自身免疫性癫痫入院诊断与免疫治疗转归的相关性

目的：回顾分析各种抗体类型自身免疫性癫痫(autoimmune epilepsy,AE)的临床资料,探讨入院诊断对癫 痫预后的影响。方法：收集 2017年1月1日至2018年11月21日中南大学湘雅医院神经内科抗神经元抗体阳性的AE病例 40例,根据入院诊断分为初诊AE组及初诊非AE组,对比两组一般资料、临床症状、脑脊液、脑电图、影像学检查等 结果,分析入院诊断对两组患者癫痫预后的影响。结果：40例AE患者年龄为(33.23±16.41)岁,男女比例为1:1.11。初 诊AE组(n=25)与初诊非AE组(n=15)在性别、年龄、抗体分布、症状学特征、脑脊液、影像学表现等方面的差异均无 统计学意义(均P>0.05)。初诊非AE组患者抗体检测距初始症状天数显著长于初诊AE组(P<0.01)。初诊非AE组患者免疫 治疗距初始症状天数显著长于初诊AE组(P<0.001),且初诊AE组的癫痫好转率显著高于初诊非AE组(P<0.05)。结论： AE患者的入院诊断与其免疫治疗转归相关,针对成年期新发癫痫或病因不明的癫痫应充分考虑AE的可能性,AE患者 一旦确诊应尽早启用免疫治疗以改善其预后。     

癫痫诊治过程中值得注意的几个问题（二）

３　如何选择抗痫药物癫痫是一种常见病,大多数患者需要长期服用抗痫药,由于可选用的抗痫药不断增加,一些新的抗痫药用于临床,一些正在临床实验阶段,因此,使抗痫药的选择增添了难度。对于每个癫痫患者,选择理想的抗痫药取决于诸多因素,如药物学特性、痫性发作类型、医疗状况、社会经济情况等。最理想的抗痫药是能够控制痫性发作而不引起难以接受的副作用,获得这一结果应该是治疗每个癫痫患者的最高目标。有人提出了“因人制宜,剪裁选用（ｔａｉｌｏｒｉｎｇｓｅｌｅｃｔｉｏｎ）抗痫药”的概念,抗痫药的选择应考虑以下几方面的因…     

自身免疫性脑炎诊断及治疗研究新进展

自身免疫性脑炎（AE）是一组抗原抗体相关疾病,其临床诊断主要依据临床表现、自身抗体检测和影像学检查等方面。在目前的临床工作中,患者出现急性或亚急性发病的认知功能障碍、痫性发作和精神症状,即可考虑AE的诊断。近年来,随着抗体检测技术的提升,医学影像学技术的发展,新类型AE逐渐被人们发现,AE的诊断及治疗也有明显改善。目前我国AE临床及基础研究尚处于起步阶段,本文就国内外AE最新的临床诊断指南、专家共识及治疗方面的研究进展进行总结,以进一步提高对该病的临床诊断率及临床疗效。     

多重抗神经元抗体阳性的自身免疫性脑炎2例

自身免疫性脑炎（AE）的临床表现复杂,尤其是罕见的多重抗神经元抗体阳性的AE。本文报告2020年6月10日、10月9日宁波市医疗中心李惠利医院收治的2例多重抗神经元抗体阳性的AE患者。例1是15岁男孩,血清及脑脊液检查显示抗N-甲基-D-天冬氨酸受体（NMDAR）抗体和抗代谢型谷氨酸受体5（mGLuR5）抗体为阳性。例2为69岁男性,脑脊液检查显示抗接触蛋白2（CASPR2）抗体和抗富亮氨酸胶质瘤失活1蛋白（LGI1）抗体均阳性,最终被确诊为AE。多重抗神经元抗体阳性的AE患者临床表现复杂多样,导致临床诊疗难度增加,需引起临床重视。     

