Efficacy Of Levetiracetam Research Articles

Efficacy of Levetiracetam for Epilepsy in Pediatric Liver Transplant Recipients With Posterior Reversible Encephalopathy Syndrome.

Liver transplant is currently the most effective option for patients with end-stage liver disease. Seizures are the most common neurologic complication after liver transplant. Posterior reversible encephalopathy syndrome is a neurologic syndrome characterized by lethargy, seizures, visual disturbances, and radiologic findings of edema in the posterior regions of the cerebral hemispheres. Levetiracetam is prescribed for a broad spectrum of seizure types but does not have a specific indication for epilepsy in children after solid-organ transplant. Our aim was to investigate the efficacy and tolerability of levetiracetam in pediatric transplant recipients with posterior reversible encephalopathy syndrome and epilepsy. We reviewed records of patients treated for epilepsy due to posterior reversible encephalopathy syndrome after liver transplant seen at our pediatric neurology clinic between January 2010 and March 2019. Patients were assessed clinically and by neurologic examination, electroencephalography, and cerebral magnetic resonance imaging. Among 134 children who had undergone liver transplant between 2010 and 2019, 10 patients (6 males, 4 females; age range,7-19 y) who were diag-nosed with posterior reversible encephalopathy syndrome and epilepsy were included in the study. All patients received levetiracetam at 20 mg/kg/day. After a mean follow-up of 28.9 months (range, 24-40 mo), 9 patients (90%) attained complete seizure freedom. One patient who had an underlying neurodegenerative disease (hemophagocytic syndrome) other than posterior reversible encephalopathy syndrome continued to have seizures under levetiracetam treatment. One patient had a mild adverse reaction (irritability) due to levetiracetam but did not require drug discontinuation. In this study, 90% of patients with posterior reversible encephalopathy syndrome became seizure free with levetiracetam treatment. Our findings suggest that levetiracetam has a favorable efficacy for epilepsy due to posterior reversible encephalopathy syndrome in pediatric liver transplant recipients with tolerable adverse effects.

Efficacy of Levetiracetam in Treatment of Childhood Stuttering.

Background:Stuttering is a kind of speech disorder that affects about 1% of total population. As the origin of this disorder is not obviously diagnosed yet, various remedies have been practiced and among them different medicines have been studied, but unfortunately no significant effective drugs have been recognized yet. As stuttering imposes a great social and mental costs to the patients and their families, finding an effective medicine will help significantly. In this study we have focused on the effects of levetiracetam (LEV) treatment on children suffering from stuttering.Methods:In this clinical trial study, 30 children aged > 3 years (median 3.8 years) with stuttering and abnormal sleep electroencephalogram (EEG) were treated by LEV and followed-up for a minimum period of 6 weeks. The starting dose of 20 mg/kg/day was increased at an interval of 1 week by 20 mg/kg/day, if necessary, up to maximum dose of 60 mg/kg/day.Results:Overall LEV was effective in 70% of patients, decreasing stuttering to at least 50%. Three children (10%) became stuttering-free and only in one (3.3%) child an increase in stuttering was observed. There were statistically significant differences for efficacy in the presence of variables such as age groups, seizure, stuttering family history, and EEG data.Conclusions:LEV is an effective drug for treatment of childhood stuttering in those that have abnormal sleep EEG.

A Comparative Study on the Efficacy of Levetiracetam and Carbamazepine in the Treatment of Rolandic Seizures in Children: An Open-Label Randomized Controlled Trial.

