Prophylactic Use Of Antiepileptic Drugs Research Articles

Neuro‐oncology practices in Australia: A Cooperative Group for Neuro‐Oncology patterns of care study

To provide data on the patterns of care in neuro-oncology practices at Australian cancer centres over the previous 12-month period. A 5-page questionnaire was sent to Cooperative Trials Group for Neuro-Oncology members at 28 Australia cancer centres. The questions included access to neuro-oncology services; treatment protocols and patterns of supportive care. Provision of neuro-oncology services was consistent in metropolitan cancer centres. Treatment protocols are virtually identical for patients with an initial diagnosis of glioblastoma multiforme (GBM), with the main variation being for older or less fit patients. Most patients (70%) received chemotherapy at recurrence, most commonly modified schedule temozolomide, with half of the cancer centers offering bevacizumab. For anaplastic astrocytoma (AA), most clinicians offer radiotherapy alone but 30% would use radiotherapy with concurrent and adjuvant temozolomide. Half of clinicians continued to use prophylactic anticonvulsants; 25% do not prescribe prophylactic antibiotics during chemoradiotherapy and half would continue anti-coagulation therapy indefinitely for thromboembolism. This is the first Australia-wide patterns of study of care in the management of gliomas. There is general consensus on the use of radiotherapy with concurrent and adjuvant temozolomide and the use of chemotherapy for recurrent GBM. The choice of chemotherapy at recurrence is not standard and the provision of bevacizumab is inconsistent. This survey highlights variation in the treatment of the elderly GBM and patients with AA as well as in areas of supportive care, in particular, the ongoing use of prophylactic anticonvulsants despite guidelines.

Prophylactic anticonvulsants in patients (pts) with primary brain tumor (PBT): Have we really agreed to a consensus?

2060 Background: Routine prophylactic antiepileptic drugs (AED) use to prevent seizures in PBT seizure-naïve pts is not supported by current guidelines. However, the best management of prophylactic AED started in the perioperative setting is still unclear. Additionally, AED can have serious side effects, might have a negative impact on cognition and may present significant drug interactions. Little is known about actual current practice patterns regarding prophylactic AED in PBT. In this report we investigated prophylactic AED use in a tertiary care institution. Methods: We reviewed medical files of 260 consecutive patients, registered in our center between 2008 and 2012, focusing on prophylactic AED use. Collected data included: patient demographics, starting date, AED type, and indication. A descriptive analysis was performed with SPSS IBM version 20.0. Results: Median age was 44.5 years (11 - 83). Most pts had an ECOG PS ≤ 1 (76.4%). Overall, AED were used by 218 pts. Most common agents were: phenytoin (68.8%), carbamazepine (27.1%) and phenobarbital (16.1%). Among 141 seizure-naïve pts, 99 (70.2%) received AED as primary prophylaxis (PP). Only 14 pts (14.1%) had the drug eventually discontinued, in a median time of 5.9 months (1.1 – 76.8m). AED were used as PP in 60% of pts with low-grade gliomas, 73.3% with anaplastic gliomas and 93.9% with glioblastomas. Twenty-seven pts (27.3%) on PP presented seizures, generally associated with tumor progression. For most of them a new anticonvulsant was added for seizure control. Of the 42 seizure-naïve pts who did not receive prophylactic AED, only two presented seizures during or within the first week post-radiotherapy. Conclusions: In our study population, prophylactic AED use in PBT was extremely high (70.2% of seizure-naive pts). Postoperatively, AED were discontinued in a small minority of pts, and even so, only after a prolonged period of time. Very few seizures occurred in pts not receiving prophylactic AED. Our results suggest that practice patterns regarding prophylactic AED in PBT still contradict established guidelines.

