Treatment Of Status Epilepticus Research Articles

Status Epilepticus Identification and Treatment Among Emergency Medical Services Agencies

This cross-sectional study examines the association between unidentified status epilepticus and prehospital benzodiazepine treatment.

Emergent Management of Status Epilepticus.

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.

Seizure control via pH manipulation: a phase II double-blind randomised controlled trial of inhaled carbogen as adjunctive treatment of paediatric convulsive status epilepticus (Carbogen for Status Epilepticus in Children Trial (CRESCENT))

BackgroundPaediatric convulsive status epilepticus is the most common neurological emergency presenting to emergency departments. Risks of resultant neurological morbidity and mortality increase with seizure duration. If the seizure fails to stop within defined time-windows, standard care follows an algorithm of stepwise escalation to more intensive treatments, ultimately resorting to induction of general anaesthesia and ventilation. Additionally, ventilatory support may also be required to treat respiratory depression, a common unwanted effect of treatment. There is strong pre-clinical evidence that pH (acid–base balance) is an important determinant of seizure commencement and cessation, with seizures tending to start under alkaline conditions and terminate under acidic conditions. These mechanisms may be particularly important in febrile status epilepticus: prolonged fever-related seizures which predominantly affect very young children. This trial will assess whether imposition of mild respiratory acidosis by manipulation of inhaled medical gas improves response rates to first-line medical treatment.MethodsA double-blind, placebo-controlled trial of pH manipulation as an adjunct to standard medical treatment of convulsive status epilepticus in children. The control arm receives standard medical management whilst inhaling 100% oxygen; the active arm receives standard medical management whilst inhaling a commercially available mixture of 95% oxygen, 5% carbon dioxide known as ‘carbogen’.Due to the urgent need to treat the seizure, deferred consent is used.The primary outcome is success of first-line treatment in seizure cessation. Planned subgroup analyses will be undertaken for febrile and non-febrile seizures. Secondary outcomes include rates of induction of general anaesthesia, admission to intensive care, adverse events, and 30-day mortality.DiscussionIf safe and effective 95% oxygen, 5% carbon dioxide may be an important adjunct in the management of convulsive status epilepticus with potential for pre-hospital use by paramedics, families, and school staff.Trial registrationEudraCT: 2021-005367-49. CTA: 17136/0300/001. ISRCTN: 52731862. Registered on July 2022.

Relative Bioavailability Study of Midazolam Intramuscularly Administered with the Needle-Free Auto-Injector ZENEO® in Healthy Adults.

Intramuscular (IM) midazolam is indicated for the treatment of status epilepticus. Administration must be efficient to rapidly terminate prolonged seizures and prevent complications. The objective of this study was to compare, in terms of relative bioavailability and bioequivalence, IM midazolam injection by needle-free auto-injector, in different settings, to IM midazolam injection by a conventional syringe and needle. In this open-label, randomized, four-period crossover study, healthy adults received single doses of midazolam (10mg) under fasting conditions. The reference treatment (conventional syringe) was administered once, on bare skin in the thigh. The tested treatment (the needle-free auto-injector ZENEO®) was administered three times: on bare skin in the thigh, on bare skin in the ventrogluteal area, and through clothing in the thigh. Repeated plasma samples were collected to obtain 36-h pharmacokinetic (PK) profiles. Primary PK parameters were area under the plasma concentration-time curve, from time zero to the last measurable time point (AUC0-t) and from time zero to infinity (AUC0-∞), and the maximum observed plasma concentration (Cmax). Forty adults were enrolled and included in the PK analysis set. In all comparisons, the 90% confidence interval (CI) of the least-squares geometric mean ratios for AUC0-t and AUC0-∞ were within the bioequivalence range of 80-125%, with low intra-individual coefficients of variation (< 20.5% for all parameters in all comparisons). Bioequivalence was also met for Cmax in all comparisons except when comparing the tested treatment through clothing versus the reference treatment, where the 90% CI lower limit was slightly outside the bioequivalence range (78.8%). With all tested treatments Cmax was slightly lower, but early mean plasma concentrations (first 10min post-dosing) were higher when compared to the reference treatment. In general, all treatments were well tolerated, with maximum sedation 0.5-1h post-injection. This study establishes that IM midazolam injection on bare skin in the thigh with the ZENEO® is bioequivalent to IM midazolam injection with a syringe and needle. An acceptable relative bioavailability, compatible with emergency practice, was also shown in multiple settings. Higher mean concentrations within the first 10min with the ZENEO® device, and quicker two-step injection suggest a faster onset of action, and thereby an earlier seizure termination, thus preventing the occurrence of prolonged seizure and neurological complications. ClinicalTrials.gov identifier: NCT05026567. Registration first posted August 30, 2021, first patient enrolled May 9, 2022.

