单侧颞叶内侧癫痫发作间期癫痫放电模式对智商的影响

目的 探讨单侧颞叶内侧癫痫病人发作间期癫痫放电模式分型及其对智商的影响.方法 回顾性分析130例单侧颞叶内侧癫痫病例资料,针对病人发作间期癫痫放电模式进行分型,对比不同分型病例之间的智商差异.结果 颞叶内侧癫痫病例的发作间期癫痫放电模式,左侧分为3型:Ⅰ型放电局限于同侧额、颞区49例(63.64％),Ⅱ型放电波及对侧额...     

人转铁蛋白修饰载阿霉素海藻酸钠纳米粒的制备与评价

摘要 背景：对抗肿瘤药物靶向治疗和肿瘤细胞多药耐药产生的问题,载阿霉素海藻酸钠纳米粒经改性,偶联人转铁蛋白,生成的人转铁蛋白修饰载药纳米粒,可用于靶向肿瘤药物载体。 目的：制备人转铁蛋白修饰的载阿霉素海藻酸钠纳米粒并进行表征鉴定,检测其表面蛋白活性。 方法：采用优化的微乳化-离子交联方法制备包覆阿霉素的海藻酸钠复合纳米粒,以水溶性碳二亚胺为交联剂,将载阿霉素海藻酸钠纳米粒与人转铁蛋白连接,制备出人转铁蛋白修饰载阿霉素海藻酸钠纳米粒。透射电镜观察纳米粒的外观大小、形态;高效液相色谱法分析纳米粒的包封率和载药量;流式细胞仪检测其表面人转铁蛋白的活性。 结果与结论：人转铁蛋白修饰载阿霉素海藻酸钠纳米粒呈球形,平均粒径为170 nm。阿霉素的加入量可影响纳米粒的包封率,当阿霉素的加入量为纳米粒的10%时,包封率和包裹量均最佳。每毫克载药纳米粒可与约65 μg人转铁蛋白连接。人转铁蛋白修饰的载药纳米粒在流式细胞仪上除去非特异性吸附后还有67.3%荧光显示,说明人转铁蛋白修饰的载药纳米粒大部分都偶联上了人转铁蛋白抗体并能保持抗体活性,从而为载药纳米粒特异性靶向肿瘤细胞提供了足够的靶向动力。微乳化-离子交联方法制备方法简便可靠,制得的人转铁蛋白修饰载阿霉素海藻酸钠纳米粒有望成为具有潜在价值的一种特异性靶向药物载体。 关键词：海藻酸钠;阿霉素;人转铁蛋白;纳米粒;靶向;生物材料与纳米技术 doi:10.3969/j.issn.1673-8225.2010.21.014     

脑电立体定位系统引导伽玛刀治疗颞叶内侧癫痫的前瞻性研究

目的探索脑电立体定位系统引导伽玛刀治疗颞叶内侧癫痫的方法,评价治疗的效果。方法分析363医院头部伽玛刀治疗室2004年1月～2007年12月确诊并行伽玛刀治疗的54例颞叶内侧癫痫患者,男性患者32例,女性患者22例,年龄8～53岁,平均25岁。采用前瞻性研究方法,进行随访观察,对治疗效果进行评价。结果本组共纳入病例54例,平均周边剂量12Gy(8～16Gy),随访1～6年,平均4.2年,疗效按Engel癫痫外科治疗结果分类及谭启富提出的癫痫外科手术结果评价标准分级:21例患者满意(占38.9%),13例显著改善(占24.1%),9例良好(占16.7%),11例效差(占20.3%);其中治疗部位与EEG、偶极子一致者43例,21例效果满意(占48.8%),10例显著改善(占23.3%),良好6例(占13.9%),6例效差(占13.9%);其余11例不一致的患者中,无一例达满意效果,3例显著改善(占27.3%),良好3例(占27.3%),5例效差(占45.4%);无死亡病例。结论长期随访结果显示良好的癫痫控制率及极低的并发症,脑电、偶极子提示位置一致,疗效好;当脑电图显示致痫灶没有局限于颞叶内侧结构,与偶极子定位结果不吻合时应首选开颅手术,术中皮层电极监测验证癫痫源灶部位。故伽玛刀治疗前必须严格选择病例,治疗靶点确定要有充分依据,严格控制剂量、容积,以提高疗效,降低并发症。     

