人脑颞叶局灶性皮层发育不良临床特征及发病机制研究

发布时间：2018-02-13 06:24

  本文关键词： 局灶性皮层发育不良 临床特征 病理分类 弥散张量成像 哺乳动物雷帕霉素靶蛋白　出处：《河北医科大学》2014年博士论文　论文类型：学位论文

【摘要】：癫痫是常见的中枢神经系统慢性疾病，我国大约有1000万癫痫患者，每年的新发病例约40万左右。在众多的癫痫患者中，约有30%的患者发作得不到有效控制，最终发展成为难治性癫痫。局灶性脑皮层发育不良(Focal cortical dysplasia, FCD)是皮质发育畸形的一种类型，是难治性癫痫的重要原因，经手术治疗的75%以上的儿童癫痫和约20%的成人癫痫存在FCD，约50%的癫痫患者是因各种不同类型的FCD所引起。自从发现以来，FCD这个定义在神经解剖学、病理学和影像学等各个领域当中被广为应用。 FCD包括一系列的病理现象，患者病理现象存在差异，临床表现也不同，研究者一直试图对其进行分类，使研究更加标准化，根据不同的应用范围和评价方法制定了各种不同的分类方法。2004年Palmini根据病理学表现是否包括异形细胞将FCD分为I型和II型，，这种分类方法在临床上使用最广泛，但也存在缺陷。2011年国际抗癫痫联盟(InternationalLeague Against Epilepsy，ILAE)在Palmini分类基础上进行了修改，增加了结合型FCD分类，将海马硬化、癫痫相关性肿瘤、血管畸形相邻的FCD命名为结合型FCD。这样FCD分为单纯型FCD和结合型FCD，单纯型FCD包括I型和II型，结合型FCD为III型。 对于2011年ILAE新分类下的FCD的研究很少，尤其是新的病理亚型结合型FCD。大约50%FCD发生在颞叶，本研究根据2011年ILAE分类对颞叶FCD不同病理亚型的临床特征、手术预后、影像学表现、超微结构及雷帕霉素受体表达进行分析。第一部分人脑颞叶局灶性皮层发育不良不同亚型临床特征分析 目的：比较2011年ILAE分类下颞叶FCD不同病理亚型的临床特征。 方法：回顾分析2005年12月31日至2011年12月31日间在河北省人民医院功能神经外科进行难治性颞叶癫痫手术患者共241例。对经过颞叶癫痫手术患者按照2011年ILAE分类对FCD不同病理亚型进行分类，并对不同病理亚型患者癫痫发作起始年龄、癫痫患病年限、手术年龄、发作频率等临床特征进行分析，观察不同病理亚型患者的临床特征是否存在差异。 结果：92例患者符合FCD诊断，结合型FCD平均发作起始年龄为19.2岁，显著高于单纯型FCD，具有统计学意义。在结合型FCD患者中，FCDIIIc型平均发作起始年龄为30.7岁，显著高于结合型FCD中的其它亚型。结合型FCD平均癫痫患病年限为7.8年，显著短于单纯型FCD。在结合型FCD的病理亚型中，FCD IIIb型平均癫痫患病年限为3.5年，FCD IIIc型平均癫痫患病年限为5.3年，显著短于结合型FCD的其它病理亚型。FCD IIIc型平均手术年龄为35.8岁，明显晚于结合型FCD的其它病理亚型。在结合型FCD的各个病理亚型中，18例FCD IIIa型患者有高热惊厥病史，占44.6%，明显多于结合型FCD的其它病理亚型。 结论：结合型FCD癫痫发作起始年龄晚，尤其是FCD IIIc型。结合型FCD手术前癫痫患病年限短，尤其是FCD IIIb型和FCD IIIc型。在结合型FCD患者中，FCD IIIc型平均手术年龄明显晚于结合型FCD的其它病理亚型。FCD IIIa型患者更容易产生高热惊厥。结合型FCD和单纯型FCD的临床特点可能存在差异。 第二部分人脑颞叶局灶性皮层发育不良不同亚型手术效果分析 目的：通过随访分析，比较2011年ILAE分类下颞叶FCD不同病理亚型的手术疗效。 方法：对手术后92例符合FCD诊断患者进行门诊、电话、信件随访。对患者进行随访后，根据患者癫痫发作情况按照Engel标准分级评价预后：I级，无影响功能的癫痫发作(除术后早期的癫痫发作)；II级，仅有稀少的影响功能的癫痫发作；III级，癫痫发作得到相当的改善(发作频率减少90%)；IV级，癫痫发作改善不明显。(Engel I+II级)为手术效果良好，(EngelIII+IV级)为手术效果不佳。 结果：成功随访患者68例，术后疗效按Engel标准评定，Engel I级35/68(51.4%)，II级18/68(26.5%)，III级10/68(14.7%)，IV级5/68(7.3%)；效果良好(Engel I+II级)为53/68(77.9%)，效果不佳(Engel III+IV级)为19/68(22.1%)。效果良好53例，其中单纯型FCD17例(70.8%)，结合型FCD36例(81.8%)，手术效果不佳15例，其中单纯型FCD7例(29.2%)，结合型FCD8例(19.2%)。单纯型FCD的手术效果良好率低于结合型FCD(P0.05)。 结论：手术是治疗癫痫相关性颞叶FCD的重要方式，有效性较高。结合型FCD的手术效果优于单纯型FCD。 第三部分人脑颞叶局灶性皮层发育不良磁共振弥散张量成像表现分析 目的：对颞叶不同病理亚型的FCD的弥散张量结果进行比较分析，以探寻弥散张量成像中的不同参数在FCD不同病理亚型中的诊断价值。 方法：对58例资料完整患者的弥散张量成像检查结果进行分析，在轴位T1WI图中，取颞叶海马显示最完整的层面，以及上下各1层面，于对颞叶固定位置放置兴趣区(region of interest,ROI)，ROI范围避免包含空腔结构及海马结构。应用软件内“对称镜像”的方法，在对侧对应部位选取ROI，ROI圆形直径20mm，测定两侧ROI内的ADC值和FA值，比较不同亚型的弥散张量成像表现差异及弥散张量成像中不同参数的诊断价值。 结果：在单纯型FCD健侧的ADC值平均为9.2±3.4(×10-10mm2/s)，患侧的ADC值平均为12.2±5.6(×10-10mm2/s)，两侧的ADC值差值平均为3.0±1.2(×10-10mm2/s)。在结合型FCD健侧的ADC值平均为8.7±3.1(×10-10mm2/s)，患侧的ADC值平均为13.1±4.3(×10-10mm2/s)，两侧的ADC值差值平均为3.4±1.9(×10-10mm2/s)。在单纯型FCD健侧的FA值平均为0.245±0.068，患侧的FA值平均为0.186±0.048，较健侧明显降低(P0.05)；两侧的FA值差值平均为0.062±0.021。