Levetiracetam Group Research Articles

Effects of levetiracetam and valproic acid treatment on liver function tests, plasma free carnitine and lipid peroxidation in childhood epilepsies

Background and aimsThe relationship between anti-epileptic usage and oxidative damage has not yet been clearly understood. In our study, we investigated oxidative stress parameters, carnitine levels, liver function tests (LFT) and their relationship in epileptic children treated with valproic acid or levetiracetam. MethodLFTs, serum free carnitine and oxidative damage markers and their relations with each other were determined in patients who are on valproic acid or levetiracetam treatment at least for 6 months. 25 patients on therapeutic doses of valproic acid, 26 patients on therapeutic doses of levetiracetam and 26 healthy volunteers as controls were included. LFTs, ammonia, carnitine, lipid peroxidation biomarker malondialdehyde (MDA) and a sensitive marker of DNA damage, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were measured. Results of patients are compared to healthy controls. The data is evaluated with IBM SPSS Statistics 22.0. ResultsAmmonia and MDA levels were elevated in patients using levetiracetam; 8-OHdG levels were elevated in both patient groups. Carnitine levels were significantly low in patients under valproic acid therapy, however they were not found to be correlated with MDA, 8-OHdG or LFTs. MDA showed positive correlation with ammonia and 8-OHdG in the levetiracetam group. ConclusionWe did not observe hepatotoxicity in patients under therapeutic doses of valproic acid. However, epileptic children under therapeutic doses of levetiracetam showed significantly elevated levels of MDA and 8-OHdG, which is supportive for oxidative damage under levetiracetam therapy. This result was observed for the first time in childhood epilepsies and further studies are needed to understand its mechanism.

Comparison between flunarizine and levetiracetam in paediatric migraine prophylaxis

Background: Migraine hampers child's life through school absence, limitation of home and social activities. The goal of prophylactic (preventive) therapy is to reduce headache frequency, headache days, and headache severity with minimum side effects.
 Objective: To evaluate the efficacy and tolerability of levetiracetam compared to flunarizine as prophylactic treatment of Migraine in children. Methods: This prospective study was carried out in the outpatient department of a tertiary care hospital in Bangladesh. A total of 105 children aged 6-15 years, diagnosed as migraine without aura, were enrolled. Patients were treated with flunarizine or levetiracetam for three months. Headache disabilities were evaluated at baseline and at the end of three months.
 Results: In flunarizine group, 54 children and in levetiracetam group, 51 children were enrolled. Among them thirty nine children in flunarizine group and 36 children in levetiracetam group completed the study. Headache frequency, headache days, VAS (Visual Analogue Scale) score and PedMIDAS (Paediatric Migraine Disability Assessment Score) score were evaluated at baseline and during the follow up. After three months, headache frequency, headache days, pain severity (Visual Analogue Scale score) reduced significantly compared to baseline (p<0.05). PedMIDAS score was also reduced from 60.35(±16.36) to 30.13(±14.28) in flunarizine group and from 64.25(±19.63) to 25.91(±18.6) in levetiracetam group (p<0.05). Some minor side effects were also reported by both groups, but were well tolerated by the patients and need not withdrawal of medication.
 Conclusion: Levetiracetam is as effective as flunarizine in paediatric Migraine Prophylaxis.
 Bang Med J (Khulna) 2018; 51 : 35-39

Levetiracetam versus phenytoin for treatment of convulsive status epilepticus in pediatric population: a randomized controlled trial

Background: Status epilepticus is a major medical and neurological emergency. Despite advances in treatment, it is still associated with significant morbidity and mortality. The objective of the study was to compare the efficacy of levetiracetam versus phenytoin in treatment of convulsive status epilepticus.Methods: A Randomized control trial, was conducted at tertiary care hospital, Udaipur, Rajasthan, over a period of March 2017 to September 2018. Total 250 patients (age group 6 months to 18 years) who were presented with status epilepticus in PICU, were enrolled. These patients were divided into two groups by simple randomization. Levetiracetam was given to one group, while phenytoin was given to another group. Efficacy was decided by cessation of clinical seizure activity within 30 minutes of starting of drug infusion and patient was observed for recurrence of seizure within 24 hours.Results: A total of 250 patients were enrolled in this study. Seizure terminated in 107 patients in phenytoin group (85.6%) and in 114 patients in levetiracetam group (91.2%). The difference was significant. Recurrence of seizure (with in 24 hour) was high in phenytoin group (14.4%) in comparison with levetiracetam group (8.8%). Most common adverse effect in both the groups on treatment was hypotension, though in phenytoin group it was significantly higher than patients on levetiracetam group (7.2% v/v 2.4%).Conclusions: Levetiracetam may be an effective alternative to phenytoin as a second line drug in the management of benzodiazepine resistant convulsive status epilepticus in children.

