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. New-onset seizures represent an early warning sign for the presence of a brain tumor and count as a good prognostic factor for survival. Recurrence or worsening of seizures during the course of disease may signal tumor progression. Each of the modalities for tumor control (i.e., surgery, radiotherapy, chemotherapy) contributes to seizure control. Nevertheless, one third of BTE shows pharmacoresistance to antiepileptic drugs (AEDs) and may severely impair the burden of living with a brain tumor. For symptomatic therapy of BTE, seizure type and individual patient factors determine the appropriate AED. Randomized controlled trials in partial epilepsy in adults to which type BTE belongs and additional studies in gliomas indicate that levetiracetam is the agent of choice, followed by valproic acid (VPA). In the case of recurring seizures,combiningthesetwodrugs(polytherapy)seemseffective and possibly synergistic. If either one is not effective or not well tolerated, lacosamide, lamotrigine, or zonisamide are additional options. A new and exciting insight is the potential contribution of VPA to prolonged survival, particularly in glioblastomas. A practice guideline on symptomatic medical management including dose schedules of AEDs is supplied. The Oncologist 2014;19:751-759 Implications for Practice: Seizures are common in low-and high-grade gliomas. New-onset seizures represent an early warning sign and count as a favorable prognostic factor for survival. Each of the modalities for tumor control (i.e., surgery, radiotherapy, chemotherapy) contributes to seizure control. For symptomatic management, levetiracetam followed by valproic acid are the evidence-based antiepileptic agents in low-grade gliomas and other types of brain tumors. In glioblastoma, valproic acid represents the first choice based on its extra effect on survival. With recurring seizures, combining both levetiracetam and valproic acid (polytherapy) seems synergistic. Lacosamide, lamotrigine, or zonisamide are additional options.
Glioblastoma (GBM) is the most common and devastating primary malignant brain tumor in adults. The past few years have seen major progress in our understanding of the molecular basis of GBM. These advances, which have contributed to the development of novel targeted therapies, will change the paradigms in GBM therapy from disease-based to individually tailored molecular target-based treatment. No validated circulating biomarkers have yet been integrated into clinical practice for GBM. There is thus a critical need to implement minimally invasive clinical tests enabling molecular stratification and prognosis assessment, as well as the prediction and monitoring of treatment response. After examination of data from recent studies exploring several categories of tumor-associated biomarkers (circulating tumor cells, extracellular vesicles, nucleic acids and oncometabolites) identified in the blood, cerebrospinal fluid and urine, this article discusses the challenges and prospects for the development of circulating biomarkers in GBM.
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. Cognitive function was examined by computerized test on cognitive speed (CTCS), which is sensitive to the type of cognitive dysfunction associated with epilepsy and use of anticonvulsants. Treatment policy included reduction of dose or discontinuation of one or more concurrent AEDs, once a seizure-free response was observed. Twelve patients were included patients, median age 41 years, 9 men versus 3 women and 6 months median duration of follow-up. An objective seizure response (75%) was observed in 9 (75%) out of 12 patients: 50%-seizure response in 3, seizure-freedom in 6, which is plainly more than seen with other types of DRE. Side-effects occurred in six patients. Cognitive function as examined by CTCS improved in six out of eight associated withlowering of concurrent AEDs. The final median dose of PER was 8 mg (varying between 2 and 12 mg). These results of an objective seizure response in 9 (75%) out of 12 patients treated by PER in DRE may be interpreted as a surrogate-marker of tumor response secondary to AMPA blockade, advancing confirmation by MR imaging. These results warrant further study of PER on tumor activity in gliomas.
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