Efficacy Of Levetiracetam Research Articles

Efficacy of Levetiracetam vs Phenobarbital as First Line Therapy for the Treatment of Neonatal Seizures

OBJECTIVE Seizures are one of the most common neurologic complications seen in a neonate. Historically, phenobarbital has been the agent of choice, but can lead to adverse neurologic outcomes, which has contributed to the use of other agents. Levetiracetam has proven great efficacy with an excellent safety profile in older patients, causing interest of its use in neonates. The objective of this study was to determine if levetiracetam would provide similar neonatal seizure resolution rates as phenobarbital. METHODS The study was a single-center, retrospective, cohort study from August 1, 2020 to August 31, 2022 investigating the efficacy and safety of using levetiracetam compared with phenobarbital as a first line treatment for neonatal seizures. The primary outcome was to assess overall seizure resolution after administration of levetiracetam or phenobarbital, without addition of a second antiseizure medication. RESULTS There were 87 patients included in the study. Fifteen neonates (27.78%) achieved seizure resolution with phenobarbital compared with 9 neonates (27.27%) who received levetiracetam first line (p = 0.959). Neonates who received phenobarbital had higher rates of adverse effects. Neonates who received a benzodiazepine prior to administration of levetiracetam had lower seizure resolution rates (p = 0.021). CONCLUSIONS These findings suggest there is no difference in using phenobarbital over levetiracetam to achieve complete seizure resolution in a neonate. Higher rates of adverse events were seen in the phenobarbital group. The use of a benzodiazepine prior to administration of levetiracetam may reduce the efficacy of levetiracetam.

Comparative Efficacy of Levetiracetam versus Phenobarbitone as First-Line Treatment for Neonatal Seizures

Comparative Efficacy of Levetiracetam versus Phenobarbitone as First-Line Treatment for Neonatal Seizures

Efficacy and safety of levetiracetam for migraine prophylaxis in children: a systematic review and meta-analysis.

Levetiracetam (LEV), an antiepileptic drug, has been effective in adult migraine prevention but lacks extensive research in children. This study evaluates LEV's efficacy and safety for pediatric migraine prophylaxis. We reviewed randomized controlled trials (RCTs) and non-RCTs in major databases through 8 January 2024, focusing on four efficacy endpoints and adverse drug reactions (ADRs). Data synthesis involved pooled relative risks or odds ratios for dichotomous outcomes and mean differences for continuous outcomes, using fixed- or random-effects models as appropriate. Eight studies with 190 participants showed that after taking LEV, the mean headache frequency decreased 5.19 per month (MD: -5.19, 95% CI: -7.11 to -3.27, p < 0.00001) and improved headache-free rates to 28% (95% CI: 0.17-0.41). More than 83% experienced a >50% reduction in monthly headache frequency. The migraine disability score decreased by 33.51 points (MD: -33.51, 95% CI: -38.46 to -28.55, p < 0.00001). ADR incidence did not significantly differ between LEV and control groups (RR: 1.06, 95% CI: 0.39 to 2.85, p = 0.91), with an overall ADR rate of 18% (95% CI: 0.13-0.24). The most common ADR was irritability (12%), leading to treatment discontinuation in 13% of cases (95% CI: 0.05-0.30). LEV has shown good efficacy in preventing pediatric migraines. However, its safety requires further confirmation through more extensive and well-designed RCTs. Identifier PROSPERO CRD42024497643.

Factors influencing serum concentrations of levetiracetam in dogs with epilepsy.

