Brain Tumor-related Epilepsy Research Articles

Efficacy of perampanel by etiology in Japanese patients with epilepsy-subpopulation analysis of a prospective post-marketing observational study.

To examine the efficacy and safety of perampanel (PER) in patients with post-stroke epilepsy (PSE), brain tumor-related epilepsy (BTRE), and post-traumatic epilepsy (PTE) using Japanese real-world data. The prospective post-marketing observational study included patients with focal seizures with or without focal to bilateral tonic-clonic seizures who received PER combination therapy. The observation period was 24 or 52 weeks after the initial PER administration. The safety and efficacy analysis included 3716 and 3272 patients, respectively. This post hoc analysis examined responder rate (50% reduction in seizure frequency), seizure-free rate (proportion of patients who achieved seizure-free), and safety in patients included in the post-marketing study who had PSE, BTRE, and PTE in the 4 weeks prior to the last observation. Overall, 402, 272, and 186 patients were included in the PSE, BTRE, and PTE subpopulations, and 2867 controls in the "Other" population (etiologies other than PSE, BTRE, or PTE). Mean modal dose (the most frequently administered dose) values at 52 weeks were 3.38, 3.36, 3.64, and 4.04 mg/day for PSE, BTRE, PTE, and "Other," respectively; PER retention rates were 56.2%, 54.0%, 52.6%, and 59.7%, respectively. Responder rates (% [95% confidence interval]) were 82% (76.3%-86.5%), 78% (70.8%-83.7%), 67% (56.8%-75.6%), and 50% (47.9%-52.7%) for PSE, BTRE, PTE, and "Other," respectively, and seizure-free rates were 71% (64.5%-76.5%), 62% (54.1%-69.0%), 50% (40.6%-60.4%), and 28% (25.8%-30.1%), respectively. Adverse drug reactions tended to occur less frequently in the PSE (14.7%), BTRE (16.5%), and PTE (16.7%) subpopulations than in the "Other" population (26.3%). In real-world clinical conditions, efficacy and tolerability for PER combination therapy were observed at low PER doses for the PSE, BTRE, and PTE subpopulations. To find out how well the medication perampanel works and whether it is safe for people who have epilepsy after having had a stroke, brain tumor, or head injury, we used information from real-life medical situations in Japan. We looked at the data of about 3700 Japanese patients with epilepsy who were treated with perampanel. We found that perampanel was used at lower doses and better at controlling seizures, and had fewer side effects for patients with epilepsy caused by these etiologies than the control group.

Exosomal TNF-α mediates voltage-gated Na+ channel 1.6 overexpression and contributes to brain tumor-induced neuronal hyperexcitability.

Patients affected by glioma frequently experience epileptic discharges; however, the causes of brain tumor-related epilepsy (BTRE) are still not completely understood. We investigated the mechanisms underlying BTRE by analyzing the effects of exosomes released by U87 glioma cells and by patient-derived glioma cells. Rat hippocampal neurons incubated for 24 hours with these exosomes exhibited increased spontaneous firing, while their resting membrane potential shifted positively by 10-15 mV. Voltage clamp recordings demonstrated that the activation of the Na+ current shifted toward more hyperpolarized voltages by 10-15 mV. To understand the factors inducing hyperexcitability, we focused on exosomal cytokines. Western blot and ELISAs showed that TNF-α was present inside glioma-derived exosomes. Remarkably, incubation with TNF-α fully mimicked the phenotype induced by exosomes, with neurons firing continuously, while their resting membrane potential shifted positively. Real-time PCR revealed that both exosomes and TNF-α induced overexpression of the voltage-gated Na+ channel Nav1.6, a low-threshold Na+ channel responsible for hyperexcitability. When neurons were preincubated with infliximab, a specific TNF-α inhibitor, the hyperexcitability induced by exosomes and TNF-α was drastically reduced. We propose that infliximab, an FDA-approved drug to treat rheumatoid arthritis, could ameliorate the conditions of glioma patients with BTRE.

