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General anesthesia (GA) earlier than recommended (as first‐ or second‐line treatment) was recently described to improve status epilepticus (SE) outcome. We aimed to assess the impact of early GA on outcome in matched groups. Data from a multicenter, prospective cohort of 1179 SE episodes in 1049 adults were retrospectively analyzed. Incident SE episodes were categorized as “early anesthesia” (eGA; GA as first‐ or second‐line treatment) or “non‐early anesthesia” (neGA; GA after second‐line treatment or not at all). Using propensity score matching, eGA episodes were paired 1:4 with neGA episodes. We assessed survival, functional outcomes at discharge (good: modified Rankin Scale = 0–2 or no worsening), SE cessation rate, SE duration, and hospital stay. Among 1049 SE episodes, 55 (5.2%) received eGA, and 994 constituted the neGA group; 220 represented the matched controls. Patients receiving eGA were younger (median = 63, interquartile range [IQR] = 56–76 vs. median = 70, IQR = 54–80 years, p = .004), had deeper consciousness impairment (80% vs. 40% stuporous/comatose, p < .001), and had more severe SE forms (89% vs. 54% generalized convulsive SE/nonconvulsive SE in coma, p < .001). Mortality, functional outcome, SE cessation rate, and duration of SE and hospital stay were similar between the eGA group and matched controls. We conclude that early anesthesia for SE treatment did not influence prognosis. [ABSTRACT FROM AUTHOR]

Background: There is not a preferred medication for treating refractory status epilepticus (RSE) and intravenous ketamine is increasingly used. Ketamine efficacy, safety, dosage, and influence of other variables on seizure cessation while on ketamine infusions are not well studied. We aimed to characterize ketamine effect on RSE, including interictal activity on electroencephalogram (EEG) and when done by Teleneurocritical care (TNCC). Methods: We conducted a multicenter, retrospective study from August 2017 to October 2022. Patients 18 years or older who had RSE and received ketamine were included. The primary outcome was effect of ketamine on RSE including interictal activity; secondary outcomes were effect of other variables on RSE, care by TNCC, ketamine infusion dynamics, adverse events, and discharge outcomes. Logistic regression was used. Results: Fifty-one patients from five hospitals met inclusion criteria; 30 patients had RSE and interictal activity on EEG. Median age was 56.8 years (IQR 18.2) and 26% had previously diagnosed epilepsy. Sixteen (31%) patients were treated virtually by TNCC. In those with RSE on EEG, ketamine was added as the fourth antiseizure medication (mean 4.4, SD 1.6). An initial bolus of ketamine was used in 24% of patients (95 mg, IQR 47.5), the median infusion rate was 30.8 mcg/kg/min (IQR 40.4), and median infusion duration was 40 h (IQR 37). Ketamine was associated with 50% cessation of RSE and interictal activity at 24 h in 84% of patients, and complete seizure cessation in 43% of patients. In linear regression, ASMs prior to ketamine were associated with seizure cessation (OR 2.6, 95% CI 0.9–6.9, p = 0.05), while the inverse was seen with propofol infusions (OR 0.02, 95% CI 0.001–0.43, p = 0.01). RSE management by in-person NCC versus virtual by TNCC did not affect rates of seizure cessation. Conclusions: Ketamine infusions for RSE were associated with reduced seizure burden at 24 h, with 84% of patients having 50% seizure reduction. Similar efficacy and safety was observed irrespective of underlying RSE etiology or when done via TNCC vs in-person NCC. [ABSTRACT FROM AUTHOR]

We aimed to provide a detailed phenotypic description of status epilepticus (SE) in a large cohort of patients with POLG disease and identify prognostic biomarkers to improve the management of this life-threatening condition. In a multinational, retrospective study with data on patients with POLG disease from seven European countries, we identified those who had SE. The age of SE onset, accompanying clinical, laboratory, imaging and genetic findings were analysed. One hundred and ninety-five patients with genetically confirmed POLG disease were recruited, of whom 67% (130/194) had epilepsy. SE was identified in 77% (97/126), with a median age of SE onset of 7 years. SE was the presenting symptom of the disease in 43% (40/93) of those with SE, while 57% (53/93) developed SE during the disease course. Convulsive SE was reported in 97% (91/94) followed by epilepsia partialis continua in 67% (56/84). Liver impairment 78% (74/95), ataxia 69% (60/87), stroke-like episodes 57% (50/88), were the major comorbidities. In the majority (66%; 57/86) with SE this became refractory or super-refractory. The presence of seizures was associated with significantly higher mortality compared to those without (P ≤ 0.001). The median time from SE debut to death was 5 months. SE is a major clinical feature of POLG disease in early and juvenile to adult-onset disease and can be the presenting feature or arise as part of a multisystem disease. It is associated with high morbidity and mortality, with the majority of patients with SE going on to develop refractory or super-refractory SE. [ABSTRACT FROM AUTHOR]

• The cause of pediatric refractory status epilepticus is unclear in many cases despite a thorough diagnosis. • Identifying etiologies may enable effective treatment of new-onset refractory status epilepticus (NORSE). • NORSE etiology was classified into genetic and non-genetic based on clinical features. • The age at onset and seizure refractoriness associate with the etiologies of NORSE. New-onset refractory status epilepticus (NORSE) is defined as a state of prolonged seizure activity that does not improve despite the appropriate administration of medications, with underlying causes unknown after the initial diagnosis of status epilepticus. Because episodes of NORSE are accompanied by severe complications and a high risk of mortality, the prompt identification of the underlying cause is crucial for effective treatment and outcome prediction. This study assessed the relationship of NORSE etiologies with baseline clinical features in pediatric population. Seventy-one pediatric patients, under 18 years of age at the initial diagnosis (4.50 ± 4.04, mean ± standard deviation), who experienced at least one episode of NORSE and underwent a comprehensive diagnostic evaluation between January 2005 and June 2020 at our center, were retrospectively selected. We reviewed clinical features at disease onset and long-term follow-up data. Uniform manifold approximation and projection (UMAP) was used to distinguish etiological clusters according to baseline clinical characteristics, and further analysis was performed based on underlying etiologies. Two distinct etiological groups—genetic and non-genetic—were identified based on the UMAP of clinical characteristics. Dravet syndrome (12/15, 80%) was more predominant in patients with a genetic diagnosis, whereas cryptogenic NORSE and encephalitis were prevalent in patients without a genetic diagnosis. The analysis of etiological categories revealed that age at the onset of status epilepticus (P=0.021) and progression to super refractory status epilepticus (SRSE) (P=0.038) were independently associated with differences in etiologies. Several clinical features in patients with NORSE, including the age of onset and the development of SRSE, can help identify underlying causes, which necessitate prompt and adequate treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Treating refractory status epilepticus (RSE) remains a challenge. Thiamylal can be used as a second- or third-line treatment; however, its potential to induce cytochrome P450 (CYP) activity may reduce the concentration of antiepileptic drugs (AEDs) administered prior to thiamylal. This report details a case of RSE patient treated with thiamylal, with monitored concentrations of thiamylal and other AEDs. Case presentation A 72-year-old healthy man developed RSE. Despite the administration of various AEDs, his seizures were not resolved. Thiamylal was then administered at an initial bolus dose of 2.1 mg/kg, followed by a continuous infusion of 4.2–5.2 mg/kg/h. The initial thiamylal concentration was observed at 7.8 μg/mL, increasing to 35.2 μg/mL before decreasing after dose reduction and cessation. Concurrently, the concentration of concomitant carbamazepine decreased from 5.59 μg/mL to 2.1 μg/mL and recovered as thiamylal concentration decreased. Lesser impacts were noted for other AEDs. Conclusions This case report underscored the efficacy of thiamylal in treating RSE. However, it also highlighted the need for clinicians to closely monitor the concentrations of concurrent AEDs, especially carbamazepine, during thiamylal therapy.

