Michael Sperling, MD, on AES Lifetime Achievement Award, Evolution in Epilepsy Care

In a field as rapidly evolving as epilepsy, there is constant growth, fluctuation, and variability. One stalwart throughout these changes has been the contributions of Michael R. Sperling, MD. Currently serving as the Baldwin Keyes Professor of Neurology and vice chair for research at the Sidney Kimmel Medical College at Thomas Jefferson University, Sperling has spent decades advancing epilepsy research and care and continues to influence the field in meaningful ways.

Sperling’s list of accomplishments is quite extensive. He founded and currently directs the Jefferson Comprehensive Epilepsy Center, became an internationally recognized clinician-scientist in the field of epilepsy, and has published over 500 peer-reviewed papers, among other contributions. His award shelves are also far from empty as Sperling earned the J. Kiffin Penry award from the American Epilepsy Society in 2018 and the Ambassador for Epilepsy award from the International League Against Epilepsy in 2021.

At the 2025 American Epilepsy Society (AES) Annual Meeting, held December 5-9, in Atlanta, Georgia, prominent clinicians working in epilepsy were honored with awards recognizing their contributions. Among them included Sperling, who received the 2025 Lifetime Achievement (Founders) Award for his sustained impact on epilepsy in both the clinical and scientific arenas.

During the meeting, NeurologyLive® caught up with Sperling, who reflected on the significance of receiving the award and acknowledged the many colleagues who supported his career. He shared his views on the current state of epilepsy care and expressed continued optimism about the advances on the horizon for patients. He also pointed to several areas of the field that warrant greater attention, including opportunities to redesign clinical trials and enable more personalized treatment strategies. Ultimately, he emphasized the essential role of collaboration in driving progress within this complex and rapidly evolving specialty.

NeurologyLive: What does receiving the Lifetime Achievement Award mean to you?

Michael Sperling, MD: It is really a great honor to be awarded the Lifetime Achievement Award, the Founders Award, by the American Epilepsy Society. It is humbling in many ways. There are many people who deserve it, and not all wind up getting such an award. I am very grateful to the Epilepsy Society for doing it and It really represents a capstone to my career.

NeurologyLive: You mentioned feeling grateful to receive the award. Who would you say helped you the most along your career path?

My career has been one of collaboration with many people. I have to credit my original mentor, Pete Engel, MD, back, when I was a fellow at UCLA. He helped launch my career in epilepsy and gave me connections and support to do research and get things done.

Mike O'Connor was a neurosurgeon I first worked with, and he was an important person since my original focus was epilepsy surgery. I have maintained that interest. Then there have been many other collaborators through the years, from research to clinical work.

Certainly my current team at Jefferson is spectacular. I am grateful to all my colleagues at Jefferson. I cannot name them all, but it is a wonderful group of neurologists, neurosurgeons, neuropsychologists, radiologists, pathologists, and others. They helped build a strong clinical program and a clinical program focused on research. I have also had collaborators outside Jefferson.

We set up a multicenter epilepsy surgery study 25 years ago, headed by Sue Spencer and Dennis Spencer at Yale, with colleagues around the country. There have been numerous collaborations internationally for genetics, and nationally and internationally for electrophysiology. All of these have made life interesting and the career rewarding.

NeurologyLive: After so many years, what makes you most optimistic for patients with epilepsy?

I think we are at an inflection point now where we have been going up gently and gradually, and the slope is increasing. There are lots of new and really hopeful projects. There are new approaches to therapy and diagnosis that are still in process but will make a big difference. We have great new tools for seizure detection, and we are only at the beginning.

One of the great limitations in treating epilepsy is that we often do not know when people are having seizures because they do not necessarily know. So new monitoring techniques to detect seizures will be a tremendous advance. And new monitoring techniques to predict when seizures will happen are also emerging. Many people are working on methods that review EEG, EKG, galvanic skin response, and other physiological parameters to predict when someone may be apt to have a seizure. That would be a huge game changer.