Patient-Centered Management of Brain Tumor-Related Epilepsy.

Brain tumor-related epilepsy is a heterogenous syndrome involving variability in incidence, timing, pathophysiology, and clinical risk factors for seizures across different brain tumor pathologies. Seizure risk and disability are dynamic over the course of disease and influenced by tumor-directed treatments, necessitating individualized patient-centered management strategies to optimize quality of life. Recent translational findings in diffuse gliomas indicate a dynamic bidirectional relationship between glioma growth and hyperexcitability. Certain non-invasive measures of hyperexcitability are correlated with survival outcomes, however it remains uncertain how to define and measure clinically relevant hyperexcitability serially over time. The extent of resection, timing of pre-operative and/or post-operative seizures, and the likelihood of tumor progression are critical factors impacting the risk of seizure recurrence. Newer anti-seizure medications are generally well-tolerated with similar efficacy in this population, and several rapid-onset seizure rescue agents are in development and available. Seizures in patients with brain tumors are strongly influenced by the underlying tumor biology and treatment. An improved understanding of the interactions between tumor cells and the spectrum of hyperexcitability will facilitate targeted therapies. Multidisciplinary management of seizures should occur with consideration of tumor-directed therapy and prognosis, and anti-seizure medication decision-making tailored to the individual priorities and quality of life of the patient.

Multi-omics technologies and molecular biomarkers in brain tumor-related epilepsy.

Brain tumors are one of the leading causes of epilepsy, and brain tumor-related epilepsy (BTRE) is recognized as the major cause of intractable epilepsy, resulting in huge treatment cost and burden to patients, their families, and society. Although optimal treatment regimens are available, the majority of patients with BTRE show poor resolution of symptoms. BTRE has a very complex and multifactorial etiology, which includes several influencing factors such as genetic and molecular biomarkers. Advances in multi-omics technologies have enabled to elucidate the pathophysiological mechanisms and related biomarkers of BTRE. Here, we reviewed multi-omics technology-based research studies on BTRE published in the last few decades and discussed the present status, development, opportunities, challenges, and prospects in treating BTRE. First, we provided a general review of epilepsy, BTRE, and multi-omics techniques. Next, we described the specific multi-omics (including genomics, transcriptomics, epigenomics, proteomics, and metabolomics) techniques and related molecular biomarkers for BTRE. We then presented the associated pathogenetic mechanisms of BTRE. Finally, we discussed the development and application of novel omics techniques for diagnosing and treating BTRE. Genomics studies have shown that the BRAF gene plays a role in BTRE development. Furthermore, the BRAF V600E variant was found to induce epileptogenesis in the neuronal cell lineage and tumorigenesis in the glial cell lineage. Several genomics studies have linked IDH variants with glioma-related epilepsy, and the overproduction of D2HG is considered to play a role in neuronal excitation that leads to seizure occurrence. The high expression level of Forkhead Box O4 (FOXO4) was associated with a reduced risk of epilepsy occurrence. In transcriptomics studies, VLGR1 was noted as a biomarker of epileptic onset in patients. Several miRNAs such as miR-128 and miRNA-196b participate in BTRE development. miR-128 might be negatively associated with the possibility of tumor-related epilepsy development. The lncRNA UBE2R2-AS1 inhibits the growth and invasion of glioma cells and promotes apoptosis. Quantitative proteomics has been used to determine dynamic changes of protein acetylation in epileptic and non-epileptic gliomas. In another proteomics study, a high expression of AQP-4 was detected in the brain of GBM patients with seizures. By using quantitative RT-PCR and immunohistochemistry assay, a study revealed that patients with astrocytomas and oligoastrocytomas showed high BCL2A1 expression and poor seizure control. By performing immunohistochemistry, several studies have reported the relationship between D2HG overproduction and seizure occurrence. Ki-67 overexpression in WHO grade II gliomas was found to be associated with poor postoperative seizure control. According to metabolomics research, the PI3K/AKT/mTOR pathway is associated with the development of glioma-related epileptogenesis. Another metabolomics study found that SV2A, P-gb, and CAD65/67 have the potential to function as biomarkers for BTRE. Based on the synthesized information, this review provided new research perspectives and insights into the early diagnosis, etiological factors, and personalized treatment of BTRE.

