Oral clomethiazole treatment for paediatric non‐convulsive status epilepticus

We report a retrospective case study of the use of clomethiazole for treatment of non‐convulsive status epilepticus in a patient not responding to benzodiazepines, illustrated by EEG and video. Clomethiazole can be considered as a safe oral option for management of non‐convulsive status epilepticus when conventional treatment has failed. [Published with video sequences online]     

惊厥性癫痫持续状态并发急性胰腺炎二例分析

目的探讨惊厥性癫痫持续状态（GCSE）并发急性胰腺炎的临床特点和治疗方法。方法 资料完整的GCSE住院患者二例，强直阵挛发作病史11、13年。急性胰腺炎诊断根据血尿淀粉酶化验和腹部超声波、CT检查。结果二例GCSE患者强直阵挛发作持续状态24h后出现继发性急性胰腺炎，经静脉应用地西泮癫痫状态停止，保守和支持治疗胰腺炎痊愈后出院。随访3个月未出现GCSE和腹痛。结论GCSE可以引起急性胰腺炎．GCSE后腹痛应进行急性胰腺炎有关指标的检查，明确诊断后避免使用具有胰腺毒性的抗癫痫药物。     

Successful treatment for refractory convulsive status epilepticus by non‐parenteral lacosamide

Lacosamide (Vimpat) is a newly licensed novel antiepileptic drug. We report a case of refractory convulsive status epilepticus (CSE) that was successfully controlled with lacosamide. The 38‐year‐old male patient was admitted for a series of complex partial seizures with secondary generalization leading to refractory CSE. During the transport to the hospital the patient was given 22.5 mg diazepam, 12.5 mg etomidate, and 5 mg midazolam without success. An additional dose of 4 mg lorazepam and a dose of 1,500 mg levetiracetam after admission were yet without clinical effect. A further treatment with lacosamide (300 mg via percutaneous gastric fistula) resulted in complete clinical remission of the epileptic activity within 30 min. The application of lacosamide resulted in cessation of CSE and was well tolerated. To our knowledge, this is the first case of successful treatment of refractory CSE with lacosamide. Further studies are needed to evaluate the safety and efficacy of lacosamide in treatment of SE.     

Inadequate benzodiazepine dosing may result in progression to refractory and non‐convulsive status epilepticus

Aims. Status epilepticus (SE) is defined as ongoing seizures lasting longer than five minutes or multiple seizures without recovery. Benzodiazepines (BZDs) are first‐line agents for the management of SE. Our objective was to evaluate BZD dosing in SE patients and its effects on clinical/electrographic outcomes. Methods. A retrospective analysis was conducted from a prospective database of SE patients admitted to a university‐based neurocritical care unit. The initial presentation and progression to refractory SE (RSE) and non‐convulsive SE (NCSE) with coma was evaluated. Outcome measures included length of stay (LOS), rates of intubation, ventilator‐dependent days, and Glasgow outcome scale (GOS). The lorazepam equivalent (LE) dosage of BZDs administered was calculated and we analysed variations in progression if 4 mg or more of LE (adequate BZDs) was administered. Results. Among 100 patients, the median dose of LE was 3 mg (IQR: 2–5 mg). Only 31% of patients received adequate BZDs. Only 18.9% of patients with NCSE without coma received adequate BZDs (p=0.04). Among patients progressing to RSE, 75.4% had not received adequate BZDs (p=0.04) and among patients developing NCSE with coma, 80.6% did not receive adequate BZDs (p=0.07). Escalating doses of BZDs were associated with a decrease in cumulative incidences of RSE (correlation coefficient r=‐0.6; p=0.04) and NCSE with coma (correlation coefficient r=‐0.7; p=0.003). Outcome measures were not influenced by BZD dosing. Conclusion. The majority of our patients were not adequately dosed with BZDs. Inadequate BZD dosing progressed to RSE and had a tendency to lead to NCSE with coma. Our study demonstrates the need to develop a hospital‐wide protocol to guide first responders in the management of SE.     

