Acute Convulsive Seizures Research Articles

Effect of “Egyptian Acute Seizure Management Guidelines” Education on Emergency Room Pediatricians

Abstract Background Acute convulsive seizure in children is the most terrifying experience to parents. Status epilepticus can be life threatening in children if not early and properly managed. There are no unified management guidelines for childhood acute seizure management in Egypt. The Egyptian acute seizure management in children's guidelines provides a framework for diagnosing and caring for children experiencing an acute convulsion, which is intended to assist health care providers Aim of the Work To assess pediatricians’ knowledge about acute seizure management in emergency department, and to evaluate the effect of education on their knowledge. Methods The current study is an interventional study, on physicians treating children with acute seizures in emergency departments, from August 2022 to May 2023, an online survey was prepared by the authors according to the “Egyptian acute seizure management in children’s guidelines”, then 3 electronic forms were designed online using Research Data Capture Software (REDCap). In the first form (pre-intervention phase) The public link is one link sent through whatsApp groups for pediatricians or general practitioner; containing their personal data and questions assessing their knowledge about acute seizure management in children, two hundred and twenty three pediatrician responded to it. The second form (intervention phase) educational materials (a PDF file contains the guidelines and educational video) sent automatically after the participant finished and submitted the pretest. One week later (post intervention phase) unique link was sent for each participant to his e-mail. Each participant initial (pre-test) and final (post-test) answers were analyzed for the level of knowledge and stratified into Poor ≤50%, 50-75% Fair and ≥ 75% good according to his/her correct answers. Results In the pre-intervention phase, the majority of the participants (66.8%) had poor knowledge about pediatric acute seizure management. Females were found to have lower knowledge levels than males. In the post-intervention phase of the study, the majority of participants (70%) who completed the post-intervention phase had good knowledge level (75%) and the rest (25%) had fair knowledge level. Conclusion We concluded that education to enhance healthcare providers' knowledge about acute pediatric seizure management is mandatory. The study's findings imply that focused education can significantly raise knowledge levels aiming at raising the standard of care given to children with acute seizures in the ER.

Benzodiazepines for the Treatment of Seizure Clusters.

Patients with epilepsy may experience seizure clusters, which are described by the US Food and Drug Administration (FDA) as intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient's usual seizure pattern. Untreated seizure clusters may increase the risk for status epilepticus, as well as decrease quality of life and increase burden on patients and care partners. Benzodiazepine therapies are the mainstay for acute treatment of seizure clusters and are often administered by nonmedical care partners outside a healthcare facility. Three rescue therapies are currently FDA-approved for this indication, with diazepam rectal gel being the first in 1997, for patients aged ≥ 2 years. Limitations of rectal administration (e.g., positioning and disrobing the patient, which may affect ease of use and social acceptability; interpatient variation in bioavailability) led to the investigation of the potential for nasal administration as an alternative. Midazolam nasal spray (MDS) was approved by the FDA in 2019 for patients aged ≥ 12 years and diazepam nasal spray (DNS) in 2020 for patients aged ≥ 6 years; these two intranasal therapies have differences in their formulations [e.g., organic solvents (MDS) vs. Intravail and vitamin E for absorption and solubility (DNS)], effectiveness (e.g., proportion of seizure clusters requiring only one dose), and safety profiles. In clinical studies, the proportion of seizure clusters for which only one dose of medication was used varied between the three approved rescue therapies with the highest single-dose rate for any time period for DNS; however, although studies for all three preparations enrolled patients with highly intractable epilepsy, inclusion and exclusion criteria varied, so the three cannot be directly compared. Treatments that have been used off-label for seizure clusters in the USA include midazolam for injection as an intranasal spray (indicated for sedation/anxiolysis/amnesia and anesthesia) and tablet forms of clonazepam (indicated for treatment for seizure disorders) and lorazepam (indicated for anxiety). In the European Union, buccal and intranasal midazolam are used for treating the indication of prolonged, acute convulsive seizures and rectal diazepam solution for the indication of epileptic and febrile convulsions; duration of effectiveness for these medications for the treatment of seizure clusters has not been established. This paper examines the literature context for understanding seizure clusters and their treatment and provides effectiveness, safety, and administration details for the three FDA-approved rescue therapies. Additionally, other medications that are used for rescue therapy in the USA and globally are discussed. Finally, the potential benefits of seizure action plans and candidates for their use are addressed. This paper is intended to provide details about the unique characteristics of rescue therapies for seizure clusters to help clarify appropriate treatment for individual patients.

