This study was undertaken to describe a cohort of pediatric patients with status epilepticus (SE) in Italy over the past decade, focusing on the variability of treatment protocols among centers, adherence to guidelines, and potential predictors of refractoriness.

This is a multicenter retrospective observational cohort study including patients aged 1 month to 18 years who experienced convulsive SE (CSE) between January 2010 and June 2022. Variables analyzed included age at CSE onset, etiology, and treatment.

We included 1374 CSE episodes in 1071 patients (median age = 3.3 years); 46% occurred in the first 3 years of life. The prominent etiology was remote symptomatic (32%). Resolution was obtained only with benzodiazepine administration in 19.2% of SE episodes. Phenytoin, phenobarbital, and midazolam by infusion were the drugs most frequently used. Maximum therapeutic response occurred with low-dose (<.2 mg/kg/h) midazolam infusion administered at an early stage, following a single dose of benzodiazepine or an antiseizure medication (ASM; 59%). Midazolam effectiveness decreased to 37% when it was used after multiple ASMs, even at high doses. CSE was refractory in 39% of cases. Predictors of refractoriness included nonadherence to current guidelines, type of CSE, and etiology.

This study emphasizes that low-dose midazolam infusion, not requiring endotracheal intubation and administered at an early phase, appears to be effective in permanently stopping seizure and preventing the evolution toward a refractory CSE. Given its proven efficacy and widespread use in many hospitals, early midazolam infusion could be considered in the management of pediatric CSE. Adherence to treatment protocols, specific etiologies, and type of CSE are correlated with refractoriness; thus, when facing SE in infants, these factors should guide treatment protocol selection, including medication choice and timing.

Status epilepticus (SE) is a neurologic emergency. Although evidence-based treatments exist for SE, treatment of refractory status epilepticus (RSE) and super refractory status epilepticus (SRSE) lacks evidence. Electroconvulsive therapy (ECT) is safe and efficacious when used to treat psychiatric disorders. Seizure control attributed to ECT in the setting of SRSE has been reported in case reports and case series. The objective of this scoping review was to understand the current knowledge regarding the safety and efficacy of ECT in aborting SRSE in the adult and pediatric populations.

This scoping review was designed based on guidelines from the Joanna Briggs Institute (JBI) and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. Databases were searched to identify relevant studies, which were independently appraised by reviewers. Peer-reviewed studies with focus on patients who were treated with ECT for SRSE were included. Patient demographic, ECT course, and clinical outcome data were collated in a prespecified proforma.

Data were extracted from 16 studies, which included a combined 40 patients. Ages were unknown for eight patients. Of the patients whose ages were known, more pediatric patients than adults were previously healthy, and seizure etiology differed between these two subgroups. SE was aborted in 80% of adult and 100% of pediatric patients. One adverse effect related to ECT was reported. Seizure recurrence, new epilepsy diagnoses, technology dependence, and death were common.

Differences between adult and pediatric patients who are treated with electroconvulsive therapy (ECT) for SRSE could reflect a combination of factors, including logistical and regulatory barriers that limit use of ECT in intensive care units (ICUs). Prospective, randomized controlled trials are needed to fully understand the risks vs benefits of ECT for SRSE compared to other treatments.

Research in critically ill children poses challenges in acquiring prospective informed consent. International ethical guidelines generally have provisions to perform research without prior consent (RWPC) in circumstances where consent is not feasible, but there is a paucity of data regarding the community acceptance of this process. The objectives of the current study were to explore the attitudes and experiences of parents of children enrolled into trials to determine understanding and acceptability of RWPC to parents of children involved.

Qualitative study of semi-structured telephone interviews in 2017 exploring themes of medical research, trial participation in RWPC. Interview transcripts underwent inductive thematic analysis with intercoder agreement, using Nvivo 14 software.

Two clinical interventional trials in Australia conducted in critically ill children without prospective consent.

Parents of children enrolled in critical care research.

None.

A total of 49 interviews were conducted and analyzed. Parents of participants were supportive of processes used in the trials and RWPC. Paperwork was often not thought to contribute to improved understanding, with verbal information more valued. There was no consensus on the optimal approach of RWPC in situations when clinical outcome was poor.

Our study in 2017 shows that parent/carer supported RWPC in two pediatric trials involving critically ill children. Parents were satisfied with existing approval methods and safeguards. Parents valued brief verbal information at the time of randomization. These historical findings support the feasibility of conducting research on time-sensitive interventions in emergency settings with RWPC, aligning with community expectations.

Levetiracetam is a widely used antiseizure drug in patients with refractory epilepsy due to its specific mechanism of action. This study aimed to develop and validate a population pharmacokinetic model (PopPK) to optimize levetiracetam dosing in patients with refractory epilepsy.

A total of 256 plasma concentrations of levetiracetam, obtained from 135 patients, were employed for PopPK model development, applying a nonlinear mixed-effects modeling methodology. Evaluation of the final model was performed by visually inspecting the goodness-of-fit plots generated, bootstrap resampling, and visual predictive check (VPC). In addition, 60 plasma concentrations, obtained from other 37 patients, were used for external validation of the developed model.

A one-compartment model with first-order elimination best described the pharmacokinetic profiles of levetiracetam. Between-patient variability (BPV) was included on apparent clearance (CL/F), and the residual error (RE) was modeled as proportional. The estimates for CL/F, apparent volume of distribution (Vd/F), and absorption rate constant (ka) of the final model were 3.73 L/h, 35.10 L, and 1.35 h-1, respectively. BPV associated with CL/F was 18.30%, and the proportional RE was 21.21%. The co-administration of other antiseizure drugs that are metabolic inducers, the glomerular filtration rate, and the body weight were identified as significant covariates for CL/F, whereas body surface area was the only covariate with significant impact on the Vd/F. The bootstrap, VPC, and external evaluation collectively validated the stability and predictive performance of the final model.

A reliable PopPK model was successfully developed and validated, offering a valuable tool for tailoring levetiracetam dosing regimens and enhancing drug effectiveness and safety in adult patients with refractory epilepsy.

