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Introduction Early posttraumatic seizures (EPTS) are a major complication after a head injury, defined as seizures developing within the first 7 days of trauma. Levetiracetam has become a popular drug for the prevention of posttraumatic seizures in institutions worldwide. However, it has been reportedly associated with adverse effects like behavioral changes and somnolence. This study aimed to compare the efficacy of a newer drug, brivaracetam, which is reported to have a better pharmacokinetic profile. These findings may be significant in providing a safer yet efficacious alternative to levetiracetam. Objective The aim of this study was to evaluate the efficacy of brivaracetam for prophylaxis of EPTS and to compare it with levetiracetam. Materials and Methods A prospective, single-blind, parallel-group (alternate allocation) controlled trial over 100 patients admitted with traumatic brain injury in the Department of Neurosurgery, Goa Medical College, Panaji, Goa, India. The data was analyzed using IBM SPSS Statistics 29.0. Results Twenty patients developed EPTS in the study group: 8 from the group receiving brivaracetam and 12 from the group receiving levetiracetam. Although the brivaracetam group had a lower incidence of EPTS, the difference was not statistically significant. Eleven patients from the levetiracetam group developed side effects, while six patients from the brivaracetam group had side effects. There was no significant difference in the incidence of side effects. Conclusion Brivaracetam has efficacy equal to that of levetiracetam for prophylaxis of EPTS. [ABSTRACT FROM AUTHOR]

ABSTRACT Levetiracetam (LEV) is an anti‐epileptic drug used extra‐label in dogs. Commercially available extended‐release formulations (LEV‐ER), administered twice daily, cannot be crushed or split, limiting their use in small dogs. A compounded LEV‐ER formulation (PO‐COMP) can purportedly be partitioned without loss of extended‐release properties. The aims of this study were to establish the pharmacokinetic parameters of PO‐COMP, divided at the tablet score, and determine the bioequivalence of partitioned PO‐COMP to an intact commercially available Food and Drug Administration‐approved human oral generic formulation of LEV‐ER (PO‐COMM). In a randomized crossover design, 12 healthy dogs received a single IV dose (30 mg/kg) of IV‐COMM, a single oral dose (500 mg) of intact PO‐COMM, or a single oral dose (500 mg) of partitioned PO‐COMP and underwent serial measurement of plasma LEV concentrations over 24 h. PO‐COMP was bioequivalent to PO‐COMM using the 90% confidence interval method for maximum concentration (−3.2% difference [CI −7.4% to −1.1%]) and area under the curve (−14.4% difference [CI −17.8% to 10.8%]). PO‐COMP may improve medication adherence and seizure control relative to immediate‐release LEV, which requires three times daily dosing. Efficacy studies of PO‐COMP are warranted. [ABSTRACT FROM AUTHOR]

Background Objectives Animals Methods Results Conclusions and Clinical Importance Myoclonus has been described in aging Cavalier King Charles Spaniels (CKCS), but the natural course of the disease and response to treatment have not been described.Report the clinical features and course of myoclonus in CKCS.Twenty‐seven caregivers provided questionnaire responses at a median of 24 months after the onset of myoclonus in their CKCS. Fifteen caregivers completed a second follow‐up questionnaire at a median of 17 months after submission of the first questionnaire.The caregivers of affected CKCS were invited to provide video footage for review. Owners of CKCS with videos demonstrating myoclonus then completed the online questionnaire for further evaluation. A second shortened questionnaire was sent to participants at least 6 months after completion of the first.Most CKCS displayed spontaneous myoclonus affecting predominantly the head (25/27). Overall, the majority had episodes that increased in frequency (20/27) and severity (17/27). Eighteen dogs had developed changes in behavior since the onset of myoclonus. These dogs were typically older and had experienced myoclonic episodes for longer than dogs without behavioral changes. Generalized epileptic seizures were reported in 4/27 dogs. Ten dogs received medical treatment. Eight were prescribed levetiracetam; all had an initial decrease in episode frequency, but a subsequent increase in both frequency and severity of episodes was common.Myoclonus in CKCS tends to progress in frequency and severity regardless of treatment. Progressive behavioral changes suggestive of cognitive decline are common. These findings support the possibility of an underlying neurodegenerative process. [ABSTRACT FROM AUTHOR]