The Clinical Efficacy and Safety of Acute Care Setting for Intravenous Levetiracetam (Focale) in Children

Abstract Background Status epilepticus (SE) is a serious neurological emergency with a high mortality rate. Although levetiracetam is an effective antiepileptic drug for managing SE, its excessive cost may limit its accessibility. Focale, a more affordable generic version, is currently available and is more than 50% less expensive than the original version. However, there is currently no study on the efficacy and safety of Focale in pediatric patients with SE. Objective This study aimed to investigate the efficacy and safety of the antiepileptic drug, Focale, in pediatric patients. Materials and Methods This was a retrospective study that examined 131 pediatric patients younger than 18 years, who were treated with Focale for seizure control and prevention between June 2019 and November 2022. Results A total of 131 patients were included in the study, of which 73 (55.7%) were male. The age group with the highest frequency was 0 to 3 years old (28.2%). Focale was used with the following indications: (1) SE (45.04%), (2) acute repetitive convulsive seizures (22.14%), (3) primary prophylaxis (26.72%), (4) acute first seizure (1.52%), and (5) patients with epilepsy with nothing per oral (4.58%). Regarding the outcomes, the seizure-controlled rate in the seizure group was 81.1%, while the seizure prevention rate was 92.7% for those who received Focale as a seizure prophylaxis. Only 2 out of 131 patients had experienced adverse effects (1.5%). Conclusion The generic intravenous levetiracetam treatment had high seizure-controlled rate in patients with seizure attacks and seizure prevention rate in the seizure prophylaxis group in pediatric patients. Side effects of this regimen in pediatric patients were low.

Bioavailability and Safety of a New Highly Concentrated Midazolam Nasal Spray Compared to Buccal and Intravenous Midazolam Treatment in Chinese Healthy Volunteers.

IntroductionBuccal midazolam treatment is licensed in the European Union for prolonged acute convulsive seizures in children and adolescents, but the buccal pathway is often hampered by jaw clenching, hypersalivation, or uncontrolled swallowing. Midazolam formulations that are more secure, reliable, and faster for use are needed in the acute setting. Pharmacokinetics and comparative bioavailability of intranasally administered midazolam and two midazolam intravenous solutions administered buccally or intravenously in healthy adults were evaluated.MethodsIn this phase 1, open-label, randomized, single-dose, three-period, three-sequence crossover study, 12 healthy adults (19–41 years) were randomly assigned to receive 2.5 mg midazolam intranasally; 2.5 mg midazolam intravenously; 2.5 mg midazolam buccally. Blood samples were collected for 10 h post dose to determine pharmacokinetic profiles. Adverse events and vital signs were recorded.ResultsIntranasal administration of 2.5 mg midazolam demonstrated a more rapid median time to Cmax compared to buccal administration of midazolam (Tmax, 12.6 min vs. 45 min; Cmax, 38.33 ng/ml vs. 24.97 ng/ml). The antiepileptic effect of intranasal and buccal midazolam treatment lasted less than 4 h and generally did not differ from intravenously administered midazolam. No serious adverse events or deaths were reported, and no treatment-emergent adverse events led to study discontinuation.ConclusionIntranasal administration of midazolam may be a preferable alternative to the currently approve buccal midazolam treatment for prolonged acute convulsive seizures in children and adolescents.Trial RegistrationThis study is registered at the Chinese Clinical Trial [http://www.chictr.org.cn] (ChiCTR2000032595) on 3 May, 2020.

