Cessation Of Seizures Research Articles

Early Neurologic Recovery, Practice Pattern Variation, and the Risk of Endotracheal Intubation Following Established Status Epilepticus.

To quantify the association between early neurologic recovery, practice pattern variation, and endotracheal intubation during established status epilepticus, we performed a secondary analysis within the cohort of patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT). We evaluated factors associated with the endpoint of endotracheal intubation occurring within 120 minutes of ESETT study drug initiation. We defined a blocked, stepwise multivariate regression, examining 4 phases during status epilepticus management: (1) baseline characteristics, (2) acute treatment, (3) 20-minute neurologic recovery, and (4) 60-minute recovery, including seizure cessation and improving responsiveness. Of 478 patients, 117 (24.5%) were intubated within 120 minutes. Among high-enrolling sites, intubation rates ranged from 4% to 32% at pediatric sites and 19% to 39% at adult sites. Baseline characteristics, including seizure precipitant, benzodiazepine dosing, and admission vital signs, provided limited discrimination for predicting intubation (area under the curve [AUC] 0.63). However, treatment at sites with an intubation rate in the highest (vs lowest) quartile strongly predicted endotracheal intubation independently of other treatment variables (adjusted odds ratio [aOR] 8.12, 95% confidence interval [CI] 3.08-21.4, model AUC 0.70). Site-specific variation was the factor most strongly associated with endotracheal intubation after adjustment for 20-minute (aOR 23.4, 95% CI 6.99-78.3, model AUC 0.88) and 60-minute (aOR 14.7, 95% CI 3.20-67.5, model AUC 0.98) neurologic recovery. Endotracheal intubation after established status epilepticus is strongly associated with site-specific practice pattern variation, independently of baseline characteristics, and early neurologic recovery and should not alone serve as a clinical trial endpoint in established status epilepticus. ClinicalTrials.gov Identifier: NCT01960075.

Levetiracetam Versus Phenytoin or Fosphenytoin for Second-Line Treatment of Pediatric Status Epilepticus: A Meta-Analysis.

To synthesize the available evidence examining the efficacy and safety of levetiracetam compared with phenytoin or fosphenytoin in benzodiazepine-refractory pediatric status epilepticus. We searched (from inception until April 27, 2020) Ovid MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. Two reviewers, independently and in duplicate, screened citations and manuscripts for eligible randomized controlled trials. Independently and in duplicate, we performed data abstraction, risk of bias assessment, and certainty assessment using Grading of Recommendations, Assessment, Development, and Evaluation. We performed meta-analyses using random-effect models or, if insufficient data, presented findings narratively. We identified seven randomized controlled trials (n = 1,575). Pooled analysis demonstrated low certainty evidence for no difference of levetiracetam on time to seizure cessation (mean difference, -3.11 min; 95% CI, -6.67 to 0.45), early seizure cessation (relative risk, 1.09, 95% CI, 0.95-1.26), or late seizure cessation (relative risk, 1.05; 95% CI, 0.93-1.18). Adverse event outcomes were limited by low event numbers. We found low certainty evidence for less respiratory depression with levetiracetam (relative risk, 0.28; 95% CI, 0.12-0.69). The efficacy of levetiracetam is comparable with phenytoin or fosphenytoin in children with benzodiazepine-refractory status epilepticus (low certainty evidence). Levetiracetam may cause less respiratory depression. Clinicians and guideline developers should weigh safety profiles when choosing between these agents.

Modified Atkins Diet vs Low Glycemic Index Treatment for Drug-Resistant Epilepsy in Children: An Open Label, Randomized Controlled Trial