Levetiracetam administration is correlated with lower mortality in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes: a retrospective study.

Background:Studies on the relationship between antiepileptic drug (AED) administration and clinical outcomes in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) remain scarce. Levetiracetam (LEV) is an AED that is neuroprotective in various neurologic disorders. This study aimed to determine the impact of LEV on the outcome of MELAS.Methods:A retrospective, single-center study was performed based on a large cohort of patients with MELAS with a history of seizures (n = 102). Decisions on antiepileptic therapies were made empirically. Patients were followed up for 1 to 8 years (median, 4 years) and divided into 2 groups based on whether LEV was administered (LEV or non-LEV). The modified Rankin scale (mRS) scores and mortality risks were analyzed in all patients.Results:LEV, carbamazepine, benzodiazepines, topiramate, oxcarbazepine, valproate, and lamotrigine were administered in 48, 37, 18, 13, 11, 9, and 9 patients, singly or in combination, respectively. The mean mRS score of the LEV group (n = 48) was lower than that of the non-LEV group (n = 54; mean ± standard deviation, 2.79 ± 1.47 vs. 3.83 ± 1.93, P = 0.006) up to the end of the study. Nevertheless, there was no difference in the proportion of subjects without disability (mRS ranging 0–1) between the groups (P = 0.37). The multivariate regressions revealed that LEV treatment was associated with lower mRS scores (odds ratio 0.32, 95% confidence interval [CI] 0.15–0.68, P = 0.003) and mortality rates (hazard ratio 0.24, 95% CI 0.08–0.74, P = 0.013). There was a significant difference in the Kaplan-Meier survival curves between the groups (χ2 = 4.29, P = 0.04).Conclusions:The LEV administration is associated with lower mortality in patients with MELAS in this retrospective study. Further laboratory research and prospective cohort studies are needed to confirm whether LEV has neuroprotective effects on patients with mitochondrial diseases.

Comparing the efficacy of sodium valproate and levetiracetam following initial lorazepam in elderly patients with generalized convulsive status epilepticus (GCSE): A prospective randomized controlled pilot study

Purpose: This randomized control study was conducted to compare the efficacy of sodium valproate (SVP) and levetiracetam (LEV) following initial intravenous lorazepam in elderly patients (age: >60years) with generalized convulsive status epilepticus (GCSE) and to identify predictors of poor seizure control.Methods: A total of 118 patients (mean age: 67.5 ± 7.5 years, M:F = 1.6:1), who had presented with GCSE were randomized into the SVP or LEV treatment arms. All patients received initial intravenous lorazepam (0.1 mg/kg) followed by one of the two antiepileptic drugs (AEDs), parenteral SVP (20–25 mg/kg) or LEV (20–25 mg/kg). Those who failed to achieve control with the initial AED, were crossed over to receive the other AED. One-hundred patients (SVP = 50; LEV = 50) completed the study.Results: SE could be controlled with lorazepam and one of the AEDs (SVP or LEV) in 71.18% (84/118). Intention-to-treat analysis showed that the two groups did not differ significantly in terms of seizure control [SVP: 41/60 (68.3%); LEV: 43/58 (74.1%), p = 0.486]. Of 100 patients who completed the study, seizure control was achieved in 38/50(76%) in the SVP and 43/50(86%) in the LEV group (p = 0.202). After crossing over to the second AED, SE could be controlled in an additional in 50% (6/12) in SVP (+LEV) group and in 14.3% (1/7) in LEV (+SVP) group. Overall, after the second AED, seizure control was achieved in 77.1% (91/118). Higher STESS was associated with poor therapeutic response (p = 0.049).Conclusions: The efficacy of SVP and LEV following initial lorazepam in controlling GCSE in elderly population was comparable, hence the choice of AED could be individualized.