Childhood convulsive status epilepticus: epidemiology, management and outcome

Convulsive status epilepticus (CSE) in childhood is a medical emergency and its aetiology and outcome mean that it should be studied separately from adult CSE. The incidence in developed countries is between 17 and 23/100,000 with a higher incidence in younger children. Febrile CSE is the commonest single group with a good prognosis in sharp distinction to CSE related to central nervous system infections which have a high mortality. The aim of treatment is to intervene at 5 min and studies indicate that intravenous (i.v.) lorazepam may be a better first-line treatment than rectal diazepam and i.v. phenytoin a better second-line treatment than rectal paraldehyde. An epidemiological study strongly supports the development of prehospital treatment with buccal midazolam becoming a widely used but unlicensed option in the community. More than two doses of benzodiazepines increase the rate of respiratory depression without obvious benefit. The 1 year recurrence rate is 17% and the hospital mortality is about 3%.     

老年惊厥性癫痫持续状态28例临床分析

目的观察老年惊厥性癫痫持续状态(CSE)的临床特点。方法收集神经重症监护室(NICU)年龄≥60岁的CSE患者28例,回顾性分析其临床特点。结果脑血管病为28例老年CSE的首位病因。接受抗癫痫药物治疗后,CSE症状控制的中位时间为0.9 h,其中16例患者在1 h内症状控制,12例为难治性癫痫持续状态(RSE)。28例患者中,存活16例、死亡12例。死亡者与存活者相比,合并中枢神经系统新发疾病(P=0.027)和RSE的比例显著不同(P=0.027)。结论老年CSE患者基础情况差,病因多样,合并有中枢神经系统新发疾病或有RSE者的死亡率高。     

Non convulsive status epilepticus following intrathecal fluorescein injection

We report a case of non convulsive status epilepticus after an intrathecal injection of fluorescein. The clinical presentation was a confusional state--the epileptic origin of which was confirmed by the electroencephalogram. This rare and relatively benign complication should not bring about worry concerning the fluorescein test used for the diagnosis of a dural defect and the identification of the site of a CSF leak.     

IV Valproate in generalized convulsive status epilepticus: a systematic review

Aim of this review was to evaluate efficacy and safety of intravenous valproate (IV VPA) in the treatment of generalized convulsive status epilepticus (GCSE) in patients of any age, synthesizing available evidences from randomized controlled trials (RCTs). RCTs on IV VPA administered in patients (no age restriction) for GCSE at any stage were searched in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials. Studies were selected and data independently extracted. Following outcomes were considered: clinical seizure cessation after drug administration, seizure freedom at 24 h, and adverse effects. Outcomes were assessed using standard methods to calculate risk ratio (RR) with 95% confidence intervals. Five trials met inclusion criteria. Two different comparisons were available (IV VPA versus phenytoin (PHT), IV VPA versus IV Diazepam), but only the former included more than one study with enough information to permit a meta-analysis. Compared with PHT, VPA had statistically lower risk of adverse effects (RR 0.31, 95% CI 0.12-0.85), with no differences in GCSE cessation after drug administration (RR 1.31, 95% CI 0.93-1.84) and in seizure freedom at 24 h (RR 0.96, 95% CI 0.88-1.06). This review suggests that IV VPA has a better tolerability than PHT in treatment of GCSE, without any statistically significant differences in terms of efficacy. More rigorous RCTs of VPA versus an appropriate comparator, in a well-defined population with a systematic definition of SE, are however required to conclude about efficacy and tolerability of VPA in clinical practice.     

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.     

Clinical features of convulsive status epilepticus: a study of 220 cases in western China

Background and purpose:  Convulsive status epilepticus (CSE) is the most common and life-threatening form of status epilepticus (SE). The aim of this study was to describe the clinical features of CSE in western China.
Methods:  Convulsive status epilepticus patients hospitalized from January 1996 to October 2007 were prospectively observed. Logistic regression was used to identify predictors of prognosis.
Results:  The average age of CSE patients ( n  = 220) was 37.5 years (SD 20.31), 50% of the patients had a history of epilepsy. The primary cause of CSE was central nervous system infection (32.7%), followed by discontinuation or reduction of antiepileptic drugs (AEDs; 15.5%). The median duration of CSE was 5 h and median duration of seizures before treatment was 2 h; both were longer in rural patients than in urban patients ( P  < 0.05). The fatality rate on discharge was 15.9%. Logistic regression analysis showed the duration of CSE [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.03–1.07], a history of epilepsy (OR 0.35, 95% CI 0.14–0.89), and respiratory depression (OR 5.96, 95% CI 2.49–14.24) were independent predictors of CSE prognosis.
Discussion:  Central nervous system infection and AEDs withdrawal in epilepsy patients were the most important causes of CSE. There is a large gap between antiepileptic therapy in China and European Status Epilepticus guidelines.     

