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Background and Objective: Antiseizure medications (ASMs) can potentially trigger psychobehavioral adverse events associated with the onset or exacerbation of psychiatric symptoms such as irritability, aggression, and hyperactivity. The objective of this study was to evaluate the effects of levetiracetam and valproic acid on changes in clinical features of anger, attention deficit hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD). The purpose was to furnish guidance on rational drug selection in children and adolescents with epilepsy to minimize psychiatric comorbidity in the treatment of epilepsy., Method: This was a prospective, observational, cohort study involving treatment-naïve children aged 7-18 years with newly diagnosed generalized or focal epilepsy who were prescribed levetiracetam or valproic acid as monotherapy for a 6-month period and regularly followed up. Psychiatric assessment was conducted at the time of the new epilepsy diagnosis and at the six-month follow-up. These assessments were performed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children Current and Lifetime Version (DSM-5), a structured psychiatric interview, as well as the State-Trait Anger Expression Style Inventory and Turgay DSM-IV Based Disruptive Behaviour Disorders Screening and Rating Scale. Anger subscores, ADHD symptoms, change in diagnosis, focal and generalized epilepsy groups, continuous seizures and seizure-free periods before and 6 months after treatment with valproic acid and levetiracetam were compared., Results: A total of 50 children, 25 in the valproic acid group and 25 in the levetiracetam group, with a mean age of 11.92 ± 3.08 years, were included in the study. There was a statistically significant increase in the ADHD subscale score post-treatment among patients receiving levetiracetam (p = 0.045) and valproic acid (p = 0.034) compared with pre-treatment. The change in both anger-in and anger-out expression scores with treatment was significantly higher in patients receiving levetiracetam (p = 0.035) compared with those receiving valproic acid (p = 0.026). Statistically, there was a significant difference in the diagnostic criteria of the levetiracetam group pre- and post-treatment (p = 0.026). The proportion of patients in whom the diagnostic criteria for ADHD+ODD were fulfilled increased from 16% before treatment to 48% after treatment, a statistically significant increase (p = 0.026)., Conclusion: This study found an increase in internalized anger features and ADHD symptom severity in children with epilepsy treated with valproic acid and levetiracetam. In those prescribed levetiracetam, there was a statistically significant rise in the proportion meeting the diagnostic criteria for ADHD + ODD. Our research is one of the first to prospectively examine the psychiatric assessment of children diagnosed with epilepsy. The remarkable results demonstrate changes in psychiatric diagnoses associated with the treatment of levetiracetam and valproic acid. Furthermore, a considerable rise in ADHD symptoms was observed in those treated with valproic acid., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Competing Interests: The authors have no conflict of interest to declare.

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) affects nearly half of the 39 million people living with HIV. HAND symptoms range from subclinical cognitive impairment to dementia; the mechanisms that underlie HAND remain unclear and there is no treatment. The HIV protein transactivator of transcription (TAT) is thought to contribute to HAND because it persists in the central nervous system and elicits neurotoxicity in animal models. Network hyperexcitability is associated with accelerated cognitive decline in neurodegenerative disorders. Here we show that the antiepileptic drug levetiracetam (LEV) attenuated aberrant excitatory synaptic transmission, protected synaptic plasticity, reduced seizure susceptibility, and preserved cognition in inducible TAT (iTAT) transgenic male mice. iTAT mice had an increased frequency of spontaneous excitatory postsynaptic currents in hippocampal slice recordings and impaired long-term potentiation, a form of synaptic plasticity that underlies learning and memory. Two-week administration of LEV by osmotic minipump prevented both impairments. Kainic acid administered to iTAT mice induced a higher maximum behavioral seizure score, longer seizure duration, and shorter latency to first seizure, consistent with a lower seizure threshold. LEV treatment prevented these in vivo signs of hyperexcitability. Lastly, in the Barnes maze, iTAT mice required more time to reach the goal, committed more errors, and received lower cognitive scores relative to iTAT mice treated with LEV. Thus, TAT expression drives functional deficits, suggesting a causative role in HAND. As LEV not only prevented aberrant synaptic activity in iTAT mice but also prevented cognitive dysfunction, it may provide a promising pharmacological approach to the treatment of HAND. SIGNIFICANCE STATEMENT: Approximately half of people living with human immunodeficiency virus (HIV) also suffer from HIV-associated neurocognitive disorder (HAND), for which there is no treatment. The HIV protein transactivator of transcription (TAT) causes toxicity that is thought to contribute to HAND. Here, the antiepileptic drug levetiracetam (LEV) prevented synaptic and cognitive impairments in a TAT-expressing mouse. LEV is widely used to treat seizures and is well-tolerated in humans, including those with HIV. This study supports further investigation of LEV-mediated neuroprotection in HAND., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

