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Acute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being replaced in many guidelines by midazolam, which terminates seizures more quickly, particularly when administered intramuscularly. While a direct correlation between seizure duration and the extent of brain injury has been widely reported, there are limited data comparing the neuroprotective efficacy of diazepam versus midazolam following acute OP intoxication. To address this data gap, we used non-invasive imaging techniques to longitudinally quantify neuropathology in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP) with and without post-exposure intervention with diazepam or midazolam. Magnetic resonance imaging (MRI) was used to monitor neuropathology and brain atrophy, while positron emission tomography (PET) with a radiotracer targeting translocator protein (TSPO) was utilized to assess neuroinflammation. Animals were scanned at 3, 7, 28, 65, 91, and 168 days post-DFP and imaging metrics were quantitated for the hippocampus, amygdala, piriform cortex, thalamus, cerebral cortex and lateral ventricles. In the DFP-intoxicated rat, neuroinflammation persisted for the duration of the study coincident with progressive atrophy and ongoing tissue remodeling. Benzodiazepines attenuated neuropathology in a region-dependent manner, but neither benzodiazepine was effective in attenuating long-term neuroinflammation as detected by TSPO PET. Diffusion MRI and TSPO PET metrics were highly correlated with seizure severity, and early MRI and PET metrics were positively correlated with long-term brain atrophy. Collectively, these results suggest that anti-seizure therapy alone is insufficient to prevent long-lasting neuroinflammation and tissue remodeling.

The mechanisms by which brain insults lead to subsequent epilepsy remain unclear. Insults including trauma, stroke, infections, and long seizures (status epilepticus, SE) increase the nuclear expression and chromatin binding of the neuron-restrictive silencing factor/RE-1 silencing transcription factor (NRSF/REST). REST/NRSF orchestrates major disruption of the expression of key neuronal genes, including ion channels and neurotransmitter receptors, potentially contributing to epileptogenesis. Accordingly, transient interference with REST/NRSF chromatin binding after an epilepsy-provoking SE suppressed spontaneous seizures for the 12 d duration of a prior study. However, whether the onset of epileptogenesis was suppressed or only delayed has remained unresolved. The current experiments determined if transient interference with REST/NRSF chromatin binding prevented epileptogenesis enduringly or, alternatively, slowed epilepsy onset. Epileptogenesis was elicited in adult male rats via systemic kainic acid-induced SE (KA-SE). We then determined if decoy, NRSF-binding-motif oligodeoxynucleotides (NRSE-ODNs), given twice following KA-SE (1) prevented REST/NRSF binding to chromatin, using chromatin immunoprecipitation, or (2) prevented the onset of spontaneous seizures, measured with chronic digital video-electroencephalogram. Blocking NRSF function transiently after KA-SE significantly lengthened the latent period to a first spontaneous seizure. Whereas this intervention did not influence the duration and severity of spontaneous seizures, total seizure number and seizure burden were lower in the NRSE-ODN compared with scrambled-ODN cohorts. Transient interference with REST/NRSF function after KA-SE delays and moderately attenuates insult-related hippocampal epilepsy, but does not abolish it. Thus, the anticonvulsant and antiepileptogenic actions of NRSF are but one of the multifactorial mechanisms generating epilepsy in the adult brain.

Status epilepticus (SE) is a life-threatening development of self-sustaining seizures that becomes resistant to benzodiazepines when treatment is delayed. Benzodiazepine pharmacoresistance is thought in part to result from internalization of synaptic GABAA receptors, which are the main target of the drug. The naturally occurring neurosteroid allopregnanolone is a therapy of interest against SE for its ability to modulate all isoforms of GABAA receptors. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been partially effective in combination with benzodiazepines in mitigating SE-associated neurotoxicity. In this study, allopregnanolone as an adjunct to midazolam or midazolam-ketamine combination therapy was evaluated for efficacy against cholinergic-induced SE. Adult male rats implanted with electroencephalographic (EEG) telemetry devices were exposed to the organophosphorus chemical (OP) soman (GD) and treated with an admix of atropine sulfate and HI-6 at 1 minute after exposure followed by midazolam, midazolam-allopregnanolone, or midazolam-ketamine-allopregnanolone 40 minutes after seizure onset. Neurodegeneration, neuronal loss, and neuroinflammation were assessed 2 weeks after GD exposure. Seizure activity, EEG power integral, and epileptogenesis were also compared among groups. Overall, midazolam-ketamine-allopregnanolone combination therapy was effective in reducing cholinergic-induced toxic signs and neuropathology, particularly in the thalamus and hippocampus. Higher dosage of allopregnanolone administered in combination with midazolam and ketamine was also effective in reducing EEG power integral and epileptogenesis. The current study reports that there is a promising potential of neurosteroids in combination with benzodiazepine and ketamine treatments in a GD model of SE. SIGNIFICANCE STATEMENT: Allopregnanolone, a naturally occurring neurosteroid, reduced pathologies associated with soman (GD) exposure such as epileptogenesis, neurodegeneration, and neuroinflammation, and suppressed GD-induced toxic signs when used as an adjunct to midazolam and ketamine in a delayed treatment model of soman-induced status epilepticus (SE) in rats. However, protection was incomplete, suggesting that further studies are needed to identify optimal combinations of antiseizure medications and routes of administration for maximal efficacy against cholinergic-induced SE.