Factors affecting serum concentrations of levetiracetam in dogs are unknown and could affect the efficacy of levetiracetam in controlling seizures in dogs with epilepsy. Higher PO doses of levetiracetam will be needed in dogs to achieve serum concentrations shown to be effective in humans. Determine factors that could influence serum levetiracetam concentrations and justify dose adjustment in some epileptic dogs. Sixty-nine client-owned dogs with epilepsy treated with levetiracetam alone or in combination, based on 127 trough serum concentration measurements of levetiracetam. Retrospective cohort study. Linear mixed models were used to assess the effect of patient signalment and concurrent drug administration on serum concentrations of levetiracetam and the effect of serum concentration of levetiracetam on seizure frequency reduction. The PO dose of levetiracetam significantly explained changes in serum levetiracetam concentration, and this causal link was stronger with monotherapy (R2 = 0.59, P < .001). Phenobarbital significantly decreased serum levetiracetam concentration in a dose dependent manner (R2 = 0.30, P = .003). Based on our model, a levetiracetam dosage of 99-216 mg/kg/day is necessary to obtain a serum levetiracetam concentration of 20 μg/mL when used alone or concurrently with 7 mg/kg/day of phenobarbital. No other factors were found to influence serum levetiracetam concentrations. No therapeutic range could be identified. Our data suggest that a dosage of 99-216 mg/kg/day of levetiracetam is needed to achieve a serum concentration known to be therapeutically effective in humans, especially when administered concomitantly with phenobarbital.

Efficacy and tolerability of levetiracetam in people with and without intellectual disabilities: A naturalistic case control study

IntroductionPeople with Intellectual Disabilities (PwID) are twenty times more likely than general population to have epilepsy. Guidance for prescribing antiseizure medication (ASM) to PwID is driven by trials excluding them. Levetiracetam (LEV) is a first-line ASM in the UK. Concerns exist regarding LEV's behavioural and psychological adverse effects, particularly in PwID. There is no high-quality evidence comparing effectiveness and adverse effects in PwID to those without, prescribed LEV. MethodsPooled casenote data for patients prescribed LEV (2000–2020) at 18 UK NHS Trusts were analysed. Demographics, starting and maximum dose, adverse effects, dropouts and seizure frequency between ID (mild vs. moderate-profound (M/P)) and general population for a 12-month period were compared. Descriptive analysis, Mann-Whitney, Fisher's exact and logistic regression methods were employed. Results173 PwID (mild 53 M/P 120) were compared to 200 without ID. Mean start and maximum dose were similar across all groups. PwID (Mild & M/P) were less likely to withdraw from treatment (P = 0.036). No difference was found between ID and non-ID or between ID groups (Mild vs M/P) in LEV's efficacy i.e. >50 % seizure reduction. Significant association emerged between ID severity and psychiatric adverse effects (P = 0.035). More irritability (14.2 %) and aggression (10.8 %) were reported in M/P PwID. ConclusionPwID and epilepsy have high rates of premature mortality, comorbidities, treatment resistance and polypharmacy but remain poorly researched for ASM use. This is the largest studied cohort of PwID trialled on LEV compared to general population controls. Findings support prescribing of LEV for PwID as a first-line ASM.

Safety and Efficacy of Levetiracetam for Prevention of Epileptic Seizures in Acute Phase of Intracerebral Bleeding

