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Febrile infection–related epilepsy syndrome (FIRES) is a devastating epileptic encephalopathy with antecedent febrile infection preceding the onset of refractory status epilepticus (RSE), without the evidence of structural, toxic, or metabolic cause. The pathophysiology of FIRES is largely unknown but has been hypothesized to be due to excessive cytokine release perpetuating the underlying seizure. Conventional immunotherapies such as steroid, IVIG, plasma exchange, and rituximab have previously been considered for the treatment of FIRES but have been disappointing. We report a successful therapeutic encounter using tocilizumab, a humanized monoclonal antibody against interleukin‐6 receptor to treat RSE in a 14‐year‐old girl with FIRES following dismal outcome using conventional immunosuppressive strategies. The overproduction of cytokines and the poor performance of immunotherapies implicate a putative role of inflammation in FIRES. Our case showed that complete termination of RSE was achieved after tocilizumab administration suggesting it may be a lifesaving drug for this catastrophic condition. [ABSTRACT FROM AUTHOR]

Objective: Refractory status epilepticus is a serious condition in which seizure continues despite use of two antiepileptic medications. Retrospective studies have shown that 29%‐43% of SE patients progress into RSE despite treatment. Mortality following RSE is high. We aimed to evaluate the predictors of outcome in patients with RSE at a tertiary care center. Methods: Sixty‐eight consecutive patients with RSE who presented to our hospital between February 2018 and January 2020 were evaluated for outcome. Result: In our study 28(41.2%), patients who failed to respond to first‐ and second‐line antiepileptic drug responded to the third‐line antiepileptic drug thus avoiding mechanical ventilation and intravenous anesthesia. Low GCS at admission (P <.001), need for mechanical ventilation and intravenous anesthesia (P =.018), and long duration of RSE before recovery (P =.035) were strongly associated with worse outcome. Duration of RSE before starting treatment (P =.147), previous history of seizure (P =.717), and age of the patient (P =.319) did not influence the outcome. Significance: In our study, we prospectively evaluated patients with RSE and followed them for one month after discharge from the hospital. Unlike some of the previous studies, we identified an interesting finding whereby a significant proportion of the patients responded to the third‐line antiepileptic drug and thus avoiding the complications related to mechanical ventilation. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to describe demographic data, semiology and etiology in a pediatric population with status epilepticus (SE) and refractory SE (RSE).Method: We retrospectively reviewed patients with the following inclusion criteria: i) age between two months and eighteen years; ii) SE diagnosis; iii) admission from January 2001 to December 2016; iv) available clinical data.Results: We enrolled 124 patients. Mean and median age was 4.6 ± 4.2 years and 3.3 [1.2-7.5] years respectively. SE had a "de novo" onset in 66.9%. Focal convulsive-SE was the most common semiology (50.8%) whilst generalised (32.3%) and nonconvulsive-SE (NCSE) (16.9%) were less represented. Some etiologies showed a different age distribution: febrile in youngest age (p = 0.002, phi 0.3) and idiopathic-cryptogenic in older children (p = 0.016, phi 0.2). A statistical significance correlation was detected between semiology and etiology (p < 0.001, Cramer's V 0.4), chemotherapy and NCSE (n = 6/21 vs 3/103, p < 0.001) as well as PRES and NCSE (n = 7/21 vs 5/103, p < 0.001). Only 17.7% had a RSE. No correlation was found in demographic and clinical data, but NCSE, acute and idiopathic-cryptogenic etiologies were more frequently associated to RSE. Encephalitis was the most common diagnosis in acute etiologies whereas unknown epilepsy in idiopathic-cryptogenic group.Conclusion: Most of our findings were previously described however we found a significant role of non-antiepileptic treatments (chemotherapy-dialysis) and comorbidity (PRES) determining acute etiology and NCSE. Acute (mostly encephalitis), idiopathic-cryptogenic (mainly unknown-epilepsy) and NCSE were frequently detected in RSE. In the above mentioned conditions a high level of suspicion was recommended. [ABSTRACT FROM AUTHOR]

Febrile infection-related epilepsy syndrome (FIRES) is a rare and devastating epileptic encephalopathy with historically abysmal neurocognitive outcomes, including a high incidence of mortality. It tends to affect children and young adults and is characterized by superrefractory status epilepticus following a recent febrile illness. Growing evidence suggests a heterogeneous etiology resulting in fulminant nonantibody-mediated neuroinflammation. For some children with FIRES, this aberrant neuroinflammation appears secondary to a functional deficiency in the endogenous interleukin-1 receptor antagonist. A precise etiology has not been identified in all FIRES patients, and current treatments are not always successful. Limited treatment evidence exists to guide choice, dosing, and duration of therapies. However, the ketogenic diet and certain targeted immunomodulatory treatments, including anakinra, appear safe and have been associated with relatively excellent clinical outcomes in some FIRES patients. Future prospective multicenter collaborative studies are needed to further delineate the FIRES heterogeneous disease pathophysiology and to determine the safety and efficacy of treatment strategies through a robust measurement of neurocognitive outcomes. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the factors affecting the mortality of refractory status epilepticus (RSE) in comparison with non‐refractory status epilepticus (non‐RSE). Material‐Method: Included in this retrospective study were 109 status epilepticus cases who were hospitalized in the neurological intensive care unit Katip Celebi University. Fifty‐two were RSE and 57 were non‐RSE. All clinical data were gathered from the hospital archives. Factors which may cause mortality were categorized for statistical analysis. Results: While elderly age, continuous clinical seizure activity, absence of former seizure, infection, prolonged stay of ICU, anesthesia, and cardiac comorbidity were significantly related to mortality in the RSE subgroup, potentially fatal accompanying diseases were significantly related to mortality in the non‐RSE subgroup. No significant relationship was found between mortality and refractoriness. Multivariate analysis revealed that a Glasgow Coma Score (GCS) at presentation of 8 or lower was the independent predictor of mortality both in the general SE population (P =.017) and in the RSE subgroup (P =.007). Intubation (P =.011) and hypotension (P =.011) were the other independent predictors of mortality in the general SE population. No independent predictor of mortality was detected in the non‐RSE subgroup. Discussion/Conclusion: Intubation, hypotension, and a low GCS at presentation could be the main factors which could alert clinicians of an increased risk of mortality in SE patients. Although non‐RSE and RSE had similar rates of mortality in the ICU, the mortality‐related factors of SE vary in the RSE and the non‐RSE subgroups. [ABSTRACT FROM AUTHOR]

