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]     

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.     

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.     

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%.     

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.     

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.     

Hidden in plain sight: Non‐convulsive status epilepticus—Recognition and management

Non‐convulsive status epilepticus (NCSE) is an electroclinical state associated with an altered level of consciousness but lacking convulsive motor activity. It can present in a multitude of ways, but classification based on the clinical presentation and electroencephalographic appearances assists in determining prognosis and planning treatment. The aggressiveness of treatment should be based on the likely prognosis and the underlying cause of the NCSE.     

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.     

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。     

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。     

EFNS guideline on the management of status epilepticus in adults

The objective of the current article 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 and in the current updated version all pertinent publications from January 2005 to January 2009. 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 4–8 mg lorazepam or 10 mg diazepam directly followed by 18 mg/kg phenytoin. If seizures continue more than 10 min after first injection, another 4 mg lorazepam or 10 mg diazepam is recommended. Refractory GCSE is treated by anaesthetic doses of barbiturates, midazolam or propofol; the anaesthetics are titrated against an electroencephalogram burst suppression pattern for at least 24 h. The initial therapy of non‐convulsive SE depends on type and cause. Complex partial SE is initially treated in the same manner as GCSE. However, if it turns out to be refractory, further non‐anaesthetising i.v. substances such levetiracetam, phenobarbital or valproic acid should be given instead of anaesthetics. In subtle SE, in most patients, i.v. anaesthesia is required.     

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.     

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.     

Treatment gap for convulsive status epilepticus in resource‐poor countries

The magnitude of the treatment gap (TG) for convulsive status epilepticus (CSE) in resource‐poor countries is unknown. Hospital‐based cohort studies from developing countries revealed that the management of CSE was usually suboptimal due to lack of advanced diagnostic and treatment facilities, significant delay in patient's presentation at hospital, and shortages of essential antiepileptic drugs (AEDs). However, there were no significant differences in the proportion of refractory status epilepticus, short‐term mortalities, and morbidities of CSE between the developed and the developing countries. Therefore, the presence of significant TG for CSE in developing countries is still an assumption without evidence. We conducted an expert survey in Asia for potential sources of TG. Experts from 16 Asian countries responded to the questionnaire. An injectable form of diazepam was available in all 16 countries even at the primary care level, but intravenous lorazepam was available only in four countries. Second‐line AEDs were widely available at tertiary care hospitals, but not at primary care hospitals. Lack of second‐line AEDs at primary care hospitals, significant delay in patient transportation to the hospital, shortages of intensive care unit facilities, and absence of trained physicians were important contributing factors to TG in Asia.     

Intravenous lacosamide as treatment option in post-stroke non convulsive status epilepticus in the elderly: A proof-of-concept,observational study

PurposeTo evaluate the efficacy and safety of intravenously administered lacosamide (iv LCM) in post-stroke non convulsive status epilepticus (NCSE) in elderly patients.MethodsWe enrolled 16 patients (7 M/9 F; 77 ± 7 years of age) with NCSE. iv LCM was used in all the patients as initial treatment (i.e. patients were directly started on LCM) at a loading dose of 400 mg over 30 min, followed by a mean maintenance dose of 400 mg per day. iv LCM was considered as effective in patients who experience no NCSE for 24 h following treatment, as evaluated by EEG recording and clinical observation.ResultsLCM was effective in treating NCSE in eight of the sixteen patients in whom epileptic activity disappeared (7/8) or was significantly reduced (1/8) within 45–60 min after administration. None of these patients relapsed in the following 24 h. No adverse events were observed. A partial anterior circulation syndrome (PACS) was present in 10 patients while a total anterior circulation syndrome (TACS) in six.ConclusionsThis pilot study suggests that LCM exhibits safety and efficacy profiles which make it an optimal candidate as a first-choice drug against post-stroke NCSE in elderly patients. A prospective comparative trial is needed to confirm these preliminary data.     

难治性癫痫持续状态患者的脑电图特征

目的 探究难治性癫痫持续状态(RSE)患者的脑电图(EEG)特征.方法 将60例全面惊厥性癫痫持续状态(GCSE)患者根据抗癫痫药物(AEDs)疗效分为RSE和非难治性癫痫持续状态(NRSE),比较两组患者EEG模式的差异.结果 所有患者中,与NRSE组比较,RSE组患者发作期EEG呈持续性放电比例更高,差异具有统计学意义(OR=5.44,95%CI=1.24~23.96,P=0.04).50例EGG呈间歇性演变的患者中,与NRSE组比较,RSE组患者发作间歇期EEG呈周期性放电与痫样放电的比例较高,差异有统计学意义(OR=29.75,4.12;95%CI=3.19~277.32,1.09~15.58;P<0.05);而RSE组患者发作后EEG为正常模式的比例较低,差异具有统计学意义(OR=0.11,95%CI=0.01~0.91,P=0.04).结论 GCSE患者如EEG出现持续性放电、周期性放电、发作间期痫样放电,应引起临床的高度重视,给以强化抗惊厥治疗.