Background: Temporal lobe epilepsy is the most common type of focal epilepsy, but hereditary factors are usually overlooked. Reelin (RELN) is considered to be the second most common pathogenic gene implicated in autosomal dominant lateral temporal epilepsy (ADLTE). However, this mutation is not frequently discovered in the Chinese population. Additionally, there are few clinical studies regarding the connection between RELN and glioma. Case presentation: The healthcare records of an 8-year-old child who experienced generalized tonic-clonic seizures (GTCS) during sleep for 7 years were retrospectively analyzed. In addition to experiencing his first seizure at the age of one, his mother also suffered from GTCS during her pregnancy, and a glioma was discovered. An investigation involving gene sequencing was conducted on the proband and his parents. He was diagnosed with ADLTE once a missense mutation in RELN (c.1799 C > T) was identified as the causal factor. The mutation was inherited from his mother. He was taking levetiracetam (500 mg twice a day) to avoid seizures, but his mother died of status epilepticus caused by glioma recurrence two years earlier. Conclusions: Genetic issues should be given more consideration in cases of temporal lobe epilepsy. If the source of the seizures is determined to be inherited, anti-seizure medications should be used for prolonged periods. Furthermore, more research is required to determine whether mutations in RELN are related to the occurrence and progression of gliomas. [ABSTRACT FROM AUTHOR]

Background Aim Design Results Conclusion Status epilepticus (SE) is defined as 5 min or more of seizure activity or two recurrent seizures without a return to baseline. Healthcare providers encounter a challenge when a patient with SE is pregnant. SE is not only detrimental to the mother but can also put the baby at risk of severe harm. SE must be treated rapidly and therefore healthcare providers have very little time to thoroughly review the risk and benefits of available antiseizure medication in this population.To evaluate the current available evidence related to the management of SE in pregnancy.A literature search of PubMed, CINAHL, ProQuest Nursing & Allied Health Source, and Web of Science databases was conducted (2012–2022) using the following search terms: ‘pregnancy’, ‘pregnant women’ OR ‘gestation’ AND ‘status epilepticus’, ‘generalized status epilepticus’, ‘generalized convulsive status epilepticus’, ‘non convulsive status epilepticus’ OR ‘non‐convulsive status epilepticus’. Full‐text randomised controlled trials, clinical trials, observational studies, and case reports published in English were included. Data were extracted and the quality of the studies was evaluated using the Mixed Methods Appraisal Tool.The literature described 29 pregnancies and 30 total foetuses. Intravenous benzodiazepine use for emergent control was reported in 45% of patients. Phenytoin and levetiracetam were primarily utilised for urgent control, with a variety of agents used for refractory SE. Ninety‐seven percent of maternal outcomes were reported as positive. The most common outcome was the birth of a healthy term infant. There were seven cases of pregnancy loss.Publications pertaining to the treatment of SE in pregnancy are limited to case reports and small observational studies. Use of a benzodiazepine followed by levetiracetam or phenytoin is appropriate, whereas valproic acid should be utilised only when necessary due to the risk of major congenital malformation. [ABSTRACT FROM AUTHOR]

Background: The management of epilepsy is mainly based on antiseizure medications (ASMs). More than 20 ASMs have been introduced in clinical practice, providing a multitude of prescription choices. To date, there are no published data on the trends in ASMs prescriptions in Morocco. Therefore, we conducted a survey among practicing neurologists in seven tertiary referral hospitals in Morocco to study the current ASMs prescription preferences and their modifying factors. Methods: Our descriptive and analytical cross-sectional study was based on a survey sent between January and April 2022 to neurologists practicing in seven tertiary referral hospitals in Morocco. Information regarding the prescription of ASMs was collected using an exploitation form and analyzed using the SPSS version 13 software. Results: Based on questionnaire responses, our results showed that Valproic acid (96.3%) and Lamotrigine (59.8%) were the two most prescribed ASMs for generalized seizure types. For focal seizure types, Carbamazepine (98.8%) and Levetiracetam (34.1%) were the most commonly prescribed drugs, whereas for combined focal and generalized seizure types, the combination of Valproic acid and Carbamazepine (38.55%) was the most prescribed. Phenobarbital was the most commonly prescribed ASM for status epilepticus (40.2%). These prescription preferences were mainly due to seizure types, cost, health insurance coverage, years of experience, and additional epileptology training (p < 0.05). Conclusion: Our results show a shift in the prescription of ASMs in Morocco. Similar to many other countries, valproic acid and carbamazepine are considered the first-line treatments for generalized and focal seizure types. Some factors remain as major challenges in enhancing epilepsy management in Morocco. [ABSTRACT FROM AUTHOR]