The development of chitosan-coated nanoliposomes has emerged as a promising strategy for enhancing the intranasal delivery of therapeutic agents targeting the central nervous system. In this study, optimized Levetiracetam-loaded nanoliposomes (Opt-LEV-NLs) were coated with 0.1% and 0.3% chitosan to improve nasal uptake and mucoadhesion. The formulations were evaluated for vesicle size, entrapment efficiency, invitro release, surface morphology, zeta potential, and pH to select the best formulation for brain targeting. Results demonstrated that 0.1% chitosan-coated nanoliposomes (Chit-NLs) retained an optimal particle size (151.72 ± 1.37 nm), suitable for nasal delivery, with a satisfactory entrapment efficiency (64.56 ± 1.03%) and effective drug release (82.51 ± 2.15%). In contrast, 0.3% Chit-NLs exhibited larger particle sizes (> 300 nm), lower release rates, and reduced suitability for intranasal delivery. TEM and zeta potential analyses confirmed the successful chitosan coating and improved mucoadhesive properties. Based on these findings, 0.1% Chit-NLs were selected as the optimized formulation for further studies. This research supports the potential of chitosan-coated nanoliposomes for enhancing the bioavailability of Levetiracetam via the intranasal route. [ABSTRACT FROM AUTHOR]

The number of available antiseizure medications with demonstrated efficacy in cats is limited. As such, there is a need to evaluate the pharmacokinetics of newer medications so that proper dosing regimens can be made. Brivaracetam (BRV) is a more potent analogue of levetiracetam, and is Food and Drug Administration approved for use in people. The goal of this study was to describe the pharmacokinetics of intravenous and oral doses of BRV in healthy cats. A cross‐over study involving eight healthy cats, that were administered 10 mg of BRV intravenously as a bolus and orally in the fasted state. Blood samples were collected over 24 h. Analysis was performed using liquid chromatography‐mass spectrometry. Data were subjected to non‐compartmental analysis. Median (min–max) of maximal concentration, time to maximal concentration, area under the curve, elimination half‐life and oral absolute bioavailability were 902 (682–1036) ng/mL, 0.6 (0.5–2.0) h, 6.4 (5.2–7.2) h, 8145 (6669–9351) ng × h/mL and 100% (85–110) respectively. BRV appeared to be well tolerated by all cats. A single dose of BRV is well tolerated both orally and intravenously. Maximal concentrations are produced rapidly and within the human reference interval considered to be therapeutic. [ABSTRACT FROM AUTHOR]

Levetiracetam (LEV) and carbamazepine (CBZ) are effective monotherapies for focal epilepsy in children. However, the best drug remains controversial. Therefore, we performed a systematic review and meta-analysis comparing LEV and CBZ monotherapy in the management of pediatric focal epilepsy (PFE). We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) published until February 2024 comparing LEV and CBZ monotherapy in PFE. Statistical analysis was performed using R version 4.2.2, heterogeneity was assessed using I2 statistics, and the risk of bias was evaluated using the RoB-2 tool. Risk Ratios (RR) with p < 0.05 were considered significant. The outcomes of interest were seizure freedom, any adverse events, adverse events leading to treatment discontinuation, dermatologic adverse events, and the frequency of at least one seizure, defined as the proportion of patients experiencing one or more seizures during the treatment period. Four RCTs comprising 381 children with a mean age of 7.32 to 9.28 years were included, of whom 186 (48.8%) received LEV monotherapy. There was no significant difference between groups (RR: 1.15; 95% CI 0.88–1.50; p = 0.31; I2 = 90%) regarding seizure freedom. The frequency of at least one seizure (RR: 0.71; 95% CI 0.52–0.97; p = 0.03; I2 = 8%) and dermatologic adverse events (RR: 0.24; 95% CI 0.09–0.64; p < 0.01; I2 = 0%) were both significantly lower in the LEV group. There were no significant differences in the presence of any adverse events (RR: 0.58; 95% CI 0.33–1.01; p = 0.05; I2 = 36%) or adverse events leading to treatment discontinuation (RR: 0.67; 95% CI 0.13–3.42; p = 0.63; I2 = 30%). Conclusion: In monotherapy, LEV was more advantageous than CBZ for PFE, with a lower frequency of seizures and fewer dermatological adverse events. However, both drugs are equally effective in achieving seizure freedom, adverse events without specification, and those that lead to treatment discontinuation. Our findings have important implications for clinical practice and decision-making in this condition. What is Known: • Both LEV and CBZ are effective monotherapies for pediatric focal epilepsy. • The use of LEV or CBZ monotherapy for the management of children with focal epilepsy remains controversial. What is New: • No significant differences were observed between the LEV and CBZ groups in terms of overall seizure freedom, safety, and tolerance. • However, LEV resulted in a lower frequency of at least one seizure and fewer dermatological adverse events than CBZ. [ABSTRACT FROM AUTHOR]

