Impact of levetiracetam and ethanol on memory, selected neurotransmitter levels, oxidative stress parameters, and essential elements in rats.

BACKGROUND: Ethanol disrupts brain activity and memory. There is evidence supporting the beneficial effect of levetiracetam on alcohol consumption. Therefore, the aim of the study was to examine whether levetiracetam has a protective activity against ethanol-induced memory impairment, alterations in selected neurotransmission activities, oxidative stress, and selected essential elements in rats. METHODS: The rats were given levetiracetam (300 mg/kg b.w. po) with ethanol for three weeks prior to behavioral tests. Spatial memory was tested using the Morris water maze, while recognition memory was evaluated using the Novel object recognition test. The GABA and glutamate concentration was determined in three rat brain regions (cerebellum, hippocampus, and cerebral cortex). Serum oxidative stress parameters and selected essential elements concentration (Cu, Mn, Zn, Fe, Mg) in the rat brain were analyzed. RESULTS: Levetiracetam administered with ethanol improved spatial memory, but did not affect abstinence-induced impairment. The drug also decreased ethanol-induced long-term recognition memory impairment. No alterations in glutamate levels were observed. GABA levels were elevated by levetiracetam in the cerebral cortex and by ethanol in the cerebellum. Ethanol increased catalase activity (CAT) and decreased superoxide dismutase activity (SOD) in the serum. Levetiracetam significantly increased the activity of SOD. Alcohol disrupted the levels of trace elements (Mn, Zn, Mg) in the rat brain. Additionally, levetiracetam alone increased Mg, Fe, and Cu concentrations while all animals receiving the drug also had significantly lower concentrations of Zn. CONCLUSIONS: Levetiracetam had differential effects against ethanol-induced impairments. These findings could have important implications for future levetiracetam treatment in patients.

Investigation of spontaneous abortion and stillbirth adverse events in epilepsy patients treated with levetiracetam: A pharmacovigilance study.

BACKGROUND: The prescription of levetiracetam during pregnancy has become more common due to its lower teratogenic risk profile. However, due to a lack of data about its association with stillbirth and spontaneous abortion, worries remain. OBJECTIVE: To investigate information on any possible association of spontaneous abortion and stillbirth adverse events with levetiracetam in women with epilepsy. METHODS: This retrospective pharmacovigilance study used disproportionality analysis to detect signals of adverse reaction of interest reported with Levetiracetam in FAERS, the FDA Adverse Event Reporting System. The ratio of reporting odds (ROR) and information component (IC) indices were used to undertake disproportionality analyses, and change point analyses were carried out to identify variations in the frequency of reporting of relevant adverse events. Sensitivity analyses included subgroup analyses by indication, treatment regimen, and reporting region. RESULTS: Overall, 2870 cases of spontaneous abortion and stillbirth with commonly used antiseizure medications were analyzed. A total of 65.5 % of these cases had epilepsy as the indication. In the entire dataset, we observed disproportionality signals of spontaneous abortion for 6 ASMs (levetiracetam, carbamazepine, lamotrigine, oxcarbazepine, topiramate, valproic acid) and disproportionality signals of stillbirth for 4 ASMs (levetiracetam, carbamazepine, lamotrigine, oxcarbazepine). In the epileptic population, disproportionality signals for stillbirth (ROR0.25 = 4.60; IC0.25 = 1.30) and spontaneous abortion (ROR0.25 = 3.98; IC0.25 = 1.20) in levetiracetam was identified. These disproportionality signals have been consistently robust over the past years, according to a temporal assessment of them. Sensitivity studies proved how reliable the findings were. CONCLUSION: Using validated pharmacovigilance methods, we found significant disproportional signals for spontaneous abortion and stillbirth associated with levetiracetam. Of these, the signals for spontaneous abortion were observed after 2011 and for stillbirth after 2014, which may be related to the rise in levetiracetam prescriptions during pregnancy in recent years. The association of spontaneous abortion and stillbirth adverse events with levetiracetam and potential biases confounding this association merit further investigation.

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

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

Subthreshold Cannabidiol Potentiates Levetiracetam in the Kainic Acid Model of Temporal Lobe Epilepsy: A Pilot Study.

