Convulsive Seizures In Children Research Articles

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.

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.

First‐ever convulsive seizures in children presenting to the emergency department: risk factors for seizure recurrence and diagnosis of epilepsy

Aetiologies of first-ever convulsive seizures may be diverse, not all leading to recurrence or epilepsy diagnosis. We aimed to describe the epidemiology of first-ever convulsive seizures in children, investigating risk factors for recurrence and epilepsy diagnosis. This was a retrospective study of children presenting with a first-ever convulsive seizure to a tertiary-care paediatric emergency department (PED) in Italy, in a 12-month period (2011-2012). One hundred and eight children (57 males, 51 females) presented to the PED for a first-ever convulsive seizure; 90.7% were 6months to 6years old (median age 1y 10mo, mean 2y 7mo, range 0mo-14y 4mo). Seizure duration was less than 5minutes in 76.8%. Seizures were 'unprovoked' in 19.4% and 'provoked' in 80.6%. At 4-year follow-up, 37.9% of patients experienced recurrence and 13.6% received a diagnosis of epilepsy. Factors significantly associated with recurrence were the 'unprovoked' nature of the first seizure, multiple seizures in the first 24hours, positive family history of febrile seizures or epilepsy, and pre-existing neurological conditions/problems. Factors significantly associated with a diagnosis of epilepsy were the 'unprovoked' nature of the first seizure, age older than 6years, pre-existing neurological conditions/problems, and focal onset of first seizure. Children presenting to the PED with first-ever convulsive seizures represent a heterogeneous group. The identification of prognostic factors for recurrence and epilepsy diagnosis may help provide tailored counselling and follow-up. Seizures were 'unprovoked' in 19.4% and 'provoked' in 80.6% of children presenting to the emergency department. At 4-year follow-up, 37.9% relapsed, and 13.6% received a diagnosis of epilepsy. 'Unprovoked' first seizure, family history of febrile seizures, and pre-existing neurological conditions were associated with recurrence. 'Unprovoked' first seizure, age younger than 6years, and pre-existing neurological conditions were associated with epilepsy diagnosis.

The effect of vagus nerve stimulator in controlling status epilepticus in children

PurposeThis study explores the effect of Vagus Nerve Stimulator (VNS) on Status Epilepticus (SE) in children with medically intractable epilepsy. MethodsRetrospective review was conducted in children with a history of at least two SE, who had VNS implantation and had at least one year follow up after the procedure. ResultsSixteen patients met inclusion/exclusion criteria. The median age of seizure onset and surgery was 1.3 years and 9.0 years, respectively. Prior to VNS implantation, 81% (13/16) of patients had ≥one seizure per month when all seizure types were combined. 75% (12/16) of patients experienced ≥one generalized convulsive seizure per month. The median number of SE prior to VNS was three (2–9), and 63% (10/16) had at least one SE during a year prior to implantation. The proportion of patients who did not have any SE one year after VNS implantation increased compared to the year prior (75% vs. 37%, p = 0.07). The seizure frequency decreased in a minority of patients when all seizure types were combined (20% at one year, p = 1.00, 44% at the last follow up, p = 0.55), but generalized convulsive seizure decreased in 69% of patients at one year (p = 0.01) and 75% of patients at last follow up (p = 0.01). ConclusionVNS appears to have favorable impact on SE and generalized convulsive seizures in children with medically intractable epilepsy.