Seizures Do Not Increase In-Hospital Mortality After Intracerebral Hemorrhage in the Nationwide Inpatient Sample

Seizures are common after intracerebral hemorrhage (ICH) but their impact on outcome is uncertain and prophylactic anti-convulsant use is controversial. We hypothesized that seizures would not increase the risk of in-hospital mortality in a large administrative database. The study population included patients in the 2006 Nationwide Inpatient Sample over the age of 18 with a principal diagnosis of ICH (ICD9 = 431). Subjects with a secondary diagnosis of aneurysm, arterio-venous malformation, brain tumor, or traumatic brain injury were excluded. Seizures were defined by ICD9 codes (345.0x-345.5x, 345.7x-345.9x, 780.39). Logistic regression was used to quantify the relationship between seizures and in-hospital mortality. Pre-specified subgroups included age strata, length of stay, and invasive procedures. 13,033 subjects met all eligibility criteria, of which 1,430 (11.0 %) had a secondary diagnosis of seizure. Subjects with seizure were younger (64 vs. 70 years, p < 0.001), more likely to get craniectomy (2.1 vs. 1.2 %, p = 0.006), ventriculostomy (8.5 vs. 6.0 %, p < 0.001), intubation (32.2 vs. 25.9 %, p < 0.001), and tracheostomy (6.4 vs. 4.2 %, p < 0.001). Seizure patients had lower in-hospital mortality (24.3 vs. 28.0 %, p = 0.003). In a multivariable model incorporating patient and hospital level variables, seizures were associated with reduced odds of in-hospital death (OR = 0.62, 95 % CI 0.52-0.75). A secondary diagnosis of seizure after ICH was not associated with increased in-hospital death overall or in any of the pre-specified subgroups; however, there may be residual confounding by severity. These findings do not support a need for routine prophylactic anti-epileptic drug use after ICH.

Prophylaxie antiépileptique en neurochirurgie réglée

In tumoral surgery, the risk factors for perioperative epilepsy can be roughly grouped into two categories: those related to the preoperative patient's conditions (type and location of the tumors, their impact on the surrounding brain…) and those specifically related to surgery (cerebral edema, parenchymal hematoma, surgical approach, complete or incomplete resection...). The first category is supposed to be responsible for preoperative and late postoperative epilepsy, while the second would be more related to the risk of epilepsy in the first postoperative week (or may be even in the first 48hours). It is well accepted (but not always respected) by the neuro-oncologists that there is no indication for preventive antiepileptic drugs (AED) in a patient with a brain tumor that has never presented seizure. However, every seizure crisis must be treated medically. Neurosurgical procedure (which is also a key factor for controlling epilepsy when it occurs. The AED should then be maintained as appropriate. In the absence of preoperative treatment, it has never been shown that prophylactic AED significantly decreases the incidence of postoperative seizures, early or late. Yet, the opposite has not been shown neither, and many groups use AED despite the risk of side effects and an uncertain risk-benefit ratio. Currently, postoperative epilepsy is much less frequent than it was 20 or 30years ago, and the risk of AED side effects also decreases with the latest generation of molecules (such as levetiracetam). So, AED risks and benefits tend to diminish in parallel, but their relationship is still to be assessed. In practice, a modern attitude would restrict prophylactic AED use to the higher risk patients (preoperative epilepsy, temporal astrocytoma, the extent of edema and mass effect...). A drug of last generation should be used, starting one week before surgery. The duration of the treatment should be limited to one week postoperatively in the absence of seizure.

Abstract 155: Risk of Seizures after Malignant MCA Stroke and Decompressive Hemicraniectomy

Background Post-stroke seizures (PSS) have a devastating effect on morale and may further impair an already compromised quality of life. The reported incidence of PSS is 5-12%, but may be higher in patients with malignant MCA stroke requiring decompressive hemicraniectomy. Seizure prophylaxis for stroke survivors is not recommended, and little guidance exists about the use of prophylactic antiepileptic drugs (AEDs) after neurosurgical procedures. We aimed to determine the incidence of seizures after hemicraniectomy in stroke survivors and to identify risk factors for development of seizures after stroke. Via telephone interview, we explored patients own experience after their stroke. Methods We reviewed charts of patients aged 18-99 with malignant MCA infarction who underwent decompressive hemicraniectomy from Jan 1, 2002 to Dec 31, 2008. We looked for seizures that occurred after their stroke and for clinical and imaging factors related to those. All patients who consented to a telephone interview were contacted to inquire about seizure history. Seizure-free survival analysis was used, with log rank testing for associations. Results We identified 38 patients, mean follow-up time was 504 days (IQR 140-857). Nearly half of patients suffered a seizure (18/38) and the seizures were difficult to control in 9/18. Four patients suffered their first seizure during initial hospitalization. For 14/18, the first seizure occurred after or around cranioplasty and mostly at home. Perioperative seizure prophylaxis was variable and did not influence seizure occurrence. Older age showed a trend towards increased seizure risk (log rank p=.09). Neither gender, race, severity, location or hemorrhagic transformation were associated with development of post-stroke seizures. Modified Rankin Scale score (mRS) at discharge was 4 or above in all patients. By last follow-up, 17/38 patients had a mRS of 3 or better. Patients who suffered a seizure did not feel well prepared for the possibility of PSS, and for some the seizures were considered a major setback. Among those who responded to the questionnaire (n=14, 12 had seizures), all would have wanted to know whether or not they were at high risk for developing PSS, and would have opted to take anti-epileptic medications for seizure prophylaxis. Conclusions The frequency of seizures after malignant MCA stroke requiring decompressive hemicraniectomy is higher than expected, and the seizures often difficult to control.