Cognitive, behavioural and sleep-related adverse effects on introduction of levetiracetam versus oxcarbazepine for epilepsy

ObjectiveThere is limited literature on cognitive, behaviour and sleep-related adverse effects of levetiracetam and oxcarbazepine among adult epilepsy patients, except for what is available from the initial efficacy trials. This study was initiated with the aim to evaluate the incidence and prevalence of various cognitive, behaviour and sleep-related adverse effects of levetiracetam versus oxcarbazepine among people with epilepsy. MethodsThe study was conducted in two parts: part A was a cross-sectional study, and part B was a longitudinal study. Trail making test A & B, digit symbol substitution test, Stroop colour and word test, controlled oral word association test and PGI memory scale, Neuropsychiatric Inventory, sleep log and ESS-I were used for assessment of cognitive, behaviour and sleep-related adverse effects. ResultsIn the cross-sectional as well as prospective study, no significant difference was observed in the cognitive performance of patients in levetiracetam and oxcarbazepine group in any of the cognitive assessment. Among 120 patients enrolled in the cross-sectional study, significantly higher number of patients in the levetiracetam group compared to the oxcarbazepine group,had agitation/aggression (20% vs10%, p = 0.047) and irritability (26.7% vs 3.3%, p = 0.007).Among 132 patients enrolled in the prospective study, significantly higher increase in the domain score of agitation/aggression (14.5% vs 1.6%, p = 0.028) and irritability (17.7% vs 1.6%, p = 0.018) was observed in the levetiracetam group compared to oxcarbazepine group. A significantly higher proportion of patients in the oxcarbazepine group had hypersomnolence (11.3% vs 1.6%, p = 0.026), as compared to the levetiracetam group. SignificanceOn cross-sectional as well as on longitudinal assessment, nearly one-fifth of patients on levetiracetam have behaviour related adverse effects, with dose modification required for half among these. Nearly 11% of patients on oxcarbazepine reported sleep-related adverse effects (higher total sleep duration per 24 h).

Clinical Efficacy and Safety of Injectable Levetiracetam Versus Phenytoin as Second-Line Therapy in the Management of Generalized Convulsive Status Epilepticus in Children: An Open-Label Randomized Controlled Trial

Background and PurposeThere is sparsity of quality evidence for the use of drugs after first-line benzodiazepines in convulsive status epilepticus in children. The aim of the study was to compare the clinical efficacy and safety of intravenous levetiracetam versus intravenous phenytoin as second-line drugs in the management of generalized convulsive status epilepticus in children.MethodsThis open-label randomized controlled trial was conducted in the Emergency Department of The Children's Hospital and The Institute of Child Health, Multan, Pakistan over a period of 4 years and 6 months from January 2014 to June 2018. This study included 600 children with generalized convulsive status epilepticus: 300 in the 40 mg/kg levetiracetam group, and 300 in the 20 mg/kg phenytoin group. Cessation of a clinical seizure (seizure cessation rate) within 30 minutes after the end of drug administration was the primary outcome in this study, and the presence or absence of adverse effects was noted as the secondary outcome. Data were analyzed using SPSS (version 20.0).ResultsThe children in the levetiracetam and phenytoin were aged 3.5±0.2 and 3.4±0.2 years (mean±SD), respectively, their seizure durations before the start of treatment were 25.1±0.6 and 23.8±0.4 minutes, and their treatment efficacies were 278/300 (92.7%) and 259/300 (83.3%). Levetiracetam was significantly more effective than phenytoin (p=0.012), with no significant difference in safety. Adverse events were observed in eight children in the phenytoin group.ConclusionsLevetiracetam is significantly more effective than phenytoin for the treatment of convulsive status epilepticus in children who have failed to respond to benzodiazepines.