Background: Epilepsy, characterized by recurrent, unprovoked seizures due to anomalous brain activity, is a significant complication for patients with intracerebral hemorrhage (ICH). The onset of epileptic convulsions during the acute phase of ICH can worsen the patient's prognosis and survival chances, making it crucial to identify a safe and effective method to prevent these seizures. Levetiracetam, a pyrrolidone derivative, is noted for its unique mechanism of action, exceptional tolerability, and advantageous pharmacokinetics, making it efficacious against various types of seizures. Objective: This study aims to evaluate the safety and efficacy of levetiracetam in preventing epileptic seizures during the acute phase of ICH and to determine its impact on neurological outcomes in this patient population. Methods: A cross-sectional investigation was conducted between October 2022 and June 2023 at Pak Emirates Military Hospital in Rawalpindi, Pakistan, involving 85 patients with spontaneous ICH confirmed by CT or MRI within 24 hours of symptom onset. Inclusion criteria included adult patients aged 18 or older, with various forms of ICH, excluding isolated subarachnoid hemorrhage, penetrating wound injury, depressed skull fracture, or early posttraumatic seizure. Patients with a Glasgow Coma Scale (GCS) score of less than 6, serum creatinine level &gt;1.7 mg/dL, history of psychosis, unprovoked seizures, cerebrovascular accidents, traumatic brain injuries, or encephalitis within the previous three years were excluded. Patients were administered an initial loading dose of levetiracetam (1,000 to 1,500 mg), followed by a maintenance dose (500 to 1,500 mg every 12 hours) based on renal function. Continuous electroencephalography (cEEG) monitoring was used to detect seizures for at least the first 72 hours of hospital admission. The primary outcome was the incidence of epileptic seizures during hospitalization, while the secondary outcome was the patient's neurological status at discharge, assessed using the Modified Rankin Scale (mRS). Data were analyzed using descriptive statistics and the Chi-square test, with a p-value of ≤0.05 considered statistically significant. Analyses were conducted using SPSS version 25. Results: The mean age of the patients was 47.89 years (SD=7.46), with 62.35% male and 37.65% female. The mean GCS score at admission was 10.52 (SD=2.13), and the mean volume of ICH was 17.5 ml (SD=3.4). At baseline, 2.35% of patients had GCS scores of 3-5, which improved to 0% after treatment. The percentage of patients with GCS scores of 13-15 increased from 65.88% to 83.52% (p=0.3730). Seizures within the first 7 days occurred in 10.58% of patients, and the overall seizure incidence during hospitalization was 20%. At discharge, 9.41% of patients had an mRS score of 0, and the percentage of patients with an mRS score of 2 increased significantly from 18.18% to 37.64% (p=0.4086*). The percentage of patients with severe disability (mRS score of 5) significantly decreased from 22.72% to 5.68% (p=0.0094*). Conclusion: Levetiracetam is effective in improving neurological outcomes and reducing the incidence of seizures in patients with acute intracerebral hemorrhage, with a manageable safety profile. These findings suggest that levetiracetam can be a valuable addition to therapeutic strategies for managing ICH-related seizures, potentially enhancing patient care and improving health outcomes.

Comparative Outcomes of Levetiracetam and Phenobarbital Usage in the Treatment of Neonatal Seizures: A Retrospective Analysis.

The primary aim of this study was to conduct a comparative analysis of the safety and efficacy of levetiracetam (LEV) and phenobarbital (PB) as first-line treatments for neonatal seizure management. This study was designed to measure and compare the incidence of adverse effects and to determine the discharge and mortality rates associated with the use of these antiseizure medications (ASMs). Through this comparison, this research sought to provide insights to optimise care for neonates experiencing seizures. This retrospective cohort study evaluated 104 neonates treated for seizures at Zeynep Kamil Hospital from 2015 to 2020 after excluding those on non-PB/LEV antiseizure medications. Seizures were characterised using electroencephalogram (EEG) and categorised according to aetiology and frequency. Treatment efficacy was gauged by seizure cessation, as confirmed using EEG. Adverse effects and demographic data were recorded. Statistical analyses were conducted using SPSS, employing the Shapiro-Wilk, independent t-test, Mann-Whitney U test, and chi-square test, with a significance threshold of p < 0.05. Overall, 104 neonates treated with first-line ASM were evaluated for efficacy; PB was administered in 68.26% of the cases, while LEV was utilised in 31.74%. The total complete response rate was 40.38%, with no significant difference between the PB and LEV groups (p = 0.309). The incidence rate ratios (IRRs) demonstrated that seizure frequency profoundly influenced treatment effectiveness, with IRRs of 2.09 for rare seizures, 3.25 for frequent seizures, and 4.01 for status epilepticus, indicating a higher treatment response rate with increasing seizure frequency. For second-line treatment, among a subset of 62 patients, PB had a slight, non-significant advantage over LEV, with an odds ratio of 1.09, suggesting a marginally better response to LEV. Adverse events were significantly more frequent in the PB group, affecting 19 of 67 neonates (28.36%), compared to only 2 of 71 neonates (2.82%) in the LEV group (p < 0.001). No significant difference was observed in the discharge rates between the two groups (PB, 67.61%; LEV, 75.76%; p = 0.674). Interestingly, the mortality rate was significantly higher in the LEV group (45.45%) than that in the PB group (22.54%; p = 0.045). This study underscores LEV's superior safety profile over PB in neonatal seizure management, evidenced by a significantly lower rate of adverse events. PB seems to be more effective in the second-line treatment of neonatal seizures. Despite the lack of significant differences in the discharge rates, the higher mortality rate associated with LEV warrants further investigation. These findings advocate the cautious selection of antiepileptic drugs in neonatal care, with a preference for LEV based on its safety profile.