Status epilepticus (SE) is a neurologic emergency defined as continued seizure activity greater than five minutes or recurrent seizure activity without return to baseline. Benzodiazepine-refractory SE is continuous seizure activity despite treatment with a benzodiazepine. Treatment of benzodiazepine-refractory SE includes levetiracetam with loading doses ranging from 20 mg/kg to 60 mg/kg up to a maximum dose of 4500 mg. While levetiracetam has minimal adverse effects, there is currently a lack of studies directly comparing the safety and efficacy of various loading doses of levetiracetam. The objective of this study was to evaluate the safety and efficacy of three loading doses of levetiracetam in the setting of benzodiazepine-refractory SE. This was a single center, retrospective cohort study of adult patients with benzodiazepine-refractory SE who were treated with levetiracetam from April 1, 2016, to August 31, 2023. Patients with documented hypersensitivity to levetiracetam, those who were pregnant or incarcerated and patients who received an alternative antiepileptic drug (AED) prior to levetiracetam were excluded. Patients with other identifiable causes of SE including hyperglycemia, hypoglycemia, hyponatremia or who were post cardiac arrest were also excluded. Patients were divided into three arms based on loading dose of levetiracetam administered (≤20 mg/kg [LEVlow], 21‐–39 mg/kg [LEVmed] or ≥40 mg/kg [LEVhigh]). The primary endpoint was the rate of seizure termination, defined as the lack of need for an additional AED within 60 min following levetiracetam administration. Secondary outcomes included the rate of intubation, and recurrent seizure activity 60 min to 24 h post seizure termination as defined by positive EEG results or need for an additional AED. Subgroup analyses were performed to assess the influence of adequate loading doses of benzodiazepines, and outpatient levetiracetam use. Overall, 740 patients were screened for inclusion, with 218 patients being included in the primary analysis. Patients were divided into three groups with an average levetiracetam loading dose of 14.5 mg/kg in the LEVlow group, 28.8 mg/kg in the LEVmed group, and 48.8 mg/kg in the LEVhigh group. There was no difference in rates of seizure termination at 60 min (92.9% LEVlow vs 89.3% LEVmed vs 84.7% LEVhigh; p = 0.377). Additionally, no difference was found in rates of recurrent seizure activity between 60 min and 24 h post levetiracetam loading dose (32.1% LEVlow vs 32.0% LEVmed vs 28.8% LEVhigh; p = 0.899). However, the LEVhigh group did have a higher rate of intubation (45.8%) compared to the LEVmed (28.2%) and LEVlow (26.8%) group (p = 0.040). The loading of levetiracetam did not result in a statistically significant difference in rate of seizure termination at 60 min nor did it appear to impact the rate of recurrent seizures at 24 h. However, we did find higher rates of intubation in patients who received levetiracetam >40 mg/kg. Further research is warranted to determine the optimal loading dose of levetiracetam in benzodiazepine-refractory SE. [ABSTRACT FROM AUTHOR]

