幼鼠低浓度甲苯吸入的成瘾性行为学研究

目的幼鼠慢性吸入低浓度甲苯对自主活动和条件性位置偏爱(CPP)行为的影响,探讨低浓度甲苯的慢性神经毒性和成瘾性。方法昆明小鼠从出生第1天起分成328.6mg/m3甲苯吸入组、空白对照组和丁香酚吸入对照组,至7周时各组随机挑选10只,进行自主活动数及CPP测试。结果①甲苯组的自主活动次数(73.0±26.5)与空白对照组(109.1±35.9)的差异具有统计学意义(P<0.05);②CPP试验中甲苯组小鼠在明箱内停留时间[(449.7±89.6)s]与空白对照组[(213.1±69.0)s]和丁香酚组[(181.2±71.2)s]的差异均有统计学意义(P<0.01)。结论小鼠幼鼠低浓度甲苯吸入能导致幼鼠神经兴奋性降低及其在成年时产生明显成瘾性。     

大鼠出生后不同时期使用氟西汀对体质量和行为远期影响的初步研究

目的 探讨大鼠出生后不同时期使用氟西汀对其体质量和行为的远期影响.方法 随机选择雄性SPrague-Dawley大鼠,在其出生后1～7 d、8～21 d分别皮内注射氟西汀(浓度2 g/L,注射剂量5 ml/kg体质量)(F1组,22只;F2组,20只)和生理盐水(0.9%NaCl,注射剂量5 ml/kg体质量)(S1组,20只;S2组,19只),并追踪观察4组大鼠体质量;大鼠成年后(出生后第90天)进行行为学检测,包括旷场实验、高架十字迷宫、新奇抑制摄食和强迫游泳实验.结果 (1)F1组大鼠体质量的增加延缓,出生后第25天,F1组体质量[(35.5±3.4)g]于S1组[(43.0±3.9)g],至出生后第90天,F1组体质量[(190.7±12.1)g]均小于S1组[(208.0±13.5)g]和F2组[(218.3±14.6)g](两样本t检验,P＜0.05).(2)幼鼠早期使用氟西汀,成年后探索性行为减少,F1组旷场行为总行程[(18.9±2.3)m]明显小于S1组[(38.9±8.1)m],F2组[(33.3±6.2)m]于S2组[(43.7±6.2)m];高架十字迷宫总穿臂次数F1组[(13.8±3.2)次]少于S1组[(37.6±6.3)次],F2组[(32.3±7.1)次]少于S2组[(57±7.3)次](两样本t检验,P＜0.05);焦虑抑郁相关行为增加,新奇抑制摄食潜伏期F1组[(432.2±45.4)s]长于S1组[(167.7±20.3)s],F2组[(270.2±27.2)s]长于S2组[(185.3±19.2)s];强迫游泳静止不动时间百分比F1组[(41.2±3.2)%]长于S1组[(26.5±2.3)%],F2组[(35.1±3.6)%]长于S2组[(27.8±2.5)%](两样本t检验,P＜0.05);且F1组大鼠的异常行为重于F2组(两样本t检验,P＜0.05).结论 幼鼠出生后早期使用氟西汀可导致大鼠体质量增加延缓,成年后出现焦虑抑郁行为,使用氟西汀越早风险越大.     

脑动脉瘤模型制作及高血压对其影响的实验研究

目的 建立脑动脉瘤动物模型并初步探讨高血压对脑动脉瘤的影响.方法 45只雄性SD大鼠按随机数字表法分为高血压组、正常血压组和正常对照组.高血压组行脑动脉瘤模型制作+双侧肾动脉狭窄术:正常血压组只建立脑动脉瘤模型:正常对照组不予任何处理.各组在术前,术后6周、12周三个时间点分别测量各组大鼠动脉收缩压.术后12周测量脑动脉瘤大小,并灌注固定,取脑动脉瘤部位血管组织,应用HE染色、Van Geson染色和Verhoeff染色进行病理检查.结果 高血压组在处死前血压明显升高[(197.48±15.44)mm Hg],与手术前的血压[(104.40±14.70)mm Hg]相比差异有统计学意义(P<0.05);处死前脑动脉瘤的长度[(2.38±0.31)mm]和宽度[(1.89±0.35)mm]与脑动脉瘤制作完成时的长度[(1.62±0.18)mm]和宽度[(1.36±0.09)mm]相比差异有统计学意义(P<0.05);正常血压组和正常对照组无明显变化.病理检查显示高血压组血管内膜消失,弹力层完全断裂;正常血压组尚存部分弹性纤维;正常对照组血管组织无改变.结论本实验采用的脑动脉瘤模型稳定性好,制作方便,具有与人类脑动脉瘤相似的形态和病理结构.高血压对脑动脉瘤的弹力蛋白和胶原蛋白有明显影响,是影响脑动脉瘤增大的重要因素之一.     