双重病理征对药物难治性颞叶内侧癫痫手术预后的影响

目的 探讨内侧颞叶硬化（MTS）合并局灶性皮质发育不良（FCD）对药物难治性颞叶内侧癫痫（MTLE）手术预后的影响。方法 回顾性分析2010年1月至2020年3月前颞叶切除术治疗的98例药物难治性MTLE的临床资料。术后2年,应用Engel分级评估预后,其中Ⅰ级为预后良好,Ⅱ～Ⅳ级为预后不良。结果 98例中,预后良好70例（71.4%）,预后不良28例（其中Engel分级Ⅱ级8例、Ⅲ级5例、Ⅳ级15例）。术后病理检查显示,39例（39.8%）存在MTS合并FCD。多因素logistic回归分析显示,MTS合并FCD是MTLE手术预后不良的独立危险因素（P=0.009,OR=1.114,95%CI 1.033～3.393）。结论 前颞叶切除术是治疗药物难治性MTLE的一种有效手术方法,MTS合并FCD的药物难治性MTLE病人手术预后较差。     

纳米化苯妥英钠抗大鼠癫痫模型疗效的研究

目的 利用癫痫动物模型评价聚氰基丙烯酸正丁酯纳米微粒(DPH-PBCA-NPs)和Tween-80修饰的DPH-PBCA-NPs抗癫痫疗效,探讨纳米载药系统的优越性.方法 构建氯化锂-匹罗卡品急性癫痫大鼠模型,按照完全随机数字表法分为5组,Ⅰ组注射Tween-80修饰的DPH-PBCA-NPs,Ⅱ组注射DPH-PBCA-NPs,Ⅲ组注射苯妥英钠水溶液,Ⅳ组注射PBCA-NPs,Ⅴ组注射生理盐水.利用视频脑电监测仪,观察EEG动态变化过程,同时观察致痫大鼠的行为学改变.结果 成功构建氯化锂-匹罗卡品急性癫痫大鼠模型,致痫大鼠在行为和EEG上均表现出了癫痫持续状态.Ⅰ组治疗有效率为91.67%,Ⅱ组有效率为54.55%,Ⅲ组有效率为50%,Ⅳ、Ⅴ组有效率为0%,差异有统计学意义(P＜0.05).结论 DPH-PBCA-NPs和Tween-80修饰的DPH-PBCA-NPs能够明显改善致痫大鼠的行为学表现和EEG结果,具有抗癫痫作用.纳米载药系统能协助药物更迅速、更有效地发挥治疗作用.

Abstract：

Objective To evaluate the effects of diphenylhydantoin sodiumpolybutylcyanoacrylate nanoparticles (DPH-PBCA-NPs) and DPH-PBCA-NPs modified with Tween-80on rat models of epilepsy, and investigate the advantage of nanoparticle as the drug delivery system.Methods The rat models of acute epilepsy induced by lithium pilocarpine were established and randomly divided into 5 groups: group Ⅰ (performing injection of DPH-PBCA-NPs modified with Tween-80), group Ⅱ (performing injection of DPH-PBCA-NPs), group Ⅲ (performing injection of diphenylhydantoin sodium), group Ⅳ (performing injection of PBCA-NPs) and group Ⅴ (performing injection of physiological saline). The changes of electroencephalogram (EEG) manifestations of these rats were observed by using video-EEG monitoring; and their behavioral changes were noted too.Results The lithium pilocarpine induced rat models of acute epilepsy were successfully established and their status epilepticus were confirmed by EEG and their behaviors. The effective rate of DPH-PBCA-NPs modified with Tween-80 and DPH-PBCA-NPs was 91.67% and 54.55%, respectively;the effective rate of rats in group Ⅲ was 50%, and the effective rate of rats in group Ⅳ and Ⅴ was 0%;DPH-PBCA-NPs modified with Tween-80 enjoyed a better effect than DPH-PBCA-NPs and DPH (P＜0.05). Conclusion DPH-PBCA-NPs and DPH-PBCA-NPs modified with Tween-80 can be used to improve the behaviors of rats with acute epilepsy and modify the results of EEG of these rats.Nanoparticles as drug delivery system can help the drugs having their effects much quickly and effectively.     

