经鼻给予TGFβ1对癫痫持续状态大鼠海马神经元的保护作用

目的探讨经鼻腔给予TGFβ1(transforming growth factor beta1,TGFβ1)对氯化锂-匹罗卡品所致癫痫持续状态(status epilepticus,SE)大鼠海马神经元的保护作用及其潜在的机制。方法健康雄性SD大鼠60只,随机分为转化生长因子(TGF)组、匹罗卡品(Pilo)组和正常对照组(control)。建立氯化锂-匹罗卡品癫痫持续状态模型。应用TUNEL染色、Fluoro-Jade B(FJB)荧光染色法分别观察各组大鼠海马神经元的原位凋亡及变性死亡情况。采用免疫组化方法检测凋亡相关基因caspase-3的蛋白表达。结果 SE后24h、48h、72h,TGF组大鼠海马FJB、TUNEL、caspase-3阳性细胞均较Pilo组显著减少(P<0.05);72h最为明显(P<0.01)。结论经鼻(IN)给予TGFβ1可以显著抑制或减轻癫痫持续状态大鼠海马神经元的变性与凋亡,从而发挥神经保护作用。其潜在的神经保护机制可能涉及下调caspase-3蛋白表达。     

Safety and efficacy of intravenous valproate in pediatric status epilepticus and acute repetitive seizures

Summary: Purpose: To evaluate the safety and efficacy of intravenous valproate (VPA) loading in children with status epilepticus (SE) or acute repetitive seizures. Methods: Retrospective review was performed on 40 pediatric patients with intravenous VPA loading. Patients were classified into two groups: SE (n = 18) and acute repetitive seizures (n = 22). Thirty‐one patients were VPA naïve and received a full loading dose of 25 mg/kg; nine had subtherapeutic plasma VPA levels and received a partial loading dose. Average infusion rate was 2.8 mg/kg/min. Heart rate and blood pressure were measured before, during, and after infusion. Results: Intravenous VPA loading stopped seizures in 18 patients with SE within 20 min. All 18 patients regained baseline mental status within 1 h of seizure cessation. Among 22 patients with acute repetitive seizures, only one had further seizures after VPA infusion. One patient in the SE group complained of transient tremors. No significant changes in blood pressure or heart rate were found in either group. Postinfusion plasma VPA levels ranged from 51 to 138 μg/ml (mean ± SD = 88 ± 21.5 μg/ml). Conclusions: Intravenous VPA loading is safe and effective for treating acute seizure emergencies in children.     

Incidence and risk factors of acute encephalopathy with biphasic seizures in febrile status epilepticus

ObjectiveTo clarify the incidence and risk factors of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) in pediatric patients with febrile status epilepticus (FSE).MethodsWe retrospectively surveyed patients with FSE (≥20 min and ≥40 min) who were younger than 6 years by mailing a questionnaire to 1123 hospitals in Japan. The survey period was 2 years. We then collected clinical data on patients with prolonged febrile seizures (PFS) ≥40 min and those with AESD, and compared clinical data between the PFS and AESD groups.ResultsThe response rate for the primary survey was 42.3%, and 28.0% of hospitals which had applicable cases responded in the secondary survey. The incidence of AESD was 4.3% in patients with FSE ≥20 min and 7.1% in those with FSE ≥40 min. In the second survey, a total of 548 patients had FSE ≥40 min (AESD group, n = 93; PFS group, n = 455). Univariate analysis revealed significant between-group differences in pH, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase, NH₃, procalcitonin (PCT), uric acid, blood urea nitrogen, creatinine (Cr), and lactate. Multivariate analysis using stratified values showed that high PCT was an only risk factor for AESD. A prediction score of ≥3 was indicative of AESD, as determined using the following indexes: HCO3^? < 20 mmol/L (1 point), Cl <100 mEq/L (1 point), Cr ≥0.35 mg/dL (1 point), glucose ≥200 mg/dL (1 point), and PCT ≥1.7 pg/mL (2 points). The scoring system had sensitivity of 84.2% and specificity of 81.0%.ConclusionIncidence data and prediction scores for AESD will be useful for future intervention trials for AESD.     