Abstract 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.

Background: Treating refractory status epilepticus (RSE) remains a challenge. Thiamylal can be used as a second- or third-line treatment; however, its potential to induce cytochrome P450 (CYP) activity may reduce the concentration of antiepileptic drugs (AEDs) administered prior to thiamylal. This report details a case of RSE patient treated with thiamylal, with monitored concentrations of thiamylal and other AEDs. Case presentation: A 72-year-old healthy man developed RSE. Despite the administration of various AEDs, his seizures were not resolved. Thiamylal was then administered at an initial bolus dose of 2.1 mg/kg, followed by a continuous infusion of 4.2–5.2 mg/kg/h. The initial thiamylal concentration was observed at 7.8 μg/mL, increasing to 35.2 μg/mL before decreasing after dose reduction and cessation. Concurrently, the concentration of concomitant carbamazepine decreased from 5.59 μg/mL to 2.1 μg/mL and recovered as thiamylal concentration decreased. Lesser impacts were noted for other AEDs. Conclusions: This case report underscored the efficacy of thiamylal in treating RSE. However, it also highlighted the need for clinicians to closely monitor the concentrations of concurrent AEDs, especially carbamazepine, during thiamylal therapy. [ABSTRACT FROM AUTHOR]

Super refractory status epilepticus (SRSE) is a condition associated with high rates of mortality and morbidity. We report the treatment protocol of magnesium sulphate infusion adapted for the management of a case of super refractory status epilepticus that lasted for 4 weeks. A young lady presented in altered sensorium with a history of fever followed by uncontrolled seizures of 2 weeks duration. Her serum tested weakly positive for GABA-B receptor antibody. Her seizures were not controlled despite being on multiple antiepileptics and anesthetic induction. Intravenous magnesium infusion was initiated and serum magnesium was titrated up to a final target concentration of 3.8–6.5 mg/dl. Seizure control was achieved after 11 days of the infusion. This case is the longest reported successful use of magnesium sulfate infusion for control of super refractory status epileptics. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Copyright of Neurologie Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Neurologie Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Folia Pharmaceutica Cassoviensia is the property of University of Veterinary Medicine & Pharmacy in Kosice and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: This study aimed to review the demographic characteristics, type, and etiology of status epilepticus (SE) cases followed in our hospital for a period of 1 year and to reveal the factors affecting the prognosis of the patients. Methods: Patients diagnosed with SE among the patients who applied to the emergency department of our hospital within a 1-year period (August 2018 and August 2019) and who were consulted to us because of epileptic seizures or changes in consciousness and behavior while being followed up in the services or intensive care unit were retrospectively screened. Results: A total of 51 patients, 28 female (54.9%) and 23 male (45.1%), were included in our study. Twenty-eight patients were under or equal to the age of 60, and 23 patients were over the age of 60. Twenty-one patients had convulsive SE, 18 patients had non-convulsive SE (NCSE), and 14 patients were transitioning from convulsive SE to NCSE. Causes of SE were; lack of anti-seizure drugs (ASD) in 9 patients, intracranial mass in 9 patients, infection in 8 patients, and cerebrovascular event in 6 patients. Refractory SE cases were mostly observed in patients who developed SE due to lack of ASD and infection. In addition to first-line treatment with benzodiazepines, intravenous (IV) phenytoin, levetiracetam, valproic acid, and oral topiramate and lacosamide treatments were used. It was observed that 26 patients who developed refractory SE were treated with IV midazolam, propofol, or thiopental infusion. It was observed that 2 patients died because of refractory seizures. Conclusion: SE is an important condition that requires rapid treatment and can be fatal. In this cross-sectional study, the demographic characteristics and etiological causes of SE cases registered in our center were presented, and the characteristics of refractory SE cases were also mentioned.

Abstract Focal cortical dysplasia (FCD) represents the most common cause of drug‐resistant epilepsy in adult and pediatric surgical series. However, genetic factors contributing to severe phenotypes of FCD remain unknown. We present a patient with an exceptionally rapid development of drug‐resistant epilepsy evolving in super‐refractory status epilepticus. We performed multiple clinical (serial EEG, MRI), biochemical (metabolic and immunological screening), genetic (WES from blood‐ and brain‐derived DNA), and histopathological investigations. The patient presented 1 month after an uncomplicated varicella infection. MRI was negative, as well as other biochemical and immunological examinations. Whole‐exome sequencing of blood‐derived DNA detected a heterozygous paternally inherited variant NM_006267.4(RANBP2):c.5233A>G p.(Ile1745Val) (Chr2[GRCh37]:g.109382228A>G), a gene associated with a susceptibility to infection‐induced acute necrotizing encephalopathy. No combination of anti‐seizure medication led to a sustained seizure freedom and the patient warranted induction of propofol anesthesia with high‐dose intravenous midazolam and continuous respiratory support that however failed to abort seizure activity. Brain biopsy revealed FCD type IIa; this finding led to the indication of an emergency right‐sided hemispherotomy that rendered the patient temporarily seizure‐free. Postsurgically, he remains on antiseizure medication and experiences rare nondisabling seizures. This report highlights a uniquely severe clinical course of FCD putatively modified by the RANBP2 variant. Plain Language Summary We report a case summary of a patient who came to our attention for epilepsy that could not be controlled with medication. His clinical course progressed rapidly to life‐threatening status epilepticus with other unusual neurological findings. Therefore, we decided to surgically remove a piece of brain tissue in order to clarify the diagnosis that showed features of a structural brain abnormality associated with severe epilepsy, the focal cortical dysplasia. Later, a genetic variant in a gene associated with another condition, was found, and we hypothesize that this genetic variant could have contributed to this severe clinical course of our patient.