To compare the efficacy of the modified Atkins diet (mAD) and low glycemic index treatment (LGIT) among children with drug-resistant epilepsy. Randomized, open labelled, controlled clinical trial. Tertiary care referral center. Children aged 6 months to 14 years with drug-resistant epilepsy. mAD (n=30) or LGIT (n=30) as an add-on to the ongoing antiseizure drugs. Proportion of children who achieved seizure freedom as defined by complete cessation of seizure at 12 weeks as primary outcome measure. Secondary outcome measures were proportion of children who achieved >50% and >90% seizure reduction at 12 weeks, and adverse effects of the two therapies. Of the 60 recruited children, 3 in the mAD group, and 3 in LGIT group were lost to follow-up. The proportion of children with seizure freedom [16.6% vs 6.6%; relative risk reduction (RRR) (95% CI), 1.5 (-10.9, 0.5); P=0.42] and >90% seizure reduction [30% vs 13.3%; RRR, -1.2 (-5.5, 0.2); P=0.21] was comparable between the mAD and LGIT group at 12 weeks. The proportion of children with >50% seizure reduction was significantly higher at 12 weeks among those who received LGIT as compared to the mADgroup [73.3% vs 43.3%; RRR (95% CI) 0.4 (0.1-0.6); P=0.03] although the effect size was small. The diet was well tolerated with lethargy being the most common adverse effect in children in mAD (53.3%) and LGIT (66.7%) groups. The present study with limited sample size shows that seizure freedom at 12 weeks was comparable between mAD and LGIT for the treatment of drug-resistant epilepsy.

Absent Words, Present Person

Hundreds of distinct epilepsy-causing genes have been identified.1 The vitamin B6-dependent epilepsies are a heterogeneous group of genetic disorders due to incomplete formation, transport, or inactivation of pyridoxal 5′-phosphate (PLP).2 The ALDH7A1 , PNPO , ALPL , ALDH4A1 , and more recently PLPBP genes have been implicated.3 Characteristic presentation of vitamin B6-dependent epilepsies includes neonatal onset of encephalopathy and seizures refractory to first-line antiseizure medications (ASMs) followed by cessation or dramatic improvement of seizures after administration of pyridoxine or PLP. Because initiation of proper treatment is essential for seizure control, timely diagnosis is critical to optimizing clinical outcome. We describe the case of a 3-year-old boy who presented with progressively worsening refractory seizures starting at 14 months of age and was subsequently diagnosed with pyridoxal phosphate homeostasis protein (PLPHP) deficiency via rapid genome sequencing during a critical care hospitalization for status epilepticus. He was started on pyridoxine with immediate cessation of seizure activity and has remained seizure-free. We review the diagnosis, management, and outcome of PLPHP deficiency, as well as implications for use of rapid genetic testing in the acute care setting.

Α Multicenter Retrospective Study Evaluating Brivaracetam in the Treatment of Epilepsies in Clinical Practice.

Brivaracetam (BRV) is the latest approved antiepileptic drug. The aim of the study was to evaluate the efficacy and tolerability of BRV in everyday clinical practice. In this retrospective, observational, multicenter study, data from epilepsy patients receiving BRV from January 2018 to July 2019 were analyzed. Patients with age ≥16 suffering from any type of epilepsy and having at least one follow up encounter after dose titration were included. 156 consecutive patients were included in the study. The mean age was 40 (16–84 years) and the mean duration of epilepsy was 21 years. Of the 156 patients, 81% were diagnosed with focal-onset seizures, 16% with generalized seizures, while 3% suffered from unclassified seizures. Nine patients received BRV as monotherapy as a switching therapy. At the first follow up visit, seizure cessation was achieved in 56 (36%) patients and the rate of ≥50% responders was 36%. Twenty four patients (15%) remained unchanged; six patients (4%) were recorded with increased seizure frequency, while the remaining 9% had a response of less than 50%. Twenty-six patients (17%) showed clinically significant adverse events, but none were life threatening. Brivaracetam seems to be an effective, easy to use and safe antiepileptic drug in the clinical setting.

Is sulthiame effective and tolerated as add-on therapy for infants with epilepsy? A Cochrane Review summary with commentary.

Is sulthiame effective and tolerated as add-on therapy for infants with epilepsy? A Cochrane Review summary with commentary.

What are the effects of intravenous immunoglobulins on seizures and quality of life of people with epilepsy? A Cochrane Review summary with commentary.

What are the effects of intravenous immunoglobulins on seizures and quality of life of people with epilepsy? A Cochrane Review summary with commentary.

