Convulsive Status Epilepticus In Children Research Articles

Treatment of Convulsive Status Epilepticus: Evidence-Based Guidelines

Sponsoring Organization: American Epilepsy Society (AES) Target Audience: Neurologists, emergency care physicians, hospitalists, and intensive care specialists Background and Objective To update recommendations on the treatment of convulsive status epilepticus in children and adults since those published in 1993 as a consensus statement, the guideline subcommittee of the AES completed a systematic review of all relevant literature through September 2014. Treatment of refractory status epilepticus was not considered. Key Recommendations Initial treatment beyond stabilization of the patient and first-aid measures; recommendation level is “A” (established …

Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society.

The optimal pharmacologic treatment for early convulsive status epilepticus is unclear. To analyze efficacy, tolerability and safety data for anticonvulsant treatment of children and adults with convulsive status epilepticus and use this analysis to develop an evidence-based treatment algorithm. Structured literature review using MEDLINE, Embase, Current Contents, and Cochrane library supplemented with article reference lists. Randomized controlled trials of anticonvulsant treatment for seizures lasting longer than 5 minutes. Individual studies were rated using predefined criteria and these results were used to form recommendations, conclusions, and an evidence-based treatment algorithm. A total of 38 randomized controlled trials were identified, rated and contributed to the assessment. Only four trials were considered to have class I evidence of efficacy. Two studies were rated as class II and the remaining 32 were judged to have class III evidence. In adults with convulsive status epilepticus, intramuscular midazolam, intravenous lorazepam, intravenous diazepam and intravenous phenobarbital are established as efficacious as initial therapy (Level A). Intramuscular midazolam has superior effectiveness compared to intravenous lorazepam in adults with convulsive status epilepticus without established intravenous access (Level A). In children, intravenous lorazepam and intravenous diazepam are established as efficacious at stopping seizures lasting at least 5 minutes (Level A) while rectal diazepam, intramuscular midazolam, intranasal midazolam, and buccal midazolam are probably effective (Level B). No significant difference in effectiveness has been demonstrated between intravenous lorazepam and intravenous diazepam in adults or children with convulsive status epilepticus (Level A). Respiratory and cardiac symptoms are the most commonly encountered treatment-emergent adverse events associated with intravenous anticonvulsant drug administration in adults with convulsive status epilepticus (Level A). The rate of respiratory depression in patients with convulsive status epilepticus treated with benzodiazepines is lower than in patients with convulsive status epilepticus treated with placebo indicating that respiratory problems are an important consequence of untreated convulsive status epilepticus (Level A). When both are available, fosphenytoin is preferred over phenytoin based on tolerability but phenytoin is an acceptable alternative (Level A). In adults, compared to the first therapy, the second therapy is less effective while the third therapy is substantially less effective (Level A). In children, the second therapy appears less effective and there are no data about third therapy efficacy (Level C). The evidence was synthesized into a treatment algorithm. Despite the paucity of well-designed randomized controlled trials, practical conclusions and an integrated treatment algorithm for the treatment of convulsive status epilepticus across the age spectrum (infants through adults) can be constructed. Multicenter, multinational efforts are needed to design, conduct and analyze additional randomized controlled trials that can answer the many outstanding clinically relevant questions identified in this guideline.

Study on etiology and treatment of convulsive status epilepticus in children

The clinical data of 182 children with convulsive status epilepticus (CSE) were analyzed. There were 21 cases with refractory status epilepticus (RSE) and 161 cases with non-refractory status epilepticus (non-RSE). Etiological factors mainly included epilepsy in 54 cases, intracranial infection in 49 cases, and complex febrile seizure in 44 cases. In the ictal stage, 102 cases were treated with clonazepam by intravenous injection, 54 cases with diazepam by intravenous injection, 46 cases with midazolam by intravenous injection, 36 cases with phenobarbital by muscular injection, and 32 cases with 6.5% chloral hydrate by nosal feeding or clyster. The etiology of CSE in children is various. Epilepsy, intracranial infection and complex febrile seizure are the main causes. Poor prognosis and high mortality often occur in RSE caused by severe viral encephalitis. So the fundamental principle of treatment is to control CSE quickly and avoid the damage of brain and other important organs. DOI: 10.3969/j.issn.1672-6731.2015.11.009

Refractory Convulsive Status Epilepticus in Children: Etiology, Associated Risk Factors and Outcome.

