The aetiology of convulsive status epilepticus: A study of 258 cases in Western China

PurposeTo investigate the characteristics of the aetiologies of convulsive status epilepticus (CSE) in Western China and to identify the relationships of these aetiologies with the prognoses.MethodsConsecutive registration and prospective observation of 258 cases of CSE in the Sichuan Epilepsy Center were performed from 1996 to 2010 to study the aetiology of CSE. The relationships of the aetiologies with the demographics, outcomes and complications of CSE were analysed using a logistic regression model.ResultsThe mean age was 37.6 ± 20.21 years. The majority of the CSE (62.4%) cases were acute symptomatic cases, and the primary cause was central nervous system (CNS) infection (33.7%). Histories of epilepsy were present in 51.9% of the patients. Pre-existing epilepsy occurred due to discontinuation or reduction of antiepileptic drugs (AEDs) in 31.3% of the CSE patients. Anoxia/poisoning (p < 0.05, OR 8.0, 95% CI 1.34–47.77) was an independent predictor of mortality. CNS infections (p < 0.001, OR 8.99, 95% CI 3.52–22.92), cerebrovascular diseases (p =0.001, OR 6.75, 95% CI 2.11–21.61) and anoxia/poisoning (p < 0.01, OR 7.64, 95% CI 1.93–30.21) were the major risk factors for complications associated with CSE.Conclusions(1) Compared to developed countries, CNS infections seemed to be more likely to be the cause of CSE in developing countries. (2) Noncompliance with AEDs among patients with epilepsy was a prominent and avoidable trigger of CSE.     

Prognostic factors of status epilepticus in adults

Aim. Status epilepticus (SE) can lead to sequelae or even death. Identifying characteristics associated with poor outcome is crucial in guiding patient treatment. Based on our retrospective patient cohorts, potential prognostic factors were analysed. Methods. Patients consecutively treated for refractory convulsive status epilepticus (CSE) between 2001 and 2010 and non‐convulsive status epilepticus (NCSE) between 2004 and 2009 were studied. Outcome was compared to prognostic variables. Index SE episodes were used for the statistical analyses. Crosstabs and independent samples t‐test were applied. Due to sample size, logistic regression was performed for the combined groups. Results. In total, 50% (9/18) of index refractory CSE and 42% (16/38) of index NCSE episodes led to sequelae. Refractory CSE requiring narcosis for >20 hours was associated with poor outcome (p=0.05). De novo presentation (p=0.0001), long‐lasting SE (>2 hours) (p=0.014), age >65 years (p=0.002), and refractory SE (p=0.047) were predictors of poor outcome following NCSE. Based on logistic regression for combined refractory CSE and NCSE, de novo presentation was identified as the strongest predictor of sequelae. Conclusions. Older age and de novo SE are predictors of sequelae following NCSE. Prolonged SE is a risk factor for poor outcome, both for refractory CSE and NCSE. Aggressive initial treatment to terminate seizures during the early phase is therefore essential.     

脑炎后癫痫持续状态进展为难治性癫痫持续状态及超级难治性癫痫持续状态的早期预测因素

目的 探讨脑炎后癫痫持续状态(SE)进展为难治性SE(RSE)及超级RSE(SRSE)的早期预测因素.方法 根据疾病进展情况将89例脑炎后SE患者分为非RSE组、RSE组及SRSE组.比较各组临床资料.结果 非RSE组、RSE组及SRSE组年龄、SE严重程度评分量表(STESS)评分、基于流行病学SE病死率评分(EMS...     

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.     