抗体阳性与抗体阴性的自身免疫性脑炎患者临床特征比较

目的比较自身免疫性脑炎(AE)待查患者中,抗体阳性(确诊)的AE患者和抗体阴性(可能)的AE患者之间的临床特征及辅助检查差异。方法回顾性分析2017年3月至2018年12月于中国科学技术大学附属第一医院诊断为AE待查的患者56例,所有患者的脑脊液和血清进行AE相关抗体[抗N-甲基-D-天冬氨酸受体抗体(NMDAR)、抗α-氨基-3-羟基-5-甲基-4-异噁唑丙酸受体抗体(AMPAR)、抗γ-氨基丁酸B受体抗体(GABABR)、抗富亮氨酸胶质瘤失活蛋白1抗体(LGI1)和抗接触素相关蛋白2抗体(CASPR2)]检测。根据抗体检测结果分为抗体阳性的AE患者和抗体阴性的AE患者,其中抗体阳性的AE患者31例,抗体阴性的AE患者25例。比较分析两组患者的临床特征和辅助检查结果的差异,以及疾病严重程度和治疗的差异。结果 31例抗体阳性的患者中,抗NMDA脑炎20例(65%),抗GABABR脑炎9例(29%),抗LGI1脑炎2例(6%)。抗体阴性的AE患者静脉滴注免疫球蛋白(IVIG)的使用率低于抗体阳性的AE组。两组患者的性别、年龄、前驱症状、神经系统症状、头颅磁共振表现、脑电图结果、脑脊液压力、脑脊液细胞数及脑脊液蛋白水平的差异均无统计学意义(P均> 0. 05),两者的入住ICU率、最高mRS评分、出院日mRS评分差异无统计学意义(P均> 0. 05)。结论 AE患者中抗体阴性的并不少见,抗体阴性的AE患者临床表现与辅助检查跟抗体阳性的AE无显著性差异,对该类患者进行临床表现和辅助检查分析是必要的。     

抗痫制剂对癫痫模型小鼠学习记忆变化的影响

目的 探讨抗痫制剂对戊四氮致痫小鼠学习、记忆力改变的影响。方法 健康成年雄性小鼠60只,随机分为空白对照组,模型对照组,抗痫制剂大剂量组、中剂量组、小剂量组和丙戊酸钠组,每组10只。抗痫制剂大、中、小剂量组小鼠分别以抗痫制剂 14.8mg/g、7.4mg/g和3.7mg/g灌胃,每天1次,连续7d;复制戊四氮诱导急性癫痫模型;水迷宫测定抗痫制剂对致痫小鼠学习和记忆力的影响。结果 与空白对照组相比,模型对照组小鼠逃避潜伏期延长,行程出错率增加(P<0.05);与模型对照组和丙戊酸钠组相比,抗痫制剂大、中、小剂量组小鼠逃避潜伏期缩短、行程出错率减少(P<0.05)。与模型对照组相比,丙戊酸钠组小鼠逃避潜伏期、行程出错率均值虽增加,但差异无统计学意义(P>0.05)。结论 模型对照组和丙戊酸钠组小鼠学习、记忆力降低;抗痫制剂能缩短模型小鼠水迷宫逃避潜伏期,减少行程出错率,明显改善致痫小鼠学习记忆能力。     

桂皮酰哌啶(7306)和对氯桂皮酰哌啶(7302)的中枢神经系统药理作用

自从应用我院合成的“抗痫灵”临床治疗癫痫以来,我院药学系抗痫灵研究小组在短期内又合成了多种抗痫灵衍化物,其中7306和7302具有较强的抗惊厥作用,将初步药理研究结果报告如下。     

抗N-甲基-D-天冬氨酸受体脑炎及其伴随痫性发作的临床特点

目的：探讨抗N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)脑炎的临床特点及其伴随痫 性发作的特征。方法：回顾性分析中南大学湘雅医院2016年1月至2018年7月确诊为抗NMDAR脑炎的20例患者资料, 包括临床特点、痫性发作特点、辅助检查、治疗方案等,并对出院患者进行半年随访。结果：抗NMDAR脑炎患者首 发症状主要为痫性发作及精神行为异常。抗NMDAR脑炎患者伴随痫性发作类型主要为全面性发作,脑电图多为广泛 慢波。与无痫性发作组比较,有痫性发作组MRI示颞叶病变和出现意识障碍的频率更高(P<0.05)。经规范治疗出院后 半年随访,20例患者改良Rankin量表(modified Rankin Scale, mRS)评分得到明显改善,未再出现痫性发作。结论：发 病期间出现意识障碍、颞叶有病灶的抗NMDAR脑炎患者,需注意有痫性发作的可能。如有痫性发作,应及时使用抗 癫痫药物及免疫治疗,并去除病因。经规范治疗后,患者预后大多较好。     

尼莫地平对青霉素诱导的大鼠癫痫的抑制作用观察

采用Ｗｉｓｔａｒ大鼠腹腔注射青霉素，造成实验性癫痫模型，对大鼠痫性发作的行为改变、海马和大脑皮质的电生理变化以及双氢吡啶类钙通道阻滞剂尼莫地平的抗痫作用进行了观察。结果显示：尼莫地平能明显抑制大鼠痫性放电和痫性发作，预先腹腔注射尼莫地平再给予青霉素则不出现痫性活动。由此表明尼莫地平是一种富有潜力的新型非镇静性抗痫剂     