Epilepsy in Patients with Gliomas.

Brain tumor-related epilepsy (BTRE) is a complication that significantly impairs the quality of life and course of treatment of patients with brain tumors. Several recent studies have shed further light on the mechanisms and pathways by which genes and biological molecules in the tumor microenvironment can cause epilepsy. Moreover, epileptic seizures have been found to promote the growth of brain tumors, making the control of epilepsy a critical factor in treating brain tumors. In this study, we summarize the previous research and recent findings concerning BTRE. Expectedly, a deeper understanding of the underlying genetic and molecular mechanisms leads to safer and more effective treatments for suppressing epileptic symptoms and tumor growth.

Effects of Levetiracetam and Lacosamide on survival and seizure control in IDH-wild type glioblastoma during temozolomide plus radiation adjuvant therapy

IntroductionThere are no clear indications for the best choice of anti-seizure medications to control brain tumor related epilepsy. In vitro studies have shown an antitumoral effect of Levetiracetam and Lacosamide on glioblastoma IDH-wild type. Research questionThis study investigates whether the use of levetiracetam and/or lacosamide impacts survival rates. The secondary aim was to evaluate the efficacy of both ASMs in controlling seizures. Materials and methodsIn this observational retrospective single-cohort study, patients underwent chemoradiation protocol after GBM surgery. They were grouped as follows: (1) use of levetiracetam, (2) use of lacosamide, (3) simultaneous use of levetiracetam and lacosamide, (4) no ASM usage. Survival curves were plotted using the Kaplan-Meier method coupled with a log-rank test for difference assesments. To evaluate the pharmacological efficacy of post-operative seizure control, a negative binomial regression was conducted. ResultsThe study included 272 patients, 174 of which underwent adjuvant chemoradiation treatment. Patients without ASM therapy had a non-significant longer median OS (compared to the other groups (log-rank = 0.37). The IRR of seizure relapse was 2.57 (p = 0.007) times higher in lacosamide users, and MGMT promoter methylation demonstrated a protective effect against postoperative seizure onset (p = 0.05), regardless of the aforementioned confounding factors. Discussion and conclusionsIn patients diagnosed with GBM IDH-WT undergoing chemoradiation therapy, the use of levetiracetam or lacosamide for controlling BTRE does not seem to modify survival. Lacosamide users exhibited a higher IRR of postoperative seizures compared to levetiracetam users, and MGMT promoter methylation appears to be a protective factor.

Apolipoprotein E3 functionalized lipid-drug conjugated nanoparticles of Levetiracetam for enhanced delivery to the brain: In-vitro cell line studies and in-vivo study

A significant portion of brain-tumor patients suffer from ‘brain-tumor-related epilepsy (BTE)’ which results in depression, anxiety and hampered quality of life. Conventional anti-epileptic drugs indicate negative interaction with other drugs augmenting the poor outcome of overall therapy. Levetiracetam (LVM) has evidenced effectiveness for BTE but its hydrophilicity restricts the passage into blood-brain barrier. The majority of lipid nanoparticles fails to load hydrophilic drug sufficiently. Therefore, lipid-drug conjugates (LDC) were synthesized using stearic acid via amide bond formation confirmed by FTIR and NMR. The nanoparticles of synthesized LDC were prepared by solvent injection method followed by functionalization with Apolipoprotein E3 (ApoE3@LDC-NP). The nanoparticles were characterized by DSC, XRD, particle size (131.6 ± 1.24 nm), zeta potential (−15.6 ± 0.09 mV), and for storage stability. In-vitro release study indicated initial burst release of 20 ± 0.63 % followed by sustained release up to 30 h (66 ± 1.40 %) for ApoE3@LDC-NP. The cell-line study on HEK293 indicated no significant cytotoxic effect and greater cell uptake through U87MG cell line. The pharmacokinetic and bio-distribution study indicated 2.5-fold greater brain-targeting of ApoE3@LDC-NP as compared to LVM solution. It proved safe in the haemolysis study and exhibited the absence of tissue necrosis. Thus, ApoE3@LDC-NP might be a promising approach for effective brain-targeting of LVM for improved clinical response in BTE.