Assessment of benzodiazepine dosing strategies for the management of status epilepticus in the emergency department.

Although guidelines recommend specific benzodiazepine doses for the treatment of generalized convulsive status epilepticus (GCSE), underdosing appears to be common. The purpose of this investigation was to assess benzodiazepine dosing strategies for the initial management of GCSE in patients presenting to the Emergency Department (ED). This was a retrospective review of adult patients who received benzodiazepines in the ED for treatment of GCSE. Characteristics of those achieving seizure cessation following initial benzodiazepine therapy were assessed. 222 patients presented to the ED and received 403 doses of benzodiazepines, of which 1.5% conformed with recommendations. First-line therapy was successful in 86.8% of patients with an average dose of 1.6mg (0.02mg/kg). No difference in dosing was noted between those experiencing early cessation and those that did not (p=0.132). Patients experiencing early cessation were significantly less likely to receive further doses, be intubated, or be admitted to the intensive care unit (ICU) or hospital (p<0.05 for all comparisons). Those that received early antiepileptic drug therapy were significantly less likely to receive additional benzodiazepine doses, be intubated, or be admitted to the ICU or hospital (p<0.05 for all comparisons). According to guideline recommendations, there was consistent underdosing of benzodiazepines noted in both prehospital and ED settings. Early seizure cessation and the early receipt of an antiepileptic drug were found to be associated with multiple significant clinical outcomes. Future investigations should explore optimal dosing strategies for benzodiazepines as well as the impact of early antiepileptic drug administration.

Acute encephalopathy in children with tuberous sclerosis complex

ObjectiveWe examined the clinical manifestations of acute encephalopathy (AE) and identify risk factors for AE in children with tuberous sclerosis complex (TSC).MethodsThe clinical data of 11 children with clinically diagnosed TSC associated with AE and 109 children with clinically diagnosed TSC alone aged 4 years or older were collected from 13 hospitals.ResultsOf the 11 children with AE, 5 had histories of febrile seizures (FS), and all had histories of febrile status epilepticus (FSE). AE developed within 24 h after fever onset in all children with seizures lasting 30 min or longer. All children developed coma after seizure cessation. Head magnetic resonance imaging (MRI) revealed widespread abnormalities in the cerebral cortex, subcortical white matter, corpus callosum, basal ganglia, and thalamus. One child died; seven had severe neurological sequelae; and the other three, mild sequelae. Logistic regression analysis revealed that a history of FSE was correlated with the development of AE.SignificanceAE in children with TSC was characterized by sudden onset after fever, followed by coma, widespread brain edema evident on MRI, and poor outcomes. A history of FSE was a risk factor for the development of AE.

Efficacy and tolerability of perampanel as adjunctive treatment of focal and generalized tonic-clonic epileptic seizures in children over 4 years of age

The article is a short review of an observational study that proves the good efficacy and tolerability of perampanel suspension in the adjunctive treatment of epilepsy in children over 4 years of age. The study demonstrated a high level of 50% responders: 47% with focal seizures, 65% with transition of focal seizures to bilateral tonic-clonic seizures, 65% with primary generalized tonic-clonic seizures. Cessation of seizures was achieved in 12%, 19% and 55% of patients, respectively. The most common side-effects were fatigue (26%), nasopharyngitis (19%), lightheadedness, irritability, fever (13% each), and vomiting (11%). There were no significant clinical negative changes in cognitive functions according to the assessment on the Aldenkamp-Baker scale, both on the total score and subscales. Also, there were no significant changes in laboratory data, vital functions and ECG parameters.

Судорожный синдром. Часть 1

Convulsive syndrome is an urgent, potentially life-threatening condition in neurological, paediatric and general practice. Over the past decade, reconsideration has been committed in relation to the defi nition of epilepsy, epileptic syndromes, including convulsive syndrome with simultaneous expansion of the arsenal of medicinal products for cessation of convulsive seizures in children and adults. In this connection, we have prepared this lecture comprising two parts: the first part considers the defi nition, pathogenesis, aetiology and diagnosis of the convulsive syndrome. The lecture is designed for neurologists, paediatricians, general practitioners, ambulance physicians and anaesthesiologists-reanimatologists. Th e system of continuing medical education (CME) considers convulsive syndrome within the framework of the programme for postgraduate training of physicians in these specialities.

