Intravenous Levetiracetam Research Articles

Intravenous levetiracetam versus phenytoin in the management of status epilepticus in adults: A systematic review of randomized-controlled trials

Intravenous levetiracetam versus phenytoin in the management of status epilepticus in adults: A systematic review of randomized-controlled trials

Efficacy and safety of levetiracetam in patients with epileptic seizures

Background: Levetiracetam (LEV) is an anti-epileptic drug (AED). Besides oral LEV, intravenous LEV was newly approved in Japan. Since serious adverse events are relatively few, the use of LEV has been increasing in emergency medicine.

Clinical usefulness of a low dosage of intravenous levetiracetam in various types and causes of status epilepticus: Retrospective study in a single center

Clinical usefulness of a low dosage of intravenous levetiracetam in various types and causes of status epilepticus: Retrospective study in a single center

Predictors of outcomes and refractoriness in status epilepticus: A prospective study

ObjectiveThe objective of this study was to determine the predictors of outcomes and refractoriness in status epilepticus (SE). MethodsThis is a prospective study of 59 adult patients with SE who were admitted to the Emergency Department between February 2012 and December 2013. The effects of clinical, demographic, and electrophysiologic features of patients with SE were evaluated. To evaluate outcome in SE, STESS, mSTESS, and EMSE scales were used. ResultsLogistic regression analysis showed that being aged ≥65years (p=0.02, OR: 17.68, 95% CI: [1.6–198.4]) for the short term and having potentially fatal etiology (p=0.027, OR: 11.7, 95% CI: [1.3–103]) for the long term were the only independent predictors of poor outcomes; whereas, the presence of periodic epileptiform discharges (PEDs) in EEG was the only independent predictor of refractoriness (p=0.032, OR: 13.7, 95% CI: [1.3–148.5]). The patients with ≥3 Status Epilepticus Severity Score (STESS) did not have poorer outcomes in the short- (p=0.157) and long term (p=0.065). There was no difference between patients with 0–2, 3–4, and ≥4 mSTESS in the short- and long term in terms of outcome (p=0.28 and 0.063, respectively). Also, there was no difference between subgroups (convulsive SE [CSE], nonconvulsive SE [NCSE], and epilepsia partialis continua [EPC]) in terms of STESS and mSTESS. When patients with EPC were excluded, both STESS and mSTESS scores of the patients correlated with poorer long-term outcomes (p=0.025 and 0.017, respectively). The patients with ≥64 points in the Epidemiology-based Mortality in SE-Etiology, age, comorbidity, EEG (EMSE-EACE) score and those with ≥27 points in EMSE-Etiology, age, comorbidity (EMSE-EAC) score did not have poorer outcomes in the short term (p=0.06 and 0.274, respectively) while they had significantly poorer outcome in the long term (p<0.001 and 0.002, respectively). In subgroup analysis, patients with CSE with ≥64 points in EMSE-EACE had significantly poorer outcome in the both short- and long term (p=0.014 and 0.012, respectively), and patients with CSE with ≥27 points in EMSE-EAC had significantly poorer outcome in the long term (p=0.03) but not in the short term (p=0.186). Outcomes did not correlate with EMSE scores in patients with NCSE and EPC. Status epilepticus was terminated with intravenous (IV) levetiracetam (LEV) in 68.75% of patients and with IV phenytoin (PHT) in 83.3% of patients. No statistically significant difference was found between the two groups in terms of efficacy (p=0.334). ConclusionBeing aged ≥65years predicts poor short-term outcomes, and having potentially fatal etiology predicts poor long-term outcomes, which highlight the importance of SE treatment management in the elderly. Both STESS and mSTESS are not predictive for poor outcomes in EPC. Excluding patients with EPC, STESS, and mSTESS could predict poor long-term outcomes but not in the short term in SE. Epidemiology-based Mortality in Status Epilepticus score could predict poor outcome in the long term better than STESS and mSTESS. Specifically, EMSE scores correlated with poor outcome in patients with CSE but not with NCSE and EPC. New scales are needed to predict outcome especially in patients with NCSE and EPC. The presence of PEDs in EEG is a predictor of RSE, and EMSE score can also be used to predict RSE. There was no difference in the efficacy of IV LEV and IV PHT in SE. This study is significant for having one of the longest follow-up periods in the literature.