Focal cortical dysplasia (FCD) represents the most common cause of drug‐resistant epilepsy in adult and pediatric surgical series. However, genetic factors contributing to severe phenotypes of FCD remain unknown. We present a patient with an exceptionally rapid development of drug‐resistant epilepsy evolving in super‐refractory status epilepticus. We performed multiple clinical (serial EEG, MRI), biochemical (metabolic and immunological screening), genetic (WES from blood‐ and brain‐derived DNA), and histopathological investigations. The patient presented 1 month after an uncomplicated varicella infection. MRI was negative, as well as other biochemical and immunological examinations. Whole‐exome sequencing of blood‐derived DNA detected a heterozygous paternally inherited variant NM_006267.4(RANBP2):c.5233A>G p.(Ile1745Val) (Chr2[GRCh37]:g.109382228A>G), a gene associated with a susceptibility to infection‐induced acute necrotizing encephalopathy. No combination of anti‐seizure medication led to a sustained seizure freedom and the patient warranted induction of propofol anesthesia with high‐dose intravenous midazolam and continuous respiratory support that however failed to abort seizure activity. Brain biopsy revealed FCD type IIa; this finding led to the indication of an emergency right‐sided hemispherotomy that rendered the patient temporarily seizure‐free. Postsurgically, he remains on antiseizure medication and experiences rare nondisabling seizures. This report highlights a uniquely severe clinical course of FCD putatively modified by the RANBP2 variant. Plain Language Summary: We report a case summary of a patient who came to our attention for epilepsy that could not be controlled with medication. His clinical course progressed rapidly to life‐threatening status epilepticus with other unusual neurological findings. Therefore, we decided to surgically remove a piece of brain tissue in order to clarify the diagnosis that showed features of a structural brain abnormality associated with severe epilepsy, the focal cortical dysplasia. Later, a genetic variant in a gene associated with another condition, was found, and we hypothesize that this genetic variant could have contributed to this severe clinical course of our patient. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to review the demographic characteristics, type, and etiology of status epilepticus (SE) cases followed in our hospital for a period of 1 year and to reveal the factors affecting the prognosis of the patients. Methods: Patients diagnosed with SE among the patients who applied to the emergency department of our hospital within a 1-year period (August 2018 and August 2019) and who were consulted to us because of epileptic seizures or changes in consciousness and behavior while being followed up in the services or intensive care unit were retrospectively screened. Results: A total of 51 patients, 28 female (54.9%) and 23 male (45.1%), were included in our study. Twenty-eight patients were under or equal to the age of 60, and 23 patients were over the age of 60. Twenty-one patients had convulsive SE, 18 patients had non-convulsive SE (NCSE), and 14 patients were transitioning from convulsive SE to NCSE. Causes of SE were; lack of anti-seizure drugs (ASD) in 9 patients, intracranial mass in 9 patients, infection in 8 patients, and cerebrovascular event in 6 patients. Refractory SE cases were mostly observed in patients who developed SE due to lack of ASD and infection. In addition to first-line treatment with benzodiazepines, intravenous (IV) phenytoin, levetiracetam, valproic acid, and oral topiramate and lacosamide treatments were used. It was observed that 26 patients who developed refractory SE were treated with IV midazolam, propofol, or thiopental infusion. It was observed that 2 patients died because of refractory seizures. Conclusion: SE is an important condition that requires rapid treatment and can be fatal. In this cross-sectional study, the demographic characteristics and etiological causes of SE cases registered in our center were presented, and the characteristics of refractory SE cases were also mentioned. [ABSTRACT FROM AUTHOR]

Background and purpose: This study aimed to evaluate whether differences in clinical outcomes exist according to treatments received and seizure activity resolution in patients with refractory status epilepticus (RSE). Methods: Consecutive episodes of non-hypoxic status epilepticus (SE) in patients ≥ 14 years old were included. Episodes of RSE were stratified in: (i) SE persistent despite treatment with first‐line therapy with benzodiazepines and one second‐line treatment with antiseizure medications (ASMs), but responsive to successive treatments with ASMs (RSE-rASMs); (ii) SE persistent despite treatment with first‐line therapy with benzodiazepines and successive treatment with one or more second-line ASMs, but responsive to anesthetic drugs [RSE-rGA (general anesthesia)]. Study endpoints were mortality during hospitalization and worsening of modified Rankin Scale (mRS) at discharge. Results: Status epilepticus was responsive in 298 (54.1%), RSE-rASMs in 152 (27.6%), RSE-rGA in 46 (8.3%), and super-refractory (SRSE) in 55 (10.0%) out of 551 included cases. Death during hospitalization occurred in 98 (17.8%) and worsening of mRS at discharge in 287 (52.1%) cases. Multivariable analyses revealed increased odds of in-hospital mortality with RSE-rGA (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.27–7.35) and SRSE (OR 3.83, 95%. CI 1.73–8.47), and increased odds of worsening of mRS with RSE-rASMs (OR 2.06, 95% CI 1.28–3.31), RSE-rGA (OR 4.44, 95% CI 1.97–10.00), and SRSE (OR 13.81, 95% CI 5.34–35.67). Conclusions: In RSE, varying degrees of refractoriness may be defined and suit better the continuum spectrum of disease severity and the heterogeneity of SE burden and prognosis. [ABSTRACT FROM AUTHOR]

Refractory status epilepticus (RSE) is a diagnosis that can be made when tonic-clonic status epilepticus (SE) and focal SE cannot be stopped by at least two anti-seizure medications after 30 and 60 minutes, respectively, from the time of commencement. It could result in mortality, loss of functionality, neurological deficiency, and other serious short- and long-term effects. This narrative review covers original clinical studies of any design and case series investigating long-term outcomes of RSE recorded after at least a year from the SE onset. The future of a patient with RSE rests mostly on the long-term effects of this severe pathological condition, which may be accompanied with systemic complications like hyperthermia, hyperkalemia, acidosis, and/or stress cardiomyopathy. Younger patients with less severe RSE of shorter duration, particularly of the convulsive kind, are reported to have better long-term outcomes. Previous studies on the factors influencing the long-term outcomes of RSE, however, did not link the outcomes to treatment options for the condition. Such circumstances currently prevent making any definitive recommendations on the treatment of RSE until future research with adequate statistical power is completed. [ABSTRACT FROM AUTHOR]

Endotracheal intubation, frequently required during management of refractory status epilepticus (RSE), can be facilitated by anesthetic medications; however, their effectiveness for RSE control is unknown. We performed a single-center retrospective review of patients admitted to a neurocritical care unit (NCCU) who underwent in-hospital intubation during RSE management. Patients intubated with propofol, ketamine, or benzodiazepines, termed anti-seizure induction (ASI), were compared to patients who received etomidate induction (EI). The primary endpoint was clinical or electrographic seizures within 12 h post-intubation. We estimated the association of ASI on post-intubation seizure using logistic regression. A sub-group of patients undergoing electroencephalography during intubation was identified to evaluate the immediate effect of ASI on RSE. We screened 697 patients admitted to the NCCU for RSE and identified 148 intubated in-hospital (n = 90 ASI, n = 58 EI). There was no difference in post-intubation seizure (26 % (n = 23) ASI, 29 % (n = 17) EI) in the cohort, however, there was increased RSE resolution with ASI in 24 patients with electrographic RSE during intubation (ASI: 61 % (n = 11/18) vs EI: 0 % (n = 0/6), p =.016). While anti-seizure induction did not appear to affect post-intubation seizure occurrence overall, a sub-group of patients undergoing electroencephalography during intubation had a higher incidence of seizure cessation, suggesting potential benefit in an enriched population.

