The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine-resistant convulsive status epilepticus: A meta-analysis of published studies

PurposeSystematic evaluation of published evidence-base of the efficacy of five antiepileptic drugs – lacosamide, levetiracetam, valproate, phenytoin and phenobarbital – in convulsive benzodiazepine-resistant status epilepticus.MethodsData sources included electronic databases, personal communication, and back tracing of references in pertinent studies. These were prospective and retrospective human studies presenting original data for participants with convulsive benzodiazepine-resistant status epilepticus. Interventions were intravenous lacosamide, levetiracetam, phenobarbital, phenytoin and valproate. Outcome measured is clinically detectable cessation of seizure activity. Level-of-evidence was assessed according to Oxford Centre of Evidence-Based Medicine and The Cochrane Collaboration's Tool for Assessment of Risk. Twenty seven studies (798 cases of convulsive status epilepticus) were identified and 22 included in a meta-analysis. Random-effects analysis of dichotomous outcome of a single group estimate (proportion), with inverse variance weighting, was implemented. Several sources of clinical and methodological heterogeneity were identified.ResultsEfficacy of levetiracetam was 68.5% (95% CI: 56.2–78.7%), phenobarbital 73.6% (95% CI: 58.3–84.8%), phenytoin 50.2% (95% CI: 34.2–66.1%) and valproate 75.7% (95% CI: 63.7–84.8%). Lacosamide studies were excluded from the meta-analysis due to insufficient data.ConclusionValproate, levetiracetam and phenobarbital can all be used as first line therapy in benzodiazepine-resistant status epilepticus. The evidence does not support the first-line use of phenytoin. There is not enough evidence to support the routine use of lacosamide. Randomized controlled trials are urgently needed.     

Two years of experience in the treatment of status epilepticus with intravenous levetiracetam

Since its introduction in 2006, 43 patients with various forms of status epilepticus (SE) have been treated with the intravenous formulation of levetiracetam (LEV) in our clinic. After ineffective treatment with benzodiazepines, intravenous LEV was administered as a short infusion (nonconvulsive and subtle SE) at a dose of 1000 or 2000 mg. In cases of convulsive SE, a fractionated injection of 1000 or 2000 mg was used. When the results for both are combined, SE could be terminated in 19 of 43 patients. Intravenous LEV was more effective in simple focal SE (3/5), complex focal SE (11/18) and myoclonic status (2/2) than in nonconvulsive (2/8) and subtle (1/2) SE. In no case was (secondarily) generalized convulsive status epilepticus (0/8) terminated. Intravenous LEV was also well-tolerated when injected in fractionated form. No severe adverse reactions were observed. As a result of this investigation, intravenous LEV in moderate doses may represent an efficacious and well-tolerated alternative for the treatment of focal (simple and complex focal) and myoclonic SE. Further investigations are needed to confirm this assumption as the patient numbers are quite low.     

Safety and pharmacokinetics of intravenous levetiracetam infusion as add-on in status epilepticus

Purpose: To evaluate the feasibility and safety of intravenous (iv) levetiracetam (LEV) added to the standard therapeutic regimen in adults with status epilepticus (SE), and as secondary objective to assess a population pharmacokinetic (PK) model for ivLEV in patients with SE. Methods: In 12 adults presenting with SE, 2,500 mg ivLEV was added as soon as possible to standardized protocol, consisting of iv clonazepam and/or rectal diazepam, as needed followed by phenytoin or valproic acid. ivLEV was administered over approximately 5 min, in general after administration of clonazepam, regardless the need for further treatment. During 24‐h follow‐up, patients were observed for any clinically relevant side‐effects. Blood samples for PK analysis were available in 10 patients. A population PK model was developed by iterative two‐stage Bayesian analysis and compared to PK data of healthy volunteers. Results: Eleven patients with a median age of 60 years were included in the per protocol analysis. Five were diagnosed as generalized‐convulsive SE, five as partial‐convulsive SE, and one as a nonconvulsive SE. The median time from hospital admission to ivLEV was 36 min. No serious side effects could be related directly to the administration of ivLEV. During PK analysis, four patients showed a clear distribution phase, lacking in the others. The PK of the population was best described by a two‐compartment population model. Mean (standard deviation, SD) population parameters included volume of distribution of central compartment: 0.45 (0.084) L/kg; total body clearance: 0.0476 (0.0147) L/h/kg; distribution rate constants, central to peripheral compartment (k₁₂): 0.24 (0.12)/h, and peripheral to central (k₂₁): 0.70 (0.22)/h. Mean maximal plasma concentration was 85 (19) mg/L. Discussion: The addition of ivLEV to the standard regimen for controlling SE seems feasible and safe. PK data of ivLEV in patients with SE correspond to earlier values derived from healthy volunteers, confirming a two‐compartment population model.     