Safety and efficacy of levetiracetam and carbamazepine monotherapy in the management of pediatric focal epilepsy: a randomized clinical trial.

Due to the limited number of studies in children with focal epilepsy and the importance of choosing the most suitable drug to control seizures in children, the administration of the most effective medication with the most negligible adverse events is vital. This study aimed to evaluate the effectiveness and adverse events of carbamazepine vs. levetiracetam monotherapy in children with focal seizures. A monocentric, randomized, controlled, double-blind, parallel-group clinical trial was designed. This study was approved by the Iranian Registry of Clinical Trials (registration number:IRCT20170216032603N2) on June 19, 2020, and conducted at the neurology department of Imam Ali Hospital, Karaj, Iran, from February 2020 to March 2021. This study assessed 120 patients with recently diagnosed focal seizures aged 2 to 14. Patients were randomly divided into two groups, who received carbamazepine (CBZ) 15 to 20mg/kg and levetiracetam (LEV) 20 to 40mg/kg daily, respectively. Patients were evaluated for improvement and complications at weeks 4, 12, and 24. Out of 120 patients included in the study, six patients were excluded due to various complications of CBZ. The mean number of seizures at the end of the fourth, twelfth, and twenty-fourth weeks were 1.09 ± 0.75, 0.62 ± 0.27, and 0.39 ± 0.12 in the carbamazepine group and 1.11 ± 0.63, 0.52 ± 0.21, and 0.37 ± 0.11 in the LEV group, respectively (P > 0.05). Similarly, the number of seizure-free patients was 34, 44, and 48 in the CBZ group compared to 41, 50, and 54 in the LEV group, respectively (P > 0.05). On the other hand, the frequency of somnolence, dermatologic complications, and agitation was considerably higher in the CBZ group (P < 0.05). Although both medicines were equally effective in seizure control, CBZ was associated with considerably more adverse events and less patient compliance. Physicians should be aware of this difference to prevent unwanted consequences.

Efficacy of levetiracetam combined with oxcarbazepine in the treatment of adults with temporal lobe epilepsy and its impact on memory and cognitive function.

To explore the effect of levetiracetam combined with oxcarbazepine on the memory and cognitive function of adult patients with temporal lobe epilepsy. This retrospective analysis included 91 adult patients with temporal lobe epilepsy treated at Xianyang Hospital from June 2020 to December 2022. Based on their medication regimen, patients were categorized into an observation group (n=51) receiving levetiracetam plus oxcarbazepine and a control group (n=40) receiving only levetiracetam. Both groups underwent 3 months of continuous treatment. Therapeutic efficacy, pre- and post-treatment memory function (assessed using the Clinical Memory Scale, CMS), cognitive function (evaluated with the Wechsler Adult Intelligence Scale-Revised in China, WAISRC), anxiety and depression levels (measured by the Hamilton Anxiety Scale, HAMA, and Hamilton Depression Scale, HAMD), as well as adverse reactions, were compared between the two groups. Independent factors influencing treatment efficacy were also analyzed. CMS and WAISRC scores significantly increased in both groups after treatment (both P=0.001), with the observation group showing more significant improvements than the control group (P=0.001). The improvements in HAMA and HAMD scores in the observation group were significantly better than the control group (all P<0.001). Adverse reaction occurrence showed no significant difference between the two groups (P>0.05). Prognostic analysis identified seizure frequency and treatment regimen as independent factors influencing efficacy. Levetiracetam combined with oxcarbazepine effectively improves cognitive dysfunction in adults with temporal lobe epilepsy, with superior efficacy to levetiracetam alone, and good safety.

