Acute spinal cord injury (SCI) in both the military and civilian settings requires immediate emergency transport to a trauma center and emergency critical care to stabilize the patient and evaluate the level and severity of injury. Critical care begins with emergency medical technicians who evaluate and transport the patient, the emergency department physicians seeing the patient on admission, and the neurosurgeons or orthopedists who must determine whether, when, and how to realign and stabilize the spine. These decisions are informed by neuroradiological findings, especially magnetic resonance imaging (MRI). Protocols for critical care in the first few weeks following SCI in the intensive care unit can include post-operative pain control, respiratory support, cardiovascular management, bowel and bladder care, the initiation of early physical and occupational therapies, and psychological support. A huge team of healthcare professionals is required, and decisions must be coordinated across multiple departments and units. Although there are established standards of care for acute SCI, these vary across trauma centers, and there are in fact very few evidence-based studies of SCI critical care to provide solid guidance for the many treatment decisions facing the team. In short, even the best teams do not know what the best practices are. We are in critical need of more information about the physiology of acute SCI, the variety of critical care treatments and strategies employed by different practitioners, and how these variables may relate to long-term functional outcomes and quality of life, especially with respect to bladder and autonomic functions and their relationship to infection. Our objective is to provide a comprehensive prospective analysis of multiple variables in acute SCI that impact long-term outcomes. The three core hypotheses are: (1) Multiple critical care variables will be predictive of both sensory-motor and autonomic outcomes, and susceptibility to infections at 6 and 12 months after injury. (2) Quantitative MRI of cord damage and biomarkers of acute immune responses to injury will predict neurological outcomes at discharge and at 6 and 12 months. (3) Advanced analytics will yield novel predictors of outcome that will facilitate subsequent clinical trials.

We propose three aims:

Aim 1: Diagnosis: Building a knowledge network for acute SCI. A detailed prospective study of critical care practices and outcomes for SCI patients admitted to University of California at San Francisco (UCSF)/San Francisco General Hospital (SFGH) and UCSF/Fresno will be conducted over a 3-year period, to build a knowledge network for acute SCI diagnostics.

Aim 2: Prognosis: Predictive models and biomarkers. Currently, predictors of outcomes in patients with SCI are mainly descriptive scales of level and impairment such as the American Spinal Injury Association (ASIA) Impairment Scale. Clinical trials employ the ASIA-ISNSCI (International Standards for Neurological Classification of Spinal Cord Injury) motor and sensory levels and scores as predictors and outcomes, but there have been fewer studies of the prognostic value of physiological variables or acute care clinical practice. We will develop multidimensional prognostic indicators for predicting outcomes and stratifying patients using detailed physiological, imaging, and genetic datasets.

Aim 3: Data analysis and sharing. SCI is infrequent, multi-dimensional, and highly variable. It is therefore imperative that the efforts of the SCI research community are shared. The development of better predictors of outcome and methods for stratification will be advanced by sharing our data. We will adopt a formal data-sharing policy built around the highly successful model of the traumatic brain injury (TBI) initiatives, TRACK-TBI (Transforming Research and Clinical Knowledge in TBI) and TED (TBI Endpoints Development).

The study will be a prospective, non-interventional, observational analysis of multivariate predictors of selected functional outcomes after SCI. The patient cohorts will come from two level-one trauma centers in northern California: The UCSF/SFGH (~40 patients/year), and the Central Valley UCSF Trauma Center in Fresno (UCSF/Fresno) (~80 patients/year). Patients will be recruited to the study within 24 hours of admission, consented, and followed until discharge to rehabilitation. Details of rehabilitation practices and treatments will be sought, but the primary outcome measures will come from neuro-exams and interviews at 6- and 12-month follow-up sessions, aimed at evaluating sensorimotor function, bowel, bladder, and cardiovascular function, and the incidence of infections (including urinary tract infections) and neuropathic pain. The level of analysis will be tiered, with highly granular data in a cohort of rapid admission SCI patients coming from UCSF/SFGH (frequently within an hour of injury) and less granular data from the larger cohort at UCSF/Fresno.

The project has the potential to significantly improve our understanding of the most acute changes after SCI and to improve our ability to predict long-term functional outcomes at the early time points after injury. And, we hope that sharing this information will help improve clinical decision making in the acute phase after injury.