Background: Anti-N-methyl-d-aspartate receptor encephalitis is a central nervous system inflammatory autoimmune disease affecting adults and children. The use of first- and second-line immunotherapies is supported. Recent reports suggest the efficacy of bortezomib in severe anti-N-methyl-d-aspartate encephalitis in adult patients not responsive to second-line treatment; there are no data about pediatric patients.Patient Description: We describe an eight-year-old child with anti-N-methyl-d-aspartate encephalitis not responsive to first- and second-line treatments who experienced marked clinical improvement after bortezomib administration.Discussion: Bortezomib is a selective and reversible inhibitor of the 26S proteasome, which is used to treat oncologic and rare autoimmune disorders in pediatric patients. As observed in adult patients, bortezomib administration induced anti-N-methyl-d-aspartate antibody titer decline and clinical improvement with an acceptable risk profile.Conclusion: This is the first report of the use of bortezomib in children with anti-N-methyl-d-aspartate encephalitis; it could be a useful therapeutic option in children with refractory anti-N-methyl-d-aspartate encephalitis. [ABSTRACT FROM AUTHOR]

Febrile Infection-Related Epilepsy Syndrome (FIRES) is a catastrophic, extremely rare epileptic encephalopathy. It strikes previously healthy school-aged children and is usually cryptogenic. Its dramatic onset with refractory status epilepticus is always preceded by a nonspecific febrile illness. The seizure activity in FIRES may last for several weeks with little to no response to antiepileptic treatment, usually resulting in the usage of anaesthetics. This acute phase is followed by a chronic, refractory epilepsy and cognitive deficit, that persist for the rest of the patient’s life. Still to this day no definite cause has been described. In this study we review the current finding in FIRES and describe a case of a 4-year-old patient with a dramatic course of the acute phase in FIRES and unusual presentation of the chronic phase, which is dominated by extrapyramidal symptoms such as dystonia. This case highlights that the clinical presentation of FIRES may differ from those frequently described in literature.

Abstract Background Nonconvulsive status epilepticus (NCSE) is a diagnosis that is often challenging and one that may progress to refractory NCSE. Ketamine is a noncompetitive N-methyl-d-aspartate antagonist that increasingly has been used to treat refractory status epilepticus. Current Neurocritical Care Society guidelines recommend intravenous (IV) ketamine infusion as an alternative treatment for refractory status epilepticus in adults. On the other hand, enteral ketamine use in NCSE has been reported in only 6 cases (1 adult and 5 pediatric) in the literature to date. Case presentation A 33-year-old woman with a history of poorly controlled epilepsy presented with generalized tonic-clonic seizures, followed by recurrent focal seizures that evolved into NCSE. This immediately recurred within 24 h of a prior episode of NCSE that was treated with IV ketamine. Considering her previous response, she was started again on an IV ketamine infusion, which successfully terminated NCSE. This time, enteral ketamine was gradually introduced while weaning off the IV formulation. Treatment with enteral ketamine was continued for 6 months and then tapered off. There was no recurrence of NCSE or seizures and no adverse events noted during the course of treatment. Conclusion This case supports the use of enteral ketamine as a potential adjunct to IV ketamine in the treatment of NCSE, especially in cases without coma. Introduction of enteral ketamine may reduce seizure recurrence, duration of stay in ICU, and morbidity associated with intubation.

