Treatment Of Status Epilepticus Research Articles

Treatment of status epilepticus: Physiology, pharmacology, and future directions.

The review presents retrospective, present views and future perspectives on the treatment of status epilepticus (SE). First, presynaptic, postsynaptic, and extrasynaptic mechanisms underlying sustaining ongoing seizure activity are highlighted. Next, mechanism-based choices of antiseizure medications capable of promptly arresting SE are introduced. Finally, challenges associated with translating the advances in laboratory research in clinical practice are discussed.

Perspective: Vagal nerve stimulation in the treatment of new-onset refractory status epilepticus.

Resistance to drug therapy is a major hurdle in new-onset refractory status epilepticus (NORSE) treatment and there is urgent need to develop new treatment approaches. Non-drug approaches such as neuromodulation offer significant benefits and should be investigated as new adjunct treatment modalities. An important unanswered question is whether desynchronizing networks by vagal nerve stimulation (VNS) may improve seizure control in NORSE patients. We present a summary of published NORSE cases treated with VNS and our own data, discuss possible mechanisms of action, review VNS implantation timing, stimulation setting titration protocols and outcomes. Further, we propose avenues for future research. We advocate for consideration of VNS for NORSE both in early and late stages of the presentation and hypothesize a possible additional benefit from implantation in the acute phase of the disease. This should be pursued in the context of a clinical trial, harmonizing inclusion criteria, accuracy of documentation and treatment protocols. A study planned within our UK-wide NORSE-UK network will answer the question if VNS may confer benefits in aborting unremitting status epilepticus, modulate ictogenesis and reduce long-term chronic seizure burden.

Status epilepticus prognosis following levetiracetam administration: Analysis of loading doses.

Recommended loading doses of levetiracetam (LEV) for status epilepticus (SE) treatment have increased over time. However, this was not evidence-based, and the benefit of the increase remains unclear. The effect of different LEV loading doses on SE prognosis was explored. This is a retrospective analysis of an SE adult registry (January 2016-December 2021), including patients receiving LEV as a second-line SE treatment. Patients were stratified according to LEV loading doses (threshold 35 mg/kg). Main outcomes were global mortality, LEV use as last SE treatment, and return to baseline conditions at discharge, exploring LEV as a dichotomized or continuous dose. Among 202 patients, 44 received LEV at ≥35 mg/kg and 158 below it. Global mortality, adjusted for SE severity and potentially fatal aetiology, was more frequent in the high LEV dose group (27.2% vs. 17.1%, odds ratio 3.14, 95% confidence interval 1.23-8.06; p = 0.017), whilst LEV prescription as last treatment and return to baseline conditions were comparable. Considering continuous LEV dosages or mortality in ongoing SE, however, no outcome reached statistical significance. Lower LEV loading doses do not seem to correlate with worse clinical outcome, challenging current guidelines. Further studies, ideally prospective, are needed on this topic.

Eslicarbazepine acetate for the treatment of status epilepticus.

Due to the high mortality of patients with refractory status epilepticus (SE), new antiseizure medications (ASMs) are needed to improve long-term outcomes. In this study, we evaluated the efficacy and safety of eslicarbazepine acetate (ESL), a new sodium channel blocker, based on the data from a large epilepsy register. Data on the efficacy and safety of ESL for the treatment of refractory SE were gathered from the Mainz Epilepsy Registry (MAINZ-EPIREG). Logistic regression was applied to identify predictors of status interruption. In total, 64 patients with remote symptomatic refractory SE were treated with ESL. No cases of idiopathic generalized epilepsy were included. The average age was 61.4 ± 11.0 years. The median number of administered ASMs before the start of ESL was three. On average, 2 days had elapsed since the onset of SE before the administration of ESL. The initial dose of 800 mg/day was increased up to a maximum daily dose of 1600 mg in case of nonresponse. In 29 of 64 patients (45.3%), the SE could be interrupted within 48 h of ESL therapy. In patients with poststroke epilepsy, the control of SE was achieved in 62% of patients (15/23). The earlier initiation of ESL therapy was an independent predictor of control of SE. Hyponatraemia occurred in five patients (7.8%). Other side effects were not observed. Based on these data, ESL may be used as an adjunct therapy for the treatment of refractory SE. The best response was found in patients with poststroke epilepsy. In addition, early initiation of ESL therapy appears to result in better control of SE. Besides a few cases of hyponatraemia, no other adverse events were detected.

