Levetiracetam Treatment Research Articles

Abnormal night melatonin level in a patient with well-controlled epilepsy without sleep disturbances – could it be associated with levetiracetam therapy: A case report

We present a case report of a 23-year old male with newly diagnosed epilepsy manifested with generalized tonic seizures. Levetiracetam (LEV) was started and the patient was seizure free. The patient demonstrated intermediate chronotype determined by the Morningness-Eveningness Questionnaire (MEQ). There was no epileptiform activity on electroencephalography (EEG) and polysomnography (PSG), sleep architecture disturbances (PSG) or daytime sleepiness (Epworth sleepiness score, Multiple sleep latency test) at the onset and after 3 months of LEV therapy. The melatonin serum levels after 3 months of LEV treatment were 22.00 pg/ml at 3 a.m. and 23.60 pg/ml at 8 a.m. - there was no normal night peak concentration. This abnormality may be associated with a later night peak melatonin concentration, the treatment with levetiracetam being a possible explanation. We consider the presented clinical case of special interest because of the combination of absence of normal night peak melatonin concentration, normal sleep parameters and non-extremely presented chronotype. We suggest that such patients could benefit from add-on therapy with melatonin.

Psychiatric disorders of the combination of levetiracetam either with lacosamide or perampanel: a retrospective cohort study.

Background The number of patients with epilepsy receiving perampanel or lacosamide as an add-on treatment following levetiracetam treatment has increased. Although levetiracetam causes psychiatric disorders, it is unclear whether they occur with the combined use of these antiepileptic drugs. Objective To determine the frequency of psychiatric disorders in patients received lacosamide or perampanel in combination with levetiracetam. Setting A single-center retrospective cohort study. Method Patients who received levetiracetam + lacosamide or levetiracetam + perampanel were selected. Medical records from the start of combination therapy contained characteristics of patients and the incidence of psychiatric disorders. Main outcome measure The frequency of psychiatric disorders, the time to onset, dose reduction or discontinuation following psychiatric disorders, and the clinical course following disorder onset. Results Forty-four patients used levetiracetam + lacosamide and 50 used levetiracetam + perampanel. The incidence of psychiatric disorders was significantly lower (p < 0.001) with levetiracetam + lacosamide (6.8%) than with levetiracetam + perampanel (44%). The incidence of affect lability was significantly higher with levetiracetam + perampanel than with levetiracetam + lacosamide (p = 0.018). The time to the onset of psychiatric disorders was within 1 month of dose initiation or increase in one case (33.3%) with levetiracetam + lacosamide and 16 cases (72.7%) with levetiracetam + perampanel. There was no significant difference in clinical characteristics and antiepileptic drug dosages owing to the presence or absence of psychiatric disorders. Conclusion As the frequency of psychiatric disorders was higher with levetiracetam + perampanel therapy, levetiracetam + lacosamide may be preferable. These disorders tended to develop within 1 month of therapy and were not dose-dependent. Antiepileptic drugs should be cautiously prescribed to avoid psychiatric disorders.

Levetiracetam Treatment Normalizes Levels of Presynaptic Endocytosis Machinery and Restores Nonamyloidogenic APP Processing in App Knock-in Mice.

Toxic amyloid-beta (Aβ) peptides, produced by sequential proteolytic cleavage of the amyloid precursor protein (APP), play a key role in the initial stage of Alzheimer’s disease (AD). Increasing evidence indicates that Aβ42 induces neuronal circuit hyperexcitability in the early stages of AD pathology. As a result, researchers have investigated treatments that modulate the excitatory/inhibitory imbalance as potential AD therapies. For example, levetiracetam, an atypical antiepileptic drug used to quell hyperexcitability, has garnered recent interest in the AD field, even though its exact mechanism(s) of action remains elusive. Here, we show that in APP knock-in mouse models of amyloid pathology, chronic levetiracetam administration decreases cortical Aβ42 levels and lowers the amyloid plaque burden. In addition, using multiplexed tandem mass tag-quantitative mass spectrometry-based proteomic analysis, we determined that chronic levetiracetam administration selectively normalizes levels of presynaptic endocytic proteins. Finally, we found that levetiracetam treatment selectively lowers beta carboxyl-terminal fragment levels, while the abundance of full-length APP remains unchanged. In summary, this work reports that chronic treatment with levetiracetam serves as a useful therapeutic in AD by normalizing levels of presynaptic endocytic proteins and altering APP cleavage preference, leading to a decrease in both Aβ42 levels and the amyloid plaque burden. These novel findings provide novel evidence for the previously documented therapeutic value of levetiracetam to mitigate AD pathology.