A multicentre randomised controlled trial of levetiracetam versus phenytoin for convulsive status epilepticus in children (protocol): Convulsive Status Epilepticus Paediatric Trial (ConSEPT) - a PREDICT study

BackgroundConvulsive status epilepticus (CSE) is the most common life-threatening childhood neurological emergency. Despite this, there is a lack of high quality evidence supporting medication use after first line benzodiazepines, with current treatment protocols based solely on non-experimental evidence and expert opinion. The current standard of care, phenytoin, is only 60% effective, and associated with considerable adverse effects. A newer anti-convulsant, levetiracetam, can be given faster, is potentially more efficacious, with a more tolerable side effect profile. The primary aim of the study presented in this protocol is to determine whether intravenous (IV) levetiracetam or IV phenytoin is the better second line treatment for the emergency management of CSE in children.Methods/Design200 children aged between 3 months and 16 years presenting to 13 emergency departments in Australia and New Zealand with CSE, that has failed to stop with first line benzodiazepines, will be enrolled into this multicentre open randomised controlled trial. Participants will be randomised to 40 mg/kg IV levetiracetam infusion over 5 min or 20 mg/kg IV phenytoin infusion over 20 min. The primary outcome for the study is clinical cessation of seizure activity five minutes following the completion of the infusion of the study medication. Blinded confirmation of the primary outcome will occur with the primary outcome assessment being video recorded and assessed by a primary outcome assessment team blinded to treatment allocation. Secondary outcomes include: Clinical cessation of seizure activity at two hours; Time to clinical seizure cessation; Need for rapid sequence induction; Intensive care unit (ICU) admission; Serious adverse events; Length of Hospital/ICU stay; Health care costs; Seizure status/death at one-month post discharge.DiscussionThis paper presents the background, rationale, and design for a randomised controlled trial comparing levetiracetam to phenytoin in children presenting with CSE in whom benzodiazepines have failed. This study will provide the first high quality evidence for management of paediatric CSE post first-line benzodiazepines.Trial registrationProspectively registered with the Australian and New Zealand Clinical Trial Registry (ANZCTR): ACTRN12615000129583 (11/2/2015). UTN U1111–1144-5272. ConSEPT protocol version 4 (12/12/2014).

Emergency treatment with levetiracetam or phenytoin in status epilepticus in children\u2014the EcLiPSE study: study protocol for a randomised controlled trial

BackgroundConvulsive status epilepticus (CSE) is the most common life-threatening neurological emergency in childhood. These children are also at risk of significant morbidity, with acute and chronic impact on the family and the health and social care systems. The current recommended first-choice, second-line treatment in children aged 6 months and above is intravenous phenytoin (fosphenytoin in the USA), although there is a lack of evidence for its use and it is associated with significant side effects. Emerging evidence suggests that intravenous levetiracetam may be effective as a second-line agent for CSE, and fewer adverse effects have been described. This trial therefore aims to determine whether intravenous phenytoin or levetiracetam is more effective, and safer, in treating childhood CSE.Methods/designThis is a phase IV, multi-centre, parallel group, randomised controlled, open-label trial. Following treatment for CSE with first-line treatment, children with ongoing seizures are randomised to receive either phenytoin (20 mg/kg, maximum 2 g) or levetiracetam (40 mg/kg, maximum 2.5 g) intravenously. The primary outcome measure is the cessation of all visible signs of CSE as determined by the treating clinician. Secondary outcome measures include the need for further anti-seizure medications or rapid sequence induction for ongoing CSE, admission to critical care areas, and serious adverse reactions. Patients are recruited without prior consent, with deferred consent sought at an appropriate time for the family. The primary analysis will be by intention-to-treat. The primary outcome is a time to event outcome and a sample size of 140 participants in each group will have 80% power to detect an increase in CSE cessation rates from 60% to 75%. Our total sample size of 308 randomised and treated participants will allow for 10% loss to follow-up.DiscussionThis clinical trial will determine whether phenytoin or levetiracetam is more effective as an intravenous second-line agent for CSE, and provide evidence for management recommendations. In addition, this trial will also provide data on which of these therapies is safer in this setting.Trial registrationISRCTN identifier, ISRCTN22567894. Registered on 27 August 2015EudraCT identifier, 2014-002188-13. Registered on 21 May 2014NIHR HTA Grant: 12/127/134

