Abstract:

Spinal cord injury (SCI) may result in paralysis, sensory impairments, and autonomic dysregulation, including autonomic dysreflexia (AD). A clinical AD diagnosis is based on an increase in systolic blood pressure (SBP) of more than 20 mmHg to a stimulus applied below the neurological level of injury (NLI). In translational research studies, we have developed a new AD model in rhesus macaques after a partial injury to the cervical spinal cord using urodynamics with bladder filling as a stimulus to evoke an SBP response. Traditional and emerging vital signs were monitored using beat-to-beat recordings and non-invasive recording devices. Here, perfusion index (PI) monitoring by photo-plethysmography (PPG), using pulse-oximetry with non-invasive sensors attached above and below the NLI, allowed for concurrent assessments of cutaneous blood flow in tissues under differential sympathetic influence after SCI. An AI approach, using machine learning, identified PI as a novel and best biomarker for detection of AD in rhesus macaques after SCI. In ongoing translational SCI research studies, AD modulation by sub-acute grafting of human stem cells into the cervical spinal cord is being evaluated in rhesus macaques. In parallel studies, we are evaluating PI as a potential biomarker also for non-invasive detection of AD in human subjects with SCI. These laboratory and clinical research studies may have implications for the development and refinement of strategies to detect clinically silent episodes of AD in a community setting. 

Biography:

Leif A Havton, MD, PhD, serves as Acting Associate Chief of Staff, Research & Development, and Staff Physician in Neurology at VA Puget Sound Health Care System, Seattle, WA, and Professor, Department of Neurology, University of Washington School of Medicine, Seattle, WA. Dr. Havton’s translational research program studies neural repair after spinal cord injury (SCI) in laboratory models and human clinical studies. The Havton laboratory has a special research interest in motor and autonomic dysregulation after SCI in both upper and lower motor neuron injury models. The Havton laboratory also develops custom electron microscopy tools for ultrastructural mapping of autonomic fibers in the peripheral nervous system, including the vagus nerve and lumbosacral nerve roots. Dr. Havton is an experienced clinical and research mentor, and he has over 25 years of experience from leading and participating in collaborative and inter-disciplinary research studies. Dr. Havton’s research program has attracted generous research support from multiple Federal agencies, including the NIH, DoD, and VA, funding from private foundations, state agencies in California and New York, as well as philanthropic support.