Chronic levetiracetam (Keppra®) treatment increases the reinforcing strength of cocaine in rhesus monkeys

BackgroundDrugs that increase inhibitory neuronal activity in the brain have been proposed as potential medications for stimulant use disorders. ObjectiveThe present study assessed the ability of chronically administered levetiracetam (Keppra®), a clinically available anticonvulsant drug that increases GABA by binding to synaptic vesicle glycoprotein 2A, to modulate the reinforcing strength of cocaine in monkeys. MethodsThree adult male rhesus monkeys (Macaca mulatta) self-administered cocaine intravenously each day under a progressive-ratio (PR) schedule of reinforcement. Two monkeys also responded to receive food pellets under a 50-response fixed-ratio schedule (FR 50) each morning. After determining a cocaine dose-response curve (0.001–0.3 mg/kg per injection, i.v.) in the evening, levetiracetam (5–75 mg/kg, p.o., b.i.d.) was administered for 12–16 days per dose. To model a treatment setting, cocaine self-administration sessions were conducted using the PR schedule every 4 days during levetiracetam treatment. After tapering the dose of levetiracetam over two weeks in the absence of cocaine sessions, cocaine dose-effect curves were re-determined. ResultsLower doses of levetiracetam produced non-systematic fluctuations in numbers of cocaine injections received in each subject, whereas the highest tested dose significantly increased the reinforcing strength of cocaine; no effects on food-maintained responding were observed. After termination of levetiracetam treatment, dose-effect curves for cocaine self-administration were shifted to the left in two monkeys. ConclusionThese data suggest that levetiracetam is not likely to be an efficacious pharmacotherapy for cocaine dependence. Rather, sensitivity to cocaine may be increased during and after levetiracetam treatment.

Neuroprotective and Angiogenesis Effects of Levetiracetam Following Ischemic Stroke in Rats.

Objective: The present study explored whether levetiracetam (LEV) could protect against experimental brain ischemia and enhance angiogenesis in rats, and investigated the potential mechanisms in vivo and in vitro. Methods: The middle cerebral artery was occluded for 60 min to induce middle cerebral artery occlusion (MCAO). The Morris water maze was used to measure cognitive ability. The rotation test was used to assess locomotor function. T2-weighted MRI was used to assess infarct volume. The neuronal cells in the cortex area were stained with cresyl purple. The anti-inflammatory effects of LEV on microglia were observed by immunohistochemistry. Enzyme-linked immunosorbent assays (ELISA) were used to measure the production of pro-inflammatory cytokines. Western blotting was used to detect the levels of heat shock protein 70 (HSP70), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF-1α) in extracts from the ischemic cortex. Flow cytometry was used to observe the effect of LEV on neuronal cell apoptosis. Results: LEV treatment significantly increased the density of the surviving neurons in the cerebral cortex and reduced the infarct size (17.8 ± 3.3% vs. 12.9 ± 1.4%, p < 0.01) after MCAO. Concurrently, the time required to reach the platform for LEV-treated rats was shorter than that in the saline group on day 11 after MCAO (p < 0.01). LEV treatment prolonged the rotarod retention time on day 14 after MCAO (84.5 ± 6.7 s vs. 59.1 ± 6.2 s on day 14 compared with the saline-treated groups, p < 0.01). It also suppressed the activation of microglia and inhibited TNF-α and Il-1β in the ischemic brain (135.6 ± 5.2 pg/ml vs. 255.3 ± 12.5 pg/ml, 18.5 ± 1.3 pg/ml vs. 38.9 ± 2.3 pg/ml on day 14 compared with the saline-treated groups, p < 0.01). LEV treatment resulted in a significant increase in HIF-1α, VEGF, and HSP70 levels in extracts from the ischemic cerebral cortex. At the same time, LEV reduced neuronal cell cytotoxicity and apoptosis induced by an ischemic stroke (p < 0.01). Conclusion: LEV treatment promoted angiogenesis and functional recovery after cerebral ischemia in rats. These effects seem to be mediated through anti-inflammatory and antiapoptotic activities, as well as inducing the expression of HSP70, VEGF, and HIF-1α.