Short‐term outcomes and major barriers in the management of convulsive status epilepticus in children: a study in Georgia

Aim. Convulsive status epilepticus is the most common childhood neurological emergency in developing countries, where poor healthcare organisation could play a negative role in the management of the condition. Unavailability of second‐line injectable anticonvulsants is an additional hindering factor in Georgia. This report reflects the results of the first study aimed at evaluating the epidemiological features of convulsive status epilepticus, as well as identifying obstacles influencing the management of patients with convulsive status epilepticus in Georgia. Methods. A prospective, hospital‐based study was performed. Paediatric patients with convulsive status epilepticus, admitted to the emergency department of a referral academic hospital from 2007 to 2012, were included in the study. Results. Forty‐eight paediatric patients admitted to hospital met the criteria for convulsive status epilepticus. Seizure duration was significantly shorter among the group with adequate and timely pre‐hospital intervention. Moreover, patients with appropriate pre‐hospital treatment less frequently required mechanical ventilation (p=0.039). Four deaths were detected during the follow‐up period, thus the case fatality rate was 8%. Only 31% of patients received treatment with intravenous phenytoin. Conclusion. The study results show that adequate and timely intervention could improve outcome of convulsive status epilepticus and decrease the need for mechanical ventilation. Mortality parameters were comparable to the results from other resource‐limited countries. More than one third of patients did not receive appropriate treatment due to unavailability of phenytoin.     

丙戊酸钠与地西泮治疗癫痫持续状态的系统评价

目的 系统评价丙戊酸钠与地西泮治疗癫痫持续状态(Status Epilepticus,SE)的有效性和安全性.方法 按照Cochrane系统评价的要求,制定纳入与排除标准.计算机检索Cochrane图书馆、Medline、Embase、中国生物医学文献数据库、中国学术期刊全文数据库等,收集国内外关于丙戊酸钠与地西泮治疗SE的随机或半随机对照试验.按系统评价的方法,由三名研究者独立进行质量评价和资料提取,采用Rev Man 5.1软件进行Meta分析.结果 共纳入9篇文献,包括400例SE患者.Meta分析结果显示:①丙戊酸钠组SE控制的有效率与地西泮组类似[RR=1.03,95％CI(0.91,1.16),P=0.65];②丙戊酸钠组SE复发率明显低于地西泮组[RR=0.41,95％ CI(0.22,0.79),P=0.007];③丙戊酸钠组药物的不良反应发生率明显低于地西泮组[RR =0.17,95％ CI(0.08,0.34),P＜0.0001].结论 丙戊酸钠可有效控制SE,药物不良反应少,癫痫复发率低,是治疗SE的理想药物.     

Non‐convulsive status epilepticus in the elderly

Altered mental state is a very common presentation in the elderly admitted to the emergency department. It has been determined that about 16% of patients aged 60 or older with confusion of unknown origin have non‐convulsive status epilepticus. The diagnosis of non‐convulsive status epilepticus is difficult in the elderly because possible aetiologies of confusion may present with the same clinical picture. Non‐convulsive status epilepticus in the elderly carries major morbidity and mortality, attributable primarily to aetiology, and treatment is complex, involving treatment of the aetiology and concomitant medical illnesses, whilst balancing the side effects and drug interactions of antiepileptic drugs.     

Good outcome is possible after months of refractory convulsive status epilepticus: lesson learned

Determining a prognosis for functional recovery after prolonged status epilepticus can be difficult. Prior case studies have shown that despite seizure control, functional outcomes are typically poor unless a reversible cause is identified. Herein we present a case of idiopathic status epilepticus with a surprisingly good outcome after a 125-day drug-induced coma.     

