Evolving Knowledge of Epilepsy Incidence and Etiology

Michael R. Sperling, MD: Approximately 3 million people in the United States have epilepsy. Of those, about 60% have focal seizures, also known as partial seizures. Focal seizures start in a part of the brain and last between 1 and 2 minutes. They involve both motor and nonmotor symptoms, for which there are many treatment options available. Together, we are going to discuss the use of new and exciting therapeutic options and provide a practical perspective on how the recent data apply to your clinical practice.

I am Michael R. Sperling, Baldwin Keyes Professor of Neurology at Thomas Jefferson University in Philadelphia, Pennsylvania, and director of the Jefferson Comprehensive Epilepsy Center and Clinical Neurophysiology Laboratory at Thomas Jefferson University. Participating today on our distinguished panel are: Dr. Kathryn Davis, assistant professor of neurology at the Hospital of the University of Pennsylvania in Philadelphia, and medical director of the Epilepsy Monitoring Unit and Penn Epilepsy Surgical Program at the University of Pennsylvania; Dr. Trevor Resnick, pediatric neurologist in the Department of Neurology at Nicklaus Children’s Hospital-Brain Institute of the Miami Children’s Health System in Miami, Florida, and clinical professor in the Department of Neurology at Herbert Wertheim College of Medicine in Miami; and Jesus Eric Pina-Garza, director of Pediatric Epilepsy at the TriStar Medical Group Children’s Specialists in Nashville, Tennessee. Thank you so much for joining us. Let’s begin.

To start, let’s first discuss diagnosis. I’d like to pose a question to our panel, and Dr. Pina-Garza will begin. Is the incidence and prevalence of epilepsy changing in any way? Are there new risk factors of which we might want to be aware? Do we need to think about new causes and etiologies for epilepsy that we haven’t thought about in the past?

Jesus E. Pina-Garza, MD: Thank you, Michael, definitely. I think that the background of epilepsy diagnosis and management is changing just like epilepsy itself. So, if we look at the last few decades, we have seen in our incidence and prevalence reports a higher number of cases. It makes a lot of sense, both in the pediatric and adult arena. In the past, the highest incidence was in children, the highest prevalence in adults. But we live longer. We have better technologies to keep people alive after brain injuries, and many of those patients may suffer from epilepsy. So that has contributed to a higher number of patients who suffer from this illness and clearly deserves more awareness.

The other part, which is related to the diagnosis and causes and things that we have to be aware of, is a complete new list of potential diagnoses. We have now the advantage of genetics that may in some cases provide us with answers. We have the discovery of autoimmune etiologies. In the past, we were aware that some patients responded to immunomodulation, but now we know why, and actually we can give a label to those diagnoses. So, clearly, there are more cases and there are more accurate diagnoses and more specific treatments.

Michael R. Sperling, MD: Would anyone like to add any comments to that?

Trevor J. Resnick, MD: Yes. Just to echo what Eric is saying, I think rather than the incidence of epilepsy necessarily having increased, our knowledge base has changed with newer diagnostic techniques and better awareness of networks. If you look at the diagram of etiologies, it’s changed because of our ability to identify different genetic mutations, looking at different markers of epilepsy and comorbidity. So the incidence may not have changed that much, but rather how we see epilepsy and how epilepsy etiology is changing a lot.

Michael R. Sperling, MD: Kate, I’ve been impressed that in recent years I’m seeing many more patients with autoimmune etiologies that we didn’t even know about more than a decade ago. What do you find in your practice and how do you diagnose these patients? What makes you suspicious?

Kathryn A. Davis, MD, MS, FAES: I think that, as you said, in the last decade there’s been an explosion in the knowledge about autoimmune diseases specific to epilepsy. And we discover new possible underlying etiologies within this realm weekly, it seems; that’s not actually the case, but it’s very frequently. I will think of an autoimmune potential cause particularly when a patient has a fairly explosive onset to their seizure disorder that’s unexplained. And I’m increasingly doing more diagnostic testing to rule out that as an etiology because it does dramatically change your treatment management. So that would involve serum studies and lumbar puncture to look for an underlying autoimmune etiology.

Michael R. Sperling, MD: So we have a bit of help. Recently, there have been several nice papers out of the Mayo Clinic group, Divyanshu Dubey, MD, is the first author on several of the papers, with 2 scoring systems. One is the APE [Antibody Prevalence in Epilepsy] scoring system, the other is the RITE [Response to Immunotherapy in Epilepsy], where one can have criteria. For each criterion within those various domains, are the seizures uncontrolled? What other kinds of symptoms? Are there coexisting cognitive or psychiatric symptoms and the like? One can actually come up with a score, and with a certain score the probability of an autoimmune etiology is rather higher. And, for that matter, one can then look at it and decide whether there’s a probability of response to therapy. So that’s been a significant advance. I think that one has to use it carefully though. You can’t apply it when people come in as status epilepticus because everybody has a positive score with new onset status. That’s one important thing. There are some of these other genetic causes that we’re learning more about. Is your sense that these are more inherited or spontaneous mutations?

Trevor J. Resnick, MD: Both.

Michael R. Sperling, MD: False dichotomy.

Trevor J. Resnick, MD: Right. Look, some are clearly inherited. The big issue that we have is that so many of these are characterized as variants of unknown significance or it’s a pathogenic mutation that in that patient it’s not necessarily pathogenic. So really it’s a landmine in terms of trying to negotiate where the specific genetic mutation in that patient is relevant or not. There are a lot of patients where you test the parents and the parents are negative, but they have a pathogenic mutation that would fit into the spontaneous mutations. But a lot of the times the parents have a mutation that does not express itself.

Transcript edited for clarity.