Aborted and refractory status epilepticus in children: a comparative analysis

PURPOSE: The aims of this retrospective study were: (1) to compare the demographics, clinical characteristics, etiology, and EEG findings of status epilepticus aborted with medication (ASE) and refractory status epilepticus (RSE), (2) to describe the treatment response of status epilepticus (SE), and (3) to determine predictors of long-term outcome in children with SE. METHODS: Medical records and EEG lab logs with ICD-9 diagnostic codes related to SE were reviewed. Patients younger than 18 years of age, hospitalized in 1994-2004 at the Mayo Clinic, Rochester, were included. RESULTS: One hundred fifty-four children had SE; 94 (61%) had ASE, and 60 (39.0%) had RSE. Family history of seizures, higher seizure frequency score, higher number of maintenance antiepileptic drugs (AEDs), nonconvulsive SE, and focal or electrographic seizures on initial EEG were associated with RSE by univariate analysis. In-hospital mortality was significantly higher in RSE (13.3%) than in ASE (2.1%). In the long term, survivors with RSE developed more new neurological deficits (p < 0.001) and more epilepsy (p < 0.004) than children with ASE. Children treated in a more aggressive fashion appeared to have better treatment responses (p < 0.001) and outcomes (p = 0.03). Predictors of poor outcome were long seizure duration (p < 0.001), acute symptomatic etiology (p = 0.04), nonconvulsive SE (NCSE) (p = 0.01), and age at admission <5 years (p = 0.05). DISCUSSION: Several patient and clinical characteristics are associated with development of RSE and poor outcome. Prospective, randomized trials that assess different treatment protocols in children with SE are needed to determine the optimal sequence and timing of medications.     

The role of AMPA receptors and their antagonists in status epilepticus

Status epilepticus (SE) is typically defined as a prolonged self‐sustaining seizure or repeated seizures showing an incomplete recovery between them. SE represents a medical emergency often associated with significant disability, morbidity, and mortality. Despite the clinical impact, the mechanisms underlying the transition from self‐limited seizures to protracted, medically refractory seizures are not completely understood. About 40% of patients in established SE are refractory to antiepileptic drugs (first‐line treatment); therefore, there is a need for more efficacious drugs. In this review, we focused on the current knowledge about the involvement of alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors during SE, the preclinical efficacy of its antagonists, and the currently published clinical studies involving drugs with this mechanism of action. We carried out an extensive literature search to recognize experimental and clinical articles both on AMPA receptors and AMPA antagonists and SE. Recently, the role of AMPA receptors during and after SE has become clearer, and it is now widely accepted that early changes occur in the initial stages and probably contribute both to the maintenance of SE and to its refractoriness to treatment. The therapeutic potential of AMPA receptor inhibition has been sustained by studies in which AMPA receptor antagonists have been shown to terminate seizures in several SE animal models. To date, promising, but limited, data in humans support the use of AMPA receptor antagonists in patients with SE. AMPA receptor antagonists could become a new therapeutic option in patients with established SE when the first trials with second‐line agents have failed or probably even better after failure of benzodiazepines as a second‐line option.     

Periodic febrile confusion as a presentation of complex partial status epilepticus

A 75-year-old woman was evaluated for recurrent episodes of fever she experienced periodically every 4-5 weeks over the last 12 months, lasting 2-3 days each. The fever was associated with continuous complex partial seizures, paralleled the seizure activity and returned to normal after the seizures had ceased. The ictal EEG recordings showed rhythmic bitemporal 3-4 Hz activity; the interictal recordings showed a spike and wave discharge over the right fronto-temporal region. Carbamazepine effectively controlled both the seizures and the fever; the latter was presumed to be an inherent manifestation of the seizure activity.     

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.     

Status epilepticus and alcohol abuse: An analysis of 82 status epilepticus admissions

In 1979-80, 82 cases of grand mal status epilepticus (71 patients, 39 male and 32 female) were admitted to the Casualty Department of Meilahti University Hospital in Helsinki, Finland. The cause of the underlying epilepsy was symptomatic in 43 cases (52.4%) and idiopathic in 19 cases (23.2%). In 6 cases (7.3%), there was a history of alcohol withdrawal seizures, and in 14 cases (17.1%) there was no earlier history of convulsions. Status epilepticus was associated with an acute or progressive cerebral disorder in 14 episodes. These comprised 6 bouts of status with brain tumour, 4 with acute stroke and 4 with brain injury. Alcohol abuse preceded the status in 29 episodes (35.4%), 23 of which occurred in men (53.5% of the male cases). Excessive use of alcohol was the only obvious precipitating factor for status in 16 cases, and in 6 cases the status presented as a prolonged alcohol withdrawal seizure. A change or irregularity of anticonvulsive drug therapy could be documented in 14 cases and an acute infection outside the central nervous system in 7 cases. Intravenous diazepam, used as the only therapy for status epilepticus, was effective in 58 of 78 episodes. In 7 cases of prolonged status, a thiopental sodium anaesthesia proved effective. The total mortality was 4.2%, including 2 deaths from concomitant extracerebral disorders and one late death from brain metastasis.     