P09.04.B PNES IN BRAIN TUMOR PATIENTS : AN UNEXPECTED CHALLENGE

Abstract BACKGROUND Epileptic seizures (ES) are common in brain tumor patients. The phenomenon of psychogenic non-epileptic seizures (PNES) amongst those patients has not been well described. PNES Phenomenology could be similar to ES, however, epileptogenic activity on electro-encephalogram (EEG) is absent. The diagnosis of PNES can be challenging in brain tumor patients since both types of seizures can present with similar symptoms and might occur together. Risk factors for the development of PNES include a history of negative events in childhood, exposure to trauma, history of psychiatric illness and chronic pain, and substance abuse. Diagnosing PNES is important for delivering the appropriate treatment, and preventing the toxic influence of unneeded treatment and procedures. MATERIAL AND METHODS The Electronic files of patients with ES and PNES were evaluated, in A retrospective analysis from the database of the Neuro-Oncology unit at Sheba Medical-Center. RESULTS 4 patients with brain tumor related epilepsy and PNES were identified: a female 22 years old with right frontal IDH1 mutated non 1p/19q deleted glioma WHO2, a 44 years old male with right frontal IDH1 mutated 1p/19q deleted glioma WHO2, a 48 years old female with left temporo-insular IDH1 mutated non 1p/19q deleted glioma WHO2 and a 65 years old female with multiple radiation induced meningiomas. Seizures semiology were compatible with the lesions. The first two patients had recent stress factors, and the last two suffered severe diagnosis-related anxiety. All patients presented initially with ES and developed PNES subsequently. They were treated with 2-4 Anti-Epileptic drugs(AED’s). They were referred to EEG video monitoring due to worsening seizures frequency despite increasing the AED’s and no evidence of tumor progression at that time. All patients had clinical seizures which did not have any epileptiform activity correlation on Video-EEG. Hence, PNES was diagnosed. Three patients underwent psychological treatment and two patients received medical therapy for underlying psychological factors contributing to PNES. Seizure frequency and number of AED's decreased in all patients. CONCLUSION In patients with brain tumors the diagnosis of PNES can be challenging but should be considered in patients with increased seizures frequency regardless of stable imaging and absence of any other provocative factors. Video EEG is pivotal for PNES diagnosis. Psychological consulting and treatment are recommended in PNES cases. Correct diagnosis and treatment will contribute to the patient's quality of life.

Volumetric Modulated Arc Therapy for Radiosurgery of Brain Metastases: A Single-Center Study

