Exercise for Brain Regeneration in Epilepsy

Nearly 100 million Americans are affected by neurological disorders with an overall cost above $765 billion for the more prevalent conditions. Given this significant burden, effective treatments to prevent dementia and new disease modifying therapies are urgently needed. Regeneration of lost neurons with new ones (i.e., neurogenesis) is compromised at early stages of dementia and in part correlates with cognitive impairment in Alzheimer's disease. Boosting the neurogenesis delays the cognitive impairment in animal models of dementia and has been proven beneficial in improving the memory in rodent studies. Aerobic exercise is the most potent known stimulator of neurogenesis in animal models. A crucial next step is to translate endogenous regenerative strategies to people. The purpose of this study is to demonstrate the feasibility and investigate the effects of an exercise program on neurogenesis and cognitive improvement in epilepsy patients.

Neurogenesis studies in healthy and dementia patients have only been performed on postmortem tissue, which prevents investigation of treatment outcomes. Patients with mesial temporal lobe epilepsy (MTLE) typically do not respond to medications and uniquely among related dementia disorders undergo corrective surgical treatment, providing a unique opportunity to study the value of regenerative interventions on hippocampal electrophysiology and neurogenesis. Using this unique approach, this study will investigate the neurogenesis and cognitive improvement in epilepsy patients. Ten people with MTLE who are recommended for surgical treatment as part of their standard care will be enrolled and randomly assigned to High Impact (n=5) and Low Impact (n=5) exercise groups. The duration of exercise programs will be 12 weeks and study arms will undergo the same protocol except for the target heart rate which will be higher in the High-Impact group. Exercise will be performed at home using a recliner bike under the supervision of caregiver and study personnel. Participants will undergo cognitive, exercise and clinical assessment at baseline and after completing the three-month exercise therapy; then surgically resected tissue will be analyzed for regeneration and epileptiform activity. The investigators will assess whether exercise would yield clinical benefits in terms of seizure frequency/intensity or cognitive ability, and whether the ability of the adult human brain to self-repair can be enhanced. It is hypothesized that the proposed exercise regimen is feasible and will improve the neurogenesis levels and cognition.

Participants will be submitted to a 12-week high-impact aerobic exercise program using a recliner bike with three sessions per week. The exercise protocol takes 45 minutes per session and consists of five minutes of warm-up, 30 minutes of cycling with progressive increase in intensity until the target heart rate (80% of maximum) is reached, followed by 10 minutes of cool down.

Participants will be submitted to a 12-week low-impact aerobic exercise program using a recliner bike with three sessions per week. The exercise protocol takes 45 minutes per session and consists of five minutes of warm-up, 30 minutes of cycling with progressive increase in intensity until the target heart rate (40% of maximum) is reached, followed by 10 minutes of cool down.

The Rey Auditory Verbal Learning Test (RAVLT) is a validated test evaluating verbal learning and memory. In this test, lists of words are read to the participants in consecutive trials. Trial V is the 5th attempt at recalling the first list of words.

The Rey Auditory Verbal Learning Test (RAVLT) is a validated test evaluating verbal learning and memory. In this test, lists of words are read to the participants in consecutive trials. Summary score is the sum of number of words learned over five learning trials.

Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) is a validated test of cognitive ability and intelligence. Matrix reasoning is among the tasks included in WAIS-IV which is used to assess non-verbal abstract problem solving and inductive reasoning.

Rey Complex Figure Test (RCFT) is a standardized test of visuospatial memory. Performance will be scored based on the delayed recall trial of the RCFT.

Inclusion Criteria: Age of 18 years or older Medically resistant mesial temporal lobe epilepsy Candidacy for standard or selective temporal lobectomy Exclusion Criteria: Age of older than 65 years Pregnancy Physical disabilities or medical conditions preventing from participation in exercise program Inability to receive exercise equipment at home Cognitive/developmental disabilities restricting the participation in exercise program

Gooch CL, Pracht E, Borenstein AR. The burden of neurological disease in the United States: A summary report and call to action. Ann Neurol. 2017 Apr;81(4):479-484. doi: 10.1002/ana.24897. No abstract available.