Background: Status epilepticus (SE) is a heterogeneous neurological emergency with significant variability in prognosis, influenced by underlying disease and pathophysiological context. Acid–base disturbances are common in critically ill patients, yet their distribution and impact in SE patients remain poorly understood. Methods: This was an observational cohort study including non-hypoxic SE patients with available blood gas analysis within the first 24 h of SE, treated at the University Hospital of Geneva, Switzerland between 2015 and 2023. Acid–base disturbances were classified using the Henderson–Hasselbalch equation, with prevalent metabolic alkalosis confirmed through the Stewart approach. Primary outcomes were in-hospital mortality, Glasgow Outcome Scale (GOS) at discharge, and return to premorbid neurologic function. Findings: Among 540 SE patients, 365 were included. Half of patients exhibited acid–base disturbances within the initial 24 h of SE, with metabolic and respiratory acidosis being the most prevalent, though not prognostically significant. After correction for possible confounders, metabolic alkalosis (6%) was associated with increased in-hospital mortality (P = 0.011; OR = 4.87, 95% CI = 1.29–7.84), worse GOS (P = 0.012; OR = 3.18, 95% CI = 1.29–7.84), and reduced likelihood of returning to premorbid function (P = 0.017; OR = 3.30, CI95% = 1.24–8.80). Following the Stewart approach, 9% of patients had predominant metabolic alkalosis, associated with worse GOS (P = 0.005; OR:3.37, 95%CI = 1.45–7.82), and reduced chance of returning to baseline (P = 0.012; OR = 3.29, CI95% = 1.30–8.32). Metabolic alkalosis was related to hypoalbuminemia and lower serum potassium. Conclusion: Metabolic alkalosis strongly predicts mortality and adverse functional outcome in SE patients. Prospective studies should assess whether early detection and correction of metabolic alkalosis and related electrolyte imbalances can improve SE prognosis. [ABSTRACT FROM AUTHOR]

Current recommendations for refractory status epilepticus (SE) unresponsive to benzodiazepines suggest a loading dose of levetiracetam (LEV) of 60 mg/kg to a maximum of 4500 mg. LEV therapeutic drug monitoring can help guide therapy and is garnering increasing attention. The objective of this study is to simulate the probability of target attainment (PTA) of fixed dose and weight‐based loading doses of LEV with respect to established therapeutic target concentrations. Meta‐regression of the current literature was performed to evaluate the relationship between intravenous LEV loading dose and seizure cessation in refractory SE patients. A previously published pharmacokinetic model was used to simulate the PTA capacity of competing single intravenous dosing schemes (fixed vs weight‐based dosing) to achieve maximum (Cpeak) and 12‐h (C12h) plasma concentrations that exceed 12 mg/L. The meta‐regression indicated that dosage was not a statistically significant modulator of seizure control at dosages between 20 and 60 mg/kg. Stochastic simulations showed all dosing schemes achieved plasma Cpeak >12 mg/L, but C12h levels were <12 mg/L in subjects over 60 kg with a fixed dose ≤2000 mg or in subjects <60 kg with a weight‐based dose <30 mg/kg. Dosages of 40 and 60 mg/kg provided ≥90% PTAs across all weights. Using a weight‐based loading dose of 40 mg/kg, up to a suggested maximum of 4500 mg, improves the likelihood of achieving a sustained therapeutic drug concentration after the initial LEV dose, whereas fixed <3000 mg may not achieve the desired concentration before maintenance dosing. [ABSTRACT FROM AUTHOR]

Benzodiazepines are the recommended first-line treatment of acute seizures. We wished to compare the efficacy, side effects, and satisfaction after midazolam administration by the buccal, intranasal, or intramuscular route in the treatment of acute seizures in children at homes and in emergency room (ER). A prospective, randomized, controlled trial was performed in children aged one month to 17 years with acute seizures lasting longer than five minutes. The primary end point was seizure cessation within 10 minutes of drug administration and no seizure recurrence within 30 minutes. In the home group, 67 patients received midazolam via buccal route, 60 via intranasal route, and 69 via intramuscular route, whereas in the ER group, 37 patients received buccal, 34 received intranasal, and 34 received intramuscular midazolam. The primary end point was achieved in 94.2% and 85.3% after intramuscular midazolam in the home and ER groups, respectively. The intranasal midazolam was successful in stopping seizures in 93.3% in the home group and 88.2% in the ER group. The buccal route was effective in 91% in the home group and 78.4% in the ER group. There were no significant differences in efficacy between all groups (P = 0.763 and P = 0.509) among the home and ER groups, respectively. There were no significant cardiorespiratory events in all groups. Intramuscular, intranasal, and buccal doses of midazolam resolved most seizures in prehospital and emergency settings. Our results indicate that there is no statistically significant difference detected between different routes of midazolam. Intranasal route showed the highest satisfaction rate among caregivers. [ABSTRACT FROM AUTHOR]