The well responsiveness of drug-resistant focal seizures in anti-AMPA2 receptor encephalitis to perampanel treatment.

Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis is an anti-neuronal surface antigen autoimmune encephalitis and is relatively rare. Our study evaluated a patient who developed anti-AMPA2 receptor encephalitis with memory deficits and refractory focal seizures as paroxysmal jerking on right face as well as dystonic seizure on right hand. On this patient, the combination treatment of levetiracetam, carbamazepine, and clonazepam, monthly periodic intravenous immunoglobin and immunosuppressive therapies for 5 months was not effective for the focal seizures, while his memory loss was slightly improved. However, adjunctive perampanel treatment led to a rapid relief of seizures. Perampanel is suggested in seizures associated with anti-AMPA receptor encephalitis by directly attenuating nerve hyperexcitability caused by glutamate and Ca2+-permeable GluA4 subunit of AMPA receptors.

Long-term safety, efficacy, and tolerability of levetiracetam in pediatric patients with epilepsy in Uygur, China: A retrospective analysis

PurposeLevetiracetam 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. MethodsThis 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. ResultsA 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. ConclusionThese 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.

Levetiracetam effectiveness as add-on therapy in Bulgarian patients with drug-resistant epilepsy.

There are no reliable prospective studies on the effectiveness of LEV in Bulgarian adult patients with drug-resistant epilepsy. The study aimed at conducting an open, prospective study on various aspects of levetiracetam (LEV) effectiveness in Bulgarian patients with drug-resistant epilepsy. The study was performed with patients with epilepsy recruited from those attending the Department of Neurology at the University Hospital in Plovdiv, Bulgaria. The patients completed diaries about seizure frequency, severity, and adverse events. There were regular documented visits at 3 or 6 months during the first year of treatment with LEV and at 6 months afterwards, with dynamic assessment of seizure frequency, severity, adverse events, and EEG recordings. LEV was applied as an add-on therapy in 135 patients (86 males, mean age 35 years). There was a relatively mild and persisting dynamic improvement of seizure severity, a satisfactory seizure frequency reduction in 49.6% of participants, a persisting mean seizure frequency reduction (48-58%) from 6 to 36 months of treatment and a high responder rate (53-60%) during the same period. New seizure types (focal with impaired awareness with /without evolution to bilateral tonic-clonic seizures) occurred in 4 patients. There were adverse events (dizziness, memory impairment, aggressiveness, numbness, non-epileptic seizures, depression, anxiety, speech disturbances, visual hallucinations, sleepiness, pelvic muscles weakness, confusion, sleep disturbances, loss of appetite, unstable gait, hair loss, acne, generalized rash) in 13.33% of patients. LEV treatment is associated with: low and persisting improvement of seizure severity, a good and persisting improvement of seizure frequency, a possible worsening of seizure control, a possible appearance of new seizure types, a good safety and tolerability.

Synaptic Vesicle Protein 2A Expression in Glutamatergic Terminals Is Associated with the Response to Levetiracetam Treatment.

Synaptic vesicle protein 2A (SV2A), the target of the antiepileptic drug levetiracetam (LEV), is expressed ubiquitously in all synaptic terminals. Its levels decrease in patients and animal models of epilepsy. Thus, changes in SV2A expression could be a critical factor in the response to LEV. Epilepsy is characterized by an imbalance between excitation and inhibition, hence SV2A levels in particular terminals could also influence the LEV response. SV2A expression was analyzed in the epileptic hippocampus of rats which responded or not to LEV, to clarify if changes in SV2A alone or together with glutamatergic or GABAergic markers may predict LEV resistance. Wistar rats were administered saline (control) or pilocarpine to induce epilepsy. These groups were subdivided into untreated or LEV-treated groups. All epileptic rats were video-monitored to assess their number of seizures. Epileptic rats with an important seizure reduction (>50%) were classified as responders. SV2A, vesicular γ-aminobutyric acid transporter and vesicular glutamate transporter (VGLUT) expression were assessed by immunostaining. SV2A expression was not modified during epilepsy. However, responders showed ≈55% SV2A-VGLUT co-expression in comparison with the non-responder group (≈40%). Thus, SV2A expression in glutamatergic terminals may be important for the response to LEV treatment.