Objective:This study was performed to investigate whether levetiracetam should be preferred to carbamazepine as a treatment choice for benign childhood epilepsy with centro Temporal spikes (BCECTS), the most common partial epilepsy of childhood.Methods:This randomized clinical trial study included 92 children with rolandic epilepsy aged 4–12 years referred to the Pediatric Neurology Clinic at Imam Hossein Hospital, Isfahan, Iran, from April 2019 to January 2020. Patients were selected consecutively and randomly assigned to two study groups (levetiracetam and carbamazepine groups). Patients were followed and revisited every 2 months for 6 months after starting the medication. The frequency and duration of seizure attacks and drug side effects were recorded before treatment and in bi-monthly visits. Data were analyzed by SPSS software Version 24 using Mann–Whitney U- test and Friedman test.Findings:In our study, the seizure frequency decrease was not significantly different between the two groups; however, patients in both groups showed significantly lower seizure frequency in 2, 4, and 6 months of follow-up compared to starting time. After a follow-up for 6 months, one out of 47 (2.1%) patients using levetiracetam showed intolerance, resulting in changing the medication. In addition, two out of 48 (4.1%) patients in the carbamazepine group had skin rashes. No significant changes had been reported regarding the duration of seizure attacks in both groups after treatment.Conclusion:This study showed encouraging results for using levetiracetam, with acceptable results and fewer side effects for the treatment of children with BCECTS in Iran.

Evaluation of the Efficacy of LevetiracetamPlus Iron in Comparison With Iron Alone in Controlling and Reducing the Frequency of Breath-Holding Spells in Children Aged 6 Months to 5 Years.

A breath-holdingspell (BHS) is defined as an apnea attack following an initial stressful event like anger, sadness, and fear, a painful event like falling or head trauma or any stressful psychology event. This study was designed to assessthe comparative efficacy of levetiracetam plus iron and iron alone in reducingthe BHS frequency in children aged 6 months to 5 years. This study was designed asa double-blinded randomized clinical trial. Sixty patients aged 6 months to 5 years were assigned into two groups, withthe first group (A) receiving onlyiron and the second group (B)receiving levetiracetam plus iron. At the end of the study, the efficacy of therapywas analyzed comparatively in these groups. In this study, the mean number of attacks was 3.94 ± 2.69 before treatment and 1.71 ± 1.99after treatmentin the group A,while it was 6.39 ± 5.7 before treatment and 0.37 ± 1.03after treatment in the group B.The mean number of attacksafter treatment was lower in group B than in group A. In fact, there was a significant difference between the two groups in terms of the number of attacks after treatment (P = 0.003). Levetiracetam plus iron is more effective than iron alone in reducing BHSs in children aged 6 months to 5 years.

Neonatal seizures – Levetiracetam versus phenobarbital

Background: Neonatal seizures (NS) are an important cause of admission in the neonatal intensive care units (NICU) in India. While the drug which stood the test of time is phenobarbitone (PB), levetiracetam (LEV) may be a better alternative with superior effects. Objective: The objective of the study was to compare the efficacy of LEV and PB for the treatment and follow-up of term neonates with NS. Materials and Methods: This open-labeled randomized controlled trial was carried out on 80 newborn babies suffering from clinically apparent seizures who were admitted in a tertiary care NICU of Bihar. All admitted term neonates who were without transient metabolic disorders (hypoglycemia or hypocalcemia) were randomly assigned. LEV (n=42) at an intravenous (IV) doses of 10 mg/kg was gradually increased to 15 mg/kg and PB (n=38) at a dose of 20 mg/kg/dose IV over 20 min gradually increased in aliquots of 10 mg/kg up to 40 mg/kg total dose. Neonates whose seizures were not controlled by the assigned drug were then crossed over to be treated with the other drug in same dose. Results: Clinical features and baseline characteristics were compared in both groups. Seizures were controlled in 66.6% neonates who received LEV, as compared to 81.5% neonates who received PB (p>0.05). Short-term adverse effects (cardiorespiratory depression and sedation) were noted in 52.6% babies in PB group in comparison to 7.1% babies in LEV group (p<0.05). Long-term neuromotor and developmental complications were less in LEV group as compared to PB group (p<0.05) at 1 year of age. Conclusion: LEV and PB, both were equally effective in control of clinical seizures irrespective of the etiology, but LEV is superior in terms of short- and long-term neurodevelopmental outcomes than PB.

Efficacy of levetiracetam combined with sodium valproate on pediatric epilepsy and its effect on serum miR-106b in children.

