Treatment Of Status Epilepticus Research Articles

Treatment for Subdural Hematoma in Infants

This chapter will discuss the treatment for infant subdural hematoma. In adult cases, treatment focused on intracranial pressure(ICP)management alone is generally sufficient, but in infant cases, special ingenuity is required. First, there are some points to keep in mind regarding surgical procedures. It is important to perform blood transfusion from an early stage, avoid exposure of bleeding points, and reduce ICP by floating the bone flap that preserves blood flow. Next, it is necessary to understand the pathophysiology peculiar to infants. Extensive lower density changes seen on head computed tomography can have a profound effect on clinical outcome. This phenomenon should not be considered as simple cerebral ischemia, but is representative of the brain damage caused by status epilepticus and hyper perfusion injury. Therefore, not only ICP management, but also treatment for status epilepticus is extremely important for postoperative management. Further, cases where abuse is the cause of subdural hematoma often display poor outcomes due to a variety of medico social factors.

Does diabetes mellitus affect the safety profile of valproic acid for the treatment of status epilepticus? A retrospective cohort study

BackgroundIn the treatment of status epilepticus less is known about the influence of comorbidities on the safety profile of anticonvulsive drugs. Especially patients with diabetes mellitus may be predisposed to certain adverse events that have been related to therapy with valproic acid. In this single-center retrospective cohort study we examined if the complications of the intravenous treatment with valproic acid is different in patients with or without diabetes.MethodsPatients who were treated for status epilepticus with intravenous valproic acid between 2008 and 2020 were identified. Primary endpoint was the discontinuation of therapy with valproic acid due to adverse events. Relevant secondary endpoints were the functional status at the time of discharge from hospital in comparison to the premorbid state and the in-hospital mortality. Both groups (patients with or without diabetes) were compared by Mann–Whitney U-Test or Pearson´s Chi2 test. To identify therapy with valproic acid as a risk factor of in-hospital mortality, a binary regression model was used.ResultsDuring the study period 408 patients and 482 episodes of status epilepticus were treated with intravenous valproic acid. Group comparisons did not reveal a significant difference in the rates of discontinuation of therapy. A difference was found in the rate of thrombocytopenia (p = 0.015), which occurred more often in patients with diabetes. In total, 36 hypoglycemic episodes could be identified, two occurred spontaneously under intravenous valproic acid. After correction for potential confounders, continuous therapy with valproic acid could not be confirmed as an independent risk factor for in-hospital mortality (p = 0.079). In patients with diabetes, the proportion of patients with a good functional state, indicated by the modified Rankin Scale, was significantly lower in both times (premorbid: 55% vs. 69%, p = 0.008; at discharge: 22% vs. 36%, p = 0.004).ConclusionsTolerability of the treatment with valproic acid was similar in patients with or without diabetes. Diabetes as a relevant comorbidity can signal a potentially increased risk of a poor outcome after status epilepticus.Trial registration: The study was registered at the German Clinical Trials Register on 8 April 2022 (DRKS 00,027,836).

Ketamine: Is It Pro-Epileptic or Anti-Epileptic? The Debate Continues. A Narrative Review with a Case Discussion

Ketamine is one of the old anaesthetic agents which has regained popularity in analgesia, trauma, emergency medicine, neurology and psychiatry. Recently several cases were reported on ketamine induced seizures in otherwise healthy children despite its popularity in the treatment of refractory status epilepticus. We present an eight-year-old prematurely born healthy boy who developed two episodes of generalized tonic clonic seizures following administration of ketamine for a short ophthalmic procedure. This case and our comprehensive narrative review of literature on pro- and anti-epileptic effects of ketamine show that the debate continues and gaps on mechanism of action, etiology and risk factors for ketamine’s epileptic activity remains. Due to the recent increase in its use further evaluation on ketamine’s epileptic effects is warranted to ensure safe and effective use of ketamine.

