midazolam seizure

Nerve agents and organophosphates (OP) are neurotoxic chemicals that induce acute seizures, status epilepticus (SE), and mortality. Long-term neurological and neurodegenerative effects manifest months to years after OP exposure. Current benzodiazepine anticonvulsants are ineffective in preventing such long-term neurobehavioral and neuropathological changes. New and effective anticonvulsants are needed for OP intoxication, especially for mitigating the long-term sequelae after acute exposure. We developed neurosteroids as novel anticonvulsants and neuroprotectants in OP exposure models...

This article describes recent advances in the use of neurosteroids as novel anticonvulsants for refractory status epilepticus (RSE) and as medical countermeasures (MCs) for organophosphates and chemical nerve agents (OPNAs). We highlight a decade-long journey to bring the synthetic neurosteroid ganaxolone (GX) from bench to clinic. RSE, including when caused by nerve agents, is associated with devastating morbidity and permanent long-term neurological dysfunction. Although recent approval of benzodiazepines such as intranasal midazolam or diazepam and intranasal midazolam offers improved of control of acute seizures, novel anticonvulsants are needed to suppress RSE and improve neurological function outcomes...

Benzodiazepine pharmacoresistance develops when treatment of status epilepticus (SE) is delayed. This response may result from gamma-aminobutyric acid A receptors (GABAA R) internalization that follows prolonged SE; this receptor trafficking results in fewer GABAA R in the synapse to restore inhibition. Increase in synaptic N-methyl-D-aspartate receptors (NMDAR) also occurs in rodent models of SE. Lacosamide, a third generation antiseizure medication (ASM), acts on the slow inactivation of voltage-gated sodium channels...

Focal cortical dysplasia (FCD) represents the most common cause of drug-resistant epilepsy in adult and pediatric surgical series. However, genetic factors contributing to severe phenotypes of FCD remain unknown. We present a patient with an exceptionally rapid development of drug-resistant epilepsy evolving in super-refractory status epilepticus. We performed multiple clinical (serial EEG, MRI), biochemical (metabolic and immunological screening), genetic (WES from blood- and brain-derived DNA) and histopathological investigations...

BACKGROUND: Postictal encephalopathy is well known after status epilepticus (SE), but its prognostic impact and triggers are unknown. Here, we aimed to establish risk factors for the development of postictal encephalopathy and to study its impact on survival after discharge. METHODS: This retrospective cohort study comprised adult patients diagnosed with first nonanoxic SE at Odense University Hospital between January 2008 and December 2017. Patients with ongoing SE at discharge or unknown treatment success were excluded...

Given the rising frequency of drug shortages in hospitals, interdisciplinary collaboration is necessary to manage medications, modify electronic medical records, and evaluate safety outcomes. One such shortage impacted lorazepam injection, a medication commonly used in palliative care to treat anxiety, agitation, and seizures. In anticipation of the lorazepam shortage in the summer of 2022, pharmacy staff collaborated with palliative care physicians to identify alternative treatment recommendations when providers were prohibited from ordering lorazepam injection...

OBJECTIVE: To investigate the initial treatment of patients with convulsive status epilepticus (CSE) in a resource-limited region of China, and to discuss the difference of in-hospital outcomes and economic costs between those with guideline-recommended initial treatment and those without. METHODS: In this retrospective study, we screened adult patients discharged with the diagnosis of CSE in four centers in west China. Individuals with different exposure to the initial drug were divided into benzodiazepine (BDZ) and non-BDZ group for outcome comparison...

BACKGROUND: Emergency seizure disorders such as status epilepticus and cluster seizures are unlikely to cease spontaneously while prolonged seizure activity become progressively more resistant to treatment. Early administration of rescue medication in canine epileptic patients, in particular benzodiazepines, at seizure onset by the owners can be life-saving and brain protecting. Clinical studies in dogs evaluating the use of rescue medication in hospital environment exist, however, the owner perspective has not been assessed to date...

Sepsis-associated encephalopathy is a severe neurologic syndrome characterized by a diffuse dysfunction of the brain caused by sepsis. This review provides a concise overview of diagnostic tools and management strategies for SAE at the acute phase and in the long term. Early recognition and diagnosis of SAE are crucial for effective management. Because neurologic evaluation can be confounded by several factors in the intensive care unit setting, a multimodal approach is warranted for diagnosis and management...