The efficacy and safety of ketamine in the treatment of super-refractory status epilepticus: a systematic review.

Ketamine, as an anesthetic, has been considered for terminating status epilepticus (SE); however, due to the urgency and severity of the condition, there are currently no randomized controlled trials internationally assessing the efficacy of ketamine for treating super-refractory status epilepticus. Similarly, there appears to be a lack of systematic reviews addressing this topic in the literature. Therefore, this systematic review aims to explore the effectiveness and safety of ketamine for terminating super-refractory status epilepticus. We conducted a systematic search on PubMed, EMBASE, and Web of Science databases. Manuscripts unrelated to the research on super-refractory status epilepticus were excluded, as were manuscripts published in non-English languages. The quality assessment and risk of bias were evaluated using the MINORS criteria. Data extraction was limited to qualitative synthesis due to the unsuitability of the data for meta-analysis. Out of 782 studies retrieved from electronic databases, 11 met the inclusion criteria. Among them, 10 studies were retrospective, and 1 study was prospective. Patient data for inclusion were sourced from the case registries of the researchers' respective hospitals. Across all included studies, the administration of ketamine significantly reduced the duration of status epilepticus and demonstrated higher safety compared to patients not receiving ketamine treatment for super-refractory status epilepticus. Additionally, early administration of ketamine correlated with improved treatment outcomes. The risk of bias across all studies was deemed low. This systematic review suggests that ketamine may be a feasible treatment option for super-refractory status epilepticus. However, given the critical nature of super-refractory status epilepticus, clinicians should prioritize its termination over evaluating the efficacy of specific medications, ensuring patient safety remains paramount. If feasible in real-world medical settings, future research should focus on designing randomized controlled trials to observe the specific efficacy and mechanisms of ketamine. Careful validation is necessary before considering ketamine as a first-line treatment for super-refractory status epilepticus.

The influence of biological rhythms on the initial onset of status epilepticus in critically ill inpatients and the study of its predictive Model

ABSTRACT This study aims to explore the relationship between the circadian rhythms of critically ill patients and the incidence of Status Epilepticus (SE), and to develop a predictive model based on circadian rhythm indicators and clinical factors. We conducted a diurnal rhythm analysis of vital sign data from 4413 patients, discovering significant differences in the circadian rhythms of body temperature, blood oxygen saturation, and heart rate between the SE and non-SE groups, which were correlated with the incidence of SE. We also employed various machine learning algorithms to identify the ten most significant variables and developed a predictive model with strong performance and clinical applicability. Our research provides a new perspective and methodology for the study of biological rhythms in critically ill patients, offering new evidence and tools for the prevention and treatment of SE. Our findings are consistent or similar to some in the literature, while differing from or supplementing others. We observed significant differences in the vital signs of epileptic patients at different times of the day across various diagnostic time groups, reflecting the regulatory effects of circadian rhythms. We suggest heightened monitoring and intervention of vital signs in critically ill patients, especially during late night to early morning hours, to reduce the risk of SE and provide more personalized treatment plans.

