Seizures and Brain Tumors
By Peter B. Weber, M.D., Neurosurgeon, Surgical Director,
Sutter Pacific Epilepsy Program at California Pacific Medical Center
Kenneth Laxer, M.D., Neurologist, Medical Director, Sutter Pacific Epilepsy Program
David King-Stephens, M.D., Neurologist, Director of Clinical Neurophysiology, Sutter Pacific Epilepsy Program
William McMullen, Jr., Ph.D., ABCN, ABPP, Neuropsychologist, Director of Neuropsychology,Sutter Pacific Epilepsy Program
Brain tumors can cause seizures. Seizures can indicate the presence of a brain tumor. In neurology and neurosurgery we evaluate new onset seizures with an MRI scan or CT scan to look for a structural lesion, like a brain tumor, that could be the cause of this seizure. In this article we explore the connection between brain tumors and seizures, and discuss their management.
The presence of a tumor or abnormal cells can irritate the surrounding brain. That irritation can generate abnormal electrical activity. Propagation of abnormal electrical activity manifests as a seizure. Seizures that spread beyond a small area may affect a person’s consciousness. The three primary forms of seizures are simple partial, complex partial, and generalized seizures. A simple partial seizure does not affect a person’s consciousness but can involve muscle twitching or sensation or even emotional symptoms. A complex partial seizure could contribute to an alteration of consciousness. A generalized seizure often results in a convulsion. Brain tumors typically cause simple partial or complex partial seizures but can result in generalized seizures as well.
Seizures occur in 1/3 to 1/2 of brain tumors (1). Some slow-growing tumors are more likely to present with seizures than others. Certain low-grade tumors will be discovered after a first-time seizure or during the workup of refractory epilepsy. Ganglioglioma, low-grade astrocytoma, and low-grade oligodendroglioma all present with a seizure 70 percent – 83 percent of the time. These seizures are more often focal seizures or complex partial seizures. The exact character of the seizure is related to the location of the tumor in the brain. The frontal, temporal, and parietal lobes are more sensitive to these irritative phenomena, and low-grade tumors in these regions are more likely to present with seizure than mass effect or other deficits.
Common Benign Brain Tumors
Meningiomas are the most common benign brain tumor. A seizure will be the presenting symptom in 50 percent – 60 percent of patients found to have meningioma. Children have more infratentorial tumors (around the brainstem and cerebellum); the infratentorial region does not generate seizures; and brain tumor is not as common a presenting symptom in children. Glioblastoma is the most common adult malignant brain tumor, and 30 percent of patients will present with seizure.
Another common brain lesion in the adult population is the metastatic tumor from a distant primary source. 18 percent of these patients will present with a first-time seizure. In the elderly population, of all patients presenting with a new-onset seizure, 11 percent of them were found to have a brain tumor(1).
Therefore, we see that brain tumors are quite often encountered in the scenario of a new onset seizure in the adult population. For this reason, each and every patient presenting with a seizure, when there is no history of seizures, should have an MRI scan. The CT scan, with and without contrast, is less sensitive but still a valuable study.
Medical management of seizures is undertaken in parallel with evaluation and treatment of the brain tumor. When considering which medication to use, a number of factors should be taken into consideration. The elderly patient may not tolerate some of the older antiepileptic medications. Some seizure medications like Dilantin may interact with chemotherapy given for malignant brain lesions. A broader choice of seizure medications is now available for patients presenting with seizure and brain tumor. Only four antiepileptic medications can be rapidly titrated intravenously—Dilantin, Depakote, Keppra, and Vimpat. Dilantin is a strong p450 enzyme inducer. Depakote can cause liver toxicity and bone marrow suppression. Therefore, these two medications may interact adversely with chemotherapy medications. Leviteracitam and Vimpat are good choices for brain tumor surgery. Leviteracitam has a lower adversereaction rate (1 percent versus 18 percent), fewer seizures after surgery (1 percent versus 4 percent, P equals 0.17), and better long-term compliance when compared to Dilantin(3). Both medications have IV forms, have low toxicity, have low-side-effect profiles, have no black box warnings, have low organ toxicities, do not interact with chemotherapy, and can be rapidly loaded. Vimpat in particular has few cognitive side effects.
