A Review of the Use of Antiepileptic Drugs in High-Grade Central Nervous System Tumors

Wallace, Elaine M.; O’Reilly, Maeve; Twomey, Marie

doi:10.1177/1049909111434367

Cited by 5 publications

(5 citation statements)

References 16 publications

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“…Glutamate release from gliomas has also been suggested to cause tumor-associated seizures (TAS)(5, 6), which affect up to half of all glioma patients(7, 8). TAS require treatment with one or more anti-epileptic drugs (AED), which produce undesirable side effects and potential drug interactions with chemotherapy treatments(9), and are often ineffective to control seizures in many patients.…”

Section: Introductionmentioning

confidence: 99%

SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma

et al. 2015

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Glioma is the most common malignant primary brain tumor. Their rapid growth is aided by tumor-mediated release of glutamate, creating peritumoral excitotoxic cell death and vacating space for tumor expansion. Glioma glutamate release may also be responsible for seizures, which complicate the clinical course for many patients and are often the presenting symptom. A hypothesized glutamate release pathway is the cystine/glutamate transporter System xc− (SXC), responsible for the cellular synthesis of glutathione. However, the relationship of SXC-mediated glutamate release, seizures, and tumor growth remains unclear. Probing expression of SLC7A11/xCT, the catalytic subunit of SXC, in patient tissue and tissues propagated in mice, we found that approximately 50% of patient tumors have elevated SLC7A11 expression. Compared with tumors lacking this transporter, in vivo propagated and intracranially implanted SLC7A11-expressing tumors grew faster, produced pronounced peritumoral glutamate excitotoxicity, induced seizures, and shortened overall survival. In agreement with animal data, increased SLC7A11 expression predicted shorter patient survival according to annotated genomic data in the REMBRANDT database. In a clinical pilot study we used Magnetic Resonance Spectroscopy (MRS) to determine SXC-mediated glutamate release by measuring acute changes in glutamate after administration of the FDA-approved SXC inhibitor, sulfasalazine. In 9 glioma patients with biopsy-confirmed expression of SXC, we found that its expression positively correlates with glutamate release, which is acutely inhibited with oral sulfasalazine. These data suggest that SXC is the major pathway for glutamate release from gliomas and that SLC7A11 expression predicts accelerated growth and peritumoral seizures.

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Section: Introductionmentioning

confidence: 99%

SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma

et al. 2015

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“…Specific evidence-based guidelines for the treatment of brain tumor-related seizures are not available (van Breemen et al, 2012;Wallace et al, 2012). Numerous authors recommend LEV as drug of first choice in this situation (Lynam et al, 2007;Rudà et al, 2010;Rossetti and Stupp, 2010;Vecht and Wilms, 2010;Pruitt, 2011;Wallace et al, 2012;Perucca, 2013;Bruna et al, 2013;Vecht et al, 2014;Piotrowski and Blakeley, 2015;Ray et al, 2015); in children one has to consider whether monotherapy is approved. The preference of LEV results from its relatively favourable profile of adverse events combined with a satisfactory anticonvulsant activity.…”

Section: Discussionmentioning

confidence: 99%

“…Specific guidelines for treating brain tumor-related seizures are not available (van Breemen et al, 2012;Wallace et al, 2012). Hence, the guidelines for drug treatment of focal seizures can also be applied to tumorrelated seizures.…”

Section: General Therapeutic Considerationsmentioning

confidence: 99%

“…According to Reif et al (2012) LEV was the most common AED in patients with tumor-related epilepsy. Numerous authors recommended LEV as the drug of first choice in this situation in children and in adults, independently of the neuropathological classification of the underlying tumor (Lynam et al, 2007;Rosetti and Stupp, 2010;Rudà et al, 2010;Ruggiero et al, 2010;Pruitt, 2011;Wallace et al, 2012;Bruna et al, 2013;Perucca, 2013;Vecht et al, 2014;Piotrowski and Blakely, 2015;Ray et al, 2015). LEV is considered as an attractive option, both as monotherapy and in combination, due to its efficacy, safety, availability of a parenteral formulation, and the pharmacokinetic profile with a lack of interactions with CTDs.…”