Roughly 80% of the global burden of epilepsy resides in low- and middle-income countries (LMICs; WHO, 2022). Despite numerous new therapies for the treatment of epilepsy, the number of patients who remain resistant to available medications is unchanged. Additionally, no therapy has yet been clinically proven to prevent or attenuate the development of epilepsy in at-risk individuals. Unfortunately, access to next generation therapies in LMICs is low, the stigma associated with epilepsy remains high, and access to adequate resources is unchanged. Thus, the global epilepsy burden disproportionately falls on LMICs such that strategies to conscientiously integrate global epilepsy risk factors into preclinical research may meaningfully advance 21st century epilepsy therapies. Brain infections are one of the main risk factors for epilepsy in resource-poor settings. Further, both infection- and autoimmune-associated encephalitis contribute to worldwide epilepsy risk and remain relatively understudied. For example, clinical SARS CoV-2 infection can induce rare instances of encephalopathy and acute seizures. Among viruses known to cause acute brain infection, enteroviruses increase risk for encephalitis-induced epilepsy, but are not associated with risk for other neurodevelopmental disorders (eg, autism spectrum or attentional deficit hyperactivity disorders). Naturally occurring models of viral infection-induced epilepsy therefore provide an exquisite opportunity to uncover novel contributors to epileptogenesis. Moreover, the convergent neuroinflammatory pathways that are associated with viral infection-induced encephalitis and autoimmune encephalitis reflect an untapped therapeutic opportunity to meaningfully reduce the global burden of epilepsy. This review summarizes the latest advances in translational research integrating encephalitis-induced seizure and epilepsy models, in tandem with progress in clinical diagnosis of inflammation and virally mediated epilepsy. This improved awareness of the shared biological underpinnings of epileptogenesis following brain infection or autoimmune encephalitis is anticipated to beneficially impact the global burden of epilepsy., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LJH has received consulting fees from Accure, Ceribell, Gilead, Marinus, Natus, Neurelis, Neuropace, Rafa Laboratories, Rapport Therapeutics, UCB, & Vial Health Technology; honoraria for speaking from Neuropace, Natus, and UCB; royalites from Wolters-Kluwer for authoring chapters for UpToDate-Neurology, and from Wiley for coauthoring the book “Atlas of EEG in Critical Care,” 1st and 2nd editions; and is co-chair of the medical and scientific advisory board for the NORSE Institute. AS Galanopoulou is the Editor-in-Chief of Epilepsia Open and associate editor of Neurobiology of Disease and receives royalties from Elsevier, Walters Kluwer, and Medlink for publications. JAK receives royalties for disease model licensing from GW Pharma, Novartis, Pfizer, Tevard, Emugen, Stoke Therapeutics, Regulus, Pfizer, Regel, Sangamo Biosciences, GSK, Biogen, and Encoded Therapeutics. None of the other authors has any conflict to disclose., (© The Author(s) 2024.)

Objective: To investigate the effects of hydrogen therapy on epileptic seizures in rats with refractory status epilepticus and the underlying mechanisms., Methods: 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 Mg 2+ -free medium and used polymerase chain reaction to investigate the neuroprotective effects of hydrogen., Results: 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., Conclusions: 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., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Background: Status Epilepticus (SE) is one of the major health problems that require immediate treatment to avoid risk of disability and death. The key treatment is to stop the symptom within an hour after it has developed. The problems of SE treatments are mostly caused by delayed diagnosis, incorrect prescription, incorrect rate of administration, inappropriate dilution of medicines. Objective: In order to provide efficient treatment and reduce the waiting time. The multidisciplinary team, under the lead of Integrated Epilepsy Research Group, has developed a ready-to-use Status Epilepticus Box (SE Box) for status epilepticus and the acute seizure at Srinagarind Hospital. Materials and Methods: A ready-to-use SE Box comprises of 4 medicines; phenytoin, phenobarbital, sodium valproate, and levetiracetam encloses with information on application of each medicine. The boxes are prepared by pharmacist. Nurses can immediately use antiepileptic drug follow doctors' prescriptions. Results: The review of seizure patients' records showed an average diagnosis time was 154.77 minutes (1 to 53 hours), an average time of medical receiving was 41.74 minutes (1 to 150 minutes). The average waiting time for receiving medicine in pharmacy department was 13.09 minutes, start from raising order by doctors to the medicine dispensing. SE Box can reduce the waiting time in pharmacy department to zero. Following a doctor's approval, nurses can administer the medicine to the patients by following the instructions available in SE Box. The instructions include loading dose, maintenance dose, administer rate, preparing method, and precautions. Conclusion: The development of anti-seizure medical system in Srinagarind Hospital, Khon Kaen University, has resulted in the production of the SE Box, an innovation that is efficient in reducing the waiting time prior to applying medication to the patients. The SE Box is ready and convenient for use. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to identify risk factors for the development of refractory status epilepticus (RSE). Methods: This was an IRB-approved, retrospective case control study that included patients admitted with status epilepticus between August 1, 2014, and July 31, 2017. Cases were defined as those with RSE, and controls were those who did not develop RSE. A bivariate analysis was conducted comparing those with RSE and those without RSE. A stepwise logistic regression model was constructed predicting for progression to RSE. Risk factors for progression to RSE were extrapolated from this model. Results: A total of 184 patients met inclusion criteria for the study (99 controls and 49 cases). After adjusting for covariates in the logistic regression, patients with convulsive seizures had a lower odds of developing RSE (odds ratio [OR] = 0.375; 95% CI = 0.148 to 0.951; P = 0.0388). Treatment with benzodiazepines plus levetiracetam had a higher odds of developing RSE (OR = 3.804; 95% CI = 1.523 to 9.499; P = 0.0042). Conclusion and Relevance: This study found that patients with convulsive seizures had a lower odds of developing RSE. In addition, patients treated with benzodiazepines and levetiracetam had a higher odds of developing RSE. This information can be used to potentially identify patients at higher risk of developing RSE, so that treatment can be modified to reduce morbidity and mortality. These results may warrant further investigation into the effectiveness of levetiracetam as a first-line agent for the treatment of SE. [ABSTRACT FROM AUTHOR]

FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase and is implicated in autosomal recessive combined oxidative phosphorylation deficiency 14. The clinical manifestation can be divided into early onset epileptic phenotype and spastic paraplegia phenotype. The purpose of this study was to report a case of juvenile manifesting refractory epilepsy caused by two novel compound heterozygous mutations in the FARS2 gene. Microscopic and histochemical examination as well as next‐generation sequencing and reconstruction of the three-dimensional structure of FARS2 protein were performed. A 17-year-old man with no developmental delays suffered from generalized tonic-clonic convulsion since 12 years of age and developed refractory status epilepticus 5 years later. No specific etiology was found following brain imaging, muscle biopsy and metabolic studies. DNA sequencing identified two novel compound heterozygous mutations in FARS2, (p.V197M and p.F402S), derived from each parents, respectively. These mutations affected the structure or thermodynamic stability of the protein. This is a case report of juvenile-onset refractory epilepsy caused by two novel compound heterozygous mutations in the FARS2 gene. This case confirms and expands the clinicalphenotype and the genotypic spectrum of the FARS2 gene. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to evaluate the protective efficacy of the neurosteroid pregnanolone (3α‐hydroxy‐5β pregnan‐20‐one), a GABAA receptor‐positive allosteric modulator, as an adjunct to benzodiazepine therapy against the chemical warfare nerve agent (CWNA) sarin (GB), using whole‐body exposure, an operationally relevant route of exposure to volatile GB. Methods: Rats implanted with telemetry transmitters for the continuous measurement of cortical electroencephalographic (EEG) activity were exposed for 60 minutes to 3.0 LCt50 of GB via whole‐body exposure. At the onset of toxic signs, rats were administered an intramuscular injection of atropine sulfate (2 mg/kg) and the oxime HI‐6 (93.6 mg/kg) to increase survival rate and, 30 minutes after seizure onset, treated subcutaneously with diazepam (10 mg/kg) and intravenously with pregnanolone (4 mg/kg) or vehicle. Animals were evaluated for GB‐induced status epilepticus (SE), spontaneous recurrent seizures (SRS), impairment in spatial memory acquisition, and brain pathology, and treatment groups were compared. Results: Delayed dual therapy with pregnanolone and diazepam reduced time in SE in GB‐exposed rats compared to those treated with delayed diazepam monotherapy. The combination therapy of pregnanolone with diazepam also prevented impairment in the Morris water maze and reduced the neuronal loss and neuronal degeneration, evaluated at one and three months after exposure. Significance: Neurosteroid administration as an adjunct to benzodiazepine therapy offers an effective means to treat benzodiazepine‐refractory SE, such as occurs following delayed treatment of GB exposure. This study is the first to present data on the efficacy of delayed pregnanolone and diazepam dual therapy in reducing seizure activity, performance deficits and brain pathology following an operationally relevant route of exposure to GB and supports the use of a neurosteroid as an adjunct to standard anticonvulsant therapy for the treatment of CWNA‐induced SE. [ABSTRACT FROM AUTHOR]

Background/objective: Perampanel is a novel anti-epileptic drug (AED) which acts as a non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist to reduce glutamate-mediated postsynaptic excitation. Previous animal studies and a few case reports/series have suggested that it may be effective to treat refractory status epilepticus (RSE).Methods: We retrospectively reviewed 67 consecutive patients with RSE, of whom 22 received perampanel. The clinical features, epidemiology-based mortality score in status epilepticus, status epilepticus severity score, seizure control, functional outcome, RSE etiology, and electroencephalogram findings were collected. Responder to perampanel was defined as seizure resolution within 4 days of therapy with perampanel being the last AED used plus no recurrence during hospitalization.Results: Eight of the 22 (36.4%) RSE patients fulfilled the definition of responder to perampanel. An additional 1 patient responded to perampanel after 4 days of treatment. In total, perampanel was the last AED in 9 (40.1%) patients. Among the 8 responders to perampanel, 5 had convulsive SE, 1 had non-convulsive SE, and 2 had focal motor SE. The responders accounted for both of the patients with focal motor SE (100%), 5 (33.3%) of the 15 patients with convulsive SE, and 1 (20%) of the 5 patients with non-convulsive SE. The ictal and inter-ictal activities also decreased after perampanel therapy, and three patients (13.6%) had preferable outcomes at last follow-up.Conclusions: Perampanel may be an effective add-on treatment for RSE even in patients who failed multiple AEDs. Our study suggests that perampanel may be more effective for focal motor SE and convulsive SE than non-convulsive SE. As most previous studies have focused on non-convulsive SE, further studies are warranted to clarify the effectiveness of perampanel for different subtypes of SE. [ABSTRACT FROM AUTHOR]