Disposition of levetiracetam in healthy adult horses.

Nine horses received 20mg/kg of intravenous (LEVIV ); 30mg/kg of intragastric, crushed immediate release (LEVCIR ); and 30mg/kg of intragastric, crushed extended release (LEVCER ) levetiracetam, in a three-way randomized crossover design. Crushed tablets were dissolved in water and administered by nasogastric tube. Serum samples were collected over 48hr, and levetiracetam concentrations were determined by immunoassay. Mean±SD peak concentrations for LEVCIR and LEVCER were 50.72±10.60 and 53.58±15.94μg/ml, respectively. The y-intercept for IV administration was 64.54±24.99μg/ml. The terminal half-life was 6.38±1.97, 7.07±1.93 and 6.22±1.35hr for LEVCIR , LEVCER, and LEVIV , respectively. Volume of distribution at steady-state was 630±73.4ml/kg. Total body clearance after IV administration was 74.40±19.20mlkg-1 hr-1 . Bioavailability was 96±10, and 98±13% for LEVCIR and LEVCER , respectively. A single dose of Levetiracetam (LEV) was well tolerated. Based on this study, a recommended dosing regimen of intravenous or oral LEV of 32mg/kg every 12hr is likely to achieve and maintain plasma concentrations within the therapeutic range suggested for humans, with optimal kinetics throughout the dosing interval in healthy adult horses. Repeated dosing and pharmacodynamic studies are warranted.

Intravenous levetiracetam vs phenytoin for status epilepticus and cluster seizures: A prospective, randomized study

PurposeStatus Epilepticus (SE) is a common medical emergency carrying a high morbidity and mortality. Levetiracetam (LEV) is a novel anticonvulsant effective against varied seizures. Few prospective studies have addressed its use in SE. We aimed to examine the efficacy of intravenous LEV in controlling SE and cluster attacks of seizures (CS), in comparison with IV phenytoin (DPH), using a prospective, randomized study design. MethodAdult patients with SE or CS, following an initial dose of IV benzodiazepine to control ongoing seizure, were randomized to receive either medication. Rates of seizure control over 24h, adverse effects and outcomes were compared. A logistic regression model was used to identify outcome predictors. Results52 patients with SE and 63 with CS received either LEV or DPH. In the SE group, LEV was effective in18/22(82%) and DPH in 22/30(73.3%) patients in controlling seizures. Among patients with CS, LEV was effective in 31/38(81.6%) and DPH in 20/25(80%). With the use of LEV, DPH or both, SE and CS were controlled among 92% and 96% of patients respectively. Adverse events included hypotension (in 2 on DPH) and transient agitation (2 on LEV). ConclusionsIV Levetiracetam controls status epilepticus or cluster seizures with an efficacy comparable to that of phenytoin. Use of these two agents consecutively may control >90% of all such conditions without resort to anaesthetic agents. Further studies should explore its efficacy in larger cohorts of epileptic emergencies.