Status epilepticus: modern views on classification, typology, methods of diagnosis and treatment with third-generation anticonvulsants (review)

Status epilepticus (SE) is a medical emergency associated with high morbidity and mortality. The guidelines of the International League Against Epilepsy use a stepwise approach to the treatment of SE depending on the response to treatment. Benzodiazepines are commonly used as initial therapy for SE. However, in approximately 40 % of cases of convulsive SE when benzodiazepines are prescribed, no improvement is observed, which indicates the occurrence of a refractory SE. For its treatment, intravenous anticonvulsants such as fosphenytoin, valproate or levetiracetam are used. But even this therapy can be ineffective in 31–47 % of cases, which is due to the development of refractory or super-refractory SE. To combat them, additional anti-seizure drugs are prescribed.

Status epilepticus in Auckland, New Zealand: Treatment patterns and determinants of outcome in a prospective population-based cohort.

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.

VIGAB-STAT—A Phase IIa Feasibility Trial of Irreversible GABA-transaminase Inhibition as Adjunct Treatment of Status Epilepticus After Cardiac Arrest (P4-2.003)

VIGAB-STAT—A Phase IIa Feasibility Trial of Irreversible GABA-transaminase Inhibition as Adjunct Treatment of Status Epilepticus After Cardiac Arrest (P4-2.003)

An Analysis of Status Epilepticus Treatment in the Emergency Department in Detroit: A Retrospective Review (P9-1.004)

An Analysis of Status Epilepticus Treatment in the Emergency Department in Detroit: A Retrospective Review (P9-1.004)

Levetiracetam Initial Dosing for Status Epilepticus Treatment in the Emergency Department (P9-1.008)

Levetiracetam Initial Dosing for Status Epilepticus Treatment in the Emergency Department (P9-1.008)

Assessment of Adherence to Status Epilepticus Treatment Guideline at a Single Institution After Initiation of Status Epilepticus Order Set (P9-1.010)

Assessment of Adherence to Status Epilepticus Treatment Guideline at a Single Institution After Initiation of Status Epilepticus Order Set (P9-1.010)

Small-molecule caspase-1 inhibitor CZL80 terminates refractory status epilepticus via inhibition of glutamatergic transmission.

Status epilepticus (SE), a serious and often life-threatening medical emergency, is characterized by abnormally prolonged seizures. It is not effectively managed by present first-line anti-seizure medications and could readily develop into drug resistance without timely treatment. In this study, we highlight the therapeutic potential of CZL80, a small molecule that inhibits caspase-1, in SE termination and its related mechanisms. We found that delayed treatment of diazepam (0.5 h) easily induces resistance in kainic acid (KA)-induced SE. CZL80 dose-dependently terminated diazepam-resistant SE, extending the therapeutic time window to 3 h following SE, and also protected against neuronal damage. Interestingly, the effect of CZL80 on SE termination was model-dependent, as evidenced by ineffectiveness in the pilocarpine-induced SE. Further, we found that CZL80 did not terminate KA-induced SE in Caspase-1-/- mice but partially terminated SE in IL1R1-/- mice, suggesting the SE termination effect of CZL80 was dependent on the caspase-1, but not entirely through the downstream IL-1β pathway. Furthermore, in vivo calcium fiber photometry revealed that CZL80 completely reversed the neuroinflammation-augmented glutamatergic transmission in SE. Together, our results demonstrate that caspase-1 inhibitor CZL80 terminates diazepam-resistant SE by blocking glutamatergic transmission. This may be of great therapeutic significance for the clinical treatment of refractory SE.

Management of Pediatric Convulsive Status Epilepticus From the Perspective of Emergency Nurses: A Cross-sectional, Multicenter Study

