Eliminating Ischemic Spinal Cord Injury and Paralysis after Aortic Aneurysm Surgery

Project Summary/Abstract Each year, 24,000 new cases of thoracoabdominal aortic aneurysms (TAAA) are diagnosed in the United States. The aging population, poor dietary habits, and smoking lead to a higher incidence of cardiovascular disease that contributes to an increasing incidence of aortic aneurysms (AA) that are repaired surgically either through open

chest repair (OR) or thoracic endovascular aortic repair (TEVAR). Both repairs can lead to paraplegia, the most feared and devastating complication of the surgery, which significantly worsens the quality of life and lifespan of the patient.1-8 The rate of paraplegia after OR is 9.2-20% while the rate after TEVAR is 15-17%1,7-10,14-18. The

global market size for aortic aneurysms in 2018 was $2.5 billion with an expected compound annual growth rate of 8.6% for 2019-2026.19 Paraplegia can cost over $2.3 million over the patient’s lifetime.20 Therefore, eliminating paraplegia after both methods of AA repair represents an extreme urgency as well as an enormous challenge.

Little progress has been made since the first aortic repair surgery resulting in paralysis, likely reflecting the lack of spinal cord (SC) tissue availability from patients and the lack of large animal models of TEVAR. Therefore, new, innovative approaches are needed to make substantial progress in the field. Paraplegia after aortic repair

is a “man-made” pathology and occurs in a controlled medical environment, thus prevention is feasible in a clinical setting. Because AA patients are admitted to the hospital one day before surgery, an unprecedented opportunity exists to collect their blood, urine, and cerebrospinal fluid (CSF) to study the molecular malfunction

leading to paraplegia after surgery. The current understanding is that the SC injury caused by OR vs TEVAR are distinct, heightening the need for specific therapeutic interventions to prevent paraplegia. It is hypothesized that SC injury after OR vs TEVAR are two different pathologies that will require specific, independent considerations.

The first objective of this proposed conference is to discuss potential mechanisms on what can be done to address the problem of paralysis after AA repair surgery, build up collaboration teams, generate new, innovative ideas in specific areas of research aimed at preventing SC injury, and bring together physicians, academia, and

industry to solve this problem. At the end of the conference, a clear road map will be anticipated of the potential strategies that will be taken from the clinical side and the basic research side to solve the problem. Discussions will focus on the worldwide clinical perspective of AA surgical repair, recent progress in the prevention of

paraplegia, and future development of more effective clinical and research strategic plans to define the goal and the plan needed to eliminate paraplegia. The second objective of the conference is to establish a national, multicenter biobank with locations throughout the country that will store blood, CSF, and urine of paralyzed and

non-paralyzed patients after AA surgery that will be critical for understanding the molecular mechanisms causing paralysis after either OR or TEVAR. Only with a better understanding of the molecular malfunctions leading to paraplegia after AA repair will we be able to design future therapeutic prevention and treatment.