Seizures and Anticonvulsants in Brain Tumours: Frequency, Mechanisms and Anti-Epileptic Management.

In cancer, epilepsy can be the manifestation of a primary brain tumour, metastatic disease, vascular or surgical complications, opportunistic infection or secondary to anti-tumour therapy. Seizures are frequently the first symptom of a brain tumour. The epilepsy is related to elevated extracellular glutamate stimulating NMDAand AMPA-receptors and to the formation of D-2HG which resembles glutamate in IDH1 mutated gliomas.

Seizure response to perampanel in drug-resistant epilepsy with gliomas: early observations.

Drug-resistant epilepsy (DRE) occurs commonly in gliomas, possibly due to a shared mechanism of AMPA-activation involving both seizure activity and tumor growth. We tested the AMPA-receptor blocker perampanel (PER) in patients with DRE in low- and high-grade gliomas. Seizure response was defined as 50% drop in seizure frequency or as seizure-freedom.

Central nervous system gliomas.

Evidence-based practical guidelines on diagnosis, prognosis, and treatment on the most frequent adult brain tumours are delineated. In Europe, 27,000 new cases of malignant glial tumours and 1000 new cases of malignant ependymal tumours are diagnosed every year. The most common glial tumours are glioblastoma multiforme and anaplastic glioma, comprising more than 50% and 10%, respectively, of the total gliomas.

Seizures and cancer: drug interactions of anticonvulsants with chemotherapeutic agents, tyrosine kinase inhibitors and glucocorticoids.

Patients with cancer commonly experience seizures. Combined therapy with anticonvulsant drugs (AEDs) and chemotherapeutic drugs or tyrosine kinase inhibitors carries inherent risks on drug-drug interactions (DDIs). In this review, pharmacokinetic studies of AEDs with chemotherapeutic drugs, tyrosine kinase inhibitors, and glucocorticoids are discussed, including data on maximum tolerated dose, drug clearance, elimination half-life, and organ exposure.

Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials.

Patients with low-grade glioma frequently have brain tumor-related epilepsy, which is more common than in patients with high-grade glioma. Treatment for tumor-associated epilepsy usually comprises a combination of surgery, anti-epileptic drugs (AEDs), chemotherapy, and radiotherapy. Response to tumor-directed treatment is measured primarily by overall survival and progression-free survival.

Seizures and gliomas--towards a single therapeutic approach.

Epilepsy often develops in patients with glioma, and the two conditions share common pathogenic mechanisms. Altered expression of glutamate transporters, including the cystine-glutamate transporter (xCT) system, increases concentrations of extracellular glutamate, which contribute to epileptic discharge, tumour proliferation and peripheral excitotoxicity. Furthermore, mutation of the isocitrate dehydrogenase 1 gene in low-grade gliomas causes production of D-2-hydroxyglutarate, a steric analogue of glutamate.

Epilepsy and brain tumors.

Seizures are common in patients with brain tumors, and epilepsy can significantly impact patient quality of life. Therefore, a thorough understanding of rates and predictors of seizures, and the likelihood of seizure freedom after resection, is critical in the treatment of brain tumors. Among all tumor types, seizures are most common with glioneuronal tumors (70-80%), particularly in patients with frontotemporal or insular lesions.

Seizures in oligodendroglial tumors.

Epilepsy develops in more than 70-90% of oligodendroglial tumors and represents a favorable indicator for long-term survival if present as the first clinical sign. Presence of IDH1 mutation is frequently associated with seizures in oligodendrogliomas, next to alterations of glutamate and GABA metabolism in the origin of glioma-associated epilepsy. Treatment by surgery or radiotherapy results in seizure freedom in about two-thirds of patients, and chemotherapy to a seizure reduction in about 50%.

Differential gene methylation in paired glioblastomas suggests a role of immune response pathways in tumor progression.

DNA and histone methylation are post-transcriptional modifications that have been recently described in gliomas. Indeed, glioma CpG island hypermethylated phenotype has been identified as prognostic biomarker and as a surrogate marker of IDH1/2 mutations. However, the role of DNA methylation in glioblastoma progression is unknown.

Seizure prognosis in brain tumors: new insights and evidence-based management.

Brain tumor-related epilepsy (BTE) is common in low- and high-grade gliomas. The risk of seizures varies between 60% and 100% among low-grade gliomas and between 40% and 60% in glioblastomas. The presence of seizures in patients with brain tumors implies favorable and unfavorable factors.

Tumour and surgery effects on cognitive functioning in high-grade glioma patients.

Background: Many high-grade glioma (HGG) patients have cognitive impairments, which impact daily functioning. Cognitive impairments can be caused by tumour-, treatment-, and patient-related factors. The effect of the tumour and of surgical resection on cognition is, however, not well known.

Seizure characteristics and prognostic factors of gliomas.

Epilepsy in neuroepithelial tumors is highly prevalent. Neurogliomas (dysembryoplastic neuroepitheliomas [DNETs] and gangliogliomas) have a seizure incidence of 80-100%, low-grade gliomas of 60-85%, and glioblastoma of 30-60%. With each type, the appearance of seizures is usually the presenting clinical symptom, and with neuroglial tumors often the only clinical sign.

Pregnancy in women with gliomas: a case-series and review of the literature.