维拉帕米对耐苯妥英钠和卡马西平癫(癎)模型大鼠电生理和行为的影响

目的 观察P-糖蛋白(PGP)拮抗剂维拉帕米对耐苯妥英钠(PHT)和卡马西平(CBZ)癫(癎)大鼠电生理指标和行为学的影响.方法 建立慢性杏仁核点燃癫(癎)大鼠模型,筛选出耐药组和治疗有效组,给予维拉帕米,观察其对各组大鼠后放电阈值(after discharge threshold,ADT)、后放电时程(after discharge duration,ADD)等电生理指标和行为学的影响.结果 相对于耐药对照组,耐药组大鼠在预先给予维拉帕米后,使用抗癫(癎)药物后ADT[(238.0±32.2)μA]明显高于耐药对照组[(177.0±23.3)μA,P＜0.05];ADD时程明显缩短,Racine行为分级明显下降(P＜0.05).结论 维拉帕米可以协助抗癫(癎)药物(AEDs)改善耐药大鼠的电生理活动,降低点燃后发作分级,提示有效抑制PGP有助于改善多药转运体高表达导致的癫(癎)耐药.     

海马硬化致耐药性颞叶内侧癫痫的耐药基因蛋白表达及意义

目的 观察耐药性颞叶内侧癫痫硬化海马中有关耐药基因蛋白的表达并探讨其临床意义.方法 对经手术治疗取自16例颞叶内侧癫痫的硬化海马标本进行免疫组化染色观察p-糖蛋白170(p-gp170)、谷胱甘肽硫转移酶-π(GST-π)、拓扑酶Ⅱ(TOP Ⅱ)、胸苷合成酶(TS)及O-6-甲基鸟嘌呤-DNA-甲基转移酶(MGMT)的表达.结果 p-gp170和GST-π在硬化海马组织中神经细胞、血管内皮细胞及胶质细胞均有表达,而以血管内皮细胞和胶质细胞阳性表达尤为突出.TOP Ⅱ、TS和MGMG在硬化海马中无明显阳性表达.结论 长期应用抗癫痫药物可能诱导p-gp170和GST-π表达增强,促进抗癫痫药物的排出与代谢,引起耐药.TOPⅡ、TS和MGMG可能与癫痫耐药机制无关.     

颞叶内侧癫痫的两种术式对发作控制的对比分析

目的观察前颞叶切除术和选择性海马、杏仁核切除术对颞叶内侧癫痫的发作控制效果是否有差别。方法 2009年1月至2010年12月在我科行前颞叶切除术的67例颞叶内侧患者为A组;2011年6月至2013年5月在我科行选择性海马、杏仁核切除术的46例颞叶内侧患者为B组;统计分析两组术后1年发作控制为Engel I-II级和Engel III-IV级的人数。结果 A组Engel I-II级56例(83.58%),Engel III-IV级11例(16.42%);B组Engel I-II级40例(86.95%),Engel III-IV级6例(13.05%)。经χ2检验两组术后对MTLE发作的控制率无统计学差异,χ2=0.243,P0.05。结论前颞叶切除术和选择性海马、杏仁核切除术对颞叶内侧癫痫发作都能获得良好的控制,两者疗效无明显差异。     

