69. Ischemic spinal nerve root injury secondary to herniated lumbar intervertebral disc

Abstract

BACKGROUND CONTEXT The painful clinical sequelae associated with sciatica secondary to intervertebral disc herniation have been traditionally attributed to mechanical compression of the spinal nerve root. More recent studies have also implicated inflammatory mediators and microvascular changes in the pathogenesis of acute sciatica. The application of nucleus pulposus (NP) to a spinal nerve root has been shown to induce thrombus formation in the associated nerve microvasculature and result in greater injury to the axons in the center than in the periphery, suggesting an ischemic mechanism of injury. The spinal nerve blood flow changes that are associated with nerve dysfunction seen in acute sciatica offer a potential target for therapeutic intervention. The VEGF angiogenic cytokines have been demonstrated to be potent stimulators of the differentiation and function of vascular endothelial cells after injury. PURPOSE To determine the relationship between the severity of spinal nerve root injury in patients with acute sciatica secondary to lumbar disc herniation (AS/LDH) undergoing surgical discectomy and the levels of VEGF-A and VEGF-B in serum, spinal nerve root lavage and disc tissue homogenate. STUDY DESIGN/SETTING ELISA cytokine immunoassay. PATIENT SAMPLE Twenty-four patients with AS/LDH of less than 16 weeks duration, undergoing laminectomy discectomy surgery. OUTCOME MEASURES VEGF-A and VEGF-Bconcentrations (pg/ml) in herniated nucleus pulposus homogenate (HNP-H), spinal nerve root lavagate (SN-L) and serum. METHODS At the time of surgery, the spinal nerve root was lavaged with 5 cc of saline, the extruded disc tissue removed surgically and serum samples were obtained. Disc and lavagate samples were stored in physiological buffer with protease inhibitors at -80° C. The concentrations of VEGF-A and VEGF-Bin disc tissue homogenate, serum and lavagate samples were measured in triplicate using ELISA immunoassay. Research ethics committee approval was obtained. RESULTS In AS/LDH patients, VAS pain and significant spinal nerve root deficit scores (3.0 - 4.0/5) correlated closely with serum and HNP-H tissue levels of VEGF-A and VEGF-B (Pearson r=0.78). In 11/24 patients, elevated VEGF-A and B concentrations correlated to a moderate degree with TNFα and IL-2, 6 and 8 inflammatory cytokine levels (r=0.61). Low concentrations of VEGF and inflammatory cytokine concentrations were seen in all SN-L test samples. CONCLUSIONS In patients with acute sciatica secondary to lumbar disc herniation, the severity of spinal nerve injury appears to be related to a combined mechanism, involving ischemic and inflammatory components. This research study was funded by grants from the National Institutes of Health, Bethesda, USA and from the University of British Columbia Orthopaedic Research Excellence Fund. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.