Refractory status epilepticus (RSE) is a life-threatening disease in children wherein the patient's convulsive seizures do not respond to adequate initial anticonvulsants. RSE is associated with high rate of mortality and morbidity. This study was aimed to survey the risk factors leading status epilepticus (SE) to RSE in children, and their early outcome. Patients with SE hospitalized in Tabriz Children's Hospital, Iran were studied during the years 2007 and 2008 with regard to their clinical profile, etiology, the treatment methods available to them and their outcome upon release from the hospital. Among 132 patients with SE, 53 patients (40.15%) suffered from RSE. Acute symptomatic etiology was a risk factor responsible for developing RSE in the patient (P=0.004). Encephalitis was the most common etiology of acute symptomatic SE. There was no significant relationship observed between RSE and the patients' age, gender, date of initial drug intake and type of seizure. The mortality rate was 8.3% and a new neurological deficit occurred in 25.7% of cases. None of RSE with encephalitis returned to the baseline status. Mortality and morbidity rates were significantly higher in children with RSE than in those with SE (P=0.006). Etiology of SE significantly influenced prognosis of it with significant incidence of RSE in acute symptomatic group. Because acute neurological insult such as encephalitis and meningitis are common causes of RSE in children, properly management of them is necessary to avoid permanent brain damage.

Management of convulsive status epilepticus in children

Convulsive status epilepticus (CSE) is the commonest neurological emergency in children, and is potentially life-threatening. The main principles of management encompass good basic life support, terminating the seizure with suitable drugs, and identifying and treating the underlying cause. The outcome is dependent on the aetiology of CSE and the duration of seizure. National resuscitation guidelines in the United Kingdom now focus on the importance of rapid recognition and treatment of CSE, with appropriate escalation of care involving intensive care at an earlier stage. In recent years, use of other drugs are being explored in various centres as part of the acute management of CSE including sodium valproate, levetiracetam and lacosamide. This ongoing research will provide further fundamental evidence-based information in shaping future guidelines for the optimal management of CSE in children.

Short-term outcomes and major barriers in the management of convulsive status epilepticus in children: a study in Georgia.

Convulsive status epilepticus is the most common childhood neurological emergency in developing countries, where poor healthcare organisation could play a negative role in the management of the condition. Unavailability of second-line injectable anticonvulsants is an additional hindering factor in Georgia. This report reflects the results of the first study aimed at evaluating the epidemiological features of convulsive status epilepticus, as well as identifying obstacles influencing the management of patients with convulsive status epilepticus in Georgia. A prospective, hospital-based study was performed. Paediatric patients with convulsive status epilepticus, admitted to the emergency department of a referral academic hospital from 2007 to 2012, were included in the study. Forty-eight paediatric patients admitted to hospital met the criteria for convulsive status epilepticus. Seizure duration was significantly shorter among the group with adequate and timely pre-hospital intervention. Moreover, patients with appropriate pre-hospital treatment less frequently required mechanical ventilation (p=0.039). Four deaths were detected during the follow-up period, thus the case fatality rate was 8%. Only 31% of patients received treatment with intravenous phenytoin. The study results show that adequate and timely intervention could improve outcome of convulsive status epilepticus and decrease the need for mechanical ventilation. Mortality parameters were comparable to the results from other resource-limited countries. More than one third of patients did not receive appropriate treatment due to unavailability of phenytoin.