OBJECTIVE: Examine the association of duration of therapeutic coma (TC) with seizure recurrence, morbidity, and mortality in refractory status epilepticus (RSE). Define an optimal window for TC that provides sustained seizure control and minimizes complications. METHODS: Retrospective, observational cohort study involving patients who presented with RSE to the University of Alabama at Birmingham or the University of California at San Francisco from 2010 to 2016. Relationship of duration of TC with primary and secondary outcomes was evaluated using two-sample t tests, simple linear regression, and chi-square tests. Multivariable linear and logistic regression models were used to identify independent predictors. Predictive ability of TC for seizure recurrence was quantified using a receiver-operating characteristic curve. Youden index was used to determine an optimal cutoff value. RESULTS: Multivariable analysis of clinical and treatment characteristics of 182 patients who were treated predominantly with propofol as anesthetic agent showed that longer duration of the first trial of TC (27.2 vs 15.6 hours) was independently associated with a higher chance of seizure recurrence following the first weaning attempt (P = 0.038) but not with poor functional neurologic outcome upon discharge, in-hospital complications, or mortality. Furthermore, higher doses of anesthetic utilized during the first trial of TC were independently associated with fewer in-hospital complications (P = 0.003) and associated with a shorter duration of mechanical ventilation and total length of stay. Duration of TC was identified as an independent predictor of seizure recurrence with an optimal cutoff point at 35 hours. SIGNIFICANCE: This study suggests that a shorter duration yet deeper TC as treatment for RSE may be more effective and safer than the currently recommended TC duration of 24-48 hours. Prospective and randomized trials should be conducted to validate these assertions.

Abstract Objective To discuss the results of the KETASER01 trial and the reasons for its failure, particularly in view of future studies. Methods KETASER01 is a multicenter, randomized, controlled, open‐label, sequentially designed, non‐profit Italian study that aimed to assess the efficacy of ketamine compared with conventional anesthetics in the treatment of refractory convulsive status epilepticus (RCSE) in children. Results During the 5‐year recruitment phase, a total of 76 RCSEs treated with third‐line therapy were observed in five of the 10 participating Centers; only 10 individuals (five for each study arm; five females, mean age 6.5 ± 6.3 years) were enrolled in the KETASER01 study. Two of the five patients (40%) in the experimental arm were successfully treated with ketamine and two of the five (40%) children in the control arm, where successfully treated with thiopental. In the remaining six (60%) enrolled patients, RCSE was not controlled by the randomized anesthetic(s). Significance The KETASER01 study was prematurely halted due to low eligibility of patients and no successful recruitment. No conclusions can be drawn regarding the objectives of the study. Here, we discuss the KETASER01 results and critically analyze the reasons for its failure in view of future trials.

Introduction: Febrile infection-related epilepsy syndrome (FIRES) is a severe childhood epilepsy with refractory status epilepticus after a typically mild febrile infection. The etiology of FIRES is largely unknown, and outcomes in most individuals with FIRES are poor. Methods: Here, we reviewed the current state-of-the art genetic testing strategies in individuals with FIRES. We performed a systematic computational analysis to identify individuals with FIRES and characterize the clinical landscape using the Electronic Medical Records (EMR). Among 25 individuals with a confirmed FIRES diagnosis over the last decade, we performed a comprehensive review of genetic testing and other diagnostic testing. Results: Management included use of steroids and intravenous immunoglobulin (IVIG) in most individuals, with an increased use of immunomodulatory agents, including IVIG, plasma exchange (PLEX) and immunosuppressants such as cytokine inhibitors, and the ketogenic diet after 2014. Genetic testing was performed on a clinical basis in almost all individuals and was non-diagnostic in all patients. We compared FIRES with both status epilepticus (SE) and refractory status epilepticus (RSE) as a broader comparison cohort and identified genetic causes in 36% of patients with RSE. The difference in genetic signatures between FIRES and RSE suggest distinct underlying etiologies. In summary, despite the absence of any identifiable etiologies in FIRES, we performed an unbiased analysis of the clinical landscape, identifying a heterogeneous range of treatment strategies and characterized real-world clinical practice. Discussion: FIRES remains one of the most enigmatic conditions in child neurology without any known etiologies to date despite significant efforts in the field, suggesting a clear need for further studies and novel diagnostic and treatment approaches. [ABSTRACT FROM AUTHOR]

Background: In this study, we identify factors associated with ketamine success in the treatment of refractory status epilepticus (SE). We also evaluate for adverse events including systemic and cerebral hemodynamic stability and fluid volume overload. Methods: In this retrospective, large, single-center, observational study over a 10-year period, 879 consecutive patients receiving intravenous (IV) ketamine were reviewed, and 81 patients were identified as receiving IV ketamine for the treatment of SE. Descriptive analysis was done to determine treatment response and adverse events in patients receiving IV ketamine for SE. Multivariable logistic regression analyses were fitted to determine prediction models for seizure cessation. Results: Permanent cessation of SE was achieved in 49 of 81 (60.5%) of patients for whom ketamine was part of the treatment plan. Of those, 36 (44.4%) were attributed to ketamine as the last drug used (ketamine-associated cessation [AC]). Prior history of epilepsy had an odds ratio of 3.19 (confidence interval 0.83–12.67, p = 0.09) associated with efficacious medication response. Increased latency to ketamine was associated with cessation of SE specifically in patients in the AC group (p = 0.077). Longer SE duration (p = 0.04), administration of ketamine loading dose (bolus; p = 0.03), and anoxia (p = 0.007) were negatively associated with AC. Administration of ketamine loading dose (p = 0.02) and anoxia (p = 0.009) were negatively associated with overall SE cessation. There was no significant impact of ketamine on cerebral hemodynamics, but evidence of fluid volume overload was seen (28.4% of patients). Conclusions: Our cohort is a large observational study showing a high success rate of permanent cessation of SE after the addition of ketamine. Using multivariable analysis, we demonstrate a significant association with seizure cessation in patients with prior history of epilepsy and those with prolonged latency to ketamine initiation. Furthermore, we describe the impact of fluid volume overload as an anticipated complication with ketamine use. [ABSTRACT FROM AUTHOR]