在结合型FCD健侧的FA值平均为0.241±0.052，患侧的FA值平均为0.156±0.052，较健侧明显降低(P0.05)；两侧的FA值差值平均为0.091±0.033，较单纯型FCD差异更明显，具有统计学意义(P0.05)。 结论：DTI可以作为颞叶FCD的重要辅助检查手段，在DTI参数ADC值和FA值中，FA值的变化更明显。在FCD的不同病理亚型中，在单纯型FCD和结合型FCD的患侧FA值较健侧相比均减少，结合型FCD减少的相对单纯型FCD更加明显。第四部分人脑颞叶癫痫相关性局灶性皮层发育不良超微结构观察分析 目的：通过对不同病理亚型FCD手术标本进行电镜观察，了解FCD超微结构改变。 方法：对单纯型FCD组，结合型FCD组和对照组的手术标本分别进行透射电镜观察，分析其超微结构的改变。 结果：1.单纯型FCD：神经元形态异常，细胞器明显减少或消失，部分神经元中可见脂褐质颗粒。线粒体嵴模糊，部分缩短或缺失。基质颗粒减少或消失。线粒体增生肥大，线粒体膜破裂。内质网扩张。胶质细胞肿胀，有髓神经纤维排列混乱，髓鞘细胞膜结构稀疏。髓鞘内外层轻度分离。2.结合型FCD：神经元细胞质水肿，细胞器数量明显减少或消失，线粒体肥大和增生。粗面内质网轻度扩张。有髓神经髓鞘明显增生增厚分层，有髓神经髓鞘增生形状极度不规则，无序排列，髓索变小，水肿，髓内容物减少，髓鞘细胞膜结构稀疏。髓鞘外层与内层分离，线粒体与微丝微管数量减少。3.对照组：未发现明显脑组织异常改变，神经元形态规则，排列紧密，核仁清楚，染色质排列均匀一致。 结论：FCD其本身也可能具有致痫性，具有癫痫发作的结构基础，结合型FCD中有髓神经纤维受损更加明显。 第五部分人脑颞叶局灶性皮层发育不良哺乳动物雷帕霉素靶蛋白表达分析 目的：通过检测不同病理亚型FCD患者术后病理组织的mTOR信号通路的表达情况，观察mTOR信号通路在FCD发病机制中的意义。 方法：应用免疫组化、免疫荧光、Western-blot方法对不同病理亚型FCD患者的AKT、mTOR、p70S6K及p-AKT、p-mTOR、p-p70S6K进行检测，观察mTOR信号通路在不同病理亚型FCD的表达。 结果：AKT、mTOR、p70S6K在正常脑组织及FCD I型组、FCD IIIa型组内可见少量锥体神经元胞体及星型胶质细胞呈弱阳性表达。在FCDIIIa型中观察到p-AKT、p-mTOR、p-p70S6K在少量锥体神经元胞体弱阳性表达，与FCD I型及正常脑组织表达程度相似。在星型胶质细胞p-AKT、p-mTOR、p-p70S6K呈明显中度阳性表达，表达部位主要在胞浆，表达强度明显强于FCD I型及正常脑组织。 结论：在FCD IIIa型中的星型胶质细胞中p-AKT、p-mTOR、p-P70S6K的表达增加，提示PI3K-AKT-mTOR通路异常激活可能是参与FCD IIIa型的发病机制。在FCD IIIa型中的星型胶质细胞中PI3K-AKT-mTOR通路异常激活，而FCD I型PI3K-AKT-mTOR信号通路没有异常激活，FCDIIIa型和FCD I型在发病机制上可能存在差异。
[Abstract]:Epilepsy is a common chronic disease of the central nervous system, there are about 10 million patients with epilepsy in China, new cases each year is approximately 400 thousand. In many of the epilepsy patients, about 30% of the patients had no effective control, and eventually become the intractable epilepsy. Focal cortical dysplasia (Focal cortical dysplasia, FCD) is a type of malformations of cortical development, is an important cause of refractory epilepsy, by more than 75% adult epilepsy surgery in the treatment of children epilepsy and 20% in the presence of FCD, about 50% of patients with epilepsy is caused by a variety of different types of FCD. Since the discovery, the definition of FCD in neuroanatomy, pathology and imaging and other fields are widely used.
FCD includes a series of pathological phenomena, pathological phenomenon differences, clinical manifestations are different, researchers have been trying to classify it, make the research more standardized, according to the scope of application of different evaluation methods and develop a variety of different classification methods in.2004 Palmini according to whether the pathology including special cells will be divided into FCD I type and II type, this classification method widely used in clinic, but there are also shortcomings in.2011 International League Against Epilepsy (InternationalLeague Against, Epilepsy, ILAE) in Palmini on the basis of classification is modified and the increase of combination FCD classification, the hippocampal sclerosis, epilepsy associated tumors, vascular malformations of the adjacent FCD name with FCD. FCD divided into simple type FCD and type FCD with pure FCD, including I and II, with FCD as III.