惊厥性癫癎持续状态患者220例的临床特征

目的 了解我院就诊的220例惊厥性癫癎持续状态(CSE)患者的临床特征,为CSE的针对性预防和治疗提供依据.方法 采用连续登记方法,前瞻性观察四川大学华西医院1996年1月至2007年10月住院的CSE患者,用Logistic回归方法分析CSE预后的预测因素.结果 纳入220例患者,其中农村患者102例(46.4%).首要病因为中枢神经系统(CNS)感染(72例,32.7%),其次为停(减)抗癫癎药物(34例,15.5%).接受抗惊厥治疗前持续时间中位数为2 h,总持续时间中位数为5 h,农村患者(分别为3.5、7.0 h)均长于城市患者(2.0、3.0 h,Z=-1.558、-3.433,均P<0.05).研究对象首选地西泮静脉推注或苯巴比妥肌肉注射治疗,35例难治性癫癎持续状态(RSE)接受静脉丙戊酸钠治疗,12例接受麻醉治疗,病死率15.9%.Logistic回归分析示CSE持续时间(χ2=20.941)、癫痫病史(χ2=4.910)、呼吸抑制(χ2=16.086)为影响CSE预后的独立因素(均P<0.05).结论 农村人口及癫癎患者是CSE发生的重要人群,CNS感染及停(减)抗癫癎药物是CSE的重要病因,我国抗惊厥治疗与欧洲癫持癎续状态指南差距较大.     

Status epilepticus in children with epilepsy: Dutch study of epilepsy in childhood

PURPOSE: To study course and outcome of epilepsy in children having had a status epilepticus (SE) as the presenting sign or after the diagnosis. METHODS: A total of 494 children with newly diagnosed epilepsy, aged 1 month through 15 years, were followed prospectively for 5 years. RESULTS: A total of 47 Children had SE. Forty-one of them had SE when epilepsy was diagnosed. For 32 (78%), SE was the first seizure. SE recurred in 13 out of 41 (32%). Terminal remission at 5 years (TR5) was not significantly worse for these 41 children: 31.7% had a TR5 <1 year versus 21.2% of 447 children without SE. They were not more often intractable. Five out of six children with first SE after diagnosis had a TR5 <1 year. Mortality was not significantly increased for children with SE. Independent factors associated with SE at presentation were remote symptomatic and cryptogenic etiology, and a history of febrile convulsions. Children with first SE after inclusion more often had symptomatic etiology. CONCLUSIONS: Although we find a trend for shorter TR5 in children with SE at presentation, outcome and mortality are not significantly worse. Etiology is an important factor for prognosis. Children with SE during the course of their epilepsy have a worse prognosis and a high recurrence rate of SE. This outcome is not due to the SE itself, but related to the etiology and type of epilepsy. The occurrence of SE is just an indicator of the severity of the disease.     

Intranasal sumatriptan for the acute treatment of migraine

Two double-blind, placebo-controlled, randomised, multicenter, multinational, parallel-group studies were carried out to identify the optimum dose of intranasal sumatriptan for the acute treatment of migraine. Study medication was taken as a single dose through one nostril in the first study, and as a divided dose through two nostrils in the second study. Totals of 245 and 210 patients with a history of migraine were recruited into the one-and two-nostril studies, respectively. In both studies, headache severity had significantly improved at 120 min after doses of 10–40 mg sumatriptan compared to placebo (P < 0.05) and the greatest efficacy rates were obtained with 20 mg sumatriptan. With 20 mg sumatriptan 78% and 74% of patients experienced headache relief in one- and two-nostril studies respectively. Sumatriptan was generally well tolerated, the most frequently reported event being taste disturbance. The results of the two studies are similar and indicate that administering sumatriptan as a divided dose via two nostrils confers no significant advantage over single-nostril administration. The publication committee members were as follows: Prof. C. Dahlöf Gothenburg; Prof. N. E. Gilhus, Bergen; Dr. V. Lüben, Giessen; Dr. R. Salonen, Tampere; Prof. J. M. Warier, Strasbourg; Ms E. Ashford, Glaxo Group Research Limited, Greenford; Mr. R. Dawson, Glaxo Group Research Limited, Greenford; Mrs D. Noronha Glaxo Group Research Limited, Greenford.Principal investigators were as follows: One nostril study France: Dr. N. Brion, Le Chesnay; Prof. G. Chazot, Lyon; Dr. P. Dano, Marseille; Prof. A. Destee, Lille; Dr. M. Schwob, Paris; Prof. J.M. Warter, Strasbourg. Germany: Dr. J. Brand, Konigstein; Dr. R. Enkelmann, St. Goar; Prof H. D. Langohr, Fulda; Dr. V. Lüben, Giesssen; Dr. M. Mockesch, Weinheim; Dr. H Pistauer, Preetz; Dr. Schimek, Giegen; Dr. E. Siegel, Munich. Norway: Dr. J. S. Aasen, Fredrikstad; Prof. N. E. Gilhus, Bergen; Dr. I. Monstad, Elverum; Dr. T. Mörland, Skien; Dr. K. Nestvold, Nordbyhagen; Dr. O. Roald, Oslo; Dr. R. Salvesen, Bodö; Prof. O. Sjaastad, Trondheim; Dr. B. Stadnes, Drammen; Dr. K. A. Tjörstad, Stavager.Two Nostril study Eire: Dr. A. Rynne, Dublin. Finland: Dr. M. Farkkila, Helsinki; Dr. H. Havanka, Kemi; Dr. T. Jolma, Pori; Dr. H. Kilpelainen, Savonlinna; Dr. E. Koivunen-Tapio, Jyvaskyla; Reunanen, Oulu; Dr. E. Sako, Turku; Dr. R. Salonen, Tampere. Sweden: Dr. B. Andersson, Gävle; Dr. C. Behring, Vasteras; Prof. C. Dahldf, Gothenburg; Dr. S. E. Eriksson, Falun; Dr. Hindfelt, Malmö; Dr. H. Hultberg, Osmo; Dr. F. Johansson, Umea; Dr. C. Muhr, Uppsala     