Continuous ketamine infusions have been studied as an adjunctive agent for refractory status epilepticus (RSE) and super refractory status epilepticus (SRSE) in older children and adults. However, minimal information exists on the efficacy, safety, and dosing for continuous ketamine in young infants. We present the clinical course of 3 young infants with RSE and SRSE who received continuous ketamine in conjunction with other antiseizure medications. The condition of these patients was refractory to an average of 6 antiseizure medications before initiation of continuous ketamine infusion. For each patient, a continuous ketamine infusion was initiated at a rate of 1 mg/kg/hr with 1 patient requiring titration to a maximum of 6 mg/ kg/hr. In 1 case, the concomitant use of continuous ketamine allowed for a reduction in the benzodiazepine continuous infusion rate. In all cases, ketamine was well tolerated especially in the setting of hemodynamic instability. Ketamine may provide a safe adjunct in the acute setting in severe RSE and SRSE. This is the first case series to document the use of continuous ketamine as a treatment modality in young infants with RSE or SRSE secondary to various underlying etiologies, without adverse events. Further studies are needed to evaluate the long-term safety and efficacy of continuous ketamine in this patient population. [ABSTRACT FROM AUTHOR]

• Decision-tree analysis provided a meaningful risk stratification based on few variables that are easily obtained at SE first evaluation. • The decision tree identified nodes with a risk of evolution to RSE ranging from 1.5% to 90.8%. • The overall percentage of success in classifying patients of the decision tree was 79.4% • CART models must be viewed as potential new method for the stratification RSE at single subject level deserving further exploration and validation. to identify predictors of progression to refractory status epilepticus (RSE) using a machine learning technique. Consecutive patients aged ≥ 14 years with SE registered in a 9-years period at Modena Academic Hospital were included in the analysis. We evaluated the risk of progression to RSE using logistic regression and a machine learning analysis by means of classification and regression tree analysis (CART) to develop a predictive model of progression to RSE. 705 patients with SE were included in the study; of those, 33 % (233/705) evolved to RSE. The progression to RSE was an independent risk factor for 30-day mortality, with an OR adjusted for previously identified possible univariate confounders of 4.086 (CI 95 % 2.390–6.985; p < 0.001). According to CART the most important variable predicting evolution to RSE was the impaired consciousness before treatment, followed by acute symptomatic hypoxic etiology and periodic EEG patterns. The decision tree identified 14 nodes with a risk of evolution to RSE ranging from 1.5 % to 90.8 %. The overall percentage of success in classifying patients of the decision tree was 79.4 %; the percentage of accurate prediction was high, 94.1 %, for those patients not progressing to RSE and moderate, 49.8 %, for patients evolving to RSE. Decision-tree analysis provided a meaningful risk stratification based on few variables that are easily obtained at SE first evaluation: consciousness before treatment, etiology, and severe EEG patterns. CART models must be viewed as potential new method for the stratification RSE at single subject level deserving further exploration and validation. [ABSTRACT FROM AUTHOR]

• The NORSE/FIRES Family Registry collects clinical and epidemiological data on individuals affected by worldwide. • We examine diagnostic and prognostic information shared, satisfaction with communication, and palliative care use during acute hospitalization. • Communication of NORSE/FIRES presentation to families has improved since the 2018 consensus definitions. • Families rate the prognostic information quality and communication satisfaction as moderate. • Enhancing diagnostic and prognostic conversations is crucial for better care, physician-patient-family relationships, and recovery. The new-onset refractory status epilepticus (NORSE)/febrile infection-related epilepsy syndrome (FIRES) Family Registry contributes to a systematic effort to collect clinical and epidemiological information on individuals affected by NORSE/FIRES. We explore diagnostic and prognostic information provided to patients and their families, their satisfaction with the communication, and utilisation of palliative care services during acute hospitalization. Communication about the diagnosis of NORSE/FIRES to families has improved since the publication of consensus definitions in 2018, with families being more likely to be told about NORSE/FIRES after 2018. Families rate the quality of prognostic information as being moderate. Palliative care services were involved in a minority of patients. Understanding and characterizing the prevalence and satisfaction of diagnostic and prognostic conversations is important for improving overall care, the quality of physician-patient-family relationships, and the recovery process for those affected by NORSE/FIRES. [ABSTRACT FROM AUTHOR]

IntroductionFebrile infection-related epilepsy syndrome (FIRES) is a severe childhood epilepsy with refractory status epilepticus after a typically mild febrile infection. The etiology of FIRES is largely unknown, and outcomes in most individuals with FIRES are poor.MethodsHere, we reviewed the current state-of-the art genetic testing strategies in individuals with FIRES. We performed a systematic computational analysis to identify individuals with FIRES and characterize the clinical landscape using the Electronic Medical Records (EMR). Among 25 individuals with a confirmed FIRES diagnosis over the last decade, we performed a comprehensive review of genetic testing and other diagnostic testing.ResultsManagement included use of steroids and intravenous immunoglobulin (IVIG) in most individuals, with an increased use of immunomodulatory agents, including IVIG, plasma exchange (PLEX) and immunosuppressants such as cytokine inhibitors, and the ketogenic diet after 2014. Genetic testing was performed on a clinical basis in almost all individuals and was non-diagnostic in all patients. We compared FIRES with both status epilepticus (SE) and refractory status epilepticus (RSE) as a broader comparison cohort and identified genetic causes in 36% of patients with RSE. The difference in genetic signatures between FIRES and RSE suggest distinct underlying etiologies. In summary, despite the absence of any identifiable etiologies in FIRES, we performed an unbiased analysis of the clinical landscape, identifying a heterogeneous range of treatment strategies and characterized real-world clinical practice.DiscussionFIRES remains one of the most enigmatic conditions in child neurology without any known etiologies to date despite significant efforts in the field, suggesting a clear need for further studies and novel diagnostic and treatment approaches.

Allopregnanolone (5α-pregnan-3α-ol-20-one) and its synthetic 3β-methyl analog, ganaxolone, are positive allosteric modulators of synaptic and extrasynaptic γ-aminobutyric acid (GABA)A receptors that exhibit antiseizure activity in diverse animal seizure models, including models of status epilepticus (SE). The 2 neuroactive steroids are being investigated as treatments for SE, including as a treatment for SE induced by chemical threat agents. Intramuscular injection is the preferred route of administration in the prehospital treatment of SE. The objective of this study was to assess the efficacy of intramuscular allopregnanolone and ganaxolone in the treatment of SE induced by the chemical threat agent tetramethylenedisulfotetramine (TETS). The test agents were administered 40 minutes after the onset of SE when mice are refractory to treatment. Allopregnanolone and ganaxolone (each at 3 mg/kg) terminated SE in, respectively, 92% and 75% of animals, and prevented mortality in 85% and 50% of animals; the mean times to termination of behavioral seizures were, respectively, 172 ± 16 and 447 ± 52 seconds. In a separate series of experiments, mice were dosed with the neuroactive steroids by intramuscular injection, and plasma and brain levels were sampled at various time points following injection to estimate pharmacokinetic parameters. Plasma Cmax (maximum concentration) values for allopregnanolone and ganaxolone were 645 and 550 ng/mL, respectively. Brain exposure of both steroids was approximately 3-fold the plasma exposure. Two-compartment pharmacokinetic analysis revealed that the central compartment Vd (volume of distribution), CL (clearance), t½ (terminal half-life), and F (intramuscular bioavailability) values for allopregnanolone and ganaxolone were, respectively, 4.95 L/kg 12.88 L/kg/h,16 minutes, 97%, and 5.07 L/kg, 8.35 L/kg/h, 25 minutes, 95%. Allopregnanolone and ganaxolone are effective in the treatment of TETS-induced SE when administered by the intramuscular route. Allopregnanolone is more rapidly acting and modestly more effective, possibly because it has greater potency on GABAA receptors.