Electroconvulsive therapy (ECT), Vagal Nerve Stimulation (VNS), Transcranial Magnetic Stimulation (TMS) and Deep Brain Stimulation (DBS) are neuromodulation therapies that have been used to treat Status Epilepticus (SE). Review the literature about the efficacy and safety of neuromodulation therapies in SE in humans. We searched studies in PubMed, Scopus, Google Scholar and Science Direct (inception to June 2018). Four review authors independently selected the studies, extracted data and assessed the methodological quality of the studies using the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines, Oxford and GRADE scales, and Murad et al., 2018 methodological quality and synthesis of case series and case reports. We analyzed 27 articles (45 patients) with 4 different neuromodulation therapies. In ECT we found 80% rate of disruption of SE and 5% of adverse events was reported. Using iVNS 15/16 (93.7%) patients resolved the SE. All patients who underwent TMS and DBS aborted SE, however, 50% of patients with DBS had severe adverse events. Case series and case reports suggest that neuromodulation therapies can abort SE in 80–100% of patients (Oxford scale and GRADE were level 4 and D) with a wide range of adverse effects, which claims for prospective studies on the relationship be-tween efficacy and safety. • Neuromodulation therapies that have been used to treat Status Epilepticus. • Review the literature about the efficacy and safety of neuromodulation therapies in SE in humans. • Neuromodulation therapies can abort SE in 80-100% of patients with a wide range of adverse effects. [ABSTRACT FROM AUTHOR]

Background: Status, refractory status and super refractory status epilepticus are common neurologic emergencies. The objective of this study is to investigate the feasibility, safety and effectiveness of a ketogenic diet (KD) for refractory status epilepticus (RSE) in adults in the intensive care unit (ICU).Methods: We performed a retrospective, single-center study of patients between ages 18 and 80 years with RSE treated with a KD treatment algorithm from November 2016 through April 2018. The primary outcome measure was urine ketone body production as a biomarker of feasibility. Secondary measures included resolution of RSE and KD-related side effects.Results: There were 11 adults who were diagnosed with RSE that were treated with the KD. The mean age was 48 years, and 45% (n = 5) of the patients were women. The patients were prescribed a median of three anti-seizure medications before initiating the KD. The median duration of RSE before initiation of the KD was 1 day. Treatment delays were the result of Propofol administration. 90.9% (n = 10) of patients achieved ketosis within a median of 1 day. RSE resolved in 72.7% (n = 8) of patients; however, 27.3% (n = 3) developed super-refractory status epilepticus. Side effects included metabolic acidosis, hypoglycemia and hyponatremia. One patient (20%) died.Conclusions: KD may be feasible, safe and effective for treatment of RSE in the ICU. A randomized controlled trial (RCT) may be indicated to further test the safety and efficacy of KD. [ABSTRACT FROM AUTHOR]

Purpose: To summarize the available evidence related to pediatric refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE), with emphasis on epidemiology, etiologies, therapeutic approaches, and clinical outcomes.Methods: Narrative review of the medical literature using MEDLINE database.Results: RSE is defined as status epilepticus (SE) that fails to respond to adequately used first- and second-line antiepileptic drugs. SRSE occurs when SE persist for 24 h or more after administration of anesthesia, or recurs after its withdrawal. RSE and SRSE represent complex neurological emergencies associated with long-term neurological dysfunction and high mortality. Challenges in management arise as the underlying etiology is not always promptly recognized and therapeutic options become limited with prolonged seizures. Treatment decisions mainly rely on case series or experts' opinions. The comparative effectiveness of different treatment strategies has not been evaluated in large prospective series or randomized clinical trials. Continuous infusion of anesthetic agents is the most common treatment for RSE and SRSE, although many questions on optimal dosing and rate of administration remain unanswered. The use of non-pharmacological therapies is documented in case series or reports with low level of evidence. In addition to neurological complications resulting from prolonged seizures, children with RSE/SRSE often develop systemic complications associated with polypharmacy and prolonged hospital stay.Conclusion: RSE and SRSE are neurological emergencies with limited therapeutic options. Multi-national collaborative efforts are desirable to evaluate the safety and efficacy of current RSE/SRSE therapies, and potentially impact patients' outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To summarize the clinical features, suggested work-up, treatment and prognosis of new-onset refractory status epilepticus (NORSE), a condition recently defined as the occurrence of refractory status epilepticus (RSE) in a patient without active epilepsy, and without a clear acute or active structural, toxic or metabolic cause; and of the related syndrome of febrile infection-related epilepsy syndrome (FIRES), also recently defined as a subgroup of NORSE preceded by a febrile illness between 2 weeks and 24 h prior to the onset of RSE.Method: Narrative review of the medical literature about NORSE and FIRES.Results: NORSE and FIRES mainly affect school-age children and young adults. A prodromal phase with flu-like symptoms precedes the SE onset in two third of NORSE cases, and by definition in all FIRES. Status epilepticus usually starts with repeated focal seizures with secondary bilateralization. Most cases evolve to super RSE (SRSE) and have unfavorable outcome, with short-term mortality of 12-27%, long-term disability and epilepsy. No specific imaging or laboratory abnormalities have been identified so far that allows an early diagnosis and half of adult cases remain of unknown etiology. A standardized diagnostic algorithm is provided and. Autoimmune encephalitis is the most frequent identified cause. In the absence of specific diagnosis, immunotherapy could be tried in addition to antiepileptic treatment.Conclusions: This review presents the rare but devastating syndrome of NORSE, including the subcategory of FIRES. Early recognition with complete work-up is primordial to identify the underlying cause and promptly start appropriate treatment. [ABSTRACT FROM AUTHOR]