Whole-brain radiation therapy and stereotactic radiosurgery are two treatment modalities commonly utilized to treat brain metastases (BMs). The aim of this study is to retrospectively analyze the main radio-oncologic and clinical-demographic aspects of a cohort of BM patients treated with Volumetric Modulated Arc Therapy for radiosurgery (VMAT-RS). This is a cross-sectional observational design study with a retrospective review of the medical records of patients with brain metastases treated with VMAT-RS between 2012 and 2018. Clinical and demographic data, with special attention to sex, age, primary tumor, brain tumor-related epilepsy (BTRE), number and brain location of BMs, Karnofsky Performance Status (KPS), the updated DS-GPA prognostic index, and the survival estimated according to the Kaplan–Meier model from the date of radiosurgery, were analyzed. One hundred and twenty-one patients with 229 BMs were treated with VMAT-RS. Patients presented 1–4 BMs, which were treated with five non-coplanar VMAT arcs. Sixty-eight percent of the patients had lung cancer, and 35% of the BMs were in the frontal lobe. The proportion of local control was 88.5%. BTRE prevalence was 30.6%. The median survival time (MST) was 7.7 months. In the multivariate analysis of the Cox regression model, KPS ≥ 70 (HRKPS < 70 = 2.59; p = 0.001) and higher DS-GPA (HRDS-GPAII = 0.55, p = 0.022; HRDS-GPAIII-IV = 0.38, p = 0.006) were associated with improved survival. In the univariate analysis, primary tumor, age, and the presence of metastases in the posterior fossa (PFBMs) were also significant. In conclusion, the VMAT-RS is a technique with an overall survival rate comparable to other radiosurgery techniques. The median survival is significantly longer for those with higher KPS and DS-GPA. Other variables, such as the type of primary tumor, age, and PFBMs, could also influence survival, although further studies are needed.

Real-life evidence about the use of intravenous brivaracetam in urgent seizures: The BRIV-IV study

PurposeUrgent seizures are a medical emergency for which new therapies are still needed. This study evaluated the use of intravenous brivaracetam (IV-BRV) in an emergency setting in clinical practice. MethodsBRIV-IV was a retrospective, multicenter, observational study. It included patients ≥18 years old who were diagnosed with urgent seizures (including status epilepticus (SE), acute repetitive seizures, and high-risk seizures) and who were treated with IV-BRV according to clinical practice in 14 hospital centers. Information was extracted from clinical charts and included in an electronic database. Primary effectiveness endpoints included the rate of IV-BRV responder patients, the rate of patients with a sustained response without seizure relapse in 12 h, and the time between IV-BRV administration and clinical response. Primary safety endpoints were comprised the percentage of patients with adverse events and those with adverse events leading to discontinuation. ResultsA total of 156 patients were included in this study. The mean age was 57.7 ± 21.5 years old with a prior diagnosis of epilepsy for 57.1% of patients. The most frequent etiologies were brain tumor-related (18.1%) and vascular (11.2%) epilepsy. SE was diagnosed in 55.3% of patients. The median time from urgent seizure onset to IV treatment administration was 60.0 min (range: 15.0–360.0), and the median time from IV treatment to IV-BRV was 90.0 min (range: 30.0–2400.0). Regarding dosage, the mean bolus infusion was 163.0 ± 73.0 mg and the mean daily dosage was 195.0 ± 87.0 mg. A total of 77.6% of patients responded to IV-BRV (66.3% with SE vs. 91% other urgent seizures) with a median response time of 30.0 min (range: 10.0–60.0). A sustained response was achieved in 62.8% of patients. However, adverse events were reported in 14.7%, which were predominantly somnolence and fatigue, with 4.5% leading to discontinuation. Eighty-six percent of patients were discharged with oral brivaracetam. ConclusionIV-BRV in emergency settings was effective, and tolerability was good for most patients. However, a larger series is needed to confirm the outcomes.

Review of Magnetic Resonance Imaging and Post-processing for the Brain Tumor-related Epilepsy Study.

20% of brain tumor patients present with seizures at the onset of diagnosis, while a further 25-40% develop epileptic seizures as the tumor progresses. Tumor-related epilepsy (TRE) is a condition in which the tumor causes recurring, unprovoked seizures. The occurrence of TRE differs between patients, along with the effectiveness of treatment methods. Therefore, determining the tumor properties that correlate with epilepsy can help guide TRE treatment. This article reviews the MRI sequences and image post-processing algorithms in the study of TRE. It focuses on epilepsy caused by glioma tumors because it is the most common type of malignant brain tumor and it has a high prevalence of epilepsy. In correlational TRE studies, conventional MRI sequences and diffusion-weighted MRI (DWI) are used to extract variables related to the tumor radiological characteristics, called imaging factors. Image post-processing is used to correlate the imaging factors with the incidence of epilepsy. The earlier studies of TRE used univariate and multivariate analysis to study the correlations between specific variables and incidence of epilepsy. Later, studies used voxel-based morphometry and voxel lesion-symptom mapping. Radiomics has been recently used to post-process the images for the study of TRE. This article will discuss the limitation of the existing imaging modalities and post-processing algorithms. It ends with some suggestions and challenges for future TRE studies.

