Refractory and Super-Refractory Status Epilepticus in Nerve Agent-Poisoned Rats Following Application of Standard Clinical Treatment Guidelines

Nerve agents (NAs) induce a severe cholinergic crisis that can lead to status epilepticus (SE). Current guidelines for treatment of NA-induced SE only include prehospital benzodiazepines, which may not fully resolve this life-threatening condition. This study examined the efficacy of general clinical protocols for treatment of SE in the specific context of NA poisoning in adult male rats. Treatment with both intramuscular and intravenous benzodiazepines was entirely insufficient to control SE. Second line intervention with valproate (VPA) initially terminated SE in 35% of rats, but seizures always returned. Phenobarbital (PHB) was more effective, with SE terminating in 56% of rats and 19% of rats remaining seizure-free for at least 24 h. The majority of rats demonstrated refractory SE (RSE) and required treatment with a continuous third-line anesthetic. Both ketamine (KET) and propofol (PRO) led to high levels of mortality, and nearly all rats on these therapies had breakthrough seizure activity, demonstrating super-refractory SE (SRSE). For the small subset of rats in which SE was fully resolved, significant improvements over controls were observed in recovery metrics, behavioral assays, and brain pathology. Together these data suggest that NA-induced SE is particularly severe, but aggressive treatment in the intensive care setting can lead to positive functional outcomes for casualties.

Prehospital midazolam use and outcomes among patients with out-of-hospital status epilepticus

ObjectiveTo examine the use of benzodiazepines and the association between low benzodiazepine dose, breakthrough seizures, and respiratory support in patients with status epilepticus.MethodsIn this cross-sectional analysis of adult patients with status epilepticus treated by an emergency medical services agency from 2013 to 2018, the primary outcome was treatment with a second benzodiazepine dose, an indicator for breakthrough seizure. The secondary outcome was receiving respiratory support. Midazolam was the only benzodiazepine administered.ResultsAmong 2,494 patients with status epilepticus, mean age was 54.0 years and 1,146 (46%) were female. There were 1,537 patients given midazolam at any dose, yielding an administration rate of 62%. No patients received a dose and route consistent with national guidelines. Rescue therapy with a second midazolam dose was required in 282 (18%) patients. Higher midazolam doses were associated with lower odds of rescue therapy (odds ratio [OR], 0.8; 95% confidence interval [CI], 0.7–0.9) and were not associated with increased respiratory support. If anything, higher doses of midazolam were associated with decreased need for respiratory support after adjustment (OR, 0.9; 95% CI, 0.8–1.0).ConclusionsAn overwhelming majority of patients with status epilepticus did not receive evidence-based benzodiazepine treatment. Higher midazolam doses were associated with reduced use of rescue therapy and there was no evidence of respiratory harm, suggesting that benzodiazepines are withheld without clinical benefit.Classification of evidenceThis study provides Class III evidence that for patients with status epilepticus, higher doses of midazolam led to a reduced use of rescue therapy without an increased need for ventilatory support.

Simultaneous Use of Two Different Tools to Assess Compliance with Antiepileptic Drugs: Experience in A Community-Based Study

Objective Antiepileptic drug (AED) therapy remains the primary form of treatment for epilepsy, noncompliance to which can result in breakthrough seizure, emergency department visits, fractures, head injuries, and increased mortality. Various tools like self-report measures, pill-counts, medication refills, and frequency of seizures can assess compliance with varying extent. Thus, assessment of compliance with AEDs is crucial to be studied. Materials and Methods Compliance was assessed using pill-count and Morisky medication adherence scale (MMAS) during home visits. A pill-count (pills dispensed–pills remaining)/(pills to be consumed between two visits) value of 0.85 to ≤1.15 was recorded as appropriate compliance. Underdose (<0.85) and overdose (>1.15) was labeled as noncompliance. Score of 1 was given to each positive answer in MMAS. Score of ≥1 was labeled as noncompliance.Statistical analysis: Relationship of demographic factors between compliant and noncompliant patients was analyzed using Chi-square test (SPSS version 21.0, IBM). Rest of the data was analyzed with the help of descriptive statistics using Microsoft Excel. p< 0.05 was considered statistically significant. Results Out of 105 patients, 54 patients were noncompliant with both pill-count and MMAS. 10 patients were noncompliant with pill-count only, while 10 were noncompliant with MMAS. Conclusion Both tools complement each other when used in combination, as use of a single tool was not able to completely detect compliance.

Breakthrough seizure associated with kratom use in patients with epilepsy

Purposeof review: Kratom (mitragynine) is a commercially available herbal supplement that is gaining popularity in the United States (U.S.). Kratom is associated with a variety of neurological effects. This review will discuss kratoms association with seizure through three cases and highlight what neurologists should know about kratom's clinical effects and legal status.Recent findings:Kratom is currently commercially available, unscheduled by the U.S. Drug Enforcement Administration (DEA), and a topic of regulatory debate in the US. Large poison center reviews have suggested that kratom use is associated with seizure. There have been limited case studies to corroborate this finding. We present three cases in which seizures were associated with kratom use in patients treated for epilepsy.Summary:Since 2008, kratom use is rising in prevalence in the U.S. aided by lack of regulation. Neurologists need to be aware of its association with seizure and other neurologic side effects.

Yield of Emergent CT in Patients With Epilepsy Presenting With a Seizure

Background: Studies of emergent neuroimaging in the management of patients presenting with a breakthrough seizure are lacking. We sought to determine how often emergent computed tomography (CT) scans are obtained in patients with known epilepsy presenting with a seizure and how often acute abnormalities are found. Methods: This multicenter retrospective cohort study was performed in the emergency department at 2 academic medical centers. The primary outcomes were percentage of visits where a CT scan was obtained, whether CT findings represented acute abnormalities, and whether these findings changed acute management. Results: Of the 396 visits included, CT scans were obtained in 39%, and 8% of these scans demonstrated acute abnormalities. Patients who were older, had status epilepticus, a brain tumor, head trauma, or an abnormal examination were all significantly more likely to undergo acute neuroimaging ( P < .05). In the multivariable model, only history of brain tumor (odds ratio [OR] 5.88, 95% confidence interval [CI], 1.33-26.1) and head trauma as a result of seizure (OR 3.92, 95% CI, 1.01-15.2) reached statistical significance in predicting an acutely abnormal scan. The likelihood of an acute imaging abnormality in visits for patients without a history of brain tumor or head trauma as a result of the seizure was 2.7% (2 visits). Both of these patients had abnormal neurological examinations. Conclusion: Obtaining an emergent CT scan for patients with epilepsy presenting with a seizure may be avoidable in most cases, but might be indicated for patients with a history of brain tumor or head trauma as a result of seizure.