The evolution of epilepsy care
Innovative targets and emerging therapies are reshaping the future of epilepsy treatment
By Jessica Binkley Lain
Epilepsy, a neurological condition characterized by recurrent seizures, affects approximately 3 million people in the United States — about 1% of the nation’s population — and is considered one of the most prevalent neurological disorders. Charles Akos Szabo, MD, professor in the Department of Neurology, Division of Epilepsy, in the Joe R. and Teresa Lozano Long School of Medicine, sheds light on the changing landscape of epilepsy treatment.
“Epilepsy is a disease defined as having an increased risk for recurring seizures,” Szabo said, noting the multifaceted nature of the condition.“Epilepsy has many causes, including head injuries, strokes, neurodevelopmental disorders or genetic predisposition. The treatment depends on several factors, like whether the seizures start in one part of the brain or simultaneously involves both sides, as well as determining the underlying cause.”
Mitigation treatments
Anti-seizure medications can control seizures in most people with epilepsy. However, in some people whose seizures do not respond to medications, surgical resective procedures to remove identifiable lesions underlying epilepsy, such as tumors, scar tissue or cortical dysplasias, are highly effective at alleviating seizures. Minimally invasive techniques like laser ablation offer similar results with reduced risk and faster recovery.
Newer implanted neurostimulation devices like responsive neurostimulation or deep brain stimulation are also safe and effective treatment options to reduce seizure activity when resective or ablative approaches may not be successful or are too risky.
“With these methods we can modulate brain activity to mitigate seizures. In addition, responsive neurostimulation also helps physicians to monitor their patients’ seizures,” Szabo said. He explained that the technique involves implanting devices that deliver targeted electrical stimulation to certain areas of the brain to brake or prevent seizures.
New drug therapies
Novel pharmacological treatments currently under investigation at the university target potassium channels rather than traditional antiseizure therapies that target sodium channels.
“The traditional treatments work by blocking or modulating sodium and calcium channels that cause increased excitation, aiming to stabilize neuronal activity and reduce seizure susceptibility. But the newer class of medications that target the potassium channel stabilize neuronal activity by rendering neurons less electrically responsive to abnormal stimulation,” Szabo explained. The new compounds are currently in phase 2 and 3 clinical trials at the university.
Szabo and his team are also engaged in pioneering research investigating sudden unexpected death in epilepsy, or SUDEP, a fatal complication of epilepsy that happens when a person with epilepsy dies unexpectedly and without an apparent cause. These studies explore potential biomarkers to better predict which people with epilepsy may be at increased risk for this potentially devastating yet avoidable outcome. Their research includes population-based studies evaluating brain or cardiac electrophysiological markers, as well as neuroimaging biomarkers, and testing of seizuredetection devices that can warn people with epilepsy and their caregivers of potentially hazardous seizures.
Animal model comparisons
For these studies, Szabo is working closely with the Texas Biomedical Research Institute, which houses a large baboon colony that includes baboons with natural genetic epilepsy. These animal models allow Szabo to evaluate physiological, neuroanatomical, genetic and epigenetic markers that may contribute to sudden unexpected death in baboons with epilepsy similar to that in humans.
“Baboons, like humans, have naturally occurring epilepsy, which makes them a valuable non-human primate model for studying genetic and epigenetic factors underlying epilepsy in humans,” Szabo said.
“Furthermore, their similarity to humans With these methods we can modulate brain activity to mitigate seizures. In addition, responsive neurostimulation also helps physicians to monitor their patients’ seizures.” Charles Akos Szabo, MD, professor in the Department of Neurology, Division of Epilepsy allows us to translate seizure characteristics and epilepsy-related changes in the brain and cardiac functioning back to the human condition,” he said, adding that the baboon provides a model not only to validate prospective human SUDEP biomarkers, but also to test treatments or devices to prevent this outcome in people with epilepsy.
As the field of epilepsy treatment continues to evolve, driven by technological innovations and a deeper understanding of underlying mechanisms, the future holds promise for more effective therapies and improved quality of life for individuals living with epilepsy, said Szabo.
“With these methods we can modulate brain activity to mitigate seizures. In addition, responsive neurostimulation also helps physicians to monitor their patients’ seizures.”
-Charles Akos, Szabo, MD, professor in the Department of Neurology, Division of Epilepsy