Valproate but not levetiracetam slows the EEG alpha peak frequency – A pharmaco-EEG study

ObjectiveStudies of the effect of valproate (VPA) on the background EEG have shown varying results. Therefore, we compared the effect of VPA and levetiracetam (LEV) on the EEG alpha peak frequency (APF). MethodsWe retrospectively examined the APF in resting-state EEG of patients undergoing inpatient video-EEG monitoring (VEM) during withdrawal of VPA or LEV. We assessed APF trends by computing linear fits across individual patients’ APF as a function of consecutive days, and correlated the APF and daily antiseizure medication (ASM) doses on a single-patient and group level. ResultsThe APF in the VPA-group significantly increased over days with falling VPA doses (p = 0.005, n = 13), but did not change significantly in the LEV-group (p = 0.47, n = 18). APF correlated negatively with daily ASM doses in the VPA-group (average of r = −0.74 ± 0.12 across patients, p = 0.0039), but not in the LEV-group (average of r = −0.17 ± 0.18 across patients, p = 0.4072). ConclusionsOur results suggest that VPA treatment slows the APF. This APF reduction correlates with the daily dose of VPA and is not present in LEV treatment. SignificanceOur study identifies a VPA-related slowing of the APF even in patients without electroencephalographic or overt clinical signs of encephalopathy.

Levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord

Spinal cord injury (SCI) leads to dramatic impairments of motor, sensory, and autonomic functions of affected individuals. Following the primary injury, there is an increased release of glutamate that leads to excitotoxicity and further neuronal death. Therefore, modulating glutamate excitotoxicity seems to be a promising target to promote neuroprotection during the acute phase of the injury. In this study, we evaluated the therapeutic effect of a FDA approved antiepileptic drug (levetiracetam-LEV), known for binding to the synaptic vesicle protein SV2A in the brain and spinal cord. LEV therapy was tested in two models of SCI—one affecting the cervical and other the thoracic level of the spinal cord. The treatment was effective on both SCI models. Treated animals presented significant improvements on gross and fine motor functions. The histological assessment revealed a significant decrease of cavity size, as well as higher neuronal and oligodendrocyte survival on treated animals. Molecular analysis revealed that LEV acts by stabilizing the astrocytes allowing an effective uptake of the excess glutamate from the extracellular space. Overall, our results demonstrate that Levetiracetam may be a promising drug for acute management of SCI.

Levetiracetam and N-Cadherin Antibody Alleviate Brain Pathology Without Reducing Early Epilepsy Development After Focal Non-convulsive Status Epilepticus in Rats.

Focal non-convulsive status epilepticus (fNCSE) is a neurological condition characterized by a prolonged seizure that may lead to the development of epilepsy. Emerging experimental evidence implicates neuronal death, microglial activation and alterations in the excitatory and inhibitory synaptic balance as key features in the pathophysiology following fNCSE. We have previously reported alterations in the excitatory adhesion molecule N-cadherin in rats with fNCSE originating from the hippocampus that subsequently also develop spontaneous seizures. In this study, fNCSE rats were treated intraperitoneally with the conventional anti-epileptic drug levetiracetam in combination with intraparenchymal infusion of N-cadherin antibodies (Ab) for 4 weeks post-fNCSE. The N-cadherin Ab was infused into the fornix and immunohistochemically N-cadherin Ab-stained neurons were detected within the dorsal hippocampal structures as well as in superjacent somatosensory cortex. Continuous levetiracetam treatment for 4 weeks post-fNCSE reduced microglia activation, including cell numbers and morphological changes, partly decreased neuronal cell loss, and excitatory post-synaptic scaffold protein PSD-95 expression in selective hippocampal structures. The additional treatment with N-cadherin Ab did not reverse neuronal loss, but moderately reduced microglial activation, and further reduced PSD-95 levels in the dentate hilus of the hippocampus. Despite the effects on brain pathology within the epileptic focus, neither monotherapy with systemic levetiracetam nor levetiracetam in combination with local N-cadherin Ab administration, reduced the amount of focal or focal evolving into bilateral convulsive seizures, seizure duration, or interictal epileptiform activity during 1 month of continuous electroenephalogram recordings within the hippocampus after fNCSE. Behavioral tests for spatial memory, anxiety, social interaction and anhedonia did not detect gross behavioral differences between fNCSE rats with or without treatment. The results reveal the refractory features of the present rodent model of temporal lobe epilepsy following fNCSE, which supports its clinical value for further therapeutic studies. We identify the persistent development of epilepsy following fNCSE, in spite of partly reduced brain pathology within the epileptic focus.