Efficacy of levetiracetam (LEV) combined with sodium valproate (SV) on pediatric epilepsy and its effect on serum miR-106b in children were investigated. One hundred and twenty children with epilepsy in Xuzhou Children's Hospital from July 2015 to July 2017 were enrolled, and divided into control group (n=60) and observation group (n=60) according to random sampling. Additionally, 100 children undergoing normal physical examination were collected as normal group. Patients in the control group were treated with SV, and patients in the observation group were treated with SV and LEV. RT-qPCR was used for detecting the relative expression of serum miR-106b in children. The clinical efficacy was evaluated. After treatment, the relative expression of serum miR-106b in the control group was significantly higher than that in the observation group (P<0.05). The difference in the control group was smaller than that in the observation group (P<0.05). According to the ROC curve analysis, when the cut-off value was 1.442, the sensitivity, specificity and area under curve (AUC) of miR-106b in the diagnosis of pediatric epilepsy were 94.00, 64.17 and 0.833 respectively. The clinical efficacy in the observation group was significantly better than that in the control group (P<0.05). Spearman's test showed that the expression of miR-106b gradually decreased with the continuous improvement of the clinical efficacy (P<0.05). The AUC of miR-106b was 0.833, 95% CI: 0.779 to 0.887, the cut-off was 1.442. LEV combined with SV is effective in the treatment of children with epilepsy, and does not increase the clinical ADR. The expression of serum miR-106b in children can be used as a clinical prognostic indicator and a potential diagnostic indicator.

Efficacy of levetiracetam as the first line anti- epileptic drug in management of neonatal seizures

Background: Neonatal seizure management has not changed much in the last 50 years. Neuronal apoptosis in animal models and cognitive impairment in human subjects has been reported with the use of Phenobarbitone. Levetiracetam is advantageous as it is effective, well tolerated and has least drug interactions.Methods: This double blinded, randomized, parallel group, active controlled study was conducted among 66 neonates in the Neonatal intensive care unit of a tertiary care hospital for a period of 18 months. Neonates with seizures fulfilling the inclusion criteria were treated either with Phenobarbitone or Levetiracetam. Seizure control was defined as no seizure activity within 40 minutes of the administration of the first drug. Failure of first line agent was treated with Phenytoin. Neonates were observed for a period of 14 weeks for recurrence of seizure and any serious adverse effects.Results: Effective seizure control was achieved in 64.7% neonates in Levetiracetam group as compared to 31.2% in Phenobarbitone group (p &lt;0.05). Early resumption of breast feeds within 6 hours of therapy was achieved in 73.5% neonates treated with Levetiracetam compared to 31.2% neonates treated with Phenobarbitone (p value = 0.001).Conclusions: Levetiracetam is a promising alternative as first line Anti-epileptic drug in neonates with seizures. Prolonged sedation was the adverse effect noted to Phenobarbitone that made breast feeding and neuro- assessment difficult. No serious adverse effects were seen with Levetiracetam.

Is it a Tie at This Point in the Game? Efficacy of Levetiracetam and Phenytoin for the Second-Line Treatment of Convulsive Status Epilepticus.

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Safety and Efficacy of Levetiracetam for the Management of Levodopa- Induced Dyskinesia in Patients with Parkinson's Disease: A Systematic Review.

Levetiracetam, a novel antiepileptic drug, has shown antidyskinetic effects in experimental animal models of Parkinson's disease (PD). The tolerability and efficacy of levetiracetam in reducing the levodopa-induced dyskinesia (LID) in PD patients have not been established. Therefore, this study aims to synthesize evidence from published prospective clinical trials about the efficacy of levetiracetam for the management of LID in PD patients. We followed the PRISMA statement guidelines during the preparation of this systematic review. A computer literature search of PubMed, EBSCO, Scopus, MEDLINE, and the web of science was carried out. We selected prospective clinical trials assessing the anti-dyskinetic efficacy of levetiracetam for treating LID in patients with PD. The Abnormal Involuntary Movement Scale (AIMS), Clinical Global Impression Score (GCI), UPDRS III, and UPDRS IV were considered as the primary outcome measures; their data were extracted and reviewed. Our review included seven clinical trials with a total of 150 patients. Of them, three studies were randomized controlled trials, and the remaining were open-label single arm trials. Four studies reported poor tolerability of the levetiracetam with mild anti-dyskinetic effects. Levetiracetam slightly improved the UPDRS-IV and AIMS scores with small effect size. In the remaining three studies, levetiracetam failed to exhibit any anti-dyskinetic effects. Current evidence does not support the efficacy of the levetiracetam for treating LID in PD patients, however, due to the limited number of published randomized control trials (RCTs), further RCTs are required.

