Revised: June 2014
Brain edema may result from tumour, surgery or radiation treatment. Symptoms may include headache, nausea with or without vomiting, worsening of presenting neurologic symptoms or decreasing level of consciousness. Oral (or intravenous) corticosteroids are very effective in reducing brain edema and alleviating the associated symptoms, often within 24 - 36 hours.
Dexamethasone is used most commonly in a range of doses from 2-16 mg per day (in divided doses) depending on symptom severity. In emergent situations, higher doses of dexamethasone may be used and mannitol may also be employed.
Side effects of dexamethasone include increased appetite, altered mood, impaired glucose tolerance, proximal myopathy, Cushingoid changes, tremor, gastric erosions or ulceration with bleeding, pseudorheumatism and others. Most of these side effects are reversible when the steroid is discontinued. Rarely, frank psychosis or avascular necrosis of the femoral head may result.
There are some possible important dexamethasone-drug interactions that should be noted: brain tumour patients are often on anti-seizure medication and their serum levels may be affected by dexamethasone (phenytoin or carbamezepine levels should be monitored); if the patient is also on chemotherapy, immunity may be further suppressed and the patient may be at increased risk for opportunistic infections (prophylactic Septra is often started if patients are on both chemotherapy and dexamethasone).
During radiation therapy, a tapering dose of dexamethasone, as clinically tolerated (to alleviate symptoms of brain edema), is prescribed, and the lowest effective dose is used. After completion of radiation therapy, the dexamethasone is tapered and discontinued over 2 - 4 weeks usually. However, there may be periods of brain edema in the few weeks following radiation and in a delayed window of time from 8 - 16 weeks following the completion of radiation therapy (early delayed radiation edema) and dexamethasone may need to be re-instituted. Occasionally, adrenal dependence is seen and prolonged tapering or continued use of low dose steroid replacement is needed.
Although alternate medications are being investigated in the hopes of avoiding the undesirable side effects of dexamethasone, to date it remains the mainstay in the control of brain edema.
Epilepsy is a common disorder in patients with primary brain tumours. Thirty percent will present with a seizure and at least 50% will have a seizure at some time (1). The most common seizure disorder in these patients is partial epilepsy with or without secondary generalization. Because of the high likelihood of recurrence, virtually all brain tumour patients who have a seizure should be started on anticonvulsants. Selection of anticonvulsant will depend on side effect profile, drug interactions, and cost. Medications most commonly prescribed for partial epilepsy include phenytoin, carbamazepine, and levetiracetam. Alternative choices include divalproex sodium, lamotrigine, clobazam, lacosamide, topiramate, oxcarbazepine and phenobarbital. Refractory cases requiring more than one agent should be referred to a Neurologist for specialized care.
Phenytoin is the most frequently used anticonvulsant, as it is available both orally and intravenously, is familiar to most physicians, can be taken once a day and has low cost. The average adult dose is 300-400 mg and can be taken at bedtime as a single oral dose. As it can take up to a week for steady-state levels to be achieved, oral or IV loading can be achieved at a dose of 15 mg/kg. The therapeutic range is 40-80 micromoles/litre but dosage should be titrated to seizure control with minimal side effects. Common toxic effects of phenytoin include drowsiness, dizziness, imbalance and confusion. Other relatively common side effects include hypersensitivity reactions (rashes, fevers), gum hyperplasia, and alterations of liver enzymes. Interactions with other medications especially dexamethasone and other anticonvulsants may require monitoring of serum levels during changes in medications.
Carbamezepine is not available intravenously and due to GI intolerance cannot be loaded orally. Treatment is usually started at 100 mg bid of the long-acting formulation and increased over the next 1-2 weeks to a target dose 800-1000 mg/day. Steady state is usually achieved in 4-7 days and the therapeutic serum concentrations range from 25-50 micromoles/litre. Toxic effects are similar to phenytoin and include imbalance, dizziness, diplopia, dysarthria and confusion. Other side effects include rashes, hepatic enzyme induction, neutropenia, hyponatremia and GI upset. The tendency to cause neutropenia make this agent less desirable for brain tumor patients that may require chemotherapy as part of their treatment.
Levetiracetam has a higher cost than phenytoin or carbamazepine but has a more favorable side effect profile and does not have significant drug interactions. It is an oral agent that can be started at therapeutic dose immediately without titration. Typical starting doses of 500 mg twice daily can be increased as high as 1500 mg twice daily as needed for seizure control. Monitoring levels is not necessary with this agent as there is no toxic level. Chief side effects include mild dizziness, drowsiness or stomach upset. On occasion mood changes and irritability have been noted.
Duration of therapy with anticonvulsants is uncertain. Because of the frequent presence of residual tumour, the residual scarring from prior surgery and radiation and the high risk of tumour recurrence, most patients will require lifelong anticonvulsant therapy. A few patients with low grade neoplasms, who had a tumour resection and have been seizure-free for a number of years, may be considered for anticonvulsant withdrawal under the direction of their neurologist or surgeon.
Driving restrictions are necessary for any patient with a seizure disorder. Brain tumour patients need specific consideration as other neurologic deficits may preclude driving i.e. visual field defects, hemiplegia, dementia, etc. British Columbia law requires a patient be seizure-free for 6 months on treatment prior to recommencing driving.
The use of prophylactic anticonvulsants in patients with brain tumours is controversial. Retrospective reviews and a few small prospective studies have failed to show a significant benefit from the early prophylactic use of anticonvulsants (2,3,4). Anticonvulsants have potentially serious side effects and have been associated with severe rashes (Stevens-Johnson syndrome) in a few patients concurrently receiving cranial radiotherapy (5). At this time the routine use of prophylactic anticonvulsants in brain tumour patients who have yet to experience a seizure is not recommended.
- Cascino GD. Epilepsy and brain tumours: implications for treatment. Epilepsia 3: s37-s44, 1990.
- Mahalay M, Dudka L. The role of anticonvulsant medications in the management of patients with anaplastic glioma. Surg Neurol 16:399-401, 1981.
- Moots PL, Maciunes RJ, Eisert DR, et al. The course of seizure disorders in patients with malignant gliomas. Arch Neurol 52:717-724, 1995.
- Glantz M, Friedberg M, Cole B, et al. Double-blind, randomized placebo-controlled trial of anticonvulsant prophylaxis in adults with newly diagnosed brain metastases. Neurology 46:985-991, 1996.
- Delattre J-Y, Safari B, Posner JB. Erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and phenytoin. Neurology 40:1144-1145, 1990.