高齢者のけいれん発作に合併した非外傷性寛骨臼骨折の1例(Nontraumatic acetabular fracture associated with convulsive seizure in an older patient: a case report)

要旨 新規発症けいれん発作の約50%が高齢者であり，救急医療において診療する機会が増加すると考えられる症候である。寛骨臼骨折は高エネルギー外傷により起こることが多く，けいれん発作に伴い生じることはあまり知られていない。今回，80歳代の男性がけいれん発作を契機に二次的外傷を伴うことなく寛骨臼骨折を合併した。CTでは，骨折とともに造影剤血管外漏出所見を認め，経カテーテル動脈塞栓術による止血を行った。けいれんに伴う骨折は，発作後の意識障害により診断が遅れ，活動性出血を伴う症例では致命的となりうる。けいれん発作は非外傷性骨折の原因となり，寛骨臼骨折は見逃してはならない合併症であるとともに，止血介入を要する可能性があるとの認識を要するものと思われる。

The Efficacy and Safety Profile of Generic Intravenous Levetiracetam in a Real-World Setting

BackgroundThere are 3 main epileptic conditions in hospital settings that may require intravenous antiepileptic treatment: status epilepticus, acute repetitive convulsive seizures, and postoperative seizures. Generic intravenous levetiracetam (IV LEV) (Focale; Great Eastern Drug Co, Bangkok, Thailand), has been reported to have comparable efficacy to original IV LEV for treating status epilepticus and acute repetitive convulsive seizures in a randomized controlled trial. At present, there are limited data on the efficacy and tolerability of generic intravenous LEV in real-world situations.ObjectiveThis study aimed to evaluate the clinical outcomes of generic IV LEV in a real-world setting.MethodsA retrospective study and analyses were conducted. All adult patients who used IV LEV at University Hospital, Khon Kaen University, Thailand from June 1, 2019, until February 15, 2020, were included. Data were analyzed and reported in terms of the efficacy and tolerability of generic IV LEV.ResultsNinety-three patients received IV LEV by 3 indications: status epilepticus, acute repetitive convulsive seizures, and postoperative seizures. The proportions of these 3 indications were 41.94% (39 patients), 9.67% (9 patients), and 48.39% (45 patients), respectively. The average seizure control rate at 24 hours was 89.25%. The seizure control rate was significantly higher in the acute repetitive convulsive seizures and postoperative seizure groups than in the status epilepticus group when generic IV LEV was given as the first-line treatment (75.00%; 88.37% vs 50.00%; P 0.035). The average length of hospital stay was 18.24 (25.40) days. There was no significant discharge status among the 3 groups (P = 0.348). Moreover, the average mortality rate was 5.38%. Side effects were reported in 14 patients (15.05%). The 2 most common side effects were vomiting and bronchospasm (3 patients; 3.22%). There were 10 patients with uncontrolled seizures at 24 hours (10.75%). The only factor associated with uncontrolled seizures at 24 hours was a history of epilepsy. The uncontrolled seizure group had a higher proportion of epilepsy patients than the seizure-controlled group (70.00% vs 33.73%; P = 0.037). Poor discharge status (not improved/death) was 18.28% (17 patients). There was no significant factor between those with an improved or poor discharge status.ConclusionsGeneric IV LEV was effective and relatively well tolerated in the 3 clinical settings (ie, status epilepticus, acute repetitive convulsive seizures, and postoperative seizures). Further clinical data are still required to confirm the results of this study.(Curr Ther Res Clin Exp. 2022; 83:XXX–XXX)

Rapid Response System for In-Hospital Large Vessel Occlusion: A Case-Control Study.

Acute ischemic stroke due to large vessel occlusion (LVO) in hospitalized patients is relatively rare but important condition. However, unlike community-onset cases, there are only few time-saving protocols for in-hospital LVO. This study aimed to evaluate the time-saving effects of rapid response system (RRS) for the management of in-hospital LVO. We retrospectively evaluated consecutive in-hospital LVO patients who underwent mechanical thrombectomy (MT) between April 2015 and January 2020. In November 2017, we added "acute hemiparesis, eye deviation, and convulsive seizures" to the activation criteria for RRS. In this protocol, the patient is immediately transported from the ward to the emergency room (ER) by Medical Emergency Team (MET). The stroke team can then start assessment in the same manner as for community-onset cases. The time metrics between those with and without RRS intervention were compared. The primary outcome was time from detection to the first assessment by stroke team and to initial CT. To investigate the validity of the revised criteria, we also analyzed all RRS-activated cases. In total, 26 patients (RRS group, 11 patients; non-RRS group, 15 patients) were included. The median time from detection to stroke team assessment (10.0 [interquartile range: IQR, 8-15] minutes vs 65.5 [18-89] minutes) and to CT (22.0 [16-31] minutes vs. 46.5 [35-93] minutes) were significantly shorter in the RRS group. RRS was activated in 34 patients (mean, 1.3/month) according to the added criteria, of whom 20 (58.8%) had cerebral infarction and 9 underwent MT. About two-thirds of the other patients developed neurological emergencies (e.g., epileptic seizure, syncope, or hypoglycemia) that required acute care. RRS has the potential to shorten response time efficiently in the management of in-hospital LVO. Prompt transportation of the patient to the ER by MET enables faster intervention by the stroke team.