Editorial: Seizures and aneurysms

Hart and colleagues1 herein provide long-term follow-up data on the frequency of seizures following the treatment of a ruptured cerebral aneurysm in patients enrolled in the International Subarachnoid Aneurysm Trial (ISAT). The ISAT population consists largely of patients with good-grade subarachnoid hemorrhage with predominantly small anterior circulation aneurysms that were considered at the time of the trial (1994–2002) to be equally amenable to both clip occlusion and coil embolization. Overall, 11% of these patients suffered a seizure after randomization. Seizures were more common in those allocated to microsurgical repair (14%) than in those allocated to endovascular repair (8%). When one looks at the risk of seizures after discharge out to 5 years, there were still more seizures in the microsurgical cohort (10% vs 6%). In addition to microsurgery, other risk factors for seizures include higher Fisher grade, delayed stroke due to vasospasm, any stroke, older patient age, and middle cerebral artery (MCA) aneurysm location. The authors have conducted 2 notable subgroup analyses to look specifically at the issue of microsurgery versus endovascular surgery. In the first analysis, the authors looked at 1288 patients (60% of the total) who had no other risk factors for seizures (no shunt, no second craniotomy, no stroke, no rebleeding). In this cohort, the risk of seizures was equal between the 2 repair techniques as long as the lesion was not an MCA aneurysm. The second analysis looked at 1458 patients (68% of the total) who had made a good recovery (modified Rankin Scale Score 0–2) by 2 months after aneurysmal SAH, and who thus would probably want to drive. In this cohort, the risk of seizures was again equal between the 2 repair techniques as long as the lesion was not an MCA aneurysm. The authors hypothesize that extensive sylvian fissure dissection and retraction are to blame for the increased risk of seizures after clip occlusion of MCA aneurysms. It is hard to know much about the surgical techniques used during the trial because they were not recorded, but the seizure data certainly argue for careful handling of tissues, sharp dissection, and minimization of retraction. Although the issue of unnecessary retraction has received increased attention in the decade following completion of this trial, the authors should be congratulated for underscoring the importance of microsurgical technique in this particular cohort of patients for whom coil embolization is usually not a good option due to unfavorable anatomy. Thus, although there may be hidden biases in the ISAT data (for example, 3-fold higher incidence of seizures in the microsurgical arm prior to treatment; nonstandard antiepileptic paradigm), the data are helpful in establishing seizure reduction after aneurysmal SAH as a major focus of care. Unfortunately, these data do not support the generalized use of prophylactic anticonvulsants in even “high-risk” patients, but rather, they provide the adjudicated baseline incidence needed to power prospective trials of anticonvulsants appropriately in select individuals.