Comparison of intravenous lidocaine and midazolam infusion for refractory convulsive status epilepticus in children

Twenty children including nine boys and eleven girls with a mean age of 3.8 years (range: 0.1–;12 years) and admitted with a diagnosis of refractory convulsive status epilepticus constituted the study group. Ten children among them were treated with intravenous lidocaine (group 1) and other ten received midazolam infusion (group 2) for control of seizures. Variables such as age, sex, neuroimaging, electroencephalographic findings, concomitant fever, neurodevelopmental delay, complications, seizure control and length of stay (days) in the intensive care unit were carefully recorded. Two out of ten (20%) patients in group 1 responded while as five out of ten (50%) patients in group 2 responded ( P = 0.1). No paraclinical side effects occurred in any patients in both the groups. Two patients needed intubation in group 1 as against seven in group 2 ( P = 0.03). Mean length of stay in the intensive care unit was 4.6 days in group 1 and 9.2 days in group 2 ( P = 0.04). No significant differences were seen with regard to age, sex, electroencephalographic findings, neuroimaging abnormalities or neurodevelopmental delay between the two groups. In conclusion, lidocaine can be used in refractory status epilepticus treatment especially when respiratory care and intubation facilities are not present.

Treatment of Convulsive Status Epilepticus in Children: We Can Do Better

Effective anticonvulsant medications for the treatment of convulsive status epilepticus are available, but treatment delays result in longer seizure

Status epilepticus

Status epilepticus (SE) is a common pediatric neurologic emergency with an incidence of 10–38 per 100,000 children per year, associated with substantial morbidity and mortality.1 An operational definition of SE, sometimes called impending SE, occurs when a seizure or a series of seizures without intervening recovery of consciousness lasts 5–10 minutes. By the traditional definition, SE is not established until the duration reaches 30 minutes. Refractory SE occurs when an adequately dosed initial benzodiazepine and one other antiseizure medication have failed to stop the seizure.2 The overall short-term mortality of convulsive SE in children is notable at 3%–5%3 and is at least twice as high for refractory SE.4 Overall morbidity for convulsive SE in children is 10%–30% and over 50% for refractory SE.3 These data indicate that longer seizures result in worse outcomes.

Intravenous levetiracetam in Thai children and adolescents with status epilepticus and acute repetitive seizures.

Intravenous levetiracetam is an option for treatment of status epilepticus (SE) and acute repetitive seizures (ARS). However, there have been relatively few studies with children and adolescents. Also, an appropriate dosage has yet to be determined. This study investigated the safety and the efficacy of levetiracetam for intravenous treatment of convulsive status epilepticus and acute repetitive seizures in children and adolescents. Retrospectively, the study reviewed the medical records of 19 male and 31 female patients under 18 years of age who had received intravenous levetiracetam treatment either for acute repetitive seizures or for convulsive status epilepticus. The patients were admitted between April 1st, 2010 and December 31st, 2011 to the Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Data were collected on underlying illnesses, etiology of seizures, indication for levetiracetam therapy, initial dosage, rate of infusion, untoward effects during infusion and emerged complications. Efficacy of treatment was defined as the termination of seizure within 30 min of completing levetiracetam infusion and no seizure recurrence within 6 h of initial treatment. The age range of the 50 patients was from one day to 18 years (mean 79.6 months). The analysis included 52 episodes of 34 acute repetitive seizures (63.4%) and 18 convulsive status epilepticus (34.6%). Infusion rates ranged from 2 to 66 mg/kg/min (mean 29.6). Cessation of seizure was obtained in 59.6% of 52 episodes. Patients with underlying drug resistant epilepsy did not respond to levetiracetam therapy as well as patients with other etiology of seizures. There were no adverse drug reactions or untoward effects observed during the therapy. Intravenous administration of levetiracetam is safe and effective for treatment of acute repetitive seizures and convulsive status epilepticus in children and adolescents. Failure of treatment may be related to underlying drug resistant epilepsy. Further study of appropriate initial dosage and pharmacokinetic variations in the patients is needed as possible explanation of the unresponsiveness.

Complications during the management of pediatric refractory status epilepticus with benzodiazepine and pentobarbital infusions.