Section: Efficacy Of Antiepileptic Drugs In Tumoral Epilepsymentioning

confidence: 99%

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Anticonvulsant therapy in brain-tumor related epilepsy

Fröscher

Kirschstein

Rösche

2016

Journal of Epileptology

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SummaryBackground. The lifetime risk of patients with brain tumors to have focal epileptic seizures is 10-100%; the risk depends on different histology. Specific guidelines for drug treatment of brain tumor-related seizures have not yet been established.Aim. This review addresses the special aspects of antiepileptic drug (AED) therapy in brain tumor-related epilepsy.Methods. We analyzed the literature up to December 2015.Results. Based on current evidence the management of tumor-related seizures does not differ substantially from that applied to epilepsies from other etiologies. Therefore, the choice of an AED is based, above all, on tolerability and pharmacokinetic interactions with chemotherapeutic drugs. Levetiracetam is recommended by many authors as first-line therapy in brain tumor-related epilepsy. Due to the possibility of interactions, the combination of enzyme-inducing AEDs and chemotherapeutic drugs, is usually not recommended as a first choice. Currently there is no evidence that prophylactic prescription of long-term AEDs in brain tumor-patients who did not present with seizures is justified. Because of the high risk of recurrence, however, AED treatment should be strongly considered after a single brain tumor-related seizure. The decision to withdraw AEDs must carefully consider the risk of seizure recurrence.Conclusion. At present levetiracetam is the preferred drug in brain tumor-related epilepsy, especially when drug interactions need to be avoided. In the future we hope to acquire more targeted drugs against this disorder by uncovering its pathogenesis.

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“…11 These patients are also predisposed to neurological impairment 11 and higher rates of depression, anxiety, and suicidality. 68 Rarely, seizure episodes can provoke potentially fatal status epilepticus or acute intracranial herniation syndromes. 26,35 Speculative benefits of AED prophylaxis include not only the prevention of early postoperative seizures, but also long-term epilepsy.…”

Section: Rationale For Anticonvulsant Prophylaxismentioning

confidence: 99%

Anticonvulsant prophylaxis for brain tumor surgery: determining the current best available evidence

Sayegh

Fakurnejad²,

Oh³

et al. 2014

JNS

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Patients who undergo craniotomy for brain tumor resection are prone to experiencing seizures, which can have debilitating medical, neurological, and psychosocial effects. A controversial issue in neurosurgery is the common practice of administering perioperative anticonvulsant prophylaxis to these patients despite a paucity of supporting data in the literature. The foreseeable benefits of this strategy must be balanced against potential adverse effects and interactions with critical medications such as chemotherapeutic agents and corticosteroids. Multiple disparate metaanalyses have been published on this topic but have not been applied into clinical practice, and, instead, personal preference frequently determines practice patterns in this area of management. Therefore, to select the current best available evidence to guide clinical decision making, the literature was evaluated to identify meta-analyses that investigated the efficacy and/or safety of anticonvulsant prophylaxis in this patient population. Six meta-analyses published between 1996 and 2011 were included in the present study. The Quality of Reporting of Meta-analyses and Oxman-Guyatt methodological quality assessment tools were used to score these meta-analyses, and the Jadad decision algorithm was applied to determine the highest-quality meta-analysis. According to this analysis, 2 metaanalyses were deemed to be the current best available evidence, both of which conclude that prophylactic treatment does not improve seizure control in these patients. Therefore, this management strategy should not be routinely used.

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A Review of the Use of Antiepileptic Drugs in High-Grade Central Nervous System Tumors

Cited by 5 publications

References 16 publications

SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma

SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma

Anticonvulsant therapy in brain-tumor related epilepsy

Anticonvulsant prophylaxis for brain tumor surgery: determining the current best available evidence

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