INTRODUCTION

In patients with meningiomas, the most common perioperative problems involve the management of epilepsy, peritumoral brain edema, and venous thromboembolism. Management difficulties arise from the heterogeneity of the patient population despite the common diagnosis of a meningioma and the lack of quality evidence to guide drug prophylaxis and treatment.

PREVENTION OF SEIZURES IN MENINGIOMA PATIENTS

Seizures are among the most common presenting symptoms in meningiomas. Various authors have reported seizures as the presenting symptom in 20% to 50% of meningiomas.^1–7 This incidence is slightly higher if only supratentorial meningiomas are considered (29%–67%).^5,8,9 This rate is similar to the incidence of 30% to 50% reported for brain tumors in general.¹⁰ Among all meningiomas, convexity, anterior third parasagittal, and sphenoid wing meningiomas have the highest incidence of seizures.^1,4 Although the incidence of meningiomas is more common in women, several studies have shown that seizures are equally common in female and male meningioma patients.^1,4,9 Similarly, the incidence of a presentation with seizures is equally common in all age groups.⁴ There is also no reported significant association of seizures with any histological type of meningioma.^1,4,11 The presence of peritumoral edema has a highly significant correlation with seizures in patients with meningiomas.^4,11 The high concentration of glutamate and aspartate has been suggested as the cause for this increased risk of seizures.^12,13

Meningioma patients who have presented with seizures are routinely treated with antiepileptics. Despite such treatment, brain tumor patients who have presented with seizures have an increased risk of recurrent seizures.¹⁴ Surgical resection of meningiomas is reported to eliminate seizures in 19.2% to 63.5% of patients who had presented with epilepsy.^5,8,9 However, one third of patients with preoperative seizures are reported to have postoperative epilepsy. Therefore, preoperative epilepsy is a significant risk factor for postoperative epilepsy.

Initiation of antiepileptic treatment in meningiomas is justified after presentation with seizures. However, as with most other brain tumors, the indication of antiepileptic prophylaxis in patients who have never had a seizure remains controversial. In general, 20% to 45% of patients with brain tumors who have never had a seizure will develop epilepsy during the course of the disease.¹⁴ Therefore, prophylactic treatment sounds logical. However, the efficiency of antiepileptic medications in preventing seizures in brain tumor patients is debated and all of the antiepileptics are associated with a broad range of side effects, some of which can be quite severe or even life threatening. In two randomized studies, the use of phenytoin was found ineffective in patients with supratentorial tumors.^15,16 The Quality Standards Subcommittee of the American Academy of Neurology published a consensus statement in 2000, recommending not to use antiepileptic drugs in patients with brain tumors routinely and to withdraw the drugs in the first week after surgery if the patients have never had a seizure.¹⁴ A more recent meta-analysis by Sirven and colleagues¹⁷ separately analyzed the seizure outcome in different brain tumor subtypes and similarly concluded that antiepileptic treatment was ineffective in patients with gliomas, metastases, or meningiomas who never had a seizure.¹⁷ However, this study did not have enough statistical power to be conclusive. A recent Cochrane Library review analyzed five clinical trials with random allocation of seizure-free brain tumor patients to phenobarbital, phenytoin, and valproate and concluded that there was no statistical difference between treatment, placebo, or observation.¹⁸ However, this systematic review also pointed out that the only study, which had statistical power, suffered from several biases that weakened its conclusions. The Cochrane Library review stated that the evidence available at present is neither in favor nor against seizure prophylaxis in patients with brain tumors.¹⁸

Seizures after surgical treatment of meningiomas may be related to the meningioma itself or to craniotomy. Development of new-onset postoperative epilepsy is reported in 5.1% to 42.9% of meningioma patients who did not have seizures preoperatively.1–5,^8,9 Approximately two thirds of these new-onset seizures are seen in the first 48 hours after surgery.^4,19 Such an early presentation of seizures is associated with a high likelihood of becoming seizure-free with antiepileptic medications. Lieu and colleagues⁴ have reported that 71.2% of patients are reported to become seizure-free after a year of antiepileptic treatment. Postoperative epilepsy is more common in patients who had iatrogenic injury to cortical veins or arteries or in cases where significant brain retraction was required during surgery. Patients who had preoperative epilepsy or those who had postoperative hydrocephalus are more commonly associated with postoperative epilepsy.^1,5,8,9,20 An association with subtotal resection is controversial.⁴ Similarly the association of parietal localization with an increased risk of postoperative epilepsy was reported by Chozick amd colleagues⁹ but not reconfirmed by others.⁴ It should be kept in mind that postoperative seizures can be secondary to meningitis or promoted by infections in other sites such as the urinary system. Laboratory investigations are prompted in the case of a postoperative seizure.

There is very scant information on the choice of antiepileptic drugs in brain tumor patients with epilepsy. Owing to lack of evidence, recommendations for the general epileptic population are extrapolated to treatment of brain tumor patients. Carbamazepine and lamotrigine are first-line treatment recommendations for symptomatic localization-related epilepsy.²¹ Although carbamazepine is one of the most effective drugs for the treatment of partial epilepsy, Wick and colleagues,²² in their study on gliomas, showed that recurrent seizures were observed in 70% of those who were treated with carbamazepine, in 51% of those who were given phenytoin, and in 44% who received valproic acid. Newer antiepileptics are commonly used as add-on drugs in the case of persistent seizures despite medical treatment. Levetiracetam and gabapentin are reported to be effective and well tolerated as add-on drugs in patients with persistent seizures.^23–25 Patients who have seizures refractory to medical treatment may be candidates for epilepsy surgery. Surgical resection of an epileptic focus related to a brain tumor has been proven to be very effective treatment modality. Seventy to ninety percent of patients are reported to become seizure free or have substantial decline in seizure frequency.^10,26