Noninvasive transcranial focal stimulation affects the convulsive seizure-induced P-glycoprotein expression and function in rats

Transcranial focal stimulation (TFS) is a noninvasive neuromodulation strategy that reduces seizure activity in different experimental models. Nevertheless, there is no information about the effects of TFS in the drug-resistant phenotype associated with P-glycoprotein (Pgp) overexpression. The present study focused on determining the effects of TFS on Pgp expression after an acute seizure induced by 3-mercaptopropionic acid (MPA). P-glycoprotein expression was analyzed by western blot in the cerebral cortex and hippocampus of rats receiving 5 min of TFS (300 Hz, 50 mA, 200 μs, biphasic charge-balanced squared pulses) using a tripolar concentric ring electrode (TCRE) prior to administration of a single dose of MPA. An acute administration of MPA induced Pgp overexpression in cortex (68 ± 13.4%, p < 0.05 vs the control group) and hippocampus (48.5 ± 14%, p < 0.05, vs the control group). This effect was avoided when TFS was applied prior to MPA. We also investigated if TFS augments the effects of phenytoin in an experimental model of drug-resistant seizures induced by repetitive MPA administration. Animals with MPA-induced drug-resistant seizures received TFS alone or associated with phenytoin (75 mg/kg, i.p.). TFS alone did not modify the expression of the drug-resistant seizures. However, TFS combined with phenytoin reduced seizure intensity, an effect associated with a lower prevalence of major seizures (50%, p = 0.03 vs phenytoin alone). Our experiments demonstrated that TFS avoids the Pgp overexpression induced after an acute convulsive seizure. In addition, TFS augments the phenytoin effects in an experimental model of drug-resistant seizures. According with these results, it is indicated that TFS may represent a new neuromodulatory strategy to revert the drug-resistant phenotype.

Lorazepam timing for acute convulsive seizure control (LoTASC)

IntroductionGuidelines specify early administration of benzodiazepines (BZD) for the management of convulsive status epilepticus. The distinction between acute convulsive seizure and status epilepticus can be misconstrued resulting in BZD administration prior to a patient meeting criteria of status epilepticus. Early BZD administration may theoretically lead to systemic vital instability. Our study aims to assess if administering lorazepam, for convulsive seizures <5 min, causes vital instability. MethodsThis is a retrospective study analyzing patients who presented with a seizure lasting <5 min between 2011 and 2016. Continuous variables of lorazepam receivers versus non- receivers were analyzed using t-test for parametric and Mann-Whitney U test for nonparametric data. Categorical variables were analyzed using Chi-Square Test. Subsequently, subjects were analyzed through univariate and multivariate regression models to determine predictors of vital instability. ResultsOut of 1052 subjects initially screened, 165 were included. Of these, 91 (55 %) received lorazepam, and 74 (45 %) did not. Through univariate and multivariate analyses, there was a significantly higher incidence of vital instability (defined as receipt of a vasopressor or intubation) in patients who received lorazepam (OR = 6.76, 95 % CI = 1.48, 30.95) (p = 0.014). This was dose-dependent (p < 0.0001). It was responsible for 22.5 % of the vital instability. Lorazepam administration significantly prolonged the intensive care unit (ICU) length of stay (0 days [IQR 0 – 0] vs [IQR 0–2.3]; p = 0.038). ConclusionOur study suggests that lorazepam administration for acute convulsive seizures not meeting convulsive status epilepticus criteria may lead to iatrogenic vital instability and need for ICU admission.