Refractoriness to antiseizure medications is still a major concern in the pharmacotherapy of epilepsy. For this reason, we decided to evaluate the combination of levetiracetam and cannabidiol, administered at a subthreshold dose, to limit the possible adverse effects of this phytocannabinoid. We administered levetiracetam (300 mg/kg/day, via osmotic minipumps), cannabidiol (120 mg/kg/day, injected once a day subcutaneously), or their combination for one week in epileptic rats. Saline-treated epileptic rats were the control group. Animals were monitored with video electroencephalography the week before and after the treatment. No changes were found in the controls. Levetiracetam did not significantly reduce the total seizure number or the overall seizure duration. Still, the overall number of seizures (p < 0.001, Duncan's new multiple range test) and their total duration (p < 0.01) increased in the week following treatment withdrawal. Cannabidiol did not change seizures when administered as a single drug. Instead, levetiracetam combined with cannabidiol resulted in a significant reduction in the overall number and duration of seizures (p < 0.05), when comparing values measured during treatment with both pre- and post-treatment values. These findings depended on changes in convulsive seizures, while non-convulsive seizures were stable. These results suggest that cannabidiol determined a remarkable potentiation of levetiracetam antiseizure effects at a subthreshold dose.

Creatine Kinase Surge: Levetiracetam-Induced Rhabdomyolysis.

Rhabdomyolysis is the breakdown of muscle cells secondary to both traumatic and non-traumatic causes. The lysing of the muscle cells can lead to the release of cell contents that can lead to acute injury and other life-threatening conditions. Levetiracetam is an anticonvulsant commonly used in generalized and partial tonic-clonic seizures. Well-known side effects include agitation, depression, anxiety, irritability, rash, and somnolence; however, there are an increasing number of case reports that report rhabdomyolysis secondary to antiepileptic use. We present a case of a 27-year-old male with new-onset seizures who was started on levetiracetam therapy and found to have elevated creatine kinase (CK), which decreased only with tapering of the drug. Our case displays the importance of considering levetiracetam as a cause of rhabdomyolysis, supporting this rare side effect of the antiseizure medication. Rhabdomyolysis is a potentially life-threatening condition that can lead to irreversible renal damage if not managed properly.

Evaluation of levetiracetam loading dose in adult patients with benzodiazepine-refractory status epilepticus.

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

A comparison of the antiepileptogenic efficacy of two rationally chosen multitargeted drug combinations in a rat model of posttraumatic epilepsy.

Post-traumatic epilepsy (PTE) is a recurrent and often drug-refractory seizure disorder caused by traumatic brain injury (TBI). No single drug treatment prevents PTE, but preventive drug combinations that may prophylax against PTE have not been studied. Based on a systematic evaluation of rationally chosen drug combinations in the intrahippocampal kainate (IHK) mouse model of acquired epilepsy, we identified two multi-targeted drug cocktails that exert strong antiepileptogenic effects. The first, a combination of levetiracetam (LEV) and topiramate, only partially prevented spontaneous recurrent seizures in the model. We therefore added atorvastatin (ATV) to the therapeutic cocktail (TC) to increase efficacy, forming "TC-001". The second cocktail - a combination of LEV, ATV, and ceftriaxone, termed "TC-002" - completely prevented epilepsy in the mouse IHK model. In the present proof-of-concept study, we tested whether the two drug cocktails prevent epilepsy in a rat PTE model in which recurrent electrographic seizures develop after severe rostral parasagittal fluid percussion injury (FPI). Following FPI, rats were either treated over 3-4 weeks with vehicle or drug cocktails, starting either 1 or 4-6 h after the injury. Using mouse doses of TC-001 and TC-002, no significant antiepileptogenic effect was obtained in the rat PTE model. However, when using allometric scaling of drug doses to consider the differences in body surface area between mice and rats, PTE was prevented by TC-002. Furthermore, the latter drug cocktail partially prevented the loss of perilesional cortical parvalbumin-positive GABAergic interneurons. Plasma and brain drug analysis showed that these effects of TC-002 occurred at clinically relevant levels of the individual TC-002 drug components. In silico analysis of drug-drug brain protein interactions by the STITCH database indicated that TC-002 impacts a larger functional network of epilepsy-relevant brain proteins than each drug alone, providing a potential network pharmacology explanation for the observed antiepileptogenic and neuroprotective effects observed with this combination.

Effectiveness of Fosphenytoin and Levetiracetam to Prevent Posttraumatic Seizures in Young Children with Accidental or Abusive Traumatic Brain Injury.