Introduction: Piracetam, a widely recognized nootropic drug, is hypothesized to enhance memory function through its influence on synaptic plasticity and neurotransmitter levels. However, despite its popularity, there remains a lack of conclusive evidence regarding its impact on memory. Therefore, the present study aims to explore the effects of piracetam on memory in individuals with impaired cognitive function, comparing it to a placebo control group., Objectives: This study will evaluate how piracetam affects memory function, compared to placebo in adults with impairment in this area., Methods: We carried out bibliographical research and meta-analysis of scientific clinical trials comparing memory function in people taking piracetam with those in the placebo group. The PubMed, Dimensions, Embase, and Cochrane Library databases were used. Statistical analysis was performed in R Studio version 4.3.1., Results: In our analysis, 199 articles were identified, of which we included eighteen studies, comprising a total of 886 patients, of which Piracetam was the treatment option in 442 (49.88 %) patients. Memory enhancement (SMD 0.75; 95 % CI [-0.19; 1.69]; p=0.12; I²=96 %) had no clinical difference between the intervention and the control group., Conclusion: Upon the conclusion of this study, it is apparent that we cannot definitively ascertain the impact of piracetam on memory function. Further research is warranted to provide a clearer understanding of the cognitive effects of piracetam in individuals with memory impairment. This investigation serves as a significant contribution to the ongoing quest to elucidate the potential benefits of piracetam in the field of cognitive neuroscience., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Factors affecting serum concentrations of levetiracetam in dogs are unknown and could affect the efficacy of levetiracetam in controlling seizures in dogs with epilepsy., Hypothesis/objectives: 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., Animals: Sixty-nine client-owned dogs with epilepsy treated with levetiracetam alone or in combination, based on 127 trough serum concentration measurements of levetiracetam., Methods: 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., Results: The PO dose of levetiracetam significantly explained changes in serum levetiracetam concentration, and this causal link was stronger with monotherapy (R 2  = 0.59, P < .001). Phenobarbital significantly decreased serum levetiracetam concentration in a dose dependent manner (R 2  = 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., Conclusion and Clinical Importance: 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., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Breath-holding spells are a benign condition primarily seen in 3% to 5% of healthy children aged between six months and five years. Although no specific treatment is recommended due to its benign nature, iron and piracetam are used in severe or recurrent cases. We planned to compare the heart rate variability (HRV) before and after treatment with 24-hour Holter monitoring in patients receiving iron and piracetam treatment and investigate the treatment's effectiveness., Methods: Twenty-five patients who applied to the outpatient clinic between 2013 and 2015 due to breath-holding spells were included in the study. The patients who received piracetam and iron therapy and underwent 24-hour rhythm Holter monitoring were evaluated retrospectively., Results: Fourteen (56%) of these patients were evaluated as having cyanotic-type and 11 (44%) patients were assessed as having pale-type breath-holding spells. A significant difference was found only between hourly peak heart rate and total power in the group receiving iron treatment. Significant differences were also found among the minimum heart rate, mean heart rate, the standard deviation of RR intervals, the mean square root of the sum of the squares of their difference between adjacent RR intervals, spectpow, and low frequency before and after the treatment in the patients who started piracetam treatment (P < 0.05)., Conclusions: Our study is critical as it is the first to investigate the effects of treatment options on various HRV in patients with breath-holding spells. There were statistically significant changes in HRV parameters in patients receiving piracetam, and the number of attacks decreased significantly. Piracetam treatment contributes positively to the breath-holding spell with regard to efficacy and HRV, therefore it can be used to treat breath-holding spells., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To explore mechanism of piracetam for the treatment of spinal cord injury in rats through mitogen-activated protein kinase (MAPK) pathway., Methods: Fifty-four healthy 6-week-old SD female rats with body weight of 80 to 100 g were divided into sham operation group, spinal cord injury group and piracetam group by random number table method, with 18 rats in each group. Spinal cord injury model was established in spinal cord injury group and piracetam group using percussion apparatus, while sham operation group did not damage spinal cord. Piracetam group was injected with piracetam injection through tail vein according to 5 ml·kg -1 standard, once a day for 3 days;the other two groups were injected with normal saline at the same dose, the same frequency and the same duration. The rats were sacrificed at 1, 3, and 7 days after surgery, and changes of Basso, Beattie and Bresnahan (BBB) locomotor rating scale was observed and compared. Enzyme-linked immunosorbent assay (ELISA) was used to detect spinal cord inflammatory factors, such as interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1β (interleukin-1β), necrosis factor-α (IL-1β) and tumor necrosis factor-α (TNF-α);HE staining was used to observe morphological changes of rats with spinal cord injury, and immunohistochemistry was used to observe expression level of aquaporin 4 (AQP4). The activation of MAPK signaling pathway in spinal cord of rats after spinal cord injury was observed by western blotting (WB)., Results: BBB scores of sham operation group on 1, 3 and 7 day were 21 points. In spinal cord injury group, the scores were (1±1), (4±1) and (7±2);piracetam group was (1±1), (5±1), (9±2), respectively;the difference between spinal cord injury group and sham operation group was statistically significant ( P <0.05). HE staining showed that no abnormality was found in sham operation group. In spinal cord injury group, bleeding and degeneration of spinal cord tissue appeared at 1 day after operation; flaky necrotic areas were appeared in spinal cord at 3 days after surgery, and spinal cord tissue began to slowly repair at 7 days after surgery. In piracetam group, the bleeding area was less than that of spinal cord injury group at 1 day after surgery;at 3 days after operation, the necrotic area was reduced and the range of nuclear disappearance was reduced; and the spinal cord began to recover slowly at 7 days after surgery. AQP4 staining of spinal cord of rats in sham operation group was weak at 1, 3 and 7 days after modeling, AQP4 staining was deepened and area increased in spinal cord injury group, AQP4 staining of piracetam group was lighter than that of spinal cord injury group, and the positive cells were slightly increased and the staining was slightly darker than that of sham operation group. At 1, 3 and 7 days, the level of IL-6, IL-10, IL-1β and TNF-α in spinal cord injury group were higher than those in sham operation group and piracetam group( P <0.05). Compared with spinal cord injury group, the area of spinal cord bleeding and necrosis were decreased by HE staining in piracetam group, and AQP4 staining was decreased by immunohistochemistry. WB results showed that P-ERK, P-JNK and P-P38 levels in spinal cord injury group at 3 days were higher than those in sham operation group and piracetam group( P <0.05)., Conclusion: Piracetam not only showed significant effect in promoting motor function recovery after spinal cord injury, but also showed positive therapeutic potential in reducing lesion area, regulating AQP4 expression to reduce edema, and reducing inflammatory response by regulating MAPK signaling pathway.

Introduction: Adverse skin reactions due to drugs such as Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) occur in 3% of people receiving anti epileptic drugs (AED). Although SJS/TEN has a low incidence, the mortality and morbidity rates are high. Indonesia has not adopted HLA-B*1502 screening prior to administration of carbamazepine (CBZ), although previous studies found a relationship between HLA-B*1502 and SJS/TEN., Methods: A hybrid decision tree and Markov model was developed to evaluate three strategies for treating newly diagnosed focal epilepsy: CBZ direct therapy, levetiracetam (LEV) direct therapy, and therapy based on HLA-B*15:02 test results. From a societal perspective, base case and sensitivity analyses were carried out over a lifetime., Results: Direct administration of CBZ appears to have a slightly lower average cost than the HLA-B*15:02 allele screening strategy. The increase in quality-adjusted life year (QALY) in HLA-B*15:02 screening before treatment related to the cost difference reached 0.519 with an incremental cost-effectiveness ratio (ICER) of around USD 984 per unit of QALY acquisition. Direct treatment of LEV increased treatment costs by almost USD 2000 on average compared to the standard CBZ strategy. The increase in QALY is 0.834 in direct levetiracetam treatment, with an ICER of around USD 2230 for each QALY processing., Conclusion: Calculation of the cost-effectiveness of lifetime epilepsy therapy in this study found that the initial screening strategy with the HLA-B*15:02 test was the most cost-effective., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Levetiracetam is the most commonly used antiepileptic drug in pregnant women due to its low teratogenic risk profile, favorable pharmacokinetic characteristics, and safety profile. Serum levels of levetiracetam vary in epilepsy during pregnancy. Therefore, the aim of the study was to evaluate the serum levels of levetiracetam during different trimesters of pregnancy by using therapeutic drug monitoring (TDM)., Materials and Methods: This was a single-center, prospective study. Pregnant women with epilepsy on levetiracetam were enrolled after getting written informed consent from them. Serum trough levels of levetiracetam were estimated at all trimesters by high-performance liquid chromatography (HPLC)., Results: The study included 16 participants with mean ± standard deviation (SD) age of 27.75 ± 4 years. There were nine (56.2%) participants with generalized seizure disorder and seven (43.8%) participants of focal seizure disorder. Among 16 patients, 10 (62.5%) participants were on levetiracetam alone and six (37.5%) participants were on levetiracetam combined with other antiepileptic drugs. In a total of 48 trough samples, 45 sample concentrations were below the therapeutic range of 12-46 mg/l and three sample concentrations were within the therapeutic range. There was a statistically significant difference in the concentration-dose ratio (CDR) of levetiracetam between the third and first trimesters (P-value 0.018)., Conclusion: There was a statistically significant difference in serum levetiracetam concentration between the third and first trimesters. A well-conducted, intensive pharmacokinetic sampling study in PWWE with a control group is needed in future to evaluate the whole pharmacokinetic profile of levetiracetam and to correlate the clinical outcome., (Copyright © 2024 Copyright: © 2024 Neurology India, Neurological Society of India.)