Approximately 10% to 20% of children with epilepsy experience status epilepticus (SE), and children with seizure clustering are at higher risk. Ketamine is growing in use for SE. This study examines the efficacy and safety of enteral ketamine in the treatment of convulsive status epilepticus (CSE) characterized by refractory seizure clusters and nonconvulsive status epilepticus (NCSE) in children with epilepsy. Patient charts were reviewed retrospectively. Children with epilepsy aged one to 21 years presenting in SE and treated with enteral ketamine between September 1, 2021 and September 1, 2022 at a pediatric tertiary care center were identified. Resolution or reduction in seizure frequency within 48 hours, clinical presentation, endotracheal intubation, hospitalization duration, side effects, and readmission were assessed. Nine patients aged two to 21 years were identified. Six patients presented in CSE characterized by recurrent seizures, and three patients presented in NCSE. Five patients had genetic epilepsies, including PCDH19- and MECP2-related epilepsy. Seven patients had resolution or reduction in seizures within 48 hours of ketamine initiation. Two patients were intubated. Hospitalization duration ranged from one to 34 days. Three patients reported side effects. Three patient readmissions with early ketamine treatment had equal or shorter hospitalizations. Enteral ketamine may prove an effective, well-tolerated option for treatment of convulsive and nonconvulsive SE in children with epilepsy, including genetic epilepsies, and may prevent intubation and shorten hospitalization time. [ABSTRACT FROM AUTHOR]

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

Objective Methods Results Interpretation The Salzburg EEG criteria for nonconvulsive status epilepticus (NCSE) have been proposed as consensus criteria for NCSE. We aimed to perform an independent study of their diagnostic accuracy.A prospective study was carried out at Oslo University Hospital, including all consecutive patients ≥15 years old who were referred for an EEG with an explicit or implicit question of NCSE from February 2020 to February 2022. Two independent EEG readers scored the included EEGs according to the Salzburg criteria and blinded to the clinical data. The reference standard was defined as the clinical diagnosis the patient received based on all available clinical and paraclinical data. Diagnostic accuracy in identifying “certain/possible NCSE” was assessed by calculating sensitivity, specificity, positive predictive value, and negative predictive value with their 95% confidence intervals.In total, 469 patients/EEGs were included in the study. The prevalence of NCSE according to the reference standard was 11% (n = 53). The criteria showed a sensitivity of 94% (95% CI: 92–96%), a specificity of 77% (95% CI: 73–81%), a positive predictive value of 34% (95% CI: 30–39%), and a negative predictive value of 99% (95% CI: 98–100%). False positives for “certain NCSE” (n = 16) included many serial seizures and stimulus‐induced rhythmic and periodic discharges (SIRPIDs), as well as a focal cortical dysplasia. False positives for “possible NCSE” (n = 79) were mainly represented by different encephalopathies and postictality.The low specificity of the Salzburg criteria calls for refinement before implementation into daily clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: New onset refractory status epilepticus (NORSE) is a rare and devastating condition characterised by the sudden onset of refractory status epilepticus (RSE) without an identifiable acute or active structural, toxic, or metabolic cause in an individual without a pre-existing diagnosis of epilepsy. Febrile infection-related epilepsy syndrome (FIRES) is considered a subcategory of NORSE and presents following a febrile illness prior to seizure onset. NORSE/FIRES is associated with high morbidity and mortality in children and adults. Methods and results: In this review we first briefly summarise the reported clinical, paraclinical, treatment and outcome data in the literature. We then report on existing knowledge of the underlying pathophysiology in relation to in vitro and in vivo pre-clinical seizure and epilepsy models of potential relevance to NORSE/FIRES. Discussion: We highlight how pre-clinical models can enhance our understanding of FIRES/NORSE and propose future directions for research. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusion Our objective was to define phenotypes of non‐lesional late‐onset epilepsy (NLLOE) depending on its presumed aetiology and to determine their seizure and cognitive outcomes at 12 months.In all, 146 newly diagnosed NLLOE patients, >50 years old, were prospectively included and categorized by four presumed aetiological subtypes: neurodegenerative subtype (patients with a diagnosis of neurodegenerative disease) (n = 31), microvascular subtype (patients with three or more cardiovascular risk factors and two or more vascular lesions on MRI) (n = 39), inflammatory subtype (patient meeting international criteria for encephalitis) (n = 9) and unlabelled subtype (all individuals who did not meet the criteria for other subtypes) (n = 67). Cognitive outcome was determined by comparing for each patient the proportion of preserved/altered scores between initial and second neuropsychological assessment.The neurodegenerative subtype had the most severe cognitive profile at diagnosis with cognitive complaint dating back several years. The microvascular subtype was mainly evaluated through the neurovascular emergency pathway. Their seizures were characterized by transient phasic disorders. Inflammatory subtype patients were the youngest. They presented an acute epilepsy onset with high rate of focal status epilepticus. The unlabelled subtype presented fewer comorbidities with fewer lesions on brain imaging. The neurodegenerative subtype had the worst seizure and cognitive outcomes. In other groups, seizure control was good under antiseizure medication (94.7% seizure‐free) and cognitive performance was stabilized or even improved.This new characterization of NLLOE phenotypes raises questions regarding the current International League Against Epilepsy aetiological classification which does not individualize neurodegenerative and microvascular aetiology per se. [ABSTRACT FROM AUTHOR]

