Vagus nerve stimulator placement, corpus callostomy, or ketogenic diet initiation could help children with pharmacoresistent epilepsy

According to a study, “Seizure control and quality of life in children with epilepsy after vagus nerve stimulator placement, corpus callostomy, or ketogenic diet initiation” [1]:

Vagus nerve stimulator placement, corpus callostomy, and ketogenic diet was successful in reducing both generalized and focal seizure types, [with] ketogenic diet showing a trend towards slightly better success.

Parents of 210 patients, who had 292 (VNS, n=150; CC, n=44; KD, n=98) treatment modalities, agreed to participate in a phone interview. 60% were male with ages ranging from 8 months to 20 years. Seizure control, cognitive and behavioral factors, quality of life and treatment satisfaction was rated via a 9-item telephone questionnaire.

Improvements observed in cognitive and behavioral domains, better seizure control and less falls positively affected quality of life. Parent overall satisfaction was greater than 75%, which far outweighed seizure reduction or behavioral improvements.

These findings support palliative management for those with pharmacoresistant epilepsy who are not candidates for surgical resection.

CURE Conversations: Timothy Simeone, PhD

Get to know our researchers! CURE Conversations features interviews with our scientists and discusses the focus of their work as well as recent breakthroughs in the field of epilepsy research. These investigators are the people behind the scenes who work diligently in the labs to unravel the mysteries of epilepsy, studying the science that will one day lead to cures for the epilepsies.

Can you share some details about what you do?
Our group investigates mechanisms of hyperexcitability and novel anti-seizure therapeutics. The epileptic brain is quite different from the non-epileptic brain in many ways, including its response to therapeutics. Therefore, we employ animal models that naturally develop epilepsy to tease out novel mechanisms that may have been missed with models that rely on wild-type brains. We utilize in vivo and in vitro electrophysiological and neurobiological techniques to examine multiple levels of activity—from whole brain to neuronal networks to single neurons to intracellular organelles (mitochondria) and signaling.

What motivated you to become interested in this area of research?
I find the brain absolutely fascinating. From single neurons to networks, it is beautiful and baffling. It seems deceptively simple on the surface, but unimaginably complex as you dive deeper. How does it work? What processes lead to dysfunction? There seem to be multiple paths that can lead to epilepsy and with each mechanistic discovery we learn something about the brain and potentially how to fix it. Fascinating and promising. I naturally gravitated towards studying epilepsy. On a more personal note, early in my graduate career it was made clear to me that many discoveries and therapeutics used for epilepsy were applicable in many other neurological disorders. I grew up with family members that are afflicted with neurological disorders of varying severity, and I knew I wanted to study something that could potentially help a wide array of people. If my team and collaborators are able to make a contribution—no matter how small—that furthers our understanding of epilepsy or translates into helping patients, we will deem our entire careers successful.

What is your current research focus?
We are currently attempting to elucidate the anti-seizure mechanism of the ketogenic diet. I was first introduced to the ketogenic diet as a post-doctoral fellow in the laboratory of Jong M. Rho, M.D. As everyone who has interacted with Dr. Rho would agree, his passion for the ketogenic diet (KD) is infectious. He instilled in me a belief that the KD holds the key to discovering novel molecular targets that will be useful in treating a significant portion of patients with refractory epilepsy. In the lab, we try to figure out what changes the KD induces in the brain of epileptic animals and then manipulate the identified targets with pharmacologic and genetic techniques to see whether seizures are changed and/or reduced.

Can you share some of the latest findings?
We have found that a molecular target useful in treating Type II Diabetes Mellitus may be responsible for much of the anti-seizure and neuroprotective effects of the KD. At the time of our initial discovery, we were completely ignorant of ongoing research indicating that this target may also have therapeutic use in other neurological disorders such as Alzheimer’s and Parkinson’s diseases. This raises the possibility that many neurological disorders may have commonalities that perhaps differ in regional expression and degrees of severity, resulting in the wide array of disorders and symptoms. Therefore, our findings from researching the KD may be applicable to other neurological disorders. We are currently preparing a manuscript detailing our findings thus far, which will hopefully be published by the time this interview is published.

What is the ultimate goal for the research and how will it impact patients with epilepsy?
Our ultimate goal is to identify viable targets that will aid in the development of new anti-seizure medication, specifically for refractory epilepsies. Ideally, these novel treatment(s) will treat the disease and not just the symptoms.

What accomplishment—personal or professional—are you most proud of?
My children are and continue to be my biggest accomplishment. They have taught me so much in such a short time. Not the least is giving me a better understanding and empathy for parents of children with epilepsy. Outwardly, I am not an emotional person, to which my wife will attest, but the stories that parents and patients share through the AES, CURE, and EFA mediums affect me deeply. The empathy my laboratory personnel (I have been lucky to find stellar technicians, students, and collaborators) and I feel for families dealing with epilepsy continues to align our investigational goals with the mission of CURE and drive our research forward.