medical College Hospital admitted from January2006to April2011with an average age of26.1y. The course of disease distribute form1to44y with an average of12.8y. All of them underwent interictal FDG-PET examination. We collected the results of FDG-PET, scalp video monitoring electroencephalogram(SVEEG), brain MRI, preoperative intracranial electroencephalogram(ICEEG), intraoperative electrocorticogram(ECoG) and the details of operation, evaluated the surgical outcome through telephone follow-up and outpatient medical records with the International League Against Epilepsy(ILAE)2001surgical outcome classification. We compared the localization rates of FDG-PET, SVEEG, and MRI for epileptogenic zone, checked the directive value of FDG-PET in the decision making and planting of invasive examinations. Relationship between the cerebral FDG metabolic pattern and surgical outcome were also evaluated.Results and Discussions:1.104patients got good surgical outcome.101of them had concordant epileptic zone located by FDG-PET. The sensitivity of FDG-PET in epileptic zone locating is97.1%, higher than MRI(83.7%,P=0.002) and SVEEG(85.6%, P=0.002). FDG-PET also successfully located the epileptic zone in all5cases of frontal lobe epilepsy and13cases of MRI-negative temporal lobe epilepsy. Metabolic abnormalities could be found in10of12posterior cortical epilepsy(PCE) cases by FDG-PET.2.8cases with multiple lobe hypometabolic foci got poor surgical outcome. Other18patients with multiple lobe hypometabolic foci were excluded from surgery. In temporal lobe epilepsy with single focal hypometabolic focus, diaschisis such as ipsilateral thalamus and cerebella metabolic changes can be used as a predictive factor of poor surgical outcome, the odds ratio(OR) is7.73(P=0.003,95%CI:1.96,30.52), as the image that hypometabolic zone spreading over extratemporal cortex also has an OR of32.54(P<0.001,95%CI:6.40,165.44). FDG-PET can be used to predict the surgical outcome and exclude patients, change the surgical decision.3. Discharges were found in25patients underwent ICEEG. The locating results of ICEEG were concordant with FDG-PET results in19of patients.10of11extratemporal epilepsy patients had concordant result of ICEEG. FDG-PET can provide sufficient information for the presurgical planning and planting of electrodes.5patients with focal temporal lobe hypometabolic zone and concordant MRI results showed consistency between ICEEG and FDG-PET. In those MRI-positive with FDG-PET-positive TLE patients, the application of ICEEG should be reevaluated. 4. Discharges were found in74of75patients underwent ECoG.74patients had concordant results between FDG-PET and ECoG. In those TLE patients underwent anterior temporal lobectomy and selective amygdalohippocampectomy, ECoG is not more informative than FDG-PET. In the patients of FLE and PCE, ECoG is still important for delineate the epilepsy foci, so FDG-PET can provide information in planning and planting of electrode as the high concordance between FDG-PET and ECoG.Conclusion:FDG-PET can be used to evaluate the eligibility and support surgical decision for the sufficient sensitivity and accuracy in localizing the seizure focus. As the patterns of the FDG-PET metabolic image are related with surgical outcome, FDG-PET can be used to exclude patients, reducing poor surgical outcomes. FDG-PET can also provide information for the prognostic planning and planting of invasive EEG examination. We conclude that FDG-PET has directive value in the surgical decision making of epilepsy.更多还原