Editorial: Postoperative antiepileptic drugs

In this issue, Komotar and colleagues1 report the results of their “meta-analysis” of publications describing the incidence of postoperative seizures with and without the use of prophylactic antiepileptic drugs (AEDs) in patients with supratentorial meningiomas. They identified 16 articles, 13 of which provided seizure outcome for patients treated with AED prophylaxis, 3 of which did the same for patients not treated with AEDs, and 3 of which compared patient groups. The patients in these series varied with respect to their duration of anticonvulsant treatment and the agent and dose used, as well as their length of follow-up. The authors’ findings agree with recent case series that have demonstrated no clear evidence that AEDs prevent the occurrence of postoperative seizures in these patients. Furthermore, the paper provides a good review of the literature, and can serve as the reference basis for future trials. The authors acknowledge the limitations of their approach to summarizing and analyzing the existing literature and suggest that more prospective studies would be needed to more completely answer the various practical questions that arise in clinical decision-making in this setting. A number of further questions do arise: 1. In other conditions, such as brain injury, early AED use decreases the risk of early, but not late, seizures. Do the authors think that there are potentially different risks or benefits resulting from strategies that would potentially reduce the risk of early versus late seizures in patients following surgery for meningioma? 2. Is there evidence that the occurrence of an early seizure changes the patient’s outcome with respect to the development of late seizures or neurological deficits? 3. Although the authors mention the potential importance of tumor location in the genesis of postoperative seizures, neither the text nor the tables compare tumor location between patients who received AEDs and those who did not. Are there data on this question, and if so, how would this inform the design of future studies? The authors do acknowledge that “meta-analyses” are methodologically imperfect and concede that their findings, though convincing, cannot be interpreted with the same certainty as a randomized controlled trial. The term “meta-analysis” seems to have myriad definitions, some rigorous, and others descriptive. It is not equivalent to a structured review, which is how I would characterize this paper. From the statistical perspective, a meta-analysis is a technique that seeks to combine results from different existing studies to obtain a more accurate estimate of effect size. The analysis should weight the sample sizes involved, such that larger samples would have more statistical impact. There are a number of statistical methods to produce this aggregate estimation of effect. Simply combining subjects into a pooled sample does not achieve this goal. “Meta-analysis,” however defined, also has a certain mystique attached to it. It is important to recognize that the results of such an analysis can be highly questionable when the included studies employ varying research methods or definitions or when the study selection process is somehow biased. Ultimately, a randomized controlled and blinded clinical trial will be necessary to answer the question of whether or not prophylactic AED therapy should be used to prevent early and late seizures after meningioma surgery. This paper provides the impetus and foundation for such a definitive trial.

Adverse cognitive effects of phenytoin in severe brain injury: A case report

Background: The use of prophylactic anticonvulsants following brain injury is controversial. When used for this reason or for treatment of early seizures, anticonvulsants, particularly phenytoin, can cause severe cognitive side-effects.Case report: This study presents a case of a woman with a severe brain injury with severe cognitive impairment who improved dramatically following withdrawal of phenytoin. The literature regarding such cognitive side-effects is contradictory with no consistent indication of choice of anticonvulsants to use in this situation.Conclusion: As a result of the dramatic improvement in this case, one should now routinely withdraw or change phenytoin treatment in all brain injury patients with significant cognitive impairment.

Post-Traumatic Epilepsy: Review

Post traumatic epilepsy is defined by recurrent seizures secondary to brain injury following head trauma and represent the most frequent cause of epilepsy in young adults. Most post traumatic epilepsies start within two years from trauma, but in some cases may present several years after the brain injury. Severe traumatic brain injuries tend to correlate with an increased risk of developing early and late post-traumatic seizures. A cranial trauma creates a potentially epileptogenic brain damage through a number of different mechanisms. Several structural, physiological and biochemical modifications occur in a brain after a head injury that promote oxidative stress mechanisms and excitotoxic mechanisms. Current evidence shows that prophylactic use of antiepileptic drugs prevent the occurrence of early post-traumatic seizure but does not influence the incidence of post-traumatic epilepsy. Some authors propose treatment with antioxidant drugs in acute phase of severe traumatic brain injuries in order to prevent early tissue changes established in the traumatized tissue.