Objective: Novel treatments are needed to control treatment‐resistant status epilepticus (SE). We report a summary of clinical cases where perampanel was used in established SE, refractory SE (RSE), or super‐refractory SE (SRSE). Methods: Medical records were retrospectively reviewed for perampanel administration in SE at five European hospitals between 2011 and 2015. Results: Of 1319 patients identified as experiencing SE, 52 (3.9%) received perampanel. Median latency from SE onset to perampanel initiation was 10 days. Patients with SE had previously failed benzodiazepines (when received) and a median of five other antiepileptic drugs (AEDs). Median initial perampanel dose was 6 mg/d, up‐titrated to a median maximum dose of 10 mg/d. Perampanel was the last drug added in 32/52 (61.5%) patients, with response attributed to perampanel in 19/52 (36.5%) patients. A greater proportion of perampanel non‐responders had SRSE (51.5%; 17/33) vs perampanel responders (31.6%; 6/19), and had failed a higher mean number of AEDs before initiating perampanel (5.9 vs 5.1, respectively). Most commonly reported adverse effects during perampanel treatment were dizziness (n = 1 [1.9%]) and somnolence (n = 1 [1.9%]). No serious adverse effects were documented, and none led to discontinuation of perampanel. Conclusions: Perampanel was administered to patients with established SE, RSE, or SRSE at greater initial doses than those administered in clinical practice to patients with epilepsy. The SE cases reported here represent a refractory and heterogeneous population, and rate of seizure cessation attributed to perampanel treatment (36.5%) represents a notable response. These data should be confirmed in a larger patient population. [ABSTRACT FROM AUTHOR]

Status epilepticus (SE) has a high mortality rate and is one of the most common neurologic emergencies. Fast progression of this neurologic emergency and lack of response to traditional antiepileptic drugs (AEDs) in most cases has challenged clinicians to use new agents. This article evaluates the efficacy and safety of AEDs released to the market after 2000 for SE, refractory status epilepticus (RSE), and super‐refractory status epilepticus (SRSE). The PubMed database was searched for clinical trials published between January 2000 and July 2018 using the search terms status epilepticus, refractory status epilepticus, super refractory status epilepticus, brivaracetam, clobazam, cannabidiol, eslicarbazepine, lacosamide, perampanel, rufinamide, stiripentol, and zonisamide. Trials that evaluated these agents in adults with SE, RSE, and SRSE were included. Brivaracetam use was identified in two retrospective reviews with success rates of 27% and 57%. One unsuccessful case report of cannabidiol use in SE was found. Four clobazam studies were identified in SE and RSE with success rates ranging from 25–100%. No evidence for the use of eslicarbazepine and zonisamide was found. Using the search terms for lacosamide identified 38 articles: 1 systematic review, 5 prospective studies, 15 retrospective reviews, and 17 case reports. Success rates and dosing varied, but studies that included focal or partial types of SE showed higher success rates. Five articles were identified regarding perampanel use in this setting. Three were retrospective reviews with success rates ranging from 17–60%, and two were case reports. Only one case report regarding the use of rufinamide was found; rufinamide titrated up to 4.4 mg/day allowed discontinuation of barbiturate and clobazam. One case report and two case series of stiripentol were found with reported efficacy between 60% and 100% in SRSE. Evidence is currently insufficient to support the use of these agents in this setting. [ABSTRACT FROM AUTHOR]

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We report the clinico-radiological characteristics of SE in the patients with cerebral venous thrombosis (CVT), and compare the relative risk of SE in determining death and disability compared with those patients with and without self-limiting seizures. Consecutive patients with magnetic resonance venography (MRV) confirmed CVT, admitted during 2006-2017, were included. Their clinical details, risk factors, and magnetic resonance imaging and MRV findings were noted. Duration of SE, Status Epilepticus Severity Score (STESS), Glasgow Coma Scale score, and response to antiepileptic drugs were noted. 6-month outcomes were noted using the modified Rankin Scale. Of 153 CVT patients, 28 (18.3%) had SE, 62 (40.5%) self-limiting seizures, and 63 (41.2%) did not have seizures or SE. The SE group had a higher incidence of focal motor deficit (71.4% vs. 33%, P = 0.006) and supratentorial lesions (93% vs 55.5%, P = 0.003) than the no-seizure group. Multivariate analysis of SE and no-SE group (includes self-limiting and no seizure) did not indicate any significant predictor, but multivariate analysis of SE and no-seizure group indicated that supratentorial lesion only predicted SE (odds ratio 5.65, 95% confidence interval 1.11-28.76; P = 0.03). Patients with SE and self-limiting seizure had similar clinical and MRI findings. In total, 17.8% had refractory SE; refractoriness was related to the pretreatment duration of SE (P < 0.001). The death and disability were not significantly different between the three groups. At 6 months, 84% patients with SE, 92.3% with self-limiting seizure, and 94.8% in no-seizure group had good recovery. [ABSTRACT FROM AUTHOR]