一次口服抗痫灵的药物动力学研究

本文应用高压液相色谱法和紫外分光光度法测定犬和大鼠血浆及脑组织匀浆中的抗痫灵含量。 根据犬一次口服抗痫灵60mg/kg的血药浓度——时间消除曲线,按二房室开放模型,一级动力学推算出抗痫灵的药物动力学各项参数如下:峰浓度为8.8414μg/kg,峰时间为1.5小时,消除半衰期为9.2小时,消除速率为0.1096~(-h),血浆清除率为0.8329L/kg·h和表观分布容积为1.9426L/kg·h。抗痫灵片剂的相对生物利用度为93.94％。 大鼠一次口服抗痫灵400mg/kg的抗惊厥效应和血浆、脑组织中的药物浓度密切相关。抗痫灵的血浆和脑组织中浓度比值约为10(9.30～12.14),说明大鼠血浆中的浓度可以反映药物的抗惊厥药理效应。     

The effect of the destruction of the caudate-putamen on the development of amygdaloid kindling and kindled seizures

To elucidate the possible roles of the caudate-putamen (CP) on the development of amygdala (AM) kindling and AM-kindled seizures, the bilateral CP were destroyed by intra-CP injection of ibotenic acid (0.5 or 1.0 microg per side) before the AM kindling or after completion of the AM kindling. Prior destruction of the CP, especially by 0.5 microg ibotenic acid injection, caused a significant delay in seizure development. However, after completion of the AM kindling, bilateral destruction of the CP significantly suppressed AM-kindled seizures in proportion to lesion size, however, all animals reached a stage 5 seizure by additional stimulations and established AM kindling. These findings suggest that the intact CP modulates the development of the AM kindling and the generalization and/or expression of the kindled AM seizures, and that the CP plays an important role in the generalization and/or expression of the kindled AM seizures.     

Curcumin inhibits amygdaloid kindled seizures in rats

Background Curcumin can reduce the severity of seizures induced by kainate acid （KA）, but the role of curcumin in amygdaloid kindled models is still unknown. This study aimed to explore the effect of curcumin on the development of kindling in amygdaloid kindled rats. Methods With an amygdaloid kindled Sprague-Dawley （SD） rat model and an electrophysiological method, different doses of curcumin （10 mg·kg^-1·d^-1 and 30 mg·kg^-1·d^-1 as low dose groups, 100 mg·kg^-1·d^-1 and 300 mg·kg^-1·d^-1 as high dose groups） were administrated intraperitoneally during the whole kindling days, by comparison with the course of kindling, afterdischarge （AD） thresholds and the number of ADs to reach the stages of class I to V seizures in the rats between control and experimental groups. One-way or two-way ANOVA and Fisher＇s least significant difference post hoc test were used for statistical analyses. Results Curcumin （both 100 mg·kg^-1·d^-1 and 300 mg·kg^-1·d^-1 ） significantly inhibited the behavioral seizure development in the （19.80±2.25） and （21.70±2.21） stimulations respectively required to reach the kindled state. Rats treated with 100mg·kg^-1·d^-1 curcumin 30 minutes before kindling stimulation showed an obvious increase in the stimulation current intensity required to evoke AD from （703.3±85.9） μA to （960.0±116.5） μA during the progression to class V seizures. Rats treated with 300 mg·kg^-1·d^-1 curcumin showed a significant increase in the stimulation current intensity required to evoke AD from （735.0±65.2） μA to （867.0±93.4） μA during the progression to class V seizures. Rats treated with 300mg·kg^-1·d^-1 curcumin required much more evoked ADs to reach the stage of class both IV （as （199.83±12.47） seconds） and V seizures （as （210.66±10.68） seconds）. Rats treated with 100 mg·kg^-1·d^-1 curcumin required much more evoked ADs to reach the stage of class V seizures （as （219.56±18.24） seconds）. Conclusion Our study suggests that curcumin has a potential antiepileptogenic effect on kindling-induced epileptogenesis.     