Nonconvulsive status epilepticus on treatment with levetiracetam

In several studies the efficacy and tolerability of levetiracetam (LEV) have been demonstrated. We report two patients who developed nonconvulsive status epilepticus on treatment with LEV. Both patients never experienced status epilepticus before. One patient had a symptomatic epilepsy with complex partial seizures following radiotherapy of astrocytoma in 1985; the second patient had complex partial seizures due to mesial temporal sclerosis. Both patients received LEV 2000 mg/day. We postulate a correlation between occurrence of nonconvulsive status and treatment with LEV. This has not been described before apart from a single report of mentally retarded patients with status epilepticus on high dosages of LEV.     

Neonatal status epilepticus controlled with levetiracetam at Sturge Weber syndrome

Sturge–Weber syndrome is a rare, sporadic, congenital neurocutaneous syndrome characterized by facial cutaneous vascular malformation, leptomeningeal angioma and eye abnormalities. Seizures develop during the first year of life, may become refractory to multiple anticonvulsants and status epilepticus may develop. A rare subtype of Sturge–Weber syndrome with bilateral facial vascular malformation, unilateral cerebral involvement and neonatal status epilepticus is reported here. Neonatal status epilepticus was successfully controlled with intravenous levetiracetam infusion.     

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.     

左乙拉西坦治疗小儿癫痫疗效的Meta分析

目的评价左乙拉西坦治疗小儿癫痫的疗效和安全性。方法计算机检索近十年(2001-2011)来PubMed、Cochrane Database of Systematic Reviews、EMbase、中国知网(CNKI)检索平台、万方数据库中纳入左乙拉西坦治疗小儿癫痫的随机对照研究(RCTs),研究者对文献质量进行严格评价和资料提取。对符合质量标准的RCTs用Review manager 5.0软件进行Meta分析。结果 6个RCTs共610名患者纳入研究,其中治疗组(使用左乙拉西坦)333例,对照组(常规治疗)277例。Meta分析结果表明治疗组患者每周癫痫发病率明显低于对照组,对于患者继发嗜睡、头痛等中枢系统不良反应及肝肾功能损害方面,RCTs结果显示无显著差异。结论左乙拉西坦治疗不良反应种类少,对各种发作类型的小儿癫痫均有良好疗效,且不增加发生其他不良结局的危险性,可作为小儿癫痫患者的首选治疗方案之一。     

Why we prefer levetiracetam over phenytoin for treatment of status epilepticus

Over last fifty years, intravenous (iv) phenytoin (PHT) loading dose has been the treatment of choice for patients with benzodiazepine‐resistant convulsive status epilepticus and several guidelines recommended this treatment regimen with simultaneous iv diazepam. Clinical studies have never shown a better efficacy of PHT over other antiepileptic drugs. In addition, iv PHT loading dose is a complex and time‐consuming procedure which may expose patients to several risks, such as local cutaneous reactions (purple glove syndrome), severe hypotension and cardiac arrhythmias up to ventricular fibrillation and death, and increased risk of severe allergic reactions. A further disadvantage of PHT is that it is a strong enzymatic inducer and it may make ineffective several drugs that need to be used simultaneously with antiepileptic treatment. In patients with a benzodiazepine‐resistant status epilepticus, we suggest iv administration of levetiracetam as soon as possible. If levetiracetam would be ineffective, a further antiepileptic drug among those currently available for iv use (valproate, lacosamide, or phenytoin) can be added before starting third line treatment.     