Utility and Safety of Perampanel in Pediatric FIRES and Other Drug-Resistant Epilepsies.

Perampanel is a novel antiepileptic drug, which antagonises AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) glutamate receptor. We describe perampanel as an adjunctive treatment for FIRES (febrile infection-related epilepsy syndrome) and other drug-resistant epilepsies. A single-centre, observational, retrospective study involving 20 pediatric patients was conducted. Perampanel was started for three patients with FIRES, achieving seizure cessation in two patients within a day and on days 19 and 32 of illness. Doses used ranged from 4 to 12 mg/day, without any adverse effects reported or discontinuation of therapy. Responder-rate for other drug-resistant epilepsies is 25%. Median time to achieve ≥50% seizure reduction was 80 days (range: 26-326 days). Adverse effect reported in 47% of the patients includes central nervous system-related, and thrombocytopenia. Eight patients discontinued perampanel, because of ineffectiveness or adverse effects. The median time on perampanel before discontinuation was 179 days (range: 94-345 days). Perampanel may be of benefit in pediatrics FIRES and is of utility in other drug-resistant epilepsies.

Recent Advances in the Diagnosis and Treatment of Neonatal Seizures.

Seizures are the most common neurological emergency in the neonates, and this age group has the highest incidence of seizures compared with any other period of life. The author provides a narrative review of recent advances in the genetics of neonatal epilepsies, new neonatal seizure classification system, diagnostics, and treatment of neonatal seizures based on a comprehensive literature review (MEDLINE using PubMED and OvidSP vendors with appropriate keywords to incorporate recent evidence), personal practice, and experience. Knowledge regarding various systemic and postzygotic genetic mutations responsible for neonatal epilepsy has been exploded in recent times, as well as better delineation of clinical phenotypes associated with rare neonatal epilepsies. An International League Against Epilepsy task force on neonatal seizure has proposed a new neonatal seizure classification system and also evaluated the specificity of semiological features related to particular etiology. Although continuous video electroencephalogram (EEG) is the gold standard for monitoring neonatal seizures, amplitude-integrated EEGs have gained significant popularity in resource-limited settings. There is tremendous progress in the automated seizure detection algorithm, including the availability of a fully convolutional neural network using artificial machine learning (deep learning). There is a substantial need for ongoing research and clinical trials to understand optimal medication selection (first line, second line, and third line) for neonatal seizures, treatment duration of antiepileptic drugs after cessation of seizures, and strategies to improve neuromorbidities such as cerebral palsy, epilepsy, and developmental impairments. Although in recent times, levetiracetam use has been significantly increased for neonatal seizures, a multicenter, randomized, blinded, controlled phase IIb trial confirmed the superiority of phenobarbital over levetiracetam in the acute suppression of neonatal seizures. While there is no single best choice available for the management of neonatal seizures, institutional guidelines should be formed based on a consensus of local experts to mitigate wide variability in the treatment and to facilitate early diagnosis and treatment.

The unmet need for rapid epileptic seizure termination (REST).

Approximately 40% of epilepsy patients will continue to experience breakthrough seizures despite stable antiepileptic drug regimens. Rescue treatments have demonstrated efficacy and safety for select seizure emergencies. Outpatient administered intranasal and rectally delivered medications are regulatory approved for acute repetitive seizures (ARS), and injectable benzodiazepines are indicated for parenteral treatment of established status epilepticus. Despite these advances, no studies have been shown to abort an ongoing seizure following patient or caregiver home administration of therapy at the first clinical sign of seizure onset. Such treatment would require rapid systemic absorption without intravenous access, and evidence of seizure cessation within minutes of administration that is superior to placebo (eg, seizure self-regulation). Rapid epileptic seizure termination (REST) treatment may apply to multiple seizure emergencies beyond ARS, including focal or generalized seizures preceded by an aura, flurries of absence or myoclonic seizures, or prolonged focal and generalized seizures at high risk of progression to status epilepticus. Novel investigational drug delivery systems have demonstrated feasibility of intraictal delivery and seizure cessation by two minutes. Ongoing randomized trials of REST treatment for diverse seizure emergencies hold the potential to decrease bouts of mental and physical incapacitation in patients with drug-resistant epilepsy.

