Management of epilepsy in brain tumors

Maschio, Marta; Aguglia, Umberto; Avanzini, G.; Banfi, Paola; Buttinelli, Carla; Capovilla, Giuseppe; Casazza, Marina; Colicchio, Gabriella; Coppola, Antonietta; Costa, Cinzia; Dainese, Filippo; Daniele, Ornella; Simone, Roberto De; Eoli, Marica; Gasparini, Sara; Giallonardo, Anna Teresa; Neve, Angela La; Maialetti, Andrea; Mecarelli, Oriano; Melis, Marta; Michelucci, Roberto; Paladin, Francesco; Pauletto, Giada; Piccioli, Marta; Quadri, Stefano; Ranzato, Federica; Rossi, Rosario; Salmaggi, Andrea; Terenzi, Riccardo; Tisei, Paolo; Villani, Flavio; Vitali, Paolo; Vivalda, Lucina Carla; Zaccara, Gaetano; Zarabla, Alessia; Beghi, Ettore

doi:10.1007/s10072-019-04025-9

Cited by 42 publications

(51 citation statements)

References 152 publications

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“…Epilepsy might be a difficult to treat condition in patients with a brain tumor. Despite several ASMs are available, the treatment often fails to control the seizures and is (19,20). According to literature evidence, there is not a consensus suggesting any specific drug in patients with BTRE.…”

Section: Discussionmentioning

confidence: 99%

“…In fact carbamazepine, phenytoin, and phenobarbital should not be considered. Today, it is commonly accepted that the newer generation drugs should be considered as first choice and among them are levetiracetam, lamotrigine, and topiramate (20,21). Valproic acid should also be considered (22).…”

Section: Discussionmentioning

confidence: 99%

“…Despite several ASMs are available, the treatment often fails to control the seizures and is associated with significant side effects. Different antiseizure medications, including tiagabine, pregabalin, oxcarbazepine, levetiracetam, valproic acid, topiramate, zonisamide, lacosamide, and lamotrigine have been used to treat BTRE ( 19 , 20 ). According to literature evidence, there is not a consensus suggesting any specific drug in patients with BTRE.…”

Section: Discussionmentioning

confidence: 99%

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Perampanel Confirms to Be Effective and Well-Tolerated as an Add-On Treatment in Patients With Brain Tumor-Related Epilepsy (PERADET Study)

et al. 2020

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Background: Epilepsy is one of the most common symptoms of brain tumors. It is often drug resistant and generally worsen patients' quality of life (QoL). Brain tumors release glutamate among other mediators, contributing to seizures onset, and this is accompanied by an increased AMPA receptors' expression on neuronal cells' membrane. Perampanel (PER) is a relatively new antiseizure medication (ASM) that acts as a selective non-competitive AMPA receptors' antagonist. Given its mechanism of action, we aimed to evaluate through a prospective, observational study, the efficacy and safety of PER as an add-on treatment in patients with brain tumor-related epilepsy (BTRE). The study was called PERADET. Methods: Thirty-six adult patients (intention to treat population-ITT) affected by BTRE, with uncontrolled focal-onset seizures treated with 1-3 ASMs were recruited from four Italian epilepsy centers. Perampanel was added-on, titrated from 2 mg/day up to a maximum of 12 mg/day. Tumor history and therapy, type, and seizures frequency, previous ASMs were collected at 6 and 12 months. A battery of QoL tests were administered at baseline, 6 and 12 months. The primary endpoint was to assess the efficacy of PER by calculating the percent change in seizure frequency and the responder rate. The secondary endpoints were tolerability, retention rate at 12 months, and improvement in quality of life. Results: At the end of 12 months, 21 patients (per protocol population-PP) were available for evaluation. In this population the responder rate (percentage of patients who experienced a 50% or greater reduction in seizure frequency) was 90.4 with 33.3% Coppola et al. Perampanel in Brain Tumor-Related Epilepsy of patients being seizure-free. In the ITT group the responder rate at the end of 12 months was 66.6 with 25% of patients being seizure free. PER was well tolerated (30.6% of patients experienced an adverse event, none was severe; three needed a treatment interruptions). Conclusions: Our study indicate that PER may be efficacious against BTRE as suggested by its mechanism of action and our current knowledge on mechanisms of brain tumor epileptogenicity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Perampanel Confirms to Be Effective and Well-Tolerated as an Add-On Treatment in Patients With Brain Tumor-Related Epilepsy (PERADET Study)

et al. 2020

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“…In closing, considering the lack of standardized protocol for tumor related epilepsy management, both before and after surgery, it should be important to plan a multidisciplinary approach considering the complex therapeutic profile of DLGGs patients [34]. In detail, a preoperative study as for epilepsy surgery with prolong Video-EEG recordings for patients with tumor related epilepsy characterized by complex semiology not directly associated with tumor location, could be useful in future studies to assess the spreading of epileptic discharges and plan the function possibility of resection and the intra-operative position of the strips.…”

Section: Limitation and Future Directionsmentioning

confidence: 99%

Predictors of Postoperative Seizure Outcome in Low Grade Glioma: From Volumetric Analysis to Molecular Stratification