Prognostic scores in status epilepticus: A systematic review and meta-analysis

The performance of prognostic scores of status epilepticus (SE) has been reported in very heterogeneous cohorts. We aimed to provide a summary of the available evidence on their respective performance. PubMed and EMBASE were searched for relevant articles. Studies were reviewed for eligibility for meta-analysis of the area under the receiver-operating characteristic curve (AUC) and for meta-analysis of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in predicting in-hospital mortality with scores in which at least two external evaluations had been published. This study was registered with PROSPERO (international prospective register of systematic reviews) (CRD42022325766). Study quality was assessed using Prediction model Risk Of Bias ASsessment Tool (PROBAST). In the meta-analysis of AUC, 21 studies were pooled for STESS (Status Epilepticus Severity Score), five for EMSE-EAC (Epidemiology-based Mortality Score in Status Epilepticus - Etiology, Age, level of Consciousness), five for EMSE-EACE (EMSE - Etiology, Age, level of Consciousness, EEG), and two for ENDIT (Encephalitis, nonconvulsive status epilepticus, Diazepam resistance, Imaging abnormalities, Tracheal intubation). The pooled AUC of STESS, EMSE-EAC, EMSE-EACE, and ENDIT was 0.74 (95% CI: 0.71–0.78), 0.68 (95% CI 0.63–0.72), 0.77 (95% CI: 0.72–0.81), and 0.78 (95% CI: 0.70–0.87), respectively. The pooled sensitivity of STESS-3, STESS-4, EMSE-EACE-64, and ENDIT-4 was 0.83 (95% CI: 0.80–0.86), 0.60 (95% CI: 0.55–0.65), 0.76 (95% CI: 0.67–0.83), and 0.70 (95% CI: 0.55–0.82), respectively. Their pooled specificity was 0.50 (95% CI: 0.48–0.52), 0.74 (95% CI: 0.72–0.76), 0.63 (95% CI: 0.59–0.67), and 0.65 (95% CI: 0.61–0.70), respectively. Their pooled PPV was 0.27 (95% CI: 0.24–0.30), 0.35 (95% CI: 0.29–0.41), 0.33 (95% CI: 0.24–0.43), and 0.20 (95% CI: 0.13–0.27). Their pooled NPV was 0.94 (95% CI: 0.93–0.96), 0.90 (95% CI: 0.89–0.92), 0.89 (95% CI: 0.80–0.98), and 0.95 (95% CI: 0.92–0.98). Variations in performance were observed in patients' subgroups, such as critically ill patients and refractory cases. Investigated scores only have acceptable AUC, sensitivity, and specificity for predicting in-hospital mortality, with the EMSE-EAC having a lower discriminative power. STESS-3 has the highest sensitivity, and STESS-4 the highest specificity, but neither combines acceptable sensitivity and specificity. All these scores had high NPV but very low PPV. Caution should be exercised in their clinical use. Further studies are required to develop more accurate scores.     

Pentobarbital and EEG burst suppression in treatment of status epilepticus refractory to benzodiazepines and phenytoin

Seven patients with complex partial or secondarily generalized tonic-clonic status epilepticus (SE) refractory to benzodiazepines (BZDs) and phenytoin (PHT) were treated with pentobarbital (PTB) coma with an EEG burst suppression (BSP) pattern. PTB administered by continuous intravenous (i.v.) infusion pump at a loading dose of 6-8 mg/kg in 40-60 min was usually sufficient to produce BSP activity and seizure control. PTB was continued 0-24 h at 1-4 mg/kg/h, adjusted to maintain blood pressure (BP) and BSP. Infusion rate was decreased if systolic BP (SBP) was less than 90 mm Hg. Normal saline fluid challenge was occasionally used to elevate BP, but in no case was it necessary to discontinue PTB infusion or use pressors. Other antiepileptic drugs (AEDs) were maintained at therapeutic levels for chronic seizure protection. Seizures were stopped in all cases. Four patients attained premorbid neurologic status, two patients briefly survived in vegetative states with recurring seizures after PTB withdrawal, and one patient died of asystole after receiving PTB for 7 h. Patients who had poor outcomes had prolonged seizures (16 h to 3 weeks) before institution of PTB anesthesia, and all had significant underlying central nervous system (CNS) pathology. PTB-induced BSP appears to be safe and effective for refractory SE if it is started soon after failure of a BZD and PHT. Ultimate prognosis depends on SE etiology.     