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Time is critical in executing acute seizure treatment, and efforts to minimize operational delays with medication preparation confer potential logistical and practical advantages. Multiple studies have demonstrated the safety and tolerability of intravenous (IV) undiluted levetiracetam (LEV) in adults; however, published pediatric data are limited. This study aims to evaluate the safety and tolerability of IV undiluted LEV in pediatrics. This was a retrospective, dual‐center, observational cohort study evaluating concentration‐related adverse drug events with IV undiluted (100 mg/mL) LEV in pediatrics over a 3‐year 3‐month timespan. A total of 60 undiluted administrations in 52 patients were included in the study. The median age was 4 years; 58.3% of patients were younger than 5 years of age. All doses were administered via a peripheral IV line. The most common IV anatomic site and peripheral IV gauge (G) was the antecubital (66.6%) and 22G catheter (63.3%). There were no documented concentration‐related adverse drug events. Regardless of IV anatomic site, IV gauge, and administered dose there were no documented concentration‐related adverse effects with IV undiluted LEV in a pediatric population. IV undiluted LEV may be considered safe and tolerable in pediatrics. Prospective pediatric studies should assess the safety and tolerability of IV undiluted LEV. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy (HE) is a serious brain disorder which associated with neurological and psychiatric manifestations. Oxidative stress and neuroinflammation and apoptosis play main roles in the development of brain damage in HE. Levetiracetam is an antiseizure drug with established antioxidant and anti-inflammatory activities. In the present study we investigated the therapeutic effects of levetiracetam against brain injury in HE and its underlying mechanisms of action. Male C57BL/6 mice were subjected to the induction of HE by the injection of thioacetamide (200 mg/kg) for 2 days. Mice were treated with levetiracetam at two doses (50 or 100 mg/kg/day) for 3 days in the treatment groups. Animals were subjected to a behavioral test and the brain tissues were dissected for histopathological, biochemical, gene expression and immunofluorescence analysis. The results showed that levetiracetam alleviated body weight loss and improved locomotor activity of mice with HE. Levetiracetam treatment decreased the histopathological changes, lipid peroxidation and protein carbonylation while restored the antioxidants (GSH, SOD and CAT) in the brain. Levetiracetam decreased the expression and activity of NF-κB, NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IFN-γ) in the brain tissue. Administration of levetiracetam inhibited iNOS/NO pathway and myeloperoxidase (MPO) activity in the brain. Moreover, caspase-3 was decreased and the ratio of Bcl2/Bax was increased in the brain of mice treated with levetiracetam. These findings suggest that levetiracetam may be a promising therapeutic agent for brain injury in HE through inhibiting the oxidative, inflammatory and apoptotic pathways. [ABSTRACT FROM AUTHOR]

Many antiseizure medications cause apoptotic cell death in developing brains. The newer antiseizure medication lacosamide is increasingly used in neonates and infants. Neurotoxicity of lacosamide and its combination with levetiracetam was studied in neonatal mice. Animals received single or repeat injections of saline, phenobarbital (75mg/kg), lacosamide (20–40mg/kg), levetiracetam (100mg/kg), lacosamide (40mg/kg) + levetiracetam (100mg/kg) and euthanized at 6 to 30 hours. Cells undergoing apoptosis were increased in the brains of phenobarbital‐treated animals. Densities of apoptotic profiles following lacosamide and levetiracetam treatment did not differ from saline‐treated controls. Findings suggest that lacosamide, levetiracetam and their combination do not cause apoptosis in developing mouse brains. ANN NEUROL 2024;96:812–818 [ABSTRACT FROM AUTHOR]