Background: Cryptogenic febrile infection-related epilepsy syndrome (FIRES) is a rare but catastrophic encephalopathic condition. We aimed to investigate the long-term outcome in adult cryptogenic FIRES. Methods: This was a retrospective study based on the prospective database in the neuro-intensive care unit of a tertiary hospital in China. Consecutive adult patients with cryptogenic FIRES between July 2007 to December 2021 were included. Long-term outcomes included function independence, the development of drug-resistant epilepsy (DRE), remote recurrent status epilepticus (SE), anti-seizure medications (ASMs), and changes in the brain Magnetic Resonance Imaging (MRI). Results: A total of 11 adult patients with cryptogenic FIRES were identified from 270 patients with SE. Four (36%) patients died in the hospital, with three of them withdrawing treatments, and one patient died 12 months after discharge. After the follow-up ranging from12 to 112months, 6 (55%) patients were still alive, and all of them achieved functional independence [modified Rankin Scale (mRS) 0-3]. 45% (5/11) patients developed DRE, 18% (2/11) had remote recurrent SE, and 55% (6/11) were on polytherapy with ASMs at the last follow-up. Most of the patients with initial normal or abnormal MRI had abnormalities in the hippocampus at follow-up, and most of the other MRI abnormalities found in the acute stage disappeared over time. Conclusion: The outcome of adult cryptogenic FIRES is daunting. More than one-third of patients die in the hospital. Survivors of cryptogenic FIRES may regain functional independence, but they usually develop DRE and receive polytherapy of ASMs for a long time. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to develop consensus‐based recommendations for the management of adult and pediatric patients with new onset refractory status epilepticus (NORSE)/febrile infection‐related epilepsy syndrome (FIRES) based on best evidence and experience. Methods: The Delphi methodology was followed. A facilitator group of nine experts was established, who defined the scope, users, and suggestions for recommendations. Following a review of the current literature, recommendation statements concerning diagnosis, treatment, and research directions were generated, which were then rated on a scale of 1 (strongly disagree) to 9 (strongly agree) by a panel of 48 experts in the field. Consensus that a statement was appropriate was reached if the median score was ≥7 and inappropriate if the median score was ≤3. The analysis of evidence was mapped to the results of each statement included in the Delphi survey. Results: Overall, 85 recommendation statements achieved consensus. The recommendations are divided into five sections: (1) disease characteristics; (2) diagnostic testing and sampling; (3) acute treatment; (4) treatment in the postacute phase; and (5) research, registries, and future directions in NORSE/FIRES. The detailed results and discussion of all 85 statements are outlined herein. A corresponding summary of findings and practical flowsheets are presented in a companion article. Significance: This detailed analysis offers insight into the supporting evidence and the current gaps in the literature that are associated with expert consensus statements related to NORSE/FIRES. The recommendations generated by this consensus can be used as a guide for the diagnosis, evaluation, and management of patients with NORSE/FIRES, and for planning of future research. [ABSTRACT FROM AUTHOR]

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Introduction: Epidemiological data on childhood status epilepticus (SE) limited in India. This study depicts clinical profiles, etiology, and outcomes of convulsive refractory SE (RSE) and compares the results with cases of nonrefractory SE (NRSE). Subjects and Methods: This observational, cross-sectional study enrolled 300 children aged 1 month to 18 years, presenting with convulsive SE at a tertiary care hospital. Details of children who progressed to RSE were compared to those without RSE. Results: In the acute symptomatic etiology group, common causes for RSE were central nervous system infections (33.8%), cryptogenic etiology (13.8%), and remote symptomatic etiology (7%). RSE iwas associated with a higher rate of complications (58% Vs 24%) as compared to NRSE. Thirty percent of cases that progressed to RSE needed ventilator support as compared to only 8% of cases in the NRSE group. RSE was also associated with higher rates of shock (25%), AKI (16%), transaminitis (25%), acute liver failure (5.69%), multiple organ dysfunction score (12.6%), and acidosis (53%) as compared to NRSE. RSE was associated with higher mortality (28%) and morbidity (32%) as compared to NRSE cases. Cryptogenic etiology led to the highest mortality (33.3%) in cases of RSE while acute symptomology was associated with the highest morbidity (62%). Conclusions: RSE is a serious pediatric emergency that requires prompt recognition and management. Clinical knowledge and early administration of appropriate antiepileptic drugs at health-care facilities is the key to reduce morbidity and mortality. [ABSTRACT FROM AUTHOR]