Suppression of Pentylenetetrazol-Elicited Seizure Activity by Intraosseous Lorazepam in Pigs

Use of the intraosseous (i.o.) route as an alternative venous access for drug administration has increased. This study examined the efficacy of i.o. lorazepam (LZP) in suppressing pentylenetetrazol (PTZ)-induced seizure activity in pigs. Domestic swine (13-20 kg) were prepared for recordings of arterial blood pressure, EEG, and electrocortical activity. Seizure activity was induced by PTZ (100 mg/kg i.v.). Sixty seconds after onset of seizure activity, animals either received no drug (control) or LZP (1.0 mg/kg) administered i.v. or i.o. via an 18- or 13-gauge spinal needle inserted in the right proximal tibia. Both i.o. and i.v. LZP significantly suppressed the duration of seizure activity (DSA) (s/min interval) within 1 min following drug administration: DSA control, 46.2 +/- 3.6; i.v. LZP, 25.0 +/- 5.1; i.o. (18-gauge) LZP, 27.6 +/- 6.0; i.o. (13-gauge) LZP, 24.0 +/- 2.4. Seizure activity was essentially abolished at 1 min following LZP infusion. In addition, both i.v. and i.o. LZP did not have significant effects on the basal heart rate and mean arterial blood pressure. The data demonstrate that in swine (1) the i.o. route is an effective alternative venous access for LZP administration, and (2) the size of spinal needles does not affect the antiepileptic efficacy of i.o. infusion of LZP.     

Electrical stimulation-induced seizures in rats: a "dose-response" study on resultant neurodegeneration

Perforant pathway stimulation (PPS) is used to study temporal lobe epilepsy in rodents. High-frequency PPS induces acute seizures, which can lead to neuron death and spontaneous epilepsy. However, the minimum duration of PPS that induces neurodegeneration in naive rodents is unknown. Freely moving Sprague-Dawley rats received one episode of continuous, bilateral PPS (range 1-180 min). Simultaneous recording from the hippocampal granule cell layer confirmed the presence of epileptiform activity and showed precisely when seizure activity was terminated by anesthesia. Fluoro-Jade B staining, 1-7 days after PPS, determined neuronal degeneration. Thirty-five minutes of continuous PPS produced no apparent neuron death anywhere in the brain. The minimum duration that caused neurodegeneration, which was confined to the dentate hilus, was 40 min. These data indicate that, in freely moving naive rats: (1) 40 min of PPS-induced seizure activity is the threshold for brain cell death, and (2) dentate hilar neurons are the most vulnerable to PPS. Further studies are warranted to determine the threshold of epileptogenic neurodegeneration.     