Treatment of electrographic seizures and status epilepticus in critically ill children: A single center experience

PurposeElectrographic seizures (ES) and electrographic status epilepticus (ESE) are common in encephalopathic children in the pediatric intensive care unit (PICU) and associated with worse short-term outcome. Survey data indicate most physicians treat ES and ESE with antiepileptic drugs (AEDs), but few data are available regarding AED usage patterns. We aimed to describe AED usage for ES and ESE in critically ill children.MethodsWe performed an observational study of patients who underwent continuous electroencephalographic (cEEG) monitoring in the PICU of a single quaternary care children's hospital. We collected data regarding age, clinical diagnoses, ES and ESE occurrence, and AEDs utilized.Results200 subjects underwent cEEG. ES occurred in 21% (41/200) and ESE occurred in 22% (43/200). Of the 84 patients with ES or ESE, 80 received non-benzodiazepine AEDs including 48% (38 of 80) with ES and 52% (42 of 80) with ESE. The most commonly administered first AEDs were levetiracetam in 38% (30/80), phenobarbital in 31% (25/80), phenytoin–fosphenytoin in 28% (22/80), and valproate in 4% (3/80). Seizures terminated after administration of the first AED in 74% (28/38) with ES and 22% (9/41) with ESE.ConclusionsLevetiracetam, phenobarbital, and phenytoin–fosphenytoin are commonly used to manage ES and ESE at our center. Over half of subjects received multiple AEDs.     

Intravenous sodium valproate in status epilepticus: review and Meta-analysis

Abstract

Objective: Status epilepticus (SE) is a common neurologic emergency. The present study constitutes a meta-analysis of published randomized control trials (RCTs) evaluating the use of intravenous sodium valproate (VPA) in SE.

Methods: MEDLINE and Cochrane databases were comprehensively searched, while retrieved RCTs and meta-analyses were manually screened. Prespecified outcome measures included seizure-cessation, 24?h-efficacy, constitute (liver enzyme increase, arrhythmias, bone-marrow suppression, hypotension and respiratory depression) and severe (life-threatening) adverse events (AEs). Evidence synthesis was performed when appropriate, using Random-Effects (RE) or Fixed-Effects (FE) model based on heterogeneity between trials (homogeneity assumed when PQ > 0.1 and I² < 50%). Outcomes were assessed using Odds-Ratios (ORs) and 95%Confidence-Intervals (95% CIs). Every available comparison was investigated in terms of efficacy and tolerability.

Results:Thirteen studies were retrieved and five comparisons were available, four of which involved two or more studies. Results were compatible with no significant difference between VPA and Phenytoin both in terms of efficacy and tolerability [seizure-cessation: FE-OR = 1.99, 95% CI = (0.83–4.75), 24?h-efficacy: FE-OR = 1.32, 95% CI = (0.60–2.89), composite AEs: FE-OR = 0.45, 95% CI = (0.17–1.21)]. Phenobarbital proved more commonly associated with composite AEs than VPA [seizure-cessation: RE-OR = 0.68, 95% CI = (0.05–9.44), 24?h-efficacy: RE-OR = 0.88, 95% CI = (0.02–33.9), composite AEs: FE-OR = 0.26, 95% CI = (0.09–0.82), severe AEs: FE-OR = 0.30, 95% CI = (0.04–2.28)]. Diazepam was determined inferior to VPA concerning safety issues [seizure-termination: FE-OR = 0.77, 95% CI = (0.34–1.79), severe respiratory depression: FE-OR = 0.06, 95% CI = (0.01–0.48), severe hypotension: FE-OR = 0.09, 95% CI = (0.01–0.72)]. The combination of Lorazepam (LZP) with VPA and the combination of LZP with Levetiracetam presented no difference in efficacy [24h-efficacy: FE-OR = 0.68, 95% CI = (0.37–1.24)].

Conclusions: Although, additional high-quality RCTs are warranted, according to our results, VPA can be considered a safe and effective option in the management of SE.     