Highlights • The patients with status epilepticus had reduced antioxidants and increased reactive oxygen and nitrogen species. • Oxidative stress was higher in the patients with comorbidity. • Glutathione negatively and malondialdehyde and nitric oxide positively correlated with age. • Oxidative stress however did not determine in-hospital death and disability at discharge. Abstract Purpose To report oxidative stress in the patients with status epilepticus (SE), and correlate these with severity, MRI and outcome. Methods Thirty-five patients with SE and 34 controls were included. Blood sample was collected at admission for measuring superoxide dismutase (SOD), catalase, protein carbonyl, glutathione, total antioxidant capacity (TAC), malondialdehyde (MDA) and nitric oxide (NO). The type of SE, duration and Status Epilepticus Severity Score (STESS) at admission and refractoriness to treatment were noted. Cranial magnetic resonance imaging (MRI) findings, in-hospital deaths and disability at discharge were noted. Results The median age of the patients was 35 and 14 were females. The median STESS was 3 (0–5), and the score was unfavorable in 21(60%) patients. MRI was abnormal in 27(77%) patients. The patients with SE had significantly lower concentrations of SOD, catalase, protein carbonyl, GSH and TAC and higher concentrations of MDA and NO compared to the controls. These levels did not differ between refractory and non-refractory SE. Glutathione level inversely correlated with age. Malondialdehyde and NO levels positively correlated with age and inversely with GSH level. Five (14.3%) patients died in hospital. At discharge, 14 patients had good and 16 had poor outcome. The oxidative stress markers did not correlate with death or disability. Conclusion Oxidative stress is increased in the patients with SE. Further study is needed in larger sample size to explore probable adjunctive treatment option. [ABSTRACT FROM AUTHOR]

Purpose: Our primary objective was to determine incidence of status epilepticus in adults admitted to 5 ITU settings in Glasgow over 18 years. We wanted to investigate if there are any change in causes and outcomes of SE over last decade. We also compared outcomes of De Novo statuts Epilpeticus (DNSE) and Stauts Epilepticus in patients with previous Epilepsy (SEPE).Methods: The NHS GGC Research Ethics Committee gave permission for this study to continue without a full ethics submission. Between 2013 and 2016, coding records were searched across NHS Greater Glasgow and Clyde for adults over the age of 16 years admitted to an Intensive Care Facility in any of the hospitals in Glasgow.Results: 633 cases were included in study. Cases were separated depending on whether there had been previous epilepsy (SEPE n = 214) or De Novo Status Epilepticus (DNSE, n = 419). Causes in both groups were listed, with 52% of those with DNSE having some contribution from substance misuse. In SEPE, this was felt to play a role in 33.7%. Duration of stay in both groups was similar, but the longest in-patient stays were in the DNSE group. Admission mortality was significantly higher in DNSE than in SEPE (13.8% versus 7.5%). This mortality risk was most closely associated with substance misuse in the group with DNSE.Conclusion: DNSE has a worse prognosis than SEPE. A presentation with DNSE is sign of a system in peril, even where episodes are provoked by alcohol and or drug use. Such episodes should spark off a chain of multispecialty care in order to address this recurring and persisting public health catastrophe. [ABSTRACT FROM AUTHOR]

Status epilepticus-related to systemic lupus erythematosus (SE-SLE) is in general attributed to fulminate neuropsychiatric lupus disease activity, yet the long-term outcome of SE-SLE is not well recognized. This is an observational study of 40 SE-SLE patients pooled from 8 cases at a single tertiary care hospital, and 32 SE-SLE patients identified on a systematic review, with focus on electro-clinical characteristics, imaging studies and the underlying etiology of SE-SLE in correlation with long-term outcome. Clinical phenotypes of SE-SLE were heterogeneous, ranging from patients with aura continua to patients in coma. Convulsive SE-SLE occurred among patients with heightened global lupus disease activity and increased cortical and subcortical brain lesion burden localized mostly in the frontal and temporal regions. There were no specific neuroimaging or laboratory abnormalities that allowed early SE-SLE diagnosis where a cluster of cases were of unclear etiology (17.5%). Most SE-SLE cases evolved to refractory SE-SLE with resistance to multiple anti-seizure medications and intravenous anesthetics requiring aggressive immune therapy that led to resolution of SE-SLE active phase. Seizure freedom occurred in 60.0% of patients and the median time to cessation of SE-SLE seizure activity after aggressive therapy was 14 days. Poor long-term outcomes were apparent in SE-SLE patients with one-year mortality (12.5%), recurrent SE-SLE (25.0%), subsequent epilepsy (37.5.1%), poor functional outcome (55.0%) and cognitive impairment (47.5%). A prolonged time to cessation of SE-SLE seizure activity was associated with unfavorable long-term outcome. Diagnostic accuracy of SE-SLE requires better understanding of the etio-pathogenesis and the spectrum of clinical presentations of SE-SLE. Prompt initiation of immune therapy improve SE-SLE outcome, yet optimal therapeutic strategies remain to be determined. Identifying novel biomarkers that distinguish between different forms of SE-SLE and target cellular inflammatory response will help with specific SE-SLE treatment guidelines and prevent poor outcome. [ABSTRACT FROM AUTHOR]

Objectives: To determine the proportion of refractory status epilepticus (RSE) and super-RSE (SRSE) among patients with status epilepticus (SE) and to analyze RSE and non-RSE (NRSE) in terms of etiology and predictors for RSE. Materials and Methods: Patients were identified from discharge summaries database with keywords of SE and records of the portable electroencephalogram (EEG) machine from January 2011 to March 2016. Results: Two hundred and eighteen events were included in the study with 114 (52.3%) males, bimodal age preponderance age