An Emergency Department Quality Improvement Project for Intravenous Levetiracetam Administration

Background: Levetiracetam is a readily available, safe anticonvulsive medication. It is frequently administered as IV piggyback with a pump, carrier fluid, and tubing. The Established Status Epilepticus Treatment Trial demonstrated levetiracetam being similarly effective to previously used treatments in doses up to 4500 mg administered over 10 minutes. Objective: We sought to compare usage, cost, and waste of IV piggyback with IV push administration of levetiractam following implementation of an IV push protocol in an academic emergency department. Methods: A three-month review of levetiracetam administration was done following protocol implementation using IV push for initial treatment of benzodiazepine-refractory status epilepticus. The review quantified the number of IV push vs IV piggyback doses for all indications and evaluated cost of supplies necessary for administration. Results: During the study period, 137 patients received 142 doses of IV levetiracetam. Fifty-one doses (36%) were given as IV push rather than IV piggyback. The majority of doses 116 (82%) were 1000-2000 mg and 11 doses (8%) 3500-4500 mg. Estimated three-month savings with complete transition of IV piggyback to IV push would exceed $6000 just in our ED. The amount of sterile solution carrier fluid was also reduced and IV pump time freed. Conclusion: Implementation of an emergency department IV push levetiracetam protocol resulted in cost savings. Opportunities remain to improve clinical implementation practices. Medication administration represents one crucial target area where healthcare systems can implement policies to reduce waste and commit to climate-smart health care.

Challenges for Emergency Medical Services in Status Epilepticus Management

Untimely treatment in status epilepticus (SE) is independently associated with increased treatment resistance, morbidity, and mortality, but time to treatment is usually longer than suggested by guidelines in clinical practice.1 SE most commonly begins outside the hospital, and treatments take longer when seizures start in this setting.2 Therefore, we explored one of the potential barriers for Emergency Medical Services (EMS) to provide optimized pediatric prehospital treatment in the United States: their protocols.

Deep brain stimulation of the anterior nuclei of the thalamus in focal epilepsy

ObjectiveTo review the therapeutic effects of deep brain stimulation of the anterior nuclei of the thalamus (ANT-DBS) and the predictors of its effectiveness, safety, and adverse effects. MethodsA comprehensive search of the medical literature (PubMed) was conducted to identify relevant articles investigating ANT-DBS therapy for epilepsy. Out of 332 references, 77 focused on focal epilepsies were reviewed. ResultsThe DBS effect is probably due to decreased synchronization of epileptic activity in the cortex. The potential mechanisms from cellular to brain network levels are presented. The ANT might participate actively in the network elaborating focal seizures. The effects of ANT-DBS differed in various studies; ANT-DBS was linked with a 41% seizure frequency reduction at 1 year, 69% at 5 years, and 75% at 7 years. The most frequently reported adverse effects, depression and memory impairment, were considered non-serious in the long-term follow-up view. ANT-DBS also has been used in a few cases to treat status epilepticus. ConclusionsWe reviewed the clinical literature and identified several factors that may predict seizure outcome following DBS therapy. More large-scale trials are required since there is a need to explore stimulation settings, apply patient-tailored therapy, and identify the presurgical predictors of patient response. SignificanceA critical review of the published literature on ANT-DBS in focal epilepsy is presented. ANT-DBS mechanisms are not fully understood; possible explanations are provided. Biomarkers of ANT-DBS effectiveness may lead to patient-tailored therapy.

Dual effects of anandamide in the antiepileptic activity of diazepam in pentylenetetrazole-induced seizures in mice.

The prototype endocannabinoid, anandamide activates both CB 1 and transient receptor potential vanilloid type 1 channels (TRPV1) receptor at different concentrations. At high concentrations, anandamide-mediated TRPV1 effects are opposite to its effects at low concentrations via CB 1 receptor. Thus, synaptic concentrations of anandamide govern the neuronal activity and consequently might affect the response of a drug. This study was undertaken to investigate the influence of high and low doses of anandamide on the anticonvulsant action of diazepam on the subcutaneous dose of pentylenetetrazole (PTZ) in Swiss mice weighing 20-25 g. Results revealed that intracerebroventricular administration of capsazepine (a TRPV1 antagonist: 1, 10, or 100 µg/mouse) and the low doses (10 µg/mouse) of anandamide, AM404 (anandamide transport inhibitor), or URB597 (fatty acid amide hydrolase inhibitor) augmented the anticonvulsant effect of diazepam. Conversely, higher dose of anandamide, AM404, URB597 (100 µg/mouse) as well as capsaicin (a TRPV1 agonist: 1, 10, or 100 µg/mouse) attenuated the protective effect of diazepam against PTZ-induced seizures. Thus, this study demonstrates that the effects of diazepam may be augmented by activating CB 1 receptors or dampened via TRPV1 receptors. The findings of the present study can be extrapolated to understand the use of TRPV1 blockers alone or in combination of benzodiazepines in the treatment of benzodiazepines-refractory status epilepticus, a condition associated with maladaptive trafficking of synaptic gamma-aminobutyric acid and glutamate receptors. However, potential clinical applications are needed to further support such preclinical studies.