IntroductionPediatric convulsive status epilepticus is one of the most common neurologic emergencies and should be managed by health care professionals as soon as possible based on current guidelines. This study aimed to determine the nursing approaches and management of pediatric convulsive status epilepticus from the perspective of emergency nurses in Turkey. MethodsA cross-sectional, multicenter study was conducted with 162 emergency nurses working in emergency departments in 35 different provinces in Turkey. The data were collected via an online form. Descriptive statistical methods were used in data analysis. ResultsMost emergency nurses (72.2%) attempted an intravenous access immediately to administer antiseizure medications during the stabilization phase. Approximately half the emergency nurses stated that rectal diazePAM was frequently administered in the initial therapy phase and intravenous diazePAM was administered in the second therapy phase. The emergency nurses had most difficulties attempting intravenous access, determining status epilepticus types, and calming the parents. DiscussionAs health care professionals and important members of the health team, emergency nurses have the responsibility to manage pediatric convulsive status epilepticus in the fastest and the most appropriate way based on current practice guidelines in emergency departments. When intravenous access is not available, nonintravenous benzodiazepines should be considered in the first-line treatment of pediatric convulsive status epilepticus, followed by immediate intravenous access.

Treating status epilepticus in adults.

This clinical review examines the treatment of status epilepticus, a condition in which epileptic seizures are prolonged and pose a significant risk of brain damage and death. International guidelines recommend the use of benzodiazepines as first-line treatment, and these should be administered promptly and in appropriate doses. Second-line treatment involves the use of high-dose anti-seizure medications to stop and prevent seizures. If seizure activity persists, general anaesthesia should be administered as soon as possible. All neurological hospital departments should have established and rehearsed protocols for treating status epilepticus.

DIAGNOSIS AND TREATMENT OF STATUS EPILEPTICUS : AN UPDATE SYSTEMATIC REVIEW

Background: Status epilepticus (SE) is a condition resulting from the failure of the mechanisms involved in termination or the initiation of mechanisms responsible for seizure prolongation. The aim: The aim of this study to show about diagnosis and treatment of status epilepticus. Methods: By the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. This search approach, publications that came out between 2014 and 2024 were taken into account. Several different online reference sources, like Pubmed, SagePub, and Google Scholar were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Result: In the PubMed database, the results of our search get 110 articles, whereas the results of our search on SagePub get 163 articles, on Google Scholar 8200 articles. Records remove before screening are 7182, so we get 2761 articles fos screening. After we screened based on record exclude, we compiled a total of 10 papers. We included five research that met the criteria. Conclusion: There are increasingly more drug options to treat SE, but rational polytherapy should consider the pharmacodynamics and kinetics of established and new antiepileptic drugs. When seizures cannot be controlled with conventional medical therapy, non-conventional treatments, including early surgical evaluation can be considered; however, high-quality evidence for these strategies are lacking. Neurointensivists are challenged to reduce secondary brain injury by managing common complications.

Efficacy and safety of ketamine for pediatric and adolescent super-refractory status epilepticus and the effect of cerebral inflammatory conditions

ObjectiveTo investigate the short-term benefits and adverse effects of ketamine in the treatment of pediatric and adolescent super-refractory status epilepticus (SRSE), with a focus on the inflammatory etiology. MethodsThis retrospective observational cohort study included a consecutive series of 18 pediatric to adolescent patients with SRSE admitted between 2008 and 2023 and treated with ketamine. Seizure frequency per hour before and after ketamine administration and response rate were calculated. Neurological decline, catecholamine administration, and adverse effects were also assessed. The patients were divided into inflammatory and non-inflammatory etiology groups. ResultsThe median age at SRSE onset was 1 year 5 months (range: 11 days-24 years), and 78% of the patients were male individuals. The median duration of treatment was 7.5 days (interquartile range: 2.8–15.5 days). Fifteen (83%) patients achieved >50% seizure reduction. The median seizure frequency before and after ketamine treatment was 5.9 and 0.9, respectively, showing a significant reduction in seizure frequency (p < 0.0001). Ten patients had inflammatory etiologies including bacterial meningitis (n = 2), viral encephalitis (n = 3), and febrile infection related epilepsy syndrome (n = 5). The inflammatory etiology group required a longer treatment duration (p = 0.0453) and showed lower seizure reduction (p = 0.0264), lower response rate (p = 0.0044), and higher neurological decline (p = 0.0003) than the non-inflammatory etiology group. Three (17%) patients experienced transient adverse events requiring intervention within 24 h of initiating ketamine administration. ConclusionsKetamine administration was associated with fewer serious adverse events and a reduced seizure frequency. Additionally, inflammatory conditions may weaken the efficacy of ketamine in patients with SRSE.