Epidemiology of first convulsive seizures in children

Objective: Aetiologies of first-ever convulsive epileptic seizures may be diverse, not all leading to diagnosis of epilepsy. We aimed to describe the epidemiology of first convulsive seizures in children and to assess risk factors for recurrence, repeat admission to the ED and subsequent development of epilepsy. Methods: Retrospective chart review of all children who presented with a first-ever convulsive seizure to Padua Paediatric ED between 01.03.2011 and 29.02.2012, with a 4-year follow-up. Univariate and bivariate statistical analysis were used for data description. For definition and classification of seizures, epilepsies and epileptic syndromes the following documents were used: Commission, 1989; Commission, 1993; Chin, 2004; Beghi, 2010; Berg, 2010; Fisher, 2014; Bergamo, 2015. Results: During the 12-month study period, 182 children presented to the ED with convulsive epileptic seizures; 108 of these presented with first-ever episode. Seizure duration was <5 min in >75%, 5–30 min in 21.3% and >30 min in 1.9% only. Aetiologic classification at discharge was: febrile seizures (FS) (71.3%), remote symptomatic seizures (5.6%), benign seizures associated with gastroenteritis (4.6%), acute symptomatic seizures (2.7%), acute on remote symptomatic seizures (1.9%), presumed idiopathic epileptic seizure (1.9%), unknown (12%). “Unprovoked” seizures (“Un”S) were 19.5%. The 4-year risk of seizure recurrence was 37.9% (60% in the “Un”S group); EEG epileptiform discharges and “Un”S aetiology were risk-factors for recurrence. The 4-year risk of diagnosis of epilepsy was 13.6% (60% in the “Un”S group); risk factors were: focal seizures, EEG epileptiform discharges, age >6 years and “Un”S aetiology of the first seizure. Conclusions: Children presenting to ED with first-ever convulsive epileptic seizures represent an heterogeneous group: while most of these have FS with an excellent prognosis, patients with “Un”S have a high risk of both seizure recurrence and receiving diagnosis of epilepsy, especially in case of focal seizures, EEG epileptiform discharges and age >6 years.

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.

Epileptic seizures as a manifestation of cow’s milk allergy: a studied relationship and description of our pediatric experience

Adverse reactions after ingestion of cow’s milk proteins can occur at any age, from birth and even amongst exclusively breast-fed infants, although not all of these are hypersensitivity reactions. The most common presentations related to cow’s milk protein allergy are skin reactions, failure to thrive, anaphylaxis as well as gastrointestinal and respiratory disorders. In addition, several cases of cow’s milk protein allergy in the literature have documented neurological involvement, manifesting with convulsive seizures in children. This may be due to CNS spread of a peripheral inflammatory response. Furthermore, there is evidence that pro-inflammatory cytokines are responsible for disrupting the blood–brain barrier, causing focal CNS inflammation thereby triggering seizures, although further studies are needed to clarify the pathogenic relationship between atopy and its neurological manifestations. This review aims to analyze current published data on the link between cow’s milk protein allergy and epileptic events, highlighting scientific evidence for any potential pathogenic mechanism and describing our clinical experience in pediatrics.

Children with convulsive epileptic seizures presenting to padua pediatric emergency department: the first retrospective population-based descriptive study in an Italian Health District.

Convulsive epileptic seizures in children represent a common cause of admission to pediatric emergency department. Data about incidence, etiology, and outcome are still lacking in literature. We retrospectively reviewed medical records of children presenting to our pediatric emergency department with convulsive seizures during a 12-month period and collected their diagnoses over the following year. In all, 182 children met the inclusion criteria, for a total of 214 visits (1.2% of all attendances, n = 24 864). Seizures lasted less than 5 minutes in 76%, 5 to 30 minutes in 20%, 30 to 60 minutes in 2%, and over 60 minutes in 2% visits ("early," "established," "refractory," convulsive status epilepticus, respectively). Incidence of "early" (seizure lasting 5-30 minutes) and "established" (seizure lasting 30-60 minutes) status epilepticus was 52/100 000/year and 7/100 000/year respectively. Most common causes were febrile seizures (56%) and remote symptomatic seizures (19%). Knowing the epidemiology of convulsive seizures in children is important to guide appropriate management and individualized follow-up.

Treatment of prolonged convulsive seizures in children; a single centre, retrospective, observational study