Refractory and Super-refractory Status Epilepticus

ContextRefractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) are neurological emergencies with considerable mortality and morbidity. In this paper, we provide an overview of causes, evaluation, treatment, and consequences of RSE and SRSE, reflecting the lack of high-quality evidence to inform therapeutic approach.SourcesThis is a narrative review based on personal practice and experience. Nevertheless, we searched MEDLINE (using PubMed and OvidSP vendors) and Cochrane central register of controlled trials, using appropriate keywords to incorporate recent evidence.ResultsRefractory status epilepticus is commonly defined as an acute convulsive seizure that fails to respond to two or more anti-seizure medications including at least one nonbenzodiazepine drug. Super-refractory status epilepticus is a status epilepticus that continues for ≥24 hours despite anesthetic treatment, or recurs on an attempted wean of the anesthetic regimen. Both can occur in patients known to have epilepsy or de novo, with increasing recognition of autoimmune and genetic causes. Electroencephalography monitoring is essential to monitor treatment response in refractory/super-refractory status epilepticus, and to diagnose non-convulsive status epilepticus. The mainstay of treatment for these disorders includes anesthetic infusions, primarily midazolam, ketamine, and pentobarbital. Dietary, immunological, and surgical treatments are viable in selected patients. Management is challenging due to multiple acute complications and long-term adverse consequences.ConclusionsWe have provided a synopsis of best practices for diagnosis and management of refractory/superrefractory status epilepticus and highlighted the lack of sufficient high-quality evidence to drive decision making, ending with a brief foray into avenues for future research.

Comparison of Efficacy between Original and Generic Intravenous Levetiracetam for Acute Repetitive Convulsive Seizure or Status Epilepticus

Comparison of Efficacy between Original and Generic Intravenous Levetiracetam for Acute Repetitive Convulsive Seizure or Status Epilepticus

Health-related quality of life and the burden of prolonged seizures in noninstitutionalized children with epilepsy

ObjectiveThis study aimed to provide information on the burden of illness and health-related quality of life (HRQoL) in children with epilepsy who experience prolonged acute convulsive seizures (PACS) in the community setting, and to investigate factors that may predict poor HRQoL in this population. MethodsNoninstitutionalized children (aged 3–16 years) who had experienced at least one PACS within the past year and had currently prescribed PACS rescue medication were enrolled in a cross-sectional study in Germany, Italy, Spain, and the United Kingdom (Practices in Emergency and Rescue medication For Epilepsy managed with Community-administered Therapy 3 [PERFECT-3]). Clinicians, parents/guardians, and patients completed web-based questionnaires regarding clinical characteristics, PACS frequency, and day-to-day impairment. Patients' HRQoL was rated by clinicians, parents/guardians, and patients themselves using the 5-dimension EuroQol questionnaire (EQ-5D) and summarized as a utility score. Potential predictors of poor HRQoL were tested in individual univariate generalized linear models and a global multivariable model. ResultsEnrolled children (N = 286) had experienced 1–400 PACS (median: 4) in the past year. Clinicians reported that 216/281 patients (76.9%) had learning disabilities of varying severity. Mean EQ-5D utility scores rated by clinicians (n = 279), parents (n = 277), and patients (n = 85) were 0.52 (standard deviation: 0.41), 0.51 (0.39), and 0.74 (0.29), respectively. Increasing PACS frequency, increasing severity of learning disability, and specialist school attendance were significantly associated with decreasing EQ-5D utility score. In the multivariable model, having learning disabilities was the best predictor of poor HRQoL. SignificanceHealth-related quality of life was very poor in many children with epilepsy whose PACS were managed with rescue medication in the community, with learning disability being the most powerful predictor of patients' HRQoL. Mean EQ-5D utility scores were lower (worse) than published values for many other chronic disorders, indicating that optimal treatment should involve helping children and their families to manage learning disabilities and day-to-day impairments, in addition to preventing seizures.

Can Generic Intravenous Levetiracetam Be Used for Acute Repetitive Convulsive Seizure or Status Epilepticus? A Randomized Controlled Trial.

