Primary spinal cord injury is followed by secondary, biochemical, immunological, cellular changes in the injured cord A review article written by Brian Kwon looking critically at the use of hypothermia for SCI. It shows that it is neuroprotective in some settings (i.e. cardiac arrest). However, there are 25 animal studies with mixed results and only eight human SCI studies. Importantly, they are all case series of local, not systemic hypothermia. And the last one published was in 1984. Rho is a critical molecule in SCI. Rho ultimately inhibits axonal growth cone proliferation. Stopping RHO therefore will promote the growth cone. There are two drugs that ultimately targets rho. These are anti nogo antibodies and cethrin both of which ultimately inhibit rho. President Obama lifted the ban on federal funding of stem cell research. This was a monumental occasion and was right around the time that the FDA approved the first trial of hESC for SCI. The FDA trial of Geron is with Thoracic ASIA A SCI patients with transplantation of ESC directly into the cord at 7 to 14 days after injury. Geron has provided evidence to the FDA that there is no teratoma formation with transplantation of a human ESC to a rat or mouse. However, we do not know what will happen in a human to human transplant. In conclusion, use of steroids in setting of SCI is diminishing. There is no clinical evidence to support use of systemic hypothermia. Current clinical trials of pharmacologic therapy include Minocycline and RILUTEK(r) (riluzole) for neuroprotection, Anti-Nogo Antibodies and Cethrin(r) for axonal growth by ultimately inhibiting Rho. There is only one small study supporting safety, not efficacy of OEC transplantation.
Cahill et. al. published a large review of the use of BMP in spinal fusions. They reviewed the nationwide inpatient database, which represents approximately 25% of use U.S. Community Hospitals from the years 2002 to 2006. This included over 300,000 fusion type procedures. They noted increased complications with the use of anterior cervical procedures specifically increased complications with increased dysphasia and wound complications. Due to these concerns, the Food and Drug Administration released last year a public health notification about the potential life threatening complications related to the use of BMP in anterior cervical spine fusions. Joseph & Rampersaud noticed a 20% incidence of heterotopic ossification in patients undergoing this procedure versus only 8% for patients who had undergone fusions without BMP. Wong et. al. published a report on five cases of neurologic injury that relate to the use of BMP and the formation of heterotopic bone. Again, the suggestion of a barrier or closure defect was brought up and this may help minimise the risks; however, further work is noted. Multiple authors have noted a phenomenon of osteolysis occurring around graft fusion sites for the use of BMP. McCullen et. al. evaluated that 32 levels in 26 patients who had undergone a TLIF procedure. It is unclear the carcinogenic and tetraogenic effects of the use of BMP in the spine and also, the effects of repeat exposures on BMP has yet to be addressed. Finally, the long term cost and benefits of the use of BMP on the health care system has yet to be fully addressed. So in conclusion, BMP2 is effective in producing fusions especially in challenging environments, deformity, smoking and infection. However, the complications continue to be a concern especially with regards to interbody fusions as well as in the cervical spine.
