嗅鞘细胞移植治疗免疫性脑脊髓炎：有免疫学排斥现象吗？

目的：研究嗅鞘细胞（OECs）的免疫原性及移植实验性免疫性脑脊髓炎（EAE）后颈淋巴系统的反应。方法：用新生ICR小鼠嗅球培养出OECs, 流式细胞术（FCM）检测其表面主要组织相容性抗原I、II类（MHC-I、MHC-II）表达情况。将经荧光染料CFSE标记OECs悬液或PBS注入EAE大鼠或正常大鼠的侧脑室,收集移植7天后颈部淋细胞,FCM检测CFSE+、抗原提呈细胞标志物CD83+及CFSE+CD83+的表达率,混合淋巴细胞培养检测淋巴细胞增殖率（PI）。结果：OECs高表达MHC-I (78.4±4.45%),中表达MHC-II(43.2±2.98%)。移植实验显示移植OECs的EAE大鼠颈部淋巴结中CD83+（3.83±0.03%）、CFSE+（2.47±0.05%）及CD83+CFSE+（1.98±0.04%）检出率及OECs诱导的PI值（1.32±0.06）均高于对照组或正常大鼠（P<0.05）。同时,PBS注射的EAE大鼠,较正常大鼠亦有较高的CD83+检出率（3.12±0.04%）及PI值（1.20±0.03）（P<0.05）。结论： OECs高表达的MHC分子提示OECs有免疫原性,移植后局部淋巴系统可出现针对OECs的抗原引流、提呈及T细胞的活化,进一步分析提示这种免疫反应的启动依赖于EAE的炎性环境,而OECs移植则加重这一过程。     

神经梅毒患者外周血T淋巴细胞亚群水平检测 及临床意义

目的 探讨外周血 T 淋巴细胞亚群 CD3+ 、CD4+ 、CD8+ 水平和 CD4+ /CD8+ 比值识别早期 神经梅毒的作用。方法 回顾性分析 2020 年 2 月至 2022 年 1 月杭州市西溪医院神经内科因梅毒就诊 的 100 例患者的临床资料,根据有无神经系统累及分为神经梅毒组和非神经梅毒组,每组 50 例。选取 同期我院的 50 名健康体检者作为对照组。比较患者和对照组受试者 CD3+ 、CD4+ 、CD8+ T淋巴细胞水 平和 CD4+ /CD8+ 比值。采用受试者工作特征（ROC）曲线分析外周血 T 淋巴细胞亚群识别早期神经梅毒 的价值。结果 神经梅毒组、非神经梅毒组和对照组的 CD4+ T 淋巴细胞水平分别为（30.48±4.08）%、 （32.16±4.08）%、（34.50±4.49）%,CD4+ /CD8+ 比值分别为（1.25±0.19）、（1.35±0.25）、（1.47±0.23）,3 组比 较差异有统计学意义（F=11.428、11.970;P＜ 0.01）;两两比较,差异均有统计学意义（均P＜ 0.05）。将神 经梅毒组患者分为早期组（n=30）、晚期组（n=20）并与对照组进行比较,结果显示 CD4+ T 淋巴细胞水平分 别为（31.23±4.28）%、（29.35±3.57）%、（34.50±4.49）%,CD4+ /CD8+ 比值分别为（1.29±0.21）、（1.18±0.13）、 （1.47±0.23）,3 组比较差异有统计学意义（F=12.289、15.350;P＜ 0.01）。晚期组的 CD4+ T淋巴细胞水 平、CD4+ /CD8+ 比值低于对照组,CD4+ /CD8+ 比值低于早期组,差异有统计学意义（P＜ 0.05）。CD4+ / CD8+ 比值预测神经梅毒的 ROC 曲线下面积为 0.725（95%CI：0.645～0.805）,高于 CD3+ 、CD4+ 和 CD8+ 。 结论 CD4+ T 淋巴细胞水平或 CD4+ /CD8+ 比值下降高度提示神经梅毒,CD4+ /CD8+ 比值更有助于早期识 别神经梅毒。     