Orphenadrine induces secondarily generalized convulsive status epilepticus in rats

The current study was aimed to assess the convulsant potency of orphenadrine (ORPH) in rats together with a screen of different conventional antiepileptic drugs (AEDs) on their efficacy to suppress it. ORPH was administered intraperitoneally (i.p.) in doses of 50-80 mg/kg in male Wistar rats. The latency to first seizure, the number of seizure episodes and the duration of overt status epilepticus (SE) as well as the incidence of deaths was scored with simultaneous electroencephalographic (EEG) recordings. Subsequently, the effects of conventional AEDs on ORPH-evoked (80 mg/kg) seizure incidence were studied. ORPH dose-dependently induced seizures in increasing number of animals, reaching 100% at a dose of 80 mg/kg, associated with low mortality and no drug-related neurotoxicity. Epileptic attacks started as complex partial fits consisting of stereotyped behavior, limb movements, head shaking and myoclonic twitches of the body. Subsequently, an overt generalized convulsive SE appeared, lasting for approximately 2 h. Among conventional AEDs: carbamazepine, ethosuximide and phenytoin had no effect while valproate (p < 0.001), diazepam (p < 0.01), and phenobarbital (p < 0.001) dose-dependently suppressed seizure activity. All the above characteristics make the new model, a useful, easy to perform experimental tool to study the pathophysiology of SE as well as the effects of new AEDs.     

Valproate is an effective, well-tolerated drug for treatment of status epilepticus/serial attacks in adults

Objective – Status epilepticus (SE) and serial attacks (SA) represent neurological emergencies, and mortality rate for SE/SA is high, ranging from 3% to 25%, depending on cause and co-morbidity. As SE/SA become more refractory to treatment over time, rapid, appropriate treatment is extremely important. Here, we report a prospective registration of the effect of intravenous (IV) valproate (VPA) on SE/SA in a group of Norwegian patients.
Patients and methods – Forty-one adult patients (18 males, 23 females) were included in the study. All had previously been unsuccessfully treated with diazepam. For 19, the main SE/SA seizure type was generalized tonic-clonic, while 16 had complex-partial seizures. Six had seizures that were difficult to classify. The treatment protocol recommended 25 mg/kg of VPA loading dose over 30 min, followed by continuous infusion of 100 mg/h for at least 24 h, then per oral administration. If seizures persisted after the loading dose, general anaesthesia (barbiturates/propofol/midazolam) was administered.
Results – No serious side effects were reported. In 76% of the cases (31 of 41), SE/SA stopped and anaesthesia was not required. Of the patients treated within 3 h, only 5% needed anaesthesia, whereas of those treated after 3–24 h, 38% needed anaesthesia. Of those who waited for more than 24 h before treatment, 60% required anaesthesia. Furthermore, 60% of the patients who needed anaesthesia were given loading doses below 2100 mg.
Conclusions – VPA seems to be a safe, effective treatment of SE/SA, but efficacy is dependent on time lapse between symptoms and VPA treatment, and administration of a sufficiently high loading dose.     

EFNS guideline on the management of status epilepticus

The objective of the current paper was to review the literature and discuss the degree of evidence for various treatment strategies for status epilepticus (SE) in adults. We searched MEDLINE and EMBASE for relevant literature from 1966 to January 2005. Furthermore, the Cochrane Central Register of Controlled Trials (CENTRAL) was sought. Recommendations are based on this literature and on our judgement of the relevance of the references to the subject. Recommendations were reached by informative consensus approach. Where there was a lack of evidence but consensus was clear we have stated our opinion as good practice points. The preferred treatment pathway for generalised convulsive status epilepticus (GCSE) is intravenous (i.v.) administration of 4 mg of lorazepam or 10 mg of diazepam directly followed by 15-18 mg/kg of phenytoin or equivalent fosphenytoin. If seizures continue for more than 10 min after first injection another 4 mg of lorazepam or 10 mg of diazepam is recommended. Refractory GCSE is treated by anaesthetic doses of midazolam, propofol or barbiturates; the anaesthetics are titrated against an electroencephalogram burst suppression pattern for at least 24 h. The initial therapy of non-convulsive SE depends on the type and the cause. In most cases of absence SE, a small i.v. dose of lorazepam or diazepam will terminate the attack. Complex partial SE is initially treated such as GCSE, however, when refractory further non-anaesthetising substances should be given instead of anaesthetics. In subtle SE i.v. anaesthesia is required.