目的观察丙戊酸钠、托吡酯诱导癫患者体重及血清瘦素水平的变化。方法40例女性癫患者按年龄、体重指数分层匹配进入丙戊酸钠、托吡酯治疗组,每组20例。在治疗前及治疗3个月后分别测定身高、体重及早晨空腹血清瘦素水平。结果9例经丙戊酸钠治疗者体重增加（≥4kg），血清瘦素水平[（13.2±3.6）ng/ml]高于治疗前[（7.4±3.0）ng/ml,P<0.01]；6例托吡酯治疗者体重减轻（≥4kg），血清瘦素水平[（3.7±1.8）ng/ml]低于治疗前[（7.4±2.6）ng/ml,P<0.01]。结论经丙戊酸钠治疗体重增加者出现瘦素抵抗，经托吡酯治疗体重减轻者血清瘦素水平降低。

目的研究卡马西平（CBZ）、丙戊酸钠（VAP）、托吡酯（TPM）对新诊断成人部分发作癫痫患者额叶相关认知功能的影响。方法采用前瞻和随机对照研究，对48例新诊断为部分发作伴或不伴全面发作的癫痫患者进行6项神经心理学测验后，随机给予CBZ、VAP、TPM单药治疗，1月后复查神经心理学检查。结果与治疗前比较CBZ组B型连线测验错误数增加（P<0.05），汉罗塔（TowerofHanoi）平均计划时间缩短（P<0.05）；VAP组Stroop读字正确数增加（P<0.01），威斯康星卡片分类测验（WSCT）错误数下降（P<0.05）、非持续错误数下降（P<0.01）；TPM组倒背数下降（P<0.01）。治疗后组间比较，有6项神经心理学指标差异有显著性，分别是顺背数（P<0.05）、词汇总数（P<0.01）、Stroop读字时间（P<0.01）、Stroop读字错误数（P<0.01）、Stroop读色纠正数（P<0.05）以及汉罗塔平均计划时间（P<0.01）。结论抗癫痫药物的化学结构和作用机制不同，所以，对认知功能的影响也不同；TPM低剂量起始，缓慢加量，较低的治疗剂量可降低其对认知功能的影响。

目的探讨代谢性谷氨酸受体1α（MGLUR1α）在马桑内酯（CL）点燃致癫模型大鼠脑组织不同区域表达的差异。方法　35只雄性SD大鼠随机分为对照组（n=5,大鼠予1.0ml/kg生理盐水肌注）和3个不同剂量CL点燃致癫模型组（分别予0.75、1.0、1.25ml/kg马桑内酯提取液肌注）。分别对点燃、未点燃、对照组大鼠行皮层脑电图描记、取脑组织作HE和MGLUR1α的免疫组化染色,观察MGLUR1α在脑组织不同区域的表达。结果点燃组大鼠在肌注马桑内酯后产生了1～5级的痫性发作，与皮层脑电图的表现相一致。MGLUR1α在点燃组大鼠海马以及海马以外的颞叶皮质的表达较之未点燃和对照组增强（P<0.05），这种表达的增强在神经元与神经胶质细胞间未发现有明显的差异。结论MGLUR1α在点燃大鼠海马和海马以外的颞叶皮质的表达较之未点燃和对照组增强，可能参与了癫痫的发生。

为了解癫痫病灶胶质增生的机理，对20例海马硬化灶及10例对照进行了P16、P53蛋白及PCNA表达的免疫组化检测。结果：P16蛋白在癫痫病灶胶质增生区较对照组表达率降低，差别有统计学意义；P53蛋白在癫痫组及对照组均呈阴性反应；PCNA在癫痫灶胶质增生区较对照组胶质细胞表达增强（P<0.01）。上述结果提示，癫痫海马硬化灶胶质增生可能与P16蛋白表达减少有关；P53蛋白表达在病变区及正常区无明显变化；PCNA参予了胶质细胞增生的调节。

认知功能损害是癫的不良后果之一。影响癫认知功能的因素很多,其中抗癫药物（AED）作为癫治疗的主要手段，它对认知功能的影响备受临床医生关注。我们采用随机对照、单药治疗的方法探讨新诊断成人部分性癫患者在用药前额叶相关认知功能的改变及AED对其影响，以便在控制癫发作的同时尽可能减少AED对认知功能的影响。