丹参对大鼠移植肝血红素氧合酶1表达的影响*

背景：器官移植前使用丹参预处理能够保护组织缺血-再灌注损伤,改善移植器官存活率。 目的：观察含丹参的冷灌注液对同种异体大鼠移植肝脏中血红素氧合酶1表达的影响,以及对供体肝脏缺血-再灌注损伤的保护作用。 方法：将SD雄性大鼠随机分成UW液组(术中使用UW液灌注保存)、丹参+UW液组(术中使用丹参+UW液灌注保存)、ZnPP预处理组(移植前24 h腹腔内注射ZnPP,术中使用丹参+UW液灌注保存),建立稳定的大鼠同种异体肝移植模型。同时取10只正常大鼠作为正常对照。 结果与结论：丹参+UW液组和UW液组血清总胆红素、谷丙转氨酶、谷草转氨酶水平明显低于ZnPP预处理组(P < 0.01)。血红素氧合酶1mRNA及其蛋白在丹参+UW液组中较UW组表达更明显,在ZnPP预处理组中表达明显受到抑制(P < 0.05)。丹参+UW液组肝脏Suzuki标准评分明显低于ZnPP预处理组及UW液组(P < 0.05)。表明丹参能上调同种异体的大鼠移植肝脏中血红素氧合酶1 mRNA及其蛋白的表达,减轻供肝缺血-再灌注损伤,保护移植大鼠肝脏。     

C6细胞热休克蛋白抗原肽复合物的提纯及抑瘤作用的研究

目的 提纯大鼠脑胶质瘤C6细胞热休克蛋白抗原肽复合物(HAC),免疫SD大鼠,观察HAC的抑瘤作用。方法 采用免疫亲和层析方法提纯大鼠脑胶质瘤C6细胞HAC,免疫20只大鼠为实验组,以另20只大鼠作为对照组,于免疫后1周,采用立体定向脑内接种方法,以C6细胞攻击两组大鼠,于肿瘤细胞攻击后第二周,取两组动物外周静脉血,测定外周静脉血淋巴细胞计数,并应用流式细胞仪技术测定外周血中CD3+CD4+和CD3+CD8+T淋巴细胞的比例。观察饲养过程中实验动物出现的症状、体征和第四周实验动物存活率。于第四周处死存活动物,取脑组织进行HE染色病理组织学检查,并用免疫组化方法分析脑胶质瘤浸润区T淋巴细胞分布情况。结果 实验组大鼠外周血淋巴细胞计数显著高于对照组(P<0.01),CD3+CD4+和CD3+CD8+T淋巴细胞的比例实验组均显著高于对照组(P<0.01)。实验组动物症状出现时间显著晚于对照组动物(P<0.01),实验组动物第四周末存活率显著高于对照组(P<0.05)。实验组胶质瘤局部浸润的CD3+和CD4+细胞数均显著高于对照组(P<0.01),实验组胶质瘤局部浸润的CD8+细胞数与对照组比较无显著差异(P>0.05),实验组胶质瘤局部浸润T淋巴细胞CD4+/CD8+显著高于对照组(P<0.01)。结论 C6细胞中HAC可以诱导大鼠产生对C6细胞的细胞免疫,提高大鼠存活率。     