Background: Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are rare, life-threatening immunologic reactions. Previous relevant literature has provided limited information regarding this disease's genetic susceptibility and management principles. Objectives: This study aimed to describe a phenobarbital-induced TEN case report with HLA-B*15:02 and HLA-B*58:01 negative, CYP2C19*1/*2. In addition, we revised the existing literature on phenobarbital-induced SJS/TEN to explore its clinical characteristics. Methods: We describe a woman undergoing treatment with Phenobarbital for status epilepticus who developed classic cutaneous findings of TEN. A systematic search was conducted in the PubMed, Medline, WanFang, and CNKI databases from 1995 to 2023. The search terms used were "Stevens-Johnson Syndrome," "Toxic Epidermal Necrolysis," and "Phenobarbital." Results: We report a case of TEN resulting from phenobarbital; it tested negative for the HLA-B*15:02 and HLA-B*58:01 allele and CYP2C19*1/*2 intermediate metabolism. Supportive treatment with steroids and antihistamines resulted in complete resolution of the skin lesions and improvement in clinical symptoms after 14 days. Physicians and clinical pharmacists should be aware of these potential phenobarbital-related adverse events and closely monitor patients with first-time use of phenobarbital. Among 19 cases were identified in the literature, with 11 (57.9%) cases of SJS, 6 (31.6%) cases of TEN, and 2 (7.2%) cases of SJS-TEN/DRESS overlap. A total of 5 (26.3%) did not survive, of which 4 (21.1%) were under 12 years old and 1 (5.3%) was over 12 years old. Conclusion: Phenobarbital-induced SJS/TEN may still occur in patients who test negative for HLA-B*15:02 and HLA-B*58:01, CYP2C19*1/*2. Most cutaneous adverse events occur early in the course of Phenobarbital therapy and should be closely monitored early in the course of treatment. In addition, Phenobarbital should be used with caution in patients with a history of asthma and allergy to antipyretics and analgesics. [ABSTRACT FROM AUTHOR]

A 32-year-old female with advanced human immunodeficiency virus infection presented to an Australian hospital with subacute, worsening symptoms of encephalitis. Metagenomic sequencing and Dengue NS3 antigen staining of brain tissue confirmed active dengue virus (DENV) encephalitis. The most recent possible DENV exposure was months prior in West Africa, indicating chronicity. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance Intravenous (IV) push (IVP) is an alternative administration method for levetiracetam, but evidence evaluating it compared to IV piggyback (IVPB) for loading doses in acutely seizing patients is limited, particularly in patients with status epilepticus (SE). This study aimed to compare the efficiency and safety of IVP versus IVPB levetiracetam loading doses.This was a single‐center sequential retrospective study conducted in adult (≥18 years) patients who received an IV levetiracetam loading dose (>2000 mg or ≥20 mg/kg) for acute or suspected seizure. The primary outcome was time to administration, compared between doses given as IVP versus IVPB. Secondary outcomes included rates of adverse events (AEs), rescue benzodiazepine or antiseizure medication administration, intubation, and intensive care unit (ICU) admission between groups.A total of 246 patients were included; 116 received IVP and 130 received IVPB loading doses. Median age was 56 years; most patients were male (62%) and White (60%) and had witnessed seizures (67%). Doses were administered for SE in 32 (27.5%) and 46 (35.4%) patients in the IVP and IVPB arms, respectively. Median time to administration was shorter in the IVP group (12 vs. 38 min, p < .001). Bradycardia (1.7% vs. 2.3%, p = .99), hypotension (7.8% vs. 12%, p = .30), sedation (6% vs. 12.3%, p = .09), intubation (10% vs. 8%, p = .37), ICU admission (32% vs. 39%, p = .31), and rescue medication administration (8.6% vs. 14.6% p = .10) were similar between groups. In SE patients, IVP was associated with shorter time to administration (12 vs. 44 min, p = .003) and lower odds of ICU admission after adjustment for age, dose, Status Epilepticus Severity Score, and seizure history (adjusted odds ratio = .23, 95% confidence interval = .06–.81).IVP reduced time to levetiracetam administration versus IVPB and was not associated with more AEs. Rescue agent use, intubation, and ICU admission were similar between arms, but IVP may reduce ICU admissions in SE patients. Prospective studies should assess the effectiveness of IVP versus IVPB. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance Many people with epilepsy experience comorbid anxiety and depression, and antidepressants remain a primary treatment for this. Emerging evidence suggests that these agents may modulate epileptogenesis to influence disease severity. Here, we assessed how treatment with the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine impacts epileptogenic, behavioral, and pathological sequelae following status epilepticus.Male Wistar rats received kainic acid to induce status epilepticus (SE) or vehicle (sham). Animals then received either fluoxetine (10 mg/kg/day) or vehicle for 8 weeks via subcutaneous osmotic pump. Video‐electroencephalography was recorded continuously until behavioral testing at day 56, including assessments of anxiety‐ and depression‐like behavior and spatial cognition. Postmortem immunocytochemistry studies examined mossy fiber sprouting.Fluoxetine treatment significantly accelerated epileptogenesis following SE, reducing the average period to the first spontaneous seizure (from 32 days [vehicle] to 6 days [fluoxetine], p < .01). Also, fluoxetine exposure magnified the severity of the resultant epilepsy, increasing seizure frequency compared to vehicle (p < .01). Exposure to fluoxetine was associated with improved anxiety‐ and depression‐like behaviors but significantly worsened cognition. Mossy fiber sprouting was more pronounced in fluoxetine‐treated rats compared to vehicle (p < .0001).Our studies demonstrate that, using a model exhibiting spontaneous seizures, epileptogenesis is accelerated and magnified by fluoxetine, an effect that may be related to more severe pathological neuroplasticity. The differential influence of fluoxetine on behavior indicates that different circuitry and mechanisms are responsible for these comorbidities. These findings suggest that caution should be exercised when prescribing SSRI antidepressants to people at risk of developing epilepsy. [ABSTRACT FROM AUTHOR]