Early infantile epileptic encephalopathy type 4: clinical, neurophysiological and therapeutic aspects

Objective . Study the clinical and neurophysiological evolution of early infantile epileptic encephalopathy type 4 (EIEE4) caused by a STXBP1 gene mutation. Material and methods. During 2016-2019, we conducted dynamic observation and treatment of a girl with EIEE4 combined with a mutation in the STXBP1 gene. DNA sequencing was performed using the Hereditary epilepsies panel (Next Generation Sequencing on the platform of Illumina HiSeq 2500, USA). Dynamic video-EEG monitoring was performed with an “Encephalan-Video RM-19/26 (Medicom MTD“, Russia). Results. In this 3.5 y.o. patient with infantile epileptic encephalopathy, a heterozygous autosomal dominant de novo mutation in the STXBP1 gene was found. This mutation (not described previously) is located in chromosome 9, specifically, in the 20th exon with genome coordinates Chr9:130453 (C.*96T>A). This child suffered from severe neonatal hypoxic-ischemic encephalopathy, which led to spastic cerebral palsy. In addition, she developed seizures as early as at the age of 6 month; the seizures (flexor tonic spasms) were paralleled with EEG changes similar to the Mar-kand-Blume-Ohtahara syndrome, namely, multiple independent spike-wave foci in combination with the partial attenuation pattern (kind of the burst-suppression pattern). Valproate monotherapy had little effect, and hormonal treatment caused a temporary improvement. Permanent clinical remission with no seizures was achieved by including leveti-racetam in the therapeutic combination. A number of studies demonstrated a high efficacy of levetiracetam in cases of STXBP1 gene mutations. At the age of 2,5years, the girl demonstrated changes in her EEG records toward the continuous spike-wave during sleep (CSWS) pattern with the morphology of benign epileptiform discharges of childhood (BEDC). Conclusions. In spite of the aggravated perinatal anamnesis, children with epileptic encephalopathy need genetic examination using the Next Generation Sequencing (NGS) methods (such as Hereditary epilepsies panel), combined with full exome sequencing. Such genetic examinations are helpful for establishing the exact etiology of epilepsy and developing a personalized approach to antiepileptic therapy.

Should Levetiracetam or Imepitoin Be Used in Preference as Second-line Treatment in Pharmacoresistent Epileptic Cats?

PICO questionIn adult cats with idiopathic epilepsy, which is poorly controlled with phenobarbital monotherapy, should levetiracetam or imepitoin be used in preference as a second line treatment in order to reduce seizure frequency?Clinical bottom lineThere is currently insufficient evidence to reliably determine whether levetiracetam or imepitoin should be used in preference as a second line treatment for the management of cats with refractory idiopathic epilepsy. There is weak evidence however to suggest clinical efficacy of levetiracetam and imepitoin in management of cats with idiopathic epilepsy. Further studies which evaluate and directly compare the efficacy of second line anticonvulsants in feline epilepsy are needed.

Synaptic vesicle protein 2A tumoral expression predicts levetiracetam adverse events.