Lipid and thyroid hormone levels in children with epilepsy treated with levetiracetam or carbamazepine: A prospective observational study

Although previous studies have investigated the influence of antiepileptic drugs (AEDs) on lipid profiles and thyroid hormone levels, there is little evidence regarding the effects of levetiracetam (LEV). Therefore, we conducted a prospective longitudinal study to evaluate the effects of LEV and carbamazepine (CBZ) treatment on lipid profile and thyroid hormone levels in patients newly diagnosed with epilepsy. Inclusion criteria were as follows: (a) age between 4 and 15 years, (b) diagnosis of epilepsy with at least two focal seizures within a year, and (c) newly treated with LEV or CBZ monotherapy. Serum lipid profile and thyroid hormone levels were measured before and after 1 and 6 months of AED initiation. Among the 21 included patients (LEV: 13 patients, CBZ: 8 patients), all but one patient in the LEV group continued AED monotherapy during the study period. Although triglyceride (TG) levels tended to be increased in the CBZ group (baseline: 58.3 ± 22.0 mg/dl, 1 month: 63.8 ± 21.6 mg/dl, 6 months: 92.3 ± 63.6 mg/dl, p = 0.22, analyses of variance (ANOVA)), there were no significant changes in total cholesterol (TC), TG levels, high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C) in either group. Serum free thyroxine (fT4) levels were significantly decreased in the CBZ group (baseline: 1.15 ± 0.06 ng/dl, 1 month: 1.00 ± 0.16 ng/dl, 6 months: 0.98 ± 0.14 ng/dl, p = 0.03, ANOVA). In contrast, there were no significant changes in fT4 or thyroid-stimulating hormone (TSH) levels in the LEV group. The results of the present study suggest that LEV monotherapy does not affect lipid profile or thyroid function while CBZ monotherapy may cause thyroid dysfunction.

Antimyoclonic Effect of Levetiracetam and Clonazepam Combined Treatment on Myoclonic Epilepsy with Ragged-Red Fiber Syndrome with m.8344A>G Mutation.

Background:Treatment of myoclonic seizures in myoclonic epilepsy with ragged-red fibers (MERRFs) has been empirical and ineffective. Guideline on this disease is not available. Additional trials must be conducted to find more suitable treatments for it. In this study, the antimyoclonic effects of monotherapies, including levetiracetam (LEV), clonazepam (CZP), valproic acid (VPA), and topiramate (TPM) compared to combination therapy group with LEV and CZP on MERRF, were evaluated to find a more advantageous approach on the treatment of myoclonic seizures.Methods:Treatments of myoclonic seizures with VPA, LEV, CZP, and TPM were reported as monotherapies in 17 MERRF patients from Qilu Hospital between 2003 and 2016, who were diagnosed through clinical data and genetic testing. After 1–4 months of follow-up (mean: 82.9 ± 28.1 days), 12 patients that exhibited poor responses to monotherapy were given a combined treatment consisting of LEV and CZP subsequently. The follow-up period was 4–144 months (mean: 66.3 ± 45.3 months), the effective rates of monotherapy group (17 patients) and combination therapy group (12 patients) were analyzed by Chi-square test.Results:The m.8344 A>G mutation was detected in all patients. There were four patients with partial response (4/17, two in the CZP group and two in the LEV group), ten patients with stable disease (10/17, six in the CZP group, three in the LEV group, and one in the TPM group), and three patients with progressive disease (3/18, two in the VPA group and one in the TPM group). Twelve of the patients with LEV combined with CZP showed a positive effect and good tolerance (12/12), eight of them demonstrated improved cognition and coordination. There was a significant difference between the monotherapy group and combination therapy group in the efficacy of antimyoclonic seizures (χ2 = 13.7, P < 0.001).Conclusions:LEV in combination with CZP is an efficient and safe treatment for myoclonic seizures in patients with this disease exhibiting the m.8344A>G mutation.

Efficacy of levetiracetam for reducing rolandic discharges in comparison with carbamazepine and valproate sodium in rolandic epilepsy

