Cervical spondylosis with spinal cord encroachment: should preventive surgery be recommended?

<p>Abstract</p> <p>Background</p> <p>It has been stated that individuals who have spondylotic encroachment on the cervical spinal cord without myelopathy are at increased risk of spinal cord injury if they experience minor trauma. Preventive decompression surgery has been recommended for these individuals. The purpose of this paper is to provide the non-surgical spine specialist with information upon which to base advice to patients. The evidence behind claims of increased risk is investigated as well as the evidence regarding the risk of decompression surgery.</p> <p>Methods</p> <p>A literature search was conducted on the risk of spinal cord injury in individuals with asymptomatic cord encroachment and the risk and benefit of preventive decompression surgery.</p> <p>Results</p> <p>Three studies on the risk of spinal cord injury in this population met the inclusion criteria. All reported increased risk. However, none were prospective cohort studies or case-control studies, so the designs did not allow firm conclusions to be drawn. A number of studies and reviews of the risks and benefits of decompression surgery in patients with cervical myelopathy were found, but no studies were found that addressed surgery in asymptomatic individuals thought to be at risk. The complications of decompression surgery range from transient hoarseness to spinal cord injury, with rates ranging from 0.3% to 60%.</p> <p>Conclusion</p> <p>There is insufficient evidence that individuals with spondylotic spinal cord encroachment are at increased risk of spinal cord injury from minor trauma. Prospective cohort or case-control studies are needed to assess this risk. There is no evidence that prophylactic decompression surgery is helpful in this patient population. Decompression surgery appears to be helpful in patients with cervical myelopathy, but the significant risks may outweigh the unknown benefit in asymptomatic individuals. Thus, broad recommendations for decompression surgery in suspected at-risk individuals cannot be made. Recommendations to individual patients must consider possible unique circumstances.</p

Inhibition of c-MYC expression through disruption of an RNA.protein interaction using antisense oligonucleotides

grantor: University of TorontoThe proto-oncogene c-'myc' encodes a protein that regulates cellular proliferation and differentiation. Conditions that alter the stability of c-'myc' mRNA can lead to overexpression of the gene resulting in uncontrolled cell growth. Synthetic therapeutic agents, known as Antisense Oligonucleotides (ODN), can bind to target mRNA and inhibit its expression. A previously characterized protein, the coding region stability determinant-binding protein (CRD-BP), binds the coding region determinant (CRD) of c-' myc' mRNA and is believed to protect it from endonucleolytic cleavage. Accordingly, we hypothesized that ODNs directed towards the CRD of c-' myc' mRNA could prevent CRD-BP·RNA interactions, thus decreasing c-'myc' expression. Using an 'in vitro' gel shift assay we demonstrated that ODNs inhibit the CRD-BP·c-' myc' mRNA interaction. The most effective ODN, CRD-ODN4, exhibited a sequence-specific and concentration-dependent inhibition of the RNA·CRD-BP interaction. Up to 65% inhibition of protein expression and 45% inhibition of mRNA expression was observed with 200 nM of CRD-ODN4. Conversely, a 2 '-O-methyl ODN derivative targeting the translational initiation codon (ODN-AUG) reduced c-'myc' protein but increased mRNA levels 2-fold. Additionally, CRD-ODN4 was more effective at inhibiting K562 cell growth. The results observed both 'in vitro' and within cells support the hypothesis that CRD-ODN4 is capable of disrupting the interaction between CRD-BP and c-'myc' mRNA and this disruption decreases c-'myc' expression and functional effects in cells. (Abstract shortened by UMI.)M.Sc

Chiropractic &amp; Osteopathy BioMed Central Review

Cervical spondylosis with spinal cord encroachment: should preventive surgery be recommended