耐药性癫约占癫患者的30%，耐药癫动物模型是研究其耐药机制和探讨治疗方法的重要工具。马桑内酯（coriarialactone, CL）是从植物马桑中提取的一种致物质,对动物反复肌注阈下剂量的CL可以建立化学点燃模型，并具有一定的耐药性[1]。P-糖蛋白（P-glycorprotein,P-gp）和多药耐药相关蛋白1（multidrugresistance-associatedprotein1,MRP1）是近年在耐药性癫患者脑组织中发现的两种与耐药性产生相关的膜蛋白[2,3]。我们通过建立大鼠CL点燃模型,观察其对卡马西平（carbamazopine, CBZ）、丙戊酸钠（valproate, VPA）及托吡酯（topiramate, TMP）等抗癫药物（AED）的治疗反应和大鼠脑部P-gp和MRP1的表达，探讨该模型的耐药性及其可能机制。

Objectie: Intensive and quantitative evaluation of the severity and frequency of seizures and ictal signs during topiramate (TPM) treatment. Methods: Twenty patients with refractory partial seizures undergoing presurgical evaluation were randomized into a low dosage (100mg daily) and a parallel medium dosage (200mg daily) group of TPM add-on medication. Study phases included a 3-day baseline video-EEG phase, a 10-day TPM titration phase without video-EEG and a 3-day TPM dose maintenance phase with video-EEG. During the baseline and the dose maintenance phase seizures were recorded using video-EEG monitoring and the following parameters were measured: duration (lasting seconds of each seizure and ictal sign), intensity (on a 0-3 scale), N/24h (numbers of attacks per 24h), D/24h (duration per 24h) of both seizures and defined ictal signs. Results: A total of 399 seizures during the baseline phase and the dose maintenance phase were intensively analyzed. Intergroup comparison suggested that duration, N/24h and D/24h of all seizures decreased more in the medium dosage group computing the reduction from baseline to the dose maintenance phase (P 0.05). There were statistically more significant reductions in the duration, intensity and N/24 h of ictal signs like hypermotoric movements, fumbling and vocalization in the medium dosage group (P 0.05). Conclusion: Topiramate has an early dose-dependant effect on ictal seizures. Short Communication: The present study intensively analyzed the duration, intensity, N/24h and D/24h of ictal seizure manifestations. The quantitative data suggested that topiramate had an early effect on ictal phenomena like ictal hypermotoric movements, fumbling and vocalization (P 0.05); effects were more prominent in the medium dosage group (200mg daily) than the low dosage group (100mg daily).

Objectie: Intensive and quantitative evaluation of the duration, intensity and frequency of tonic and clonic signs of secondarily generalized tonic-clonic seizures (GTCS) in patients with harmacoresistant partial seizures during topiramate (TPM) treatment. Methods: Thirty patients suffering from refractory partial seizures with secondarily GTCS undergoing presurgical evaluation were randomized into a low dosage (100mg daily) and a parallel medium dosage (200mg daily) group of TPM add-on medication (15 patients for each group). Study phases included a 3 days baseline video-EEG phase, a 10 days TPM titration phase without video-EEG and a 3 days TPM dose maintenance phase with video-EEG. During the baseline and the dose maintenance phase seizures were recorded using video-EEG monitoring and the following parameters were measured for each recorded secondarily generalized tonic and clonic signs: duration (lasting seconds), intensity (on a 0-3 scale), frequency (numbers per 24h). Results: A total of 46 complex partial seizures with secondarily generalized tonic-clonic signs during the baseline phase and 20 during the dose maintenance phase were intensively analyzed. More patients in the medium dosage group than in the low dosage groups were free from secondarily GTCS during the dose maintenance phase (nine vs. two, P 0.05). Intergroup comparison suggested that the duration of all tonic signs decreased more in the medium dosage group computing the reduction from baseline to the dose maintenance phase (P 0.05). There were statistically more significant reductions in the duration and intensity of clonic signs in the medium dosage group (P 0.05). Conclusion: TPM has an early dose-dependant effect on secondarily GTCS in patients with pharmacoresistant partial seizures. Short Communication: The present study intensively analyzed the duration, intensity, and frequency of secondarily generalized tonic and clonic signs in patients with pharmacoresistant partial seizures. The quantitative data suggested that TPM had a robust early inhibitory effect on secondarily generalized tonic-clonic signs; effects were more prominent in the medium dosage group (200mg daily) than in the low dosage group (100 mg daily).

