Brain tumors and epilepsy

Paula Gerber, M.D.
Director, Epilepsy Monitoring Unit
Providence Portland Medical Center
The Oregon Clinic

Published September 2009

An estimated 12 to 16 percent of adults with newly diagnosed epilepsy have brain tumors, and seizures develop in 30 to 40 percent of adult patients with brain tumors.

Seizure is often the first clinical symptom of a brain neoplasm, especially in cases of low-grade neoplasms. Seizures are more common in slow-growing tumors such as oligodendrogliomas, meningiomas, gangliogliomas and dysembryoplastic neuroepithelial tumors.

Metastatic lesions tend to have a smaller risk for seizures, though they still occur in approximately 20 percent of cases. Metastatic melanoma is an exception as it tends to involve gray matter and multiple lesions, increasing the likelihood of seizure. A supratentorial location and a superficial location involving gray matter increase the risk for seizure. Also, proximity to the rolandic fissure (primary motor cortex) increases the risk.

Seizures caused by brain tumors, as with any focal lesion, will be of partial or focal onset. As such, they can cause a variety of symptoms for the patient. The symptoms and behavior of the patient during the seizures is determined by the area of cortex involved.

Temporal lobe seizures can be the most challenging to recognize as they can be clinically subtle. These seizures can manifest with olfactory and gustatory hallucinations, transient nausea, transient staring and lapses of consciousness. Staring spells, “spacing out” or daydreaming are relatively common complaints, so it can be difficult clinically to distinguish seizures from normal behavior of this type.

Clinicians should ask about automatic behaviors, such as lip-smacking, chewing, repetitive hand motions or repetitive vocalizations. A consistent aura, such as a bad smell or taste, should raise concern for seizure. Temporal lobe seizures can cause transient sensations of déjà vu or fear, and can be associated with transient autonomic symptoms, such as tachycardia and flushing. Patients may become agitated and may try to run from the room or the house without being aware. These episodes are frequently misdiagnosed as panic attacks. Postictal confusion and fatigue are common, and patients with left-temporal seizures can have significant postictal dysphasia.

Seizures arising from the frontal lobe also can be a challenge, and are frequently misdiagnosed. A variety of behaviors can be seen. Frontal lobe seizures can cause hypermotor behavior, such as thrashing or bicycling motions. Patients can have preserved consciousness during these events and usually there is no significant postictal confusion. Thus, the events can be misdiagnosed as non-epileptic or “pseudoseizures.” They often arise out of sleep and can be mistaken for sleep disorders. Another common frontal lobe seizure type is tonic, causing focal stiffening or extension of the extremities. These can be misdiagnosed as muscle cramps, especially if they involve the legs.

Seizures arising from either sensory or motor cortex are more straightforward. Seizures from the motor strip usually have a classic “Jacksonian march” in which clonic jerking begins in the face, spreads to the arm, then the leg, and finally can evolve into a generalized convulsion. A similar “sensory march” can occur, with spreading numbness or paresthesias.

Patients with tumors can have a significant postictal hemiparesis (opposite the side of seizure onset) known as “Todd’s paralysis.” Patients with a first generalized convulsion should be questioned whether there was any asymmetry of their movements. Did their head or eyes turn to one side? Did one side extend or stiffen before the other? Were they weak on one side afterward? Any lateralized features would suggest that the seizure is of partial-onset, with secondary generalization, and requires evaluation for a focal lesion.

Case presentation
A 46-year-old left-handed woman was in her usual state of health until two months prior to presentation, when she had an unusual episode at work. It consisted of a sensation of upper-body tingling, followed by heat, sweating and racing thoughts, as though her mind was “swarming.” This lasted about 45 seconds. A few weeks later she had a febrile illness and had several more similar episodes. The episodes were relatively stereotyped. A few weeks prior to presentation she had an episode at work in which she briefly blanked out. Following this, she felt very sick and fatigued and had difficulty concentrating. She was unable to remember co-workers’ names or her usual passwords for her computer.

She saw her primary care doctor, who ordered an MRI of her brain. It showed an area of increased tissue volume and increased T2 signal in the right amygdala. There was no abnormal enhancement. The diagnosis was probable low-grade glioma. She was evaluated by a neurosurgeon for biopsy and possible resection. Because she was left-handed, a Wada test was performed to assess language dominance. In this test, an intracarotid injection of either sodium amobarbital or sodium methohexital is performed, and testing of language and memory is done while essentially half of the patient’s brain is “asleep.” This allows for isolated testing of the functions of one hemisphere.

In this case, the patient’s language function was found to be located in the right hemisphere. This put her at higher risk for a decline in verbal memory if the right hippocampus (adjacent to the tumor) were to be removed. The tumor was fortunately not adjacent to the primary language centers. A cautious resection of the amygdala was performed and the patient tolerated it well. She will receive concomitant radiotherapy and chemotherapy.

Regarding her presenting symptoms, a probable diagnosis of partial-onset seizures was made and she was started on levetiracetam. EEG was normal. She has remained seizure-free since being on treatment.

Comments
This case highlights both the potentially subtle presentation of partial-onset seizures and the importance of obtaining brain imaging in all cases of suspected seizure, as a potentially life-threatening neoplasm was discovered. The patient’s hand dominance presented an additional concern. While most people with left-handedness still have a left-dominant brain, some do have right-hemisphere dominance.

Finally, EEG is a useful and important tool in diagnosing seizures. Focal epileptiform abnormalities can give a clue as to the location of seizure onset and can be supportive, though not diagnostic by themselves, of the diagnosis of seizures. However, a normal EEG does not rule out epilepsy. If the patient is asymptomatic during the recording it is possible that no epileptiform activity will be seen.

References
D.C. Hesdorffer (2008). Chapter 6: “Risk Factors” in Epilepsy: A Comprehensive Textbook, Vol. 1, J. Engel and T.A. Pedley, eds., 57-63.

J.D. Recht and M. Glantz (2008). Chapter 264: “Neoplastic Diseases” in Epilepsy: A Comprehensive Textbook, Vol. 2, J. Engel and T.A. Pedley, eds., 2637-42.

J. Engel, P.D. Williamson, A. Berg, P. Wolf (2008). Chapter 43: “Classification of Epileptic Seizures” in Epilepsy: A Comprehensive Textbook, Vol. 2, J. Engel and T.A. Pedley, eds., 511-519.