ObjectivesTo evaluate treatment of children with Prolonged Convulsive Seizures (PCS) at the University Medical Centre Groningen (UMCG). Material and methodsPCS were identified from an UMCG database of children with epilepsy aged <18 years who had their first (a)febrile seizure between 2000 and 2010. PCS were included if they lasted ≥10 min and occurred between January 2000 and October 2012 in children aged >1 month. Order, timing, and location of treatment were analysed. Treatment of PCS before and after 2005 was compared with recommendations from a Dutch 2005 treatment guideline for Convulsive Status Epilepticus (CSE) in children aged >1 month. Results269 PCS occurring in 102 children were included (53.9% male, median age 2.8 years; range 0.1–13.7 years). Seventy episodes concerned a first PCS. Most first and subsequent PCS started outside the hospital (78.6% and 82.4%, respectively) and lasted 10–30 min (42.4% and 51.4%, respectively). Cessation occurred after two administrations of any therapy in first (median, range 0–7) and subsequent PCS (median, range 0–10). First treatment choice was rectal diazepam in first (59.6%) and subsequent (43.9%) PCS, but since 2006 a trend towards buccal midazolam was observed in subsequent PCS. Clonazepam was frequently used as second treatment choice in first (43.8%) and subsequent (27.3%) PCS, although not mentioned in the guideline. ConclusionIn our study cohort rectal diazepam is still first choice in the management of PCS despite proven superior efficacy of buccal midazolam. Clonazepam is frequently used although it is not formally recommended in a Dutch guideline.

The administration of rescue medication to children with prolonged acute convulsive seizures in a non-hospital setting: an exploratory survey of healthcare professionals’ perspectives

Timely administration of rescue medication for prolonged convulsive seizures lasting more than 5 min is necessary to prevent progression to status epilepticus in children. The Practices in Emergency and Rescue Medication for Epilepsy Managed with Community Administered Therapy (PERFECT™) initiative was set up to gain a better understanding of how prolonged convulsive seizures in children are managed when they occur outside of the hospital. We present the findings from an exploratory telephone survey of 128 healthcare professionals (HCPs) (85 pediatric neurologists and neurologists, 28 community pediatricians, and 15 epilepsy nurses) from six EU countries, conducted as part of the PERFECT™ initiative. Among HCPs, there was greater awareness of local protocols and lesser awareness of national or international guidelines. HCPs were not very aware of how prolonged convulsive seizures were managed outside of the hospital and had few professional links to schools or other settings where these seizures were most likely to occur. Approximately one third believed that lack of confidence and fear of liability were barriers to caregivers administering treatment in schools, as was insufficient training of caregivers in the wider community on the management of prolonged convulsive seizures. Results of this HCP survey have identified several clear gaps that need to be addressed: clearer guidance that spans all settings of care, greater dissemination of such guidelines across the chain of care, more open communication and better links between HCPs and schools, and systematic training of all relevant caregivers on the appropriate management of prolonged convulsive seizures.

First line management of prolonged convulsive seizures in children and adults: good practice points

Over the past decades, it has become clear that the most efficient way to prevent status epilepticus is to stop the seizure as fast as possible, and early treatment of prolonged convulsive seizures has become an integral part of the overall treatment strategy in epilepsy. Benzodiazepines are the first choice drugs to be used as emergency medication. This treatment in the early phases of a seizure often implies a 'pre-medical' setting before intervention of medically trained persons. In this paper, we propose "good practice points" for first line management of prolonged convulsive seizures in children and adults in a 'pre-medical' setting.

PND15 Cost-Effectiveness of Buccolam® (Licensed Oromucosal Midazolam) Compared to Benzodiazepines for the Treatment of Acute Prolonged Epileptic Seizures in Germany

BUCCOLAM (oromucosal midazolam) is approved for the treatment of prolonged, acute, convulsive seizures in children and was the first product to receive a Paediatric-Use Marketing Authorisation (PUMA) in September 2011. The product label includes use by parents and other carers such as teachers. Current care in Germany for first line treatment consists mainly of rectal diazepam with some use of buccal lorazepam, clonazepam and chloral hydrate. Some non-family carers can be reluctant to administer these products due to concerns about social acceptability, dignity or labelling issues. A decision tree model has been developed to assess the cost of BUCCOLAM compared to current care for prolonged acute convulsive seizures initially occurring in the community setting. The model evaluates costs along the treatment pathway when a child has a seizure including whether or not carers administer treatment, whether an ambulance is required and whether or not patients are taken to hospital and require an inpatient stay. Data were obtained from a variety of sources including clinical effectiveness estimates from McIntyre et al. 2005, and a Delphi panel. Costs were taken from published sources. Estimates of the total eligible population were taken from epilepsy prevalence data and the Delphi panel. Over one year, compared to the mix of treatments representing current care, BUCCOLAM showed a reduction in per patient costs of €3,469. Compared to treatment with rectal diazepam alone, the most commonly used treatment, BUCCOLAM showed a cost reduction of €3,533. It was expected that ∼36,000 patients would be eligible. At an uptake of 20% BUCCOLAM would reduce health care expenditure by €19.4 million in the first year. Treatment with BUCCOLAM is cost-saving compared to current care and treatment with rectal diazepam through a reduction in the need for ambulance call-outs and hospital stays.

Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: A randomised trial

Status epilepticus and acute prolonged seizures are the most commonly occurring neurological emergencies in children. Such events have high morbidity and mortality rates along with poor long-term outcomes, depending on their duration and causes. Therefore, such seizures warrant urgent treatment using appropriate doses of anticonvulsants. Benzodiazepines, phenobarbital, and phenytoin are the most commonly used anticonvulsants for controlling status epilepticus and acute prolonged seizures. However, these medications have several well-known adverse effects. Previous studies on both adults and children have shown the efficacy and safety of rapid infusion of valproate in controlling status epilepticus. However, few well-designed randomised trials have been carried out in children, and there remains a paucity of data regarding intravenous sodium valproate use in children. Therefore, our aim was to compare the efficacy and safety of rapid loading of valproate with those of intravenous phenobarbital in children with status epilepticus and acute prolonged seizures. Sixty children (30 in each group) with convulsive status epilepticus and acute prolonged seizures were enrolled and randomly assigned to receive either valproate or phenobarbital. The main outcome variable was termination of all convulsive activity within 20 min of starting anticonvulsant infusion. Intravenous rapid loading of valproate was successful in seizure termination in (27/30, 90%) of patients compared to phenobarbital (23/30, 77%) (p = 0.189). Clinically significant adverse effects occurred in 74% patients of the phenobarbital group and 24% patients of the valproate group (p < 0.001). In conclusion, rapid loading of valproate is effective and safe in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children. Intravenous valproate should be considered as a suitable choice for terminating status epilepticus and acute prolonged seizures in children.

Intranasal versus intravenous lorazepam for control of acute seizures in children: A randomized open‐label study

Intravenous lorazepam is considered the drug of first choice for control of acute convulsive seizures. However, resource or personnel constraints necessitate the study of alternative routes and medications. This study compared the efficacy and adverse effects of intranasal versus intravenous lorazepam in children aged 6-14 years who presented with acute seizures. This was a randomized open-label study conducted at an Indian hospital from August 2008 to April 2009. One hundred forty-one consecutive children aged 6-14 years who presented convulsing to the emergency room were included. After stabilization, the children were randomized to receive either intravenous or intranasal lorazepam (0.1 mg/kg, maximum 4 mg). The primary outcome measure was clinical seizure remission within 10 min of drug administration. The study was registered with clinicaltrials.gov (NCT00735527). Seventy patients were randomized to receive intravenous and 71 to receive intranasal lorazepam. The patients in the two groups were comparable at baseline. Clinical seizure remission within 10 min of drug administration was found in 80% of the intravenous group as compared to 83.1% of intranasal group. The lower limit of 95% confidence interval for effect size was approximately -9.7%, with an a priori cutoff for noninferiority of -10%. Intranasal administration of lorazepam is not found to be inferior to intravenous administration for termination of acute convulsive seizures in children.

Efficacy and usability of buccal midazolam in controlling acute prolonged convulsive seizures in children

Efficacy and usability of buccal midazolam in controlling acute prolonged convulsive seizures in children

Efficacy and usability of buccal midazolam in controlling acute prolonged convulsive seizures in children