The Midazolam RAMPART Study Medical Records Project: A Unique Use of Real-World Data in a Complex Collaborative Partnership to Support a New Drug Application

IntroductionThis project aimed to retrospectively obtain, review, and extract key safety data from medical records of participants enrolled in RAMPART, the NIH-supported Rapid Anticonvulsant Medication Prior to ARrival Trial of intramuscular midazolam versus intravenous lorazepam for pre-hospital treatment of status epilepticus, to support a US new drug application (NDA) for intramuscular midazolam.MethodsA collaborative partnership was established between the NDA sponsor, the RAMPART trial lead academic institution, US government agencies, and contract research organizations to retrieve, review, and extract relevant safety data from the medical records of RAMPART participants and summarize those data to include in an NDA submitted to the US Food and Drug Administration (FDA).ResultsKey data in the medical records of 890 RAMPART trial participants (1020 enrollments, including 130 repeat enrollments) were reviewed and extracted into a project database. Safety events occurred in 771 (86.6%) participants, and included additional information not collected in the RAMPART trial. This database also enabled subgroup analyses based on medical history and prior/concurrent medications, building upon previous analyses according to age, sex, and race. No previously unrecognized safety patterns were identified, and no association was observed between efficacy and medical history or medication usage.ConclusionsThe use of unstructured real-world retrospective medical record data can effectively support an NDA submission in place of conducting another interventional clinical trial. This retrospective medical records review and extraction of additional safety data contributed to the FDA approval of intramuscular midazolam for the pre-hospital treatment of status epilepticus in 2018.ClinicalTrials.govNCT00809146.

Benzodiazepines in the Management of Seizures and Status Epilepticus: A Review of Routes of Delivery, Pharmacokinetics, Efficacy, and Tolerability.

Status epilepticus (SE) is an acute, life-threatening medical condition that requires immediate, effective therapy. Therefore, the acute care of prolonged seizures and SE is a constant challenge for healthcare professionals, in both the pre-hospital and the in-hospital settings. Benzodiazepines (BZDs) are the first-line treatment for SE worldwide due to their efficacy, tolerability, and rapid onset of action. Although all BZDs act as allosteric modulators at the inhibitory gamma-aminobutyric acid (GABA)A receptor, the individual agents have different efficacy profiles and pharmacokinetic and pharmacodynamic properties, some of which differ significantly. The conventional BZDs clonazepam, diazepam, lorazepam and midazolam differ mainly in their durations of action and available routes of administration. In addition to the common intravenous, intramuscular and rectal administrations that have long been established in the acute treatment of SE, other administration routes for BZDs—such as intranasal administration—have been developed in recent years, with some preparations already commercially available. Most recently, the intrapulmonary administration of BZDs via an inhaler has been investigated. This narrative review provides an overview of the current knowledge on the efficacy and tolerability of different BZDs, with a focus on different routes of administration and therapeutic specificities for different patient groups, and offers an outlook on potential future drug developments for the treatment of prolonged seizures and SE.Graphical

Evaluation and Treatment of Adult Status Epilepticus in the Emergency Department

Evaluation and Treatment of Adult Status Epilepticus in the Emergency Department

Real-World Midazolam Use and Outcomes With Out-of-Hospital Treatment of Status Epilepticus in the United States