Levetiracetam Versus Phenytoin for Seizure Prophylaxis Following Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Seizure following traumatic brain injury (TBI) constitutes a common complication that requires effective prevention to improve the outcome of TBI. Phenytoin has been the only recommended antiepileptic drug (AED) for seizure prophylaxis; however, several shortcomings have affected its use. Intravenous levetiracetam has been available since 2006 and has been increasingly accepted as a seizure prophylaxis for brain injury, mainly due to its favorable pharmacokinetic features and minimal adverse events profile. However, the efficacy and safety of levetiracetam versus phenytoin for seizure prophylaxis following TBI are not well clarified. The aim of this study was to assess the efficacy and safety of levetiracetam versus phenytoin for seizure prophylaxis following TBI. We conducted a search of the MEDLINE, EMBASE, and Cochrane library databases to March 2016, and screened original research that included patients with TBI who received levetiracetam. We included randomized controlled trials (RCTs) or controlled observational cohort studies that compared levetiracetam and phenytoin, as well as uncontrolled case series regarding prophylactic levetiracetam following TBI. The outcomes included early or late seizure prophylaxis and safety. The estimates of seizure prophylaxis were pooled using a meta-analysis, and the estimates for the case series were pooled using descriptive statistics. A total of 1614 patients from 11 studies were included in this review, of whom 1285 patients from eight controlled studies (one RCT and seven cohort studies) were included in the meta-analysis. Levetiracetam was not superior to phenytoin with regard to early seizure prophylaxis (risk ratio [RR] 1.10, 95% confidence interval [CI] 0.64-1.88); the estimate of early seizure incidence was 0.05 (95% CI 0.02-0.08). Three studies that assessed late seizure did not indicate the superiority of levetiracetam to phenytoin. There were no differences in mortality during hospitalization or after 6months, or in the number of patients with adverse reactions between levetiracetam and phenytoin. Levetiracetam does not appear to be superior to phenytoin in efficacy or safety with regard to early or late seizure prophylaxis following TBI; however, no class I evidence was identified. Additional evidence from high-quality studies is required.

Levetiracetam Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

Levetiracetam (LEV) is an antiepileptic agent targeting novel pathways. Coupled with a favorable safety profile and increasing empirical clinical use, it was the fifth drug tested by Operation Brain Trauma Therapy (OBTT). We assessed the efficacy of a single 15 min post-injury intravenous (IV) dose (54 or 170 mg/kg) on behavioral, histopathological, and biomarker outcomes after parasagittal fluid percussion brain injury (FPI), controlled cortical impact (CCI), and penetrating ballistic-like brain injury (PBBI) in rats. In FPI, there was no benefit on motor function, but on Morris water maze (MWM), both doses improved latencies and path lengths versus vehicle (p < 0.05). On probe trial, the vehicle group was impaired versus sham, but both LEV treated groups did not differ versus sham, and the 54 mg/kg group was improved versus vehicle (p < 0.05). No histological benefit was seen. In CCI, there was a benefit on beam balance at 170 mg/kg (p < 0.05 vs. vehicle). On MWM, the 54 mg/kg dose was improved and not different from sham. Probe trial did not differ between groups for either dose. There was a reduction in hemispheric tissue loss (p < 0.05 vs. vehicle) with 170 mg/kg. In PBBI, there was no motor, cognitive, or histological benefit from either dose. Regarding biomarkers, in CCI, 24 h glial fibrillary acidic protein (GFAP) blood levels were lower in the 170 mg/kg group versus vehicle (p < 0.05). In PBBI, GFAP blood levels were increased in vehicle and 170 mg/kg groups versus sham (p < 0.05) but not in the 54 mg/kg group. No treatment effects were seen for ubiquitin C-terminal hydrolase-L1 across models. Early single IV LEV produced multiple benefits in CCI and FPI and reduced GFAP levels in PBBI. LEV achieved 10 points at each dose, is the most promising drug tested thus far by OBTT, and the only drug to improve cognitive outcome in any model. LEV has been advanced to testing in the micropig model in OBTT.

Safe use of perampanel in a carrier of variegate porphyria

Acute symptomatic seizures occur in 10–20% of patients with acute intermittent porphyria in relapse. There are rarer reports of porphyria in people with chronic epilepsy who are mostly drug resistant....