We compared the efficacy of lacosamide to other frequently used second-line anti-seizure medications (ASMs) for adult status epilepticus (SE) by conducting a retrospective analysis of an institutional SE registry between January 2013 and December 2022. Clinical outcomes assessed at discharge were categorized as return to baseline, new disability, or death; we also considered SE termination after the second-line ASM and the need for mechanical ventilation. Potential confounders included the Status Epilepticus Severity Score (STESS), sex, adequacy of initial SE treatment, treatment delay, and potentially fatal etiology. Over 10 years, 961 adult SE episodes were analyzed; 868 were treated with the following second-line ASMs: 413 levetiracetam (47.6%), 110 valproate (12.7%), and 75 lacosamide (8.6%), as well as lower rates of 18 other ASMs including benzodiazepines (not further analyzed). Univariable analysis identified STESS, treatment delay, and adequacy of initial SE treatment as potential confounders. On multivariable analysis adjusting for these variables, patients with episodes treated with second-line lacosamide, levetiracetam, or valproate demonstrated statistically equivalent rates of seizure cessation, need for mechanical ventilation, and clinical outcomes at hospital discharge. We conclude that lacosamide appears to represent a reasonable alternative to levetiracetam and valproate, and warrants consideration for inclusion in future randomized controlled trials for control of SE.

To explore specialists' opinions on the current management of pediatric convulsive status epilepticus (CSE) in Italy and the main factors influencing the applicability of guidelines.

We conducted a national survey of child neurologists, pediatric emergency physicians, and intensivists. Within the multidisciplinary Italian Paediatric Status Epilepticus (IPSE) Group, a web-based 48-multiple-choice questionnaire was developed to explore treatment choices, use of internal protocols and guidelines, and self-perceived competencies in the treatment of CSE.

Responses were received from 250 clinicians from 34 Italian hospitals (response rate 71%). Intravenous midazolam (iv-MDZ) was the preferred benzodiazepine (BDZ) when iv access was available (90%). When iv-access was unavailable, 75% of clinicians used BDZs; rectal diazepam was the most indicated (65.6%). Concerning second-line treatment, the choices were equally distributed between phenytoin (55.2%), levetiracetam (52.4%), and phenobarbital (52.4%). MDZ infusion at a dosage < 0.23 mg/kg/h was also a frequent choice (38%). A PICU in the hospital influenced this latter choice, resulting in a significantly greater use of iv-MDZ by pediatric emergency physicians working in these hospitals. Answers' variability was related to organizational aspects such as the availability of on-duty specialists and diagnostic tools in emergency settings.

This survey confirmed that first-line treatment of pediatric CSE relied on iv-MDZ and that the heterogeneity of therapeutic choices started from the second-line treatment in real life. The survey also highlighted the need to consider the organizational heterogeneity among settings and to involve different specialties in an integrated and feasible approach.

The Paediatric Research in Emergency Departments International Collaborative (PREDICT) has operated as an emergency research network in Australia and Aotearoa New Zealand for 20 years. A focus on both knowledge generation and, over the last decade, knowledge translation research has produced more than 200 network publications. Active research sites have increased from the original 12 sites to 47, with enhanced representation of where children with acute illness present in both countries. We outline ongoing challenges across the network, which will be relevant for those providing acute paediatric care and to other emergency clinicians interested in multicentre research collaboration.

This article provides current evidence on how and when to treat unprovoked first seizures in children and adults, guides intervention with appropriate doses and types of modern and effective therapies for acute repetitive (cluster) seizures, and reviews evidence for the diagnosis and management of established, refractory and super-refractory status epilepticus.

Artificial intelligence shows promise as a clinical assistant in decision making after a first seizure. For nonanoxic convulsive refractory status epilepticus third-phase treatment, equipoise exists regarding whether it is better to add a second IV nonsedating antiseizure medication given via loading dose (eg, brivaracetam, lacosamide, levetiracetam, fosphenytoin or valproic acid) or to start an anesthetizing continuous IV infusion antiseizure medication such as ketamine, midazolam, propofol or pentobarbital.

After a first seizure, the risk of a second seizure is about 36% at 2 years and 46% after 5 years. The risk is doubled in the presence of EEG epileptiform discharges, a brain imaging abnormality, a nocturnal first seizure, or prior brain trauma. For acute repetitive seizures, providers should give a proper dose of benzodiazepines based on the patient's weight and needs. First-phase treatment for convulsive established status epilepticus is the immediate administration of full doses of benzodiazepines. Second-phase treatment for convulsive established status epilepticus is a full loading dose of IV fosphenytoin, levetiracetam, valproic acid, or if necessary, phenobarbital.

The updated definition of status epilepticus (SE) by the International League Against Epilepsy in 2015 included two critical time points (t1: at which the seizure should be regarded as an "abnormally prolonged seizure"; and t2: beyond which the ongoing seizure activity can pose risk of long-term consequences) to aid in diagnosis and management and highlights the importance of early treatment of SE more clearly than ever before. Although Japan has witnessed an increasing number of pre-hospital drug treatment as well as first- and second-line treatments, clinical issues have emerged regarding which drugs are appropriate. To address these clinical concerns, a revised version of the "Japanese Guidelines for the Treatment of Pediatric Status Epilepticus 2023" (GL2023) was published. For pre-hospital treatment, buccal midazolam is recommended. For in-hospital treatment, if an intravenous route is unobtainable, buccal midazolam is also recommended. If an intravenous route can be obtained, intravenous benzodiazepines such as midazolam, lorazepam, and diazepam are recommended. However, the rates of seizure cessation were reported to be the same among the three drugs, but respiratory depression was less frequent with lorazepam than with diazepam. For established SE, phenytoin/fosphenytoin and phenobarbital can be used for pediatric SE, and levetiracetam can be used in only adults in Japan. Coma therapy is recommended for refractory SE, with no recommended treatment for super-refractory SE. GL2023 lacks adequate recommendations for the treatment of nonconvulsive status epilepticus (NCSE). Although electrographic seizure and electrographic SE may lead to brain damages, it remains unclear whether treatment of NCSE improves outcomes in children. We plan to address this issue in an upcoming edition of the guideline.

Super-refractory status epilepticus (SRSE) is an extremely serious neurological emergency. Risk factors and mechanisms involved in transition from refractory status epilepticus (RSE) to SRSE are insufficiently studied.

This was a multicenter retrospective cohort study of consecutive patients diagnosed and treated for RSE at two reference hospital over 5 years in Ecuador. A total of 140 patients were included. Potential demographic, clinical, and treatment variables that may predict progression from refractory to SRSE were analyzed.