Effectiveness of lidocaine infusion for status epilepticus in childhood: a retrospective multi-institutional study in Japan

We evaluated the usefulness of intravenous lidocaine therapy for managing of status epilepticus (SE) during childhood in a retrospective multi-institutional study. Questionnaires were sent to 28 hospitals concerning patients admitted for SE who were managed with lidocaine, assessing patient characteristics, treatment protocols and efficacy. In 279 treated patients, 261 SE occurrences at ages between 1 month and 15 years were analyzed. SE was classified as showing continuous, clustered, or frequently repeated seizures. Considering efficacy and side effects in combination, the usefulness of lidocaine was classified into six categories: extremely useful, useful, slightly useful, not useful, associated with deterioration, or unevaluated. In 148 SE cases (56.7%), lidocaine was rated as useful or extremely useful. Multivariate analysis indicated lidocaine was to be useful in SE with clustered and frequently repeated seizures, and SE attributable to certain acute illnesses, such as convulsions with mild gastroenteritis. Efficacy was poor when SE caused by central nervous system (CNS) infectious disease. Standard doses (approximately 2mg/kg as a bolus, 2mg/kg/h as maintenance) produced better outcomes than lower or higher doses. Poor responders to the initial bolus injection of lidocaine were less likely to respond to subsequent continuous infusion than good initial responders. We recommend lidocaine for use in SE with clustered or frequently repeated seizures, and in SE associated with benign infantile convulsion and convulsions with mild gastroenteritis. Lidocaine should be initiated with a bolus of 2mg/kg. If SE is arrested by the bolus, continuous maintenance infusion should follow; treatment should proceed to different measures when SE shows a poor response to the initial bolus of lidocaine.     

Anticonvulsant effects of carbamazepine on spontaneous seizures in rats with kainate-induced epilepsy: comparison of intraperitoneal injections with drug-in-food protocols

PURPOSE: The present study evaluated the effectiveness of intraperitoneal (IP) injections and oral administration of carbamazepine (CBZ) in food on the frequency of spontaneous motor seizures in rats with kainate-induced epilepsy. The purpose was to develop a convenient drug-in-food approach for continuous, long-term administration of potential antiepileptic drugs (AEDs). METHODS: Single IP injections of CBZ (10-100 mg/kg) were compared to vehicle injections via six AED-versus-vehicle tests using a repeated-measures, crossover protocol. Similar protocols were used with CBZ-containing or control food pellets. RESULTS: CBZ significantly reduced motor seizure frequency at 30 and 100 mg/kg after single IP injections, and these doses completely blocked motor seizures during a 6-h postdrug epoch in 25% and 70% of the animals, respectively. Single administrations of 30 mg/kg and 100 mg/kg CBZ in food also significantly reduced motor seizures, and blocked seizures in 33% and 89% of the rats, respectively. CBZ administered in food three times per day (100 mg/kg x3 CBZ in food) continuously blocked nearly all motor seizures over a 5-day period, and completely suppressed motor seizures in 50% of the animals tested. CONCLUSIONS: CBZ strongly suppresses spontaneous motor seizures, and single doses of CBZ in food are as effective as IP injections in rats with kainate-induced epilepsy. CBZ administered regularly in food continuously blocks nearly all motor seizures, and may provide a relatively simple method to test AEDs in chronic models of epilepsy.     

Levetiracetam versus lorazepam in status epilepticus: a randomized,open labeled pilot study

For the management of status epilepticus (SE), lorazepam (LOR) is recommended as the first and phenytoin or fosphenytoin as the second choice. Both these drugs have significant toxicity. Intravenous levetiracetam (LEV) has become available, but its efficacy and safety has not been reported in comparison to LOR. We report a randomized, open labeled pilot study comparing the efficacy and safety of LEV and LOR in SE. Consecutive patients with convulsive or subtle convulsive SE were randomized to LEV 20 mg/kg IV over 15 min or LOR 0.1 mg/kg over 2–4 min. Failure to control SE within 10 min of administration of one study drug was treated by the other study drug. The primary endpoint was clinical seizure cessation and secondary endpoints were 24 h freedom from seizure, hospital mortality, and adverse events. Our results are based on 79 patients. Both LEV and LOR were equally effective. In the first instance, the SE was controlled by LEV in 76.3% (29/38) and by LOR in 75.6% (31/41) of patients. In those resistant to the above regimen, LEV controlled SE in 70.0% (7/10) and LOR in 88.9% (8/9) patients. The 24-h freedom from seizure was also comparable: by LEV in 79.3% (23/29) and LOR in 67.7% (21/31). LOR was associated with significantly higher need of artificial ventilation and insignificantly higher frequency of hypotension. For the treatment of SE, LEV is an alternative to LOR and may be preferred in patients with respiratory compromise and hypotension.     