The broad-spectrum activity of perampanel: state of the art and future perspective of AMPA antagonism beyond epilepsy.

Glutamate is the brain's main excitatory neurotransmitter. Glutamatergic neurons primarily compose basic neuronal networks, especially in the cortex. An imbalance of excitatory and inhibitory activities may result in epilepsy or other neurological and psychiatric conditions. Among glutamate receptors, AMPA receptors are the predominant mediator of glutamate-induced excitatory neurotransmission and dictate synaptic efficiency and plasticity by their numbers and/or properties. Therefore, they appear to be a major drug target for modulating several brain functions. Perampanel (PER) is a highly selective, noncompetitive AMPA antagonist approved in several countries worldwide for treating different types of seizures in various epileptic conditions. However, recent data show that PER can potentially address many other conditions within epilepsy and beyond. From this perspective, this review aims to examine the new preclinical and clinical studies-especially those produced from 2017 onwards-on AMPA antagonism and PER in conditions such as mesial temporal lobe epilepsy, idiopathic and genetic generalized epilepsy, brain tumor-related epilepsy, status epilepticus, rare epileptic syndromes, stroke, sleep, epilepsy-related migraine, cognitive impairment, autism, dementia, and other neurodegenerative diseases, as well as provide suggestions on future research agenda aimed at probing the possibility of treating these conditions with PER and/or other AMPA receptor antagonists.

Application of diversified health education in patients with brain tumor-related epilepsy and their family members

Application of diversified health education in patients with brain tumor-related epilepsy and their family members

Retracted: Correlation of Clinicopathological Factors with Brain Tumor-Related Epilepsy in Glioma.

[This retracts the article DOI: 10.1155/2022/4918294.].

Efficacy and Tolerability of Perampanel in Brain Tumor-Related Epilepsy: A Systematic Review

(1) Background: Epilepsy is a frequent comorbidity in patients with brain tumors, in whom seizures are often drug-resistant. Current evidence suggests that excess of glutamatergic activity in the tumor microenvironment may favor epileptogenesis, but also tumor growth and invasiveness. The selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist perampanel (PER) was demonstrated to be efficacious and well-tolerated in patients with focal seizures. Moreover, preclinical in vitro studies suggested a potential anti-tumor activity of this drug. In this systematic review, the clinical evidence on the efficacy and tolerability of PER in brain tumor-related epilepsy (BTRE) is summarized. (2) Methods: Five databases and two clinical trial registries were searched from inception to December 2022. (3) Results: Seven studies and six clinical trials were included. Sample size ranged from 8 to 36 patients, who received add-on PER (mean dosage from 4 to 7 mg/day) for BTRE. After a 6-12 month follow-up, the responder rate (% of patients achieving seizure freedom or reduction ≥ 50% of seizure frequency) ranged from 75% to 95%, with a seizure freedom rate of up to 94%. Regarding tolerability, 11-52% of patients experienced non-severe adverse effects (most frequent: dizziness, vertigo, anxiety, irritability). The retention rate ranged from 56% to 83%. However, only up to 12.5% of patients discontinued the drug because of the adverse events. (4) Conclusions: PER seems to be efficacious, safe, and well-tolerated in patients with BTRE. Further randomized studies should be conducted in more homogeneous and larger populations, also evaluating the effect of PER on tumor progression, overall survival, and progression-free survival.