Super-refractory status epilepticus was identified in 67/140 (48%) of patients. In univariate analyses, level of consciousness on hospital admission (Glasgow Coma Score < 12, odds ratio [OR] 2.9, p < 0.01), traumatic brain injury (OR 2.3, p = 0.05), acute etiology (OR 3.0, p = 0.04), higher Status Epilepticus Severity Score (STESS) (OR 1.7, p < 0.01), and new clinical or electrographic seizure within 6 h (OR 4.2, p < 0.01) of starting anesthetic infusion were important factors related to super-refractory disease. The best independents predictors of SRSE when the presence of other potential factors were considered for multivariate analysis. Two models were calculated to avoid interactions between similar variables. Glasgow Coma Score on hospital admission < 12 (OR 3.1 [95% confidence interval {CI} 1.16-8.29], p = 0.02) and new clinical or electroencephalography (EEG) seizure after first 6 h of starting anesthetic infusion (OR 3.1 [95% CI 1.36-7.09], p = 0.01) were associated with higher risk of progression to SRSE in model 1. In contrast, model 2 indicated that patients with STESS ≥ 3 points (OR 2.9 [95% CI 1.24-6.65], p = 0.01) and new clinical or EEG seizure after 6 h starting anesthetic infusion (OR 3.0 [95% CI 1.32-6.97], p = 0.01) were the factors independently related to super-refractory disease.

The rate of patients with RSE admitted to intensive care units developing SRSE was high. Low level of consciousness on admission, higher STESS scores, and patients who did not achieve total control of clinical or EEG seizure in the first 6 h of starting intravenous anesthetic infusion may be early indicators of SRSE.

Intravenous push (IVP) administration of anti-seizure medications is becoming increasingly popular among emergency departments. IVP administration eliminates the need for compounding and preparation by the pharmacy department, as well as the need to gather infusion materials or set up a patient's tubing and pump, all of which translate to faster drug administration. This is important given the time-sensitive nature of status epilepticus treatment. This review will discuss several anti-seizure medications, including phenytoin, fosphenytoin, valproic acid, levetiracetam, brivaracetam and lacosamide, for which evidence supports the safe and efficacious use of IV push administration.

Status epilepticus is a common neurological emergency that is characterised by prolonged or recurrent seizures without recovery between episodes and associated with substantial morbidity and mortality. Prompt recognition and targeted therapy can reduce the risk of complications and death associated with status epilepticus, thereby improving outcomes. The most recent International League Against Epilepsy definition considers two important timepoints in status epilepticus: first, when the seizure does not self-terminate; and second, when the seizure can have long-term consequences, including neuronal injury. Recent advances in our understanding of the pathophysiology of status epilepticus indicate that changes in neurotransmission as status epilepticus progresses can increase excitatory seizure-facilitating and decrease inhibitory seizure-terminating mechanisms at a cellular level. Effective clinical management requires rapid initiation of supportive measures, assessment of the cause of the seizure, and first-line treatment with benzodiazepines. If status epilepticus continues, management should entail second-line and third-line treatment agents, supportive EEG monitoring, and admission to an intensive care unit. Future research to study early seizure detection, rescue protocols and medications, rapid treatment escalation, and integration of fundamental scientific and clinical evidence into clinical practice could shorten seizure duration and reduce associated complications. Furthermore, improved recognition, education, and treatment in patients who are at risk might help to prevent status epilepticus, particularly for patients living in low-income and middle-income countries.

Generalized Convulsive status epilepticus (SE) is a neurological emergency because prolonged convulsions can cause respiratory compromise and neuronal injury. Compromised GABA-mediated inhibition is a defining feature of SE, and many current therapies are benzodiazepines, which are allosteric modulators of GABA-A receptors. Many patients with medically refractory epilepsy are at risk for SE. Newly available nasally delivered benzodiazepines: midazolam and diazepam given for seizure clusters may prevent SE. Although three different benzodiazepines, diazepam, lorazepam and midazolam terminate early SE, midazolam is preferred. It is administered via the intramuscular route, which saves time and is at least as practical or more effective than intravenous lorazepam. Unfortunately, many early SE patients are receiving inadequate doses of benzodiazepines. Patients who fail to respond to adequate doses of benzodiazepines are considered to be in established SE. Levetiracetam, fosphenytoin, and valproic acid are equally safe and effective in treating established SE. The rate of cardiovascular complications: cardiac arrhythmias and hypotension were low in patients treated with phenytoin, levetiracetam, or valproic acid. In contrast, overall, 25 ​% of patients in established SE were intubated, and this was in response to respiratory compromise in many patients. Interestingly, children treated with fosphenytoin were more likely to require intubation than those treated with valproic acid or levetiracetam. Better therapies are needed for the treatment established SE, because all three drugs were effective in less than 50 ​% of the patients.

Status epilepticus (SE) is the most severe presentation of epilepsy. Currently, SE is defined according to 2 sequential time frames: time 1, after which it is unlikely that the seizure will resolve spontaneously, therefore requiring the initiation of therapy; and time 2, when long-term consequences become more likely. For convulsive SE, these time frames are well defined: 5 minutes for time 1 and 30 minutes for time 2. "Time is brain" in the treatment of SE, as delays in diagnosis and treatment are associated with worse outcomes. After clinical stabilization, the first step is the administration of intravenous (IV) benzodiazepines. Rapid initiation of treatment and use of appropriate dosing are more important than the selection of a specific benzodiazepine. Following this, treatment continues with the use of an IV antiseizure medication (ASM). In Brazil, the recommended options available are phenytoin and levetiracetam. Status epilepticus is considered refractory to treatment if seizures persist after the administration of benzodiazepines and IV ASM. The cornerstone of this stage is the induction of therapeutic coma using IV anesthetic drugs (IVADs), although evidence is limited regarding the choice among midazolam, propofol, or barbiturates. Super-refractory SE is defined when seizures persist despite continuous infusion of IVADs or recur after these drugs are tapered. There is very limited data regarding the treatment of super-refractory SE. In the absence of randomized controlled trials, treatment should be guided by the physician's experience, clinical judgment, and established therapeutic options from previous reports.

This is the eighth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recent published resuscitation evidence reviewed by the International Liaison Committee on Resuscitation task force science experts. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research.

This is the eighth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recent published resuscitation evidence reviewed by the International Liaison Committee on Resuscitation task force science experts. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research.

To systematically review the efficacy and safety of second-line medications for status epilepticus (SE).

Electronic searches were conducted in PubMed, Embase, and The Cochrane Library for randomized controlled trials of second-line medications for SE from inception to January 2024. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Network meta-analysis was performed using R 4.2.2 software.

A total of 23 randomized controlled trials were analyzed, examining the efficacy of 5 different treatment regimens: levetiracetam (LEV), phenytoin (PHT), fosphenytoin (FPHT), valproate (VPA), and phenobarbital (PHB). The results of the network meta-analysis indicated that the seizure control rate ranking was as follows: PHB (98.1%) > LEV (60.7%) > FPHT (40.3%) > PHT (33.0%) > VPA (17.8%). The surface under the cumulative ranking (SUCRA) values revealed that PHB had the highest ranking (SUCRA, 91.8%), followed by VPA (SUCRA, 69.3%), PHT (SUCRA, 56.1%), and FPHT (SUCRA, 5.9%) for the recurrence of seizures within 24 hours. Subgroup analysis revealed that PHB was most effective for seizure control in both pediatric and adult populations, VPA demonstrated superior efficacy in children across various indicators, LEV was deemed the safest option for children and elderly individuals, and VPA was identified as the safest choice for adult patients.