Efficacy of Levetiracetam as Add-On Therapy in the Treatment of Seizures in Neonates

Introduction: There is no consensus regarding the efficacy of add-on therapy with levetiracetam (LEV) in the treatment of seizures in neonates. The aim of this study was to evaluate the efficacy of add-on therapy with LEV for achieving >80% seizure reduction after phenobarbital (PB) treatment. Methods: Retrospective cohort study of near term neonates admitted to the neonatal intensive care unit with EEG-confirmed seizures despite treatment with PB as first-line therapy and using LEV as 2nd-, 3rd- or 4th-line treatment. Antiseizure medication was administered according to national guidelines. All neonates were monitored with 2-channel amplitude-integrated electroencephalography. The total seizure burden in minutes, 2 h before and 4 h after administration of LEV, was calculated using raw EEG. Primary outcome was the efficacy of LEV in achieving >80% seizure reduction. The efficacy of additional midazolam (MDZ) and lidocaine (LDC) was also calculated. Results: A total of 47 full-term neonates were included. The mean total loading dose of LEV was 40 mg/kg (36–44 mg/kg). Seizure etiology consisted of hypoxic-ischemic encephalopathy (n = 11), hemorrhagic or ischemic stroke (n = 16), central nervous system infection (n = 8), genetic (n = 8), metabolic disorders (n = 3), and unknown (n = 1). Following LEV administration, >80% seizure reduction was observed in 17% (8/47) of neonates, whereas it was 23% (6/26) after MDZ and 92% (23/25) after LDC administration. Discussion: Although the cumulative loading dose of LEV was low and the group of infants studied was heterogeneous, the efficacy of LEV as add-on therapy for the treatment of seizures in neonates was limited. The highest seizure reduction rate was seen after LDC administration.

Levetiracetam may be an unsuitable choice for patients with PRRT2-associated self-limited infantile epilepsy

IntroductionSelf-limited infantile epilepsy (SeLIE) is a benign epilepsy. Previous studies have shown that monotherapy with most antiseizure medications can effectively relieve seizures in patients with SeLIE, but the efficacy of levetiracetam has not been investigated.ObjectiveThis study aimed to investigate the efficacy of levetiracetam in the treatment of SeLIE patients with PRRT2 mutations.MethodsThe clinical data of 39 SeLIE patients (21 males and 18 females, aged 4.79 ± 1.60 months) with pathogenic variants in PRRT2 or 16p11.2 microdeletion were retrospectively analyzed. Based on the use of initial antiseizure medication (ASM), the patients were classified into two groups: Levetiracetam group (LEG) and Other ASMs group (OAG). The difference of efficacy between the two groups was compared.ResultsAmong the 39 SeLIE patients, 16 were LEG (10 males and 6 females, aged 5.25 ± 2.07 months), with whom two obtained a seizure-free status (12.50%) and 14 ineffective or even deteriorated (87.50%). Among the 14 ineffective or deteriorated cases, 13 were seizure-controlled after replacing levetiracetam with other ASMs including topiramate, oxcarbazepine, lamotrigine, and valproate, and the remaining one finally achieved remission at age 3. Of the 39 patients, 23 were OAG (11 males and 12 females; aged 4.48 ± 1.12 months), of whom 22 achieved seizure remission, except for one patient who was ineffective with topiramate initially and relieved by oxcarbazepine instead. Although there were no significant differences in gender and age of onset between the two groups, the effective rate was significantly different (12.50% in LEG vs. 95.65% in OAG) (P < 0.01).ConclusionThe findings showed that patients with SeLIE caused by the PRRT2 mutations did not benefit from the use of levetiracetam, but could benefit from other ASMs.