Hippocampal hyperactivity is a novel pharmacological target in the treatment of schizophrenia. We hypothesized that levetiracetam (LEV), a drug binding to the synaptic vesicle glycoprotein 2 A, normalizes hippocampal activity in persons with schizophrenia and can be measured using neuroimaging methods. Thirty healthy control participants and 30 patients with schizophrenia (28 treated with antipsychotic drugs), were randomly assigned to a double-blind, cross-over trial to receive a single administration of 500 mg oral LEV or placebo during two study visits. At each visit, we assessed hippocampal function using resting state fractional amplitude of low frequency fluctuations (fALFF), cerebral blood flow (CBF) with arterial spin labeling, and hippocampal blood-oxygen-level-dependent (BOLD) signal during a scene processing task. After placebo treatment, we found significant elevations in hippocampal fALFF in patients with schizophrenia, consistent with hippocampal hyperactivity. Additionally, hippocampal fALFF in patients with schizophrenia after LEV treatment did not significantly differ from healthy control participants receiving placebo, suggesting that LEV may normalize hippocampal hyperactivity. In contrast to our fALFF findings, we did not detect significant group differences or an effect of LEV treatment on hippocampal CBF. In the context of no significant group difference in BOLD signal, we found that hippocampal recruitment during scene processing is enhanced by LEV more significantly in schizophrenia. We conclude that pharmacological modulation of hippocampal hyperactivity in schizophrenia can be studied with some neuroimaging methods, but not others. Additional studies in different cohorts, employing alternate neuroimaging methods and study designs, are needed to establish levetiracetam as a treatment for schizophrenia., (© 2023. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy. Levetiracetam (LEV) is an antiepileptic drug whose mechanism of action at the genetic level has not been fully described. Therefore, the aim of the present work was to evaluate the relevant gene expression changes in the dentate gyrus (DG) of LEV-treated rats with pilocarpine-induced TLE. Whole-transcriptome microarrays were used to obtain the differential genetic profiles of control (CTRL), epileptic (EPI), and EPI rats treated for one week with LEV (EPI + LEV). Quantitative RT-qPCR was used to evaluate the RNA levels of the genes of interest. According to the results of the EPI vs. CTRL analysis, 685 genes were differentially expressed, 355 of which were underexpressed and 330 of which were overexpressed. According to the analysis of the EPI + LEV vs. EPI groups, 675 genes were differentially expressed, 477 of which were downregulated and 198 of which were upregulated. A total of 94 genes whose expression was altered by epilepsy and modified by LEV were identified. The RT-qPCR confirmed that LEV treatment reversed the increased expression of Hgf mRNA and decreased the expression of the Efcab1 , Adam8 , Slc24a1 , and Serpinb1a genes in the DG. These results indicate that LEV could be involved in nonclassical mechanisms involved in Ca 2+ homeostasis and the regulation of the mTOR pathway through Efcab1 , Hgf , SLC24a1 , Adam8 , and Serpinb1a , contributing to reduced hyperexcitability in TLE patients.

Objectives: Critically ill patients eliminate levetiracetam (LEV) more rapidly than healthy controls, yet low doses are commonly used for seizure prophylaxis in the ICU setting. We compared the rates of achievement of target serum levels and new onset seizure (clinical and/or electrographic) among patients who received low (500 mg bid) versus high (750-1,000 mg bid) dose LEV., Design: Prospective, observational study., Setting: Tertiary care, academic center., Patients: We included patients who received prophylactic LEV following traumatic brain injury, intracerebral hemorrhage, spontaneous subarachnoid hemorrhage, or supratentorial neurosurgery between 2019 and 2021. Patients with a history of seizure, antiseizure medication use, or renal failure requiring dialysis were excluded., Interventions: None., Measurements: LEV levels were obtained at steady state. The impact of low-dose versus high-dose LEV on the primary outcome of target LEV levels (12-46 μg/mL), and the secondary outcome of clinical and/or electrographic seizure, were assessed using multivariable logistic regression analyses adjusting for age, LEV loading dose, BMI, primary diagnosis and creatinine clearance (CrCl)., Main Results: Of the 205 subjects included in analyses, n = 106 (52%) received LEV 500 mg bid (median 13 mg/kg/d), and n = 99 (48%) received LEV 750-1,000 mg bid (median 25 mg/kg/d). Overall, 111 of 205 patients (54%) achieved target levels: 48 (45%) from the low-dose group versus 63 (64%) from the high-dose group (odds ratio [OR] 2.1; 95% CI, 1.1-3.7; p = 0.009). In multivariable analyses, high-dose LEV predicted target levels (adjusted OR [aOR] 2.23; 95% CI, 1.16-4.27; p = 0.016), and was associated with lower seizure odds (aOR 0.32; 95% CI, 0.13-0.82; p = 0.018) after adjusting for age, loading dose, BMI, diagnosis, and CrCl., Conclusions: Underdosing of LEV was common, with only 54% of patients achieving target serum levels. Higher doses (750-1,000 mg bid) were more than twice as likely to lead to optimal drug levels and reduced the odds of seizure by 68% compared with low-dose regimens (500 mg bid)., Competing Interests: Dr. Frontera’s institution received funding from the National Institute on Aging; she received funding from Physician Education Resource, the National Institute of Neurological Disorders and Stroke, and the National Heart, Lung, and Blood Institute. Dr. Valdes received funding from the National Institutes of Health (NIH); and received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objective: To assess the clinical efficacy and plasma concentrations of levetiracetam in a goat with seizures., Animal: A 5-month-old doeling., Clinical Presentation, Progression, and Procedures: The goat was referred because of progressive anorexia and lethargy over 3 days. Clinical signs consisted of weakness, obtundation, opisthotonos, anisocoria, and cortical blindness. Initial evaluation was most consistent with polioencephalomalacia., Treatment and Outcome: Neurologic improvement occurred within 4 hours of thiamine administration, with appetite returning over 12 hours. On day 3 of hospitalization, the goat suffered acute onset repetitive seizures that were incompletely responsive to standard interventions over 3 hours. Administration of IV levetiracetam (60 mg/kg) produced resolution of seizure activity within 20 minutes. Levetiracetam was continued twice daily IV, then PO after day 6. Plasma concentrations were above or within therapeutic ranges (5 to 45 μg/mL) as previously established for other species, following both IV and PO levetiracetam. Oral administration (60 mg/kg, PO, q 12 h) resulted in plasma levetiracetam concentrations of 48.1 μg/mL 2 hours after a dose and 23.4 μg/mL 2 hours prior to the next dose., Clinical Relevance: Levetiracetam is a newer anticonvulsant commonly used in humans and small animals due to its efficacy, cost, and wide safety margin. Its use has not previously been reported in domestic small ruminants. In this case, levetiracetam showed excellent clinical efficacy in the face of refractory seizures, with no apparent side effects. Plasma concentrations during oral administration were at the high end of the therapeutic range, indicating absorption in a nonmonogastric species. Further studies are warranted to determine optimal dosing in small ruminants.