Management of penetrating brain injury

Penetrating brain injury (PBI), though less prevalent than closed head trauma, carries a worse prognosis. The publication of Guidelines for the Management of Penetrating Brain Injury in 2001, attempted to standardize the management of PBI. This paper provides a precise and updated account of the medical and surgical management of these unique injuries which still present a significant challenge to practicing neurosurgeons worldwide. The management algorithms presented in this document are based on Guidelines for the Management of Penetrating Brain Injury and the recommendations are from literature published after 2001. Optimum management of PBI requires adequate comprehension of mechanism and pathophysiology of injury. Based on current evidence, we recommend computed tomography scanning as the neuroradiologic modality of choice for PBI patients. Cerebral angiography is recommended in patients with PBI, where there is a high suspicion of vascular injury. It is still debatable whether craniectomy or craniotomy is the best approach in PBI patients. The recent trend is toward a less aggressive debridement of deep-seated bone and missile fragments and a more aggressive antibiotic prophylaxis in an effort to improve outcomes. Cerebrospinal fluid (CSF) leaks are common in PBI patients and surgical correction is recommended for those which do not close spontaneously or are refractory to CSF diversion through a ventricular or lumbar drain. The risk of post-traumatic epilepsy after PBI is high, and therefore, the use of prophylactic anticonvulsants is recommended. Advanced age, suicide attempts, associated coagulopathy, Glasgow coma scale score of 3 with bilaterally fixed and dilated pupils, and high initial intracranial pressure have been correlated with worse outcomes in PBI patients.

Predicting the risk of poststroke epilepsy—why and how?

After a stroke, seizures and later development of epilepsy can have a devastating impact on patient outcome and quality of life. Predicting the risk of developing poststroke epilepsy is currently an inexact science, and improving the accuracy of this process could lead to more-targeted use of prophylactic antiepileptic drugs for a defined period of time.

Antiepileptic drug therapy in the perioperative course of neurosurgical patients

Antiepileptic agents are widely used in the perioperative course of neurosurgical patients - for prophylactic and therapeutic reasons. However, the evidence supporting their use is extremely small and adverse events are common. This review highlights the current controversies. Prophylactic use of antiepileptic agents is unfavorable for patients with subarachnoid hemorrhage. In patients with brain tumors, prophylactic use is not recommended. If the drugs are used nevertheless, stopping after the first postoperative week must be strongly recommended. After traumatic brain injury, early prophylactic use might prevent late post-traumatic seizures. The new antiepileptic drug levetiracetam seems to have a better safety profile, which makes it more suitable for prophylactic use. However, in all groups, evidence concerning the choice of drugs and duration of prophylaxis is lacking. Current research is focusing on prevention of epileptogenesis. Therapeutic use of antiepileptic drugs is supported by evidence. These drugs should be continued perioperatively. However, they might induce severe adverse events during adjuvant treatments like radiotherapy or chemotherapy in patients with brain tumors. Despite lacking evidence, prophylactic antiepileptic drug use is common in the perioperative course of neurosurgical patients. More research is needed to deal better with epileptogenesis and to define the right drug for the right patient at the right time.

The role of prophylactic anticonvulsants in the management of brain metastases: a systematic review and evidence-based clinical practice guideline

QuestionDo prophylactic anticonvulsants decrease the risk of seizure in patients with metastatic brain tumors compared with no treatment? Target population These recommendations apply to adults with solid brain metastases who have not experienced a seizure due to their metastatic brain disease. Recommendation Level 3 For adults with brain metastases who have not experienced a seizure due to their metastatic brain disease, routine prophylactic use of anticonvulsants is not recommended.Only a single underpowered randomized controlled trial (RCT), which did not detect a difference in seizure occurrence, provides evidence for decision-making purposes.

Prophylactic Antiepileptic Drug Use is Associated with Poor Outcome Following ICH