Efficacy and safety of using eslicarbazepine in treating focal epilepsy in clinical practice (based on international Euro-Esli study and personal experience)

The latest data on the eslicarbazepine (ESL) efficacy, tolerability and safety in treatment of focal epilepsy are presented based on the results of the European study in clinical practice Euro-Esli that enrolled 2058 patients from 14 European centers, a detailed subgroup analysis, as well as our own data on the follow-up of 65 patients with focal epilepsy receiving ESL in monotherapy or combination therapy. According to the Euro-Esli study, a 12-months follow-up allowed to conclude that therapy retention comprised 73.4%; percentage of responders was 75.6%, whereas proportion of patients with complete seizure cessation was 41.3 %. Regarding ESL efficacy it may be concluded that our personal data were comparable to those obtained during the international study Euro-Esli so that retention was 80%; percentage of responders was 75.4%, whereas seizure-free rate was 58.5%. As for the ESL safety profile our study demonstrated that adverse events (AEs) were registered at lower rate in as few as 21.5% of patients compared to 34% found in the Euro-Esli study. No unexpected serious AEs during the long-term follow-up period were documented in the both studies, which evidence about favorable ESL safety profile elderly patients, patients with comorbid intellectual and mental disorders as well as patients with post-stroke epilepsy.

Efficacy of Levetiracetam in neonatal seizures: a systematic review

Background Neonatal seizures represent the most frequent presenting sign of any neurological abnormality secondary to various etiologies in the neonatal period. Phenobarbitone (PB) has been used as first-line anti-epileptic drug in the treatment of seizures but concerns have been raised regarding its neuro-apoptotic effects over the developing brain. Levetiracetam (LEV) is a newer anti-epileptic drug with neuroprotective property and has been used in adults and pediatric patient but its use in neonates have very limited experience. Recently many neonatal studies have sought the role of LEV in the management of neonatal seizures. Aims and objective To evaluate the efficacy of Levetiracetam in the management of neonatal seizures. Search methods The literature search was done for this systematic review by searching the Cochrane Central Register of Controlled Trials (CENTRAL), and other various electronic databases including PubMed and various sites for ongoing trials and abstracts of conferences. Results Two eligible studies were analyzed that fulfilled the inclusion criteria of the systematic review. Fifteen studies were excluded due to the non-fulfillment of inclusion criteria. The primary outcome of both studies was to see the efficiency of LEV in controlling neonatal seizures when compared to PB. Better seizure control after a single loading dose of LEV was seen. Rates of seizure cessation at 24 h was also better in the LEV arm. Neonatal seizures secondary to hypoxic-ischemic encephalopathy (HIE) and receiving therapeutic hypothermia were better controlled with LEV. The side effect of LEV was significantly less when compared to PB. Conclusion Levetiracetam has shown to have promising anti-epileptic properties for the management of neonatal seizure with better efficacy and less or no side effects. There is a need to conduct more randomized controlled trials seeking the role of LEV in the acute management of neonatal seizures and also for assessing its neuroprotective role and neurodevelopmental outcome in these neonates.

English

BACKGROUND The rapidity with which a medication can be delivered to the systemic circulation and then into the brain always play a significant role in reducing the mortality and morbidity. We wanted to determine and compare the efficacy of intranasal midazolam with that of intravenous lorazepam in the control of acute onset seizures and side effects. METHODS This is an open labelled randomized control trial conducted in the Emergency Department of KIMS Hospital, which is a multi-specialty tertiary care centre in south Kerala, India, among children with acute seizure between 6 months and 15 years of age. They received intranasal midazolam or intravenous lorazepam. RESULTS 65.2 % (15) of the children in whom intranasal midazolam was given, seizures were controlled within 5 minutes from ER presentation, whereas in lorazepam group, only 34.8 % (8) children ceased to seizure within 5 minutes. P value was 0.039. CONCLUSIONS The overall time to cessation of seizure after arrival at hospital was faster with intranasal midazolam than intravenous lorazepam. No untoward side effects were noticed. KEYWORDS Acute Seizure in Children, Intranasal Midazolam, Lorazepam, Randomized Trial