Introduction: Post-traumatic seizure (PTS) prophylaxis is recommended in patients with traumatic brain injury (TBI) at high risk for PTSs, but consensus on the optimal pharmacologic therapy has not yet been established. Levetiracetam is frequently used for seizure prophylaxis in combat-related TBI, but its efficacy and safety in this patient population has not yet been described., Methods: A retrospective cohort of 687 consecutive casualties transferred to the CONUS from October 2010 to December 2015 was analyzed. Seventy-one patients with combat-related injuries and radiographic evidence of skull fractures or intracranial hemorrhage were included. Data collection included demographics and injury characteristics including initial Glasgow Coma Scale, computed tomography findings, interventions, and 6-month Glasgow Outcome Score., Results: All patients in this cohort were male, with an average age of 25 (median 24; Interquartile range (IQR) 4.5) and an average Injury Severity Score of 28 (median 27; IQR 15). The most common mechanism of injury was explosive blast (76%). Penetrating TBI was common (51%). Most patients (88.7%) were administered seizure prophylaxis. Of these, the majority (61/63) received levetiracetam, and the additional two were administered phenytoin. The remaining 11.3% of patients were deemed not to require seizure prophylaxis. The incidence of seizures while on prophylaxis was low (2.8%) and occurred in patients who suffered transcranial gunshot wounds and ultimately died. No serious adverse effects were attributed to levetiracetam., Conclusions: Levetiracetam appears to be a safe and effective medication for PTS prophylaxis in combat casualties. The rate of PTSs in combat-related TBI on appropriate prophylaxis is low., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Piracetam is the most widely used drug in breath-holding spells (BHS); however, its efficacy might not be satisfying to parents. This study aimed to compare the efficacy of docosahexaenoic acid (DHA) plus piracetam with piracetam alone in reducing the frequency and severity of BHS in infants and preschool children., Methods: This randomized clinical trial included two groups diagnosed with BHS. Group I included 50 patients who received DHA plus piracetam. Group II (control group) included 50 children who were managed with piracetam plus a placebo. Children were re-evaluated at one, three, and six months after treatment. Occurrences of BHS and drug side effects were recorded. The primary outcome was to evaluate the effect of the combined treatment of piracetam and DHA on the frequency and severity of spells., Results: BHS were reported in only 16% of children six months after treatment with piracetam and DHA compared with 50% of those treated with piracetam only (P value = 0.001)., Conclusion: DHA plus piracetam is more effective than piracetam alone in decreasing the frequency and severity of BHS in children., Competing Interests: Declaration of competing interest No financial or nonfinancial benefits have been received or will be received from any party related directly or indirectly to the subject of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background/objective: Levetiracetam is used for seizure prophylaxis in patients presenting with subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI). We aim to characterize the optimal levetiracetam dosage for seizure prophylaxis., Methods: This retrospective cohort study included adult patients at an academic tertiary hospital presenting with SAH or TBI who received levetiracetam at a total daily dose (TDD) equivalent to or greater than 1000 mg. The primary outcome was combined seizure incidence, including clinical and subclinical seizures., Results: We identified 139 patients (49.6% male, mean age 53 years) for inclusion. For patients receiving a 1000-mg TDD, the administration was 500 mg twice daily. For patients receiving >1000-mg TDD, 77/78 patients received 1000 mg twice daily and one patient received 750 mg twice daily. Patients receiving 1000-mg TDD had a higher seizure incidence than those receiving >1000-mg TDD (p = 0.01), despite no difference in examined confounders, including history of alcoholism (p = 0.49), benzodiazepine use (p = 0.28), or propofol use (p = 0.17). No difference in adverse effects was observed (anemia, p = 0.44; leukopenia, p = 0.60; thrombocytopenia, p = 0.86)., Conclusions: Patients may experience a reduced incidence of clinical and electroencephalographic seizures with levetiracetam dosing >1000-mg TDD.

Background: Status Epilepticus (SE) is a life-threatening neurological emergency requiring appropriate therapy to terminate seizure activity. SE is managed with supportive measures and ultra-short-acting benzodiazepines. However, limited data is available in the paediatric population regarding the next best option when this fails. This study aimed at finding new data to recommend levetiracetam or phenytoin as the second-line option., Methods: One hundred and thirty-seven patients with status epilepticus were randomized into two groups; group-I was given IV Levetiracetam (LEV) at 20 mg/kg/dose over 5 minutes followed by a maintenance dose of 20mg/kg/dose BID, whereas Group II received phenytoin at 20mg/kg IV loading dose followed by a maintenance dose of 5-8 mg/kg/day divided BID. The primary outcome was seizure cessation, defined as the termination of the apparent convulsion 30 min after the administration of phenytoin or levetiracetam. Secondary outcomes were the use of different anti-convulsants for continued management, admittance to critical treatment, and severe adverse events (including mortality, Stevens-Johnson syndrome, rash, airway problems, cardiovascular instability, extravasation, and severe agitation). Data was recorded via a clinical proforma and was analyzed by SPSS software version 25. All numerical data were expressed in mean±SD forms, and frequency was determined for qualitative baseline data. Secondary outcomes were tested through the χ2 test, A p-value of ≤0.05 was considered statistical significance., Results: Levetiracetam terminated seizures in 94% of children compared to 77% in those treated with phenytoin. The mean time to seizure termination was 19.94±3.76 minutes for the LEV Group as compared to 23.791±9.1 min for the PHT group. (p=0.046). Regarding safety, a profile study shows LEV has fewer and less severe side effects compared to Phenytoin., Conclusions: Levetiracetam is a safe, well-tolerated, and effective treatment as a second-line antiepileptic drug in the management of status epilepticus.