BACKGROUND: Seizures occur frequently in pediatric patients with traumatic brain injury (TBI), particularly abusive head trauma (AHT). There are limited data on the effectiveness of fosphenytoin and levetiracetam to prevent posttraumatic seizures. METHODS: We performed a retrospective single center cohort study of children < 3 years old admitted with mild [Glasgow Coma Scale (GCS) score 13-15], moderate (GCS 9-12), and severe (GCS 3-8) TBI at a level I trauma center from 2011 to 2021. Antiseizure medications were used at the discretion of the treating physicians. Nonparametric tests were used to compare antiseizure medication prophylaxis and TBI etiology. RESULTS: A total of 717 patients (263 with AHT, 454 with accidental TBI) were included, of whom 135 (19%) received fosphenytoin, 152 (21%) received levetiracetam, and 430 (60%) did not receive any seizure prophylaxis. Over the study period, the use of fosphenytoin prophylaxis decreased (R2 = 0.67, p = 0.004), whereas the use of levetiracetam increased (R2 = 0.51, p = 0.008). Additionally, the occurrence of early posttraumatic seizures decreased (R2 = 0.58, p = 0.006). Children with AHT were more likely to receive any seizure prophylaxis than those with accidental TBI (52% vs. 27%; p < 0.001) and were more likely to have ≥ 1 seizure during hospitalization (22% vs. 4%; p < 0.001). Among children who received seizure prophylaxis, those who received fosphenytoin had a higher occurrence of seizures than those who received levetiracetam (33% vs.18%; p = 0.004). After controlling for age, admission year, TBI mechanism, and severity of injury, we observed no differences in seizure occurrence between groups. CONCLUSIONS: In children < 3 years old with TBI, no differences were observed in occurrence of seizures between patients who received fosphenytoin and patients who received levetiracetam prophylaxis after controlling for patient factors including severity of injury. Levetiracetam may be an equally effective alternative to fosphenytoin for seizure prophylaxis for early posttraumatic seizure prevention in this age group.

Intravenous levetiracetam versus intravenous phenytoin as second Line treatment in pediatric convulsive status epilepticus- open label randomized controlled trial.

Background: Benzodiazepines (BZDs) are recommended as the initial therapy of choice in status epilepticus (SE). The age-old second-line treatment for BZD refractory convulsive SE is intravenous phenytoin (PHT) based predominantly on nonrandomized clinical trial data. We did this study to compare the efficacy and safety of intravenous levetiracetam (LEV) and PHT as second-line antiseizure medication (ASM) for children with SE. Methodology: A prospective, randomized controlled, open-label study was conducted in children 3 months to 15 years of age with SE in Pediatric Emergency. A total of 41 children were randomly allocated to either group 1 (Levetiracetam) or group 2 (Phenytoin) on the basis of computer-generated randomization. Children who were already on antiseizure medications, either LEV or PHT, or receiving these drugs outside for SE were excluded. Data analysis was done by SPSS V25. Results: The most common age group presenting with SE was 12 months to 5 years. Clinical cessation of seizure 5 minutes after the completion of drugs was 85% (17/20) in Levetiracetam group and 90.5% (19/21) in Phenytoin group. Recurrence of seizure within 24 hours was noted in 35% (7/20) in Levetiracetam group and 38.1% (8/21) in Phenytoin group. There was no statistically significant difference noted in both the groups in terms of seizure cessation, adverse events, and recurrence. Conclusion: The efficacy and safety of LEV were found to be comparable to those of PHT in controlling seizure as second-line ASM in SE.

Association between Levetiracetam Use and Survival in Patients with Glioblastoma: A Nationwide Population-Based Study.

Purpose: This study aimed to investigate whether levetiracetam (LEV), the most used antiepileptic drug, influences survival in patients with glioblastoma (GBM), using a national database. Materials and Methods: This study used data from the Korea Health Insurance Review and Assessment database. Patients diagnosed with GBM between 2007-2018 treated with standard therapy were included. The study population was divided into long-term (≥60 days) and short-term (<30 days) LEV groups. A separate long-term valproic acid (VPA) group (≥60 days) was identified for comparison. Demographics, disease characteristics, and treatment parameters were collected. Kaplan-Meier method and Cox regression were used to compare survival outcomes between the groups. Results: Overall, 2,971 patients were included, with 1,319 and 1,652 in the short-term and long-term LEV groups, respectively. The median overall survival (OS) for the entire population was 19.15 months post-surgery. Kaplan-Meier analysis revealed a significantly longer median OS in the long-term LEV group versus the short-term LEV group. After adjusting for confounders, Cox proportional hazard analysis revealed an association of long-term LEV use with improved survival, which was also observed in a subgroup analysis of patients without preoperative seizure history. The long-term LEV group demonstrated longer median OS, compared with the long-term VPA group. Conclusion: Our nationwide population-based study found an association between long-term LEV use and improved survival in patients with GBM, regardless of preoperative seizure history. Prospective studies are needed to validate these findings and investigate the potential impact of LEV on the survival outcomes of patients with GBM.