PHB continues to be a prominent option for managing SE, although its safety profile warrants careful consideration. Meanwhile, both VPA and LEV offer distinctive advantages in the treatment of SE, with each demonstrating commendable safety profiles.

Since bromides were first used in 1857 to treat epilepsy, numerous antiseizure medications (ASM) have been developed. Many of these are available for the treatment of epilepsy and status epilepticus today. With so many ASM available, questions arise as to whether all of these medications are needed and when should they be used. As precision medicine begins to play a larger role in determining targeted treatments for specific types of epilepsy, a complete understanding of various medications is needed. Additionally, access to several of these medications can be limited in the United States and are especially limited globally. All these factors can make proper selection of ASM challenging and difficult for clinicians. This review highlights important aspects of older and newer medications, developments in precision medicine for epilepsy, increasing understanding of effective treatments for status epileptics, and a global perspective on ASM availability.

Dravet syndrome (DS) is an infantile onset developmental and epileptic encephalopathy. Sodium channel blockers are known to exacerbate seizures in this syndrome. Due to its high incidence, the management of prolonged seizures is crucial for DS patients. There is still ambiguity regarding the use of intravenous phenytoin for prolonged seizure in DS patients mainly due to the lack of data, raising concern about the safety of it use. We conducted a retrospective study (from January 2009 to January 2020) aiming to assess the management of prolonged seizures in DS with a focus on the use of intravenous phenytoin. Data were collected for patients admitted to our hospital for seizures lasting >5 min. Among 52 identified patients in our database, 23 experienced 59 prolonged seizures managed in our hospital. Only four seizures ceased without rescue medication. Notably, the use of intravenous phenytoin was not associated with discernible adverse effects and was effective in stopping status epilepticus in 71% of cases. This study suggests the safety and efficacy of intravenous phenytoin for prolonged seizure in DS. There is a need for broader investigations of emergency treatments for evidence-based recommendations for the emergency plan of each patient.

Despite burgeoning interest in trials in status epilepticus over the last 20 years, outcomes have yet to improve and a number of high profile studies have failed to deliver for a range of reasons. The range of reasons a trial may fail to meet the intended outcomes are discussed. Recent well designed, adequately powered studies in established status epilepticus failed to meet primary endpoints, but are nonetheless influencing practice, reflecting the importance of interpreting results in the context of broader literature, safety and practical considerations. Studies in refractory and super-refractory status epilepticus have yet to do so, frequently failing to deliver as hoped despite huge financial and human cost. The importance of reviewing regulatory frameworks, and our approach to trial design to address important clinical questions is reviewed, reflecting on lessons from the COVID-19 RECOVERY trials, and other disease areas, together with the potential associated with the use artificial intelligence tools. This paper is based on a presentation made at the 9th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures in April 2024.

To compare levetiracetam and phenytoin as prophylaxis for the short-term development of status epilepticus (SE) during care of pediatric patients with acute severe traumatic brain injury (TBI).

Nonprespecified secondary analysis using propensity score matching.

We used the Approaches and Decisions in Acute Pediatric TBI Trial (ADAPT NCT04077411) dataset (2014-2017).

Patients less than 18 years old with Glasgow Coma Scale Score less than or equal to 8 who received levetiracetam or phenytoin as a prophylactic anticonvulsant therapy.

None.

Of the 516 total patients who qualified for the case-control study, 372 (72.1%) patients received levetiracetam, and 144 (27.9%) received phenytoin. After propensity score matching, the pair-matched analysis with 133 in each group failed to identify an association between levetiracetam versus phenytoin use and occurrent of SE (3.8% vs. 0.8%, p = 0.22), or mortality (i.e., in-hospital, 30-d and 60-d). However, on closer inspection of the statistical testing, we cannot exclude the possibility that selecting levetiracetam rather than phenytoin for prophylaxis was associated with the following: up to a mean difference of 7.3% greater prevalence of SE; up to a mean difference of 13.9%, 12.1%, and 13.9% greater mortality during the hospital stay, and 30-, and 60-days after hospital arrival, respectively. Last, analysis of 6 months Glasgow Outcome Scale Extended score in those without premorbid comorbidities, there was an association between favorable outcomes and use of phenytoin rather than levetiracetam prophylaxis.

In ADAPT, the decision to use prophylactic levetiracetam versus phenytoin failed to show an association with occurrence of subsequent SE, or mortality. However, we are unable to exclude the possibility that selecting levetiracetam rather than phenytoin for prophylaxis was associated with greater prevalence of SE and mortality. We are unable to make any recommendation about one prophylactic anticonvulsant medication over the other, but recommend that further larger, contemporary studies in severe pediatric TBI are carried out.

Modern drugs have changed epilepsy, which affects people of all ages. However, for young people with epilepsy, the framework of drug development has stalled. In the wake of the thalidomide catastrophe, the misconception emerged that for people < 18 years of age drugs, including antiseizure medications (ASMs), need separate proof of efficacy and safety, overall called "pediatric drug development". For ASMs, this has changed to some degree. Authorities now accept that ASMs are effective in < 18 years as well, but they still require "extrapolation of efficacy," as if minors were another species. As a result, some of the pediatric clinical epilepsy research over the past decades was unnecessary. Even more importantly, this has hampered research on meaningful research goals. We do not need to confirm that ASMs work before as they do after the 18th birthday. Instead, we need to learn how to prevent brain damage in young patients by preventing seizures and optimize ASMs' uses. Herein we discuss how to proceed in this endeavor.

Status epilepticus is a neurologic emergency that can be life- threatening. The key to effective management is recognition and prompt initiation of treatment. Management of status epilepticus requires a patient-specific-approach framework, consisting of four axes: (1) semiology, (2) etiology, (3) EEG correlate, and (4) age. This article provides a comprehensive overview of status epilepticus, highlighting the current treatment approaches and strategies for management and control.

Administering appropriate doses of antiseizure medication in a timely manner is vital for halting seizure activity. Benzodiazepines are the first-line treatment, as demonstrated by three randomized controlled trials in the hospital and prehospital settings. Benzodiazepines can be administered through IV, intramuscular, rectal, or intranasal routes. If seizures persist, second-line treatments such as phenytoin and fosphenytoin, valproate, or levetiracetam are warranted. The recently published Established Status Epilepticus Treatment Trial found that all three of these drugs are similarly effective in achieving seizure cessation in approximately half of patients. For cases of refractory and super-refractory status epilepticus, IV anesthetics, including ketamine and γ-aminobutyric acid-mediated (GABA-ergic) medications, are necessary. There is an increasing body of evidence supporting the use of ketamine, not only in the early phases of stage 3 status epilepticus but also as a second-line treatment option.