Objectives: Status epilepticus (SE) is a severe neurological condition associated with a poor prognosis. Refractory status epilepticus (RSE) is a treatment-resistant form of SE with an even worse prognosis. The exact mechanisms underlying the development of RSE are not fully understood. The aim of this study was to investigate the factors contributing to the development of RSE in SE patients and to identify predictors of RSE occurrence., Methods: This retrospective study was conducted on patients diagnosed with SE and RSE between 2014 and 2024. Demographic information, comorbid conditions, and blood sample data of the patients were recorded for statistical analysis. The statistical analyses used included the Mann-Whitney U test, Chi-square test, Fisher's exact test, ROC curve analysis, and logistic regression., Results: A total of 82 SE patients were included in the study. Of these, 44 were non-RSE patients (control group), and 38 were RSE patients. Significant differences were observed between the groups in terms of median age (p = 0.001), blood glucose level (p = 0.023), pan-immune inflammation value (PIV) (p = 0.002), Monocyte/Lymphocyte Ratio (MLR) (p = 0.009), Neutrophil/Albumin Ratio (NAR) (p = 0.003), Systemic Immune Inflammation Index (SII) (p = 0.013), Eosinophil/Lymphocyte Ratio (ELR) (p = 0.016), Eosinophil/Neutrophil Ratio (ENR) (p = 0.006), and Eosinophil/Monocyte Ratio (EMR) (p = 0.002). The multivariate logistic regression model identified the presence of arterial hypertension as the only factor significantly associated with the development of RSE (p < 0.001). In the ROC curve analysis, PIV (AUC = 0.696) and NAR (AUC = 0.689) were found to be predictive factors for RSE., Conclusions: The findings obtained in the current study suggest that systemic inflammation and arterial hypertension may be associated with the progression of SE to RSE. Further research is needed to confirm these findings and integrate them into routine clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Exposure to organophosphorus nerve agents irreversibly inhibits acetylcholinesterase and may lead to cholinergic crisis and seizures. Although benzodiazepines are the standard of care after nerve agent-induced status epilepticus, when treatment is delayed for up to 30 min or more, refractory status epilepticus can develop. Adult male rodents are often utilized for evaluation of therapeutic efficacy against nerve agent exposure. However, there may be age and sex differences in toxicity and in therapeutic response. We previously reported that juvenile rats are less susceptible to the lethal effects of soman compared to adults, while pups are the most susceptible. Here, we report on age and sex differences in delayed midazolam treatment efficacy on survival, seizures and brain pathology. Male and female pups, juvenile and adult rats were exposed to an equitoxic dose of soman and treated with atropine sulfate and the oxime asoxime chloride (HI-6 dimethanesulphonate) 1 min after exposure and with midazolam 40 min after seizure onset, determined by EEG in juvenile and adult rats, and by behavior in pups. Survival, seizure data, and spontaneous recurrent seizures were evaluated. Brains were processed to assess neurodegeneration, neuroinflammation, and blood brain barrier (BBB) integrity. Juvenile and adult rats exposed to soman and treated with midazolam had BBB disruption, epileptogenesis, neurodegeneration, microglial activation, and astrogliosis; adult rats had poorer outcomes. Pups and juvenile rats exposed to soman had poor survival prior to midazolam treatment but most survived once treated; overall, neurodegeneration or disrupted BBB integrity was not detected in midazolam-treated pups. We found that age is a determinant factor in soman-induced toxicity and response to standard medical countermeasures. In addition, we observed sex differences in response to soman in juveniles and males with respect to body weight growth curves and in neuronal loss in juveniles and adults. Adjunct therapies to midazolam are warranted and it is important to evaluate both age and sex as factors in therapeutic response., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lucille Lumley reports financial support was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Data for the use of ketamine (Ket) in treatment of refractory and super-refractory status epilepticus (RSE, SRSE) is lacking despite its widespread growing use. We examined the efficacy of ketamine plus midazolam (MDZ) infusions for treating RSE versus midazolam alone. We hypothesized that ketamine initiation would result in earlier seizure termination., Methods: Data was obtained from electronic health records (EHR) of adult patients who received intravenous anesthetic agents for RSE in our neurointensive care unit. Two cohorts were identified. The MDZ cohort received midazolam as the only intravenous anesthetic agent for RSE. The Ket+MDZ cohort received midazolam infusion followed by ketamine infusion. The primary outcomes were time from midazolam infusion start to SE end in both cohorts, and time from ketamine infusion start (Ket Start) to SE end in the Ket+MDZ cohort versus midazolam infusion start (MDZ start) to SE end in the MDZ cohort., Results: 73 patients were included (MDZ cohort n=17, Ket + MDZ cohort n=56). Cohorts did not differ significantly in age, sex, race, RSE etiology, or GCS on admission. Mean APACHE II score was higher in the Ket +MDZ cohort (26 ± 7.32 SD) versus the MDZ cohort (22 ± 5.89 SD)(P=.015). In survival analyses, cohorts did not differ significantly in time from midazolam start to SE end (HR=0.965, 95 % CI=0.556-1.673, P=.899; median [IQR]: MDZ: 25 h [4.5-58]; Ket+MDZ: 21.5 h [IQR 13.5-49]). Time from Ket start (Ket+MDZ group) versus time from MDZ start (MDZ group) to SE end was significantly shorter in the Ket+MDZ cohort (HR=1.895, 95 % CI=1.083-3.314, P=.025). The pattern of results was similar when including APACHE II and MDZ maximum dosage as covariates., Conclusion: Time to SE end was significantly shorter after addition of ketamine infusion to midazolam infusion, versus after initiation of midazolam infusion monotherapy. Patients with higher disease severity favored Ket+MDZ. Randomized controlled trials are warranted in determining optimal anesthetics in RSE and SRSE., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Epidemiological data on childhood status epilepticus (SE) limited in India. This study depicts clinical profiles, etiology, and outcomes of convulsive refractory SE (RSE) and compares the results with cases of nonrefractory SE (NRSE). Subjects and Methods: This observational, cross-sectional study enrolled 300 children aged 1 month to 18 years, presenting with convulsive SE at a tertiary care hospital. Details of children who progressed to RSE were compared to those without RSE. Results: In the acute symptomatic etiology group, common causes for RSE were central nervous system infections (33.8%), cryptogenic etiology (13.8%), and remote symptomatic etiology (7%). RSE iwas associated with a higher rate of complications (58% Vs 24%) as compared to NRSE. Thirty percent of cases that progressed to RSE needed ventilator support as compared to only 8% of cases in the NRSE group. RSE was also associated with higher rates of shock (25%), AKI (16%), transaminitis (25%), acute liver failure (5.69%), multiple organ dysfunction score (12.6%), and acidosis (53%) as compared to NRSE. RSE was associated with higher mortality (28%) and morbidity (32%) as compared to NRSE cases. Cryptogenic etiology led to the highest mortality (33.3%) in cases of RSE while acute symptomology was associated with the highest morbidity (62%). Conclusions: RSE is a serious pediatric emergency that requires prompt recognition and management. Clinical knowledge and early administration of appropriate antiepileptic drugs at health-care facilities is the key to reduce morbidity and mortality.

Abstract Objective Cholinergic‐induced status epilepticus (SE) is associated with a loss of synaptic gamma‐aminobutyric acid A receptors (GABAAR) and an increase in N‐methyl‐D‐aspartate receptors (NMDAR) and amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors (AMPAR) that may contribute to pharmacoresistance when treatment with benzodiazepine antiseizure medication is delayed. The barbiturate phenobarbital enhances inhibitory neurotransmission by binding to a specific site in the GABAAR to increase the open state of the channel, decrease neuronal excitability, and reduce glutamate‐induced currents through AMPA/kainate receptors. We hypothesized that phenobarbital as an adjunct to midazolam would augment the amelioration of soman‐induced SE and associated neuropathological changes and that further protection would be provided by the addition of an NMDAR antagonist. Methods We investigated the efficacy of combining antiseizure medications to include a benzodiazepine and a barbiturate allosteric GABAAR modulator (midazolam and phenobarbital, respectively) to correct loss of inhibition, and ketamine to reduce excitation caused by increased synaptic localization of NMDAR and AMPAR, which are NMDA‐dependent. Rats implanted with transmitters to record electroencephalographic (EEG) activity were exposed to soman and treated with atropine sulfate and HI‐6 one min after exposure and with antiseizure medication(s) 40 minutes after seizure onset. Results The triple therapy combination of phenobarbital, midazolam, and ketamine administered at 40 minutes after seizure onset effectively prevented soman‐induced epileptogenesis and reduced neurodegeneration. In addition, dual therapy with phenobarbital and midazolam or ketamine was more effective than monotherapy (midazolam or phenobarbital) in reducing cholinergic‐induced toxicity. Significance Benzodiazepine efficacy is drastically reduced with time after seizure onset and inversely related to seizure duration. To overcome pharmacoresistance in severe benzodiazepine‐refractory cholinergic‐induced SE, simultaneous drug combination to include drugs that target both the loss of inhibition (eg, midazolam, phenobarbital) and the increased excitatory response (eg, ketamine) is more effective than benzodiazepine or barbiturate monotherapy.

