Background After traumatic spinal cord injury (SCI), there is increased risk of venous thromboembolism (VTE), but chemoprophylaxis (PPX) may cause expansion of intraspinal hematoma (ISH). Methods Single-center retrospective study of adult trauma patients from 2012–2015 with SCI. Exclusion criteria: VTE diagnosis, death, or discharge within 48 hours. Patients were dichotomized based on early (≤48 hours) heparinoid and/or aspirin PPX. ISH expansion was diagnosed intraoperatively or by follow-up radiology. We used multivariable Cox proportional hazards to estimate the effect of PPX on risk of VTE and ISH expansion controlling for age, ISS, complete SCI, and mechanism as static covariates and operative spine procedure as a time-varying covariate. Results 501 patients with SCI were dichotomized into early PPX (n=260, 52%) and no early PPX (n=241, 48%). Early PPX patients were less likely blunt-injured (91% vs 97%) and had fewer operative spine interventions (65% vs 80%), but age (median 43 vs 49 years), ISS (median 24 vs 21), admission ISH (47% vs 44%), and VTE (5% vs 9%) were similar. Cox analysis found that early heparinoids was associated with reduced VTE (HR 0.37, 95% CI 0.16–0.84) and reduced pulmonary embolism (PE) (HR 0.20, 95% CI 0.06–0.69). The estimated number needed to treat with heparinoids was 10 to prevent one VTE and 13 to prevent one PE at 30 days. Early aspirin was not associated with reduced VTE or PE. Seven patients (1%) had ISH expansion, of which 4 were on PPX at time of expansion. Using heparinoid and aspirin as time-varying covariates, neither heparinoids (HR 1.90, 95% CI 0.32–11.41) nor aspirin (HR 3.67, 95% CI 0.64–20.88) was associated with ISH expansion. Conclusion Early heparinoid therapy was associated with decreased VTE and PE risk in SCI patients without concomitant increase in ISH expansion. Level of Evidence Level IV (Therapeutic)

As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs) provide great capability for tissue regeneration, particularly in spinal cord injury (SCI). However, despite significant progress made in translation of iPSC-derived neural progenitor cells (NPCs) to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NPCs before transplantation are top priorities to overcome. In this study, we developed a safe and cost-effective pipeline to generate clinically relevant NPCs. We first isolated cells from patients’ urine and reprogrammed them into iPSCs by non-integrating Sendai viral vectors, and carried out experiments on neural differentiation. NPCs were purified by A2B5, an antibody specifically recognizing a glycoganglioside on the cell surface of neural lineage cells, via fluorescence activated cell sorting. Upon further in vitro induction, NPCs were able to give rise to neurons, oligodendrocytes and astrocytes. To test the functionality of the A2B5+ NPCs, we grafted them into the contused mouse thoracic spinal cord. Eight weeks after transplantation, the grafted cells survived, integrated into the injured spinal cord, and differentiated into neurons and glia. Our specific focus on cell source, reprogramming, differentiation and purification method purposely addresses timing and safety issues of transplantation to SCI models. It is our belief that this work takes one step closer on using human iPSC derivatives to SCI clinical settings.

Neuropathic pain develops in 40-70% of spinal cord injury (SCI) patients and markedly compromises quality of life. We examined plasma from SCI patients for autoantibodies to glial fibrillary acidic protein (GFAP) and collapsin response mediator protein-2 (CRMP2) and evaluated their relationship to the development of neuropathic pain. In study 1, plasma samples and clinical data from 80 chronic SCI patients (1-41 years post-SCI) were collected and screened for GFAP autoantibodies (GFAPab). Results from study 1 indicated that GFAPab were present in 34 of 80 (42.5%) patients, but circulating levels did not correlate with the occurrence of neuropathic pain. In study 2, longitudinal plasma samples and clinical data were collected from 38 acute SCI patients. The level of GFAPab measured at 16 ± 7 days post-SCI was found to be significantly higher in patients that subsequently developed neuropathic pain (within 6 months post-SCI) than patients who did not (T = 219; p = 0.02). In study 3, we identified CRMP2 as an autoantibody target (CRMP2ab) in 23% of acute SCI patients. The presence of GFAPab and/or CRMP2ab increased the odds of subsequently developing neuropathic pain within 6 months of injury by 9.5 times (p = 0.006). Our results suggest that if a causal link can be established between these autoantibodies and the development of neuropathic pain, strategies aimed at reducing the circulating levels of these autoantibodies may have therapeutic value.

Traumatic spinal cord injury (SCI) is a devastating injury causing significant morbidity and mortality. Experimental studies have demonstrated that SCI induced cellular damage and disruption of the blood-spinal cord-barrier can initiate an autoimmune response. This response is thought to be pathogenic and contribute to poor outcome. The objective of this research was to investigate whether human SCI mounts an autoimmune response to self-antigens. Plasma samples were collected longitudinally from SCI patients (n=18) at acute (T1, <48 hr) and subacute (T2, 2-4 wk) time points to probe western blots of human brain homogenates in order to screen patients for the presence of putative autoantibodies. To identify the corresponding antigens, 2-dimensional (2D) gel electrophoresis, western blot and liquid chromatography coupled with mass spectrometry (LC-MS/MS) analyses were performed. We found that 4 of 18 patients (22%) had novel immunoreactive bands ranging in size from 36-42 kDa present in subacute, but not in acute, plasma samples suggesting post-injury production. To identify the cross-reacting antigens, we separated brain proteins by 2D gel electrophoresis and identified 9 immunoreactive spots. Amino acid sequence analysis of these spots identified peptides that mapped to glial fibrillary acidic protein (GFAP). Our results suggest that approximately 22% of SCI patients generated autoantibodies to GFAP. Future studies will be required to determine if these autoantibodies contribute to the pathogenic sequelae of SCI.

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: Hydrocephalus is a rare complication of traumatic spine injury. A literature review reflects the rare occurrence with cervical spine injury. We present a case of traumatic injury to the lumbar spine from a gunshot wound, which caused communicating hydrocephalus. The patient sustained a gunshot wound to the lumbar spine and had an L4-5 laminectomy with exploration and removal of foreign bodies. At the time of surgery, the patient was found to have dense subarachnoid hemorrhage in the spinal column. He subsequently had intermittent headaches and altered mental status that resolved without intervention. The headaches worsened, so a computed tomography scan of the brain was obtained, which revealed hydrocephalus. A ventriculoperitoneal shunt was placed, and subsequent computed tomography scan of the brain showed reduced ventricle size. The patient returned to rehabilitation with complete resolution of hydrocephalus symptoms. Intrathecal hemorrhage with subsequent obstruction or decreased absorption of cerebrospinal fluid at the distal spinal cord was thought to lead to communicating hydrocephalus in this case of lumbar penetrating trauma. In patients with a history of hemorrhagic, traumatic spinal injury who subsequently experience headaches or altered mental status, hydrocephalus should be included in the differential diagnosis and adequately investigated.