Background: Status epilepticus is a common and potentially life-threatening neurological emergency with a high risk for cognitive and neurobiological impairment. Our aim was to evaluate the neuroprotective effects of centrally administered irisin and acute exhausting exercise against oxidative brain injury and memory dysfunction due to a pentylenetetrazole (PTZ)-induced single seizure. Male Sprague Dawley rats with intracerebroventricular (icv) cannulas were randomly divided into intraperitoneally (ip) saline-injected control and PTZ-injected (45 mg/kg) seizure groups. Both the control and PTZ groups were then treated with irisin (7.5 µg/kg, 2 µl, icv), saline (2 µl, icv) or were forced to an acute bout of strenuous exercise before the ip injection of saline (control) or PTZ. Seizures were evaluated using the Racine score. To evaluate memory performance, a passive avoidance test was performed before and after PTZ injection. Following euthanasia at the 24th hour of seizure induction, brain tissues were removed for histopathological examination and for evaluating oxidative damage, antioxidant capacity, and neurotransmitter levels. Results: Glutamate/GABA imbalance observed in PTZ rats was corrected by irisin administration (p < 0.001/p < 0.01), while irisin prevented the generation of reactive oxygen species and lipid peroxidation (p < 0.05 − 0.001) and replenished the antioxidant catalase and glutathione levels (p < 0.01–0.01) in the cerebral tissue, and reduced the histologically evident neuronal injury due to a single seizure (p < 0.05 − 0.01). Irisin also delayed the onset of seizures (p < 0.05) and improved memory dysfunction (p < 0.05), but did not affect the severity of seizures. The acute exhaustive swimming exercise completed before PTZ-seizure depressed glutamate level (p < 0.001), maintained the oxidant/antioxidant balance, alleviated neuronal injury (p < 0.05 − 0.01) and upregulated cerebral BDNF expression (p < 0.05). Conclusion: In conclusion, acute high-intensity exercise or exogenously administered irisin provides neuroprotection by maintaining the balance of excitatory/inhibitory neurotransmitters and oxidant/antioxidant systems. [ABSTRACT FROM AUTHOR]

Introduction: It is important to identify the early predictors of adverse outcome neonatal seizures to provide advanced care and to prevent complications. Hence, the present study was conducted to ascertain short term outcomes of neonatal seizures and percentage of mortality and severe neurological impairments and to assess significance of demographic, perinatal, clinical and etiological parameters as predictors of short-term outcome. Methodology: This retrospective hospital record survey was conducted at Special Newborn Care Unit (SNCU), Department of Pediatrics, Govt. R.D.B.P Jaipuria Hospital, Jaipur, Rajasthan among Neonates admitted in SNCU with clinical diagnosis of Neonatal seizures during last two years (from 1st May, 2018 to 28th Feb.,2020). Medical records of the hospital were assessed and relevant demographic details, significant maternal (antenatal) history, perinatal history like Apgar score, need for advanced resuscitation, time of onset, duration of seizure, presence of status epilepticus etc were thoroughly evaluated. Short-term outcomes were categorized as Favorable and Adverse Neurodevelopmental Outcome. Results: Most of the neonates with seizures were discharged with no or mild neuro impairment (66%). Mortality and adverse neurodevelopmental outcome was among 17%. Most common cause of mortality in neonatal seizures was BA HIE (76.5%) followed by IVH (11.8%) and brain malformation (11.8%). Most common cause of severe neuro impairment was HIE (76.5%). Other causes were meningitis (11.8%), hypoglycemia (5.9%) and IVH (5.9%). Adverse neuro-developmental outcome was significantly associated with Pre term birth (51.9%), Small for date subjects (83.3%) and Low birth weight (51.3%), one minute APGAR score ≤6 (43.7%) and five-minute APGAR score ≤6 (50%), seizure onset within 24 hours of birth (51.2%), status epilepticus (54.5%), severe abnormality on neuro examination (52.6%) and severe findings on cranial imaging (49%). Conclusion: Scrutiny of factors like Pre term birth, Low birth weight, small for date, one minute APGAR score ≤6, 5 minute APGAR score ≤6, seizure onset within 24 hours of birth, status epilepticus, severe findings on neuro examination or on cranial imaging, can help in early identification of neonates at risk of adverse neuro-developmental outcome and initiate timely intervention for these neonates. [ABSTRACT FROM AUTHOR]