咪达唑仑非静脉途径治疗儿童癫(癎)持续状态有效性和安全性的Meta分析

目的 评价咪达唑仑非静脉途径单药治疗儿童癫(癎)持续状态的有效性和安全性.方法 分别以咪达唑仑(midazolam)、癫(癎)持续状态(status epilepticus)、儿童(children)等中英文词汇为检索词,计算机检索近15年美国国立医学图书馆生物医学信息检索系统、ScienceDirect数据库,以及中国知网中国知识基础设施工程、维普中文科技期刊数据库、万方数据库;同时辅助手工检索和Google Scholar等搜索引擎在互联网检索关于咪达唑仑非静脉途径单药治疗癫(癎)持续状态的随机对照临床试验.采用Jadad量表和RevMan 5.3统计软件进行文献质量评价和Meta分析.结果 经剔除重复和不符合纳入标准者,258篇文献中共纳入6项随机对照临床试验计766例次癫(癎)持续状态患儿.Meta分析显示:非静脉途径咪达唑仑组与静脉注射地西泮组疗效差异无统计学意义(RD=-0.070,95％CI:-0.200 ～ 0.060;P=0.290),但疗效优于经直肠地西泮组(RD=0.170,95％CI:0.030～ 0.320;P=0.020);经鼻黏膜咪达唑仑组与静脉注射地西泮组急诊入院至癫痼发作停止时间(SMD=-1.570,95％CI:-3.280 ～ 0.140;P=0.070)和药物显效时间(SMD=0.240,95％CI:-0.110 ～ 0.590;P=0.170)差异均无统计学意义;非静脉途径咪达唑仑组与静脉或非静脉途径地西泮组药物不良反应差异亦无统计学意义(RD =-0.010,95％CI:-0.030～0.200;P=0.500).结论 咪达唑仑非静脉途径单药治疗儿童癫痫持续状态安全、有效,但尚待更多高质量多中心大样本随机对照临床试验加以验证.     

Status epilepticus and frequent seizures: incidence and clinical characteristics in pediatric epilepsy surgery patients

PURPOSE: The literature suggests that pediatric epilepsy surgery cases that present in status epilepticus (SE) are an unusual occurrence. However, this concept is based on case reports, and the incidence and clinical characteristics of these patients have not been systematically assessed. METHODS: The cohort consisted of resective epilepsy surgery cases from 2000 to 2005 (n = 115), and they were classified as presenting with continuous SE requiring medical suppression therapy (n = 6) or intermittent SE (greater than 3 seizures/hour; n = 17). The SE categories were compared with extratemporal surgery patients without SE (non-SE; n = 64) for differences in clinical variables abstracted from the medical record. RESULTS: Continuous SE was noted in 5% and intermittent SE in 15% of resective surgery cases, and all had extratemporal cortical involvement. Compared with continuous SE and non-SE cases, intermittent SE patients were younger at surgery with shorter duration of seizures, and had an increased incidence of active infantile spasms during video scalp EEG monitoring. Compared with non-SE cases, the continuous and intermittent SE groups required a larger number of antiepileptic medications presurgery and 6-months postsurgery, underwent hemispherectomy more frequently, and had an increased incidence of hemimegalencephaly and Rasmussen encephalitis and a lower occurrence of infarct/ischemia and infectious etiologies. Seizure control was over 71% up to 2 years postsurgery, and there were no differences between patient groups. Finally, seizure frequency per hour was greater in continuous SE cases compared with the intermittent SE group. CONCLUSIONS: Children presenting with continuous or intermittent SE are not rare in pediatric epilepsy surgery centers, and such cases are more commonly associated with infantile spasms, Rasmussen's syndrome, and hemimegalencephaly pathologies. Seizure outcome after surgery was not altered in pediatric patients because they had presented with continuous or intermittent SE.     