Preferential Antiseizure Medications in Pediatric Patients with Convulsive Status Epilepticus: A Systematic Review and Network Meta-Analysis

The optimal choice for first- and second-line antiseizure medications for pediatric patients with convulsive status epilepticus remains ambiguous. The present study aimed to estimate the comparative effect on the efficacy and safety of different antiseizure medications in pediatric patients with status epilepticus and provide evidence for clinical practice. We searched PubMed, EMBASE, and the Cochrane Library for eligible randomized controlled trials. Inclusion criteria included: (1) pediatric patients; (2) diagnosis of status epilepticus; and (3) randomized controlled trials. Exclusion criteria were: (1) mixed population without a pediatric subgroup analysis; (2) not status epilepticus; (3) received the study drug prior to admission; (4) sample size fewer than 30; and (5) not randomized controlled trials. Primary outcome was seizure cessation. Secondary outcomes were seizure recurrence within 24h, respiratory depression, and admission to an intensive care unit. The hierarchy of competing antiseizure medications was presented using the surface under the cumulative ranking curve. Eight first-line antiseizure medication studies involving 1686 participants and eight second-line antiseizure medication studies involving 1711 participants were eligible for analysis. Midazolam, diazepam, lorazepam, and paraldehyde were administered as first-line antiseizure medications. Valproate, phenobarbital, phenytoin, fosphenytoin, and levetiracetam were investigated as second-line antiseizure medications. No significant differences were observed across first- and second-line antiseizure medications. Midazolam ranked the best for primary and secondary outcomes among the first-line antiseizure medications. Phenobarbital ranked the best for seizure cessation and a lower risk of admission to the intensive care unit. Valproate had superiority in preventing recurrence within 24h. Levetiracetam had the lowest probability of developing respiratory depression. This study demonstrated the hierarchy of competing interventions. Midazolam could be a better option for first-line treatment. Phenobarbital, levetiracetam, and valproate had their respective superiority in the second-line intervention. This study may provide useful information for clinical decision making under different circumstances.

Decreased Cerebrospinal Fluid Orexin-A (Hypocretin-1) Concentrations in Patients after Generalized Convulsive Status Epilepticus.

The effects of status epilepticus on the orexin/hypocretin system have yet to be investigated. The present study aimed to assay orexin-A/hypocretin-1 in the cerebrospinal fluid (CSF) of patients after generalized convulsive status epilepticus (GCSE). The study groups included 20 GCSE patients, 24 patients diagnosed with epilepsy but remaining in remission (ER), and 25 normal controls (CTR). Diagnostic lumbar puncture was performed in GCSE patients within 3–10 days of seizure cessation, as well as in the ER and to CTR subjects. Among all GCSE patients, the outcome was graded according to the modified Rankin Scale (mRS) at 1-month follow-up. Orexin-A levels were measured in unextracted CSF samples, using a commercial radioimmunoassay. There was a significant overall difference in median CSF orexin-A concentrations between GCSE, RE, and CTR patients (p < 0.001). The lowest concentrations were noted in the GCSE group compared to ER (p < 0.001) or CTR (p < 0.001). CSF orexin-A levels in GCSE patients inversely correlated with clinical outcome as assessed on the mRS at 1-month follow-up (r = −0.55; p = 0.1). In conclusion, CSF orexin-A levels may serve as a biomarker of increased turn-over of the peptide or post-SE neuronal damage, and implicates the orexin system in the pathogenesis of SE.

Levetiracetam for convulsive status epilepticus in childhood: systematic review and meta-analysis

ImportanceProlonged seizures are life-threatening emergencies associated with significant morbidity.ObjectiveTo determine the efficacy and safety of levetiracetam in treating convulsive status epilepticus (CSE) in childhood.Data sources and study selectionsPubMed, Embase, the...