Sir, Patten et al. in their interesting study compared complications in the management of refractory status epilepticus (RSE) treated with benzodiazepine and pentobarbital infusions. The authors addressed that children with RSE, who required pentobarbital therapy had a longer hospital stay and were more likely develop hypotension, require inotropic support, need intubation, mechanical ventilation, peripheral nutrition, and blood products. Furthermore, they were more likely to develop hypertension and movement disorder after or during weaning.[1] I presume that these results ought to be cautiously taken owing to the presence of the following three limitations. (1) The data were taken from a single center. (2) The study period was relatively short (3 years). (3) The size of the studied cohort was small (n = 28). Conducting a large scale multicenter study over an extended period could better evaluate that the issue. Despite the aforementioned three limitations, the observation in Patten et al's. study[1] on more complications associated with pentobarbital infusion compared to benzodiazepine infusion renders pentobarbital less recommended first-line in treating patients with RSE. This observation supports the recently published Indian consensus guidelines on the management of childhood convulsive status epilepticus[2] and recommendations of the Italian League Against Epilepsy,[3] which stress that the initial management of RSE should consist of a parenteral benzodiazepine (lorazepam, diazepam, or midazolam) by any route feasible and when first-line anti-epileptic drugs fail, sodium phenytoin, and phenobarbital should be used. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Consensus guidelines on management of childhood convulsive status epilepticus.

Status epilepticus has a wide etiological spectrum, and significant morbidity and mortality. Management using a pre-determined uniform protocol leads to better outcomes. Multiple protocols for management of childhood status epilepticus are available, without much consensus. A 'Multi-disciplinary Consensus Development Workshop on Management of Status Epilepticus in Children in India' was organized. The invited experts included Pediatricians, Pediatric neurologists, Neurologists, Epileptologists, and Pediatric intensive care specialists from India, with experience in the relevant field. Experts had previously been divided into focus groups and had interacted on telephone and e-mail regarding their group recommendations, and developed consensus on the topic. During the meeting, each group presented their recommendations, which were deliberated upon by the house and a consensus was reached on various issues; the document was finalized after incorporating suggestions of experts on the draft document. To provide consensus guidelines on evaluation and management of convulsive status epilepticus in children in India (excluding neonatal and super-refractory status epilepticus). Each institution should use a pre-determined protocol for management of status epilepticus; pre-hospital management and early stabilization is the key to a satisfactory outcome of status epilepticus. Pharmacotherapy should not be delayed for any investigations; the initial management should consist of a parenteral benzodiazepine by any route feasible. Subsequent management has been detailed. The group also felt the need for more epidemiological research on status epilepticus from India, and identified certain research areas for the purpose.

Efficacy and safety of intramuscular midazolam versus rectal diazepam in controlling status epilepticus in children

ObjectiveThe aim of this study was to evaluate the efficacy and safety of intramuscular midazolam in controlling convulsive status epilepticus in children, by comparing it with rectal diazepam. MethodsIn this randomized trial, 100 children (50 in each group) with convulsive status epilepticus aged 1 month to 16 years were enrolled and randomly assigned into two groups to receive either 0.3 mg/kg intramuscular midazolam or 0.5 mg/kg rectal diazepam. Main outcome measure was stopping of all motor activity after drug administration. Another measures were times between patient's arrival to emergency department till drug administration, between drug administration to seizure cessation, and between patient's arrival to seizure cessation. ResultsBoth medication were effective for seizure control and no significant difference was found between successful treatments after administering the medication (P = 0.061). In the midazolam group, in 96% (48/50) of cases treatment was successful and in the diazepam group, in 94% (47/50) of cases treatment was successful. Time from arrival to administering the medication was significantly shorter in midazolam group (P = 0.017). The majority of seizures in midazolam group were stopped in less than 66 s (median) compared to 130 s (median) for diazepam group, (P < 0.001). No serious adverse effects were seen in both groups. ConclusionIM midazolam is not superior but may be at least as effective as rectal diazepam for controlling of status epilepticus in children. Midazolam via IM route could be one of the choices in children with convulsive status seizures who have difficult IV access.

Syndromes with very low risk of acute prolonged seizures.