PurposeThe main purpose of this study was to compare the efficacy of levetiracetam (LEV) with the older antiepileptic drugs (AEDs) for preventing atypical evolution in children with Rolandic epilepsy (RE). Accordingly, the present study compared the efficacy of older AEDs (carbamazepine (CBZ) and valproate sodium (VPA)) with LEV in reducing rolandic discharges (RDs) on interictal electroencephalogram (EEG) in children with RE. MethodsPatients in this heterogenous study were subdivided into CBZ, VPA and LEV groups in accordance with the initial monotherapy. The CBZ and VPA groups were studied retrospectively, but the LEV group was studied prospectively. Appearances of discharges were counted and these rates were computed. In comparison with the baseline RD frequency, EEG response to AED treatment was classified such as complete disappearance and response (≥50% reduction in RD frequency). The time taken to attain complete disappearance or response in EEG responders was assessed for each AED treatment group. ResultsResponders comprised 10 (11.2%) of the 89 patients treated with CBZ, 41 (56.2%) of the 73 patients with VPA, and 25 (71.4%) of the 35 patients with LEV. Mean interval to achievement of EEG response in the CBZ, VPA, and LEV groups were 36.3, 23.1, and 14.7 months, respectively. EEG response was achieved significantly more rapidly with LEV than with CBZ (p < 0.001) or VPA (p < 0.005). Seizure control was not significantly different in all 3 investigated drugs. ConclusionsLEV seems to be superior to CBZ and VPA in its ability to suppress RDs in children with RE.

Impact of carbamazepine, lamotrigine, and levetiracetam on vascular risk markers and lipid-lowering agents in the elderly.

To examine serologic markers of vascular risk under treatment with commonly used antiepileptic drugs (AEDs) in the elderly in a randomized setting, and to determine whether the reduced exposure to hydroxymethylglutaryl-CoA reductase inhibitors ("statins") caused by carbamazepine reduces the effectiveness of the drugs as lipid-lowering agents. Standard lipid fractions, lipoprotein(a), and C-reactive protein (CRP) were examined in a subset of those participating in the STEP-ONE trial, in which elderly patients with new epilepsy were randomized to treatment with carbamazepine, lamotrigine, or levetiracetam. Separate comparisons were made by individual AED, among those treated with statins, and, for CRP, among those treated with anti-inflammatory drugs. One hundred ninety-four patients had the aforementioned serologic measurements. In patients not taking statins, those treated with carbamazepine had higher total cholesterol than those treated with levetiracetam (+16.6 mg/dL, P = 0.053), with values from patients on lamotrigine intermediate, whereas cholesterol fractions were subject to drug-gender interactions which did not show a consistent pattern. Lipoprotein(a) was significantly lower in lamotrigine patients than in the carbamazepine and levetiracetam groups. After accounting for the effects of steroids, CRP was higher in carbamazepine patients than in other patients. Patients taking a statin had lower lipid levels than those not taking a statin regardless of AED, but the differences between statin-treated and non-statin-treated patients were much larger (50%-100% or more) in the lamotrigine and levetiracetam groups than in the carbamazepine group (P = 0.035 for interaction effect of statin use and AED on total cholesterol). Here, we demonstrate that carbamazepine significantly interferes with the ability of statins to lower total cholesterol, thus making it a poor choice for hyperlipidemic patients or those with cardiovascular disease. Native AED effects on lipids were inconsistent and subject to drug-gender interaction, in contrast with other studies; further investigation is necessary to determine if these latter findings are genuine or spurious.

Randomized Controlled Trial between Levetiracetam and Phenobarbital in the Treatment of Neonatal Seizure due to Perinatal Asphyxia

Background: Seizure occurs more frequently in neonatal period and incidence of seizure is 50%-68% in perinatal asphyxia. At present phenobarbital is the drug of choice for treating neonatal seizure, which has some adverse effects on neurodevelopment status. Levetiracetam is a novel antiepileptic agent well-tolerated and effective in focal, generalized and neonatal seizure as well and lacks the adverse effects like phenobarbital. The present study was undertaken to compare the safety and efficacy of levetiracetam to phenobarbital in the treatment of neonatal seizure due to perinatal asphyxia.Methodology: This interventional study (Randomized Controlled Trial) was conducted in Department of Neonatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka and Dhaka Medical College Hospital, Dhaka, Bangladesh from 1st January’ 2014 to 30th June’ 2015. Intravenous levetiracetam injection, 50 mg/kg loading followed by 10 mg/kg 8 hourly maintenance was used and phenobarbital intravenous 20-40 mg/kg loading and 2.5 mg/kg/dose 12 hourly maintenance was given as per institutional protocol.Results: Sixty-nine term asphyxiated neonates (intention to treat population) provided analyzable data. Seizure control was found significantly higher (p = 0.011) higher in levetiracetam group in comparison to phenobarbital group (71% vs 40%). Need for more than one drug was significantly lower in levetiracetan group (p=0.011). Adverse effects were found significantly (p=0.001) lower in levetiracetam group (9% vs 43%). No serious adverse effect was observed in any group and most common adverse effect was somnolence in both group followed by irritability. Restlessness, sedation and shallow breathing were found only in phenobarbital group.Conclusion: Levetiracetam is more effective and safe in comparison to phenobarbital in the treatment of neonatal seizure due to perinatal asphyxia.Bangladesh J Child Health 2018; VOL 42 (2) :67-72