As with other neurologic emergencies, "time is brain" when treating status epilepticus. Antiseizure medication should be initiated quickly to achieve seizure cessation. There is a need to explore newer generations of antiseizure medications and nonpharmacologic modalities to treat status epilepticus.

Currently nearly one-quarter of admissions to pediatric intensive care units (PICUs) worldwide are for neurocritical care diagnoses that are associated with significant morbidity and mortality. Pediatric neurocritical care is a rapidly evolving field with unique challenges due to not only age-related responses to primary neurologic insults and their treatments but also the rarity of pediatric neurocritical care conditions at any given institution. The structure of pediatric neurocritical care services therefore is most commonly a collaborative model where critical care medicine physicians coordinate care and are supported by a multidisciplinary team of pediatric subspecialists, including neurologists. While pediatric neurocritical care lies at the intersection between critical care and the neurosciences, this narrative review focuses on the most common clinical scenarios encountered by pediatric neurologists as consultants in the PICU and synthesizes the recent evidence, best practices, and ongoing research in these cases. We provide an in-depth review of (1) the evaluation and management of abnormal movements (seizures/status epilepticus and status dystonicus); (2) acute weakness and paralysis (focusing on pediatric stroke and select pediatric neuroimmune conditions); (3) neuromonitoring modalities using a pathophysiology-driven approach; (4) neuroprotective strategies for which there is evidence (e.g., pediatric severe traumatic brain injury, post-cardiac arrest care, and ischemic stroke and hemorrhagic stroke); and (5) best practices for neuroprognostication in pediatric traumatic brain injury, cardiac arrest, and disorders of consciousness, with highlights of the 2023 updates on Brain Death/Death by Neurological Criteria. Our review of the current state of pediatric neurocritical care from the viewpoint of what a pediatric neurologist in the PICU needs to know is intended to improve knowledge for providers at the bedside with the goal of better patient care and outcomes.

Objective: Levetiracetam is widely used in the emergency setting. Safety and tolerability of undiluted levetiracetam is prevalent in adults but is limited in pediatrics. The purpose is to determine the safety and tolerability of rapid administration of undiluted levetiracetam in pediatric patients. Methods: A retrospective, single-center, observational study was conducted in pediatric patients who received undiluted levetiracetam intravenous push. The primary outcome was adverse reactions, extravasation, need for intravenous line replacement, and discontinuation due to adverse reactions. The secondary outcome was turnaround time between ordering and administering first doses. Results: One hundred fourteen patients were included. Injection site reactions occurred in 7 patients. Extravasation occurred in 4 patients. Two patients required intravenous line replacement. There were no adverse events leading to discontinuation of levetiracetam. No difference was seen in the time from order to administration. Conclusion: Rapid administration of undiluted levetiracetam in pediatric patients was safe and well tolerated.

Determination of the real-world performance of a health care system in the treatment of status epilepticus (SE).

Prospective, multicenter population-based study of SE in Auckland, New Zealand (NZ) over 1 year, with data recorded in the EpiNet database. Focus on treatment patterns and determinants of SE duration and 30-day mortality. The incidence, etiology, ethnic discrepancies, and seizure characteristics of this cohort have been published previously.

A total of 365 patients were included in this treatment cohort; 326 patients (89.3%) were brought to hospital because of SE, whereas 39 patients (10.7%) developed SE during a hospital admission for another reason. Overall, 190 (52.1%) had a known history of epilepsy and 254 (70.0%) presented with SE with prominent motor activity. The mean Status Epilepticus Severity Score (STESS) was 2.15 and the mean SE duration of all patients was 44 min. SE self-terminated without any treatment in 84 patients (22.7%). Earlier administration of appropriately dosed benzodiazepine in the pre-hospital setting was a major determinant of SE duration. Univariate analysis demonstrated that mortality was significantly higher in older patients, patients with longer durations of SE, higher STESS, and patients who developed SE in hospital, but these did not maintain significance with multivariate analysis. There was no difference in the performance of the health care system in the treatment of SE across ethnic groups.

When SE was defined as 10 continuous minutes of seizure, overall mortality was lower than expected and many patients had self-limited presentations for which no treatment was required. Although there were disparities in the incidence of SE across ethnic groups there was no difference in treatment or outcome. The finding highlights the benefit of a health care system designed to deliver universal health care.

Seizures represent a significant comorbidity in children with acute encephalitis syndrome (AES). Despite this, there is a notable absence of randomized controlled trials (RCTs) directly comparing antiseizure medications (ASMs) in children with AES.

This RCT aimed to assess the efficacy and safety of phenytoin and levetiracetam in controlling seizures among children with AES. Both ASMs were administered with a loading followed by maintenance dose. After a 12-week period, children exhibiting a normal electroencephalogram and no seizure recurrence underwent tapering and discontinuation of ASM. Clinical follow-up occurred daily for the first week, and subsequently at 4, 12, and 24 weeks, evaluating seizure recurrence, incidence of status epilepticus, cognition, behavior, functional status, ASM acquisition cost, and adverse effects.

A total of 100 children (50 in each group) were enrolled. Within the first week, 5 and 3 children in the phenytoin and levetiracetam groups expired. Up to 1 week or death (whichever occurred earliest), 46 (92 %) and 44 (88 %) children remained seizure-free. Intention-to-treat analysis for both best and worst-case scenarios showed insignificant differences (p=0.52 and 1.0). No children experienced seizure recurrence after 1 week in either group. The number of patients with breakthrough status epilepticus, need for mechanical ventilation, duration of hospital stay, presence of epileptiform abnormalities in repeat electroencephalogram at 12 weeks, functional outcomes at 1, 12, and 24 weeks, as well as cognition and behavioral profiles at 24 weeks, were comparable in both groups (p>0.05 for all). However, the incidence of treatment-emergent adverse events (TEAEs) causally related to study medications was significantly higher in the phenytoin group (p=0.04).

Levetiracetam and phenytoin are comparable in efficacy in terms of achieving clinical seizure control in children with acute encephalitis syndrome, although levetiracetam group demonstrated fewer adverse effects.

Survey of treatment practices and adherence to pediatric status epilepticus (PSE) management guidelines in India.

This eSurvey was conducted over 35 days (15th October to 20th November 2023) and included questions related to hospital setting; antiseizure medications (ASMs); ancillary treatment; facilities available; etiology; and adherence to PSE management guidelines.