TLR4、MRP8在内侧颞叶癫痫幼大鼠海马中表达的动态变化

目的观察氯化锂-匹罗卡品致痫幼大鼠各期海马中Toll-样受体4(TLR4)、髓样相关蛋白8(MRP8)表达的变化,探讨其是否与内侧颞叶癫痫(MTLE)发生有关。方法 21d SD雄性大鼠90只,随机分对照组(30只)和模型组(60只),腹腔注射氯化锂。17～18h后模型组腹腔注射匹罗卡品诱导癫痫持续状态(SE);对照组予等量生理盐水取代匹罗卡品腹腔注射。按自发发作出现和稳定时间(自发痫性发作在致痫后约3w出现,8w趋稳定),对照组和模型组随机分6个亚组:急性模型组(SE后2h)、潜伏模型组(SE后3w)、慢性自发发作组(SE后8w)及相对应时间点对照组。每亚组动物10只。免疫组化、免疫印迹、RT-PCR技术测定各亚组幼大鼠海马内TLR4、MRP8的表达。结果 TLR4、MRP8在模型组海马内表达明显增多,以CA3、CA1、DG区显著;与对照组相比,差异有显著性(P0.05)。模型亚组内,TLR4、MRP8在急性期和慢性期表达明显增高,而潜伏期无明显表达变化;3组比较差异有显著性(P0.05)。结论大鼠海马内TLR4、MRP8表达增多可能与MTLE发生有关。探讨其机制可能为MTLE的治疗提供新的靶点。     

难治性颞叶内侧癫痫外科治疗对项目记忆和源记忆的影响研究

目的 探讨外科治疗对难治性颞叶内侧癫痫患者短期内的项目记忆及源记忆的影响.方法 对18例诊断为难治性颞叶内侧癫痫患者,行选择性海马杏仁核切除术(其中左侧7例,右侧11例),并在手术前及手术后3个月选用实义词和实物简图分别进行项目记忆和源记忆测试,对结果进行分析.结果 所有患者随访3～12个月,平均6.78个月,疗效满意13例(72.2%),显著改善4例(22.2%),良好1例(5.6%);颞叶内侧癫痫患者手术治疗前和术后3个月的项目记忆指标值分别为0.7609±0.1225和0.6296±0.1313,源记忆指标值分别为0.7384±0.1369和0.6806±0.1533,差异均有统计学意义(P＜0.05).左侧患者手术治疗前和术后3个月的项目记忆指标值分别为0.7576±0.0763和0.6580±0.0834,源记忆指标值分别为0.7024±0.1432和0.5952±0.1950,差异均有统计学意义(P＜0.05).右侧患者手术治疗前和术后3月的项目记忆指标值分别为0.7631±0.1483和0.6116±0.1556,差异有统计学意义(P＜0.05),而源记忆指标值分别为0.7614±0.1345和0.7348±0.0937,差异无统计学意义(P＞0.05).结论 外科治疗难治性颞叶内侧癫痫效果满意,短期内可能会造成患者的项目记忆和源记忆损害,特别是对左侧手术患者的影响较大,而对右侧手术患者的影响主要表现为项目记忆损害.     

Efficacy of temporal lobe surgery for epilepsy in patients with negative MRI for mesial temporal lobe sclerosis

Epilepsy surgery is a successful treatment for refractory temporal lobe epilepsy (TLE). Reports suggest fewer seizure-free outcomes for patients with TLE and who have a negative brain MRI (nMRI) for mesial temporal sclerosis. Data were collected prospectively from patients with nMRI who underwent temporal lobe surgery for TLE characterized by unilateral ictal temporal lobe seizure onset based on a scalp video electroencephalogram or invasive subdural electrode recordings. A total of 86 patients were followed for at least 24 months after surgery. Outcome was evaluated using the Engel classification. Seizure control was obtained by 55% (47/86) of patients (Class [CL]-I), 27% (23/86) showed significant improvement (CL-II) and 19% (16/86) were deemed surgical failures. Shorter duration of epilepsy, later onset of seizures, and ictal theta rhythm (5-7 Hz) were the most significant predictors of postoperative seizure control. Although hypometabolism on positron emission tomography scan and significant memory disparity (>2.5/8) were not significant prognosticators independently, cumulatively they were predictors for favorable outcome.     

Familial mesial temporal lobe epilepsy (FMTLE)