Objectives: Previous studies have shown that gene expressions can be regulated in the hippocampus of rats after seizures induced by kainic acid (KA). The aim of this study was to examine the potential regulatory impact of KA administration on gene expression levels of enzymes responsible for drug metabolism in rat hippocampal tissue. Materials and Methods: Rats received intraperitoneal injections of KA and saline at a dose of 10 mg/kg. Behavioral changes were observed in experimental animals following the administration of KA. Four hours after receiving treatments, all rats were decapitated, and the brains were removed. Hippocampal tissues were used for total RNA isolation, and cDNA synthesis was performed by reverse transcription polymerase chain reaction (PCR). Gene expression levels of enzymes responsible for drug metabolism were determined by quantitative PCR using the RT2 Profiler PCR Array Rat Drug Metabolism PCR array system containing the relevant primers for a total of 84 genes. The gene expression levels of drug-metabolizing enzymes were quantified using the comparative Ct (2-ΔΔ(delta delta)Ct) method. The Student’s t-test was used for data analysis. Results: Our results indicate that KA treatment caused significant changes in the gene expression levels of metallothionein 3, glucose phosphate isomerase, adenosine triphosphate-binding cassette protein C1, cytochrome P450 enzymes (Cyp2c6v1, Cyp3a23/3a1, Cyp2c7), glutathione peroxidase 1, 4, and 5, glutamic acid decarboxylase 1 and 2, paraoxonase 2, carbohydrate sulfotransferase 1, glutathione S-transferases (Gsta3, Gstm1, Gstm4), microsomal glutathione S-transferase 3, carboxylesterase 2C, fatty acid amide hydrolase, pyruvate kinase-muscle, arachidonate 5-lipoxygenase, apolipoprotein E, cytochrome b5 reductase 5, xanthine dehydrogenase, N-acetyltransferase 1, glucokinase regulator, hexokinase 2, myristoylated alanine rich protein kinase C substrate, and stannin in the hippocampus compared with the control (p < 0.05). Conclusion: As a conclusion, it can be said that the seizure activity triggered by KA has the potential to change the gene expression levels of the enzymes responsible for drug metabolism in the hippocampus of rats. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the aetiology, management and outcomes of convulsive status epilepticus (CSE) in children and highlight the factors influencing patient outcomes in such cases. Methods: In a retrospective study spanning the 2020-2023 period, 93 children with CSE treated at Sultan Qaboos University Hospital's emergency department (ED), high dependency unit (HDU) and intensive care unit (ICU) were analysed. The Modified Rankin Scale at discharge was used to determine CSE outcomes. Results: Among the 93 children studied (mean age 4.84 ± 3.64 years), predominantly Omani (92.47%), 14 aetiologies were noted. Of them, acute symptomatic (37.7%) and febrile status (31.2%) were the primary causes of CSE. Diazepam was administered as the first-line treatment in 58 (67.44%) cases, with a median seizure duration of 45 minutes. Successful seizure control was achieved in 71 (76.34%) cases within 60 minutes. A return to baseline was observed in 55.9% of cases, while mortality and disability were noted in 5.38% and 38.7% of cases, respectively. For 17 cases, aetiology and duration significantly impacted patient outcomes (P <0.05). Conclusion: Acute symptomatic status is the most common aetiology of CSE. A longer duration of CSE is associated with higher mortality and neurological disability. Prompt and appropriate management of CSE is essential. Furthermore, identifying and treating the underlying cause of CSE is a crucial step in reducing its duration and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background/Objectives: To determine the impact of psychiatric disorders on epilepsy treatment outcomes and healthcare utilization in children with epilepsy (CWE) based on the presence or timing of the onset of psychiatric disorders. Methods: This retrospective controlled study enrolled children (age < 18 years) with newly diagnosed epilepsy into four groups stratified by the presence and timing of the onset of psychiatric disorders (None: no psychiatric disorders; Before: psychiatric disorders only preceding the epilepsy diagnosis; After: new psychiatric disorders diagnosed only after the epilepsy diagnosis; Mixed: different psychiatric disorders diagnosed both before and after epilepsy diagnosis) and compared the intergroup differences in epilepsy treatment outcomes and healthcare utilization. Results: Among the CWE (n = 37,678), 13,285 (35.26%) had comorbid psychiatric disorders. The After (n = 7892), Mixed (n = 3105), and Before (n = 2288) groups had significantly longer treatment periods than those in the None group (p < 0.001). Compared with the None group, the remaining groups had significantly higher frequencies of outpatient visits, emergency room visits, and admissions and higher rates of status epilepticus and drug-resistant epilepsy (p < 0.001, respectively), with higher odds ratios [95% confidence interval] for status epilepticus (2.92 [2.68–3.18]) and drug-resistant epilepsy (3.01 [2.85–3.17]) in the After group. Conclusions: Psychiatric comorbidities, diagnosed before and after epilepsy diagnosis, negatively affected the treatment outcomes. CWE without prior psychiatric disorders that were newly diagnosed during epilepsy treatment had the worst outcomes and the highest healthcare utilization rates. [ABSTRACT FROM AUTHOR]