Intravenous levetiracetam in critically ill children.

Background:To report the effectiveness and safety of intravenous (IV) levetiracetam (LEV) in the treatment of critically ill children with acute repetitive seizures and status epilepticus (SE) in a children's hospital.Materials and Methods:We retrospectively analyzed data from children treated with IV LEV.Results:The mean age of the 108 children was 69.39 ± 46.14 months (1-192 months). There were 58 (53.1%) males and 50 (46.8%) females. LEV load dose was 28.33 ± 4.60 mg/kg/dose (10-40 mg/kg). Out of these 108 patients, LEV terminated seizures in 79 (73.1%). No serious adverse effects were observed but agitation and aggression were developed in two patients, and mild erythematous rash and urticaria developed in one patient.Conclusion:Antiepileptic treatment of critically ill children with IV LEV seems to be effective and safe. Further study is needed to elucidate the role of IV LEV in critically ill children.

Intravenous levetiracetam versus phenobarbital in children with status epilepticus or acute repetitive seizures.

PurposeThis study compared the efficacy and tolerability of intravenous (i.v.) phenobarbital (PHB) and i.v. levetiracetam (LEV) in children with status epilepticus (SE) or acute repetitive seizure (ARS).MethodsThe medical records of children (age range, 1 month to 15 years) treated with i.v. PHB or LEV for SE or ARS at our single tertiary center were retrospectively reviewed. Seizure termination was defined as seizure cessation within 30 minutes of infusion completion and no recurrence within 24 hours. Information on the demographic variables, electroencephalography and magnetic resonance imaging findings, previous antiepileptic medications, and adverse events after drug infusion was obtained.ResultsThe records of 88 patients with SE or ARS (median age, 18 months; 50 treated with PHB and 38 with LEV) were reviewed. The median initial dose of i.v. PHB was 20 mg/kg (range, 10–20 mg/kg) and that of i.v. LEV was 30 mg/kg (range, 20–30 mg/kg). Seizure termination occurred in 57.9% of patients treated with i.v. LEV (22 of 38) and 74.0% treated with i.v. PHB (37 of 50) (P=0.111). The factor associated with seizure termination was the type of event (SE vs. ARS) in each group. Adverse effects were reported in 13.2% of patients treated with i.v. LEV (5 of 38; n=4, aggressive behavior and n=1, vomiting), and 28.0% of patients treated with i.v. PHB (14 of 50).ConclusionIntravenous LEV was efficacious and safe in children with ARS or SE. Further evaluation is needed to determine the most effective and best-tolerated loading dose of i.v. LEV.

Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial

Generalised convulsive status epilepticus (GCSE) should be treated quickly. Benzodiazepines are the only drug treatment available so far that is effective before admission to hospital. We assessed whether addition of the antiepileptic drug levetiracetam to the benzodiazepine clonazepam would improve prehospital treatment of GCSE. We did a prehospital, randomised, double-blind, phase 3, placebo-controlled, superiority trial to determine the efficacy of adding intravenous levetiracetam (2.5 g) to clonazepam (1 mg) in treatment of GCSE in 13 emergency medical service centres and 26 hospital departments in France. Randomisation was done at the Paris Descartes Clinical Research Unit with a list of random numbers generated by computer. Adults with convulsions lasting longer than 5 min were randomly assigned (1:1) by prehospital physicians to receive levetiracetam or placebo in combination with clonazepam. All physicians and paramedics were masked to group assignments. If the status epilepticus lasted beyond 5 min after drug injection, a second dose of 1 mg clonazepam was given. The primary outcome was cessation of convulsions within 15 min of drug injection. We analysed the modified intention-to-treat population that had received at least one injection of clonazepam and levetiracetam or placebo, excluding patients without valid consent and those randomised more than once. The trial is registered at EudraCT, number 2007-005782-35. Between July 20, 2009, and Dec 15, 2012, 107 patients were randomly assigned to receive placebo and 96 were assigned to receive levetiracetam. The trial was discontinued on Dec 15, 2012 when interim analysis showed no evidence of a treatment difference, and 68 patients in each group were included in the modified intention-to-treat analysis. Convulsions stopped at 15 min of drug injection in 57 of 68 patients (84%) receiving clonazepam and placebo and in 50 of 68 patients (74%) receiving clonazepam and levetiracetam (percentage difference -10.3%, 95% CI -24.0 to 3.4). Three deaths, 19 of 47 (40 %) serious adverse events, and 90 of 197 (46%) non-serious events were reported in the levetiracetam group, and four deaths, 28 of 47 (60%) serious events, and 107 of 197 (54%) non-serious events were reported in the placebo group. The addition of levetiracetam to clonazepam treatment presented no advantage over clonazepam treatment alone in the control of GCSE before admission to hospital. Future prehospital trials could assess the efficacy of clonazepam alone as a first-line treatment in status epilepticus and the efficacy of a second injection of clonazepam with another antiepileptic drug as second-line treatment. UCB Pharma.