Few studies on the new classification of 2011 under ILAE FCD, especially the pathological subtype of type FCD. with about 50%FCD in the temporal lobe, according to clinical features, the 2011 ILAE classification of temporal lobe FCD in different subtypes of surgical outcomes, imaging features, expression of hormone receptor and ultrastructure of ray Palmer mold. The first part is the analysis of human temporal lobe of focal cortical dysplasia in different subtypes of clinical features
Objective: To compare the clinical features of different pathological subtypes of FCD in the temporal lobes of the temporal lobes in the 2011 ILAE classification.
Methods: a retrospective analysis from December 31, 2005 to December 2011 31 during the day for patients with intractable temporal lobe epilepsy surgery 241 cases in Hebei People's Hospital Department of neurosurgery. The function of patients with temporal lobe epilepsy surgery according to the classification of ILAE in 2011 to FCD in different subtypes are classified, and the onset age of different subtypes of patients with epilepsy, epilepsy duration, surgical age the clinical features, seizure frequency were analyzed, to observe the clinical characteristics of patients with different pathological subtypes of whether there is a difference.
Results: 92 patients with the diagnosis of FCD, the average age at onset was 19.2 years with FCD, was significantly higher than that of pure FCD, with statistical significance. In combination with FCD, FCDIIIc average onset age was 30.7, significantly higher than with other subtypes of type FCD. According to FCD the average prevalence of epilepsy for 7.8 years, was significantly shorter than the pure FCD. in combination with FCD pathological subtype, FCD III B average prevalence of epilepsy for 3.5 years, FCD IIIc average prevalence of epilepsy for 5.3 years, significantly shorter than other pathological subtypes of.FCD type IIIc type FCD with the average operative age was 35.8 years. Combined type FCD was significantly later than other pathological subtypes. In combination with the FCD type of various pathological subtypes, 18 cases of FCD type IIIa patients with a history of febrile seizures, accounted for 44.6%, significantly more than the combined FCD of other pathological subtypes.