Delayed tezampanel and caramiphen treatment but not midazolam protects against long-term neuropathology after soman exposure.

Prolonged status epilepticus (SE) can cause brain damage; therefore, treatment must be administered promptly after seizure onset to limit SE duration and prevent neuropathology. Timely treatment of SE is not always feasible; this would be particularly true in a mass exposure to an SE-inducing agent such as a nerve agent. Therefore, the availability of anticonvulsant treatments that have neuroprotective efficacy even if administered with a delay after SE onset is an imperative. Here, we compared the long-term neuropathology resulting from acutely exposing 21-day-old male and female rats to the nerve agent soman, and treating them with midazolam (3 mg/kg) or co-administration of tezampanel (10 mg/kg) and caramiphen (50 mg/kg), at 1 h postexposure (~50 min after SE onset). Midazolam-treated rats had significant neuronal degeneration in limbic structures, mainly at one month postexposure, followed by neuronal loss in the basolateral amygdala and the CA1 hippocampal area. Neuronal loss resulted in significant amygdala and hippocampal atrophy, deteriorating from one to six months postexposure. Rats treated with tezampanel-caramiphen had no evidence of neuropathology, except for neuronal loss in the basolateral amygdala at the six-month timepoint. Anxiety was increased only in the midazolam-treated rats, at one, three, and six months postexposure. Spontaneous recurrent seizures appeared only in midazolam-treated rats, at three and six months postexposure in males and only at six months in females. These findings suggest that delayed treatment of nerve agent-induced SE with midazolam may result in long-lasting or permanent brain damage, while antiglutamatergic anticonvulsant treatment consisting of tezampanel and caramiphen may provide full neuroprotection.

Status epilepticus and benzodiazepine treatment: Use, underdosing and outcome - insights from a retrospective, multicentre registry

ObjectiveTo explore the reasons for and outcomes of non- or undertreatment with benzodiazepines (BZDs) in status epilepticus (SE). MethodsWe retrospectively analysed all SE patients from the urban area of Cologne over two years. Results328 SE patients were eligible, and only 72% were initially treated with BZDs. Of these, only 21.6% were treated sufficiently with BZDs according to current guidelines. SE patients not initially treated with BZDs were significantly older, had less often known epilepsy, had a prolonged arrival time to the emergency room, and presented more often with a non-generalised convulsive semiology. Regarding adequate dosages, patients with a generalised convulsive SE seemed to benefit from a sufficient BZD dosing with significantly shortened mean ventilation duration (37.1 to 208 h), decreased mean intensive care unit (1.7 to 5 days) and in-hospital stay (4.1 to 8.8 days). In contrary, aggressive BZD treatment in non-generalised convulsive SE resulted in a longer inpatient stay (9.2 to 5.8 days) and lower favourable outcome rates at discharge (16% to 63%). ConclusionsThe current SE treatment guidelines for first-line BZD therapy in SE were violated in most patients. Sufficient BZD dosing was beneficial in generalised convulsive SE, but not in other forms of SE. SE semiology might be crucial for treatment decisions with BZDs. Further treatment evidence especially in non-generalised convulsive SE is urgently needed.

In the fast lane: Receptor trafficking during status epilepticus.

Status epilepticus (SE) remains a significant cause of morbidity and mortality and often is refractory to standard first-line treatments. A rapid loss of synaptic inhibition and development of pharmacoresistance to benzodiazepines (BZDs) occurs early during SE, while NMDA and AMPA receptor antagonists remain effective treatments after BZDs have failed. Multimodal and subunit-selective receptor trafficking within minutes to an hour of SE involves GABA-A, NMDA, and AMPA receptors and contributes to shifts in the number and subunit composition of surface receptors with differential impacts on the physiology, pharmacology, and strength of GABAergic and glutamatergic currents at synaptic and extrasynaptic sites. During the first hour of SE, synaptic GABA-A receptors containing γ2 subunits move to the cell interior while extrasynaptic GABA-A receptors with δ subunits are preserved. Conversely, NMDA receptors containing N2B subunits are increased at synaptic and extrasynaptic sites, and homomeric GluA1 ("GluA2-lacking") calcium permeant AMPA receptor surface expression also is increased. Molecular mechanisms, largely driven by NMDA receptor or calcium permeant AMPA receptor activation early during circuit hyperactivity, regulate subunit-specific interactions with proteins involved with synaptic scaffolding, adaptin-AP2/clathrin-dependent endocytosis, endoplasmic reticulum (ER) retention, and endosomal recycling. Reviewed here is how SE-induced shifts in receptor subunit composition and surface representation increase the excitatory to inhibitory imbalance that sustains seizures and fuels excitotoxicity contributing to chronic sequela such as "spontaneous recurrent seizures" (SRS). A role for early multimodal therapy is suggested both for treatment of SE and for prevention of long-term comorbidities.