Guidelines recommend 10-mg intramuscular midazolam as the first-line treatment option for status epilepticus. However, in real-world practice, it is frequently administered intranasally or intravenously and is dosed lower. Therefore, we used conventional and instrumental variable approaches to examine the effectiveness of midazolam in a national out-of-hospital cohort. This retrospective cohort study of adults with status epilepticus used the ESO Data Collaborative research dataset (January 1, 2019, to December 31, 2019). The exposures were the route and dose of midazolam. We performed hierarchical logistic regression and 2-stage least squares regression using agency treatment patterns as an instrument to examine our outcomes, rescue therapy, and ventilatory support. There were 7,634 out-of-hospital encounters from 657 EMS agencies. Midazolam was administered intranasally in 20%, intravenously in 46%, and intramuscularly in 35% of the encounters. Compared with intramuscular administration, intranasal midazolam increased (risk difference [RD], 6.5%; 95% confidence interval [CI], 2.4% to 10.5%) and intravenous midazolam decreased (RD,-11.1%; 95% CI,-14.7% to-7.5%) the risk of rescue therapy. The differences in ventilatory support were not statistically significant (intranasal RD,-1.5%; 95% CI,-3.2% to 0.3%; intravenous RD,-0.3%; 95% CI,-1.9% to 1.2%). Higher doses were associated with a lower risk of rescue therapy (RD,-2.6%; 95% CI,-3.3% to-1.9%) and increased ventilatory support (RD, 0.4%; 95% CI, 0.1% to 0.7%). The instrumental variable analysis yielded similar results, except that dose was not associated with ventilatory support. The route and dose of midazolam affect clinical outcomes. Compared with intramuscular administration, intranasal administration may be less effective and intravenous administration more effective in terminating status epilepticus, although the differences between these and previous results may reflect the nature of real-world data as opposed to randomized data.

Management of Refractory Status Epilepticus: An International Cohort Study (MORSE CODe) Analysis of Patients Managed in the ICU.

Status epilepticus that continues after the initial benzodiazepine and a second anticonvulsant medication is known as refractory status epilepticus (RSE). Management is highly variable because adequately powered clinical trials are missing. We aimed to determine whether propofol and midazolam were equally effective in controlling RSE in the intensive care unit, focusing on management in resource-limited settings. Patients with RSE treated with midazolam or propofol between January 2015 and December 2018 were retrospectively identified among 9 centers across 4 continents from upper-middle-income economies in Latin America and high-income economies in North America, Europe, and Asia. Demographics, Status Epilepticus Severity Score, etiology, treatment details, and discharge modified Rankin Scale (mRS) were collected. The primary outcome measure was good functional outcome defined as a mRS score of 0-2 at hospital discharge. Three hundred eighty-seven episodes of RSE (386 patients) were included, with 162 (42%) from upper-middle-income and 225 (58%) from high-income economies. Three hundred six (79%) had acute and 79 (21%) remote etiologies. Initial RSE management included midazolam in 266 (69%) and propofol in 121 episodes (31%). Seventy episodes (26%) that were initially treated with midazolam and 42 (35%) with propofol required the addition of a second anesthetic to treat RSE. Baseline characteristics and outcomes of patients treated with midazolam or propofol were similar. Breakthrough (odds ratio [OR] 1.6, 95% CI 1.3-2.0) and withdrawal seizures (OR 2.0, 95% CI 1.7-2.5) were associated with an increased number of days requiring continuous intravenous anticonvulsant medications (cIV-ACMs). Prolonged EEG monitoring was associated with fewer days of cIV-ACMs (1-24 hours OR 0.5, 95% CI 0.2-0.9, and >24 hours OR 0.7, 95% CI 0.5-1.0; reference EEG <1 hour). This association was seen in both, high-income and upper-middle-income economies, but was particularly prominent in high-income countries. One hundred ten patients (28%) were dead, and 80 (21%) had good functional outcomes at hospital discharge. Outcomes of patients with RSE managed in the intensive care unit with propofol or midazolam infusions are comparable. Prolonged EEG monitoring may allow physicians to decrease the duration of anesthetic infusions safely, but this will depend on the implementation of RSE management protocols. Goal-directed management approaches including EEG targets may hold promise for patients with RSE. This study provides Class III data that propofol and midazolam are equivalently efficacious for RSE.

