H. F. El Sayed1, E. Tili2, J. Michaille3,4, H. E. Awad2 1Ohio State University,Department Of Surgery,Columbus, OH, USA 2Ohio State University,Department Of Anesthesiology,Columbus, OH, USA 3University Of Bourgogne,Dijon, , France 4Ohio State University,Department of Cancer Biology And Genetics,Columbus, OH, USA
Introduction:
Approximately 24,000 new cases of thoracic aortic aneurysms are diagnosed each year in the USA. Spinal cord ischemia (SCI) and paralysis is a devastating complication following thoraco abdominal aortic aneurysm (TAAA) open and endovascular repair. The rates of paralysis after TAAA repair range 5-15%, even with the adjunctive non-pharmacological preventive strategies such as cerebrospinal fluid (CSF) drainage and blood pressure management. However, our current strategies are not sufficiently effective to prevent and/or treat SCI after TAAA repair. Furthermore, the rates of paralysis in new interventions, such as thoracic endovascular aortic repair (TEVAR), the risk of paralysis is not significantly lower than open repair methods. Currently, there is no standard of- care pharmacological preventive treatment and, to our knowledge, no molecule is being tested for this purpose. Paraplegia is one of the most feared and devastating complications following TAAA and endovascular repair. Patients who developed paralysis after TEVAR suffer from high morbidity and mortality.
Methods:
We are working to identify microRNA signatures present in the CSF samples of patients undergoing TAAA repair, with and without paresis/paralysis. We aim to identify microRNAs that are associated with paresis/paralysis and that can be used as biomarkers of this event. Our study is limited to those patients where a spinal drain for CSF drainage is inserted (not emergency patients) to allow us repeated CSF sampling. Samples are being collected before surgery and 6, 12, 24, and 48 hours after surgery in all patients. Additional samples are collected in cases with neurological complications (ie. Patients that develop delayed paresis and come back at the hospital, as it was the case with the last patient) to differentiate between microRNAs present in the CSF of paralyzed vs non-paralyzed patients, as well as before and after TEVAR. We are also planning to run similar experiments with the plasma of these patients, to see if we will be able to identify a blood microRNA signature related to spinal cord ischemia. This method is less invasive and can be used for all patients, regardless of the spinal drain availability.
Results:
CSF samples are the analyzed for microRNA expression using NanoString technology arrays. Candidate microRNAs are further validated by qRT-PCR techniques using Taqman probes. Our current preliminary data make us confident that we will be able to identify microRNAs that can be used as biomarkers of paresis/weakness event.
Conclusion:
Patients that show the presence of the identified candidate microRNAs in their CSF, will be considered at high risk or “predisposed” to develop paresis and as such these patients should be followed up after they leave the hospital. We posit that the identified microRNAs can be further used for development of future therapeutics aimed at prevention of paralysis.