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Pauletto

Tomasino

et al. 2020

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The importance of the extent of resection (EOR) has been widely demonstrated as the main predictor for survival, nevertheless its effect on tumor related epilepsy is less investigated. A total of 155 patients were enrolled after a first-line surgery for supratentorial Diffuse Low Grade Gliomas (DLGGs). Postoperative seizure outcome was analyzed stratifying the results by tumor volumetric data and molecular markers according to 2016 WHO classification. Receiver operating characteristic (ROC) curves were computed to asses EOR, residual tumor volume, and ∆T2T1 MRI index (expressing the tumor growing pattern) corresponding to optimal seizure outcome. A total of 70.97% of patients were seizure-free 18 months after surgery. Better seizure outcome was observed in IDH1/2 mutated and 1p/19q codeleted subgroup. At multivariate analysis, age (p = 0.014), EOR (p = 0.030), ∆T2T1 MRI index (p = 0.016) resulted as independent predictors of postoperative seizure control. Optimal parameters to improve postoperative seizure outcome were EOR ≥ 85%, ∆T2T1 MRI index ≤ 18 cm 3 , residual tumor volume ≤ 15 cm 3 . This study confirms the role of EOR and tumor growing pattern on postoperative seizure outcome independently from the molecular class. Higher ∆T2T1 MRI index, representing the infiltrative component of the tumor, is associated with worse seizure outcome and strengthens the evidence of common pathogenic mechanisms underlying tumor growth and postoperative seizure outcome.to manifest with focal and focal-to-bilateral tonic-clonic seizures, and more than 50% of cases show pharmaco-resistance, which contributes negatively on quality of life [3][4][5]. Recent studies have pointed out that epileptogenesis and tumor growth in DLGG may share common pathogenic mechanisms that can influence each other, thus representing two aspects of the same disease [6]. In this context, several genetic alterations have been identified as risk factors of glioma-related epilepsy. Mutations of the gene encoding the isocitrate-dehydrogenase1 (IDH1) and 2 (IDH2) can be found in about 70%-80% of DLGG [7]. These mutations have been associated with metabolic changes that are potentially epileptogenic, in accordance with the capability of IDH-mutated glioma cells to penetrate and surround the neurons in the gray matter [8,9].Seizure outcome represents an important challenge in the daily management of DLGG patients. In particular, decision-making still varies across surgical centers given the lack of well-established and universally recognized predictors of seizure outcomes.In the last decades, numerous studies, based on the objective evaluation of the extent of resection (EOR) has been published, demonstrating that an extensive surgery leads to increased overall patient survival and decreased malignant progression [10][11][12][13][14].Although EOR has also been shown to be one of the main strongest significant predictor markers for seizure outcome [7,[15][16][17][18], its predictive role has not been completely clarified in complex predictor models for epilep...

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“…The use of enzyme‐inducing AEDs may accelerate the metabolism of concomitant corticosteroids and chemotherapeutic agents 6,8‐10 . Guidelines for the management of patients with BTRE therefore advise against the use of enzyme‐inducing AEDs and recommend newer generation AEDs as first‐choice treatment, to be started after the first seizure 11 …”

Section: Introductionmentioning

confidence: 99%

Effectiveness and tolerability of lacosamide as add‐on therapy in patients with brain tumor–related epilepsy: Results from a prospective, noninterventional study in European clinical practice (VIBES)

et al. 2020

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Objective: To evaluate the effectiveness and tolerability of lacosamide added to one or two antiepileptic drugs (AEDs) in the treatment of patients with brain tumor-related epilepsy (BTRE), and to evaluate patients' global impression of change and quality of life (QoL). Methods: This was a prospective, multicenter, single-arm, noninterventional study with a 6-month observation period (EP0045; NCT02276053). Eligible patients (≥16 years old) had active BTRE secondary to low-grade glioma (World Health Organization grade 1 and 2) and were receiving treatment with one or two AEDs at baseline. Lacosamide was initiated by the treating physician in the course of routine clinical practice. Primary outcomes were 50% responders (≥50% reduction in focal seizure frequency from baseline) and Patient's Global Impression of Change (PGIC) at month 6. Secondary outcomes included seizure-free status and Clinical Global Impression of Change (CGIC) at month 6, change in QoL (5-Level EuroQol-5 Dimension Quality of Life Assessment) and symptom outcomes (MD Anderson Symptom Inventory-Brain Tumor) from baseline to month 6, and Kaplan-Meier estimated 6-month retention on lacosamide. Safety variables included adverse drug reactions (ADRs). Results: Patients were recruited from 24 sites in Europe. Ninety-three patients received lacosamide (mean [standard deviation] age = 44.5 [14.7] years; 50 [53.8%] male; median baseline focal seizure frequency = five seizures/28 days [range = 1-280]), of whom 79 (84.9%) completed the study. At 6 months, 66 of 86 (76.7%) patients were 50% responders and 30 of 86 (34.9%) were seizure-free. Improvements on PGIC were reported by 49 of 76 (64.5%) patients. Based on CGIC, 52 of 81 (64.2%) patients improved. QoL and symptoms outcome measures remained stable. 648 | RUDÀ et al.

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Management of epilepsy in brain tumors

Cited by 42 publications

References 152 publications

Perampanel Confirms to Be Effective and Well-Tolerated as an Add-On Treatment in Patients With Brain Tumor-Related Epilepsy (PERADET Study)

Perampanel Confirms to Be Effective and Well-Tolerated as an Add-On Treatment in Patients With Brain Tumor-Related Epilepsy (PERADET Study)

Predictors of Postoperative Seizure Outcome in Low Grade Glioma: From Volumetric Analysis to Molecular Stratification

Effectiveness and tolerability of lacosamide as add‐on therapy in patients with brain tumor–related epilepsy: Results from a prospective, noninterventional study in European clinical practice (VIBES)

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