[Therapeutic effect and mechanism of piracetam for the treatment of spinal cord injury in rats through MAPK pathway].

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-1ß (interleukin-1ß), necrosis factor-α (IL-1ß) 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-1ß 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.

Cognitive effects of piracetam in adults with memory impairment: A systematic review and meta-analysis.

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.

Factors influencing serum concentrations of levetiracetam in dogs with epilepsy.

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 (R2 = 0.59, P < .001). Phenobarbital significantly decreased serum levetiracetam concentration in a dose dependent manner (R2 = 0.30, P = .003). Based on our model, a levetiracetam dosage of 99-216 mg/kg/day is necessary to obtain a serum levetiracetam concentration of 20 µg/mL when used alone or concurrently with 7 mg/kg/day of phenobarbital. No other factors were found to influence serum levetiracetam concentrations. No therapeutic range could be identified. 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.

Therapeutic Drug Monitoring of Levetiracetam in Different Trimesters of Pregnant Women with Epilepsy in a Tertiary Care Center: A Prospective Study.

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.

Effect of Piracetam and Iron Treatment on Heart Rate Variability in Patients With Breath-Holding Spell.

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.

Cost-effectiveness analysis of HLA-B*15:02 screening before treatment of epilepsy in Indonesia.

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.

Changes in the Dentate Gyrus Gene Expression Profile Induced by Levetiracetam Treatment in Rats with Mesial Temporal Lobe Epilepsy.

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 Ca2+ homeostasis and the regulation of the mTOR pathway through Efcab1, Hgf, SLC24a1, Adam8, and Serpinb1a, contributing to reduced hyperexcitability in TLE patients.

Successful use of intravenous and oral levetiracetam in a goat to control refractory seizures secondary to suspected polioencephalomalacia.

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.

Modulation of hippocampal activity in schizophrenia with levetiracetam: a randomized, double-blind, cross-over, placebo-controlled trial.

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.

Optimal Dosing of Levetiracetam for Seizure Prophylaxis in Critically Ill Patients: A Prospective Observational Study.

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).

Docosahexaenoic Acid Plus Piracetam Versus Piracetam Alone for Treatment of Breath-Holding Spells in Children: A Randomized Clinical Trial.

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.

Use of Levetiracetam for Post-Traumatic Seizure Prophylaxis in Combat-Related Traumatic Brain Injury.

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.

Levetiracetam dosing for seizure prophylaxis in neurocritical care patients.

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.

Status epilepticus prognosis following levetiracetam administration: Analysis of loading doses.

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.

Experience of Subcutaneous Levetiracetam in Palliative Care.

BACKGROUND: Seizures are common in palliative care patients and its control is essential in the management of these patients as it helps to reduce suffering at the end of life. Subcutaneous levetiracetam has been used off-license for seizure control in palliative care. OBJECTIVE: The objective of the study was to describe our experience with subcutaneous levetiracetam in two hospitals in Bogota, Colombia. METHODS: We conducted a retrospective review of patients treated with subcutaneous levetiracetam in two hospitals in Colombia during 2019-2021. Data were extracted from medical records, and participants were followed up as outpatients. RESULTS: Twenty-one patients were included into the study. No severe adverse effects or rise in ictal frequency were documented. Twelve patients died during hospitalization and nine continued treatments as outpatients. The principal diagnosis was structural focal epilepsy. The daily dose of levetiracetam ranged from 1,000 mg to 3,000 mg, and the duration of treatment varied among subjects between 1 and 360 days. CONCLUSION: Subcutaneous levetiracetam was well tolerated and effective in controlling seizures in palliative care when oral administration or intravenous access was not an option. Randomized controlled trials are needed to elucidate the efficacy and tolerability of subcutaneous levetiracetam in clinical practice.

Use of antiepileptic drugs as prophylaxis against posttraumatic seizures in the pediatric population: a systematic review and meta-analysis.

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.

Clinical value of therapeutic drug monitoring for levetiracetam in pediatric patients with epilepsy.

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.