Effects of Levetiracetam on Childhood-onset Refractory Epilepsy Classified by Level of Intellectual Disability

The efficacy of levetiracetam (LEV) for childhood-onset refractory epilepsy was retrospectively evaluated from medical records, based on the level of intellectual disability. The study sample included 84 patients (68 adults, 16 children) with childhood- onset refractory epilepsy who had been treated with LEV (dose: adult, 1000 mg/day; children, 30 mg/kg/day) for approximately 1.7 years. The responder rates (≥ 50% and ≥ 75% reduction in seizure frequency from baseline) were 85.7% and 42.9% for focal seizures in adults with normal intelligence; the responder rates for focal seizures in adults with intellectual disabilities were average 69.0% and 6.9%, respectively. Serious adverse events were not observed. A high level (≧75%) of reduction can be expected for focal seizures in adults with normal intelligence but cannot be expected in adults with intellectual disabilities. Further studies are required to investigate these.

Efficacy of Levetiracetam versus Phenytoin in Neonatal Seizure in Rural Area of Thailand

Background: Neonatal seizure is an emergency condition that affects neurodevelopment and mortality. The appropriate treatment and seizure termination is crucial. Previous studies determined the efficacy of different types of antiseizure medications (ASMs), but there is no consensus toward second-line ASMs in neonatal seizure. Objective: To compare the efficacy of second-line ASMs in neonatal seizure, compared between levetiracetam and phenytoin. Materials and Methods: The present study was a retrospective study. The author recruited patients with diagnosis of neonatal seizure admitted at Maharat Nakhon Ratchasima Hospital, Thailand, between January 1, 2018 and December 31, 2020. Patients who had clinical seizure refractory and were given first-line ASM (intravenous phenobarbital) and received second-line ASMs as intravenous levetiracetam or intravenous phenytoin were included. Etiologies of seizure, seizure types, and other demographic data were recorded. The efficacy of levetiracetam and phenytoin were determined by comparing the duration of seizure, the need for third-line ASMs, and morbidity as developmental outcome, diagnosis of cerebral palsy, and mortality rate. Results: Twenty-five patients (68% male) were recruited. Sixty-four percent were diagnosed with hypoxic ischemic encephalopathy (HIE). The most common seizure type was subtle seizure at 56%. Levetiracetam was given to 56% and phenytoin was given to 44% as second-line ASMs. The duration of seizure was significantly different at 28.12 minutes in levetiracetam and 42.72 minutes in phenytoin (p=0.01). The drug adherence was higher in the levetiracetam group. Regarding third-line ASMs, 28.7% of the levetiracetam group and 45.45% of phenytoin group needed third-line ASMs, but this was not statistically significant. Mortality was 20% and 48% were diagnosed as cerebral palsy. There was no significant difference in mortality and morbidity between the two groups. Conclusion: Levetiracetam had no superior efficacy than phenytoin in neonatal seizure. Keywords: Neonatal seizure; Levetiracetam; Phenytoin; Efficacy

Comments on a Randomized Parallel Non-inferiority Trial to Evaluate the Safety and Efficacy of Levetiracetam in Comparison to Magnesium Sulfate in the Management of Severe Preeclampsia

Comments on a Randomized Parallel Non-inferiority Trial to Evaluate the Safety and Efficacy of Levetiracetam in Comparison to Magnesium Sulfate in the Management of Severe Preeclampsia

Comparison of Efficacy and Safety of Levetiracetam Versus Phenytoin for Post-craniotomy Seizure Prophylaxis.

Background: Superiority of levetiracetam over phenytoin for postcraniotomy seizure prophylaxis in patients with a supratentorial brain tumor is controversial. We aimed to evaluate the efficacy of levetiracetam versus phenytoin for postcraniotomy seizure prophylaxis in supratentorial brain tumor. Methods: In a randomized controlled trial study, 80 patients with a supratentorial brain tumor who underwent craniotomy were allocated to levetiracetam or phenytoin group, 40 patients each. Seizure prophylaxis was started 5 days before the surgery and continued until 90 days after surgery. Phenytoin group received 100 mg oral phenytoin 3 times a day. The levetiracetam group received 500 mg oral levetiracetam 2 times a day. The primary outcome was the incidence of postcraniotomy seizures. The secondary outcome measure was the safety profile of the drugs. Results: All patients of the phenytoin group and 39 patients of levetiracetam completed the study. Two seizures developed in the study population, 1 in the phenytoin group (2.5%) and 1 in the levetiracetam group (2.6%) (P = 0.710). Renal or hepatic dysfunction was not observed in any patients. Wound hematoma was seen in 5 patients (12.5%) of the phenytoin and 6 patients (15.4%) of the levetiracetam group (P = 0.481). Skin rash developed in 3 patients (7.5%) of the phenytoin group and no patient of the levetiracetam group (P = 0.132). Thrombocytopenia was detected in 1 patient of the phenytoin group (2.5%) and no patient of the levetiracetam group (P = 0.511). None of the adverse events led to drug withdrawal. Conclusion: These results reveal no superiority of levetiracetam over phenytoin for postcraniotomy seizure prophylaxis in supratentorial brain tumor.