IntroductionIntravenous levetiracetam (IV LEV) is approved for treatment status epilepticus (SE). However, the drug’s high cost must be considered when deciding on a treatment strategy. This study aimed to compare the efficacy of brand-name and generic IV LEV for acute repetitive convulsive seizure (ARCS) or SE.MethodsForty patients aged 18 years or older who had been diagnosed with SE or ARCS were included in this double-blind study. Patients were randomly assigned at a 1:1 ratio (via computer-generated code) to receive either brand-name or generic IV LEV. The primary outcomes were seizure control and the number of seizure exacerbations during the 24 h after drug administration, while the secondary outcomes were electroencephalographic (EEG) findings, serious adverse events, and clinical outcome at hospital discharge.ResultsForty patients were randomly assigned administration with either brand-name IV LEV (10 SE and 10 ARCS patients) or generic IV LEV; 7 SE and 13 ARCS patients). There was no significant difference in patients’ baseline characteristics. The seizure control rate was 75% in the brand-name IV LEV group and 65% in the generic IV LEV group (p value: 0.490). Five (25%) patients in the brand-name IV LEV group, and six (30%) patients in the generic IV LEV group developed seizure exacerbations within 24 h after drug administration (p value 0.723). There were no reports of drug-related adverse events. Two of the patients taking brand-name IV LEV and one taking the generic IV LEV died (p value > 0.999).ConclusionTreatment with the generic IV LEV had comparable outcomes with brand-name IV LEV. The generic IV LEV may be an alternative medication for the treatment of SE and ARCS to reduce treatment costs.Trial RegistrationTCTR20190513001.FundingGreat Eastern Drug Company.

Buccal Midazolam Solution for the Management of Prolonged Acute Convulsive Seizures: A Cost Analysis.

BackgroundThere is little published evidence on how pack size impacts on health system costs. In the UK, children and adolescents aged 10 to < 18 years with prolonged acute convulsive seizures (PACS) occurring in the community setting are usually managed by the administration of buccal midazolam: Epistatus® or Buccolam®. These two preparations have markedly differing cost structures, being sold at different prices and presented as single units versus 4-packs, respectively. Consequently, the cost-per-PACS and overall budget impact of the two products cannot be simply inferred but is instead dependent on the likelihood of use. Also relevant to its likelihood of use is midazolam’s status as a controlled substance under the Misuse of Drugs Act.Objective and MethodsThe purpose of this economic analysis was to present the cost implications of single-unit versus multi-pack prescribing of a rescue medication based on likelihood of use. There is little published evidence to inform the likelihood of a midazolam dose being used once prescribed. A Delphi survey was conducted with physicians (n = 5), nurses (n = 11) and pharmacists (n = 24) from the community and hospital healthcare settings in the UK to explore the frequency distribution of prolonged seizures in the general epileptic population per 6-month period, along with common patterns of prescribing. This informed a model of the budgetary impact of single-unit (Epistatus®) versus 4-pack (Buccolam®) prescribing.ResultsRespondents cited both ‘wastage’ and ‘dispensing more than is likely to be used of a controlled drug’ as poor clinical practice, which suggests that prescribing in multiples of four should be reserved for patients who are likely to experience PACS at a higher frequency. The Delphi survey and subsequent regression analysis found that PACS frequency distribution follows an exponential drop, with over half (55%) of patients experiencing zero to one prolonged seizure(s) per 6-month period. Despite this, the majority (70%) of low PACS frequency patients are prescribed buccal midazolam in multiples of four by their treating physician. When looking at overall budgetary impact, the strategy of prescribing single-unit Epistatus® versus 4-pack Buccolam® is cost saving in low PACS frequency patients who do not require multiple units (referred to as spare loading), at − £15.33 per patient per 6 months. If spare loading is universally applied to all patients irrespective of seizure frequency, the mean incremental cost of single unit Epistatus® instead of 4-pack Buccolam® equates to £51.23 per patient per 6 months. If spare loading is reserved for higher PACS frequency patients (two or more per 6 months), the universal prescribing of single-unit Epistatus® versus 4-pack Buccolam® would result in a mean incremental cost of £17.82 per patient per 6 months.ConclusionsThe availability of single-unit Epistatus® allows for greater flexibility in prescribing. Physicians should attempt to categorise patients according to past PACS frequency with low PACS patients being prescribed single unit Epistatus® (with/without spare loading) and 4-pack Buccolam® reserved for patients in whom a high volume of usage is anticipated.Electronic supplementary materialThe online version of this article (10.1007/s41669-019-0164-x) contains supplementary material, which is available to authorized users.