Nonconvulsive status epilepticus characteristics in glioma patients: a retrospective study

PurposeEpilepsy is a common complication of gliomas. The diagnosis of nonconvulsive status epilepticus (NCSE) is challenging because it causes impaired consciousness and mimics glioma progression. NCSE complication rate in the general brain tumor patient population is approximately 2%. However, there are no reports focusing on NCSE in glioma patient population. This study aimed to reveal the epidemiology and features of NCSE in glioma patients to enable appropriate diagnosis.MethodsWe enrolled 108 consecutive glioma patients (45 female, 63 male) who underwent their first surgery between April 2013 and May 2019 at our institution. We retrospectively investigated glioma patients diagnosed with tumor-related epilepsy (TRE) or NCSE to explore disease frequency of TRE/NCSE and patient background. NCSE treatment approaches and Karnofsky Performance Status Scale (KPS) changes following NCSE were surveyed. NCSE diagnosis was confirmed using the modified Salzburg Consensus Criteria (mSCC).ResultsSixty-one out of 108 glioma patients experienced TRE (56%), and five (4.6%) were diagnosed with NCSE (2 female, 3 male; mean age, 57 years old; WHO grade II 1, grade III 2, grade IV 2). All NCSE cases were controlled by stage 2 status epilepticus treatment as recommended in the Clinical Practice Guidelines for Epilepsy by the Japan Epilepsy Society. The KPS score significantly decreased after NCSE.ConclusionHigher prevalence of NCSE in glioma patients was observed. The KPS score significantly decreased after NCSE. Actively taking electroencephalograms analyzed by mSCC may facilitate accurate NCSE diagnosis and improve the activities of daily living in glioma patients.

Ketamine as advanced second-line treatment in benzodiazepine-refractory convulsive status epilepticus in children.

Status epilepticus (SE) is one of the most common neurological emergencies in children. To date, there is no definitive evidence to guide treatment of SE refractory to benzodiazepines. The main objectives of treatment protocols are to expedite therapeutic decisions and to use fast- and short-acting medications without significant adverse effects. Protocols differ among institutions, and most frequently valproate, phenytoin, and levetiracetam are used as second-line treatment. After failure of first- and second-line medications, admission to the intensive care unit and continuous infusion of anesthetics are usually indicated. Ketamine is a noncompetitive N-methyl-D-aspartate receptor antagonist that has been safely used for the treatment of refractory SE in adults and children. In animal models of SE, ketamine demonstrated antiepileptic and neuroprotective properties and synergistic effects with other antiseizure medications. We reviewed the literature to demonstrate the potential role of ketamine as an advanced second-line agent in the treatment of SE. Pharmacological targets, pathophysiology of SE, and the receptor trafficking hypothesis are reviewed and presented. The pharmacology of ketamine is outlined with related properties, advantages, and side effects. We summarize the most recent and relevant publications on experimental and clinical studies on ketamine in SE. Key expert opinion is also reported. Considering the current knowledge on SE pathophysiology, early sequential polytherapy should include ketamine for its wide range of positive assets. Future research and clinical trials on SE pharmacotherapy should focus on the role of ketamine as second-line medication.

Inflammation as Treatment Target for Status Epilepticus.

Status epilepticus (SE) is a serious neurological disease that manifests as prolonged seizures that last more than 5 minutes and between such episodes, patients do not regain consciousness. It can result in cognitive defects, brain damage, or even death. It is commonly known that one of the causes can be an inflammatory process, but here we will focus on inflammation as a result of new onset refractory status epilepticus and, related to this, new promising forms of SE treatment. Particular emphasis has been focused on new-onset refractory status epilepticus (NORSE). Based on public research databases, drugs with anti-inflammatory activity - commonly used in different spheres of medicine - have been reviewed as potentially treating status epilepticus. There is seizable clinical research suggesting that drugs that decrease inflammatory processes might be effective in terminating status epilepticus. There is growing evidence showing that adding anti-inflammatory drugs to basic antiepileptic treatment enhances the efficiency of the therapeutic process, with special potential in NORSE cases.