Conclusion: the combination of FCD type of seizure onset age of late, especially FCD IIIc. Combined FCD preoperative epilepsy in a short time, especially FCD III and FCD IIIc. B in combination with FCD, the average age of surgery for FCD type IIIc was significantly later than that in combination with other.FCD subtypes in patients with type IIIa type FCD more prone to convulsion. Combined with clinical features of FCD type and simple type FCD may differ.
Analysis of the effect of different subtypes of subtypes of focal temporal cortical dysplasia in the second parts of the human brain
Objective: To compare the curative effect of different pathological subtypes of FCD in the temporal lobes of the temporal lobe in 2011 through the follow-up analysis.
Methods: 92 cases after surgery with the diagnosis of FCD patients were outpatient, telephone, mail follow-up. The patients were followed up, according to the patient's seizures in accordance with the Engel standard to evaluate the prognosis grading: grade I, without affecting the function of the seizures (except for early postoperative seizure); grade II, influence function only rare seizures; epilepsy III level, improve considerably (90% reduction in seizure frequency); grade IV, seizures did not improve obviously. (Engel I+II) for the good operation effect, (EngelIII+IV) surgery was ineffective.
Results: 68 cases were successfully followed up patients, the postoperative curative effect according to Engel standard, Engel I 35/68 (51.4%), II 18/68 (26.5%), III 10/68 (14.7%), IV 5/68 (7.3%); good effect (Engel I+II) 53/68 (77.9%), poor effect (Engel III+IV 19/68) (22.1%). The effect is good in 53 cases, FCD17 cases of simple type (70.8%), FCD36 (81.8%) cases with surgery, 15 cases were ineffective, which FCD7 cases of simple type (29.2%), FCD8 (19.2%) cases with surgery. Effect of simple type FCD good rate is lower than the combination of type FCD (P0.05).
Conclusion: operation is an important way to treat temporal lobe FCD in epilepsy, and its effectiveness is higher. The effect of combined type FCD is better than that of simple FCD..
Analysis of magnetic resonance diffusion tensor imaging in the third part of the temporal lobe focal cortical dysplasia of the human brain
Objective: To compare and analyze the diffusion tensor results of FCD in different pathological subtypes of temporal lobe, so as to explore the diagnostic value of diffusion-tensor imaging in different pathological subtypes of FCD.
Methods: diffusion tensor imaging findings of 58 patients with complete data were analyzed in the axial T1WI diagram, the temporal hippocampus showed the most complete level, and the 1 level, in Duinie leaf fixed position of region of interest (region of, interest, ROI, ROI) to avoid including the cavity structure and scope the application software in the hippocampus. "Mirror symmetry" method, on the side of the site selection of ROI, ROI circular diameter 20mm, determination of ROI on both sides within the ADC and FA values, the diagnostic value of different parameters of the performance difference of diffusion tensor imaging and diffusion tensor imaging in different subtypes.
缁撴灉锛氬湪鍗曠函鍨婩CD鍋ヤ晶鐨凙DC鍊煎钩鍧囦负9.2卤3.4(脳10-10mm2/s),鎮ｄ晶鐨凙DC鍊煎钩鍧囦负12.2卤5.6(脳10-10mm2/s),涓や晶鐨凙DC鍊煎樊鍊煎钩鍧囦负3.0卤1.2(脳10-10mm2/s).鍦ㄧ粨鍚堝瀷FCD鍋ヤ晶鐨凙DC鍊煎钩鍧囦负8.7卤3.1(脳10-10mm2/s),鎮ｄ晶鐨凙DC鍊煎钩鍧囦负13.1卤4.3(脳10-10mm2/s),涓や晶鐨凙DC鍊煎樊鍊煎钩鍧囦负3.4卤1.9(脳10-10mm2/s).鍦ㄥ崟绾�鍨婩CD鍋ヤ晶鐨凢A鍊煎钩鍧囦负0.245卤0.068,鎮ｄ晶鐨凢A鍊煎钩鍧囦负0.186卤0.048,杈冨仴渚ф槑鏄鹃檷浣

本文编号：1507523