脑膜炎患者脑脊液中肿瘤坏死因子α、乳酸脱氢酶及其同工酶检测的临床意义

目的 探讨脑膜炎患者脑脊液(CSF)中肿瘤坏死因子α(TNF-α)、乳酸脱氢酶(LDH)及其同工酶检测的临床意义.方法 收集53例化脓性脑膜炎患者(化脑组)、58例病毒性脑膜炎患者(病脑组)、49例结核性脑膜炎患者(结脑组)、60例非神经系统感染性疾病患者(对照组)的CSF样本,采用酶联免疫吸附法(ELISA)测定TNF-α水平,采用酶测速率法测定LDH的活性,采用琼脂糖凝胶电泳法测定LDH同工酶含量,并进行比较.结果 3组脑膜炎患者CSF TNF-α含量明显高于对照组[(25.64±20.08)pg/L],其中化脑组[(462.24±368.13)pg/L]明显高于病脑组[(73.47±68.74)pg/L]及结脑组[(62.97+40.58)pg/L](均P＜0.01),病脑组与结脑组间差异无统计学意义.化脑组CSF LDH水平[(201.37±148.06)U/L]显著高于其他各组(均P＜0.01),结脑组[(170.32±86.45)U/L]明显高于病脑组[(79.54±43.71)U/L](P＜0.01);但病脑组[(79.54±43.71)U/L]与对照组[(64.56±49.68)U/L]间差异无统计学意义.化脑组LDH4[(22.83±2.08)U/L]、LDH5[(35.26±2.18)U/L]明显高于其他各组,LDH1[(7.84±1.15)U/L]、LDH2[(13.01±1.46)U/L]明显低于其他各组(均P＜0.01);结脑组LDH3[(29.48±3.24)U/L]较对照组[(16.13±3.95)U/L]明显升高(P＜0.01);而病脑组同工酶谱与对照组比较差异无统计学意义.结论 CSF中TNF-α、LDH及LDH同工酶水平检测有助于不同类型脑膜炎的鉴别诊断.     

小剂量MK-801对大鼠参照记忆、空间工作记忆和逆反学习能力的影响

目的 探讨腹腔注射N-甲基-D-天冬氨酸 (NMDA )受体拮抗剂地卓西平马来酸盐(MK-801)对大鼠认知功能的影响.方法 成年雄性SD大鼠随机分为MK-801组和对照组,分别腹腔注射小剂量生理盐水或MK-801(0.1 mg/kg)20 min后在Morris水迷宫中评定MK-801对大鼠参照记忆、空间工作记忆和逆反学习能力的影响.结果 参照记忆任务中,与对照组相比MK-801组逃避潜伏期延长(P<0.05),且在目标象限的探索时间百分比[(22.7±2.9)%]与相邻象限[(24.0±0.9)%]和对立象限[(29.3±2.4)%]的差异无统计学意义 (P>0.05);空间工作记忆任务中,对照组匹配试次潜伏期显著短于样本试次[(37.6±6.0) vs (61.5±6.3),P<0.05],而MK-801组两试次潜伏期差异无统计学意义[(53.8±7.8) vs (62.2±7.1),P>0.05];逆反学习任务中,与对照组相比MK-801组潜伏期明显延长(P<0.05),且在空间探索中新旧目标象限探索时间百分比差值小于对照组[(-0.01±4.7) vs (23.5±6.2),P<0.01].结论 腹腔注射小剂量MK-801破坏了大鼠的参照记忆、空间工作记忆和逆反学习,提示其在多个认知维度上可模拟精神分裂症患者的认知缺陷.     