Acute Convulsive Seizures: When is It Too Early to Treat?

Acute convulsive seizures are overwhelming events that require immediate attention from clinicians and practitioners, especially when witnessed in a hospital setting. Adequate management of inpatient-witnessed seizures lies in understanding the time-related pathophysiologic stages of the seizure. The anatomical location of the seizure origin is as important as seizure stage but might not be easy to determine in the acute setting, especially if the seizure is nonfocal. Although investigating and treating the cause of a seizure has high priority, understanding the interplay between the pathophysiologic responses and the various bodily responses are crucial in treatment. This interplay has interesting dynamics that change within minutes. Knowing such dynamics allows clinicians and practitioners to choose their best treatment options in the best time interval when a seizure occurs in an acute care facility. Our commentary provides an overview of such dynamics and how they can change the misconceptions that many clinicians and practitioners have in dealing with an acute convulsive seizure.

Effect of rescue medication on seizure duration in non-institutionalized children with epilepsy.

Characterize the real-world management of and outcomes for children with epilepsy receiving rescue medication for prolonged acute convulsive seizures (PACS) in the community. PERFECT-3 (Practices in Emergency and Rescue medication For Epilepsy managed with Community-administered Therapy 3) was a European, retrospective observational study. Eligible patients were non-institutionalized children with epilepsy aged 3-16 years who had experienced ≥1 PACS in the past year and had ≥1 currently prescribed PACS rescue medication. Investigators provided clinical assessments and parents/guardians completed questionnaires. Statistical tests were post hoc; p values are descriptive. At enrollment (N=286), most patients had prescriptions for diazepam (69.2%) and/or midazolam (55.9%); some had two (26.6%) or three (2.4%) prescribed rescue medications. Most patients experienced PACS despite regular anti-epilepsy medication. According to parents, the average duration of their child's seizures without rescue medication was <5min in 35.7% of patients, 5-<20min in 42.6%, and ≥20min in 21.7% (n=258); withrescue medication seizure duration was <5min in 69.4% of patients, 5-<20min in 25.6%, and ≥20min in 5.0%. Rescue medication use was significantly associated with average seizures lasting <5min (χ2=58.8; p<0.0001). At the time of their most recent PACS, 58.5-67.8% of children reportedly received rescue medication within 5min of seizure onset, and 85.4-94.1% within 10min. This study provides the first real-world data that rescue medications administered in the community reduce the duration of PACS in children with epilepsy. Study limitations including potential recall bias are acknowledged.

Oromucosal midazolam in patients with prolonged acute convulsive seizures: An Italian experience

Objective: In pediatric age, convulsive seizures lasting more than 5 minutes represent a life- threatening condition. Oromucosal midazolam is a promising first-line treatment option, which is approved in the EU for the treatment of prolonged, acute, convulsive seizures (PACS), in patients aged between 6 months and 18 years. The aim of this study is to evaluate the effectiveness of oromucosal midazolam and, to compare with rectal diazepam efficacy. Methods: We included all consecutive patients followed-up at Bambino Gesù Children's Hospital in Rome who received oromucosal midazolam treatment between January 2015 and July 2016. A telephone survey was carried out to evaluate effectiveness, tolerability and convenience of the administration route of oromucosal midazolam in terminating PACS. Moreover, when rectal diazepam was previously used, has been asked a comparative effectiveness between the two benzodiazepines. Results: We enrolled 293 patients (149 males), aged between 6 months and 18 years (9±4,61 years old; median: 9 years) at the time of prescription, with a 16-month follow-up in average (16±5,24 months). Most of them (98/203, 48%) had a symptomatic epilepsy and 90% (268/273) received oromucosal midazolam care plan for the first time. We will present the results of the telephone survey. Conclusion: In the previous reported clinical trials, oromucosal midazolam was at least as effective as rectal diazepam in the treatment of PACS in children and was generally well tolerated. The results of this survey showed that oromucosal midazolam has several advantages if compared with rectal diazepam, the previous gold standard of treatment, such as having a more convenient and socially acceptable administration route.