Myoclonus in comatose patients with electrographic status epilepticus after cardiac arrest: Corresponding EEG patterns, effects of treatment and outcomes

ObjectiveTo clarify the significance of any form of myoclonus in comatose patients after cardiac arrest with rhythmic and periodic EEG patterns (RPPs) by analyzing associations between myoclonus and EEG pattern, response to anti-seizure medication and neurological outcome. DesignPost hoc analysis of the prospective randomized Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation (TELSTAR) trial. SettingEleven ICUs in the Netherlands and Belgium. PatientsOne hundred and fifty-seven adult comatose post-cardiac arrest patients with RPPs on continuous EEG monitoring. InterventionsAnti-seizure medication vs no anti-seizure medication in addition to standard care. Measurements and Main ResultsOf 157 patients, 98 (63%) had myoclonus at inclusion. Myoclonus was not associated with one specific RPP type. However, myoclonus was associated with a smaller probability of a continuous EEG background pattern (48% in patients with vs 75% without myoclonus, odds ratio (OR) 0.31; 95% confidence interval (CI) 0.16–0.64) and earlier onset of RPPs (24% vs 9% within 24 hours after cardiac arrest, OR 3.86;95% CI 1.64–9.11). Myoclonus was associated with poor outcome at three months, but not invariably so (poor neurological outcome in 96% vs 82%, p = 0.004). Anti-seizure medication did not improve outcome, regardless of myoclonus presence (6% good outcome in the intervention group vs 2% in the control group, OR 0.33; 95% CI 0.03–3.32). ConclusionsMyoclonus in comatose patients after cardiac arrest with RPPs is associated with poor outcome and discontinuous or suppressed EEG. However, presence of myoclonus does not interact with the effects of anti-seizure medication and cannot predict a poor outcome without false positives.

Propofol versus sodium thiopentone for the treatment of status epilepticus and refractory status epilepticus in dogs

ABSTRACT Aims To compare the effect on mortality and length of hospital stay of propofol with that of sodium thiopentone for the management of dogs with status epilepticus (SE) and refractory status epilepticus (RSE). Methods In this cohort study, medical records of a veterinary referral clinic in Argentina were retrospectively searched for dogs that were hospitalised and required induction of therapeutic coma (TC) with either propofol or sodium thiopentone for the management of SE or RSE of any cause. A logistic regression model was performed to evaluate the association between the type of anaesthetic used and in-hospital mortality adjusting for the type of epilepsy (idiopathic, structural, or reactive). Kaplan-Meier estimated survival curves for the length of hospital stay by the type of anaesthetic drug were compared using the log-rank test (deaths were considered censored events). Cox proportional hazards regression was used to estimate hazard ratios for time to hospital discharge, unadjusted and adjusted for type of epilepsy. Results A total of 24 dogs with SE were included in the study: eight treated with propofol and 16 treated with sodium thiopentone. Four dogs treated with propofol (proportion = 0.50; 95% CI = 0.15–0.84), and eight treated with sodium thiopentone (proportion = 0.50; 95% CI = 0.50–0.74) died during hospitalisation. The median hospitalisation time was 43 (IQR 24–56) hours for dogs that were treated with propofol and 72 (IQR 64–96) hours for dogs that were treated with sodium thiopentone. There was no evidence of a difference in the median duration of TC in dogs treated with propofol (12 (IQR 8–24) hours) or with sodium thiopentone (12 (IQR 7.5–20) hours; p = 0.946). In the logistic regression model, no evidence of association between the anaesthetic protocol for the management of RSE and in-hospital mortality, adjusted for the type of epilepsy, was found (OR 1.09 (95% CI = 0.17–6.87); p = 0.925). Cox regression analysis revealed a difference in the time to hospital discharge, adjusted by the type of epilepsy, between treatment groups (HR = 0.05 (95% CI = 0.01–0.54); p = 0.013). Conclusions and clinical relevance The time spent in hospital before discharge was longer in dogs with RSE treated with sodium thiopentone compared to those treated with propofol. However, as the sample size was very small, the results obtained in the present study should be analysed with caution. Further studies including a greater number of dogs are required.