The provision of rescue medication is an important component in the treatment of epilepsy. An intervention within five to ten minutes in the case of an acute prolonged seizure may preserve the patient from status epilepticus (SE). However, the risk of convulsive SE (CSE) differs markedly between patients depending on individual factors. This report summarizes the literature on risk factors for CSE in children with epilepsy and adolescents, and discusses the hypothesis that some electroclinical syndromes engender a very low risk of CSE. The most important risk factor for SE is the history of a previous event. The longer a patient lives without SE, the lower the risk will be. CSE occurs significantly less frequently in idiopathic epilepsies compared to epilepsies with symptomatic or unknown aetiology. It is very rarely observed in patients with (non-encephalopathic) idiopathic generalised epilepsies, i.e. childhood absence epilepsy or juvenile myoclonic epilepsy. However, non-compliance or inappropriate treatment may trigger CSE in these syndromes. A very low risk can be assumed for children with Rolandic epilepsy, while CSE occurs in a considerable percentage of patients with Panayiotopoulos syndrome. Although the risk of CSE in otherwise normal children with cryptogenic focal epilepsy is uncertain, it is presumably low under successful continuous medication. In conclusion, the choice for or against the prescription of rescue medication remains an individual decision. Consequently, for several electroclinical syndromes, a per se provision of rescue medication does not appear justified.

Electrographic seizures after status epilepticus

The percentage of children who demonstrate electrographic seizures after convulsive status epilepticus has been unknown. In this issue of The Journal, Sánchez Fernández et al from Boston Children's Hospital and Harvard Medical School report the results of a multicenter retrospective study of the clinical and electroencephalographic (EEG) features of 98 children (1 month to 21 years of age; median age 5 years) who underwent continuous EEG monitoring following clinical convulsive status epilepticus. Electrographic seizures were identified in 32 children (33%), and 11 had only electrographic seizures. Fifteen had electrographic status epilepticus. Recurrence of electrographic seizures after convulsive status epilepticus was associated with a diagnosis of epilepsy, and the presence of interictal epileptiform discharges. It was also noted that the children with electrographic seizures had longer stays in the pediatric intensive care unit. These results, therefore, fill a gap in the literature in showing that one-third of children demonstrate electrographic seizures following convulsive status epilepticus and one-third of those have electrographic-only seizures. The data identify risk factors for such seizures. Article page 339▶ Electrographic Seizures after Convulsive Status Epilepticus in Children and Young Adults: A Retrospective Multicenter StudyThe Journal of PediatricsVol. 164Issue 2PreviewTo describe the prevalence, characteristics, and predictors of electrographic seizures after convulsive status epilepticus (CSE). Full-Text PDF

Childhood convulsive status epilepticus may lead to progressive hippocampal volume loss

Childhood convulsive status epilepticus may lead to progressive hippocampal volume loss

Hippocampal volume loss following childhood convulsive status epilepticus is not limited to prolonged febrile seizures

PurposeChildhood convulsive status epilepticus (CSE), in particular prolonged febrile seizures (PFS), has been linked with mesial temporal sclerosis (MTS). Previous studies have shown that hippocampal injury occurs in the acute phase immediately following CSE, but little is known about the longer term evolution of such injury. This study aimed to investigate the longer term outcome of childhood CSE with sequential magnetic resonance imaging (MRI) looking for progressive hippocampal injury during the first year post-CSE.MethodsEighty children (0.18–15.5 years) underwent brain MRI 1 month post-CSE, 50 with a repeat MRI at 6 months and 46 with repeat MRI at 12 months post-CSE. Thirty-one control subjects without neurologic problems had a single brain MRI for comparison. Hippocampal volumes were measured from each MRI scan by two independent observers, and hippocampal growth rates were estimated in each patient with suitable imaging.Key FindingsHippocampal volume loss was found in 20–30% of patients and was not associated with the etiology or clinical features of CSE, including seizure duration or focality. A borderline association was found between a history of previous seizures (p = 0.063) and the number of previous febrile seizures (p = 0.051), suggesting that multiple insults may be important in the pathogenesis of progressive hippocampal injury.SignificanceIt is apparent that progressive hippocampal damage can occur after CSE of any etiology and is not limited to PFS. Repeated seizures may play an important role, but further follow-up is needed to determine any other risk factors and proportion of children showing initial volume loss progress to clinical MTS and temporal lobe epilepsy.