BACKGROUND: Non-convulsive status epilepticus (NCSE) is defined as status epilepticus (SE) with no obvious motor phenomenon and is diagnosed based on electroencephalogram (EEG). Refractory SE (RSE) is the persistence of seizures despite treatment with an adequately dosed first-line and second-line agents. Although guidelines for convulsive RSE include third-line agents such as intravenous anesthetic drugs (midazolam, propofol, or barbiturates), the therapeutic approach to NCSE is not well outlined...

BACKGROUND: Pediatric refractory status epilepticus (RSE) often requires management with anesthetic infusions, but few data compare first-line anesthetics. This study aimed to compare the efficacy and adverse effects of midazolam and ketamine infusions as first-line anesthetics for pediatric RSE. METHODS: Retrospective single-center study of consecutive study participants treated with ketamine or midazolam as the first-line anesthetic infusions for RSE at a quaternary care children's hospital from December 1, 2017, until September 15, 2021...

Sex differences are common in human epilepsy. Although men are more susceptible to seizure than women, the mechanisms underlying sex-specific vulnerabilities to seizure are unclear. The organophosphate (OP), diisopropylfluorophosphate (DFP), is known to cause neurotoxicity and status epilepticus (SE), a serious neurologic condition that causes prolonged seizures and brain damage. Current therapies for OP poisoning and SE do not consider neuronal variations between male and female brains. Therefore, we investigated sex-dependent differences in electrographic seizure activity and neuronal injury using the DFP model of refractory SE in rats...

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 NMDA receptor antagonist, has been partially effective in combination with benzodiazepines in mitigating SE-associated neurotoxicity...

Acute exposure to nerve agents induces a peripheral cholinergic crisis and prolonged status epilepticus (SE), causing death or long-term brain damage. To provide preclinical data pertinent to the protection of infants and newborns, we compared the antiseizure and neuroprotective effects of treating soman-induced SE with midazolam (MDZ) versus tezampanel (LY293558) in combination with caramiphen (CRM), in 12- and 7-day-old rats. The anticonvulsants were administered 1 h after soman exposure; neuropathology data were collected up to 6 months post-exposure...

BACKGROUND: Mexiletine, a class IB antiarrhythmic, is a structural analog of lidocaine. Our knowledge of mexiletine overdose is based on lidocaine overdose reports. Only a few cases of mexiletine overdose have been reported, including fatal overdoses. Mexiletine toxicity primarily affects the central nervous, cardiovascular, and gastrointestinal systems. CASE: A 16-year-old female was brought to our hospital by ambulance after taking an unknown dose of mexiletine in a suicide attempt...

Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards...

Organophosphate (OP) compounds are highly toxic and include pesticides and chemical warfare nerve agents (CWNA). OP exposure inhibits the acetylcholinesterase enzyme, causing cholinergic overstimulation that can evolve into status epilepticus (SE) and produce lethality. Furthermore, OP-induced SE survival is associated with mood and memory dysfunction and spontaneous recurrent seizures (SRS). In Male Sprague-Dawley rats, we assessed hippocampal pathology and chronic SRS following SE induced by administration of OP agents POX (2 mg/kg, s...

OBJECTIVE: We investigated the management and outcome of early and established status epilepticus including timing, dosing and selection of benzodiazepines along with the timing and efficacy of second line treatments. METHODS: Retrospective single tertiary centre observational cohort study to identify all cases of SE between January 2019 and February 2022. RESULTS: 252 cases were identified. Seizures terminated spontaneously in 136 (54%) cases...

BACKGROUND: Tuberculosis is an airborne disease caused by Mycobacterium tuberculosis. Intracranial tuberculoma is a rare complication of extrapulmonary tuberculosis due to hematogenous spread to subpial and subependymal regions. Intracranial tuberculoma can occur with or without meningitis. OBSERVATIONS: A 3-year-old male who had recently emigrated from Sudan presented to the emergency department with right-sided seizures lasting 30 minutes, which were aborted with levetiracetam and midazolam...

BACKGROUND AND OBJECTIVES: Prehospital Advanced Life Support (ALS) is important to improve patient outcomes in children with seizures, yet data is limited regarding national prehospital variation in ALS response for these children. We aimed to determine the variation in ALS response and prehospital administration of antiepileptic medication for children with seizures across the United States. METHODS: We analyzed children <19 years with 9-1-1 dispatch codes for seizure in the 2019 National Emergency Medical Services Information System dataset...