A total of 170 respondents participated, majority of them were working in tertiary level hospitals (94.1%) as pediatric intensivists (56.5%) and pediatricians (19.4%), and were in clinical practice for 2-10 years (46.5%). Majority use intravenous (IV) midazolam and levetiracetam as first- and second-line ASMs (67.1 and 51.2%, respectively). In cases with refractory status epilepticus (RSE), the most commonly used ASM is midazolam infusion (92.4%). For super-refractory status epilepticus (SRSE), the commonly used third-line ASMs include midazolam infusion (34.1%), thiopentone infusion (26.5%), high dose phenobarbitone (18.2%), and ketamine infusion (15.3%). Overall, in cases with SRSE, 44.7% respondents use ketamine infusion, 42.5% use add-on oral topiramate, and 34.7% use high-dose phenobarbitone (1-3 mg/kg/hour) infusion. Most respondents targeted both clinical and EEG seizure control (48.8%). Ancillary treatment used for SRSE included IV pyridoxine (57.1%), methylprednisolone (45.3%), IVIG (42.4%), ketogenic diet (40.6%), and second-line immunomodulation (33.5%). Most common causes were febrile SE, viral encephalitis, and febrile illness-related epilepsy syndrome (60.6%, 52.4%, and 37.1%, respectively). Facilities available included pediatric intensive care units (PICU) (97.1%), mechanical ventilation (98.2%), pediatric neurologist (68.8%), MRI brain (86.5%), EEG (69.4%), and viral PCR (58.2%). The compliance with guidelines for timing of initiation of ASM ranged from 63.5 to 88.8%.

Intravenous midazolam bolus/es, levetiracetam, and midazolam infusion are commonly used first-, second-, and third-line ASMs, respectively. There were wide variations in use of ASMs for RSE and SRSE, ancillary treatment, and compliance to PSE management guidelines.

Suthar R, Angurana SK, Nallasamy K, Bansal A, Muralidharan J. Survey of Pediatric Status Epilepticus Treatment Practices and Adherence to Management Guidelines (Pedi-SPECTRUM e-Survey). Indian J Crit Care Med 2024;28(5):504-510.

Background: Levetiracetam is a readily available, safe anticonvulsive medication. It is frequently administered as IV piggyback with a pump, carrier fluid, and tubing. The Established Status Epilepticus Treatment Trial demonstrated levetiracetam being similarly effective to previously used treatments in doses up to 4500 mg administered over 10 minutes. Objective: We sought to compare usage, cost, and waste of IV piggyback with IV push administration of levetiractam following implementation of an IV push protocol in an academic emergency department. Methods: A three-month review of levetiracetam administration was done following protocol implementation using IV push for initial treatment of benzodiazepine-refractory status epilepticus. The review quantified the number of IV push vs IV piggyback doses for all indications and evaluated cost of supplies necessary for administration. Results: During the study period, 137 patients received 142 doses of IV levetiracetam. Fifty-one doses (36%) were given as IV push rather than IV piggyback. The majority of doses 116 (82%) were 1000-2000 mg and 11 doses (8%) 3500-4500 mg. Estimated three-month savings with complete transition of IV piggyback to IV push would exceed $6000 just in our ED. The amount of sterile solution carrier fluid was also reduced and IV pump time freed. Conclusion: Implementation of an emergency department IV push levetiracetam protocol resulted in cost savings. Opportunities remain to improve clinical implementation practices. Medication administration represents one crucial target area where healthcare systems can implement policies to reduce waste and commit to climate-smart health care.

Current first-line therapies for seizure management recommend benzodiazepines, which target gamma-aminobutyric acid type A channels to stop the seizure activity. However, seizures may be refractory to traditional first-line therapies, transitioning into status epilepticus and becoming resistant to gamma-aminobutyric acid type A augmenting drugs. Although there are other antiseizure medications available for clinicians to use in the intensive care unit, these options can be less readily available outside of the intensive care unit and entirely absent in the prehospital setting. Instead, patients frequently receive multiple doses of first-line agents with increased risk of hemodynamic or airway collapse. Ketamine is readily available in the prehospital setting and emergency department, has well-established antiseizure effects with a favorable safety profile, and is a drug often used for several other indications. This article aimed to explore the utilization of ketamine for seizure management in the prehospital setting, reviewing seizure pathophysiology, established treatment mechanisms of action and pharmacokinetics, and potential benefits of early ketamine use in status epilepticus.

Recent studies suggest rapid administration of high-dose, undiluted levetiracetam is safe in adults; however, no information exists in pediatric patients. The purpose of this study was to evaluate the safety and tolerability of undiluted levetiracetam at a pediatric institution.

Retrospective, single-center, cohort study.

Pediatric Academic Medical Center.

All patients who received high-dose >60 mg/kg (-10%) up to 4500 mg undiluted or diluted intravenous levetiracetam were included.

Rapid intravenous administration of undiluted versus diluted levetiracetam.

A total of 776 levetiracetam doses were included, 358 doses administered and 418 doses wasted. The doses administered (61 undiluted and 297 diluted) accounted for a total of 252 patients (39 received undiluted, and 213 received diluted levetiracetam) (median [minimum-maximum range] age, 2 years [1 day to 32.7 years]; mean (standard deviation [SD]) weight, 20.1 kg [22.1 kg]). The incidence of hemodynamic disturbances and infusion-related reactions was not statistically significant between undiluted (24.6%) and diluted (26.3%) groups (p = 0.87). The median (interquartile range [IQR]) time difference between first-line antiseizure medication and levetiracetam administration in patients with status epilepticus was 18 min (10.5-30.5) in the undiluted group versus 36.5 min (21.8-67.3) in the diluted group (p < 0.01). Additionally, there was a significant amount of drug waste from dispensed but not administered doses of the diluted bag compared to undiluted vials (57.6% diluted vs. 18.7% undiluted, p < 0.001).

Undiluted levetiracetam was not associated with an increased incidence of adverse effects compared to diluted levetiracetam in high-doses, up to 4500 mg given over 5 min in pediatric patients.

Comparative effectiveness research is meant to determine which commonly employed medical interventions are most beneficial, least harmful, and/or most costly in a real-world setting. While the objectives for comparative effectiveness research are clear, the field has failed to develop either a uniform definition of comparative effectiveness research or an appropriate set of recommendations to provide standards for the design of critical care comparative effectiveness research trials, spurring controversy in recent years. The insertion of non-representative control and/or comparator arm subjects into critical care comparative effectiveness research trials can threaten trial subjects' safety. Nonetheless, the broader scientific community does not always appreciate the importance of defining and maintaining critical care practices during a trial, especially when vulnerable, critically ill populations are studied. Consequently, critical care comparative effectiveness research trials sometimes lack properly constructed control or active comparator arms altogether and/or suffer from the inclusion of "unusual critical care" that may adversely affect groups enrolled in one or more arms. This oversight has led to critical care comparative effectiveness research trial designs that impair informed consent, confound interpretation of trial results, and increase the risk of harm for trial participants.