Levetiracetam: antiepileptic properties and protective effects on mitochondrial dysfunction in experimental status epilepticus

PURPOSE: To assess the anticonvulsant activity of the novel antiepileptic drug, levetiracetam (LEV) in a model of self-sustaining limbic status epilepticus, and to measure the consequence of LEV treatment on the pattern of mitochondrial dysfunction known to occur after status epilepticus (SE). METHODS: The rat perforant pathway was stimulated for 2 h to induce self-sustaining status epilepticus (SSSE). Stimulated rats were assigned to one of three treatment groups, receiving intraperitoneal injections of saline, 200 mg/kg LEV, or 1,000 mg/kg LEV, 15 min into SSSE and at 3 times over the next 44-h period. All animals received diazepam after 3-h SSSE to terminate seizures. Forty-four hours later, the hippocampi were extracted and prepared for electrochemical high-performance liquid chromatography (HPLC), to measure reduced glutathione levels, and for spectrophotometric assays to measure activities of mitochondrial enzymes (aconitase, alpha-ketoglutarate dehydrogenase, citrate synthase, complex I, and complex II/III). These parameters were compared between treatment groups and with sham-operated rats. RESULTS: LEV administration did not terminate seizures or have any significant effect on spike frequency, although rats that received 1,000 mg/kg LEV did exhibit improved behavioral seizure parameters. Significant biochemical changes occurred in saline-treated stimulated rats compared with shams: with reductions in glutathione, alpha-ketoglutarate dehydrogenase, aconitase, citrate synthase, and complex I activities. Complex II/III activities were unchanged throughout. Rats that received 1,000 mg/kg LEV had significantly improved biochemical parameters, in many instances, comparable to sham control levels. CONCLUSIONS: Despite continuing seizures, administration of LEV (1,000 mg/kg) protects against mitochondrial dysfunction, indicating that in addition to its antiepileptic actions, LEV may have neuroprotective effects.     

Refractory idiopathic absence status epilepticus: A probable paradoxical effect of phenytoin and carbamazepine

PURPOSE: To compare the frequency of seizures and status epilepticus and their response to first-line drugs in patients with idiopathic generalized epilepsies receiving carbamazepine or phenytoin to those receiving other drugs or no treatment. METHODS: We performed a retrospective chart review of all cases of idiopathic generalized epilepsies treated by the authors between 1985 and 1994. We compared seizure frequency and mean intravenous benzodiazepine dose required to control absence status epilepticus, intraindividually in subjects on carbamazepine or phenytoin before and after discontinuation of these compounds, and interindividually to subjects without treatment or receiving other drugs. RESULTS: Bouts of absence or tonic-clonic status epilepticus and seizures in subjects treated with phenytoin or carbamazepine at therapeutic concentrations were considerably more frequent and proved intractable to treatment with valproic acid or benzodiazepines, compared with a cohort of subjects also with idiopathic generalized epilepsies, but naive to, or receiving subtherapeutic or therapeutic doses of other agents. CONCLUSIONS: Our observations strongly suggest that therapeutic concentrations of phenytoin and carbamazepine exacerbate idiopathic generalized epilepsies. Subjects in whom absence is one of the seizure types seem at a particularly high risk for responding paradoxically. These findings underscore the value of accurate classification of seizures and particularly the syndromic approach to diagnosis and point to the potential for iatrogenic complications with indiscriminate use of antiseizure drugs.     

咪达唑仑持续静脉维持治疗儿童癫持续状态疗效观察

目的观察咪达唑仑持续静脉维持治疗癫持续状态(SE)的疗效。方法38例SE患儿应用咪达唑仑持续静脉维持治疗,开始以0.1～0.2mg/kg静脉注射,随后以0.1～0.4mg/(kg.h)持续静脉维持,根据发作状态调整剂量大小。结果26例SE患儿应用咪达唑仑维持治疗后样发作停止。4例患儿症状部分缓解,6例患儿无效,2例患儿因基础疾病死亡。咪达唑仑应用过程中无严重不良反应出现。结论应用咪达唑仑治疗SE有效安全。     

非抽搐性癫痫持续状态五例及文献复习

目的 探讨非抽搐性癫痫持续状态(NCSE)患者的临床表现及持续脑电监测的脑电图(EEG)特征.方法 对自2008年11月至2009年12月北京大学人民医院急诊科收治的5例NCSE患者行持续EEG监测检查,观察其EEG特征及临床表现.结果 5例均出现发作性意识障碍,其中4例出现烦躁、易怒或躁狂,3例表现出精神运动迟滞和遗忘,2例出现言语自动症和失认,1例出现定向障碍.所有患者的EEG均出现广泛性但一侧明显的异常放电.静脉注射地两泮后,3例患者临床症状迅速改善.结论 NCSE并非罕见,持续EEG监测能查出本病,早期诊断,及时治疗可改善患者预后,临床应注意与其他引起意识紊乱的疾病相鉴别.     