Abstract PD-044: COMPARISON OF IV LEVETIRACETAM AND PHENYTOIN COMBINATION VERSUS IV PHENYTOIN- PLACEBO COMBINATION IN CHILDREN WITH BENZODIAZEPINE RESISTANT CONVULSIVE SE- DOUBLE BLIND RANDOMIZED CONTROLLED TRIAL

Aims & Objectives: Background and Aim Current guidelines recommend initial benzodiazepine followed by phenytoin to control status epilepticus (SE). However, with this regimen seizures may remain uncontrolled in 50–60% of cases. Prolongation of seizures makes it refractory. We therefore planned this study to see if combination therapy controls seizures early. Aims: To compare seizure control with phenytoin + levetiracetam versus phenytoin monotherapy. Methods Sixty children 3m-12years, presenting to pediatric emergency between January-December 2017 in SE not controlled with initial 2 doses of benzodiazepines were enrolled. They were randomized into Group A (phenytoin + levetiracetam) or Group B (phenytoin + placebo). Primary outcome was seizure termination within 30 minutes of therapy. Standard care was provided to all. Serum levels of phenytoin and/or levetiracetam were measured at 1 hour of infusion. Patients were monitored for drug related adverse events. Trial was registered in Clinical Trials Registry of India (CTRI/2017/17/011050). Nonparametric continuous data was analyzed with student t-test and categorical variables with Chi square test. Results Seizure control was achieved in 25/28 children (75%) in Group A and 23/32 children (72%) in Group B, p=0.77. One child (3.6%) had recurrence of seizure within 8 hour in Group A and 3 (9.4%) in Group B (RR 0.35 95% 0.035–3.65) p=0.616. Serum levels of levetiracetam and phenytoin levels were similar in both the groups. No significant drug adverse effects were noted Conclusions Trend towards better seizure control was seen in phenytoin + levetiracetam group as compared to phenytoin alone though results were not statistically significant due to small sample size.

Evaluation of levetiracetam and valproic acid as monotherapy on quality of life in patients of generalized tonic clonic epilepsy

Background: Quality of life plays an important role in patients of epilepsy and is the most neglected part during management. The antiepileptic drugs treatment results in seizure control but adversely affect the quality of life in patients.Methods: An observational analytical study was conducted in the Department of pharmacology with Department of Neurology of Himalayan Institute of Medical Sciences, Dehradun over 12 months. 85 patients fulfilling the inclusion criteria with diagnosis of generalized tonic clonic seizures (GTCS) were enrolled and divided into two groups based on physicians discretion and followed up for 12 weeks. Patients were evaluated for quality of life by QOLIE-10 self administered questionnaire at 0 and 12 weeks, assessed for seizure control and drug related adverse effects.Results: 85 patients were enrolled and divided into two treatment arms as per physician discretion, levetiracetam (41) and valproic acid group (44). Study drugs showed significant improvement in quality of life, levetiracetam showed mean change that was significantly greater than valproic acid (p=0.003) at 12 weeks. Patients who failed to achieve seizure control at 6 weeks were 17% patients in levetiracetam and 20% in valproic acid group, reason being non-adherence which was 17% and 20% respectively. Adverse events recorded with Levetiracetam (10), most common being increased sleep and with valproic acid (18), with most common being increased sleep and weight gain.Conclusions: Levetiracetam treatment resulted in better quality of life, with similar seizure control but decreased number of adverse effect then Valproic acid.