Efficacy of Levetriacetam and Phenytoin as Combination Therapy in Infants Presented with Status Epilepticus

Levetiracetam may be an effective and safer alternative to phenytoin as a second-line intravenous anticonvulsant for the treatment of juvenile convulsive status epilepticus. Objective of this study was to determine the efficacy of Levitriacetam and Phenytoin as combination therapy in infants presented with status epilepticus. Material and Methods: In this cross observational sectional study (01-02-2020 to 31-07-2020) at department of pediatrics mayo hospital Lahore. study the infants were enrolled of either gender and age less than 1 year that were suffering from a seizure with 5 minutes or more of continuous clinical seizure activity or recurrent seizure activity without recovery between seizures.Then these cases were started with both Phenytoin (Loading: 15 - 20 mg/kg IV *Maintenance: 5 - 8 mg/kg/d) and Levitriacetam (Loading dose5 10 mg/kg IV and Maintenance dose 10 – 30 mg/kg/dose q12 hours ) and were observed daily to look for fits. Efficacy was labelled as yes where there were no fits for 48 hours after the treatment. Results: In this study there were total 120 cases and out of these 74 (61.67%) were males and 46 (38.33%) females. Mean age of the subjects was 4.57±3.97 months. Mean duration of symptoms was 2.23±1.47 days. Out of 120, tonic clonic seizures were noted in 78 (65%) of the cases and 30 (25%) of the cases had family history of epilepsy. Efficacy was noted in 84 (70%) of the cases. Conclusion: Combination of Levetriacetam and Phenytoin is highly efficacious in infants presented with status epilepticus. Keywords; Levetriacetam, Phenytoin, Status epilepticus, Fits, Infantile seizures

Antiseizure and Neuroprotective Efficacy of Midazolam in Comparison with Tezampanel (LY293558) against Soman-Induced Status Epilepticus.

Acute exposure to nerve agents induces status epilepticus (SE), which can cause death or long-term brain damage. Diazepam is approved by the FDA for the treatment of nerve agent-induced SE, and midazolam (MDZ) is currently under consideration to replace diazepam. However, animal studies have raised questions about the neuroprotective efficacy of benzodiazepines. Here, we compared the antiseizure and neuroprotective efficacy of MDZ (5 mg/kg) with that of tezampanel (LY293558; 10 mg/kg), an AMPA/GluK1 receptor antagonist, administered 1 h after injection of the nerve agent, soman (1.2 × LD50), in adult male rats. Both of the anticonvulsants promptly stopped SE, with MDZ having a more rapid effect. However, SE reoccurred to a greater extent in the MDZ-treated group, resulting in a significantly longer total duration of SE within 24 h post-exposure compared with the LY293558-treated group. The neuroprotective efficacy of the two drugs was studied in the basolateral amygdala, 30 days post-exposure. Significant neuronal and inter-neuronal loss, reduced ratio of interneurons to the total number of neurons, and reduction in spontaneous inhibitory postsynaptic currents accompanied by increased anxiety were found in the MDZ-treated group. The rats treated with LY293558 did not differ from the control rats (not exposed to soman) in any of these measurements. Thus, LY293558 has significantly greater efficacy than midazolam in protecting against prolonged seizures and brain damage caused by acute nerve agent exposure.

Treatment of status epilepticus in pediatrics: curriculum learning combined with in-situ simulations

BackgroundAppropriate and timely treatment of status epilepticus (SE) reduces morbidity and mortality. Therefore, skill-based identification and management are critical for emergency physicians.PurposeTo assess whether the ability of training physicians, residents, nurses, and others to respond to SE as a team could be improved by using curriculum learning [Strategies and Tools to Enhance Performance and Patient Safety of Team (TeamSTEPPS) course training] combined with in-situ simulations of emergency department (ED) staff.ApproachA pre-training-post-training design was used on SE skills and teamwork skills. Emergency training, residents, and N1 and N2 nurses completed the SE skill and teamwork assessments (pre-training) through in-situ simulation. Next, the participating physicians and nurses attended the SE course [Strategies and Tools to Enhance Performance and Patient Safety of Team (TeamSTEPPS) course training], followed by conscious skill practice, including in-situ simulation drills every 20 days (eight times total) and deliberate practice in the simulator. The participants completed the SE skill and teamwork assessments (post-training) again in an in-situ simulation. Pre-training-post-training simulated SE skills and teamwork performance were assessed. The simulation training evaluation showed that the training process was reasonable, and the training medical staff had different degrees of benefit in increasing subject interest, improving operational skills, theoretical knowledge, and work self-confidence.FindingsSixty doctors and nurses participated in the intervention. When comparing the SE skills of 10 regular training physicians pre-training and post-training, their performance improved from 40% (interquartile range (IQR): 0–1) before training to 100% (IQR: 80.00–100) after training (p < 0.001). The teamwork ability of the 10 teams improved from 2.43 ± 0.09 before training to 3.16 ± 0.08 after training (p < 0.001).ConclusionSE curriculum learning combined with in-situ simulation training provides the learners with SE identification and management knowledge in children and teamwork skills.