Background and Purpose: Recommended loading doses of levetiracetam (LEV) for status epilepticus (SE) treatment have increased over time. However, this was not evidence-based, and the benefit of the increase remains unclear. The effect of different LEV loading doses on SE prognosis was explored., Methods: This is a retrospective analysis of an SE adult registry (January 2016-December 2021), including patients receiving LEV as a second-line SE treatment. Patients were stratified according to LEV loading doses (threshold 35 mg/kg). Main outcomes were global mortality, LEV use as last SE treatment, and return to baseline conditions at discharge, exploring LEV as a dichotomized or continuous dose., Results: Among 202 patients, 44 received LEV at ≥35 mg/kg and 158 below it. Global mortality, adjusted for SE severity and potentially fatal aetiology, was more frequent in the high LEV dose group (27.2% vs. 17.1%, odds ratio 3.14, 95% confidence interval 1.23-8.06; p = 0.017), whilst LEV prescription as last treatment and return to baseline conditions were comparable. Considering continuous LEV dosages or mortality in ongoing SE, however, no outcome reached statistical significance., Conclusions: Lower LEV loading doses do not seem to correlate with worse clinical outcome, challenging current guidelines. Further studies, ideally prospective, are needed on this topic., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Purpose: To identify pediatric patients who require therapeutic drug monitoring (TDM) of levetiracetam (LEV)., Methods: We retrospectively investigated 2413 routine therapeutic drug monitoring data on serum LEV concentration from 1398 pediatric patients (age, 0-15 years). Samples were grouped by age (infants, < 1 year; preschool children, 1-5 years; primary school children, 6-11 years; and adolescents, 12-15 years), and the LEV concentration-to-dose (CD) ratio was calculated., Results: The mean CD ratio was highest in adolescents (analysis of variance, p < 0.001); 22.5 % and 15.7 % higher in adolescents than in preschool children and school children, respectively (Scheffé test, p < 0.001); and higher in infants than in preschool children. Preschool children had the lowest ratio and tended to show an increase in the ratio from age 2 to 5 years. Use of enzyme-inducing antiseizure medication reduced the CD ratio by 6.1 % in infants, 12.2 % in preschool children, 5.9 % in primary school children, and 9.4 % in adolescents. The mean CD ratio was 2.7 %, 26.9 %, and 39.3 % higher in preschool children, primary school children, and adolescents with defined chronic kidney disease (CKD) than in the respective age group of patients without CKD. The therapeutic concentration range for a long-term LEV therapy was 11 to 32 μg/mL., Conclusions: LEV pharmacokinetics are significantly different between infant and preschool children, so TDM of LEV is clinically useful in these patients. In pediatric patients at higher risk for CKD, glomerular filtration rate and LEV levels should be carefully monitored., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Introduction: Traumatic brain injury (TBI) can induce early or late post-traumatic seizures (PTS). While PTS incidence is low, prophylaxis is used despite a lack of consensus on agent or duration. Levetiracetam (LEV) for early PTS prophylaxis is preferred due to its safety and efficacy. The purpose of this study was to evaluate LEV for early PTS prophylaxis., Methods and Materials: A single-center, retrospective chart review of TBI patients ≥18 years who received LEV for early PTS prophylaxis between August 2018-July 2019. The primary outcome was LEV duration. Secondary outcomes were incidence of seizure, intensive care unit (ICU) and hospital length of stay (LOS)., Results: Of the 137 included, mean age was 59 ± 20 years and 69.3% were male. The mean admission GCS was 13 ± 4 and 77.4% had mild TBI. Median LEV duration was 7 (IQR 4-10) days and 13.9% met recommended 7-day duration. Those prescribed LEV >7 days had more than twice the median LEV duration than those prescribed ≤7 days [10.25 (8.5-15.5) vs 4 (1.5-4.5) days, p < 0.0001]. Electroencephalography-confirmed PTS occurred in 2.2%, with an early PTS incidence of 0.73%. Median ICU and hospital LOS were 2 (IQR 1-7) and 7 (IQR 3-16) days, respectively., Conclusions: The incidence of PTS was low as most patients in our study had mild or moderate TBI. Early PTS prophylaxis with LEV for 7 days is appropriate, although the majority of patients did not meet the recommended duration. Efforts to standardize and implement PTS prophylaxis protocols are needed., (Copyright © 2022 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Background: Although levetiracetam has been increasingly used as an alternative to phenytoin for early posttraumatic seizure prophylaxis following traumatic brain injury (TBI), an optimal dosing strategy has not been elucidated. The objective of this study is to determine whether different dosing strategies of levetiracetam are associated with the incidence of early posttraumatic seizures when used as prophylaxis following TBI., Methods: This retrospective single-center cohort study included admitted patients ≥ 18 years of age with a diagnosis of TBI and receiving levetiracetam for early posttraumatic seizure prophylaxis between July 1, 2013, and September 1, 2019. The primary outcome of this study was to evaluate three different dosing strategies of levetiracetam (≤ 1000 mg/day, 1500 mg/day, and ≥ 2000 mg/day) and associated rates of early posttraumatic seizures. Secondary outcomes were to summarize absolute total daily maintenance doses of levetiracetam among patients who experienced early posttraumatic seizures compared with those who did not, to determine the impact of three different dosing strategies on hospital length of stay and in-hospital mortality, and to assess patient-specific variables on the occurrence of posttraumatic seizures. Overlap propensity score weighting was used to address the potential for confounding., Results: Of the 1287 patients who received levetiracetam for early posttraumatic seizure prophylaxis during the study time frame, 866 patients met eligibility criteria and were included in the study cohort (289 patients in the ≤ 1000 mg/day group, 137 patients in the 1500 mg/day group, and 440 patients in the ≥ 2000 mg/day group). After weighting, the cumulative incidence of early posttraumatic seizure was 2.9% in the ≤ 1000 mg/day group, 8.8% in the 1500 mg/day group, and 9% in the ≥ 2000 mg/day group. The 1500 mg/day and ≥ 2000 mg/day levetiracetam groups had a 209% and 216% increase in the subdistribution hazard of early posttraumatic seizures compared with the ≤ 1000 mg/day levetiracetam group, respectively, but these differences were not statistically significant., Conclusions: In conclusion, the results of this study demonstrate no statistically significant difference in the cumulative incidence of early posttraumatic seizures within 7 days of TBI between three different levetiracetam dosing strategies. After weighting, the ≤ 1000 mg/day levetiracetam group had the lowest rates of early posttraumatic seizures, death without seizure, and in-hospital mortality., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

We aim to assess the effect of anti-epileptic drug (AED) prophylaxis for early or late posttraumatic seizures, targeting the pediatric population with traumatic brain injury (TBI). We systematically searched for studies reporting the incidence of posttraumatic seizures in pediatric patients who suffered from TBI and received AEDs prophylactically following their TBI incident. Studies that included adult patients, adult and pediatric patients but did not report results for the pediatric population separately, and patients who did not suffer from a TBI were excluded. Studies that did not indicate the use of antiepileptic drugs prophylactically following TBI were excluded. A total of 10 studies were included involving 4621 posttraumatic brain injury patients of the pediatric age population (<18). Five studies assessed the effect of prophylaxis on early seizures, four on late seizures and one on any seizure. The mean incidence of posttraumatic seizures with AED prophylaxis was 8% for early seizures and 7.1% for late seizures. Moreover, one study revealed no benefit of AED prophylaxis for early posttraumatic seizures. Meta-analysis revealed a significant difference in the incidence of early posttraumatic seizures with antiepileptic prophylaxis. However, no significant difference for late posttraumatic seizures has been shown. In conclusion, AED prophylaxis seems to be effective against early posttraumatic seizures for the pediatric population, with levetiracetam possibly being more effective. Also, there is no observed benefit for late posttraumatic seizures., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: One of the newest antiseizure medication is levetiracetam (LEV). It might be effective in various indications, not only related to convulsions. Central nervous system disorders are common during anticonvulsant therapy. The aim of this study was to assess the effect of LEV on various types of memory and anxiety in rats., Methods: Adult male Wistar rats (n = 58) were given LV p.o. as a single (100 mg/kg or 500 mg/kg) or repeated doses (300 mg/kg). The effect of the drug on memory was assessed in the Morris water maze (MWM) (spatial memory), the passive avoidance (PA) (emotional memory) and the novel object recognition (NOR) (recognition memory). The anxiety was evaluated in the elevated plus maze (EPM)., Results: LEV administered as repeated doses disturbed the long-term recognition memory in NOR and locomotor activity in EPM. A single dose affected emotional memory in PA. LEV did not alter spatial memory in MWM., Conclusions: LEV may cause memory and locomotor disturbances, but some of these adverse effects seem to be temporary and limited to the effect of acute dose., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Neonatal seizures represent the most frequent presenting sign of any neurological abnormality secondary to various etiologies in the neonatal period. Phenobarbitone (PB) has been used as first-line anti-epileptic drug in the treatment of seizures but concerns have been raised regarding its neuro-apoptotic effects over the developing brain. Levetiracetam (LEV) is a newer anti-epileptic drug with neuroprotective property and has been used in adults and pediatric patient but its use in neonates have very limited experience. Recently many neonatal studies have sought the role of LEV in the management of neonatal seizures., Aims and Objective: To evaluate the efficacy of Levetiracetam in the management of neonatal seizures., Search Methods: The literature search was done for this systematic review by searching the Cochrane Central Register of Controlled Trials (CENTRAL), and other various electronic databases including PubMed and various sites for ongoing trials and abstracts of conferences., Results: Two eligible studies were analyzed that fulfilled the inclusion criteria of the systematic review. Fifteen studies were excluded due to the non-fulfillment of inclusion criteria. The primary outcome of both studies was to see the efficiency of LEV in controlling neonatal seizures when compared to PB. Better seizure control after a single loading dose of LEV was seen. Rates of seizure cessation at 24 h was also better in the LEV arm. Neonatal seizures secondary to hypoxic-ischemic encephalopathy (HIE) and receiving therapeutic hypothermia were better controlled with LEV. The side effect of LEV was significantly less when compared to PB., Conclusion: Levetiracetam has shown to have promising anti-epileptic properties for the management of neonatal seizure with better efficacy and less or no side effects. There is a need to conduct more randomized controlled trials seeking the role of LEV in the acute management of neonatal seizures and also for assessing its neuroprotective role and neurodevelopmental outcome in these neonates.