OPTIMIZING LEVETIRACETAM SURFACTANT-BASED NANOVESICLES (LEV-NVS) GEL FOR TREATING EPILEPSY USING EXPERIMENTAL DESIGN

Objective: To develop and estimate the intranasal delivery of Levetiracetam surfactant-based nanovesicles (Lev-Nvs) as a brain-targeted antiepileptic delivery system prepared via solvent evaporation technique. Methods: Optimized formulation F (OPT) chosen by the Design-Expert® program gave the highest entrapment efficiency (EE%) was incorporated into the gel. An experimental design was adopted utilizing various (span 65) surfactants and different cholesterol ratios. The (Lev-Nvs) nanovesicles were formulated by solvent evaporation technique and evaluated for in vitro characterization parameters such as zeta sizer, Transmission Electron Microscopy (TEM), zeta potential. The nasal gel was evaluated for drug-excipient interactions utilizing Fourier Transform Infrared Spectroscopy (FTIR) and subjected to in vitro and in vivo release studies. Results: The results indicated that the entrapment efficiency (EE%) of Levetiracetam surfactant-based nano-vesicles (Lev-Nvs) could be modulated by the alterations in surfactant and cholesterol concentrations. Optimized formulation F (OPT) showed an entrapment efficiency of (87.9±1.06 %), (206.7±20.43 nm) particle size, (-34.1) zeta potential and (0.979) PDI. The nanovesicle nasal gels of the F(OPT) were prepared using Carbopol 940 at different concentrations. G 0.375 formulation showed the best in vitro drug release (87.36%) after 12 h. Finally, the comparative in vivo pharmaco-kinetics release studies on rats revealed considerable, sustained release of the nanovesicle nasal gel and higher relative bioavailability than an equivalent dose of oral solution (293.85%). Conclusion: Our study proves the improved efficacy of Levetiracetam as a surfactant-based nanovesicle intranasal gel in the brain targeting antiepileptic medication.

Targeted anticonvulsive treatment of IDH-wildtype glioblastoma based on DNA methylation subclasses.

Seizures occur in one-third of glioblastoma patients, and in another third, seizures develop during the course of the disease.1 Nevertheless, the choice of antiseizure medication (ASM) remains challenging, and many patients need an increase in dosage or a polytherapy to achieve seizure control.2 We recently demonstrated that the DNA methylation subclass RTK II has a strong epileptogenic potential, as a high frequency of preoperative and follow-up seizures was observed.1 Here, we investigated the efficacy of levetiracetam to achieve seizure control and define therapeutic targets in RTK I, RTK II, and mesenchymal (MES) glioblastoma. We studied 201 patients with IDH-wildtype glioblastoma from 2 neurooncological centers (Hamburg and Bonn) and DNA methylation was analyzed using the Illumina EPIC array. Differential methylation analysis was performed, examining differentially methylated CpG sites of genes that are therapeutic targets of the most clinically relevant ASM. To further identify RNA expression of these genes, we queried the TCGA database to vertically integrate DNA methylation and RNA expression (n = 68). This study was approved by the medical ethics committee of the Hamburg chamber of physicians (PV4904). Informed written consent was obtained from all patients.