Objective: Intravenous (IV) push (IVP) is an alternative administration method for levetiracetam, but evidence evaluating it compared to IV piggyback (IVPB) for loading doses in acutely seizing patients is limited, particularly in patients with status epilepticus (SE). This study aimed to compare the efficiency and safety of IVP versus IVPB levetiracetam loading doses. Methods: This was a single‐center sequential retrospective study conducted in adult (≥18 years) patients who received an IV levetiracetam loading dose (>2000 mg or ≥20 mg/kg) for acute or suspected seizure. The primary outcome was time to administration, compared between doses given as IVP versus IVPB. Secondary outcomes included rates of adverse events (AEs), rescue benzodiazepine or antiseizure medication administration, intubation, and intensive care unit (ICU) admission between groups. Results: A total of 246 patients were included; 116 received IVP and 130 received IVPB loading doses. Median age was 56 years; most patients were male (62%) and White (60%) and had witnessed seizures (67%). Doses were administered for SE in 32 (27.5%) and 46 (35.4%) patients in the IVP and IVPB arms, respectively. Median time to administration was shorter in the IVP group (12 vs. 38 min, p <.001). Bradycardia (1.7% vs. 2.3%, p =.99), hypotension (7.8% vs. 12%, p =.30), sedation (6% vs. 12.3%, p =.09), intubation (10% vs. 8%, p =.37), ICU admission (32% vs. 39%, p =.31), and rescue medication administration (8.6% vs. 14.6% p =.10) were similar between groups. In SE patients, IVP was associated with shorter time to administration (12 vs. 44 min, p =.003) and lower odds of ICU admission after adjustment for age, dose, Status Epilepticus Severity Score, and seizure history (adjusted odds ratio =.23, 95% confidence interval =.06–.81). Significance: IVP reduced time to levetiracetam administration versus IVPB and was not associated with more AEs. Rescue agent use, intubation, and ICU admission were similar between arms, but IVP may reduce ICU admissions in SE patients. Prospective studies should assess the effectiveness of IVP versus IVPB. [ABSTRACT FROM AUTHOR]

• VPA therapy for six months resulted in insulin resistance, alteration in weight, and metabolic hormones (leptin and adiponectin). • These changes were independent of serum level or pharmacokinetic of VPA. • In LEV group, no such changes were observed despite increased serum LEV level and decreased Vd and CL of LEV after six months of therapy. • These findings may be considered for optimization of ASM treatment regimen in adult patients with obesity or metabolic dysfunctions. To evaluate the incidence of insulin resistance and its association with change in serum anti-seizure medication (ASM) level and their pharmacokinetic, body composition and metabolic hormones after six months of levetiracetam (LEV) exposure in persons with epilepsy (PWE) in comparison to valproate (VPA). This prospective-longitudinal study included clinically diagnosed PWE on VPA or LEV monotherapy (for<3 months). At enrolment, body weight/composition, BMI were measured and blood samples were collected for assessing metabolic dysfunctions by estimation of serum insulin, insulin resistance [in terms of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)], leptin, adiponectin, lipid profile along with ASMs level. Subjects were followed up for six months and all the above parameters were reassessed. A total of 150 PWE were screened based on inclusion and exclusion criteria, and 105 number of subjects were enrolled (n = 35 in VPA and n = 70 in LEV group). Out of them, 92 subjects (n = 32 in VPA; n = 60 in LEV) completed six months follow-up. After six months, serum insulin level increased significantly in VPA group compared to baseline p < 0.001). Insulin resistance (HOMA-IR>2.5) was observed in 14.28 % of PWE in VPA group. Significantly higher percentage-change in body-weight (p = 0.003), leptin and decreased adiponectin were found in VPA-group compared to baseline ((p = 0.003, 0.02, 0.001, <0.001, respectively). These changes were independent of serum level or pharmacokinetic of VPA. On the other hand, no such changes were observed in LEV-group despite increased serum LEV level and altered pharmacokinetic parameters after six months. Six months treatment with VPA resulted in insulin resistance and metabolic dysfunctions in PWE. These alterations were not correlated with change in VPA serum level. These changes were not observed in LEV therapy suggesting its better safety profile. This may be considered while prescribing the ASM like VPA and LEV in adult patients with obesity or insulin resistance and diabetes. [ABSTRACT FROM AUTHOR]