The effect of complicated febrile convulsion on hippocampal function and its antiepileptic treatment significance.

BackgroundThis study aimed to explore the effects of complex febrile seizures on hippocampal function and the significance of antiepileptic therapy.MethodsA total of 150 children with complex febrile seizures admitted to our hospital from July 2017 to July 2020 were included in the study. The VPA group was given sodium valproate treatment; the LEV group was given levetiracetam treatment; and the observation group was given basic treatment. The efficacy of the patients was evaluated after medication. A complex febrile seizure young mouse model was constructed, and the hippocampal cell morphology and BCL-2 expression of the mice pups were analyzed. A Morris water maze was used to detect the changes in cognitive function of the young mice with complex febrile seizures.ResultsAfter treatment, the recurrence-free rate of the VPA group was significantly higher than that of the observation group (P=0.0045). After 1 month and 6 months, the improvement rate of EEG in VPA group was significantly higher than that in observation group (P<0.05). After treatment, the levels of BCL-2 in the VPA group and the LEV group decreased and were significantly lower than the observation group during the same period (P<0.05), and the M/C of the two groups was significantly higher than the observation group (P<0.05). The neuronal cells in the hippocampus of the young rats in the VPA group and the LEV group were regular, the matrix was more uniform, and nuclear pyknotic cells were occasionally seen. The pathological changes were less obvious than the model group, followed by the degree of pathological changes (0.92±1.31, 0.94±1.24). The incubation period of pups in the model group was significantly higher than that of the normal group, VPA group, and LEV group (P<0.05), and the number of crossing the station area was significantly less than that of the normal group, VPA group, and LEV group (P<0.05).ConclusionsAntiepileptic drugs are effective in preventing the recurrence of complicated febrile seizures (CFS), and the main mechanism may be related to the targeted regulation of BCL-2 on the apoptosis of the hippocampus in the nervous system.

Operation Brain Trauma Therapy: An Exploratory Study of Levetiracetam Treatment Following Mild Traumatic Brain Injury in the Micro Pig.

Operation brain trauma therapy (OBTT) is a drug- and biomarker-screening consortium intended to improve the quality of preclinical studies and provide a rigorous framework to increase the translational potential of experimental traumatic brain injury (TBI) treatments. Levetiracetam (LEV) is an antiepileptic agent that was the fifth drug tested by OBTT in three independent rodent models of moderate to severe TBI. To date, LEV has been the most promising drug tested by OBTT and was therefore advanced to testing in the pig. Adult male micro pigs were subjected to a mild central fluid percussion brain injury followed by a post-injury intravenous infusion of either 170 mg/kg LEV or vehicle. Systemic physiology was assessed throughout the post-injury period. Serial serum samples were obtained pre-injury as well as at 1 min, 30 min, 1 h, 3 h, and 6 h post-injury for a detailed analysis of the astroglial biomarker glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1. Tissue was collected 6 h following injury for histological assessment of diffuse axonal injury using antibodies against the amyloid precursor protein (APP). The animals showed significant increases in circulating GFAP levels from baseline to 6 h post-injury; however, LEV treatment was associated with greater GFAP increases compared to the vehicle. There were no differences in the numbers of APP+ axonal swellings within the pig thalamus with LEV treatment; however, significant alterations in the morphological properties of the APP+ axonal swellings, including reduced swelling area and increased swelling roundness, were observed. Additionally, expression of the neurite outgrowth marker, growth-associated protein 43, was reduced in axonal swellings following LEV treatment, suggesting potential effects on axonal outgrowth that warrant further investigation.

Assessment of the biomarkers of hepatotoxicity following carbamazepine, levetiracetam, and carbamazepine-levetiracetam adjunctive treatment in male Wistar rats.

