Levetiracetam‐induced thrombocytopenia in a patient with status epilepticus

Levetiracetam has broad‐spectrum activity in epilepsy. In contrast to phenytoin, levetiracetam has an ideal pharmacokinetic profile without any severe haemodynamic side effects and therefore intravenous loading of levetiracetam is commonly used in adult patients with status epilepticus, especially those who have medical problems. However, levetiracetam‐induced serious adverse effects, such as thrombocytopenia and pancytopenia, have been reported in the literature. Here, we describe a case of status epilepticus after cardiac arrest treated with levetiracetam in which severe thrombocytopenia developed and was successfully managed by discontinuation of levetiracetam. Our report aims to increase awareness of this rare cause of thrombocytopenia among clinicians and provide a review of the literature.     

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.     

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.     

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 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.     

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.     

Time-dependent decrease in the effectiveness of antiepileptic drugs during the course of self-sustaining status epilepticus

An animal model of self-sustaining status epilepticus (SSSE) induced in rats by brief intermittent perforant path stimulation (PPS) was examined with regard to the effects of two conventional antiepileptic drugs, diazepam and phenytoin. Thirty or sixty minutes PPS induced SSSE characterized by continuous behavioral and electrographic seizures lasting for hours. Both diazepam (10 mg/kg i.v.) and phenytoin (50 mg/kg i.v.) prevented the establishment of SSSE when administered 10 min prior to PPS. The injection of diazepam to seizing animals, 10 min after the end of 30 min PPS, was significantly less effective than pretreatment in attenuating SSSE. Administration of diazepam after 60 min PPS was characterized by a further decrease of its efficacy. Phenytoin was effective in aborting SSSE when injected 10 min after 30 min PPS. However, its efficacy was vastly decreased if injected 40 min after 30 min PPS, or 10 min after 60 min PPS. It is concluded that antiepileptic drugs, while highly effective in blocking the induction of SSSE, failed to affect its maintenance. SSSE induced by PPS is an advantageous animal model of refractory status epilepticus, which may be used in preclinical studies of novel antiepileptic drugs.     

醒脑静注射液辅助静脉用丙戊酸钠治疗癫(癎)持续状态效果观察

目的:探讨醒脑静注射液配合丙戊酸钠治疗癫(癎)持续状态的疗效.方法:选择我院2013年8月～2016年1月收治的癫(癎)持续状态患者74例为研究对象,以随机数字表法分组,观察组37例,对照组37例,对照组单用丙戊酸钠治疗,观察组采取醒脑静注射液辅助静脉用丙戊酸钠治疗,对两组患者疗效进行观察.结果:观察组总有效率为92％,对照组为81％,两组比较差异有统计学意义(P＜0.05);观察组起效时间及完全控制时间均较对照组短,两组比较差异有统计学意义(P＜0.05);观察组复发率与不良反应发生率分别为8％和11％,对照组分别为11％和21％,两组比较差异均有统计学意义(P＜0.05).结论:醒脑静注射液辅助静脉用丙戊酸钠治疗癫(癎)持续状态效果显著,此两药具有相互协同作用,可快速起效,安全性高,利于远期预后.     

Convulsive status epilepticus: clinical profile in a developing country

PURPOSE: In developing countries optimal care of status epilepticus (SE) is associated with major barriers, particularly transportation. METHODS: A prospective study of SE was performed between 1994 and 1996 to determine the clinical profile, response to treatment and outcome, Glasgow Outcome Scale (GOS). RESULTS: Of the 85 patients admitted, the mean age was 33 years (8-75 years), 16% <16 years of age. The mean duration of SE before admission was 18.02 h (1-72 h). Only 23 (28%) patients, all locals, presented within <3 h of onset. Etiology included acute symptomatic (54%), remote symptomatic (7%), cryptogenic (19%), and established epilepsy (20%). Central nervous system infections accounted for 24 (28%) of the etiologies. Seventy-five (88%) patients responded to first-line drugs and 10 (12%) required second-line drugs. The mean duration of SE was significantly long in nonresponders (Mean +/- SD: 32.6 +/- 20.11 vs. 15.2 +/- 18.32, p < 0.006). Duration (p < 0.01; OR 1.04, 95% CI 1.01-1.07) and acute symptomatic etiology (p < 0.038; OR 10.38, 95% CI 1.13-95.09) were the independent predictors of no-response to first-line drugs. Of the nine deaths (10.5%), eight were in acute symptomatic group. Predictors of mortality included female sex (p < 0.017, OR 13.41, 95% CI 1.59-115.38) and lack of response to first-line drugs (p < 0.0001, OR 230.27, 95% CI 8.78-6037.19). Longer duration was associated with poor GOS 1-4 (p = 0.001). Of the 37 patients with <6 h, 81% had GOC5 outcome. CONCLUSION: This study suggests that longer duration of SE and acute symptomatic etiology are independent predictors of lack of response to first-line drugs. Failure to respond to first-line drugs and duration predict the outcome.     

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.     

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.     

Anticonvulsant effect of intraventricular antiepileptic drugs. Experimental study

Abstract

The effect of intraventricular administration of antiepileptic drugs on an experimental model of epileptic seizures in rats has been investigated. Animals were tested in the electroshock test measuring the time duration of the tonic phase of the convulsion. Drugs tested were sodium phenobarbital (200-500-1000 μg), phenytoin (50-100-200-500 μg), midazolam (100-200-500 μg) and sodium valproate (500-1000-2000 μg), delivered via a catheter stereotactically placed into the lateral ventricle. Control animals were tested with saline. All antiepileptic drugs showed different degrees of reduction in the duration of the tonic phase before reaching doses that produced neurological symptoms. Our results demonstrate the feasibility to control experimental seizures by means of intraventricular injection of antiepileptic drugs. [Neurol Res 1995; 17: 190-192]     

Efficacy and safety of perampanel oral loading in postanoxic super‐refractory status epilepticus: A pilot study

Refractory nonconvulsive status epilepticus (NCSE) occurs in 10%‐30% of patients following resuscitation after cardiac arrest. Both the optimal treatment and prognosis of postanoxic status epilepticus remain uncertain. We analyzed acute electroencephalographic changes, neurological outcome at 3 months, and adverse effects in consecutive postanoxic patients with super‐refractory NCSE treated with add‐on oral loading of perampanel. Eight postanoxic patients with super‐refractory NCSE were treated with perampanel (dose range = 6‐12 mg). All patients had continuous electroencephalographic monitoring showing definite generalized NCSE and favorable multimodal prognostic indicators (presence of brainstem reflexes, presence of bilateral N20 responses, absence of periodic discharges/generalized epileptic periodic discharges). In six patients (75%), status epilepticus resolved within 72 hours after administration of perampanel, without changing the comedication. Neurological outcomes at 3 months were return to normal or minimal disability in four patients (50%). A mild cholestatic liver injury, which required no specific treatment, was observed in five patients (62.5%). Perampanel 6‐12 mg oral loading appeared to be an effective option in selected patients with postanoxic super‐refractory NCSE with good prognostic indicators. In this patient population, our safety data indicate a risk of cholestasis.