Objective To compare the clinical efficacy and safety of levetiracetam and oxcarbazepine in the treatment of focal epilepsy. Methods A total of 476 patients with focal epilepsy treated at Fujian Provincial Hospital from October 2020 to October 2022 were selected. Based on their medication, they were divided into the levetiracetam group (n = 275) and the oxcarbazepine group (n = 201). Both groups underwent continuous treatment for 12 months. The overall effective rate and incidence of adverse reactions in both groups and different subgroups were analyzed. Results The overall effective rate in the levetiracetam group was 57.82% (159/275), and in the oxcarbazepine group was 46.77% (94/201). The overall effective rate in the levetiracetam group was higher than that in the oxcarbazepine group (χ2 = 5.696, P = 0.017). Efficacy analysis of levetiracetam monotherapy across different age subgroups showed statistically significant differences (χ2 = 6.785, P = 0.034), with the overall effective rate in younger patients being higher than that in minors (χ2 = 3.898, P = 0.048) and middle-aged/older patients (χ2 = 4.946, P = 0.026). Levetiracetam was more effective in patients with initially normal imaging compared to those with abnormal imaging (χ2 = 5.349, P = 0.021). In the oxcarbazepine monotherapy subgroup analysis, oxcarbazepine was also more effective in patients with initially normal imaging (χ2 = 10.036, P = 0.002). Efficacy analysis of the same subgroup with different medications indicated that for younger patients with focal epilepsy, levetiracetam was superior to oxcarbazepine (χ2 = 6.591, P = 0.010). In the levetiracetam group, 13 cases (4.73%) experienced adverse reactions, while the oxcarbazepine group had 19 cases (9.45%). The incidence of adverse reactions in the oxcarbazepine group was higher than that in the levetiracetam group (χ2 = 4.135, P = 0.042). Conclusions Compared to oxcarbazepine monotherapy, levetiracetam monotherapy demonstrated better clinical efficacy in treating focal epilepsy, particularly in younger patients. The incidence of adverse reactions in levetiracetam was lower. Both medications were more effective in patients with initially normal imaging compared to those with abnormal imaging. [ABSTRACT FROM AUTHOR]

Status epilepticus (SE) is a life-threatening neurological condition with significant mortality. Rapid management is essential to minimize the mortality and disability of SE. Two recent trials provided evidence to guide SE management in early and established stages. The Rapid Anticonvulsant Medication Prior To Arrival Trial (RAMPART, 2011) showed that intramuscular midazolam is a better alternative for early convulsive SE in prehospital settings. The Established Status Epilepticus Treatment Trial (ESETT, 2020) supported the use of sodium valproate and levetiracetam as second-line treatment for its efficacy and shorter administration time. However, there are challenges to revising the status epilepticus management in resource-limited settings, in pre-hospital, first- and second-line treatment, as well as management of refractory and super-refractory SE. These challenges included restrictions or lack of training in the administration of benzodiazepine in the prehospital setting, limited availability and accessibility of newer antiseizure medications (ASMs) in emergency departments and smaller hospitals, and low clinicians’ awareness of the latest evidence. A collaborative effort to educate, improve awareness, and make certain ASMs more readily available is recommended to achieve a better clinical outcome in SE.

Abstract Perampanel belongs to a novel class of antiseizure medications (ASMs). Studies examining the effect of hemodialysis on perampanel serum levels in clinical settings are lacking. We aimed to evaluate the changes in serum perampanel levels during hemodialysis. We studied patients with seizures who received oral perampanel between April 2020 and March 2023 and whose serum concentration of perampanel was measured before and after hemodialysis. We analyzed the serum concentrations of levetiracetam and lacosamide for comparison. Fourteen patients, with a mean age of 76.1 ± 7.88 years, were included. The dose of perampanel was 2.14 ± 1.27 mg. The hemodialysis clearance rate of perampanel, levetiracetam, and lacosamide was 0 ± 13%, 69 ± 11%, and 59.6 ± 8.2%, respectively. The post‐dialysis CD ratio decreased significantly with levetiracetam but not with perampanel. Adverse but acceptable effects of perampanel were observed in two patients. The serum concentrations of several ASMs have been shown to be reduced during hemodialysis. Our study revealed that the serum perampanel concentration does not decrease during hemodialysis. Owing to the low rate of adverse effects and the stability of perampanel serum concentration during hemodialysis, perampanel could be a favorable choice as an ASM for patients with seizures undergoing hemodialysis. Plain Language summary Our study looked at how hemodialysis affects the serum levels of perampanel, a new type of medication for seizures. In 14 patients who started treatment between April 2020 and March 2023, perampanel serum levels did not decrease during hemodialysis, unlike other seizure medications. This shows that perampanel can be a good option for patients with seizures who need hemodialysis, with fewer side effects compared to other medications.