Developments in Tumor-Related Epilepsy

Members of the Brain Tumor-Related Epilepsy Research Consortium shared the latest methods to treat tumor-related epilepsy (TRE) at the 70^th annual meeting of the American Epilepsy Society. They focused on innovations in surgery, minimally invasive procedures, and potential new drug therapies.

About 4% of people with epilepsy have brain tumors. And in patients with brain tumors, the frequency of epilepsy is more than 30%. Seizures are the often the first clinical sign of brain tumors, but they can also develop later.¹

The condition can be tricky to treat because it involves handling two complicated neurological disorders at once. TRE is associated with a widespread epileptic network with complex epileptogenic mechanisms, explained Sandeep Mittal, MD, professor and chairman of neurosurgery at Wayne State University. It is poorly controlled by antiepileptic drugs, and the best management of tumor-related focal epilepsies remains controversial.

“You may get suboptimal seizure control with a lesionectomy alone,” he said.

Mittal and his Wayne State colleague, Dr. Aashit K. Shah, interim chair and professor of neurology, backed surgical approaches that remove both the tumor and epileptic brain tissue. They said surgery for TRE should have two goals: to reduce the chances the tumor will become malignant, and to eliminate seizures.

Intracranial EEG helps pinpoint the epileptogenic zone, especially for patients who may have epilepsy with multiple foci. Also, in most patients with TRE, at least part of the epileptogenic zone lies distant from the tumor margin-beyond 1.5 cm. Mittal and Shah have found that intracranial EEG-guided resection of brain tumors, plus the entire epileptogenic zone, results in excellent seizure outcomes.²

Mittal also recommended using a systems biology approach to treating TRE to help determine exactly why some brain regions produce seizures and others do not, identify cellular changes in the human epileptic neocortex, and develop biomarkers of lesional and non-lesional epilepsy.

Brain surgeon Kris Smith, MD, with the Barrow Neurological Institute in Phoenix, advocated a minimally invasive approach to treat TRE, using a “keyhole craniotomy” technique that accesses the brain through a small incision behind the ear.³ Smith said the surgery better preserves brain function, and enables faster healing. “The brain is not exposed, so it is less likely to be injured.”

Smith advised maximal resection because, “large tumors do not require large openings.” MRI-guided Laser Interstitial Thermal Therapy is another useful treatment tool, he said.

On the biotechnology front, Mark Cunningham, PhD explained how the excitatory neurotransmitter glutamate plays a role in both epileptic seizures and tumor growth.

In studies using brain tissue slices from neurosurgical patients, Cunningham has found that the anti-epileptic drug Perampanel blocks the action of glutamate at the AMPA receptors in the brain-inhibiting seizure activity and tumor growth.

“Perampanel’s mechanism is perfectly suited to the pathology of the condition (tumor-related epilepsy),” Cunningham said.

Next steps include clinical trials to test the drug’s potential as a first-line drug for tumor-related seizures.

Consortium director Jeffrey Politsky, PhD, associate director of the Northeast Regional Epilepsy Group in New Jersey, and Sandeep Mittal, MD, coordinated the session. The Brain Tumor-Related Epilepsy Research Consortium is an international group of tumor and epilepsy experts. Their mission is to improve the quality of life of people of all ages with brain tumor-related epilepsy. 

Politsky J, Mittal S, coordinators, Special Interest Groups: Tumor-Related Epilepsy-Scientific Developments and Their Impact of Treatment, 2016, American Epilepsy Society Annual Meeting, www.aesnet.org.

References:

1. Shah AK. Intracranial EEG in tumor-related pharmacoresistant epilepsy, 2016 Dec 5, American Epilepsy Society Annual Meeting, www.aesnet.org.

2. Mittal S, et al. Intracranial EEG analysis in tumor-related epilepsy: Evidence of distant epileptic abnormalities. Clin Neurophysiol. 2016 Jan;127(1):238-244.

3. Little AS, et al. Modifications to the subtemporal selective amygdalohippocampectomy using a minimal-access technique: seizure and neuropsychological outcomes. J Neurosurg. 2009 Dec; 111 (6):1263-1274.