Intracerebral hemorrhage (ICH) is associated with a risk of early seizure and guidelines recommend consideration of prophylactic antiepileptic drugs (AEDs) for some patients, although the utility is uncertain. We analyzed data from the placebo arm of the Cerebral Hemorrhage and NXY-059 Trial (CHANT), an international multicenter randomized trial of a potential neuroprotectant that enrolled patients within 6 h of the onset of acute ICH. Logistic regression analyses were performed to determine whether early AED use was associated with poor outcome at day 90, defined as a modified Rankin Scale of 5 or 6 (severely disabled or dead). Excluding patients who were previously on AEDs, the primary analysis included 295 patients. The median ICH volume at admission was 14.9 (interquartile range, IQR 7.9-32.7) ml and the mean was 23.3 (+/-SD 22.8) ml. Seizures occurred in 5 patients (1.7%) after enrollment and 82 patients (28%) had a poor outcome at day 90. AEDs were initiated on 23 patients (8%) without documented seizure during the first 10 days of the trial. In logistic regression, initiation of AEDs was robustly associated with poor outcome (OR 6.8; 95% CI: 2.2-21.2, P = 0.001) after adjustment for other known predictors of outcome after ICH (age, initial hematoma volume, presence of intraventricular blood, initial Glasgow coma score, and prior warfarin use). In this clinical trial cohort, seizures were rare after the first few hours following ICH. In addition, prophylactic AED use was associated with poor outcome independent of other established predictors. Given the potential for residual confounding in this cohort, a randomized trial needs to be performed.

Epilepsy in cerebral glioma: timing of appearance and histological correlations

A prospective study of patients with glioma was carried out. Special attention was paid to the first seizure, to the histology, and to the efficacy and prophylactic role of antiepileptic drugs (AEDs). Prognostic factors were analyzed. Between February 1st 2004 and April 1st 2006 patients who underwent surgical treatment at the Neurosurgery Department of Bolzano for primary or recurrent glioma were prospectively followed until April 1st 2007. Seizures at onset occurring in the absence of interictal epileptiform abnormalities were regarded as remote symptomatic seizures and not treated. Sixty-four individuals were registered in the study; epilepsy diagnosis was made in 27 cases and in 24 of these seizures were the onset symptom. The correlation with histological grading showed that seizures were more frequent in low-grade glioma and in secondary glioblastoma. Although epilepsy was less frequent in high-grade glioma, in these patients seizures were more difficult to control. Poor seizure control was associated with motor and sensitive focal seizures and presence of neurological deficit. Patients without epilepsy and not taking AEDs never developed seizures during the follow-up. Our study clearly shows that epilepsy is more frequent in low-grade gliomas but seizures are more difficult to control in high-grade gliomas. In both cases seizures are a quite exclusive symptom at the onset that never appears during the stable course of the disease. Amongst glioblastoma multiforme (GBM), epilepsy is more frequent in GBM developing through progression from low-grade astrocitoma. Moreover, our study strongly indicates that the prophylactic use of AEDs in glioma is not justified.

Use of Prophylactic Anticonvulsants in Neurologic Critical Care: A Critical Appraisal

Seizures are commonly encountered in the setting of brain injury in neurologic critical care. Though seizure prophylaxis with the use of antiepileptic drugs is frequently utilized in variety of brain injury paradigms, it is often not based on evidence and is controversial. Significant difficulties arise from interpretation of supporting literature due to lack of definitions for early-vs.-late-seizures, variable end points with seizure prophylaxis, as well as methodologic inconsistencies for seizure detection. This descriptive review summarizes the existing literature on the use of prophylactic anticonvulsants in clinical paradigms commonly encountered in neurologic critical care and highlights the important controversies concerning their use.

Optimizing therapy of seizures in patients with brain tumors

The mechanism of epilepsy in brain tumor patients is probably multifactorial, and its incidence depends on tumor type and location. Refractory epilepsy is common in patients with structural brain lesions, and a role for multidrug-resistance proteins has been suggested. The medical treatment of epilepsy in brain tumor patients has mainly been studied retrospectively, and the optimal management of seizures with antiepileptic drugs (AEDs) is unclear. Enzyme-inducing anticonvulsants are generally not recommended because they can lead to insufficient serum levels of concomitantly administered chemotherapeutic drugs. Although valproic acid is an enzyme inhibitor and may therefore lead to toxic levels of simultaneously administered chemotherapeutic agents, this does not appear to be a major problem in patients with brain tumors. Preliminary observations of add-on treatment with the AEDs levetiracetam or gabapentin suggest that these non-enzyme-inducing AEDs can be useful for control of seizures in patients with brain tumors. Conversely, prophylactic use of AEDs in brain tumor patients is generally not recommended.