Electrographic Seizures after Convulsive Status Epilepticus in Children and Young Adults: A Retrospective Multicenter Study

To describe the prevalence, characteristics, and predictors of electrographic seizures after convulsive status epilepticus (CSE). This was a multicenter retrospective study in which we describe clinical and electroencephalographic (EEG) features of children (1 month to 21 years) with CSE who underwent continuous EEG monitoring. Ninety-eight children (53 males) with CSE (median age of 5 years) underwent subsequent continuous EEG monitoring after CSE. Electrographic seizures (with or without clinical correlate) were identified in 32 subjects (33%). Eleven subjects (34.4%) had electrographic-only seizures, 17 subjects (53.1%) had electroclinical seizures, and 4 subjects (12.5%) had an unknown clinical correlate. Of the 32 subjects with electrographic seizures, 15 subjects (46.9%) had electrographic status epilepticus. Factors associated with the occurrence of electrographic seizures after CSE were a previous diagnosis of epilepsy (P = .029) and the presence of interictal epileptiform discharges (P < .0005). The median (p25-p75) duration of stay in the pediatric intensive care unit was longer for children with electrographic seizures than for children without electrographic seizures (9.5 [3-22.5] vs 2 [2-5] days, Wilcoxon test, Z = 3.916, P = .0001). Four children (4.1%) died before leaving the hospital, and we could not identify a relationship between death and the presence or absence of electrographic seizures. After CSE, one-third of children who underwent EEG monitoring experienced electrographic seizures, and among these, one-third experienced entirely electrographic-only seizures. A previous diagnosis of epilepsy and the presence of interictal epileptiform discharges were risk factors for electrographic seizures.

Treatment of convulsive status epilepticus in childhood: Recommendations of the Italian League Against Epilepsy

The Italian League Against Epilepsy Commission Guidelines Subcommittee on Status Epilepticus (SE) has published an article on the management of SE in adults, and now presents a report on the management of convulsive status epilepticus (CSE) in children, excluding the neonatal period. Children's greater susceptibility than adults to epileptic seizures results from many factors. Earlier maturation of excitatory than inhibitory synapses, increased susceptibility and concentration of receptors for excitatory neurotransmitters, peculiar composition of the receptor subunits resulting in slower and less effective inhibitory responses, all cause the high incidence of SE in the pediatric population. The related morbidity and mortality rates, although lower than in adults, require immediate diagnosis and therapy. The division into focal and generalized, nonconvulsive and convulsive SE is applied in children and adolescents, as is the distinction in the three different stages according to the time elapsed since the start of the event and the response to drugs (initial, defined, and refractory SE). In children and adolescents, an "operational definition" is also accepted to allow earlier treatment (starting at 5-10 min). Maintenance and stabilization of vital functions, cessation of convulsions, diagnosis, and initial treatment of potentially "life-threatening" causes are the objectives to be pursued in the management of children with CSE. The need for early pharmacologic intervention stresses the need for action in the prehospital setting, generally using rectal diazepam. In hospital, parenteral benzodiazepines are used (lorazepam, diazepam, or midazolam). When first-line drugs fail, sodium phenytoin and phenobarbital should be used. As alternatives to phenobarbital, the following can be considered for treatment of refractory CSE: valproate, levetiracetam, and lacosamide. In cases with refractory CSE, pharmacologic options can be thiopental, midazolam, or propofol in continuous intravenous infusions to suppress electroencephalographic bursts and convulsive activity. These drugs need to be administered in intensive care units to ensure the monitoring and support of vital signs and brain electrical activity.

P48 – 1793 Treatment of convulsive status epilepticus in the UMCG: a retrospective, observational study

Objectives: Little is known about clinical practice with respect to the application of guidelines in the treatment of Convulsive Status Epilepticus (CSE). This retrospective, observational study evaluated treatment of episodes of CSE in children at the University Medical Centre Groningen (UMCG). Material and methods: Episodes of CSE were derived from the UMCG database of children with epilepsy aged 1 month. Treatments used in the UMCG were compared with recommendations from two most recent Dutch treatment guidelines for CSE in children aged >1 month. Results: 269 episodes of CSE occurring in 69 children (53.6% male, median age 4.3 years; range 0.1-16.3 years) were included; 219 (81.4%) of the episodes started outside the hospital, 118 (43.9%) had remote symptomatic aetiology, 96 (35.7%) were accompanied by fever. Half of the CSE episodes lasted