Treatment Of Status Epilepticus Research Articles

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.

Clinical practice guidelines on the management of status epilepticus in adults: A systematic review.

Status epilepticus (SE) is the second most common neurological emergency in adults. Despite improvements in the management of acute neurological conditions over the last decade, mortality is still durably high. Because a gap has emerged between SE management based on clinical practice guidelines (CPGs) and actual clinical practice, we conducted a systematic review of CPGs, assessing their quality, outlining commonalities and discrepancies in recommendations, and highlighting research gaps. We searched the PubMed and EMBASE databases and other gray literature sources (nine among guideline registries, evidence-based medicinedatabases, point-of-care tools; seven websites of governmental organizations and international neurologic societies) in December 2021 (updated in November 2023). The units of analysis were CPGs that included recommendations on the diagnostic and/or therapeutic management of SE in adults. The quality of the CPGs was assessed using the AGREE II tool. Fifteen CPGs were included. The "Applicability" domain was assigned the lowest median score of 10%. The domains "Stakeholder Involvement", "Rigor of Development," and "Editorial Independence" were as well generally underrated. Recommendations on general and diagnostic management and on organizational interventions were fragmented and scattered. Recommendations on pre-hospital and hospital treatment of early-onset and refractory SE were broadly agreed, whereas there was less agreement on the treatment model and medications for established SE and super-refractory SE. The CPGs for the management of SE developed in recent years are flawed by several methodological issues and discrepancies in the coverage of important topics. The gap between CPG-based management of SE and actual clinical practice may be due in part to the inherent limitations of the CPGs produced so far.

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.

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.

Surgical management of status epilepticus: A systematic review.

Status Epilepticus (SE), unresponsive to medical management, is associated with high morbidity and mortality. Surgical management is typically considered in these refractory cases. The best surgical approach for affected patients remains unclear; however, given the lack of controlled trials exploring the role of surgery. We performed a systematic review according to PRIMSA guidelines, including case reports and series describing surgical interventions for patients in SE. Cases (157 patients, median age 12.9 years) were followed for a median of 12 months. Patients were in SE for a median of 21 days before undergoing procedures including: focal resection (36.9%), functional hemispherectomy (21%), lobar resection (12.7%), vagus nerve stimulation (VNS) (12.7%), deep brain stimulation (DBS) (6.4%), multiple subpial transection (MST) (3.8%), responsive neurostimulation (RNS) (1.9%), and cortical stimulator placement (1.27%), with 24 patients undergoing multiple procedures. Multiple SE semiologies were identified. 47.8% of patients had focal seizures, and 65% of patients had focal structural abnormalities on MRI. SE persisted for 36.8 ± 47.7 days prior to surgical intervention. SE terminated following surgery in 81.5%, terminated with additional adjuncts in 10.2%, continued in 1.9%, and was not specified in 6.4% of patients. Long-term seizure outcomes were favorable, with the majority improved and 51% seizure-free. Eight patients passed away in follow-up, of which three were in SE. Seizures emerging from one hemisphere were both more likely to immediately terminate (OR 4.7) and lead to long-term seizure-free status (OR 3.9) compared to nonunilateral seizures. No other predictors, including seizure focality, SE duration, or choice of surgical procedure, were predictors of SE termination. Surgical treatment of SE can be effective in terminating SE and leading to sustained seizure freedom, with many different procedures showing efficacy if matched appropriately with SE semiology and etiology. PLAIN LANGUAGE SUMMARY: Patients with persistent seizures (Status Epilepticus) that do not stop following medications can be treated effectively with surgery. Here, we systematically review the entirety of existing literature on surgery for treating status epilepticus to better identify how and when surgery is used and what patients do after surgery.

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.

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.

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.

The Role of Early Intubation in Status Epilepticus with Out-of-Hospital Onset: A Large Prospective Observational Study.