We propose a novel approach to performing critical care comparative effectiveness research trials that mandates the documentation of critical care practices prior to trial initiation. We also classify the most common types of critical care comparative effectiveness research trials, as well as the most frequent errors in trial design. We present examples of these design flaws drawn from past and recently published trials as well as examples of trials that avoided those errors. Finally, we summarize strategies employed successfully in well-designed trials, in hopes of suggesting a comprehensive standard for the field.

Flawed critical care comparative effectiveness research trial designs can lead to unsound trial conclusions, compromise informed consent, and increase risks to research subjects, undermining the major goal of comparative effectiveness research: to inform current practice. Well-constructed control and comparator arms comprise indispensable elements of critical care comparative effectiveness research trials, key to improving the trials' safety and to generating trial results likely to improve patient outcomes in clinical practice.

According to the 2017 ILAE's official definition, epilepsy is a slow brain disease state characterized by recurrent episodes. Due to information released by ILAE in 2017, it can be divided into four types, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and unknown epilepsy. Since 1989, 24 new antiepileptic drugs have been approved to treat different types of epilepsy. Besides, there are a variety of antiepileptic medications under clinical monitoring. These novel antiepileptic drugs have plenty of advantages. Over the past 33 years, there have been many antiepileptic drugs on the mearket, but no one has been found that can completely cure epilepsy. In this paper, the mentioned drugs were classified according to their targets, and the essential information, and clinical studies of each drug were described. The structure-activity relationship of different chemical structures was summarized. This paper provides help for the follow-up research on epilepsy drugs.

Epilepsy is a chronic neurological disease characterized by the presence of spontaneous seizures, with a higher incidence in the pediatric population. Anti-seizure medication (ASM) may produce adverse drug reactions (ADRs) with an elevated frequency and a high severity. Thus, the objective of the present study was to analyze, through intensive pharmacovigilance over 112 months, the ADRs produced by valproic acid (VPA), oxcarbazepine (OXC), phenytoin (PHT), and levetiracetam (LEV), among others, administered to monotherapy or polytherapy for Mexican hospitalized pediatric epilepsy patients. A total of 1034 patients were interviewed; 315 met the inclusion criteria, 211 patients presented ADRs, and 104 did not. A total of 548 ASM-ADRs were identified, and VPA, LEV, and PHT were the main culprit drugs. The most frequent ADRs were drowsiness, irritability, and thrombocytopenia, and the main systems affected were hematologic, nervous, and dermatologic. LEV and OXC caused more nonsevere ADRs, and PHT caused more severe ADRs. The risk analysis showed an association between belonging to the younger groups and polytherapy with ADR presence and between polytherapy and malnutrition with severe ADRs. In addition, most of the severe ADRs were preventable, and most of the nonsevere ADRs were nonpreventable.

Over the last decade, significant advancements have been made in status epilepticus (SE) management, influenced by landmark trials such as ESETT and RAMPART. The objectives of this study were to explore the evolution of drug treatments for patients with SE, to investigate its association with outcomes and mortality, and to evaluate differences in treatment patterns between adults and children for a potential shift in medication trends due to the above mentioned trials.

The medical records of patients with SE treated at University Hospital Frankfurt between 2012 and 2021 were evaluated for medication trends and outcomes. Children and adults were analyzed separately and jointly.

This study included 1151 SE episodes in 1021 patients (mean age = 53.3 ± 28.3 years; 52.5 % female [n = 533]). The overall percentage of patients with SE treated prehospital was stable over the last decade. More than half (53.6 %) of children were treated prehospital, compared with less than one-third (26.7 %) of adults. Prehospital midazolam use increased over time, while diazepam use decreased. Lorazepam was the most commonly used benzodiazepine in hospitals in 2012-2013, used in 40.8 % of all episodes. However, its use declined to 27.2 % in 2020-2021, while midazolam use increased to 44.0 %. While the use of older antiseizure medications (ASMs) such as phenobarbital (p = 0.02), phenytoin (p < 0.001), and valproate (p < 0.001) decreased, the use of newer ASMs such as levetiracetam and lacosamide significantly increased (p < 0.001). Propofol and continuous midazolam infusion remained the most used third-line therapy drugs. Overall mortality was 16.5 % at discharge and 18.9 % at 30 days. Mortality rates did not change between 2012 and 2021.

Midazolam has become the preferred benzodiazepine in pre- and in-hospital settings, both in children and adults. The same applies to the increased use of levetiracetam and lacosamide over time in children and adults, while phenobarbital, phenytoin, and valproate use decreased. Continuous midazolam infusion and propofol remain the most frequently used anesthetic drugs. Mortality and outcome remain stable despite changes in medication patterns.

In 2017, one of us reviewed advances in epilepsy (Manford in J Neurol 264:1811-1824, 2017). The current paper brings that review up to date and gives a slight change in emphasis. Once again, the story is of evolution rather than revolution. In recognition that most of our current medications act on neurotransmitters or ion channels, and not on the underlying changes in connectivity and pathways, they have been renamed as antiseizure (ASM) medications rather than antiepileptic drugs. Cenobamate is the one newly licensed medication for broader use in focal epilepsy but there have been a number of developments for specific disorders. We review new players and look forward to new developments in the light of evolving underlying science. We look at teratogenicity; old villains and new concerns in which clinicians play a vital role in explaining and balancing the risks. Medical treatment of status epilepticus, long without evidence, has benefitted from high-quality trials to inform practice; like buses, several arriving at once. Surgical treatment continues to be refined with improvements in the pre-surgical evaluation of patients, especially with new imaging techniques. Alternatives including stereotactic radiotherapy have received further focus and targets for palliative stimulation techniques have grown in number. Individuals' autonomy and quality of life continue to be the subject of research with refinement of what clinicians can do to help persons with epilepsy (PWE) achieve control. This includes seizure management but extends to broader considerations of human empowerment, needs and desires, which may be aided by emerging technologies such as seizure detection devices. The role of specialist nurses in improving that quality has been reinforced by specific endorsement from the International League against Epilepsy (ILAE).

We investigated the management and outcome of early and established status epilepticus including timing, dosing and selection of benzodiazepines along with the timing and efficacy of second line treatments.

