Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level.

Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient's environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P < 0.001) independently from mechanical ventilation and preserved sensory function by multiple regression analysis. We present evidence that spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner.

Long-term functional outcome in patients with acquired infections after acute spinal cord injury.

OBJECTIVE: To investigate whether prevalent hospital-acquired pneumonia and wound infection affect the clinical long-term outcome after acute traumatic spinal cord injury (SCI). METHODS: This was a longitudinal cohort study within the prospective multicenter National Spinal Cord Injury Database (Birmingham, Alabama). We screened datasets of 3,834 patients enrolled in 20 trial centers from 1995 to 2005 followed up until 2016. Eligibility criteria were cervical SCI and American Spinal Cord Injury Association impairment scale A, B, and C. Pneumonia or postoperative wound infections (Pn/Wi) acquired during acute medical care/inpatient rehabilitation were analyzed for their association with changes in the motor items of the Functional Independence Measure (FIMmotor) using regression models (primary endpoint 5-year follow-up). Pn/Wi-related mortality was assessed as a secondary endpoint (10-year follow-up). RESULTS: A total of 1,203 patients met the eligibility criteria. During hospitalization, 564 patients (47%) developed Pn/Wi (pneumonia n = 540; postoperative wound infection n = 11; pneumonia and postoperative wound infection n = 13). Adjusted linear mixed models after multiple imputation revealed that Pn/Wi are significantly associated with lower gain in FIMmotor up to 5 years after SCI (-7.4 points, 95% confidence interval [CI] -11.5 to -3.3). Adjusted Cox regression identified Pn/Wi as a highly significant risk factor for death up to 10 years after SCI (hazard ratio 1.65, 95% CI 1.26 to 2.16). CONCLUSION: Hospital-acquired Pn/Wi are predictive of propagated disability and mortality after SCI. Pn/Wi qualify as a potent and targetable outcome-modifying factor. Pn/Wi prevention constitutes a viable strategy to protect functional recovery and reduce mortality. Pn/Wi can be considered as rehabilitation confounders in clinical trials.