The effect of levetiracetam on rat bone mineral density, bone structure and biochemical markers of bone metabolism

Some data suggest that exposure to levetiracetam (LEV) might be associated with a risk for bone health in the model of orchidectomized rats. The aim of this study was to investigate if there is any significant risk of LEV for bone health in the model of gonadally intact animals.Wistar rats were divided into a control group and a test group, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed SLD enriched with LEV for 12 weeks. Dual energy X-ray absorptiometry was used to measure BMD of the whole body, femur and lumbar vertebrae. The concentrations of bone markers were examined in bone homogenate. Both femurs and tibiae were used for biomechanical testing.We found in the LEV group significantly decreased absolute and relative values of adipose tissue, higher whole-body BMD, higher right tibia cortical thickness, and a significantly increased concentration of Bone Alkaline Phosphatase (BALP) and cross-linked C-telopeptide of type I collagen (CTX-I) compared with the control group.The results suggest that the long-term administration of LEV in the model of gonadally intact rats does not have a negative effect on bone. Significant increase in BMD and cortical thickness of the right tibia may indicate even a positive influence on the properties of bone. Further studies will be necessary in animals and humans to confirm these findings.

IV Levetiracetam versus IV Phenytoin in Childhood Seizures: A Randomized Controlled Trial.

Objectives:To compare the efficacy of IV phenytoin and IV levetiracetam in acute seizures.Design:Randomized controlled trial.Setting:Tertiary care hospital, November 2012 to April 2014.Patients:100 children aged 3–12 yrs of age presenting with acute seizures.Intervention:Participants randomly received either IV phenytoin 20 mg/kg (n = 50) or IV levetiracetam 30 mg/kg (n = 50). Patients who were had seizures at presentation received IV diazepam prior to these drugs.Outcome Measures:Primary: Absence of seizure activity within next 24 hrs.Secondary: Stopping of clinical seizure activity within 20 mins of first intervention, change in cardiorespiratory parameters, and achievement of therapeutic drug levels.Results:Two groups were comparable in patient characteristics and seizure type (P > 0.05). Of the 100 children, 3 in levetiracetam and 2 in phenytoin group had a repeat seizure in 24 hrs, efficacy was comparable (94% vs 96%, P > 0.05). Of these, 18 (36%) in phenytoin and 12 (24%) in levetiracetam group received diazepam. Sedation time was 178.80 ±97.534 mins in phenytoin and 145.50 ±105.208 mins in levetiracetam group (P = 0.346). Changes in cardiorespiratory parameters were similar in both groups except a lower diastolic blood pressure with phenytoin (P = 0.023). Therapeutic drug levels were achieved in 38 (76%) children both at 4 and 24 hrs with phenytoin, compared to 50 (100%) and 48 (98%) at 1 and 24 hrs with levetiracetam (P < 0.05).Conclusion:Intravenous levetiracetam and phenytoin have similar efficacy in preventing seizure recurrences for 24 hrs in children 3–12 years presenting with acute seizures.

Anger Assessment in Patients Treated With Brivaracetam.

To assess state and trait anger, adjusted by epilepsy type, seizure control, anxiety-depression status and quality of life, in patients treated with brivaracetam (BRV) from an open study. We evaluated prospectively consecutive patients with partial onset seizures in an open-label study. Patients had 5 years or longer of epilepsy and were taking between 1 and 3 antiepileptic drugs. They were treated with BRV and compared with a control group selected from outpatients attending our epilepsy unit who met the following criteria: age ≥16 years and diagnosis of epilepsy with focal-onset seizures at least 1 year before inclusion in the study. The following tests were assessed: State-Trait Anger with the Expression Inventory-2, Hospital Anxiety and Depression Scale, and Quality of Life in Epilepsy Inventory. We recruited 39 patients, 17 treated with BRV and 22 with other drugs, including 13 with levetiracetam (LEV). Mean age was 47.3 years, 43.6% were men. Symptomatic cases, 66% and 52% temporal lobe epilepsy. Antiepileptic drug polytherapy was present in 82.1% of the cases (100% BRV vs 68.2% control group). Demographic and clinical characteristics, as well as Quality of Life in Epilepsy Inventory and Hospital Anxiety and Depression Scale scores were similar in both groups. When compared with the subgroup of LEV groups did not differ significantly on their Hospital Anxiety and Depression Scale scores. This small, open study suggests that BRV increases anger measures less than LEV in epilepsy patients. However, larger, blinded control studies are required to establish whether this apparent difference can be confirmed.