Retrospective single tertiary centre observational cohort study to identify all cases of SE between January 2019 and February 2022.

252 cases were identified. Seizures terminated spontaneously in 136 (54%) cases. 116 (46%) were given benzodiazepines, of which 29 (25%) were given at least one benzodiazepine by family/carers, and 72 (62.1%) received benzodiazepines by ambulance services. Benzodiazepines terminated seizures in 83 (71.6%) cases. The commonest benzodiazepine used was buccal midazolam (35.5%). Median time to first benzodiazepine was 14.5 (6-27) minutes. There was a positive correlation between time to first benzodiazepine and time to seizure cessation, progression to second- and third-line treatment, and respiratory complications (p<0.05). 73 (62.9%) cases received a correct benzodiazepine dose. Benzodiazepine underdosing was associated with longer seizure duration (p<0.05). 33 (28.4%) cases progressed to second-line treatment where mean time to treatment was 59.4 min (±32.3 min). The commonest second-line treatment was Levetiracetam (53.8%), followed by Phenytoin (43.6%) with SE termination in 57.5% cases. 14 (12.1%) cases progressed to third-line treatment; mean time to treatment was 60.6 min (±22.24 min). Respiratory complications occurred in 17 (6.75%) cases; none due to benzodiazepines. There were two deaths in refractory SE.

Early administration of benzodiazepines and optimal dosing is associated with a higher rate of SE termination. Levetiracetam was the most commonly used second line treatment.

The timely abortion of status epilepticus (SE) is essential to avoid brain damage and long-term neurodevelopmental sequalae. However, available anti-seizure treatments fail to abort SE in 30% of children. Given the role of the tropomyosin-related kinase B (TrkB) receptor in hyperexcitability, we investigated if TrkB blockade with lestaurtinib (CEP-701) enhances the response of SE to a standard treatment protocol and reduces SE-related brain injury.

SE was induced with intra-amygdalar kainic acid in postnatal day 45 rats under continuous electroencephalogram (EEG). Fifteen min post-SE onset, rats received intraperitoneal (i.p.) CEP-701 (KCEP group) or its vehicle (KV group). Controls received CEP-701 or its vehicle following intra-amygdalar saline. All groups received two i.p. doses of diazepam, followed by i.p. levetiracetam at 15 min intervals post-SE onset. Hippocampal TrkB dimer to monomer ratios were assessed by immunoblot 24 hr post-SE, along with neuronal densities and glial fibrillary acid protein (GFAP) levels.

SE duration was 50% shorter in the KCEP group compared to KV (p < 0.05). Compared to controls, SE induced a 1.5-fold increase in TrkB dimerization in KV rats (p < 0.05), but not in KCEP rats which were comparable to controls (p > 0.05). The KCEP group had lower GFAP levels than KV (p < 0.05), and both were higher than controls (p < 0.05). KCEP and KV rats had comparable hippocampal neuronal densities (p > 0.05), and both were lower than controls (p < 0.05).

Given its established human safety, CEP-701 is a promising adjuvant drug for the timely abortion of SE and the attenuation of SE-related brain injury.

The aim of this study was to explore the differences in status epilepticus (SE) management among pediatric neurology, emergency medicine, and intensive care specialists in Turkey.

A 22-item questionnaire regarding first-, second-, and third-line management strategies of SE including demographic characteristics and common etiologies according to the specialty of participants was mailed to 370 specialists working in Turkey.

A total of 334 participants (response rate 90%) comprising 136 pediatric neurologists, 102 pediatric emergency medicine specialists, and 96 pediatric intensive care specialists completed the survey. While intensive care specialists frequently managed SE due to metabolic and autoimmune reasons, the most common etiologies encountered by emergency medicine specialists were epilepsy and infections. More than half of the intensive care specialists (64.6%) reported using non-BZD antiseizure medications in the 5th minute of the seizure. Most of the neurologists (76.4%) preferred to administer intravenous (IV) levetiracetam infusion as a second-line agent. About half of intensive care specialists and neurologists tried immunomodulatory therapies in super-refractory SE. Intensive care and emergency medicine specialists were less likely to favor ketogenic diet and pyridoxine therapy for the treatment of super-refractory SE. The rate of requesting EEG monitoring to recognize nonconvulsive SE (NCSE) was found to be very low except for neurologists.

There was no consensus among neurologists, intensive care specialists, and emergency medicine specialists in the management of SE in Turkey. Familiarity with particular antiseizure medications and the etiologies they manage seem to be the most important factors influencing the attitudes.

Status epilepticus is one of the most common life-threatening neurological emergencies in childhood with the highest incidence in the first 5 years of life and high mortality and morbidity rates. Although it is known that a delayed treatment and a prolonged seizure can cause permanent brain damage, there is evidence that current treatments may be delayed and the medication doses administered are insufficient. Here, we summarize current knowledge on treatment of convulsive status epilepticus in childhood and propose a treatment algorithm. We performed a structured literature search via PubMed and ClinicalTrails.org and identified 35 prospective and retrospective studies on children <18 years comparing two and more treatment options for status epilepticus. The studies were divided into the commonly used treatment phases. As a first-line treatment, benzodiazepines buccal/rectal/intramuscular/intravenous are recommended. For status epilepticus treated with benzodiazepine refractory, no superiority of fosphenytoin, levetirazetam, or phenobarbital was identified. There is limited data on third-line treatments for refractory status epilepticus lasting >30 min. Our proposed treatment algorithm, especially for children with SE, is for in and out-of-hospital onset aids to promote the establishment and distribution of guidelines to address the treatment delay aggressively and to reduce putative permanent neuronal damage. Further studies are needed to evaluate if these algorithms decrease long-term damage and how to treat refractory status epilepticus lasting >30 min.

Pediatric convulsive status epilepticus (cSE) is a neurologic emergency with potential for morbidity and mortality. Rapid treatment and escalation of therapies to achieve early seizure control is paramount in preventing complications and providing the best patient outcomes. Although guidelines recommend early treatment, cessation of out-of-hospital SE is undermined by treatment delay and inadequate dosing. Logistical challenges include prompt seizure recognition, first-line benzodiazepine (BZD) availability, comfort and expertise in administration of BZD, and timely arrival of emergency personnel. In-hospital, SE onset is additionally impacted by delays to first- and second-line treatment and availability of resources. This review presents an evidence-based, clinically oriented review of pediatric cSE, including its definitions and treatments. It provides evidence and rationale for timely treatment of first-line BZD treatment followed by prompt escalation to second-line antiseizure medication therapies for established SE. Treatment delays and barriers to care are discussed, with practical considerations for opportunities for areas of improvement in the initial treatment of cSE.