Hydrogen treatment reduces electroencephalographic activity and neuronal death in rats with refractory status epilepticus by inhibiting membrane NR2B phosphorylation and oxidative stress.

To investigate the effects of hydrogen therapy on epileptic seizures in rats with refractory status epilepticus and the underlying mechanisms. Status epilepticus was induced using pilocarpine. The effects of hydrogen treatment on epilepsy severity in model rats were then monitored using Racine scores and electroencephalography (EEG), followed by western blot of plasma membrane N-methyl-D-aspartate receptor subtype 2B (NR2B) and phosphorylated NR2B expression. We also generated a cellular epilepsy model using Mg2+-free medium and used polymerase chain reaction to investigate the neuroprotective effects of hydrogen. There were no significant differences in Racine scores between the hydrogen and control groups. EEG amplitudes were lower in the hydrogen treatment group than in the control group. In epilepsy model rats, hippocampal cell membrane NR2B expression and phosphorylation increased gradually over time. Although hippocampal cell membrane NR2B expression was not significantly different between the two groups, NR2B phosphorylation levels were significantly lower in the hydrogen group. Hydrogen treatment also increased superoxide dismutase, mitochondrial (SOD2) expression. Hydrogen treatment reduced EEG amplitudes and NR2B phosphorylation; it also decreased neuronal death by reducing oxidative stress. Hydrogen may thus be a potential treatment for refractory status epilepticus by inhibiting membrane NR2B phosphorylation and oxidative stress.

Status Epilepticus Type, Etiology, and Treatment: One-year Data

Status Epilepticus Type, Etiology, and Treatment: One-year Data

Fenfluramine for the treatment of status epilepticus: use in an adult with Lennox–Gastaut syndrome and literature review

BackgroundNovel treatments are needed to control refractory status epilepticus (SE). This study aimed to assess the potential effectiveness of fenfluramine (FFA) as an acute treatment option for SE. We present a summary of clinical cases where oral FFA was used in SE.MethodsA case of an adult patient with Lennox–Gastaut syndrome (LGS) who was treated with FFA due to refractory SE is presented in detail. To identify studies that evaluated the use of FFA in SE, we performed a systematic literature search.ResultsFour case reports on the acute treatment with FFA of SE in children and adults with Dravet syndrome (DS) and LGS were available. We report in detail a 30-year-old woman with LGS of structural etiology, who presented with generalized tonic and dialeptic seizures manifesting at high frequencies without a return to clinical baseline constituting the diagnosis of SE. Treatment with anti-seizure medications up to lacosamide 600 mg/d, brivaracetam 300 mg/d, valproate 1,600 mg/d, and various benzodiazepines did not resolve the SE. Due to ongoing refractory SE and following an unremarkable echocardiography, treatment was initiated with FFA, with an initial dose of 10 mg/d (0.22 mg/kg body weight [bw]) and fast up-titration to 26 mg/d (0.58 mg/kg bw) within 10 days. Subsequently, the patient experienced a resolution of SE within 4 days, accompanied by a notable improvement in clinical presentation and regaining her mobility, walking with the assistance of physiotherapists. In the three cases reported in the literature, DS patients with SE were treated with FFA, and a cessation of SE was observed within a few days. No treatment-emergent adverse events were observed during FFA treatment in any of the four cases.ConclusionsBased on the reported cases, FFA might be a promising option for the acute treatment of SE in patients with DS and LGS. Observational data show a decreased SE frequency while on FFA, suggesting a potentially preventive role of FFA in these populations.Key pointsWe summarize four cases of refractory status epilepticus (SE) successfully treated with fenfluramine.Refractory SE resolved after 4–7 days on fenfluramine.Swift fenfluramine up-titration was well-tolerated during SE treatment.Treatment-emergent adverse events on fenfluramine were not observed.Fenfluramine might be a valuable acute treatment option for SE in Dravet and Lennox–Gastaut syndromes.