Oligoprotective Activity of Levetiracetam Against Glutamate Toxicity: An in vitro Study.

INTRODUCTION: The role of glutamate in the development of some brain pathological conditions, such as multiple sclerosis, has been well described. Levetiracetam (LEV), a new broad-spectrum antiseizure medicine, is widely used to control certain types of seizures. METHOD: Apart from its anti-seizure activity, LEV exerts neuroprotection via anti-inflammatory, antioxidant, and antiapoptotic effects. The current study was designed to evaluate the protective potential of LEV against glutamate-induced injury in OLN-93 oligodendrocytes. METHOD: At first, the potential negative impact of LEV on OLN-93 viability was evaluated. After that, the cells were concurrently treated with LEV (0-100 µM) and glutamate (8 mM) for 24 h. The viability, redox status, and the rate of apoptosis of OLN-93 cells were then assessed using 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl-2H-tetrazolium bromide (MTT), 2',7' dichlorodihydrofluorescein diacetate (H2DCFDA), 2-thiobarbituric acid reactive substances (TBARS) and annexin V/propidium iodide (PI) assays, respectively. Moreover, caspase-3 expression, as a marker of cell apoptosis, was evaluated by western blotting. RESULTS: LEV at 1-800 µM did not have any negative effect on cell survival. Treatment with LEV (50 and 100 µM) substantially enhanced the cell viability following glutamate insult. The cytoprotective activity of LEV (50 and 100 µM) against glutamate toxicity was accompanied by reduced Reactive Oxygen Species (ROS) accumulation and Malondialdehyde (MDA) level. Moreover, 100 µM of LEV inhibited apoptosis and decreased the expression level of cleaved caspase-3 following glutamate exposure. CONCLUSION: Taken together, the results suggested that LEV has protective effects against glutamate-mediated cytotoxicity in OLN-93 cells. The oligoprotective action of LEV was shown to be exerted via inhibition of oxidative stress and cellular apoptosis.

Levetiracetam versus carbamazepine monotherapy in the management of pediatric focal epilepsy: A systematic review and meta-analysis of randomized controlled trials.

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

Effect of Levetiracetam on Oxidant-Antioxidant Activity during Long-Term Temporal Lobe Epilepsy in Rats.

Epilepsy is a disorder characterized by a predisposition to generate seizures. Levetiracetam (LEV) is an antiseizure drug that has demonstrated oxidant-antioxidant effects during the early stages of epilepsy in several animal models. However, the effect of LEV on oxidant-antioxidant activity during long-term epilepsy has not been studied. Therefore, the objective of the present study was to determine the effects of LEV on the concentrations of five antioxidant enzymes and on the levels of four oxidant stress markers in the hippocampus of rats with temporal lobe epilepsy at 5.7 months after status epilepticus (SE). The results revealed that superoxide dismutase (SOD) activity was significantly greater in the epileptic group (EPI) than in the control (CTRL), CTRL + LEV and EPI + LEV groups. No significant differences were found among the groups' oxidant markers. However, the ratios of SOD/hydrogen peroxide (H2O2), SOD/glutathione peroxidase (GPx) and SOD/GPx + catalase (CAT) were greater in the EPI group than in the CTRL and EPI + LEV groups. Additionally, there was a positive correlation between SOD activity and GPx activity in the EPI + LEV group. LEV-mediated modulation of the antioxidant system appears to be time dependent; at 5.7 months after SE, the role of LEV may be as a stabilizer of the redox state.

A Comparison of Pre- and Post-Treatment Cranial MRI Characteristics in Patients with Pediatric Epilepsy Receiving Levetiracetam.

Background and Objectives: This study was performed for the purpose of assessing whether antiepileptic levetiracetam treatment produces a change in brain volumes in children with epilepsy. To that end, we compared the volumes of the basal ganglia (caudate nucleus, putamen, globus, hip-pocampus, and thalamus) at magnetic resonance imaging (MRI) before and after treatment (months 18-24) in pediatric epilepsy patients using levetiracetam. Materials and Methods: This retrospective study involved a volumetric comparison of patients presenting to the Balikesir University Medical Faculty pediatric neurology clinic between 01.08.2019 and 01.11.2023 and diagnosed with epilepsy, and who underwent cranial MRI before and 18-24 months after treatment at the radiology department. The demographic and clinical characteristics (age, sex, family history of epilepsy, type of epilepsy, and EEG features (normal, abnormal, epileptiform)) of the patients included in the study were recorded. Results: The comparison of basal ganglia volumes at cranial MRI before and at months 18-24 of treatment revealed significant differences in the left caudate nucleus, right putamen, left putamen, left globus pallidus, right thalamus, left thalamus, and right hippocampal regions. Conclusions: In conclusion, differing findings are encountered at cranial imaging in patients with epilepsy, depending on the seizure frequency, activity, and the type of antiepileptic drugs used. This study compared basal ganglia volumes on cranial MRIs taken before and 18-24 months after treatment in pediatric epilepsy patients using levetiracetam. A significant increase was observed in the volumes of basal ganglia (caudate nucleus, putamen, globus pallidus, hippocampus, and thalamus) on the MRIs of pediatric epilepsy patients using levetiracetam.