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%.     

超难治性癫痫持续状态病例分析及文献复习

目的：探讨超难治性癫痫持续状态的诊断、治疗和预后。方法回顾分析了2009年10月收治的1例癫痫持续状态的患者,先后静脉给予地西泮、氯硝西泮和咪达唑仑等常规药物治疗,其癫痫发作才逐渐得到控制。检索复习癫痫持续状态的相关文献。结果目前国内外未见大宗样本报道。诊断尚存在争议,但治疗原则较为一致,采用渐进性贯序疗法。结论癫痫持续状态多由于严重的脑损伤导致,但某些患者没有明确病因也可能出现难治性癫痫持续状态。治疗多采用阶梯式治疗方法,预后较差。     

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.     

Non-convulsive status epilepticus during lithium treatment at therapeutic doses

Abstract The purpose of this study is to report the case of a patient with normal lithium serum levels who developed non-convulsive status epilepticus (NCSE). A 52-year-old woman with bipolar disorder type I (DSM-IV) treated with lithium experienced bradypsychism and episodes of confusion and spatial disorientation without signs or symptoms of lithium intoxication. Lithium serum levels were in the normal range. A brain MR scan was negative; the electroencephalogram (EEG) revealed a background 3–4 Hz delta rhythm and diffuse spike discharges. Prompt EEG and clinical response to intravenous diazepam therapy was observed. Based on these findings, a diagnosis of NCSE was made and lithium therapy was withdrawn, resulting in symptom remission and EEG normalization. The treatment was resumed after two months to test the correlation between NCSE and lithium therapy. Resumption of therapeutic range lithium induced the same clinical symptoms and EEG patterns; the therapy was thus definitively discontinued. The present data—signalling the temporal correlation of clinical and EEG changes with drug administration and withdrawal—suggest that even in the therapeutic range lithium treatment may trigger NCSE onset in predisposed subjects.     

Regulatory aspects of status epilepticus

In this article, we consider four aspects of the regulatory standing of status epilepticus and the difficulties these raise in relation to trials and licensing. These formed the basis of a discussion held at the 6th London?Innsbruck Colloquium on Status Epilepticus, held on April 6, 2017.     

Treatment of refractory complex-partial status epilepticus with propofol: case report

PURPOSE: We report a case of a 65-year-old woman who had a subarachnoid and intraventricular hemorrhage secondary to rupture of an anterior communicating artery aneurysm and developed nonconvulsive status epilepticus of the complex-partial type, refractory to phenytoin (PHT), phenobarbital (PB), valproate (VPA), and lorazepam (LZP). METHODS: Three weeks after diagnosis of nonconvulsive status epilepticus, general anesthesia was induced with propofol and titrated to burst suppression on the electroencephalogram (EEG). RESULTS: During propofol infusion, the serum VPA level declined markedly, and despite >3 g daily doses, did not return to the therapeutic range, until several days after propofol was discontinued. Continuous propofol infusion was stopped after 7 days, and the patient recovered consciousness. Despite further complications, she gradually regained normal function and was discharged home 4 months after surgery. CONCLUSIONS: This is the first case of nonconvulsive status epilepticus successfully treated with propofol.     

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.     

成人顽固性癫痫持续状态的临床分析

目的 探讨成人顽固性癫痫持续状态（RSE）的危险因素、临床特点、治疗及预后。方法 54例癫痫持续状态（SE）．58次发作事件，分为RSE组和非顽固性癫痫持续状态（NRSE）组．对病因、诱因、临床表现、辅助检查、预后等进行对比分析。结果 RSE占SE的43．1％，病毒性脑炎是RSE最主要的病因（P=0．001），相反，既往癫痫发作在NRSE中更常见（P=0．000），相应地药物治疗的改变引起的SE多为NRSE（P=-0．003）；RSE组GCS评分及预后较NRSE组均差（均P=0．000）。结论 SE经一、二线抗癫痫药治疗后仍有很大一部分难以控制，病毒性脑炎是导致RSE的一个重要病因，其预后较差．目前对RSE的治疗还缺乏十分合理的方案。