The efficacy of levetiracetam (LEV) in controlling seizures in patients with brain tumor-related epilepsy (BTRE) depends on tumoral expression of synaptic vesicle protein 2A (SV2A). Although LEV is generally well tolerated, neuropsychiatric adverse events (NPAEs) might occur, limiting compliance and seizure control. We aimed to assess the influence of tumoral SV2A expression on the occurrence of LEV-related NPAEs in patients with glioma. Specimens from patients enrolled in the multicenter COMPO study, with glioma and BTRE treated with LEV, undergoing neurosurgery were retrieved. Immunohistochemistry-based expression of SV2A in tumoral and peritumoral tissue was scored in a four-point scale from absent (score = 0) to strong (score = 3). Low immunoreactivity (IR) corresponded to scores < 2. Staining ratios (tumoral SV2A IR/peritumoral SV2A IR) were grouped into low (≤ 0.5) and high (> 0.5). NPAEs were assessed longitudinally with the Neuropsychiatry Inventory 12 test (NPI-12). Overall, 18 patients were eligible for analysis. All received LEV monotherapy, with 67% developing NPAEs. Patients with NPAEs had significantly lower median SV2A intensity score compared to patients without NPAEs (score 1 vs 0, p = 0.025). Low staining ratio (≤ 0.5) associated with higher NPAE occurrence compared to SR > 0.5 (85.7% vs 0%, p < 0.01). A SR ≤ 0.5 predicted a consistent increase in risk of NPAEs (OR 45.0; 95% CI 1.8-1128; p = 0.02). Our results suggest that SV2A expression in tumoral and peritumoral tissue correlates with the occurrence of LEV-related NPAEs. Thus, considering that SV2A expression also influences LEV effectiveness, SV2A staining might help in tailoring treatment to patients.

Short-Term Neurodevelopmental Outcome in Term Neonates Treated with Phenobarbital versus Levetiracetam: A Single-Center Experience

Background Phenobarbital (PB) has been traditionally used as the first-line treatment for neonatal seizures. More recently, levetiracetam (LEV) has been increasingly used as a promising newer antiepileptic medication for treatment of seizures in neonates. Objectives The aim of our study was to compare the effect of PB vs. LEV on short-term neurodevelopmental outcome in infants treated for neonatal seizures. Method This randomized, one-blind prospective study was conducted on term neonates admitted to the Neonatal Intensive Care Unit of S. Bambino Hospital, University Hospital “Policlinico-Vittorio Emanuele,” Catania, Italy, from February 2016 to February 2018. Thirty term neonates with seizures were randomized to receive PB or LEV; the Hammersmith Neonatal Neurological Examination (HNNE) was used at baseline (T0) and again one month after the initial treatment (T1). Results We found a significantly positive HNNE score for the developmental outcomes, specifically tone and posture, in neonates treated with LEV. There was no significant improvement in the HNNE score at T1 in the neonates treated with PB. Conclusion This study suggests a positive effect of levetiracetam on tone and posture in term newborns treated for neonatal seizures. If future randomized-controlled studies also show better efficacy of LEV in the treatment of neonatal seizures, LEV might potentially be considered as the first-line anticonvulsant in this age group.

Levetiracetam for prophylactic treatment of pediatric migraine: A randomized double-blind placebo-controlled trial.

Few drugs are available for migraine prophylaxis in children. Levetiracetam is a broad-spectrum anti-seizure drug that has been suggested to be effective in reducing adult migraine episodes. We assessed the safety and efficacy of levetiracetam in the prevention of pediatric migraine. A randomized double-blind placebo-controlled trial was performed. Eligible participants were aged 4-17 years old with at least four migrainous episodes monthly or had severe disabling or intolerable episodes. Primary endpoints were the mean changes in monthly frequency and intensity of headaches from the baseline phase to the last month of the double-blind phase. Safety endpoint was the adverse effects reported. Sixty-one participants (31 taking levetiracetam and 30 taking placebo) completed the study. All had a significant reduction in frequency and intensity of episodes that was significantly greater in the levetiracetam arm. Sixty eight percent of individuals in the treatment group reported more than 50% reduction of episodes at the end of the trial compared with 30% in the placebo group (p-value: 0.007). Irritability, day-time sedation, and mild tic were reported. Levetiracetam may be useful in migraine prevention and may decrease migraine episodes and severity. The study is prospectively registered with Iranian Registry of Clinical Trials; IRCT.ir, number IRCT2017021632603N1.