Administration of Levetiracetam via Subcutaneous Infusion for Seizure Control in the Palliative Care Setting: A Narrative Review.

This narrative review aims to summarise the information available on the use of subcutaneous (SC) levetiracetam (LEV) in the adult palliative care setting using clinical texts, databases, journals, and grey literature. A search strategy utilising Embase, Medline CINALH and Cochrane databases, as well as Google Scholar, was conducted with the mapped search terms "levetiracetam", "subcutaneous" and "palliative". LEV intravenous (IV) proprietary products are used subcutaneously, including as continuous subcutaneous infusions (CSCIs), in the adult palliative care setting. The total LEV daily dose ranged from 250 mg to 5000 mg and LEV was administered with various diluents at varying volumes. The data identified a clinical desire to mix LEV with other medications; however, the current evidence on combination compatibility is observational only and drug stability in combinations is lacking. The majority of information in the literature on SC LEV use is based on case reports and retrospective audits. Case reports, whilst at times offering more clinical detail, represent specific circumstances not necessarily applicable to a larger patient cohort. The findings of retrospective audits are limited by the documentation and detail reported at the time of patient care that may not be designed for data collection.

Efficiency and safety of high-dose undiluted intravenous push levetiracetam loading doses compared to intravenous infusion in seizing patients: A retrospective cohort study.

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

Is there any concern of insulin resistance and metabolic dysfunctions with antiseizure medications? A prospective comparative study of valproate vs. levetiracetam.

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

Antiaris africana aqueous extract inhibits chronic demyelination and seizures in mice.

Demyelinating diseases are commonly associated with epileptic seizures and have limited management options. Hence, the need to investigate potential options for management of such seizures. Antiaris Africana extract (AE) was investigated for effect in chronic demyelinating seizures. Cuprizone treatment induced short but frequent spike discharges in mice. Antiaris Africana extract (300 mg/kg) treatment abolished epileptiform discharges. Cuprizone administration caused severe demyelination in the corpus callosum. After the demyelination phase, myelin content decreased to 22.86 ± 1.92 % in the cuprizone-only group. However, there was an increase to 52.14 ± 3.91 % in cuprizone-only group and 62.00 ± 2.78 % in the Antiaris africana extract group respectively, after a 4-week cuprizone cessation period. Treatment with AE and LEV visibly altered myelin growth. Antiaris africana extract treatment produced significant (P < 0.001, F (3, 16) = 698.4) increase in locomotor activity similar to LEV (P < 0.001,F (2, 12) = 678.7) and DZP (P < 0.001, F (2, 12) = 620.4) and improved beam traversal time (18.71 ± 2.244 s; 95 % CI: 13.22-24.20) while causing significantly (P < 0.05, F (2, 15) = 6.667) fewer stepping errors. Antiaris africana extract inhibits seizures induced by chronic demyelination and has beneficial effects on motor coordination.

Hyponatremia-Induced Epileptic Seizure Provoked by Levetiracetam and Pain Medication Intake in a Patient with Central Diabetes Insipidus.

Introduction: Causes of epileptic seizures are often multifactorial but for an effective therapy, they should be uncovered in detail. Case Presentation: We present a 67-year-old male patient with a central diabetes insipidus, who experienced a generalized tonic-clonic seizure. The patient was treated with levetiracetam for prevention of further seizures, opioids and non-steroidal anti-inflammatory drugs, i.e., ibuprofen because of severe back pain due to vertebral compression fractures. In this setting, he developed significant hyponatremia and experienced another epileptic seizure. After stopping analgesics and switching from levetiracetam to lacosamide, sodium levels returned to normal and the patient remained free of seizures since then. Conclusion: The interrelationships of medical therapy, sodium levels and epileptic seizures in the context of central diabetes insipidus are discussed.