Purpose: The aim of this study was to develop a new animal model of pharmacoresistant temporal lobe epilepsy (TLE) by repeated intramuscular injection of Coriaria lactone (CL) at subthreshold dosages and to explore the mechanisms that might be involved. Methods: Healthy male Sprague-Dawley rats (n=160) were randomized into four groups during the kindling process: three groups (n=50 for each group) received CL injection at subthreshold dosages (1.25, 1.5, and 1.75mg/kg, respectively), and ten received normal saline (NS) injection as a control group. The maximal human adult dosage of carbamazepine (CBZ), valproate (VPA), and phenytoin (PHT) was administered as monotherapy to different groups of kindled rats for 1 month (n=20 for each group). Changes in EEG recording, seizure number, intensity (expressed as grade 1-5 according to Racine stage), and duration, including spontaneous seizures during different interventions, were compared. The expression of P-170, a multiple drug resistance gene (MDR1) encoding P-glycoprotein, was measured in brain samples from different groups of experimental rats by using an image analysis and measurement system (ImagePro-Plus 4.0). Results: A total of 70 (46.7%) rats were fully kindled with a median of 15 (seven to 20) CL injections. Electrocorticogram (ECoG) including hippocampal (EHG) monitoring revealed the temporal lobe origins of epileptiform potentials, which were consistent with the behavioral changes observed. Spontaneous seizures occurred with frequency and diurnal patterns similar to those of human TLE. The antiepileptic drugs (AEDs) tested lacked a satisfactory seizure control. The maximal P-170 expression was in the kindled rats with AED treatment; the next highest was in the kindled rats without AED intervention. Nonkindled SD rats with CL injection also had increased P-170 expression compared with control SD rats. Conclusions: The study provided a simple and stable animal TLE kindling model with pharmacoresistant properties. The pharmacoresistance observed in the kindled rats to CBZ, VPA, and PHT at maximal human adult dosages together with the increased P-170 expression was a distinct feature of this model. This model might be used in further investigations of the mechanisms involved in pharmacoresistant TLE and for developing new AEDs.

Purpose: To quantify changes in ictal seizure semiology during rapid withdrawal of carbamazepine (CBZ) and valproate (VPA) from a monoregimen in presurgical evaluation. Methods: Therapeutic intensive seizure analysis (TISA) with video-EEG monitoring was used in 33 patients with armacoresistant partial epilepsy undergoing complete withdrawal of CBZ (20 patients) or VPA (13 patients) from a monoregimen. Monitoring phases included a 3-day baseline phase, a 3-day rapid antiepileptic drug (AED) withdrawal phase, and another 3-day AED-free phase with AEDs in subtherapeutic levels. Seizure variables as complete processes and their various elements (ictal signs) were analyzed, including duration (seconds), intensity (on a scale of 0 to 3), frequency (number per 3 days), and total duration of seizures and ictal signs in 3 days (seconds). The localization of seizure patterns on ictal EEG recording (EEG seizure onset) and the first appearing clinical ictal phenomena (initial ictal signs) were recorded. Results: A total of 188 seizures in the CBZ group and 57 seizures in the VPA group were investigated. Compared with the baseline phase, the CBZ group showed increases in duration, frequency of seizures, various ictal signs, and secondarily generalized tonic and clonic signs during the following two phases. Significantly increased values of the VPA group were observed in seizure duration and frequency of hypermotoric phenomena during the AED-free phase. More patients in the CBZ group had secondarily generalized clonic signs during the AED-free phase. EEG seizure onset and initial ictal signs showed no obvious changes between study phases. Conclusions: Withdrawal of CBZ is followed more quickly by an increase of seizure frequency and severity than is the case for VPA withdrawal. Both CBZ and VPA withdrawal influences seizure propagation rather than the seizure-onset characteristics, which speaks in favor of its use in presurgical evaluation.