A Prolonged convulsive seizure is the most common neurological medical emergency with poor outcome. An ideal anticonvulsant should be easy-to-use, effective, and safe, and it should also have a long-lasting effect. Benzodiazepines, give via the intravenous or rectal route have generally been used as first-line drugs. In small children, IV access can be difficult and time consuming. Midazolam is a potent anticonvulsant and is rapidly absorbed from the rectal, nasal, and buccal mucosa. Our aim was to evaluate the efficacy and usability of buccal midazolam in controlling seizures in children with acute prolonged seizures, by comparing it with rectal diazepam. Ninety-eight patients were enrolled, with 49 patients in each treatment group. In the buccal midazolam group, 42 (88%) patients were controlled in less than 4 min of drug administration, and all of the patients were controlled within 5 min of drug administration. In the rectal diazepam group, 24 (49%) patients were controlled in less than 4 min and 40 (82%) patients were controlled within 5 min of drug administration. The time for drug administration and drug effect was significantly less with buccal midazolam than with rectal diazepam (p value < 0.001) . In the buccal midazolam group, 46 (94%) parents were satisfied with their child’s treatment and route of drug administration while in the rectal diazepam group, 7 (14%) parents were satisfied. Buccal midazolam was significantly more acceptable than rectal diazepam (p value < 0.001) . In conclusion, buccal midazolam may be as effective as rectal diazepam but more convenient to use in the controlling acute prolonged seizures in children, especially in situations in which there is a difficulty in gaining IV access, for example, in infants.

Elevated CK‐MB mass and plasma brain‐type natriuretic peptide concentrations following convulsive seizures in children and adolescents: Possible evidence of subtle cardiac dysfunction

To evaluate the presence of myocardial injury during convulsive seizures in children and adolescents by determining serum concentrations of cardiac troponin I (cTnI), creatine kinase-MB mass (CK-MB mass), and plasma brain-type natriuretic peptide (BNP). Thirty-one children (20 boys; mean age, 6.6 +/- 5.34 years) with convulsive seizures and 50 healthy children were enrolled. Serum cTnI, CK-MB mass, and plasma BNP concentrations were analyzed 12 h after the seizure and repeated 7 days thereafter in the patient group and obtained one time in the control group. The difference between serum concentrations of cTnI obtained 12 h and 7 days after the seizure was not statistically significant. cTnI levels 12 h postictal and those in control subjects also were not significantly different. CK-MB mass and BNP at the 12th h were higher than those obtained on the 7th day (p < 0.05 and p < 0.001, respectively). Children with seizures had increased levels of CK-MB mass and BNP 12 h after seizure than control subjects (p < 0.05 and p < 0.001, respectively). The results of electrocardiography (ECG) recordings, which were obtained up to 30 min after seizure activity, were completely normal in patients with seizure. Normal cTnI levels are not indicative of overt myocardial necrosis in patients with seizures. However, markedly elevated BNP concentrations together with elevated CK-MB mass levels do suggest subtle cardiac dysfunction in patients with seizure, and further large-scale studies are warranted.

Outcome after prolonged convulsive seizures in 186 children: low morbidity, no mortality.

Prolonged convulsive seizures are a common neurological emergency and a potential cause of neuronal damage and functional sequelae. We explored the role of seizure duration and various background factors for neurological sequelae in children with prolonged convulsive seizures. The population-base of this study was all children (age < 16 years) who had been admitted to the Tampere University Hospital, Finland between 1993 and 1999 with convulsive seizures lasting more than 5 minutes. Patients were followed up individually (mean length of follow-up 2 years 1 month, range 0 to 7 years 8 months). All available data on the prolonged seizure episodes and clinical follow-up were analyzed retrospectively by a detailed review of all medical charts and records. In 186 children (94 males, 92 females; mean age 4 years 5 months, SD 3 years 10 months, range 1 month to 15 years 4 months) there were 279 separate convulsive seizure episodes lasting over 5 minutes, yielding an annual incidence of 47.5 out of every 100000 episodes. Seizure aetiology was idiopathic in 26.2% of episodes, febrile in 41.9%, remote symptomatic in 28%, and acute symptomatic in 3.9% of episodes. Mean duration of all seizure episodes was 42.5 minutes (SD 46.1 minutes) and was significantly correlated with the aetiology: shortest in the febrile group (mean 35.4 minutes) and longest in the acute symptomatic group (mean 88.6 minutes; p < 0.001). There was no mortality related directly to these acute seizure episodes. The most common sequela was an onset of epilepsy in 40 children (22%). Permanent neurological sequelae were noted in only four patients (2.2%; mean seizure duration 16 minutes) and non-permanent sequelae in six patients (3.2%; mean seizure duration 38 minutes). Neurological sequelae of prolonged convulsive seizures in children are rare and are related to aetiological factors rather than the duration of a single seizure. The role of acute seizures in the evolution of epilepsy in children remains obscure.