Background and Objectives: About 30% of patients with glioma need an add-on antiseizure medication (ASM) due to uncontrolled seizures on ASM monotherapy. This study aimed to determine whether levetiracetam combined with valproic acid (LEV + VPA), a commonly prescribed duotherapy, is more effective than other duotherapy combinations including either LEV or VPA in patients with glioma., Methods: In this multicenter retrospective observational cohort study, treatment failure (i.e., replacement by, addition of, or withdrawal of an ASM) for any reason was the primary outcome. Secondary outcomes included (1) treatment failure due to uncontrolled seizures and (2) treatment failure due to adverse effects. Time to treatment failure was estimated from the moment of ASM duotherapy initiation. Multivariable cause-specific Cox proportional hazard models were estimated to study the association between risk factors and treatment failure. The maximum duration of follow-up was 36 months., Results: A total of 1,435 patients were treated with first-line monotherapy LEV or VPA, of which 355 patients received ASM duotherapy after they had treatment failure due to uncontrolled seizures on monotherapy. LEV + VPA was prescribed in 66% (236/355) and other ASM duotherapy combinations including LEV or VPA in 34% (119/355) of patients. Patients using other duotherapy vs LEV + VPA had a higher risk of treatment failure for any reason (cause-specific adjusted hazard ratio [aHR] 1.50 [95% CI 1.07-2.12], p = 0.020), due to uncontrolled seizures (cause-specific aHR 1.73 [95% CI 1.10-2.73], p = 0.018), but not due to adverse effects (cause-specific aHR 0.88 [95% CI 0.47-1.67], p = 0.703)., Discussion: This observational cohort study suggests that LEV + VPA has better efficacy than other ASM combinations. Similar toxicities were experienced in the 2 groups., Classification of Evidence: This study provides Class III evidence that for patients with glioma with uncontrolled seizures on ASM monotherapy, LEV + VPA has better efficacy than other ASM combinations., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Introduction: Levetiracetam (LEV) is one of the most widely used anti-seizure medications (ASMs) in clinical practice. This is due both to a different mechanism of action when compared to other ASMs and its easy handling. Indeed, because of its interesting pharmacokinetic properties, it is often used outside of the labeled indications, notably in the neurocritical setting as prophylaxis of epileptic seizures., Areas Covered: A literature search was conducted and the most relevant studies on the pharmacokinetic properties of LEV were selected by two independent investigators. Current evidence on the use of ASM prophylaxis in the neurocritical setting was also reviewed, highlighting and discussing the strengths and limits of LEV as drug of choice for anti-epileptic prophylaxis in this scenario., Expert Opinion: LEV has a 'near-ideal' pharmacokinetic profile, which makes it an attractive drug for ASM prophylaxis in neurocritical care. However, current recommendations restrict ASMs prophylaxis to very selected circumstances and the role of LEV is marginal. Moreover, studies are generally designed to compare LEV versus phenytoin, whereas studies comparing LEV versus placebo are lacking. Further, randomized trials will be needed to better elucidate LEV utility and its neuroprotective role in the neurocritical setting.

Introduction: In seizure-naive brain tumor patients, the efficacy of perioperative prophylactic antiepileptic drug treatment remains controversial. In case of administration, the common preferred drug is levetiracetam (LEV) because of its favorable pharmacological profile. Research to date has not sufficiently determined how LEV affects cognition in the short term, as is the case in the perioperative period. The objective of this prospective study was to examine the neurocognitive functioning of seizure-naive brain tumor patients after receiving LEV perioperatively., Methods: Fortythree patients with supratentorial brain tumor scheduled for surgery received LEV three days before until six days after surgery as seizure prophylaxis. Cognitive functioning (NeuroCogFX), LEV plasma-levels, hematotoxicity, side-effects, as well as health-related quality of life (HRQoL, Qolie31), were recorded preoperatively before (Baseline) and after onset of LEV (Pre-Op), 4-6 days postoperatively (Post-Op) and 21 days postoperatively (Follow-Up)., Results: No significant changes in cognitive functioning and HRQoL were seen after onset of preoperative LEV. There was a significant improvement of NeuroCogFX total-score at Follow-Up (p = 0.004) compared to Baseline. The overall-score Qolie31 showed simultaneous improvement patterns as cognitive functioning (p < 0.001). The most frequent side effect related to study drug was somnolence (in 28.6% of patients)., Conclusions: A significant improvement of cognitive functioning, as well as an improvement in HRQoL, were detected postoperatively. This is presumably due to the debulking effect of the surgery. Nevertheless, LEV has no detrimental effect on cognitive functioning in the perioperative phase in seizure-naive brain tumor patients., Trial Registration: This study was registered prospectively (Date: 25/11/2015; EudraCT: 2015-003,916-19)., (© 2022. The Author(s).)

Purpose: Phenytoin is one of the most used antiepileptic drugs (AEDs), but it has serious potential side effects and drug interactions. Although studies have shown levetiracetam to have a much lower side-effect profile, its efficacy when compared with phenytoin is debatable. In our study, we aimed to determine the factors that cause seizure recurrence and to compare the efficacy of levetiracetam and phenytoin in the treatment of convulsive status epilepticus (CSE) and acute repetitive seizures (ARS)., Methods: In this study, 185 patients diagnosed with CSE or ARS and aged between 1 month and 18 years who received intravenous levetiracetam or phenytoin as a second-line AED were retrospectively evaluated., Results: A total of 185 patients were included in the study, 85 (45.9%) girls and 100 (54.1%) boys.While 54.1% (n = 100) of the patients were given phenytoin, levetiracetam was administered to 45.9% (n = 85) of them. The rates of cessation of seizure and prevention of seizure recurrence for 24 h were 84% for phenytoin and 78.8% for levetiracetam, without a significant difference (p > 0.05). Having active seizures on admission to the emergency department and an age of < 36 months were significantly related to seizure recurrence (p < 0.01)., Conclusions: Our results support that the intravenous administration of levetiracetam as the second-line treatment for CSE and ARS in children is as effective as the intravenous administration of phenytoin., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Valproic acid (VPA) and levetiracetam (LEV) are used in epilepsy treatment. However, their use to treat short-bowel syndrome has not been reported. We herein report a 68-year-old man who was hospitalized for symptomatic epilepsy following cerebral infarction. He had a history of superior mesenteric arterial occlusion, and only 30 cm of his jejunum was intact. VPA and LEV were administered, and good blood levels were achieved at clinical doses. This suggests that the gastrointestinal tract absorption of LEV and VPA is good even in patients with short-bowel syndrome and a 30-cm jejunum.

We evaluated a 39-year-old pregnant woman with right temporal lobe epilepsy. During the second trimester, seizure deterioration was responsive to an increased daily dose of levetiracetam (LEV). However, immediately after delivery, new non-habitual seizures emerged along with a sharply increased LEV concentration. The frequency of habitual seizures also slightly increased. The non-habitual seizures completely disappeared, and the frequency of the habitual seizures improved to the baseline level after the LEV dosage was reduced. Thus, a paradoxical effect of an increased LEV blood concentration was assumed to be a potential cause of these events. Peripartum pharmacokinetic fluctuations in LEV levels should be monitored carefully.

Introduction: The ability to administer medications via rapid intravenous bolus has the potential to allow for the rapid attainment of therapeutic drug levels and to limit the amount of unnecessary fluid volumes infused. The purpose of this review was to evaluate the efficacy and safety of undiluted or minimally diluted levetiracetam bolus doses., Areas Covered: A total of six pieces of the literature were evaluated in this review. Doses of up to 4,500 mg of intravenous levetiracetam were found to be both efficacious and safe when administered undiluted or minimally diluted in either a peripheral or central line. Product concentrations of levetiracetam ranged from 50 mg/mL to 100 mg/mL, with volumes ranging from 10 to 30 mL. Maintenance doses of up to 1,500 mg twice daily were demonstrated to be both efficacious and safe when administered undiluted or minimally diluted. Injection site pain and agitation were the most commonly reported adverse drug effects., Expert Opinion: Although hospitals and clinicians must be judicious with regard to training and the safety concerns of bolus intravenous push doses, and will need to address numerous logistical concerns, this practice is supported by practice guidelines and should be readily employed.