The occurrence of pregnancy in women with brain tumors confronts both patients and physicians with difficult decision making at each stage of pregnancy. We studied the course of events of nine pregnancies in seven women with low-grade glioma in our hospital over a 10 year period. Five patients had a surgical resection, one a biopsy and one woman was followed by wait-and-see policy before pregnancy.

Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme.

Background: To examine the efficacy of valproic acid (VPA) given either with or without levetiracetam (LEV) on seizure control and on survival in patients with glioblastoma multiforme (GBM) treated with chemoradiation.

Methods: A retrospective analysis was performed on 291 patients with GBM. The efficacies of VPA and LEV alone and as polytherapy were analyzed in 181 (62%) patients with seizures with a minimum follow-up of 6 months.

Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951.

Purpose: Anaplastic oligodendroglioma are chemotherapy-sensitive tumors. We now present the long-term follow-up findings of a randomized phase III study on the addition of six cycles of procarbazine, lomustine, and vincristine (PCV) chemotherapy to radiotherapy (RT).

Patients And Methods: Adult patients with newly diagnosed anaplastic oligodendroglial tumors were randomly assigned to either 59.

Enzyme induction with antiepileptic drugs: cause for concern?

Several commonly prescribed antiepileptic drugs (AEDs)-including phenobarbital, phenytoin, and carbamazepine-stimulate the synthesis of a broad range of monooxygenase and conjugating enzymes. These agents are well known to reduce the duration and action of many lipid- and non-lipid-soluble drugs, including anticoagulants, cytotoxics, analgesics, antiretrovirals, glucocorticoids, statins, antihypertensives, oral contraceptives, psychoactive drugs, immunosuppressants, and of course, other AEDs. This process, therefore, may be associated with a number of clinical problems including higher cancer mortality, progressive AIDS, transplant rejection, and unwanted pregnancy.

Local progression and pseudo progression after single fraction or fractionated stereotactic radiotherapy for large brain metastases. A single centre study.

Purpose: The 1-year local control rates after single-fraction stereotactic radiotherapy (SRT) for brain metastases > 3 cm diameter are less than 70%, but with fractionated SRT (FSRT) higher local control rates have been reported. The purpose of this study was to compare our treatment results with SRT and FSRT for large brain metastases.

Materials And Methods: In two consecutive periods, 41 patients with 46 brain metastases received SRT with 1 fraction of 15 Gy, while 51 patients with 65 brain metastases received FSRT with 3 fractions of 8 Gy.

Cerebral ganglioneuroblastoma of adult onset: two patients and a review of the literature.

Ganglioneuroblastoma is a rare tumor variant of neuroblastoma. Only five cases have been observed in the adult brain, and we report here on two more adult patients with cerebral ganglioneuroblastoma. Additionally, a review was carried out on all 50 published adult cases with ganglioneuroblastoma, located in the adrenal gland (9), mediastinum (8), retroperitoneal area (7), the brain parenchyma (7), or the spinal cord (3).

Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma.

Objective: This analysis was performed to assess whether antiepileptic drugs (AEDs) modulate the effectiveness of temozolomide radiochemotherapy in patients with newly diagnosed glioblastoma.

Methods: The European Organization for Research and Treatment of Cancer (EORTC) 26981-22981/National Cancer Institute of Canada (NCIC) CE.3 clinical trial database of radiotherapy (RT) with or without temozolomide (TMZ) for newly diagnosed glioblastoma was examined to assess the impact of the interaction between AED use and chemoradiotherapy on survival.

Seizures in low- and high-grade gliomas: current management and future outlook.

Major difficulties in patients with epilepsy and brain tumors include refractory seizures, potential interactions between anticonvulsants and chemotherapeutic agents and enhanced risks of toxicity, including cognitive deterioration. For seizure control, levetiracetam, valproic acid, topiramate and lamotrigine can each be considered as agents of first choice. We advocate starting with levetiracetam monotherapy, based on efficacy, good tolerability and the absence of interactions.

Adjustment of treatment increases quality of life in patients with epilepsy: a randomized controlled pragmatic trial.

Background And Purpose: Complaints about side-effects of antiepileptic drugs (AEDs) may be overlooked in clinical practice. We assessed the value and risks of an active intervention policy for reported complaints in a randomized controlled pragmatic trial.

Methods: This randomized controlled pragmatic trial included 111 adults treated for epilepsy in seven general hospitals.

Efficacy of anti-epileptic drugs in patients with gliomas and seizures.

Although seizures in brain tumor patients are common, the knowledge on optimal anti-seizure therapy in this patient group is limited. An observational study was carried out using a database of all patients from the neuro-oncology service during the period 2000-2005, with data on seizure characteristics, therapy with AEDs, the underlying brain tumor and its treatment. A total of 140 brain tumor patients were studied of whom 23.

Relationship between volume, dose and local control in stereotactic radiosurgery of brain metastasis.

The aim of this study is to analyse the efficacy of linear accelerator stereotactic radiosurgery (SRS) on prognostic factors, local control rate and survival in patients with brain metastasis. Patients with either a single metastasis or up to 4 multiple brain metastases with a maximum tumour diameter of 40 mm for each tumour and a Karnofsky Performance Status (KPS) > or = 70 were eligible for SRS. SRS was applied to 150 lesions in 86 consecutive patients with a median age of 60 years (median 1 and mean 1.