Perampanel in Brain Tumor-Related Epilepsy: A Systematic Review

Brain tumor-related epilepsy (BTRE) is a common comorbidity in patients with brain neoplasms and it may be either the first symptom or develop after the tumor diagnosis. Increasing evidence suggests that brain tumors and BTRE share common pathophysiological mechanisms. Glutamatergic mechanisms can play a central role in promoting both primary brain tumor growth and epileptogenesis. Perampanel (PER), which acts as a selective antagonist of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, may play a role both in the reduction in tumor growth and the control of epileptiform activity. This systematic review aimed to summarize the pre-clinical and clinical evidence about the antitumor properties, antiseizure effects and tolerability of PER in BTRE. Eight pre-clinical and eight clinical studies were identified. The currently available evidence suggests that PER can be an effective and generally well-tolerated therapeutic option in patients with BTRE. In vitro studies demonstrated promising antitumor activity of PER, while no role in slowing tumor progression has been demonstrated in rat models; clinical data on the potential antitumor activity of PER are scarce. Additional studies are needed to explore further the effects of PER on tumor progression and fully characterize its potentialities in patients with BTRE.

Levetiracetam as a first-line antiseizure medication in WHO grade 2 glioma: Time to seizure freedom and rates of treatment failure.

The high seizure burden seen in World Health Association (WHO) grade 2 gliomas is well documented. This study aims to identify factors that influence the probability of seizure freedom (12 months of seizure remission) and treatment failure (antiseizure medication [ASM] cessation or introduction of an alternative) in patients with WHO grade 2 glioma. This is a retrospective observational analysis of patients from a regional UK neurosurgical center with histologically proven (n= 146) WHO grade 2 glioma and brain tumor related epilepsy. Statistical analyses using both Kaplan-Meier and Cox proportional hazards models were undertaken, with a particular focus on treatment outcomes when the commonly prescribed ASM levetiracetam (n= 101) is used as first line. Treatment with levetiracetam as a first-line ASM resulted in a significant increase in the probability of seizure freedom (p< .05) at 2 years compared with treatment with an alternative ASM. Individuals presenting with focal seizures without bilateral tonic-clonic progression were between 39% and 42% significantly less likely to reach seizure freedom within 10 years (p< .05) and 132% more likely to fail treatment by 5 years (p< .01) when compared to individuals who had seizures with progression to bilateral tonic-clonic activity. ASM choice did not significantly affect treatment failure rates. More than two-thirds of patients with WHO grade 2 glioma related epilepsy treated with levetiracetam first line achieve seizure freedom within 2 years and it is a reasonable first-choice agent. Experiencing mainly focal seizures without progression infers a significant long-term reduction in the chance of seizure freedom. Further studies are needed to inform ASM selection.

Perampanel in adjunctive therapy of patients with brain tumor-related epilepsy: real-world data