Use of seizure medications is recommended in the patient who presents with seizure. Seizure medications are continued for an interval of three – six months after diagnosis and surgery, at which time the medications can be weaned if the patient has remained seizure-free.
Prophylactic use of seizure medications for elective brain tumor surgery in the absence of seizures is controversial and generally not recommended6. Acute short-term use of medications during hospitalization is reasonable, and levetiracetam and Vimpat seem to have some benefits over Dilantin and are available in both oral and intravenous forms(3). Removal of the brain tumor will assist in management of the seizures. For the first-time seizure and a new diagnosis of tumor, the tumor is removed if it is in a resectable location. Gross total resection of the lesion (especially of low-grade gliomas) portends better seizure control after surgery (80 percent of patients will be controlled when there is gross total resection versus 50 percent when subtotal resection)(5). Use of brain mapping techniques assists in maximizing tumor resection when tumors are in eloquent cortex.
A meningioma typically is a slow-growing benign lesion that invaginates the surface of the brain but in most cases does not invade into the substance of the brain tissue. Removal of the tumor will in most cases be associated with control of the seizures. In the case of meningiomas, there is little benefit from use of anticonvulsant medications in preventing early or late seizures after surgery(2). Therefore, antiepileptic medications are indicated only in management of meningiomas when patients present with seizures or when seizures occur after surgery. In those patients who present with seizures and undergo successful removal of the lesion, the medications can be weaned after a seizure-free interval of three to six months.
In the spectrum of disease related to brain tumors and seizures, some patients present with or develop refractory seizures that do not relent despite adequate medical management with antiepileptic medications. For intractable seizures, epilepsy surgery techniques to resect epileptic cortex in association with planned tumor removal provide the highest rate of success for control of seizures. Electrocorticography (recording of electrical activity from the surface of the brain using implanted or intraoperative surface electrodes) supplemented by awake or asleep mapping techniques for infiltrating brain tumors increases chances of success when success is measured by control seizures after surgery. When the lesion is in eloquent cortex and causes refractory seizures, using grid electrodes and/or awake mapping techniques allows us to maximize tumor removal and minimize risks of postoperative deficits.
Brain tumors can cause seizures, and seizures can indicate the presence of a brain tumor. Management of seizures is pursued in conjunction with management of the brain tumor. The choice of seizure medications may be influenced by the patient’s age, type of tumor, and the physician’s ability to control the seizures with any given medication. Newer-generation seizure medications provide some benefits over older varieties. Seizures contribute to worsened quality of life in tumor and non-tumor patients. The pursuit of freedom from seizures in conjunction with removal of the tumor should be the goal of the care team.
Image caption: Figure 3: This tumor was located in the left-hemisphere language cortex. Brain mapping techniques allowed for complete removal of the lesion without compromising cortical function: The patient experienced no deficits postoperatively.
Image caption: Figure 4: In this case, intraoperative electrical recordings and stimulation mapping techniques were used to identify eloquentcortex and identify epileptic cortex. Knowing where the abnormalelectrical activity originates and the location of eloquent cortex allows maximal tumor resection in combination with removal of epileptic cortex while sparing vital cortical functions.
- Thapar Rutka Laws. Brain edema. p 163. In Brain Tumors Kaye and Laws
- Prophylactic antiepileptic drug therapy in patients undergoing supratentorial meningioma resection: a systematic analysis of efficacy. Komotar RJ, Raper DM, Starke RM, Iorgulescu JB, Gutin PH. J Neurosurg. 2011
- Medical management of patients with brain tumors. Pruitt AA. Curr Treat Options Neurol. 2011 Aug;13 (4):413-26.
- Efficacy and tolerability of levetiracetam versus phenytoin after supratentorial neurosurgery. Milligan TA, Hurwitz S, Bromfield EB. Neurology. 2008 Aug 26;71(9):665-9.
- Predictors of seizure freedom after resection of supratentorial low-grade gliomas. Englot DJ, Berger MS, Barbaro NM, Chang EF. J Neurosurg. 2011
- Optimal seizure management in brain tumor patients. van Breemen MS, Vecht CJ. Curr Neurol Neurosci Rep. 2005 May;5(3):207-13.