Levetiracetam in the Treatment of Epileptic Seizures After Liver Transplantation.

After liver transplantation, patients may develop seizures or epilepsy due to a variety of etiologies. The ideal antiepileptic drugs for these patients are those with fewer drug interactions and less hepatic toxicity. In this study, we present patients using levetiracetam to control seizures after liver transplantation.We retrospectively enrolled patients who received levetiracetam for seizure control after liver transplantation. We analyzed the etiology of liver failure that required liver transplantation, etiology of the seizures, outcomes of seizure control, and the condition of the patient after follow-up at the outpatient department. Hematological and biochemical data before and after the use of levetiracetam were also collected.Fifteen patients who received intravenous or oral levetiracetam monotherapy for seizure control after liver transplantation were enrolled into this study. All of the patients remained seizure-free during levetiracetam treatment. Two patients died during the follow-up, and the other 13 patients were alive at the end of the study period and all were seizure-free without neurological sequelae that interfered with their daily activities. No patients experienced liver failure or rejection of the donor liver due to ineffective immunosuppressant medications. The dosage of immunosuppressants did not change before and after levetiracetam treatment, and there were no changes in hematological and biochemical data before and after treatment.Levetiracetam may be a suitable antiepileptic drug for patients who undergo liver transplantation due to fewer drug interactions and a favorable safety profile.

Levetiracetam versus phenytoin in management of status epilepticus

The purpose of this study was to compare safety and efficacy of intravenous (IV) levetiracetam (LEV) with IV phenytoin (PHT) in management of status epilepticus (SE). The second-line treatment of SE is limited to a few drugs available in an IV formulation such as PHT, fosphenytoin and valproate. The relative lack of serious side effects and favourable pharmacokinetics of LEV made it a promising option in management of SE. Randomized trials comparing relative efficacy of second-line agents are remarkably lacking. In this study, consecutive patients of SE (n=44) were randomized to receive either IV PHT (20mg/kg) or IV LEV (20mg/kg). The primary end point was successful clinical termination of seizure activity within 30min after the beginning of the drug infusion. Secondary end points included recurrence of seizures within 24hours, drug related adverse effects, neurological outcome at discharge, need for ventilatory assistance, and mortality during hospitalization. Both LEV and PHT were equally effective with regard to primary and secondary outcome measures. PHT achieved control of SE in 15 (68.2%) patients compared to LEV in 13 (59.1%; p=0.53). Both the groups showed comparable results with respect to recurrence of seizures within 24hours (p=0.34), outcome at discharge as assessed by functional independence measure (p=0.68), need of ventilatory assistance (p=0.47) and death (p=1). From this study it can be concluded that LEV may be an attractive and effective alternative to PHT in management of SE.