丹参对原位肝移植大鼠供肝冷保存再灌注损伤的保护作用☆

目的: 研究表明，丹参对心、脑、肝等重要器官的缺血再灌注损伤有保护作用。制备大鼠异体原位肝移植模型，验证丹参对大鼠肝移植缺血再灌流损伤的保护作用。 方法：实验于2006-10/2007-08在南方医院中心实验室及动物实验中心完成，动物实验方法符合动物伦理学要求。①实验材料及分组：选用SD大鼠40只，按随机数字表法分为假手术组、模型对照组和丹参注射液组，假手术组8只，模型对照组、丹参注射液组各8对（供体与受体）。②实验方法：建立原位肝移植模型，在供肝灌注冷保存时，以4 ℃ 乳酸林格氏液为基液，丹参注射液组灌注保存液中加60 mL/L丹参注射液；模型对照组不加丹参。③实验评估：移植术后6 h处死各组大鼠取样，检测血清谷草转氨酶、谷丙转氨酶及乳酸脱氢酶活性；测定肝组织中丙二醛含量及超氧化物歧化酶、谷胱甘肽过氧化物酶活性，并对比观察移植肝病理形态学改变。 结果：模型对照组和丹参注射液组16只受体大鼠及假手术组8只大鼠全部进入结果分析，无脱失。①丹参注射液组和模型对照组移植肝再灌注后血清谷丙转氨酶、谷草转氨酶及乳酸脱氢酶活性均高于假手术组(P < 0.01)；丹参注射液组低于模型对照组(P < 0.01)。②丹参注射液组肝组织中丙二醛含量较模型对照组明显下降(P < 0.01)，超氧化物歧化酶和谷胱甘肽过氧化物酶的活性则明显升高 (P < 0.01)。③丹参注射液组较模型对照组肝组织肝细胞坏死程度减轻，炎性细胞浸润减少，肝组织再灌注损害程度减轻。 结论：丹参对原位肝移植肝脏的缺血再灌注损伤有保护作用，从而减轻氧自由基及脂质过氧化，保护细胞膜，改善肝功能。     

应用供体抗原特异性CD4+CD25+ Treg细胞延长大鼠移植肾的存活

背景：随着磁分选技术的完善,体外分选、扩增足量的对移植抗原具有特异性的细胞已成为可能,但就其在体内应用剂量及免疫耐受的效能问题目前鲜有报道。 目的：探索供体抗原特异性CD4+CD25+Treg细胞在体内应用诱导移植免疫耐受的量效关系。 方法：以SD大鼠为供体、Wistar大鼠为受体,建立同种异体肾移植动物模型;体外分选、富集Wistar大鼠脾脏CD4+CD25+Treg细胞,并诱导其对SD大鼠供体抗原的特异性表型;根据不同数量(2×105、5×105、1×106、2×106)供体抗原特异性CD4+CD25+Treg细胞在肾移植中单剂量尾静脉注射,并以未注射组为对照。术后15 d分析移植肾脏存活状况。术后4,9,15 d采血检测各组肌酐水平,同时进行移植肾脏病理检查,按照Banff Schema标准进行诊断,并根据Watanabe的方法进行半定量评分。 结果与结论：术后15 d内对照组死亡率最高83.3%,2×105组次之66.7%,2×106组为58.3%,5×105组为33.3%,1×106组则全部存活;各实验组术后4,9,15 d血肌酐水平均明显低于对照组(P < 0.05,P < 0.01);术后第9,15天,2×105组、5×105组血肌酐水平均明显高于1×106组、2×106组(P < 0.05);术后第4,9,15天移植肾脏病理检查的半定量评分结果显示,各时间段5×105组、2×105组与对照组间差异无显著性意义,各时间段1×106组与2×106组优于对照组 (P < 0.05)。结果初步证实供体抗原特异性CD4+CD25+Treg细胞受体内应用能够改善大鼠移植肾功能,延长移植肾存活时间,1×106为相对理想的单次应用剂量。     

甘露醇促进人脐血CD34+细胞通过血脑屏障静脉迁移至高血压脑梗死大鼠脑组织

背景：单纯脐血细胞经静脉移植治疗脑梗死疗效有限，移植细胞经血脑屏障迁入脑内数量不足为重要原因之一。 目的：观察血脑屏障开放剂甘露醇对人脐血CD34+细胞经静脉移植治疗高血压大鼠脑梗死疗效的影响。 方法：分离人脐血CD34+细胞，脂质体方法转染pEGFPF质粒，制备pEGFP-CD34+细胞；45只雄性SD大鼠经线栓法建立大脑中动脉栓塞模型，造模后24 h随机分为3组：实验组注射1×106 GFP-CD34+细胞，继之注射20%甘露醇2 g/kg；阳性对照组注射1×106 GFP-CD34+细胞；空白对照组注射等量生理盐水。 结果与结论：①荧光显微镜下实验组每张切片脑组织GFP标记阳性的绿色荧光细胞计数平均值显著多于阳性对照组。②移植后第7天治疗组与其他各组神经功能损害评分差异无显著性意义；移植后28 d，各组神经功能均有不同程度恢复，实验组神经功能恢复明显优于阳性对照组和空白对照组(P < 0.05)。③实验组与其他两组相比，大鼠脑梗死体积均显著减少。④实验组脑组织匀浆胶质细胞源性神经营养因子水平较阳性对照组、空白对照组明显增高。提示血脑屏障开放剂甘露醇促进静脉移植CD34+细胞通过血脑屏障迁入至脑组织，并增强静脉移植CD34+细胞治疗脑梗死的疗效。     