This study examined some of the biomarkers of hepatotoxicity following chronic treatment with carbamazepine (CBZ), levetiracetam (LEV), and CBZ + LEV adjunctive treatment in male rats. Twenty-four male Wistar rats (140-150 g) were randomized into four groups (n = 6) to receive oral dose of normal saline (0.1 mL), CBZ (25 mg/kg), LEV (50 mg/kg) or sub-therapeutic dose of CBZ (12.5 mg/kg) together with LEV (25 mg/kg) for 28 days. Activities of the liver enzymes and oxidative stress markers were determined while liver histomorphology was also carried out. Data were analyzed using descriptive and inferential statistics. The results were presented as mean ± SEM in graphs or tables, while the level of significance was taken at p < 0.05. The activities of alkaline-phosphatase and malondialdehyde concentrations increased significantly in all the drug treatment groups, while the activities of superoxide dismutase decreased significantly following CBZ, and CBZ + LEV treatment. Alanine-aminotransferase activities increased significantly in the CBZ and CBZ + LEV treated rats compared with control. The liver section of CBZ treated rats showed mild vascular congestion. None of these AEDs treatment is devoid of hepatotoxicity. However, the adverse effects in CBZ were greater than LEV, or CBZ + LEV adjunctive treatment.

Association of headache, anxiety, and depression with the treatment of levetiracetam for epilepsy

The current case report bears the details of the adverse drug reactions (ADRs) associated after the administration of the levetiracetam for the management of newly diagnosed epilepsy in a female patient aged 37 years. Datum related to the patient, medications and observed ADRs were noted after getting the consent from the patient during which she has explained her experiences after the beginning of the consumption of the said drug. The Naranjo's scale and World Health Organisation, Uppsala Monitoring Centre scales analysis for the assessment of the correctness of the ADR paved for the certainty of the side effect. Drug regimen modification was initiated by the neurologist after the complaints of uneasiness from the patient after which she was identified to be complying with the other medication. Therefore, it can be said that if any patient on antiepileptic medications experiences discomfort, must bring those issues in light as there is always other options available for the management of the epilepsy without delay.

Evaluation of the Levetiracetam treatment on reduction of epileptic discharges in electroencephalogram in children with epilepsy.

Objectives:Epilepsy is a relatively common disease in childhood. In some patients, the electroencephalogram (EEG) is abnormal despite the clinical control of seizures. Studies have identified the adverse effects of epileptic discharges on cognition, learning, behavior, and seizure recurrence in children. This study investigated the Levetiracetam effect on epileptic discharges in the interictal phase of EEG in epileptic children.Materials & Methods: This clinical trial was conducted on 54 epileptic children aged 2 to 15 years, whose clinical seizures were controlled by sodium valproate in the last six months but still had epileptic discharges in EEG. The participants were divided into two groups: an intervention group (21 people), for which Levetiracetam was added to sodium valproate, and a control group (33 people), for which treatment with sodium valproate alone was continued. The patients were then followed for one year.Results:The percent normalization of epileptic discharges in the intervention and control groups was 66.7% and 57.1% (P = 0.500), respectively. Also, the mean time for the normalization of epileptic discharges in the intervention and control groups was 12.60±8.25 and 20.57±12.67 months (P = 0.042), respectively.Conclusion:In children with controlled seizures whose EEG was still abnormal, sodium valproate therapy alone and combined with Levetiracetam effectively reduced the severity of epileptic discharges. However, the addition of Levetiracetam to sodium valproate normalized EEG more rapidly.

Early intervention with levetiracetam prevents the development of cortical hyperexcitability and spontaneous epileptiform activity in two models of neurotrauma in rats