大鼠马桑内酯全身型点燃效应癫痫模型

作者用亚抽搐量的马桑内酯作反复肌肉注射,造成了大鼠点燃效应癫痫模型。这是一种较理想的慢性实验性癫痫模型。     

Effect of adenosine A2A receptor antagonist ZM241385 on amygdala-kindled seizures and progression of amygdala kindling

The purpose of this study was to evaluate the effect of adenosine A2A receptor antagonist ZM241385 on amygdala-kindled seizures and its roles in epileptogenesis. Electrodes were implanted into the right amygdala of male adult Wistar rats. Kindling was accomplished by using stimulus strength of 500 μA applied daily to the amygdala until 10 consecutive stage 5 seizues were induced. Then effect of ZM241385 was studied in fully kindled rats after intracerebroventricular administra-tion of the drug. In addition, the effect on kindling progression was evaluated through ZM241385 in-jection before daily stimulation. In all experiments, behavioral changes in the rats in response to ZM241385 were monitored closely. The results showed that, in fully amygdala-kindled rats, ZM241385 (0.001-0.1 nmol/L) decreased afterdischage duration (ADD), motor seizure duration (MSD), stage 5 duration (S5D) and seizure duration (SD), but only the effect on ADD was dose-dependent. The doses of 0.001-0.1 nmol/L had no influence on stage 4 latency (S4L) and sei-zure stage (SS). The dosages of 0.0001 and 1 nmol/L of ZM241385 did not exert any effect on all sei-zure parameters. In contrast to the results in fully amygdala-kindled rats, ZM241385 (0.001-0.1 nmol/L) had minimal or no effects on the progression of amygdala-kindled seizures. We are led to the conclusion that although ZM241385 had no influence on the progression of amygdala-kindled sei-zures, it had potent anti-convulsant profile and little adverse effects at the dosage of 0.001-0.1 nmol/L, suggesting that the agent is effective against the amygdala-kindled seizures.     

柴胡总皂甙对戊四氮慢性点燃大鼠痫性发作及脑电图的影响

目的 评价柴胡有效成分中柴胡总皂甙对戊四氮（PTZ）慢性点燃大鼠痫性发作及脑电图的影响。方法 将48只健康SD大鼠随机等分为6组,即空白组、生理盐水组、丙戊酸钠（VPA）组和柴胡总皂甙高、中、低3种剂量组,除空白组不做处理外．其他组采用腹腔注射PTZ进行慢性点燃造模,造模同时给予以上不同处理因素,连续4周．在此期间记录大鼠痫性发作级别及次数,最后描记大鼠脑电图。结果 柴胡总皂甙高、中、低3个剂量组在实验2周时可以降低大鼠的痫性发作率,其中以高剂量组显著（P〈0．05）,柴胡皂甙高剂量组应用4周时能明显降低PTZ慢性点燃大鼠的点燃率（P〈0．05）,并明显降低痫性发作级别（P〈0．01）;各组间脑电图也存在一定差异。结论 柴胡总皂甙可拮抗PTZ慢性点燃大鼠的痫性发作．并有一定的对抗PTZ慢性点燃作用。     

杏仁核电点燃癫痫对大鼠穿梭箱被动回避反应的记忆保持能力的作用

目的:探讨杏仁核电点燃癫痫对大鼠穿梭箱被动回避反应的记忆保持能力的影响.方法:大鼠每24 h进行一次电刺激直至完 全点燃,然后利用穿梭箱系统检测慢性电点燃癫痫对大鼠被动回避反应的记忆保持能力的作用;另一组动物于训练前5 min给予杏仁核电刺激诱发癫痫大发作,观察癫痫的急性发作对记忆保持能力的作用.结果:在被动回避反应训练过程以及测试第1天,慢 性点燃癫痫组和对照组动物进入暗箱的反应潜时没有明显差异;在测试第5天,慢性点燃癫 痫组动物进入暗箱的反应潜时比对照组动物明显增加.另外,癫痫的急性发作使大鼠在测试 第1天和第5天进入暗箱的反应潜时明显缩短.结论:慢性杏仁核电点燃癫痫 可使大鼠被动回避反应的记忆保持能力增加,而癫痫的急性发作减弱了大鼠的记忆保持能力 .     

