Practice parameter: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors [RETIRED]

Abstract

Overview. The Quality Standards Subcommittee seeks to develop scientifically sound, clinically relevant practice parameters for the practice of neurology. Practice parameters are strategies for patient management that assist physicians in clinical decision making. A practice parameter is one or more specific recommendations based on analysis of evidence on a specific clinical problem. These might include diagnosis, symptoms, treatment, or procedure evaluation. American Academy of Neurology (AAN) members have requested the publication of a practice parameter on the use of prophylactic anticonvulsants in patients with primary and metastatic brain tumors.Justification. Physicians often administer anticonvulsant medication prophylactically to patients with brain tumors, despite the lack of definitive evidence that prophylactic anticonvulsant therapy is effective in preventing first seizures. [1][2][3][4] If anticonvulsant medications were free of side effects, their prophylactic use might be attractive even without such evidence. However, discomfort, expense, and inconvenience result from drug treatment and periodic monitoring of serum drug concentrations. Typical anticonvulsant-induced side effects, including cognitive impairment, myelosuppression, liver dysfunction, and dermatologic reactions (ranging from minor rashes to life-threatening Stevens-Johnson syndrome), appear to occur more frequently in patients with brain tumors than in other patient groups, 3,5-16 although direct comparison studies have not been published. A spectrum of side effects unique to patients with brain tumors must also be considered. Phenytoin, carbamazepine, and phenobarbital reduce the efficacy of corticosteroids, 17-21 which are administered almost universally to brain tumor patients. In addition, the ability of these anticonvulsants to stimulate the cytochrome P450 enzyme system results in markedly accelerated metabolism of a wide spectrum of chemotherapeutic agents including nitrosoureas, paclitaxel, cyclophosphamide, topotecan, irinotecan, thiotepa, 9-aminocampo-thecin, adriamycin, and methotrexate.22-34 As a result, inadequate chemotherapeutic dosing of brain tumor patients has been identified recently as a widespread and critically important problem. 35 Conversely, corticosteroids and many chemotherapeutic agents alter the metabolism of anticonvulsants, making anticonvulsant under-and overdosing more common. [35][36][37][38][39][40][41][42][43][44][45] The potential immunosuppressive effect of anticonvulsant medications represents an additional risk to this already immunocompromised patient population. [46][47][48][49] In 1998, more than 170,000 patients were diagnosed with brain metastases, and more than 34,000 developed primary brain tumors. [50][51][52] Twenty to 40% of all brain tumor patients have experienced a seizure by the time their brain tumor is diagnosed. 3,4,11,12,[14][15][16][53][54][55][56][57][58][59][60][61] In these patients, the need for anticonvulsant medication is clear. Patients who have not experienced a seiz...

Analysis of the Adherence to Seizure Prophylaxis Guidelines in Neurosurgery Patients

“…Despite lack of evidence showing AED are beneficial, agreement is seen among neurosurgeons with the use of AEDs during the peri-and post-operative period (within 7-14 days of the surgery) as the risk of seizures is the highest during this timeframe [6] . Indeed, this does not contradict the AAN guidelines as they recommend an AED, if started, to be discontinued after 7 days post-surgery if the patient is medically stable and has not experienced a seizure [7] . Overall, the current body of literature does not support the routine use of seizure prophylaxis in patients with primary or secondary brain lesions, whether they undergo neurosurgery or not.…”

Dural Metastasis with Subdural Hemorrhage from Prostate Cancer

“…Unless seizures occur, the use of prophylactic anticonvulsants, particularly phenytoin (Dilantin), is not encouraged [18,19]. In combination with radiotherapy, phenytoin may cause Stevens-Johnson syndrome (erythema multiforme major) [19].…”

ACR Appropriateness Criteria® Pre-Irradiation Evaluation and Management of Brain Metastases

“…Possible explanations for the high incidence of seizures in patients with brain metastases from melanoma, as opposed to other histologies, include the tendency for these metastases to be located in the superficial cerebral cortex rather than at the junction between gray and white matter. The meta-analysis by Glantz et al 34 did not indicate a significant benefit to anticonvulsants in patients with malignant melanoma brain metastases but concluded that further prospective studies of prophylactic anticonvulsants were warranted in this subgroup. The panel consensus is to not start anticonvulsants prophylactically in patients with brain metastases due to any primary cancer, including melanoma (see Variant 3 and Variant 4).…”

“…A meta-analysis estimated that 15% of patients with brain metastases present with seizures, and most of them are found to have supratentorial lesions. 34 Patients who present with seizures or who develop seizures during therapy should be started on antiseizure medications. Randomized prospective studies have found no significant reduction in the incidence of first seizures in brain tumor patients placed on prophylactic anticonvulsants.…”

“…[35][36][37] New onset of seizures was experienced by approximately 25% of patients treated with prophylactic anticonvulsants, not significantly different than the percentage of patients experiencing new onset of seizures in the control arm. The meta-analysis by Glantz et al 34 concluded that there was no evidence that prophylactic anticonvulsants significantly decreased the incidence of first seizure. In the aggregate, these 12 studies included in the meta-analysis recorded a 26% incidence of seizures at or before brain tumor diagnosis (range, 14%-51%), and a 19% incidence of seizures after brain tumor diagnosis (range, 10%-45%).…”