The Use of Prophylactic Anticonvulsants in Patients with Brain Tumours—A Systematic Review

Should patients with newly diagnosed brain tumours receive prophylactic anticonvulsants to reduce seizure risk? What is the best practice for patients with brain tumours who are taking anticonvulsant medications but who have never had a seizure? Patients with primary or metastatic brain tumours who have never had a seizure still have a 20% risk of experiencing a seizure over the course of their disease. Because considerable practice variation exists in regard to the management of patients with brain tumours who have never had a seizure, and because conflicting evidence has been reported, the Neuro-oncology Disease Site Group (dsg) of Cancer Care Ontario's Program in Evidence-based Care felt that a systematic review of the evidence was warranted. Outcomes of interest were incidence of seizures and adverse effects of prophylactic anticonvulsant therapy. The medline and Cochrane Library databases were systematically searched for relevant evidence. The review included fully published reports or abstracts of randomized controlled trials (rcts), systematic reviews, meta-analyses, and practice guidelines. The present systematic review was reviewed and approved by the Neuro-oncology dsg, which comprises medical and radiation oncologists, surgeons, neurologists, a nurse, and a patient representative. The literature search located one evidence-based practice guideline, one systematic review, and five rcts that addressed prophylactic anticonvulsants for patients with brain tumours. Evidence for the best management of seizure-naïve patients who are already taking anticonvulsants was limited to one retrospective study and exploratory analyses within several rcts. BENEFITS AND HARMS: Pooled results of the five rcts suggest that the incidence of seizures in patients who receive prophylactic anticonvulsants is not significantly different from that in patients who do not receive anticonvulsants (relative risk: 1.04; 95% confidence interval: 0.70 to 1.54; p = 0.84). This analysis accords with results from a published meta-analysis. Evidence is insufficient to determine whether patients who are currently taking anticonvulsants but who have never had a seizure should taper the anticonvulsants. Patients who received anticonvulsants reported adverse effects, including rash, nausea, and hypotension, but whether these effects are a result of the anticonvulsants or of other treatments could not be determined. Based on the available evidence, the routine use of postoperative anticonvulsants is not recommended in seizure-naïve patients with newly diagnosed primary or secondary brain tumours, especially in light of a significant risk of serious adverse effects and problematic drug interactions. Because data are insufficient to recommend whether anticonvulsants should be tapered in patients who are already taking anticonvulsants but who have never had a seizure, treatment must be individualized.

Antiepileptic therapy in patients with central nervous system malignancies

More than 200,000 patients are diagnosed with primary or metastatic brain tumors each year in the United States. Of these patients, 20% to 40% will develop seizures at presentation, and another 20% to 40% will require treatment for seizures during their illness. Although the use of antiepileptic drugs (AEDs) in patients who have had seizures seems reasonable, the issue of prophylactic AED use for patients who have not had a seizure is an intensely debated subject. The American Academy of Neurology released a position statement in May 2000 addressing the use of anticonvulsants in newly diagnosed brain tumor patients who have never had a seizure. After a review of the literature, including all trials showing class I evidence, multivariate analysis using calculated odds ratios failed to show a prophylactic benefit of preventing a first seizure versus the risk of side effects and recommended not using prophylactic anticonvulsants in newly diagnosed patients with brain tumor. Despite this recommendation, a recent survey of the American Association of Neurologic Surgeons revealed that most neurosurgeons still use anticonvulsants prophylactically in patients with brain tumor. This review mainly includes primary brain tumors, but most of the concepts are transferable to patients with metastatic tumors.

Optimal seizure management in brain tumor patients

The mechanism of epilepsy in brain tumor patients is probably multifactorial, and its incidence depends on tumor type and location. Refractory epilepsy is common in patients with a structural brain lesion, and a role for multidrug resistance proteins has been suggested. Until now, the medical treatment of epilepsy in brain tumor patients has only been studied retrospectively. Therefore, the optimal seizure management by antiepileptic drugs (AEDs) in this patient category is essentially unsure. Choices depend on the outcome of retrospective studies, a few nonrandomized series, extrapolation from other studies in symptomatic epilepsy, and anticipated interactions, most notably between AEDs and anticancer agents. The newly developed AEDs levetiracetam and gabapentin are recommended because of good results in preliminary studies and because they do not show interactions with anticancer agents. The use of prophylactic AEDs in brain tumor patients is disputable and generally not advised.