Abstract Febrile infection–related epilepsy syndrome (FIRES) is a devastating immune inflammatory–mediated epileptic encephalopathy. Herein, we discuss a previously healthy 8‐year‐old boy with FIRES in whom high dosages of conventional and nonconventional anesthetics were ineffective in treating SE, as were ketogenic diet, intravenous corticosteroids, and immunoglobulins. After 29 days of prolonged SRSE, the patient was successfully treated with sevoflurane paired with plasma exchange, for a total of five days, thus obtaining a stable EEG suppression burst pattern with no adverse events. Anakinra at the dosage of 100 mg b.i.d. was started seven days after sevoflurane and plasma exchange had been discontinued and was effective in ensuring non‐recurrence of SE. Sevoflurane as bridge therapy for immunosuppressive treatment could be considered an early, safe, and effective option in treating convulsive SE in which an autoimmune‐inflammatory etiology can reasonably be hypothesized.

Objective: To discuss the results of the KETASER01 trial and the reasons for its failure, particularly in view of future studies. Methods: KETASER01 is a multicenter, randomized, controlled, open‐label, sequentially designed, non‐profit Italian study that aimed to assess the efficacy of ketamine compared with conventional anesthetics in the treatment of refractory convulsive status epilepticus (RCSE) in children. Results: During the 5‐year recruitment phase, a total of 76 RCSEs treated with third‐line therapy were observed in five of the 10 participating Centers; only 10 individuals (five for each study arm; five females, mean age 6.5 ± 6.3 years) were enrolled in the KETASER01 study. Two of the five patients (40%) in the experimental arm were successfully treated with ketamine and two of the five (40%) children in the control arm, where successfully treated with thiopental. In the remaining six (60%) enrolled patients, RCSE was not controlled by the randomized anesthetic(s). Significance: The KETASER01 study was prematurely halted due to low eligibility of patients and no successful recruitment. No conclusions can be drawn regarding the objectives of the study. Here, we discuss the KETASER01 results and critically analyze the reasons for its failure in view of future trials. [ABSTRACT FROM AUTHOR]

Refractory status epilepticus (RSE) requires multimodal treatment approaches to achieve rapid seizure cessation and neuroprotection. A ketogenic diet (KD) has demonstrated efficacy as a nutritional therapeutic option for adult RSE. However, the group of adult RSE patients who would benefit from adopting a KD needs to be determined to appropriately select the patients indicated for a KD. Therefore, we conducted a nonrandomized retrospective cohort study to explore the therapeutic efficacy of a KD by investigating the moderation effect of a KD on the association between the clinical characteristics of RSE patients and their functional outcomes. This study investigated 140 RSE patients, including 32 patients treated with a KD; among these patients, 28 (81%) achieved seizure cessation. We found that KD moderated the reduction in the modified Rankin scale (mRS) score at discharge among patients who were older, had higher seizure severity scores, were under continuous intravenous anesthetic therapy (CIVAD), and had super-RSE. Age and seizure severity scores, but not CIVAD or super-RSE, were associated with a KD-moderated change in mRS score at 3 months. Thus, we consider that our study provides evidence of a neuroprotective effect of KD in the most severe RSE patients with very few remaining therapeutic options, but future randomized controlled trials in these subgroups of KD patients are necessary. [ABSTRACT FROM AUTHOR]

During status epilepticus (SE), synaptic γ-aminobutyric acid A receptors (GABAA Rs) become internalized and inactive, whereas spare N-methyl-d-aspartate receptors (NMDARs) assemble, move to the membrane, and become synaptically active. When treatment of SE is delayed, the number of synaptic GABAA Rs is drastically reduced, and a GABAA agonist cannot fully restore inhibition. We used a combination of low-dose diazepam (to stimulate the remaining GABAA Rs), ketamine (to mitigate the effect of the NMDAR increase), and valproate (to enhance inhibition at a nonbenzodiazepine site) to treat seizures in a model of severe cholinergic SE. High doses of diazepam failed to stop electrographic SE, showing that benzodiazepine pharmacoresistance had developed. The diazepam-ketamine-valproate combination was far more effective in stopping SE than triple-dose monotherapy using the same individual drugs. Isobolograms showed that this drug combination's therapeutic actions were synergistic, with positive cooperativity between drugs, whereas drug toxicity was simply additive, without positive or negative cooperativity. As a result, the therapeutic index was improved by this drug combination compared to monotherapy. These results suggest that synergistic drug combinations that target receptor changes can control benzodiazepine-refractory SE.

Background: Status epileptics are classically defined as seizures that are continuous for 30 minutes or longer or repetitive seizures between which the patient does not regain consciousness. This study reports a case of a boy with a 2-hour seizure. Case Presentation: We present the case of a 7-year-old boy, who is known to have tuberous sclerosis (TSC2 gene mutation). On the day of presentation, the seizure had started with aura (epigastric pain with weakness in the face), then started to seize in a form left focal jerky movement with generalization associated with rolling up of the eyes, and lasted for 5 minutes; it was aborted clinically by lorazepam 0.1 mg/kg IV. However, the electroencephalography (EEG) showed subclinical seizure. The patient received a loading dose of phenytoin, 20 mg/kg IV, with no changes in the EEG; then Keppra (three doses) with a total of 40 mg/kg IV was given, but subclinical seizure still persisted. The patient was given one dose of Ketamine IV of 1 mg/kg, which resulted in complete cessation of the seizure activity within 3 minutes after injection, which was confirmed by prolonged EEG monitoring. The total duration of the seizure was 2 hours. Conclusion: Ketamine can be considered as a third-line drug in refractory status epilepticus. [SJEMed 2021; 2(1.000): 92-95]

Introduction: Status epilepticus (SE) is a life-threatening neurological emergency requiring immediate medical intervention and is associated with high mortality and morbidity. The aim of this research was evaluation of clinical and etiological profile of refractory status epilepticus (RSE) among children aged between 1 month and 18 years. Material and methods: The study was done between January 1, 2017 and December 24, 2019. All children with the age limits mentioned above, who presented convulsive SE, subsequently with development in refractory status epileptic (RSE), were included in the study. Patients were investigated and evaluated according to a standard protocol. Subsequently, the characteristics of children with RSE and those without an evolution in RSE were compared. Results: 55 children, out of whom 32 boys with SE were enrolled in the study, of which 20 children (36%) developed RSE. Central nervous system (CNS) infections were the most common causes of SE and development of RSE (51% in SE and 53% in RSE, p > 0.05). Noncompliance of antiepileptic medication served as the second cause for evolution of RSE. The overall mortality rate was 10.9%, the chances of death in RSE (20%) being higher than in SE (5.7%). The unfavorable prognosis was seven times higher in children with RSE, compared to children who developed SE. Conclusions: In the management of CNS infections, pediatricians should be aware of the high risk of developing RSE. In addition, the possibility of developing RSE should be considered and promptly managed in an intensive care unit in order to reduce the risk of mortality and morbidity of this severe neurological condition.