Status epilepticus (SE) is a life-threatening neurological emergency that requires prompt diagnosis and treatment. SE may be classified into convulsive and non-convulsive types, based on the presence of rhythmic jerking of the extremities. Clinically, tonic-clonic convulsive SE (CSE) is divided into four subsequent stages: Early, established, refractory and super-refractory. Initial elements of resuscitation include airway protection, haemodynamic resuscitation and seizure control. Further treatment should then be guided by the diagnostic workup. Rapid treatment of early SE is achieved with intravenous (IV) lorazepam or intramuscular midazolam. In established SE, IV antiepileptic drugs (AEDs) (phenytoin/fosphenytoin, valproate, levetiracetam, phenobarbital) are most commonly used, but there is no Class I evidence for choosing one over the other. Considered overall, cumulative data from the literature are consistent with valproate and levetiracetam, being a safe and effective therapeutic alternative to phenobarbital and phenytoin for treatment of established SE. Refractory SE (RSE) and super-RSE are treated with anaesthetic medications (propofol, midazolam, thiopental/pentobarbital, ketamine), non-anaesthetic drugs (lidocaine, magnesium, pyridoxine), AEDs (levetiracetam, lacosamide, topiramate, lacosamide, pregabalin, gabapentin) and other cause-directed treatments with low success rates. Potential non-pharmacologic interventions to be considered in super-RSE include hypothermia, electroconvulsive therapy, ketogenic diet, immunomodulatory treatments, emergency resective epilepsy surgery, cerebrospinal fluid drainage and vagal nerve or deep brain stimulation or transcranial magnetic stimulation. Diagnosis of non-CSE requires continuous electroencephalography and involves a high index of suspicion in all patients with an altered mental status of unclear cause or with a prolonged postictal state. Treatment options include addressing underlying causes and aggressive pharmacologic interventions with a benzodiazepine, phenytoin and valproate.

NORSE (new-onset refractory status epilepticus) and FIRES (febrile infection-related epilepsy syndrome) represent presentations of new-onset status epilepticus without apparent underlying structural, metabolic, or toxic etiology. The cause of NORSE/FIRES remains cryptogenic in up to half of cases, and an abnormal response of the innate immune system has been implicated. Consensus guidelines recommend broad diagnostic investigation and empiric treatment with immunotherapy. NORSE/FIRES is associated with poor outcomes including cognitive impairment and epilepsy, but early recognition and treatment may be important for improving outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this study, we report on a case of probable sporadic Creutzfeldt-Jakob disease (sCJD) diagnosed after a difficult course of status epilepticus (SE) in a patient with poststroke epilepsy. The patient was admitted with progressive cognitive decline and convulsive SE; therefore, it was initially thought that the patient had developed SE due to nonadherence to antiseizure medication (ASM) use, but despite treatment with ASMs after admission, no improvement was noted in consciousness disturbance or lateralized periodic discharges (LPDs) on electroencephalogram (EEG) examination. After a refractory course, the progression of LPDs to generalized periodic discharges (GPDs) on EEG and abnormal magnetic resonance imaging (MRI) findings met the diagnostic criteria of sCJD. Even if the patient had epilepsy, such as poststroke epilepsy, as in this case, it is essential to consider other underlying causes, including CJD in cases of superrefractory SE., Competing Interests: The authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Japan Neurosurgical Society.)

Background Status epilepticus (SE) is a common neurologic emergency with high rates of mortality and morbidity. Objective To analyze the clinical characteristics, causes, management, and outcomes of patients with SE in a tertiary care hospital in Morocco. Methods A retrospective study was conducted from January 2019 to December 2021, including all patients admitted to the medico-surgical general intensive care unit (ICU) with a diagnosis of SE. We recorded demographic characteristics, SE clinical history, management, causes, and discharge outcomes. Results Overall, 82 patients with SE were included, the median age was 39.5 years (18-95), 61% of the patients were male, the majority of semiology was convulsive SE (93%, N: 77), epilepsy of unknown cause was the most common diagnosis (41.2%, N: 34), and the most known etiology was acute/subacute cerebrovascular events (12 patients, 14.4%). All patients received benzodiazepines, 96.4% of them received phenobarbital as a second line of treatment, 65 patients required anesthesia, 52 patients developed one complication at least - the most common complication being systemic infection, and the mortality rate was noted to be 38% among patients with SE (N: 31). In this study, the factors associated with mortality were ischemic stroke (as an etiology of SE (p=0.048), history of epilepsy (p=0.005), poor therapeutic adherence (p=0.001), cardiovascular complications, presence of multiple complications (p=0.0001), pneumonia (p=0.0001), and the recurrence of SE (p=0.050). Conclusions We provide a single-center retrospective analysis of admissions in SE and note that mortality among SE patients is high in our settings. Improving prehospital emergency care and implementing elective ICU admission for patients at high risk could improve the mortality rate., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Bechri et al.)

Febrile infection-related epilepsy syndrome (FIRES) is a rare epileptic syndrome characterized by new-onset refractory status epilepticus preceded by a febrile illness. Limited literature exists regarding the relationship between primary immunodeficiencies and immune-mediated epilepsy, and the relationship between new-onset refractory status epilepticus and common variable immunodeficiency (CVID) is not well-understood. We present a case of a 21-year-old female with a history of recurrent sinus infections, asthma, thrombocytopenia, atrioventricular nodal reentrant tachycardia, and neonatal seizures who presented with fever and new-onset status epilepticus. She was ultimately diagnosed with a heterozygous variant in TNFRSF13B c.311G>A (p.Cys104Tyr), which encodes for a tumor necrosis factor receptor implicated in CVID., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Yang et al.)