On the diagnostic side, we have great tools. MRI has been a game changer over the past thirty five to forty years. Other imaging and electrophysiology techniques will help us too. Genetics has exploded in the last five to ten years, with new genes being discovered every month. That will be important and hopefully lead to new therapies. The pipeline of new drugs is still expanding. I am old enough to go back to the days when we had four main drugs for focal epilepsy. Now the number is two dozen, and many of them are better than what we had before.

New surgical techniques are wonderful. The fact that you can do a thermal ablation, make a tiny hole three millimeters in diameter, put in a probe, thermally ablate cortex, pull it out, and the patient goes home in a day with minimal pain, is strikingly better than doing a whole craniotomy. Newer approaches like gene therapy, cell transplant, and potentially optogenetics will be game changers. Other types of compounds, beyond ordinary chemicals, are being explored. Future therapies may alter DNA or RNA expression, and some are already in investigational phases. I am very hopeful there will be a big change in the future.

NeurologyLive: What areas need more attention in the epilepsy community?

There are several things. We focus a lot on seizures in people with epilepsy, but people also have intractable spikes, sometimes quite frequent, especially in children. Spikes interfere with brain processing. In my lab, we have shown that hippocampal spikes interrupt encoding of new information. Spikes during the night may interfere with memory consolidation.

Spikes outside the hippocampus may also alter the function of that tissue. I would like to see a new approach where we are not only looking at seizures but also looking at electrophysiological disturbances between seizures and trying to block those to reduce comorbidities.

People with epilepsy likely have altered connectivity, altered synaptic connections, differences in brain chemistry, and differences in white matter. Many of these things can be tackled.

We also need to go more in the direction of preventing epilepsy. We know the major risk factors. This might be the most important area, looking at injuries that occur and developing therapies to prevent seizures after those injuries.

Let me pause. There is one other thing I want to say, and it slipped my mind... oh, okay. The other critical thing, almost a holy grail, is this. When people with epilepsy come to see me and I give them a prescription, I say there is a 45 or 50 percent chance this will work and a 50 percent chance it will not. It would be wonderful to know which drugs will work for which people, in advance or immediately after giving the drug.

We need something measurable, such as changes in imaging or biomarkers, that tells us early that the drug is beneficial. Right now, I know a treatment works only when they come back and say they have not had a seizure. We need predictive biomarkers, some before treatment and others immediately after, that show the desired change in brain function.

NeurologyLive: How can we design more creative clinical trials and optimize treatment?

We are limited by what the FDA will accept, and that is an important and necessary limitation. The FDA is concerned with safety and efficacy. But we have to think about different ways of designing trials that are open to people with different kinds of epilepsy and different severities. Right now, people who enter trials usually have frequent seizures and refractory epilepsy. That is not how most people with epilepsy live. People with occasional seizures do not qualify. It would be good to have other methods, maybe measuring time to next seizure or inter seizure intervals.

Also, epilepsy has more than seizures. It causes cognitive changes, mood changes, and multiple impacts. We need to look at treatment effects on those too. A successful drug trial might say patients on a drug had a 38 percent reduction in seizures versus 15 percent on placebo. I do not know what that means. Is 38 percent useful? Probably not very. We need treatments that make a big difference. We have enough that make modest differences. The FDA has to rethink how it evaluates meaningful outcomes. A statistical improvement does not necessarily correlate with employability, mood, disability, cognition, risk of dying, or independence. We really have to think about the whole picture.

NeurologyLive: Is there anything else you would like to say about the award or the epilepsy field?

Epilepsy management, including diagnosis, treatment, and research, has to be collaborative. We are long past the days of someone working in a little lab by themselves and making the kinds of changes you can make with larger collaborations.

I had the pleasure of serving as Editor in Chief of Epilepsia for nine years. That job ended last year. Over those nine years, I saw more papers submitted as national and international collaborations.

Drug studies from Europe now involve all the centers collaborating across countries. Electrophysiology research I have done includes me in Philadelphia, my colleague in Zurich, another in Germany, another at Mayo Clinic, and another at Stony Brook.

We need to facilitate and foster these collaborations. The more people involved, to a point, the more ideas, the better the insights, and the more generalizable the data. That is what will be useful for all of us.

Transcript edited for clarity. Click here for more AES 2025 coverage.