Levetiracetam versus phenytoin for treatment of convulsive status epilepticus in pediatric population: a randomized controlled trial

Background: Status epilepticus is a major medical and neurological emergency. Despite advances in treatment, it is still associated with significant morbidity and mortality. The objective of the study was to compare the efficacy of levetiracetam versus phenytoin in treatment of convulsive status epilepticus.Methods: A Randomized control trial, was conducted at tertiary care hospital, Udaipur, Rajasthan, over a period of March 2017 to September 2018. Total 250 patients (age group 6 months to 18 years) who were presented with status epilepticus in PICU, were enrolled. These patients were divided into two groups by simple randomization. Levetiracetam was given to one group, while phenytoin was given to another group. Efficacy was decided by cessation of clinical seizure activity within 30 minutes of starting of drug infusion and patient was observed for recurrence of seizure within 24 hours.Results: A total of 250 patients were enrolled in this study. Seizure terminated in 107 patients in phenytoin group (85.6%) and in 114 patients in levetiracetam group (91.2%). The difference was significant. Recurrence of seizure (with in 24 hour) was high in phenytoin group (14.4%) in comparison with levetiracetam group (8.8%). Most common adverse effect in both the groups on treatment was hypotension, though in phenytoin group it was significantly higher than patients on levetiracetam group (7.2% v/v 2.4%).Conclusions: Levetiracetam may be an effective alternative to phenytoin as a second line drug in the management of benzodiazepine resistant convulsive status epilepticus in children.

Efficacy of Levetiracetam as first-line treatment in neonatal seizure

Efficacy of Levetiracetam as first-line treatment in neonatal seizure

Clinical Use and Efficacy of Levetiracetam for Absence Epilepsies.

Levetiracetam is prescribed for a broad spectrum of seizure types but does not have a specific indication for absence epilepsy. We hypothesized that levetiracetam is commonly prescribed for children with absence epilepsies and evaluated the efficacy of this medication for absence epilepsy treatment in clinical practice. We also hypothesized that electroencephalographic (EEG) findings could help predict levetiracetam efficacy. We reviewed the charts of all patients treated for new-onset absence epilepsies at our pediatric neurology clinic between January 2011 and January 2016. Among 158 children diagnosed with absence epilepsies, 72 were treated with levetiracetam. Levetiracetam was discontinued in 74% (n = 53/72) because of incomplete seizure control (59%, n = 35/72) and/or intolerable side effects (41%, n = 24/72) after a median 8.5 months (interquartile range 2, 17 months). Among patients for whom levetiracetam was effective, 44% (n = 8/18) had polyspikes on their initial EEG, versus 27% (n = 14/52) of patients for whom levetiracetam was discontinued ( P = .17). The maximal prescribed dose was lower for children in whom levetiracetam was effective (29 ± 13 mg/kg/d) than those for whom levetiracetam failed (42 ± 20 mg/kg/d; P = .005). In routine clinical practice, levetiracetam is often chosen for patients with absence seizures. However, only about one-quarter of children with absence epilepsy in this study became seizure free with levetiracetam. When effective, levetiracetam can control absence epilepsy at a relatively low dose. Lack of seizure control requiring continued dose escalation should prompt early consideration of a therapeutic medication transition.

Efficacy of levetiracetam for reducing rolandic discharges in comparison with carbamazepine and valproate sodium in rolandic epilepsy

PurposeThe main purpose of this study was to compare the efficacy of levetiracetam (LEV) with the older antiepileptic drugs (AEDs) for preventing atypical evolution in children with Rolandic epilepsy (RE). Accordingly, the present study compared the efficacy of older AEDs (carbamazepine (CBZ) and valproate sodium (VPA)) with LEV in reducing rolandic discharges (RDs) on interictal electroencephalogram (EEG) in children with RE. MethodsPatients in this heterogenous study were subdivided into CBZ, VPA and LEV groups in accordance with the initial monotherapy. The CBZ and VPA groups were studied retrospectively, but the LEV group was studied prospectively. Appearances of discharges were counted and these rates were computed. In comparison with the baseline RD frequency, EEG response to AED treatment was classified such as complete disappearance and response (≥50% reduction in RD frequency). The time taken to attain complete disappearance or response in EEG responders was assessed for each AED treatment group. ResultsResponders comprised 10 (11.2%) of the 89 patients treated with CBZ, 41 (56.2%) of the 73 patients with VPA, and 25 (71.4%) of the 35 patients with LEV. Mean interval to achievement of EEG response in the CBZ, VPA, and LEV groups were 36.3, 23.1, and 14.7 months, respectively. EEG response was achieved significantly more rapidly with LEV than with CBZ (p < 0.001) or VPA (p < 0.005). Seizure control was not significantly different in all 3 investigated drugs. ConclusionsLEV seems to be superior to CBZ and VPA in its ability to suppress RDs in children with RE.