Background. Brain tumor-related epilepsy (BTRE) is an important and insufficiently studied interdisciplinary problem. In a significant part of brain tumor patients, the disease onsets with epileptic seizures. The course of tumor-associated epilepsy is often pharmacoresistant and requires rational polytherapy. To date, there are no uniform recommendations on the choice of an antiepileptic drug (AED) for the initial therapy of BTRE.Objective: retrospective analysis of the efficacy/tolerability of adjunctive therapy with perampanel in relation to epileptic seizures in patients with epilepsy associated with glial brain tumors and metastases.Material and methods. The analysis included 51 patients with glial tumors and brain metastases who were prescribed perampanel as part of adjunctive therapy. Its effectiveness against focal seizures (FS) and bilateral tonic-clonic seizures (BTCS) was evaluated at follow-up periods of &gt;1≥3≥6 months. A decrease in the frequency of seizures by 50% or more (responders) or by 100% (seizure freedom) was analyzed. An analysis of the influence of intervening factors in a multifactorial model, an assessment of the effectiveness of perampanel as a whole and a stratified assessment of intervening factors were carried out. The frequency and profile of adverse events (AEs) were also evaluated, including their possible association with the use of other AED.Results. In the multifactorial model, independent predictors of the clinical effect were the onset of the disease in the form of FS at &gt;1≥3≥6 months follow-up. None of AEDs used in the first line of therapy demonstrated an impact on the clinical effect. There were no predictors of clinical effect in patients with BTCS during the entire follow-up period. Out of 51 patients, 48 (94.1%) were responders, and in 36 of them (70.6%) the seizure freedom was registered. Among patients with FS, the proportion of responders was 83.3–90.9% at different follow-up periods, including 31.2–50.0% who showed seizure freedom. Among patients with BTCS, 86.7–92.3% became responders, including 56.1–88.5% who achieved seizure freedom. AEs were noted in 7 (13.7%) patients, the most common was aggression – 4 patients (7.8%). There were no cases required reduction the dose or discontinuation the treatment with perampanel due to AEs. In most patients at &gt;1≥3≥6 months follow-up, the median was 6 mg/day.Conclusion. The study performed in real-world practice confirmed the high efficiency and safety of perampanel in the adjunctive therapy of epileptic seizures associated with glial brain tumors and metastases, which together with the low potential of drug interactions allow us recommend the drug to this contingent of patients.

Correlation of Clinicopathological Factors with Brain Tumor-Related Epilepsy in Glioma.

Objectives Glioma patients with brain tumor-related epilepsy (BTRE) have a complex profile due to the simultaneous presence of two pathologies, glioma and epilepsy; however, they have not traditionally received as much attention as those with more malignant brain tumors. The underlying pathophysiology of brain tumor-related epilepsy remains poorly understood. The purpose of this study was to investigate the possible correlation between molecular neuropathology and glioma with BTRE and a wide range of BTRE-associated molecular markers of glioma patients. Methods A retrospective cohort study of 186 glioma patients was evaluated at our hospital, of which 64 had BTRE. The chi-square test, Spearman rank correlation, and multivariate logistic analyses were used to identify clinicopathological factors associated with BTRE in glioma patients. Results Of the 186 patients examined in this study, 64 (34.4%) had BTRE. Based on the analysis of the characteristics of these patients, the results showed that patient age (over 40 years; P = 0.007), low WHO grade (grade I, II; P = 0.001), IDH-1 positive mutation (P = 0.027), low ATR-X expression level (OR = 0.44; 95% CI: 0.21, 0.92), and low Ki-67 PI (OR = 0.25; 95% CI: 0.10, 0.68) were associated with the occurrence of BTRE. In our cohort, BTRE patients did not differ by sex, tumor location, or expression of olig-2 and CD34. The results of the matching study showed that low Ki-67 PI and negative ATR-X expression levels were independent factors for a higher incidence of preoperative seizures in glioma patients. Conclusion The current study updates existing information on genetic markers in gliomas with BTRE and explores the correlation of a wide range of clinicopathological factors and glioma patients with BTRE and suggests three putative biomarkers for BTRE: positive IDH1 mutation, low Ki-67 PI, and negative ATR-X expression. These factors may provide insights for developing a more thorough understanding of the pathogenesis of epilepsy and effective treatment strategies aimed at seizure control.

293P Molecular biomarkers correlation in symptomatic tumor-related epilepsy: A preliminary study on 151 cases of brain tumors

The annual incidence of malignant brain tumors is 7.08 per 100,000 inhabitants in Italy and epilepsy is one of the most common presenting symptoms. Patients with brain tumor-related epilepsy (BTRE) suffer from two challenging pathologies simultaneously: glioma and epilepsy. The pathogenesis of BTRE is not fully described. The integration of molecular data and histology changed the diagnostic approach and prognostic characterization for patients with brain tumors. The aim of this study is to explore the associations between histo-molecular patterns and epilepsy features, in a group of patients suffering from brain tumors.