Introduction Familial mesial temporal lobe epilepsy (FMTLE) is characterized by prominent psychic and autonomic seizures, often without hippocampal sclerosis (HS) or a previous history of febrile seizures (FS), and good prognosis. The genetics of this condition is largely unknown.We present the electroclinical and genetic findings of 15 MTLE Italian families. Patients and methods FMTLE was defined when two or more first-degree relatives had epilepsy suggesting a mesial temporal lobe origin. The occurrence of seizures with auditory auras was considered an exclusion criterion. Patients underwent video-EEG recordings, 1.5-Tesla MRI particularly focused on hippocampal analysis, and neuropsychological evaluation. Genetic study included genotyping and linkage analysis of candidate loci at 4q, 18q, 1q, and 12q as well as screening for LGI1/Epitempin mutations. Results Most of the families showed an autosomal dominant inheritance pattern with incomplete penetrance. Fifty-four (32 F) affected individuals were investigated. Twenty-one (38.8 %) individuals experienced early FS. Forty-eight individuals fulfilled the criteria for MTLE. Epigastric/visceral sensation (72.9 %) was the most common type of aura, followed by psychic symptoms (35.4 %), and déjà vu (31.2 %). HS occurred in 13.8% of individuals, three of whom belonged to the same family. Prognosis of epilepsy was generally good. Genetic study failed to show LGI1/Epitempin mutations or significative linkage to the investigated loci. Discussion FMTLE may be a more common than expected condition, clinically and genetically heterogeneous. Some of the reported families, grouped on the basis of a specific aura, may represent an interesting subgroup on whom to focus future linkage studies.     

Surgical outcome of patients with mesial temporal lobe epilepsy related to hippocampal sclerosis

Seizure outcome in mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) that was evaluated according to a noninvasive protocol was assessed in 165 patients and reported using both Engel's and ILAE classifications. The mean postoperative follow-up was 5.0 +/- 2.7 years. At the end of first year, 77.1% of patients were in Engel-I, and 52.7% were in ILAE-I. Antiepileptic drugs (AEDs) were discontinued in 41 patients (42.7%), all remained seizure-free for >or= 2 years that could be accepted as "cure." Thirty-six patients had recurrences, 19 had running-down phenomena. Anterior temporal lobectomy (ATL) was performed in 27 patients with a better outcome when compared to patients operated by selective anterior hippocampectomy. Clinical risk factors for better and worse outcome, which show some similarity in different reports, seem to veil the main reason, which is the accurate delineation of epileptogenic zone considering the presence of different subgroups and underlying developmental pathologies.     

经颞下回-侧脑室入路选择性海马杏仁核切除术治疗内侧颞叶癫痫

目的 探讨经颞下回-侧脑室入路选择性海马杏仁核切除术治疗内侧颞叶癫痫的手术方法 、疗效及并发症. 方法 对确诊为药物难治性内侧颞叶癫痫的62例患者,经颞部锁孔开颅,切除中前段颞下回,进入颞角前外侧区,选择性切除海马杏仁核及海马旁回等内侧颞叶结构.结果 62例患者术后随访至少24～80个月,无严重手术并发症;Engel癫痫疗效分级;Ⅰ级45例(72.6%),Ⅱ级12例(19.4%),Ⅲ级5例(8.0%). 结论 经颢下回-侧脑室入路选择性海马杏仁核切除术是治疗内侧颞叶癫痫的有效方法 ,其手术创伤小,可妥善保护语言区和视放射,安全性高.     

不同手术入路治疗海马硬化性颞叶内侧癫痫的比较

目的 比较常用的四种手术方式在治疗海马硬化性颞叶内侧癫痫(MTLE/HS)中的优缺点.方法 106例顽固性MTLE/HS患者中23例行经皮层脑室入路选择性海马杏仁核切除术;23例行经侧裂选择性海马杏仁核切除术;30例行前内侧颞叶切除术;30例行经颞下选择性海马杏仁核切除术.随访6个月-9年.采用Engel分级量表评价癫痫治疗效果,并比较并发症发生率.结果 四种术式在对癫痫发作的治疗效果比较上差异无统计学意义,无手术死亡,在并发症发生率方面差异无统计学意义.结论 对于经严格筛选的MTLE/HS,四种手术方式在疗效和安全性方面相当,可根据个人手术经验加以选择.     