强迫症患者治疗前后脑诱发电位的比较研究

目的 探讨强迫症(OCD)诱发脑电指标变异的意义。方法 应用美国Nicolet Spirit脑诱发电位仪,记录35例OCD患者(OCD组)和28名健康人(NC组)的事件相关电位P300、脑干听觉反应(ABR)和视觉诱发电位(VEP)。对其中23例OCD患者于治疗5个月后再次检测P300、ABR和VEP。结果 (1)治疗前,OCD组P300-P3靶波幅[(3.51±1.60)μV]低于NC组[(5.90±2.10)μV,P<0.01];ABR-波V绝对潜伏期[(6.40±0.41)ms]长于NC组[(5.50±0.33)ms,P<0.01],波V波幅[(0.35±0.10)μV]高于NC组[(0.16±0.09)μV,P<0.01];VEP-P2潜伏期[(199±39)ms]长于NC组[(183±28)ms,P<0.05]。(2)治疗后,OCD组随强迫思维和行为改善,脑电诱发电位中仅P300-P3靶波幅升高[治疗前后分别为(4.50±1.30)μV和(6.01±1.50)μV;P<0.01],VEP-P2潜伏期缩短[分别为(199±30)ms和(183±28)ms;P<0.05],余各项差异均无显著性。结论 OCD患者P300和VEP变化与临床状态有关,ABR的变异则有待继续跟踪。     

幼年大鼠癫痫持续状态后电生理和行为学的研究

目的观察幼年大鼠发生癫痫持续状态(status epilepticus,SE)后的电生理和行为学改变,并判断其表现是否符合Lennox-Gastaut综合征(Lennox-Gastaut syndrome,LGS)的电临床特点。方法 3周龄雄性Wistar大鼠50只,随机分为模型组(n=30)与对照组(n=20),模型组幼鼠腹腔注射氯化锂-匹鲁卡品诱发SE,对照组幼鼠用等量生理盐水代替匹鲁卡品。1周后,采用改进的颅内电极方法进行2周长程视频脑电监测,观察分析幼鼠脑电图背景活动、癫痫放电、癫痫发作及其相应症状学改变情况。脑电监测结束后,进行Morris水迷宫认知功能测试,观察记录幼鼠在水迷宫中寻找水下平台的潜伏期及游泳距离。结果共26只模型组幼鼠成功诱发SE并存活,对照组(n=20)表现正常。长程视频脑电监测期间,对照组幼鼠脑电背景活动正常,未见癫痫发作。模型组幼鼠发作间期癫痫放电显著增多,睡眠期可见弥漫性慢棘-慢波活动;共监测到3种癫痫发作类型:不典型失神发作、强直发作和肌阵挛发作。在水迷宫测试中,模型组幼鼠的潜伏期及游泳距离明显长于对照组(P0.05)。结论模型组幼鼠在发生SE后出现多种类型癫痫发作、异常脑电图表现及认知功能减退,该动物模型的电临床表现符合LGS的临床特征。     

高血压性脑出血患者血肿周围组织基质金属蛋白酶-9和细胞间黏附分子-1的表达及意义

目的 探讨脑出血后血肿周围组织基质金属蛋白酶-9(MMP-9)和细胞间黏附分子-1(ICAM-1)的表达与脑水肿的关系.方法 ①解剖39例脑出血后不同时间死亡患者的脑组织,自出血灶边缘向外1～3 cm及出血灶对侧相应部位的脑组织进行取材,出血灶对侧设为对照组.②采用HE染色、免疫组织化学技术观察不同时间点出血灶周围MMP-9与ICAM-1在脑组织中的表达和变化规律,实验结果应用SPSS 11.5软件进行统计学分析.结果 ①脑出血2 h后出血灶周围血管内皮细胞即有MMP-9的表达[(1.2±0.8)个/高倍视野],5～10 h后血肿周围MMP-9阳性微血管数明显增高[(4.1±0.8)个/高倍视野],45～48 h达到高峰[(10.6±1.4)个/高倍视野],96～120 h后逐渐减弱[(5.0±1.1)个/高倍视野],与对照组比较,差异均有统计学意义(P＜0.05),360～408 h接近零表达.对照组没有MMP-9表达.②脑出血后2 h出血灶周围血管和神经细胞即有ICAM-1的表达[(2.1±0.3)个/高倍视野],17～24 h血肿周围ICAM-1阳性微血管数开始明显增加[(6.0±1.1)个/高倍视野],72 h达到高峰[(11.1±0.9)个/高倍视野],168～312 h后逐渐减弱[(4.1±0.6)个/高倍视野],仍高于对照组(P＜0.05).此外,对侧脑实质内可见少量阳性神经细胞及ICAM-1阳性微血管.③MMP-9和ICAM-1之间有明显的相关性.结论 脑出血后出血灶周围MMP-9及ICAM-1的表达增加,对脑出血后脑水肿的形成可能有促进作用;MMP-9与ICAM-1之间可能有协同作用.     

