A Clinical Trial Investigating Exercise on Neuronal Regeneration and Cognitive Functioning in Epilepsy
Abstract number :
3.185
Submission category :
2. Translational Research / 2A. Human Studies
Year :
2024
Submission ID :
639
Source :
www.aesnet.org
Presentation date :
12/9/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Alisha Cayce, – University of Southern California
Shariq Mohammad, PhD – University of Southern California
Michael A Bonaguidi, PhD – University of Southern california
Christianne Heck, MD, MMM, FAES – University of Southern California
Aidin Abedi, MD – University of Southern California
Nadiya Atai, MD PhD – University of Southern California
Jonathan J Russin, MD – University of Southern California
Rationale:
Animal models of Epilepsy have explored regenerative interventions of neurogenesis decline through exercise and have been able to demonstrate an increase in neurogenesis and cognitive performance upon exercise intervention (Mendonca F.N., et Al 2017). Neurogenesis is also important for human cognition, and we know that there is a decline in neurogenesis with longer disease duration (Amomthumkandy et Al 2022). In humans, there is currently no regenerative method to increase neurogenesis in Epilepsy patients, thus it was pertinent to conduct a clinical trial with Mesial Temporal Lobe patients who will undergo surgical resectioning of their hippocampus to determine if exercise could be an appropriate intervention to promote neurogenesis.
Methods: A 12 week exercise intervention was administered to MTLE patients. Fitness assessments were administered pre and post exercise intervention, assessing blood pressure, VO2 max, and total distance of a 4 and 6 minute walking test. Seizure frequency was noted to determine patient safety throughout the trial. Neuropsychological assessments that included domains: WHO-UCLA AVLT for learning (Trial V) and memory (summary score), Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) for intelligence, and Rey Complex Figure Test (RCFT) for visuospatial memory were conducted pre and post intervention. Surgically resected tissue upon completion of the exercise trial was processed for immunohistochemistry with Dcx and Prox1 markers to quantify immature neuron levels.
Results: Preliminary data from two completed patients show positive effects of the exercise intervention. Patient 1 presented improvement in their resting heart rate of 4% and physical working capacity of 15% increase at 150 bpm, and their walking distance increased by 40% in the 6 minute test. Additionally, they demonstrated improvement in intelligence, nonverbal reasoning, processing speed, and auditory verbal learning tests. Patient 2 improved VO2 max capacity by 27% and cognition in visual memory. Both patients did not increase seizure frequency during the trial. Neurogenesis levels for both patients were in line with cross-sectional historical controls with disease durations of 11 years and 24 years, who had not undergone the exercise intervention.
Conclusions: In an attempt to determine the link between exercise on overall fitness, cognition and neurogenesis, we have demonstrated some improvements in intelligence, nonverbal reasoning and verbal learning tests with 2 completed patients. Ongoing recruitment will increase sample size to verify our preliminary conclusions.
Funding: Eli and Edythe Broad Innovation Awards in Stem Biology and Regenerative
Medicine: Path to Public Funding
Translational Research