LY294002对小鼠体内调节性T细胞的影响

背景：研究已证实,磷酸肌醇3激酶特异性阻滞剂LY294002在体外具有剂量依赖性抑制细胞活性的作用,可以用于诱导肿瘤细胞凋亡,但LY294002对正常免疫系统的影响尚不清楚。 目的：观察抗肿瘤药物LY294002对C57BL/6小鼠体内调节性T细胞的影响。 设计、时间及地点：以调节性T细胞比例为观察对象,分组对比实验,于2008-08/12在广州南方医科大学珠江医院移植免疫研究所完成。 材料：14只8周龄SPF级C57BL/6小鼠随机分成实验组与对照组,每组7只。LY294002购自广州英韦创津公司。 方法：实验组腹腔注射LY294002溶液200 μL(0.1 mg),对照组给予等体积PBS。10 h后后眼眶静脉从采血,并分离脾脏、胸腺,制备单细胞悬液,流式细胞术检测小鼠外周血、脾细胞和胸腺细胞中的CD4+CD25high T 细胞。 主要观察指标：小鼠外周血、脾细胞和胸腺细胞中CD4+CD25high T 细胞的比例。 结果：实验组小鼠外周血、脾脏、胸腺中CD4+CD25high T细胞比例分别为(0.787±0.036)%,(0.921±0.063)%,(1.230± 0.131)%,对照组小鼠外周血、脾脏、胸腺中CD4+CD25high T细胞比例分别为(0.640±0.030)%,(0.639±0.046)%,(0.857±0.077)%,实验组和对照组比较差异有显著性意义(P < 0.01,P < 0.05)。 结论：腹腔注射LY294002可提升小鼠体内调节性T细胞的比例,提示其有可能会抑制机体免疫反应,从而不利于治疗。     

缺血预处理减轻大鼠减体积肝移植损伤并促进肝再生

背景：近年来,肝移植技术迅速发展,如何预防缺血再灌注损伤并有效保护肝再生成为研究的热点。缺血预处理是保护肝缺血损伤的有效方法,但其确切机制尚存争议。 目的：研究缺血预处理在大鼠减体积肝移植肝损伤和肝再生中的作用及机制。 方法：动物随机分为3组,肝移植组建立大鼠减体积肝移植模型。缺血预处理+肝移植组在供肝灌注前阻断第1肝门行缺血预处理10 min,再灌注15 min。假手术组在开腹后游离肝周韧带,然后关腹。分别于术后0.5,2,6,24 h取材。通过血清谷丙转氨酶水平和移植肝组织病理检查评估肝损伤。半定量免疫组织化学和western blot法测定氧化还原蛋白1表达水平,检测移植肝细胞增殖细胞核抗原评估肝再生情况。 结果与结论：与肝移植组相比,缺血预处 理+肝移植组术后6,24 h受体血清谷丙转氨酶明显降低(P < 0.05;P < 0.01)。病理学分析显示肝移植组术后24 h可见到门脉周围大量炎细胞浸润,肝窦扩张明显,肝组织损伤较重;而缺血预处理+肝移植组则损伤较轻。半定量免疫组织化学显示缺血预处 理+肝移植组移植肝中Ref-1蛋白表达明显增加,这一结果同样在westernblot检测中得到验证：缺血预处理+肝移植组移植肝术后24 h Ref-1蛋白表达较肝移植组明显增强 (P < 0.05)。同时,术后2,6和24 h 缺血预处理+肝移植组增殖细胞核抗原阳性细胞数较肝移植组明显增加(P < 0.05)。结果提示缺血预处理可减轻大鼠减体积肝移植术后早期移植物肝损伤并促进肝再生,这与Ref-1蛋白高表达密切相关。     