男性精神分裂症患者攻击行为与脑电图频谱分析及事件相关电位P300的相关性研究

目的 探讨精神分裂症患者攻击行为的脑电生理学预测因子.方法 收集30对有或无攻击行为的男性精神分裂症患者的脑电图频谱分析结果、事件相关电位P＜,300＞测量资料,进行比较和分析,考察影响患者攻击行为的脑电生理学指标.结果 (1)两组简明精神病量表总分及各因子分的差异均无统计学意义(P＞0.05).(2)有攻击组(30例)右侧前额区8波[(23.32±3.30)%]、θ波[(18.22±2.84)%]和右侧额区(F4)[(19.04±3.30)%]和前颞区θ波的相对功率[(17.90±3.29)%]均大于非攻击组[30例;分别为(21.23±3.54)%、(16.54±1.86)%、(17.43±1.98)%、(16.22±1.80)%;P＜0.5].(3)有攻击组Cz点P<,3>潜伏期[(321±45)ms]长于非攻击组[(287±43)ms],P<,3>波幅[(3.4±1.6)μV]低于非攻击组[(4.8±2.2)μV],差异均有统计学意义(P＜0.05).(4)P<,3>潜伏期、F<,4>θ波依次进入回归方程.根据偏回归系数建立的Logistic回归方程总正确预测率为73.3%.结论 P<,3>潜伏期、F<,4>θ波对男性精神分裂症患者攻击行为有较好的预测价值.     

TNP-470联合化疗抑制胶质母细胞瘤的实验研究

目的 探讨TNP-470联合化疗药物卡氮芥(BCNU)对人U-251胶质母细胞瘤细胞裸鼠皮下移植瘤生长的作用.方法 将人U-251胶质母细胞瘤细胞株注射至裸鼠皮下,第7天荷瘤裸鼠随机分为4组:TNP-470治疗组、BCNU治疗组、TNP-470和BCNU联合治疗组、对照组.测体质量及肿瘤大小,以山羊抗小鼠CD105多克隆抗体免疫组化染色计数肿瘤微血管密度(MVD).结果 治疗后第21天联合治疗组移植瘤体积[(108.93±17.63)mm3]明显小于TNP-470治疗组[(576.10±114.29)mm3]及BCNU治疗组[(473.01±48.04)mm3](P均＜0.01);各治疗组移植瘤体积均小于对照组[(1512.61±470.25)mm3](P均＜0.01);TNP-470治疗组与BCNU治疗组间移植瘤体积差异无统计学意义(P＞0.05).治疗后第21天联合治疗组的抑瘤率(92.80%±11.37%)显著高于TNP-470治疗组(61.91%±6.29%)和BCNU治疗组(68.73%±9.65%)(P均＜0.01),TNP-470治疗组与BCNU治疗组间抑瘤率无统计学意义(P＞0.05).联合治疗组移植瘤MVD[(4.23 4±0.83)个/视野]明显低于TNP470治疗组[(5.70±0.85)个/视野]和BCNU治疗组[(8.60±0.87)个/视野](P均＜0.05);TNP-470治疗组移植瘤MVD显著低于BCNU治疗组(P＜0.05);各治疗组移植瘤MVD均较对照组[(11.32±1.50)个/视野]显著降低(P均＜0.05).结论 TNP-470联合化疗药物BCNU对人U-251胶质母细胞瘤细胞裸鼠皮下移植瘤的生长有显著抑制作用.     

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.