Comparison of levetiracetam as second-line drug with fosphenytoin in convulsive status epilepticus among children

Background: Status epilepticus (SE) is the most common neurologic emergency in the pediatric age group often serious and life-threatening. Although newer drugs were used, morbidity and mortality are still high. This study was done to compare the efficacy of levetiracetam with the existing second-line drug fosphenytoin in the treatment of SE. Subjects and Methods: This was a prospective, randomized parallel group trial from Pediatric Intensive Care Unit of a Tertiary Care Institute. One hundred children were recruited according to the inclusion and exclusion criteria, 50 in fosphenytoin group and 50 in levetiracetam group. Two groups were compared with respect to clinical cessation of seizures, recurrence, adverse event, and outcome. Results: Male-to-female ratio was 1.45:1. Seizure were controlled in 37 (74%) in fosphenytoin group and 28 (56%) in levetiracetam group) (P = 0.059). The mean time for cessation of seizures was 11.16 ± 3.58 min in fosphenytoin group as compared to was 12.78 ± 3.07 min in levetiracetam group (P = 0.059) The seizure recurrence in first 24 h (18 [36%] vs. 12 [24%]) (P = 0.643) and development of shock (14 [28%] vs. 11 [22%]) (P = 0.488) was comparable in two groups. Overall mortality was 10 (20%) in fosphenytoin group as compared to 7 (14%) levetiracetam group (P = 0.281). Conclusions: Efficacy of intravenous levetiracetam is comparable to fosphenytoin as a second-line medication in the management of convulsive SE in children.

Levetiracetam plus Oxcarbazepine Combination Treatment Downregulates Serum Multidrug Resistance Protein 1 Levels and Upregulates Neuropeptide Y Levels in Children with Epilepsy

The aim of the present study was to investigate the usefulness of multidrug resistance protein 1 (MDR1) and neuropeptide Y (NPY) levels in predicting the efficacy of levetiracetam (LEV) plus oxcarbazepine (OXC) treatment administered to children with epilepsy and to determine their prognosis. Overall, 193 children with epilepsy admitted to the hospital were enrolled and randomly divided into two groups according to different treatment methods: group A (n = 106, treated with LEV plus OXC combination) and group B (n = 87, treated with OXC only). After treatment, compared with group B, group A exhibited a remarkably higher total effective rate and a significantly lower total adverse reaction rate. Areas under the curve for MDR1 and NPY for predicting ineffective treatment were 0.867 and 0.834, whereas those for predicting epilepsy recurrence were 0.916 and 0.829, respectively. Electroencephalography abnormalities, intracranial hemorrhage, neonatal convulsion, premature delivery, and MDR1 and NPY levels were independent risk factors for poor prognosis in children with epilepsy. Serum MDR1 and NPY levels exhibited a high predictive value for early epilepsy diagnosis, treatment efficacy assessment, and prognostication in children with epilepsy treated with LEV plus OXC combination.

Comparing Prophylactic Effect of Levetiracetam, Sodium Valproate, and Propranolol in Pediatric Migraine: A Randomized Clinical Trial.

Epidemiologic studies point to an increased prevalence of migraine in children in recent decades. Migraine treatment involves acute and prophylactic therapy. Recently, such anti-epileptic drugs as Levetiracetam have been used to treat adult migraines. The present study aimed to compare the efficacy of Levetiracetam, Sodium Valproate, and Propranolol in preventing migraine headaches in children. In this clinical trial, children with migraine were randomly divided into three groups. Each group consisted of 13 children. Two groups were treated with Propranolol and Sodium Valproate, respectively. Another group (the case) was treated with Levetiracetam. The patients were assessed based on headache score, PedMIDAS, and headache frequency before and three months after the intervention. Finally, the data was analyzed using descriptive and analytical statistical methods. Levetiracetam significantly reduced the headache severity (P=0.026), frequency (P=0.024), and PedMIDAS score (P=0.001) in children with migraine. However, no significant difference was found between the three groups. The percentage of patients who experienced pain relief was detected as 69.24%, 92.31%, and 30.76% in the Propranolol, Sodium Valproate, and Levetiracetam groups, respectively. This study concluded that Levetiracetam can be used as a migraine prophylaxis drug in children.