银杏内酯K通过PI3K/Akt/mTOR通路促进血管生成改善缺血性卒中

目的 探究银杏内酯 K（Ginkgolide K ，GK）通过磷脂酰肌醇 -3- 激酶（PI3K）/ 蛋白激酶 B （Akt）/ 哺乳动物雷帕霉素靶蛋白（mTOR）信号通路对缺血性卒中小鼠血管内皮生长因子（VEGF）表达 和脑血管生成的作用。方法 将 40 只 C57BL/6 小鼠随机分为对照组、大脑中动脉闭塞（MCAO）组、低 剂量 GK（GK-L）组（3.5 mg/kg）、中剂量 GK（GK-M）组（7 mg/kg）和高剂量（GK-H）组（14 mg/kg），每组各 8 只。建立 MCAO 模型和氧葡萄糖剥夺发（OGD）体外模型；采用改良后的神经系统严重程度评分（mNSS） 评估法检测小鼠神经功能缺损；2，3，5- 三苯基氯化四氮唑（TTC）染色检测小鼠脑缺血面积；免疫荧 光染色检测小鼠梗死灶周围皮质血管生成和星形胶质细胞覆盖。培养 hCMEC/D3 细胞，分为对照组， OGD 组、OGD+CK 组、OGD+LY 组（LY 为 PI3K 信号通路抑制剂）和 OGD+GK+LY 组，采用细胞计数试 剂盒 -8（CCK-8）检测内皮细胞活性；Western blot 检测内皮细胞缺氧诱导因子 1α（HIF-1α）、VEGF 和 PI3K/Akt/mTOR 通路相关基因蛋白表达；细胞划痕实验检测内皮细胞迁移能力；血管形成实验检测内 皮细胞管腔形成能力。结果 与 MCAO 组［（5.37±1.25）分、（11.99±1.72）%］比较，GK-M 组和 GK-H 组 小鼠 mNSS 评分［分别为（3.37±1.32）、（2.23±0.38）分］和脑缺血面积［（4.75±0.89）%、（2.42±0.42）%］ 均 显 著 降 低（P＜ 0.05）。 与 MCAO 组 EdU+ /CD31+ 细 胞 数、EdU+ /GFAP+ 细胞数和星形胶质细胞覆盖 率［分 别 为（3.33±0.58）个、（4.33±1.53）个、（69.20±5.60）%］比 较，GK 组 小 鼠 EdU+ /CD31+ 细胞数 ［（13.67±2.08）个，t=3.576］、EdU+ /GFAP+ 细 胞 数［（8.33±1.53）个，t=6.008］和 星 形 胶 质 细 胞 覆 盖 率 ［（82.26±7.77）%］显著升高（均P＜ 0.05）。与对照组细胞活力、HIF-1α、VEGF 蛋白表达、Akt 和 mTOR 磷酸化水平［分别为（100.31±3.01）%、（0.09±0.03）、（0.13±0.03）、（0.20±0.04）、（0.18±0.03）］比较，OGD 组细胞活力［（52.37±9.06）%］、HIF-1α（0.17±0.02）和 VEGF 蛋白表达（0.18±0.03）、Akt 和 mTOR 磷酸 化水平［（0.28±0.06），（0.38±0.05）］均显著升高（均P＜ 0.05）；与 OGD 组比较，OGD+GK 组细胞 HIF-1α （0.22±0.03）和 VEGF 蛋白表达（0.23±0.03）、Akt 和 mTOR 磷酸化水平［（0.48±0.09），（0.52±0.05）］、细胞 活力［（61.07±3.48）%］、迁移率［（85.26±11.03）%］和管状结构数量［（81.97±5.79）%］均显著升高（均 P＜0.05），OGD+LY组则表现出相反变化；PI3K信号通路抑制剂LY294002可逆转GK对OGD细胞的影响。 结论 GK 通过 PI3K/Akt/mTOR 信号通路上调 VEGF 表达促进脑血管生成，改善小鼠缺血性卒中。     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.