Effect of Levetiracetam Monotherapy in Nonlesional Focal Childhood Epilepsy

This article compares the efficacy and tolerability of carbamazepine (CBZ) and levetiracetam (LEV) when used as initial monotherapy in children with nonlesional focal epilepsy. Patients with nonlesional focal epilepsy were subdivided into two groups according to the initial monotherapy: a LEV group administered LEV at an initial dose of 5 mg/kg/day and a CBZ group. Seizure response, adverse events, medication dose, reasons for discontinuing medication, adherence, and random serum levels were recorded. The overall percentage of patients who failed initial treatment and reasons for each treatment failure were determined. Data were analyzed from 183 children who received CBZ monotherapy and 46 children who received LEV monotherapy for ≥12 months. Overall, 126 patients (68.9%) became seizure-free with CBZ, compared with 37 patients (80.4%) with LEV. Moreover, four patients in CBZ and four patients in LEV groups showed a >50% reduction in seizure frequency. The efficacy rate was significantly higher and the adverse event rate was significantly lower in the LEV group than in the CBZ group (p = 0.0129 and p = 0.0039, respectively). LEV may offer superior efficacy and a lower risk of adverse effects compared with CBZ. LEV as initial monotherapy may represent a valuable treatment option for children with nonlesional focal childhood epilepsy.

Vitamin D deficiency in children with epilepsy taking valproate and levetiracetam as monotherapy

ObjectiveThe aim of this study is to evaluate if valproate (VPA) and levetiracetam (LEV) as monotherapy are associated with vitamin D deficiency among children with epilepsy. Material & methodsA cross-sectional clinical (seizure types, aetiology of epilepsy, dosage, drug levels, and duration of AED treatment) and blood testing (calcium, phosphorus, 25-OHD and PTH) study was accomplished in 90 epileptic children (AED group: 59 receiving VPA, and 31 receiving LEV) and a control group (244 healthy subjects). 25-OHD levels were categorized as low (<20ng/ml), borderline (20–29ng/ml), or normal (>30ng/ml) ResultsThe average dosage of VPA and LEV was 20.7±4.7mg/kg/d and 24.1±7.9mg/kg/d, respectively. The mean duration of VPA therapy was 2.5±1.4years, and with LEV was 2.3±1.6years. Mean calcium and 25-OHD levels were significantly higher (p <0.05) in the control group. There was a negative correlation (p <0.01) between 25-OHD and VPA levels (r=−0.442). Vitamin D deficiency (%) was significantly higher (p <0.05) in VPA (24.1%) and LEV (35.5%) groups than in control group (14%). The multiple logistic regression analysis showed that VPA monotherapy (OR: 1.9, CI 95%: 1.1–3.8) and LEV monotherapy (OR: 3.3, CI 95%: 1.5–7.5) were associated with an increased risk of vitamin D deficiency. ConclusionsThe prevalence of vitamin D deficiency is common in children with epilepsy taking VPA or LEV. Hence vitamin D status of children treated with VPA and LEV should be regularly monitored and vitamin D supplements should be considered on an individual basis.

Antinociceptive and pronociceptive effect of levetiracetam in tonic pain model

Levetiracetam (LEV) is a novel anticonvulsant with proven antinociceptive properties. However, the antinociceptive and pronociceptive effect of this drug has not yet been fully elucidated in a tonic pain model. Thirty-six male rats (Wistar) were randomized into six groups and underwent the formalin test as follows: rats in the control group were administered 50μL of 1% formalin in the paw; sham-group rats were administered 50μL of saline in the paw to mimick the application of formalin; the four experimental groups were administered LEV intragastrically (ig) (50, 100, 200 and 300mg/kg), and 40min later 50μL of 1% formalin was injected in the paw. LEV exhibited antinociceptive effect in the 300mg/kg LEV group (p<0.05) and a pronociceptive effect in the 100mg/kg LEV group (p<0.05) and in the 50mg/kg LEV group (p<0.001). The antinociceptive and pronociceptive effect of LEV in a tonic pain model is dose-dependent.