Personalized prediction model for seizure-free epilepsy with levetiracetam therapy: a retrospective data analysis using support vector machine.

To predict the probability of a seizure-free (SF) state in patients with epilepsy (PWEs) after treatment with levetiracetam and to identify the clinical and electroencephalographic (EEG) factors that affect outcomes. Retrospective analysis of PWEs treated with levetiracetam for 3years identified 22 patients who were SF and 24 who were not. Before starting levetiracetam, 11 clinical factors and four EEG features (sample entropy of α, β, θ, δ) were identified. Overall, 80% of each the two groups were chosen to establish a support vector machine (SVM) model with 5-fold cross-validation, hold-out validation and jack-knife validation. The other 20% were used to predict the efficacy of levetiracetam. The mean impact value (MIV) algorithm was used to rank the relativity between factors and outcomes. Compared with SF patients, not SF patients displayed a specific decrease in EEG sample entropy in α band from the F4 channel, β band from Fp2 and F8 channels, θ band from C3 channel (P<0.05). The SVM model based on the clinical and EEG features yielded 72.2% accuracy of 5-fold cross-validation, 75.0% accuracy of jack-knife validation, 67.7% accuracy of hold-out validation in the training set and had a high prediction accuracy of 90% in test set (sensitivity was 100%, area under the receiver operating characteristic curve was 0.96). The feature of β band from Fp2 weighs heavily in the prediction model according to the mean impact value algorithm. The efficacy of levetiracetam on newly diagnosed PWEs could be predicted using an SVM model, which could guide antiepileptic drug selection.

The novel, catalytic mTORC1/2 inhibitor PQR620 and the PI3K/mTORC1/2 inhibitor PQR530 effectively cross the blood-brain barrier and increase seizure threshold in a mouse model of chronic epilepsy

The mTOR signaling pathway has emerged as a possible therapeutic target for epilepsy. Clinical trials have shown that mTOR inhibitors such as everolimus reduce seizures in tuberous sclerosis complex patients with intractable epilepsy. Furthermore, accumulating preclinical data suggest that mTOR inhibitors may have anti-seizure or anti-epileptogenic actions in other types of epilepsy. However, the chronic use of rapalogs such as everolimus is limited by poor tolerability, particularly by immunosuppression, poor brain penetration and induction of feedback loops which might contribute to their limited therapeutic efficacy. Here we describe two novel, brain-permeable and well tolerated small molecule 1,3,5-triazine derivatives, the catalytic mTORC1/C2 inhibitor PQR620 and the dual pan-PI3K/mTOR inhibitor PQR530. These derivatives were compared with the mTORC1 inhibitors rapamycin and everolimus as well as the anti-seizure drugs phenobarbital and levetiracetam. The anti-seizure potential of these compounds was determined by evaluating the electroconvulsive seizure threshold in normal and epileptic mice. Rapamycin and everolimus only poorly penetrated into the brain (brain:plasma ratio 0.0057 for rapamycin and 0.016 for everolimus). In contrast, the novel compounds rapidly entered the brain, reaching brain:plasma ratios of ∼1.6. Furthermore, they significantly decreased phosphorylation of S6 ribosomal protein in the hippocampus of normal and epileptic mice, demonstrating effective mTOR inhibition. PQR620 and PQR530 significantly increased seizure threshold at tolerable doses. The effect of PQR620 was more marked in epileptic vs. nonepileptic mice, matching the efficacy of levetiracetam. Overall, the novel compounds described here have the potential to overcome the disadvantages of rapalogs for treatment of epilepsy and mTORopathies directly connected to mutations in the mTOR signaling cascade.