Intravenous levetiracetam treatment in status epilepticus: A prospective study

To assess the efficacy of intravenous (IV) levetiracetam (LEV) in the treatment of status epilepticus (SE) and treatment outcomes. This study was conducted on patients, who were classified according to the clinical characteristics of their seizures, in the emergency department, neurology, and other services of our hospital. Patients were administrated IV LEV for the treatment of their SE after failing to respond to IV diazepam. We prospectively investigated 30 patients, 16 females and 14 males whose ages ranged between 17 and 90 years (55.6 ± 19.6). Fourteen patients had convulsive SE (CSE), 11 had nonconvulsive SE (NCSE), and 5 had epilepsia partialis continua (EPC). The patients were given IV LEV with dosages ranging between 1000 and 4000 mg/day. Twenty-nine of the patients continued to receive LEV orally as maintenance treatment. The most common etiologies were cerebrovascular diseases (n = 7) and brain tumors (n = 6). SE was terminated in 23 (76.6%) patients. In the 12 months that followed SE, 9 of our patients (30%) died and 4 patients could not be contacted. Fifteen patients reported having no adverse effects, whereas three had mild adverse effects. No major adverse effects or complications causing disability were observed in twelve patients who were unconscious. Treatment with IV LEV is well-tolerated and effective both in focal and generalized SE. IV LEV has the combined advantage of efficacy, safety, and ease of use, which qualifies it to be the first choice after benzodiazepines (BZD) in the treatment of SE. This is the first prospective study of IV LEV treatment in status epilepticus and has the longest follow-up period, one year.

Intravenous levetiracetam in clinical practice – Results from an independent registry

PurposeMost common clinical studies with antiepileptic drugs do not reflect medical everyday practice due to their strict in- and exclusion criteria and specifications of treatment regimens. Here we present a large non-interventional registry with the intention to evaluate the spectrum of applications in daily use and the efficacy and tolerability of intravenously given levetiracetam (LEV-iv). MethodsIn a prospective approach of 17 neurological and neuropediatric centres in Germany LEV-iv treated patients of all ages were included over a period of 10 months. The observational period was 10 days with daily documentation of LEV-iv administration, type and frequency of seizures, currently used drugs and doses, and adverse events (AEs). In addition, treatment efficacy and tolerability were assessed by patients and physicians at study end as well as practicability of LEV-iv using a five-step scale. ResultsIn 95 patients LEV-iv was administered, 93 were included into the analysis. The median LEV-iv dose was 1500mg (range 110–6000mg) per day. Median age was 66 years (range 0.7–90.3 years). The majority of patients (n=70, 75%) suffered from status epilepticus (SE, n=55, 59%) and acute seizure clusters (n=15, 16%). Of those with SE, 41 patients (75%) had SE for the first time. Acute seizure clusters and SE terminated in 83% after LEV-iv administration. A total of 29 adverse events were reported in 17 of the 95 patients from the safety set. Ten of these were at least possibly related to LEV-iv treatment. Slight decrease of blood pressure during the infusion (3 patients each) was captured most frequently. No serious side effect was observed. Physicians rated the efficacy and tolerability of LEV-iv treatment as good or very good in 78% and 82% of the cases, respectively. ConclusionIn this large observational study of everyday practise the use of LEV-iv exhibited a remarkable good response and tolerability in patients with acute onset seizures (mostly SE). Further randomized controlled studies, like the established status epilepticus trial (ESET) are needed to confirm these findings.

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.

Cases of non-standard approach to treatment of super-refractory status epilepticus

Authors assume that super-refractoriness is probably characterized by the specific pathophysiological mechanisms of status epilepticus development and can't be treated using standard treatment schemes. By the example of two clinical cases, we have analyzed the efficacy of complex treatment of super-refractory nonconvulsive and myoclonic status using intravenous valproate, central anesthetics (thiopental sodium, propofol), levetiracetam and cortexin. Preliminary results suggest that cortexin and levetiracetam as add-on to standard treatment may be vitally important drugs for the patients.