Preclinical pharmacokinetics and tolerability of a novel meglumine-based parenteral solution of topiramate and topiramate combinations for treatment of status epilepticus.

For an antiseizure medication (ASM) to be effective in status epilepticus (SE), the drug should be administered intravenously (i.v.) to provide quick access to the brain. However, poor aqueous solubility is a major problem in the development of parenteral drug solutions. Given its multiple mechanisms of action, topiramate (TPM) is a promising candidate for the treatment of established or refractory SE, as supported by clinical studies using nasogastric tube TPM administration. However, TPM is not clinically available as a solution for i.v. administration, which hampers its use in the treatment of SE. Here, we describe a novel easy-to-use and easy-to-prepare i.v. TPM formulation using the U.S. Food and Drug Administration (FDA)-approved excipient meglumine. During formulation development, we compared the solubility of TPM in bi-distilled water with vs without a range of meglumine concentrations. Furthermore, the solubility of combinations of TPM and levetiracetam and TPM, levetiracetam, and atorvastatin in aqueous meglumine concentrations was determined. Subsequently, the pharmacokinetics and tolerability of meglumine-based solutions of TPM and TPM combinations were evaluated in rats, including animals following fluid percussion injury or pilocarpine-induced SE. The amino sugar meglumine markedly enhances the aqueous solubility of TPM. A comparison with data on dissolving TPM using sulfobutylether-β-cyclodextrin (Captisol) demonstrates that meglumine is much more effective for dissolving TPM. Furthermore, meglumine can be used to prepare drug cocktails where TPM is co-administered with another ASM for SE treatment. The tolerability studies of the meglumine-based TPM solution and meglumine-based TPM combinations in normal rats and the rat fluid percussion injury and pilocarpine-induced SE models demonstrate excellent tolerability of the novel drug solutions. Preclinical studies on antiseizure efficacy in the SE model are underway. In conclusion, the novel meglumine-based solution of TPM presented here may be well suited for clinical development.

A Commentary on Electrographic Seizure Management and Clinical Outcomes in Critically Ill Children

Continuous EEG (cEEG) monitoring is the gold standard for detecting electrographic seizures in critically ill children and the current consensus-based guidelines recommend urgent cEEG to detect electrographic seizures that would otherwise be undetected. The detection of seizures usually leads to the use of antiseizure medications, even though current evidence that treatment leads to important improvements in outcomes is limited, raising the question of whether the current strategies need re-evaluation. There is emerging evidence indicating that the presence of electrographic seizures is not associated with unfavorable neurological outcome, and thus treatment is unlikely to alter the outcomes in these children. However, a high seizure burden and electrographic status epilepticus is associated with unfavorable outcome and the treatment of status epilepticus is currently warranted. Ultimately, outcomes are more likely a function of etiology than of a direct effect of the seizures themselves. We suggest re-examining our current consensus toward aggressive treatment to abolish all electrographic seizures and recommend a tailored approach where therapeutic interventions are indicated when seizure burden breaches above a critical threshold that may be associated with adverse outcomes. Future studies should explicitly evaluate whether there is a positive impact of treating electrographic seizures or electrographic status epilepticus in order to justify continuing current approaches.

Insight into Drug Resistance in Status Epilepticus: Evidence from Animal Models.

Status epilepticus (SE), a condition with abnormally prolonged seizures, is a severe type of epilepsy. At present, SE is not well controlled by clinical treatments. Antiepileptic drugs (AEDs) are the main therapeutic approaches, but they are effective for SE only with a narrow intervening window, and they easily induce resistance. Thus, in this review, we provide an updated summary for an insight into drug-resistant SE, hoping to add to the understanding of the mechanism of refractory SE and the development of active compounds. Firstly, we briefly outline the limitations of current drug treatments for SE by summarizing the extensive experimental literature and clinical data through a search of the PubMed database, and then summarize the common animal models of refractory SE with their advantages and disadvantages. Notably, we also briefly review some of the hypotheses about drug resistance in SE that are well accepted in the field, and furthermore, put forward future perspectives for follow-up research on SE.

Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial

BackgroundGeneralised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20–40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE.MethodsThis was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90.ResultsA total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89–1.19); p = 0.58]. There were no between-group differences for secondary outcomes.ConclusionsVPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15.Trial registration No. NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.