Ictal automatisms with preserved responsiveness in a patient with left mesial temporal lobe epilepsy

PURPOSE: To describe the possible mechanism of ictal automatisms with preserved responsiveness (APRs) in a patient with left mesial temporal lobe epilepsy, which had not been reported previously. METHODS: Ictal EEGs recorded from bilateral foramen ovale electrodes with scalp-sphenoidal electrodes were analyzed in respect to the ictal semiology. RESULTS: The patient had a right hemispheric language dominance in the dextral. Electroclinical analysis revealed that the onset of oroalimentary automatisms coincided with the involvement of the left mesial and lateral temporal structures by spreading ictal discharges. The ictal discharge spreading was limited to the ipsilateral hemisphere throughout the seizure, which explained the intact consciousness and preserved responsiveness of the patient. CONCLUSIONS: This case suggests that APRs take place in seizures originating from the nondominant temporal lobe, during which ipsilateral mesial and lateral temporal structures are diffusely involved without spreading to the contralateral side.     

难治性颞叶癫痫的外科治疗(附35例临床分析)

目的总结并分析难治性颞叶癫痫患者术前定位、手术方式和经验。方法回顾性分析2009年6月至2011年6月,采用颞前叶+海马杏仁核切除术治疗的颞叶癫痫病人35例,其中术前MRI及术后病理证实伴有海马硬化者32例,所有病例术中均在皮层电极监测下切除颞叶皮质及同侧海马、杏仁核,手术后均应用抗癫痫药物治疗,术后随访1～3年。结果在35随访病例中,癫痫发作控制结果显示EngelⅠ级24例,Ⅱ级8例,Ⅲ级3例,Ⅳ级0例。其中有12例病人术后2年逐渐停用抗癫痫药物。结论联合应用VEEG、MRI及EcoG能准确确定致痫灶,提高颞叶癫痫手术疗效。手术方式选择及显微理念的应用,能有效减少术后并发症的发生,避免出现永久性神经功能缺失。     

Design considerations for a multicenter randomized controlled trial of early surgery for mesial temporal lobe epilepsy

Purpose: To describe the trial design for the multicenter Early Randomized Surgical Epilepsy Trial (ERSET). Patients with pharmacoresistant epilepsy are generally referred for surgical treatment an average of two decades after onset of seizures, often too late to avoid irreversible disability. ERSET was designed to assess the safety and efficacy of early surgical intervention compared to continued pharmacotherapy. Methods: ERSET is a randomized controlled, parallel group clinical trial with blinded outcome adjudication. Participants are patients with mesial temporal lobe epilepsy (MTLE) older than the age of 12 who have had pharmacoresistant seizures for not >2 years and are determined by detailed evaluation to be surgical candidates prior to randomization. The primary outcome measure is seizure freedom in the second year of a 2‐year follow‐up period. Health‐related quality of life (HRQOL), neurocognitive function, ancillary outcomes, and adverse events were also measured. Results: Significant methodologic problems addressed by the study design included the following: recruitment of participants early in the course of epilepsy; establishment of operational definitions for “pharmacoresistant” and “early”; and standardization of diagnostic testing, medical treatment, and surgical interventions across multiple centers. Discussion: Rigorous trial designs to assess surgical interventions in epilepsy are necessary to provide evidence to guide treatment. This article is the first of a series; trial results will be reported in subsequent publications.     

The impact of temporal lobe epilepsy on musical ability

PurposePatients with temporal lobe epilepsy (TLE) often show impairment of cognitive processing in different domains. We aimed to evaluate whether also musical ability is impaired in TLE.MethodsWe enrolled patients with lesional TLE and without any other neurological or psychiatric disorder. The side and the etiology of the epilepsy were confirmed by EEG and by MRI. We applied a self-developed test of musical ability which evaluates the ability to identify melodies, pitch, rhythm, and emotional content of music. In addition, we compared the results of the patients to the results of age and sex matched healthy control subjects. All patients and subjects were without specific musical training.ResultsPatients with left TLE showed a significantly lower score in melody recognition, patients with right TLE showed a significantly lower score in identification of emotion in music. In all other aspects of music ability, no significant difference between left and right TLE could be found. We observed a significantly lower total score in patients with left TLE, but not with right TLE, as compared to healthy subjects. There were no differences with respect to sex.ConclusionOur data confirm that the recognition of melodies shows left hemisphere dominance whereas the identification of emotions in music shows right hemisphere dominance in patients without musical training. Furthermore, our data show that the impairment of cognitive processing in TLE is reflected even in higher cognitive functions such as music processing. However, this impairment was mild.