• P2X7R signaling regulates both glial and neuronal genes during seizures. • P2X7R deficiency in microglia reduces seizure severity and leads to an anti-inflammatory phenotype in microglia during seizures. • P2X7R deficiency in neurons increases seizure severity. • Increased expression of P2X7Rs on GABAergic interneurons reduces seizure severity in acquired and genetic models of epilepsy. The purinergic ATP-gated P2X7 receptor (P2X7R) is increasingly recognized to contribute to pathological neuroinflammation and brain hyperexcitability. P2X7R expression has been shown to be increased in the brain, including both microglia and neurons, in experimental models of epilepsy and patients. To date, the cell type-specific downstream effects of P2X7Rs during seizures remain, however, incompletely understood. Effects of P2X7R signaling on seizures and epilepsy were analyzed in induced seizure models using male mice including the kainic acid model of status epilepticus and pentylenetetrazole model and in male and female mice in a genetic model of Dravet syndrome. RNA sequencing was used to analyze P2X7R downstream signaling during seizures. To investigate the cell type-specific role of the P2X7R during seizures and epilepsy, we generated mice lacking exon 2 of the P2rx7 gene in either microglia (P2rx7 : Cx3cr1 -Cre) or neurons (P2rx7 : Thy-1 -Cre). To investigate the protective potential of overexpressing P2X7R in GABAergic interneurons, P2X7Rs were overexpressed using adeno-associated virus transduction under the mDlx promoter. RNA sequencing of hippocampal tissue from wild-type and P2X7R knock-out mice identified both glial and neuronal genes, in particular genes involved in GABAergic signaling, under the control of the P2X7R following seizures. Mice with deleted P2rx7 in microglia displayed less severe acute seizures and developed a milder form of epilepsy, and microglia displayed an anti-inflammatory molecular profile. In contrast, mice lacking P2rx7 in neurons showed a more severe seizure phenotype when compared to epileptic wild-type mice. Analysis of single-cell expression data revealed that human P2RX7 expression is elevated in the hippocampus of patients with temporal lobe epilepsy in excitatory and inhibitory neurons. Functional studies determined that GABAergic interneurons display increased responses to P2X7R activation in experimental epilepsy. Finally, we show that viral transduction of P2X7R in GABAergic interneurons protects against evoked and spontaneous seizures in experimental temporal lobe epilepsy and in mice lacking Scn1a , a model of Dravet syndrome. Our results suggest a dual and opposing action of P2X7R in epilepsy and suggest P2X7R overexpression in GABAergic interneurons as a novel therapeutic strategy for acquired and, possibly, genetic forms of epilepsy. [ABSTRACT FROM AUTHOR]

Aim: To compare the efficacy of intravenous clonazepam (CLZ) for the initial management of convulsive status epilepticus (CSE) in children as a function of the first‐line in‐hospital dose used. Method: This monocentric retrospective study included children who received a first dose of CLZ for CSE at Montpellier University Hospital, France, between January 2016 and June 2019. Data from medical records (clinical, treatment, course) were collected and compared as a function of the first CLZ dose used. Results: Among the 310 children treated for CSE, 105 received at least one CLZ dose (median age 3 years; quartile 1–quartile 3 [Q1–Q3] = 1 years 2 months–6 years 6 months). Among these 105 patients, 24 (22%) received a dose less than 0.03 mg/kg (low dose) and 69 (65%) received a dose of at least 0.03 mg/kg (high dose). Seizure cessation rate was not different between the low‐ and high‐dose groups (62.5% vs 76%; odds ratio 0.53, 95% confidence interval [CI] 0.19–1.44, p = 0.29). The administration of a second dose of CLZ was more frequent in the low‐ than the high‐dose group (37.5% vs 16%; odds ratio 3.2, 95% CI 1.1–9.1, p = 0.04). Interpretation: Our study did not find any difference in seizure termination rate as a function of CLZ dose in children with CSE. However, a second CLZ dose was more frequently needed in the group receiving low (less than 0.03 mg/kg) CLZ. [ABSTRACT FROM AUTHOR]

Introduction: Seizures may occur in up to 30% of non-Hodgkin lymphoma patients who received anti-CD19 CAR T-cell therapy, yet the optimal anti-seizure medication (ASM) prevention strategy has not been thoroughly investigated. Methods: Consecutive patients affected by refractory non-Hodgkin lymphoma who received anti-CD19 CAR T-cells were included. Patients were selected and assessed using similar internal protocols. ASM was started either as a primary prophylaxis (PP-group) before CAR T-cells infusion or as a pre-emptive therapy (PET-group) only upon the onset of neurotoxicity development. Results: One hundred fifty-six patients were included (PP-group = 88, PET-group = 66). Overall, neurotoxicity and severe neurotoxicity occurred in 45 (29%) and 20 (13%) patients, respectively, equally distributed between the two groups. Five patients experienced epileptic events (PET-group = 3 [4%]; PP-group = 2 [2%]). For all the PET-group patients, seizure/status epilepticus occurred in the absence of overt CAR-T-related neurotoxicity, whereas patients in the PP-group experienced brief seizures only in the context of critical neurotoxicity with progressive severe encephalopathy. ASMs were well-tolerated by all patients, even without titration. No patients developed epilepsy or required long-term ASMs. Conclusion: Our data suggest that both primary and pre-emptive anti-seizure prophylaxis are safe and effective in anti-CD19 CAR T-cell recipients. Clinical rationale suggests a possible more favourable profile of primary prophylaxis, yet no definitive conclusion of superiority between the two ASM strategies can be drawn from our study. [ABSTRACT FROM AUTHOR]