For Penn Medicine epilepsy specialists, clinical excellence and innovative research go hand-in-hand. Penn experts hold prominent roles within groups that support and spearhead advances in epilepsy, including the National Associations of Epilepsy Centers, Epilepsy Foundation, American Clinical Neurophysiology Society and Epilepsy Study Consortium.
"We really focus on how we can improve patient care," says Kathryn A. Davis, MD, MTR, director of Penn Epilepsy Center. As established leaders in the field, Dr. Davis and her colleagues explore novel techniques and treatments that could directly benefit patients.
Advancing Intracranial EEG Analysis
At Penn Neurology and Penn’s Epilepsy Monitoring Unit, providers offer the full range of epilepsy diagnostics, including intracranial EEG (iEEG), a less common procedure. Dr. Davis and colleagues Brian Litt, MD, professor of neurology and professor of neurosurgery, and Erin Conrad, MD, assistant professor of neurology, seek to make iEEG findings more useful in guiding treatment.
In a recent study published in Brain, they developed a normative iEEG atlas that helps identify abnormal networks. By comparing iEEG results to the atlas, providers can better pinpoint epileptic areas and determine treatment options. The team aims to enhance the atlas with more data from centers across the nation.
"A major effort at our center is designing a system for collecting intracranial data from epilepsy centers worldwide so that we at Penn and others can use it as a way of improving how we approach these patients in the long term," says Dr. Davis.
The three clinician-investigators, led by Dr. Conrad, have created an additional model to identify where seizures start using iEEG recordings during sleep. Their findings, published in Epilepsia, showed that certain spike patterns during non-REM sleep best localized seizures, especially for temporal lobe epilepsy.
Drs. Litt and Davis also published recent study results in Epilepsia on treatment to individual patients. They found biomarkers in iEEG recordings that predict a patient’s success with responsive neurostimulation (RNS), a neuromodulation technique for epilepsy.
Using Imaging to Localize Seizures
In parallel, the Penn team also searches for ways to optimize diagnostic tests using the least invasive methods possible.
"We’re studying advanced multimodal neuroimaging to better understand seizure networks and improve our ability to localize where in the brain seizures are coming from," says Dr. Davis. "We know that if you can find that abnormality, those patients will have a much better surgical outcome."
Her laboratory’s current clinical trial aims to develop noninvasive imaging tools that map seizure networks. Currently, a third of epilepsy patients have nonlesional 3T MRI studies and need further iEEG tests to find answers. This study tests the hypothesis that advanced imaging biomarkers may relate to and predict iEEG findings, potentially reducing the need for invasive tests.
As participants in the study, patients with refractory temporal lobe epilepsy receive 3T MRI, 7T MRI and iEEG monitoring. Using 7T MRI, Dr. Davis’s laboratory can look for subtle abnormalities at a much higher resolution. The results not only inform participants’ immediate clinical care, but also allow Penn specialists to quantify structure-function coupling and search for biomarkers.
Identifying New Anti-Epileptic Drugs
Penn neurologists have also developed an active epilepsy drug trial program, offering recent advances in epilepsy medication and testing anti-seizure medications (ASMs) in new patient populations. For many years, new ASMs have worked with about the same efficacy as previous medications. But two recently approved medications — cenobamate and fenfluramine — have had much more success.
As a study site in two pivotal cenobamate trials, Penn evaluated the ASM in patients with focal onset seizures and primary generalized tonic-clonic seizures. Cenobamate (YKP3089) uniquely combines both anti-excitatory and pro-inhibitory mechanisms, which may improve the imbalance of activity in the brain that causes seizures.
The phase 3 cenobamate safety study, published in Epilepsia and co-authored by Associate Professor of Clinical Neurology at Penn, Michael Gelfand, MD, PhD, found no drug reaction with eosinophilia and systemic symptoms (DRESS) and showed the ASM to be well-tolerated long-term.
"It’s really exciting to have not just another medicine to add to the list, but ones that actually control seizures better," says Dr. Davis. "We also have ongoing clinical trials of medications with preliminary data really indicating they may be more effective as well."
Dr. Gelfand leads Penn’s current epilepsy drug trials, which investigate:
- AUT00201 for myoclonus epilepsy and ataxia (NCT pending)
- Darigabat (CVL-865) for refractory, focal onset seizures
- Inhaled dry powder cannabidiol (RLS103) for photosensitive epilepsy
The development of rescue medications for seizures also stood at a standstill for many years, with rectal diazepam gel being the primary option for patient use at home. In an exciting advance, two intranasal sprays that work within 10 minutes recently came on the market. The Penn team continues to investigate even faster methods of delivery, including an inhaled option called Staccato® alprazolam that may work within just 90 seconds.
Exploring Noninvasive Brain Stimulation for Epilepsy
"In the last 10 years, we’ve seen a shift in the surgical management and treatment of drug-resistant patients to less invasive therapies," notes Dr. Davis about recent advances in epilepsy. "I’ve seen patients completely unwilling to consider surgery now flip to being willing to consider less invasive interventions."
Penn neurologist Taneeta Mindy Ganguly, MD, investigates one of those interventions — transcranial cathodal direct current stimulation (tDCS) — in her current epilepsy research trial. This form of brain stimulation delivers constant current through scalp electrodes placed over target areas.
Leading the Penn study site, Dr. Ganguly tests the safety, efficacy and tolerability of tDCS in patients with focal epilepsy and/or focal to bilateral tonic-clonic seizures. Successful tDCS would allow providers to control drug-resistant seizures without surgery or a permanent device.
Finding Biomarkers as Part of the Human Epilepsy Project
Penn is also a member of the Human Epilepsy Project (HEP), an international coalition of clinicians, scientists, healthcare workers and patients with the goal of enhancing care for new-onset epilepsy.
Penn Neurology serves as a recruiting study site for the Human Epilepsy Project 3, which aims to improve the field's understanding of generalized epilepsy. Investigators plan to identify biomarkers that predict how individuals will respond to treatment and how epilepsy will impact their lives.
Penn enrolls both patients who have just been diagnosed and patients with an established diagnosis and treatment response. At the same time, the team contributes to HEP's international bank of DNA, electrophysiology data, biochemical profiles and imaging that will benefit future studies.
Additional Resources from the Penn Epilepsy Center