Spotlight on the November 24 Issue

#### Notable in Neurology This issue features an article quantifying the effects of cognitive training on behavioral outcome measures in patients with Parkinson disease and another considering the use of nonvenous drugs as first-line treatment for controlling acute convulsive seizures and status epilepticus. Another article focuses on the ability of bedside information to risk stratify stroke in acute dizziness presentations. ### Increased CSF biomarkers of angiogenesis in Parkinson disease![Graphic][1]</img> The authors analyzed angiogenesis biomarkers in Parkinson disease (PD) and their association with clinical characteristics, blood-brain barrier permeability, and cerebrovascular … [1]: /embed/inline-graphic-1.gif

Efficacy of nonvenous medications for acute convulsive seizures: A network meta-analysis.

This is a network meta-analysis of nonvenous drugs used in randomized controlled trials (RCTs) for treatment of acute convulsive seizures and convulsive status epilepticus. Literature was searched according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for RCTs examining treatment of acute convulsive seizures or status epilepticus with at least one of the study arms being a nonvenous medication. After demographic and outcome data extraction, a Bayesian network meta-analysis was performed and efficacy results were summarized using treatment effects and their credible intervals (CrI). We also calculated the probability of each route-drug combination being the most clinically effective for a given outcome, and provided their Bayesian hierarchical ranking. This meta-analysis of 16 studies found that intramuscular midazolam (IM-MDZ) is superior to other nonvenous medications regarding time to seizure termination after administration (2.145 minutes, 95% CrI 1.308-3.489), time to seizure cessation after arrival in the hospital (3.841 minutes, 95% CrI 2.697-5.416), and time to initiate treatment (0.779 minutes, 95% CrI 0.495-1.221). Additionally, intranasal midazolam (IN-MDZ) was adjudged most efficacious for seizure cessation within 10 minutes of administration (90.4% of participants, 95% CrI 79.4%-96.9%), and persistent seizure cessation for ≥1 hour (78.5% of participants, 95% CrI 59.5%-92.1%). Paucity of RCTs produced evidence gaps resulting in small networks, routes/drugs included in some networks but not others, and some trials not being connected to any network. Despite the evidence gaps, IM-MDZ and IN-MDZ exhibit the best efficacy data for the nonvenous treatment of acute convulsive seizures or status epilepticus.

Parent and caregiver knowledge, beliefs, and responses to convulsive seizures in children in Kingston, Jamaica - A hospital-based survey.

The objective of this study was to determine the knowledge and beliefs about seizures and actions during seizures of parents/caregivers of Jamaican children hospitalized for convulsive seizures. This was a cross-sectional study of parents and caregivers of children with acute convulsive seizures hospitalized at the Bustamante Hospital, Kingston, Jamaica between May 1 and October 31, 2013. Subjects were identified by admission records. Parents/caregivers were invited to participate. A questionnaire on the demographics, knowledge, beliefs, and response of parents/caregivers during the child's current seizure episode was administered face to face. Data were analyzed for frequencies: groups were compared using chi-square analysis for categorical variables, Student's t-test for normally distributed data, and the Mann-Whitney U-test for data not normally distributed. There were fifty participants: 39 (78%) mothers, mean (SD) age - 33.8 (10.1) years. All sought medical care first. Twenty-two (44%) had plausible beliefs about the cause of seizures. Twenty-seven (54%) knew of appropriate actions during a seizure, 10 (20%) knew of appropriate precautions, and 11 (22%) responded appropriately during the seizure. Eleven (22%) reported receiving seizure education. Witnessing a previous seizure, education level, and seizure education were associated with knowledge of seizures (p<0.05). Socioeconomic status was higher in those with plausible beliefs about seizures and lower in those who took appropriate action during a seizure (p<0.05). Parents/caregivers of children with convulsive seizures have appropriate health-care seeking behavior, but most do not have appropriate knowledge about seizures. Few take appropriate action during the episode. A public education program is needed to improve parental knowledge of and response to convulsive seizures.