Reponse of second-line treatment in focal status epilepticus: A tertiary hospital experience

ObjectiveTo investigate the response to various antiseizure medications (ASMs) in the treatment of focal status epilepticus (SE) in the established phase, and the effect of administering several ASMs prior to sedation. MethodsAll SE cases in patients aged > 16 years treated with non-BZDs ASMs were prospectively collected in our centre from February 2011 to April 2019. In total, 281 episodes were analysed. ResultsMedian age at SE onset was 65.1 years; 47 % were focal motor and 53 % focal non-motor episodes. SE cessation was achieved in 79 % episodes with second-line drugs, whereas a third line (anesthetics) was required in 47 episodes. SE cessation was achieved in only 27 % with the first ASM, 48 % with the second, and 51 % with the third. Prompt resolution of the SE episode with a first or second ASM was associated with a better outcome than episodes requiring a larger number of drugs (p = 0.024). The first option in our sample was levetiracetam in 70 % of cases. Among the total of non-responding SE cases treated with levetiracetam as the first ASM option, 107 were subsequently given lacosamide (seizure cessation in 53.3 %) and 34 valproic acid (seizure cessation in 29.4 %) (p = 0.015). ConclusionOur findings further support the notion that early termination of SE with a first or second ASM confers a better functional outcome. The large difference in response between the first ASM and consecutive ones suggests that the sum of different ASMs might be the key to resolving focal SE.

Ameliorating effects of cinnamon and curcumin on oxidative stress in lithium-pilocarpine induced status epilepticus model

The lithium-pilocarpine (Li-Pc) model of status epilepticus (SE) is most convenient and is frequently used for pathophysiological and management strategies in search of new, safe and effective therapeutic agents including the natural remedies for SE. Oral administration of cinnamon (CIN) and curcumin (CUR) can reduce neuroinflammation which is a common feature of neurodegenerative pathophysiological disorders. Although many studies on CUR effects on SE has been undertaken, to our best knowledge no study has been conducted on studying the effect of CIN on SE. The present study explores the neuroprotective effects of natural food products CUR and CIN on Li-Pc induced SE in rats. SE was induced in experimental rats using lithium – pilocarpine model. Besides control groups, the animals were also grouped as treatment groups which received CIN and CUR pre-treatment before induction of SE. Besides severity of the seizures, cognitive dysfunctions, oxidative stress parameters were also estimated in the forebrain tissue of all group of animals. Treatment with CIN and CUR significantly ameliorated the frequency and severity of epileptic seizures in a dose-dependent manner. The cognitive dysfunctions as well as the oxidative stress indices (enzymatic as well as non-enzymatic) were ameliorated significantly and dosedependently by CIN and CUR pre-treatment in the order CUR&lt;CIN in all parameters. Possible therapeutic application of CIN and CUR as antiepileptic and as antioxidant for the treatment of SE has a great potential and warrants further studies

Valproate in status epilepticus: Correlation between loading dose, serum levels, and clinical response.

Background and purposeIntravenous valproate (VPA) is an established treatment of status epilepticus (SE), but optimal loading dose was not fully assessed. We aimed at analyzing the correlation between VPA loading dose and subsequent plasma levels with clinical response in SE.MethodsThis was a retrospective study in one referral center of all consecutive VPA‐naïve SE episodes treated with VPA between January 2013 and June 2019, in which total VPA trough plasma levels after intravenous loading dose were available. Response to VPA, defined as last antiseizure medication introduced before SE resolution (without the need for additional treatment), was correlated with VPA loading dose and trough level. Correlations were adjusted for other SE characteristics.ResultsAmong 128 SE episodes, 53 (41%) responded to VPA. Median VPA loading dose was 25.2 mg/kg (range, 7–58 mg/kg). Loading doses and total plasma levels were not associated with the probability of response or mortality. Correcting for other possible confounders (number of previously tried treatment, demographics, SE severity) did not alter these findings. Only 3.8% of SE episodes that responded to VPA received >30 mg/kg.ConclusionsA high loading dose (>30 mg/kg) is not associated with a greater response rate in patients with SE. Therefore, it seems to bring little benefit. If confirmed in further studies, a dosage of 25–30 mg/kg appears adequate in SE.