Background: this study aimed to evaluate the role of early airway management and intubation in status epilepticus (SE) with out-of-hospital onset. Methods: We included all patients with out-of-hospital SE onset referred to the emergency department of the Academic Hospital of Modena between 2013 and 2021. Patients were compared according to out-of-hospital airway management (intubation versus non-intubation) and a propensity score was performed for clinical variables unevenly distributed between the two groups. Results: We evaluated 711 patients with SE. A total of 397 patients with out-of-hospital SE onset were eventually included; of these, 20.4% (81/397) were intubated before arrival at the hospital. No difference was found in the clinical characteristics of patients after propensity score matching. The 30-day mortality in the propensity group was 19.4% (14/72), and no difference was found between intubated (7/36, 19.4%) and non-intubated (7/36, 19.4%) patients. No difference was found in SE cessation. Compared to non-intubated patients, those who underwent out-of-hospital intubation had a higher risk of progression to refractory or super-refractory SE, greater worsening of mRS values between hospital discharge and admission, and lower probability of returning to baseline condition at 30 days after SE onset. Conclusions: Early intubation for out-of-hospital SE onset is not associated with improved patient survival even after balancing for possible confounders. Further studies should evaluate the timing of intubation and its association with first-line treatments for SE and their efficacy. In addition, they should focus on the settings and the exact reasons leading to intubation to better inform early management of SE with out-of-hospital onset.

Ketamine in the treatment of refractory and super-refractory status epilepticus: Experience from two centres

PurposeThere is insufficient evidence on the management of refractory status epilepticus (RSE) and super-RSE (SRSE). Ketamine is a N-methyl-d-aspartate receptor antagonist in the treatment of these entities. Our objectives were to study the effectiveness and safety of ketamine in the treatment of adult patients with RSE and SRSE, to determine the factors that can influence the response to ketamine, and to explore its use in patients without mechanical ventilation. MethodsAdult patients who had received intravenous ketamine for the treatment of RSE or SRSE at Hospital Universitario Clínico San Carlos (Madrid, Spain) or Hospital Universitari Vall d'Hebron (Barcelona, Spain) from 2017 to 2023 were retrospectively analysed. ResultsThis study included 58 adult patients, mean (standard deviation) age 60.2 (15.7) years, of whom 41 (70.7 %) were male; 33 (56.9 %) patients responded to ketamine without recurrence, with a low rate of adverse effects (8.6 %). The presence of SRSE at the time of ketamine initiation (OR 0.287, p = 0.028) and the time elapsed between status epilepticus onset and ketamine administration (OR 0.991, p = 0.034) were associated with worse response to ketamine. Patients treated without mechanical ventilation had similar rates of response without recurrence (62.5% vs 56.9 %) and lower mortality (37.5% vs 53.5 %) compared to the overall group. ConclusionKetamine is an effective drug with few adverse effects. Prompt administration should be considered in patients with RSE requiring anaesthesia, in patients with SRSE, and in patients with RSE who do not respond to standard antiseizure drugs and in whom mechanical ventilation is not advised.

Management of status epilepticus in pregnancy: a clinician survey

BackgroundStatus epilepticus in pregnancy (SEP) is rare and life-threatening for both mother and fetus. There are well-established guidelines for the management of women with epilepsy during pregnancy; however, there is little evidence guiding the management of SEP, leading to uncertainty among treating physicians. Therefore, this survey aims to investigate the real-world practices of physicians treating SEP to explore management approaches for improvements in care.MethodsAn anonymous, electronic survey was created and distributed to neurointensivists and neurologists between September and December 2021.ResultsOne hundred physicians initiated the survey and 95 completed it in full: 87 (87%, 87/100) identified neurology as their primary specialty, 31 had subspecialty training in neurocritical care, and 48 had subspecialty training in epilepsy and/or clinical neurophysiology. Over half of the survey respondents (67%, 67/100) reported having participated in the management of SEP, with 48.9% (49/98) having done so in the past year. Most survey respondents (73%, 73/100) reported that their management approach to SEP is different than that of non-pregnant patients. Survey respondents were more likely to involve epilepsy consultants when treating SEP (58.5%, 58/99) and the vast majority involved Obstetrics/Maternal Fetal Medicine consultants (90.8%, 89/98). Survey respondents showed a clear preference for levetiracetam (89.7%, 87/97) in the treatment of benzodiazepine refractory status epilepticus followed by lacosamide (61%, 60/98) if an additional second line agent was needed. Valproate and phenobarbital were unlikely to be used. There was less agreement for the management of refractory and super-refractory SEP.ConclusionsLevetiracetam is the most frequently used anti-seizure medication (ASM) for benzodiazepine-refractory SEP. Survey participants tended to manage SEP differently than in non-pregnant patients including greater involvement of interdisciplinary teams as well as avoidance of ASMs associated with known teratogenicity.