A systematic review of the epidemiology of status epilepticus

Population-based data on the incidence, aetiology, and mortality associated with status epilepticus (SE) are required to develop preventative strategies for SE. Through a systematic review, we aimed to assess the methodological quality as well as similarities, and differences between available population based studies in order to arrive at conclusions on the epidemiology of SE. All population-based studies where primary outcome was incidence, aetiology or mortality of SE were identified through a systematic search and synthesized. Methodological quality of studies were independently rated by two examiners using a unique scoring system. Seven population-based projects on SE yielding nine published reports and five abstracts were reviewed. Quality scores were in the range of 19-34 with a possible maximum of 40 (kappa scores 0.67-1.0). The incidence of SE has a bimodal distribution with peaks in children aged less than a year and the elderly. Most SE were acute symptomatic. Short-term mortality was 7.6-22% and long-term mortality was 43%. Age and aetiology were the major determinants of mortality. There are few population-based studies on SE but most are of good quality. Most studies are primarily or exclusively based on adult populations. There is limited information on the association of ethnicity and socio-economic status and SE.     

Neuromodulation techniques for status epilepticus: A review

BackgroundElectroconvulsive therapy (ECT), Vagal Nerve Stimulation (VNS), Transcranial Magnetic Stimulation (TMS) and Deep Brain Stimulation (DBS) are neuromodulation therapies that have been used to treat Status Epilepticus (SE).ObjectiveReview the literature about the efficacy and safety of neuromodulation therapies in SE in humans.MethodsWe searched studies in PubMed, Scopus, Google Scholar and Science Direct (inception to June 2018). Four review authors independently selected the studies, extracted data and assessed the methodological quality of the studies using the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines, Oxford and GRADE scales, and Murad et al., 2018 methodological quality and synthesis of case series and case reports.ResultsWe analyzed 27 articles (45 patients) with 4 different neuromodulation therapies. In ECT we found 80% rate of disruption of SE and 5% of adverse events was reported. Using iVNS 15/16 (93.7%) patients resolved the SE. All patients who underwent TMS and DBS aborted SE, however, 50% of patients with DBS had severe adverse events.ConclusionsCase series and case reports suggest that neuromodulation therapies can abort SE in 80–100% of patients (Oxford scale and GRADE were level 4 and D) with a wide range of adverse effects, which claims for prospective studies on the relationship be-tween efficacy and safety.     

Use of levetiracetam in hospitalized patients

PURPOSE: The objective of the study was to analyze the short-term efficacy and safety of levetiracetam (LEV) to treat repetitive seizures in hospitalized patients. METHODS: During admission to a tertiary hospital, we retrospectively identified patients with repetitive seizures who were treated for the first time with LEV during a hospital stay. LEV was considered effective if seizure cessation or >75% seizure reduction occurred in the 24 h after starting LEV (compared with the previous 48 h), requiring no further antiepileptic drug (AED) treatment. RESULTS: Thirty patients (12 men, 18 women) were included. Mean age was 59.7 years. Most frequent seizure type was focal motor in 12 (40%) of 30 patients. Most frequent etiology was stroke: nine (30%) of 30 patients. Relevant medical conditions included atrial fibrillation (three) and hepatic disease (three). Concomitant medications included oral anticoagulants (seven), corticosteroids (two), and chemotherapy (two). Four patients received LEV as the only AED. Six patients with focal SE and 20 (66.6%) patients with clusters of seizures but not in SE received LEV as add-on treatment after lack of response to first-line AEDs. Mean LEV dose during first day was 1,119 mg. Mean daily maintenance dose was 1,724 mg. LEV was effective in 24 (80%) patients, all four patients who received it as the only AED, four of six patients with focal SE, and 16 of 20 patients with clusters of seizures. Three (10%) elderly patients with seizures secondary to stroke and chronic obstructive pulmonary disease (COPD) reported moderate/severe somnolence and dizziness, leading to treatment discontinuation in one. On discharge, 20 (66.7%) patients continued on LEV, nine (30%) as the only AED. CONCLUSIONS: LEV is effective and safe to treat repetitive seizures in hospitalized patients, including patients in focal SE.