Treatment of Toxin-Related Status Epilepticus With Levetiracetam, Fosphenytoin, or Valproate in Patients Enrolled in the Established Status Epilepticus Treatment Trial

We describe a subset of patients with toxin-related precipitants of seizures/status epilepticus enrolled in the Established Status Epilepticus Treatment Trial (ESETT). The ESETT was a prospective, double-blinded, adaptive trial evaluating levetiracetam, valproate, and fosphenytoin as second-line agents in benzodiazepine-refractory status epilepticus in adults and children. The primary outcome was the absence of seizures and improvement in the level of consciousness 1 hour after study drug administration. In this post hoc analysis, the safety and efficacy of second-line agents in a subset of patients with toxin-related seizures are described. A total of 249 adults and 229 children were enrolled in the ESETT. Toxin-related seizures occurred in 29 (11.6%) adults and 1 child (0.4%). In adults, men were more likely to have toxin-related seizures than women (25 of 145, 17.2% versus 4 of 104, 3.9%). The most common toxin-related precipitants were alcohol withdrawal and cocaine, 11(37%) of 30 patients each. Cocaine was used with other substances by most patients 10 (91%) of 11, most commonly with an opioid 7 (64%) of 11. For alcohol withdrawal-related seizures, treatment successes with levetiracetam, valproate, and fosphenytoin were 3 (100%) of 3, 3 (50%) of 6, and 1 (50%) of 2, respectively. For cocaine-related seizures, treatment success was 1 (14%) of 7 for levetiracetam, 0 (0%) of 1 for valproate, and 1 (33%) of 3 for fosphenytoin. One patient who used cocaine and an opioid received fosphenytoin and developed life-threatening hypotension. In the ESETT, approximately 1 in 10 adult patients with status epilepticus presented with a toxin-related seizure. Alcohol withdrawal and cocaine/opioid use were the most common toxin-related precipitants. Toxin-related benzodiazepine-refractory status epilepticus was successfully treated with a single dose of second-line antiseizure medication in 42% of the patients.

Diazepam diminishes temozolomide efficacy in the treatment of U87 glioblastoma cell line.

AimsMany patients with glioblastoma (GBM) suffer from comorbid neurological/psychiatric disorders and, therefore, are treated with psychopharmacological agents. Diazepam (DIA) is widely adopted to treat status epilepticus, alleviate anxiety, and inhibit chemotherapy‐associated delayed emesis in GBM patients. Even though temozolomide (TMZ) and DIA could be found as possible combination therapy in clinical practice, there are no reports of their combined effects in GBM. Hence, it may be of interest to investigate whether DIA enhances the antitumor efficacy of TMZ in GBM cells.MethodsU87 human GBM was used to examine the effects of combined TMZ and DIA on cell viability, and the oxygen consumption within the cells, in order to evaluate mitochondrial bioenergetic response upon the treatment.ResultsThe cooperative index showed the presence of antagonism between TMZ and DIA, which was confirmed on long‐term observation. Moreover, the level of apoptosis after the TMZ treatment was significantly decreased when administered with DIA (p < 0.001). Concomitant use of TMZ and DIA increased the basal cell respiration rate, the oxidative phosphorylation rate, and maximal capacity of mitochondrial electron transport chain, as well as the activities of complexes I and II, vs. TMZ alone (p < 0.001).ConclusionComparing our results with data reported that DIA elicits cell cycle arrest in the G0/G1 phase and favors senescence reveals that DIA diminishes TMZ efficacy in concomitant use in the treatment of GBM. However, due to its great potency to hinder GBM proliferation and metabolism, it could be considered using DIA as maintenance therapy after TMZ cycles.