Insights into the sequence of structural consequences of convulsive status epilepticus: a longitudinal MRI study

While acute hippocampal magnetic resonance imaging (MRI) changes have been demonstrated, the long-term structural consequence of status epilepticus remains unclear. Also the timing of previously reported fornix abnormalities in patients with mesial temporal sclerosis (MTS) is unknown. We report longitudinal volumetic MRI and diffusion tensor imaging (DTI) findings of the hippocampus and fornix in a patient following status epilepticus. Left hippocampal atrophy demonstrated progression beyond 6 months poststatus epilepticus while the right hippocampus and bilateral fornices demonstrated stable volumetric and diffusion abnormalities throughout the study. Our findings provide evidence that status epilepticus can induce permanent hippocampal damage with the delayed timing of the structural changes being consistent with programmed cell death.     

Induction of prolonged electrographic seizures in vitro has a defined threshold and is all or none: implications for diagnosis of status epilepticus

PURPOSE: To study whether induction of prolonged (>30-min duration) in vitro electrographic seizure discharges resembling status epilepticus (SE) is graded or all-or-none, and to determine the critical factors mediating SE induction. METHODS: Prolonged electrographic seizure discharges were induced in combined hippocampal-entorhinal cortical (HEC) brain slices by electrical stimulation of the Schaeffer collaterals. Discharges were recorded by using field-potential electrodes in the dentate gyrus, CA3, CA1, and entorhinal cortex. Slices were prepared from rats that were (a). 21- to 30-day-old naive, (b). 60- to 120-day old naive, (c). epileptic, and (d). status post a prior traumatic brain injury. RESULTS: Induction of SE discharges was dependent on the duration, but not amplitude of the preceding stimulus train-induced afterdischarge in HEC slices from 21- to 30-day-old control, brain-injured, and epileptic animals, but not from 60- to 120-day-old animals. In slices from 21- to 30-day-old control animals, once afterdischarges exceeded 4 min in duration, SE was induced in 50% of slices, and after >or=6 min 37 s seizure activity; SE was induced in 95% of slices. A defined SE threshold also was evident in brain-damaged rats, including rats in which an epileptic condition was induced by pilocarpine injection 4-16 weeks before recording, and rats subjected to a fluid percussive head trauma 1-8 weeks before recording. However, in these brain-damaged animals, mean SE threshold was considerably lower (24 and 44 s, respectively). HEC slices from 60- to 120-day-old controls for the brain-injured and epileptic animals did not develop SE even after 20 stimulations, demonstrating the pronounced effect of brain injury and epilepsy on the development of SE in the HEC slice preparation compared with that in age-matched controls. CONCLUSIONS: In vitro, SE discharges have a defined temporal threshold for initiation. Once a seizure exceeds 6-7 min in duration in control animals, and 30-55 s in brain-damaged animals, the probability of SE induction is greatly increased. This demonstrates that brain injury lowers the afterdischarge duration required to produce SE and suggests that brains injured from trauma or SE are more susceptible to develop status epilepticus.     

Valproate versus diazepam for generalized convulsive status epilepticus: a pilot study

Background and purpose: Evidence‐based data to guide the management of status epilepticus (SE) after failure of primary treatment are still scarce and the alternate needs to be found when phenytoin (PHT) is not available or contraindicated. Comparison of intravenous (IV) valproate (VPA) and diazepam (DZP) infusion has not been conducted in adults with SE. This prospective randomized controlled trial is thus designed to evaluate the relative efficacy and safety of IV VPA and continuous DZP infusion as second‐line anticonvulsants. Methods: After failure of first‐line anticonvulsants treatment, patients with generalized convulsive status epilepticus (GCSE) were randomized to receive either IV VPA or continuous DZP infusion. Primary outcome was the proportion of patients with effective control. Side effects were also evaluated. Results: There were 66 cases enrolled, with the mean age of 41 ± 21 years. Seizure was controlled in 56% (20/36) of the DZP group and 50% (15/30) of the VPA group (P = 0.652). No patient in the VPA group developed respiratory depression, hypotension, or hepatic dysfunction, whereas in the DZP group, 5.5% required ventilation and 5.5% developed hypotension. Time (hour) for regaining consciousness after control was near‐significantly longer in the DZP group [13(3.15–21.5)] than in the VPA group [3(0.75–11)] (P = 0.057). Virus encephalitis and long duration of GCSE were independent risk factors of drug resistance. Conclusions: Both IV VPA and continuous DZP infusion are effective second‐line anticonvulsants for GCSE. IV VPA was well tolerated and free of respiratory depression and hypotension, which may develop in the DZP group. Outcome parameters were not significantly different between groups.