This study examined the antiepileptogenic potential of the antiseizure drug (ASD) levetiracetam (LEV) using the in vitro traumatized-slice and in vivo controlled cortical impact (CCI) models of traumatic brain injury (TBI) in rats when administered early after the injury. For the in vitro model, acute coronal slices (400–450 μm) of rat neocortex (P21–32) were injured via a surgical cut that separated the superficial layers from the deeper regions. Persistent stimulus-evoked epileptiform activity developed within 1–2 h after trauma. In randomly selected slices, LEV (500 μM) was bath-applied for 1 h starting immediately or delayed by 30–80 min after injury. Treated and untreated slices were examined for epileptiform activity via intracellular and extracellular recordings. For the in vivo model, rats (P24–32) were subjected to a non-penetrating, focal, CCI injury targeting the neocortex (5.0 mm diameter; 2.0 mm depth). Immediately after injury, rats were given either a single dose of LEV (60–150 mg/kg, i.p.) or the saline vehicle. At 2–3 weeks after the injury, ex vivo cortical slices were examined for epileptiform activity. The results from the traumatized-slice experiments showed that in vitro treatment with LEV within 60 min of injury significantly reduced (> 50%) the proportion of slices that exhibited stimulus-evoked epileptiform activity. LEV treatment also increased the stimulus intensity required to trigger epileptiform bursts in injured slices by 2–4 fold. Consistent with these findings, LEV treatment of CCI-injured rats (n = 15) significantly reduced the proportion of animals that exhibited spontaneous and stimulus-evoked epileptiform bursts in ex vivo cortical slices compared to saline-treated controls (n = 15 rats), and also significantly increased the stimulus intensity required to evoke epileptiform bursts. These results suggest that early administration of LEV has the potential to prevent or reduce posttraumatic epileptogenesis and that there may be a narrow therapeutic window for successful prophylactic intervention.

Effects of atorvastatin and aspirin on post-stroke epilepsy and usage of levetiracetam.

Objective:Atorvastatin and aspirin have been used in treating different forms of epilepsy. However, their effect on post-stroke epilepsy (PSE) still needs to be validated by large-scale clinical studies. In addition, their impact on the use of the antiepileptic drug levetiracetam for post-stroke epilepsy remains to be explored. Thus, the aim of this study was to further evaluate the effect of atorvastatin and aspirin on PSE and their effect on the usage of the antiepileptic drug levetiracetam in PSE patients.Methods:Patients, aged 65 to 85 years, with newly diagnosed post-ischemic stroke epilepsy from August 30, 2014 to August 30, 2018 were included in the study, with the exclusion of those with coexisting conditions.Results:Initially, 1321 patients were included, and 780 remained in the study at the 1-year follow-up. During the study, atorvastatin treatment with or without aspirin reduced the number of clinical epileptic episodes in PSE patients. It also reduced the dosage of levetiracetam and achieved better control of epilepsy compared to levetiracetam mono-treatment. Aspirin co-treatment with levetiracetam did not result in a significant improvement. However, the combination of aspirin with atorvastatin significantly reduced the number of seizures compared to atorvastatin treatment alone.Conclusion:Atorvastatin and aspirin co-treatment with levetiracetam can reduce epilepsy in PSE patients and reduce the dosage of levetiracetam required for effective control of PSE.

Pharmacological suppression of seizure‐like activity in the PS2APP model of amyloidosis

AbstractBackgroundSeizure activity is significantly increased in patients with Alzheimer Disease relative to healthy controls. Concurrently, the J20 mouse model of amyloidosis has increased seizure‐like activity, and compounds that lower this activity can lead to cognitive benefits in this model. Here we aim to extend these studies to the PS2APP mouse model of amyloidosis.MethodLocomotor activity was measured for 60 min in C57BL/6J mice with a beam‐break based monitoring system (PAS Open Field, San Diego Instruments) using a between‐subjects design with 9‐10 mice/dose group. EEG/EMG headmounts were implanted into PS2APP mice with amyloid‐beta pathology. Data was recorded for 6h using a Pinnacle Technologies recording system and processed with MATLAB (Mathworks) routines. EEG spikes were detected using a thresholded line‐length algorithm.A within subject crossover‐design was used for vehicle vs. Levetiracetam treatment and data from 13 PS2APP mice was analyzed.ResultLocomotor activity measures showed that an acute dose of 200 mg/kg of the anti‐seizure medication Levetiracetam did not affect activity levels. EEG recordings demonstrated that the frequency of seizure‐like spikes during sleep was increased from 38 spikes/h in 4 months old PS2APP mice to 75 spikes/h in 13 months old PS2APP mice. This measure was reduced by ∼60% in 13 months old PS2APP mice in response to acute treatment with 200 mg/kg of Levetiracetam.ConclusionSeizure‐like activity is increased in patients with Alzheimer’s disease and in mouse models of amyloidosis. Our Levetiracetam studies confirm that pharmacological intervention can normalize seizure‐like activity in PS2APP mice. Medications with different mechanism of action need to be tested for their ability to reduce spike activity and improve cognition in this animal model.Ultimately, it will be important to see if such pharmacological effects translate to humans and if reductions in seizure activity are linked to functional improvements.