Objective: Syntaxin binding protein 1 (STXBP1) plays an important role in the release of synaptic vesicles. STXBP1-related encephalopathy is a brain dysfunction caused by STXBP1 variation. Levetiracetam (LEV) exerts antiepileptic effects by binding to synaptic vesicle protein 2A (SV2A). This study aimed to analyze the prognosis of LEV treatment of STXBP1 encephalopathy (STXBP1-E) and the correlation among genotype, phenotype, and LEV efficacy., Methods: Patients with pathogenic STXBP1 variants were collected from multiple centers, and their clinical history, video electroencephalogram (vEEG) characteristics, imaging examination data, and anti-seizure medication (ASM) history were systematically analyzed. The ASMs related to the prognosis were explored., Results: Forty patients with STXBP1-E were enrolled in this study. The detailed ASM usage of 37 patients was recorded without intervening in ASM selection. At the endpoint of six months treatment, the results of Fisher's exact test showed that in all ASMs, LEV affected the prognosis of patients with STXBP1-E. LEV was effective in improving the partial remission rate but did not achieve seizure freedom. However, LEV monotherapy could achieve seizure freedom in patients with other early-onset epileptic and encephalopathy. For refractory West syndrome (WS) or Ohtahara syndrome (OS), LEV combined with other ASMs could improve the seizure remission rate., Conclusion: LEV increased the seizure reduction rate and improved the vEEG characteristics in patients with STXBP1-E, but not seizure freedom. LEV combined with other ASMs could increase the seizure reduction rate, especially for refractory WS or OS. Thus, LEV could be considered after identifying the pathogenicity of STXBP1 variants., (Copyright © 2021. Published by Elsevier Ltd.)

Cognitive impairments such as dementia are considered the biggest challenges for public health. Benzodiazepines are often prescribed for treatment of anxiety disorder but they are associated with elevated risk of dementia. The present study has been designed to evaluate the neuroprotective effect of telmisartan and metformin on diazepam-induced cognitive dysfunction in mice. Piracetam was used as an established nootropic agent. Mice were divided into 8 groups, group1; control group which received normal saline. groups 2, 3 and 4 were received telmisartan 0.3 mg/kg/day, metformin 100 mg/kg/day and piracetam 200 mg/kg/day respectively. group 5; DZP group that injected with diazepam 2.5 mg/kg, groups 6, 7 and 8 were received diazepam 2.5 mg/kg + telmisartan 0.3 mg/kg/day, metformin 100 mg/kg/day and piracetam 200 mg/kg/day respectively. All drugs were administrated for 15 successive days. Cognitive skills of the animals were examined with Elevated plus maze and Passive Shock Avoidance tests. Investigations of oxidative stress markers were performed. Gene expression levels of TNF-α, NFκB, Caspase 3 and AMPK were analyzed using RT-PCR. Histological and immunohistochemical techniques were performed in hippocampus using H&E, cresyl violet stain, anti GFAP and anti COX-2 immunostain. The study revealed that administration of diazepam increased initial and retention transfer latency as well as it decreased step down latency that means it caused memory impairment. There was a significant increase in hippocampal expression levels of TNF-α, NFκB, and Caspase 3 and downregulation of AMPK expression levels associated with increased neurodegeneration, astrocytes activation and COX-2 immunohistochemical staining. This study indicates that diazepam caused a decline in cognitive function depending on hippocampal activity. Telmisartan, a common antihypertensive agent and metformin, a traditional antidiabetic drug improved this cognitive dysfunction through their anti-oxidant and anti-inflammatory effect as they decreased initial and retention transfer latency as well as it increased step down latency. Also they decreased TNF-α, NFκB, and Caspase 3 and upregulated AMPK expression, moreover they ameliorated the hippocampal morphological alterations, GFAP and COX-2 immunoexpression., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Contemporary research indicates the role of neuroinflammation/inflammatory markers in epilepsy. In addition, comorbidities such as anxiety and poor health-related quality of life are vital concerns in clinical care of pediatric patients with epilepsy. This open-label, prospective, observational study evaluated the effect of valproate and add-on levetiracetam on serum levels of C-C motif ligand 2 (CCL2) and Interleukin-1 beta (IL-1β) in pediatric patients with epilepsy. We also studied effect of valproate and add-on levetiracetam on anxiety and health-related quality of life (HRQoL) in specified age subgroups., Methods: Children aged 1 to 12 years, diagnosed with epilepsy (generalized or focal seizures), treated with valproate (n = 40) and valproate with add-on levetiracetam (n = 40) were included. All patients were followed up for 16 weeks and assessed for changes in serum CCL2 and IL-1β levels. Spence Children Anxiety Scale short version (SCAS-S) and QOLCE-16 scales were used to measure anxiety and HRQoL, respectively, in specific age groups., Results: The serum CCL2 level decreased significantly (p < .001) from 327.95 ± 59.07 pg/ml to 207.02 ± 41.50 pg/ml in the valproate group and from 420.65 ± 83.72 pg/ml to 250.06 ± 46.05 pg/ml in the add-on levetiracetam group. Serum IL-1β level did not change significantly in both groups. Spence Children Anxiety Scale short version scores were decreased and QOLCE-16 scores were increased significantly (p < .001) in both valproate and add-on levetiracetam groups., Conclusions: The results of our study suggest that valproate and levetiracetam led to decrease serum CCL2 levels without any change in serum IL-1β levels in children with epilepsy. Anti-inflammatory property of valproate and levetiracetam might underlie their antiepileptic effect and CCL2 could be a potential marker of drug efficacy in epilepsy. Also, valproate and levetiracetam reduced anxiety and improved quality of life in children with epilepsy in the age groups evaluated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Context.—: Therapeutic drug monitoring has traditionally been widely used for first-generation antiepileptic drugs (AEDs) such as carbamazepine and phenytoin. The last 2 decades have seen the introduction of second- and third-generation AEDs (eg, lamotrigine, levetiracetam, and topiramate) into clinical practice., Objective.—: To use data from the College of American Pathologists Therapeutic Drug Monitoring, Extended Proficiency Testing Survey to determine the performance of assays used for therapeutic drug monitoring of newer AEDs, including comparison of enzyme immunoassay and chromatographic techniques., Design.—: Six years of proficiency testing surveys were reviewed (2013-2018)., Results.—: Steady growth was seen in participant volumes for newer AEDs. The analytical performance of automated enzyme immunoassays for lamotrigine, levetiracetam, and topiramate was similar to that of chromatographic methods, consistent with published literature using patient samples for comparisons. The majority of participating laboratories now use enzyme immunoassays to measure levetiracetam., Conclusions.—: Survey results reflect steadily growing interest in therapeutic drug monitoring of newer AEDs. The increasing availability of robust immunoassays for new AEDs should facilitate their clinical utility, especially for clinical laboratories that do not perform chromatographic assays for therapeutic drug monitoring.

