Epilepsia^® Prize 2018 Clinical Science

An interview with Divyanshu Dubey. Read the winning article “Predictive models in the diagnosis and treatment of autoimmune epilepsy” at http://onlinelibrary.wiley.com/doi/10.1111/epi.13797/abstract

Who are you?

I am a neurologist in training. After graduation from Netaji Subhash Chandra Bose Medical College (Jabalpur, India), I completed a neurology residency at the University of Texas Southwestern Medical Center (Dallas, Texas) and then an autoimmune neurology fellowship at the Mayo Clinic in Rochester, Minnesota. Due to my interest in both central and peripheral neuroinflammatory disorders, I am currently in a fellowship in neuromuscular medicine at Brigham and Women’s Hospital and Massachusetts General Hospital in Boston, Massachusetts.

What got you interested in epilepsy research?

Working with my father, a child neurologist in Jabalpur, India, I gained an early exposure to pediatric epilepsy and neurodevelopmental disorders. This influenced my choice to enter into neurology. Throughout my academic training, I have been extremely lucky to have wonderful mentors who have provided guidance for my research endeavors. I have been fortunate to have research experiences that inspired me to better understand the role of autoimmunity in neurological disorders, especially epilepsy.

My interest in autoimmune epilepsy was promoted by my residency mentors, Dr. Steven Vernino and Dr. Olaf Stuve, and this was further nurtured during my training at the Mayo Neuroimmunology Laboratory and Autoimmune Neurology Clinic with Dr. Sean Pittock, Dr. Andrew McKeon, and Dr. Eoin Flanagan.

At the beginning of neurology residency, I initiated retrospective studies on autoimmune epilepsy and encephalopathy, evaluating the clinical presentation, EEG, and management of these under-recognized but treatable disorders. The results from these studies formulated the basis of the antibody prevalence in epilepsy (APE) score. We followed these studies by a meta-analysis of predictors of outcome of autoimmune epilepsy. We also conducted a prospective study evaluating epilepsy of unknown etiology for autoantibodies over a period of 1 year; nearly 20 percent of patients were seropositive for specific neural autoantibodies. The importance of autoimmune epilepsy and encephalopathy was also highlighted by our population-based epidemiology study which identified increasing recognition of autoimmune encephalitis over the years. These findings emphasize the potential for research in this exciting and upcoming field of neurology.

Explain for our general readership what question your study addressed and how you went about designing your study?

This study provides an objective framework to guide neural antibody testing and treatment of suspected autoimmune epilepsy. Establishing an autoimmune etiology and early initiation of immunotherapy can influence seizure outcomes. A scoring system based on clinical features and initial neurological assessment may enable earlier clinical diagnosis. Prediction of positive immunotherapeutic response justifies prompt initiation of immunotherapy, potentially limiting the extent of neurological disability.

What were the results and how do you interpret your findings?

In this study, we attempted to validate the APE score as a predictive model of neural antibody positivity in epilepsy cases. Patients were ascertained from Mayo Clinic’s index-linked medical record system from three Mayo Clinic centers (Rochester, MN; Scottsdale, AZ; and Jacksonville, FL) by searching for those whose serum, CSF, or both were evaluated in the Mayo Neuroimmunology Laboratory for neural antibodies. We modified the score to assess response to immunotherapy and outcome, and thus validated a second outcome measure, the Response to Immunotherapy in Epilepsy (RITE) score.What were the results and how do you interpret your findings?
In this study, we have validated the utility of the APE and RITE scores as predictive models for autoimmune epilepsy and initial immunotherapy response, respectively. With a high sensitivity and specificity, the APE score may guide the clinicians regarding decisions for further autoimmune evaluation including autoantibody testing. On the other hand, the RITE score may help select patients for immunotherapy trials and aid in counselling patients and caregivers. In certain cases, decisions to initiate immunotherapy can be complicated, especially if antibody evaluation is negative or antibodies of lower specificity for autoimmune epilepsy are detected. In such circumstances, the RITE score provides an evidence-based approach for therapeutic decision making. If the RITE score is low (<7), it may support redirection of diagnostic and therapeutic resources towards non-autoimmune etiologies. Alternatively, in patients with confirmed specific neural antibodies or a high APE score (≥4) (supporting an autoimmune etiology), a low RITE score may predict poor response to initial immunotherapy, guiding earlier consideration of second-line agents.

What next steps in epilepsy research are you taking and what are your career goals?

Autoimmune neurology has an immense potential for growth. I hope to utilize the clinical and laboratory experience gained during my training to continue research that will advance the mechanistic understanding, diagnostic techniques, and therapeutic options for autoimmune epilepsy. I am looking forward to joining the team at Mayo Clinic and Mayo Neuroimmunology Laboratory to continue this endeavor in the future.

What does the Epilepsia Prize mean for you, your laboratory, research institute, and your future?

I am extremely grateful to be given such a prestigious award at such an early stage of my career. Many people have contributed to the research being honored here. I am sure I speak for all of them when I say that we are incredibly proud that our work is being recognized. This award highlights the importance of autoimmunity within epilepsy. I believe this positive reinforcement will strengthen our resolve to continue meaningful clinical and translational research within autoimmune neurology.

Astrid Nehlig and Michael Sperling
Editors-in-Chief, Epilepsia