PTX腹腔注射致SD鼠点燃癫痫模型

目的：观察不同剂量印防已毒（PTX）致SD鼠慢性点燃癫痫模型及药物对该模型的影响,方法：采用TPX腹腔注射制作SD鼠慢性点燃模型,并将其分为对照组,癫痫I组（PTX,1．5mg.kg^-1.d^-1),癫痫II组（TPX,2mg^-1.d^-1)和苯巴比妥钠干预组,观察发作情况,并做脑电图记录,结果：注药第20d时,对照组无癫痫发作,癫痫I组71％SD鼠（10／14）完全点燃;癫痫II组4只死亡,2只Ⅳ级,2只Ⅴ级;苯巴比妥钠干预组17％SD鼠（1／6）完全点燃,完全点燃的SD鼠在脑电图上出现典型尖波,棘波发放,结论：在该实验中,PTX腹腔注射致SD鼠点燃癫痫模型的较好剂量是1．5mg/kg^-1.d^-1,苯巴比妥钠可阻止该模型的形成。     

Subacute and chronic electrical stimulation of the hippocampus on intractable temporal lobe seizures: preliminary report

Recent animal experiments show that the application of an electrical stimulus to the amygdala or hippocampus following the kindling stimulus produced a significant and long-lasting suppressive effect on this experimental model of epilepsy. This is a preliminary report on the development of a surgical neuromodulatory procedure by chronic electrical stimulation of the hippocampus (CHCS) for control of intractable temporal lobe seizures in patients in whom anterior temporal lobectomy is not advisable, i.e., patients with bilateral temporal foci or a unilateral focus spreading to surrounding cerebral regions of the dominant hemisphere.This work was divided in two main consecutive stages. In the first stage, we demonstrated that subacute hippocampal stimulation (SAHCS) blocks intractable temporal lobe epileptogenesis with no additional damage to the stimulated tissue, and in a second stage, we attempt to demonstrate that CHCS may produce a sustained, long-lasting antiepileptic condition without additional undesirable effects on language and memory. In addition, taking advantage of this unique and ethically permissible situation, we attempt to determine whether or not the antiepileptic effects of SAHCS and CHCS are due to inhibition of the stimulation of hippocampal tissue by means of a number of electrophysiological, single photon computed tomography (SPECT) perfusion, and autoradiographic techniques.SAHCS during 3-4 weeks prior to anterior temporal lobectomy applied to a critical area located either at the anterior Pes hippocampus close to the amygdala or at the parahippocampal gyrus close to the entorhinal cortex abolished clinical seizures and significantly decreased the number of interictal spikes at focus after 5-6 days. Microscopy analysis of the stimulated tissue showed no evident histopathological differences between stimulated vs. non-stimulated hippocampal tissues. Additionally, CHCS persistently blocked temporal lobe epileptogenesis for 3-4 months with no apparent additional undesirable effects on short memory. Also, inhibition of the stimulated hippocampus seems to be one of the possible mechanisms underlying the beneficial antiepileptic effects of SAHCS and CHCS. This was revealed by increased threshold and decreased duration of the afterdischarges induced by hippocampal stimulation, flattening of the hippocampal-evoked response recovery cycles, SPECT hypoperfusion of the hippocampal region, and increased hippocampal benzodiazepine receptor binding.Future studies increasing the number and time of follow-up of patients under hippocampal stimulation are necessary before considering CHCS a reliable procedure for controlling intractable temporal lobe seizures.     

PTX腹腔注射致SD鼠点燃癫痫模型

目的 :观察不同剂量印防已毒 (PTX)致SD鼠慢性点燃癫痫模型及药物对该模型的影响。方法 :采用PTX腹腔注射制作SD鼠慢性点燃模型 ,并将其分为对照组、癫痫I组 (PTX ,1 5mg·kg- 1 ·d- 1 )、癫痫II组 (PTX ,2mg- 1 ·d- 1 )和苯巴比妥钠干预组 ;观察发作情况 ,并做脑电图记录。结果 :注药第 2 0d时 ,对照组无癫痫发作 ,癫痫I组 71 %SD鼠(1 0 /1 4)完全点燃 ;癫痫II组 4只死亡、2只IV级、2只V级 ;苯巴比妥钠干预组 1 7%SD鼠 (1 /6 )完全点燃。完全点燃的SD鼠在脑电图上出现典型尖波、棘波发放。结论 :在该实验中 ,PTX腹腔注射致SD鼠点燃癫痫模型的较好剂量是 1 5mg·kg- 1 ·d- 1 ,苯巴比妥钠可阻止该模型的形成     

灵芝孢子粉在点燃模型的作用研究

目的研究灵芝孢子粉对大鼠点燃模型的作用。方法建立大鼠戊四唑(pentylenetetrazole,PTZ)化学性点燃,观察孢子粉对点燃发作的影响。结果孢子粉500 mg.kg-1抑制PTZ化学点燃的发作(P<0.05)。结论孢子粉对PTZ化学点燃的发作有拮抗作用。