Objectives: The aim of this study is to report the results of a second cycle audit of the use of subcutaneous levetiracetam (Keppra ® ) and an updated literature review of management of seizures in palliative care patients. Methods: A comprehensive literature review on the use of subcutaneous levetiracetam performed in 2016 was updated. A retrospective audit of the use of subcutaneous levetiracetam for inpatients at Sir Michael Sobell House Hospice during the period of 2019-2020 was performed. Ethical approval was not required and was therefore not sought. Results: We report an additional 66 cases identified through an updated literature review and our audit. Fourteen articles were identified from the literature review, reporting a total of 120 cases where subcutaneous levetiracetam was administered. We report 19 further cases of subcutaneous levetiracetam administration between April 2019 and April 2020. Doses ranged from 500 mg to 4000 mg daily. Doses above 2000 mg were administered using a T60 syringe driver. The oral-to-subcutaneous conversion ratio was 1:1 in all but one case where the dose had to be reduced to fit a T34 syringe driver, after which the T60s were purchased. Levetiracetam was not mixed with other medications, but administered alone using water as the diluent for injection. Where necessary, the dose was appropriately adjusted for renal function. No site reactions were reported. Conclusions: Combined analysis of the 139 cases of subcutaneous levetiracetam administration suggests that this treatment continues to have a role in management of seizures at the end of life. Clinical outcomes suggest that therapeutic levels may be achieved, although there are only very limited data available with a few cases worldwide to support this. Randomized controlled trials are urgently needed to establish the efficacy and tolerability of subcutaneous levetiracetam administration.

Purpose: We aimed to evaluate the blood concentration of levetiracetam (LEV), as a second-line drug, in patients with status epilepticus (SE) in an emergency clinical setting., Methods: We prospectively evaluated 20 consecutive patients with SE admitted to our department between July 2017 and July 2019. LEV (2500 mg) was administered via bolus infusion after diazepam infusion, followed by 500 mg every 12 h for 48 h and then 500 mg orally. The primary outcomes were LEV blood concentration 15 min, 12 h, 48 h, and 96 h after administration and the proportion of patients showing trough LEV concentration within the therapeutic range. The secondary outcomes were the discontinuation of apparent convulsive seizure, epileptic wave on electroencephalogram, tracheal intubation, adverse events related to blood parameters, and abnormal findings in vital signs examination., Results: Median blood LEV (2500 mg) concentration at 15 min after administration was 81.6 μg/mL. The median trough concentration after 12, 48, and 96 h was 28.8, 10.5, and 9.1 μg/mL, respectively. Moreover, 95% of patients had trough concentration above the lower limit of the therapeutic blood concentration (>12 μg/mL) after 12 h. Regarding secondary outcomes, endotracheal intubation, seizure suppression, and abnormal electroencephalogram findings were observed in approximately 40%, 90%-95%, and 41% of patients, respectively. No abnormal findings were noted in blood tests and vital sign examination, although the AST/ALT levels increased in 10% of the patients., Conclusion: After bolus administration of 2500 mg, the blood LEV concentration reached the therapeutic window in patients with early-stage SE., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: Levetiracetam is approved as an add-on therapy to treat refractory partial seizures in pediatric patients over four years old. The efficacy and safety in pediatric patients with epilepsy in Uygur, China, is unknown. Therefore, the objective of this study was to investigate the safety, efficacy, and tolerability of levetiracetam in pediatric patients with epilepsy in Uygur, China., Methods: This retrospective study compared the efficacy and safety of levetiracetam monotherapy and in combination with other antiseizure medications (ASMs) in 1055 pediatric patients with epilepsy treated with levetiracetam. The seizure frequencies at 1, 2, and 3 years after starting levetiracetam therapy were recorded and compared with the baseline yearly frequency. Safety variables included the incidence and type of adverse reactions., Results: A total of 680 (64%) pediatric patients responded to levetiracetam therapy with a more than 50% reduction in the frequency of seizures. Seizure-free rates increased over time, 13%, 15%, and 18% at 1, 2, and 3 years, respectively. The number of baseline ASMs and the order of levetiracetam introduction were highly significant, impacting the likelihood of seizure remission during a 3-year follow-up period (p < 0.001). During levetiracetam treatment, 233 pediatric patients (22%) experienced at least one adverse reaction., Conclusion: These significant findings indicate that levetiracetam is likely to become a widely prescribed ASM for epilepsy in pediatric clinical practice because of its long-term safety, efficacy, and tolerability., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Frequency of clinical seizures may be as high as 16% in patients with spontaneous intracerebral hemorrhage (ICH). Current guidelines recommend against antiepileptic drug (AED) prophylaxis, but this recommendation is based on older trials, and the effect of newer AEDs is uncertain. The aim of this review was to study effects of AEDs on seizure occurrence and outcome in patients with spontaneous ICH., Methods: We searched key databases using combinations of the following terms: "levetiracetam," "prophylaxis," "ICH," "intracerebral hemorrhage," "intraparenchymal hemorrhage." Selected studies were reviewed for level of evidence and overall quality of data using Grading of Recommendations, Assessment, Development and Evaluations criteria. A meta-analysis was performed to evaluate seizure prevention, functional outcome, and mortality in patients with seizure prophylaxis compared with no prophylaxis following spontaneous ICH., Results: Seven articles met inclusion criteria and were graded level III studies. Administration of AEDs was not associated with reduced seizure risk (odds ratio 1.14, 95% confidence interval 0.47-2.77, P = 0.77). There was an association between AED prophylaxis and poor functional outcome (odds ratio 1.65, 95% confidence interval 1.17-2.31, P = 0.004) but not mortality (odds ratio 1.04, 95% confidence interval 0.62-1.72, P = 0.89). The overall quality of evidence using Grading of Recommendations, Assessment, Development and Evaluations criteria was low., Conclusions: This systematic review and meta-analysis including recent studies focusing on newer AEDs supports the 2015 guidelines regarding AED use in spontaneous ICH. There are some important caveats, including a possible confounding association between AED use and higher ICH score and the overall poor quality of the available data. A randomized clinical trial may be helpful., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background:  Ischemia-reperfusion injury plays an important role in flap failure. Ischemic preconditioning technique is the only proven method for preventing ischemia-reperfusion injury, but it is not used widely in daily practice because of difficulties such as prolonging the operation time, need for surgical experience, and increasing the risk of complications. This study has been performed with the assumption that piracetam may be a simple and inexpensive alternative to the preconditioning technique due to its antioxidant, antiaggregant, rheological, anti-inflammatory, antiapoptotic, cytoprotective, and immune modulating effects., Methods:  Thirty-two rats were divided into four groups and latissimus dorsi musculocutaneous flaps were raised. No extra procedure was applied, and no treatment was given to the control group. Four hours of ischemia was created by clamping the thoracodorsal pedicle in the second group. The animals in the third group were treated with 10 minutes of ischemia and reperfusion periods as a preconditioning procedure before the 4 hours of ischemia. Animals in the fourth group received systemic piracetam 30 minutes before and 6 days after reperfusion. Nitric oxide and myeloperoxidase levels in serum and tissue, acute inflammatory cell response, and vascular proliferation in tissue were examined at the postoperative 24th hour and 10th day., Results:  Myeloperoxidase activity in both preconditioning and piracetam groups, was significantly lower than the ischemia-reperfusion group. Acute inflammatory cell response was similarly decreased in both preconditioning and piracetam groups compared with ischemia-reperfusion group. Tissue measurements of nitric oxide were also significantly higher in both preconditioning and piracetam groups than in the ischemia-reperfusion group. However, vascular proliferation increased in the preconditioning group, while it did not show any significant change in the piracetam group., Conclusion:  This study shows that systemic piracetam treatment provides protection against ischemia-reperfusion injury in musculocutaneous flaps and can offer a simple and inexpensive alternative to the preconditioning technique., Competing Interests: None declared., (Thieme. All rights reserved.)

Competing Interests: Competing interests: None declared.