Management of convulsive status epilepticus: recent updates.

Convulsive status epilepticus (SE) is a medical emergency associated with high morbidity and mortality. Recently, clinical trials and meta-analyses investigating medical treatment of SE have been published. Benzodiazepine is well known as the first-line treatment for SE. Recent evidence suggests the equivalence of intravenous fosphenytoin, valproate, and levetiracetam for treatment of established SE. There is lack of evidence regarding treatment for refractory SE. Intravenous midazolam is commonly used, and recent evidence supports the use of ketamine. Additional studies are needed to improve the management of convulsive SE.

Synergistic effects of applying static magnetic fields and diazepam to improve EEG abnormalities in the pilocarpine epilepsy rat model

The lithium-pilocarpine rat model is a well-known model of temporal epilepsy. Recently we found that transcranial static magnetic stimulation (tSMS) delay and reduce the signs of EEG in this model. We aim to test the effect of combining the therapeutic action of tSMS and diazepam, a drug used to treat status epilepticus. We induce epilepsy in 12 Sprague–Dawley rats. Animals were classified as “magnet” when a magnetic neodymium cylinder was placed over the skull or “control” when a stainless-steel replica was used. Diazepam was injected 60-min after the second doses of pilocarpine injection. We found a reduction in the number of spikes/minute for magnet condition compared with sham condition, reaching significance at 60 min after diazepam injection. The Root-Mean-Square shown a significant reduction in magnet animals compared with those receiving diazepam (Tukey’s-test 30 and 60 min after diazepam injection, p < 0.01; 40 and 50 min after diazepam injection, p < 0.05). Furthermore, the power spectrum analysis shown a reduction in delta, theta, alpha and beta bands, on the diazepam + magnet animals compared to the diazepam + sham group. Analysis of high-frequency oscillations revealed an increased in the ripples due to pilocarpine being reduced by diazepam. Our results demonstrate that application of tSMS previously to diazepam potentiates the effect of the drug by reducing the electroencephalographic pattern associated with epileptiform discharges. We suggest a new synergistic cooperation between pharmacology and neuromodulation as a future treatment for epilepsy.

Status Epilepticus: Convulsive and Nonconvulsive

Status epilepticus(SE)is common, particularly among neurological emergency physicians. SE includes convulsive SE(CSE)and nonconvulsive SE(NCSE). Recently, the number of elderly patients with status epilepticus has increased. Most patients were diagnosed with NCSE. Prolonged SE often impairs neuronal function and is sometimes life threatening. Prompt diagnosis of SE and treatment initiation are essential for good outcomes. However, an accurate diagnosis of NCSE is difficult because the clinical symptoms of NCSE may vary, and electroencephalography may show various characteristics. Recent advances in the diagnosis and treatment of SE have been reported, particularly with regard to electroencephalography(EEG)and newly available drugs.

Comparison of levetiracetam as second-line drug with fosphenytoin in convulsive status epilepticus among children

Background: Status epilepticus (SE) is the most common neurologic emergency in the pediatric age group often serious and life-threatening. Although newer drugs were used, morbidity and mortality are still high. This study was done to compare the efficacy of levetiracetam with the existing second-line drug fosphenytoin in the treatment of SE. Subjects and Methods: This was a prospective, randomized parallel group trial from Pediatric Intensive Care Unit of a Tertiary Care Institute. One hundred children were recruited according to the inclusion and exclusion criteria, 50 in fosphenytoin group and 50 in levetiracetam group. Two groups were compared with respect to clinical cessation of seizures, recurrence, adverse event, and outcome. Results: Male-to-female ratio was 1.45:1. Seizure were controlled in 37 (74%) in fosphenytoin group and 28 (56%) in levetiracetam group) (P = 0.059). The mean time for cessation of seizures was 11.16 ± 3.58 min in fosphenytoin group as compared to was 12.78 ± 3.07 min in levetiracetam group (P = 0.059) The seizure recurrence in first 24 h (18 [36%] vs. 12 [24%]) (P = 0.643) and development of shock (14 [28%] vs. 11 [22%]) (P = 0.488) was comparable in two groups. Overall mortality was 10 (20%) in fosphenytoin group as compared to 7 (14%) levetiracetam group (P = 0.281). Conclusions: Efficacy of intravenous levetiracetam is comparable to fosphenytoin as a second-line medication in the management of convulsive SE in children.