Chadi Tannoury

The molecular basis of intervertebral disc degeneration

BACKGROUNDnIntervertebral disc (IVD) degeneration remains a clinically important condition for which treatment is costly and relatively ineffective. The molecular basis of degenerative disc disease has been an intense focus of research recently, which has greatly increased our understanding of the biology underlying this process.nnnPURPOSEnTo review the current understanding of the molecular basis of disc degeneration.nnnSTUDY DESIGNnReview article.nnnMETHODSnA literature review was performed to identify recent investigations and current knowledge regarding the molecular basis of IVD degeneration.nnnRESULTSnThe unique structural requirements and biochemical properties of the disc contribute to its propensity toward degeneration. Mounting evidence suggests that genetic factors account for up to 75% of individual susceptibility to IVD degeneration, far more than the environmental factors such as occupational exposure or smoking that were previously suspected to figure prominently in this process. Decreased extracellular matrix production, increased production of degradative enzymes, and increased expression of inflammatory cytokines contribute to the loss of structural integrity and accelerate IVD degeneration. Neurovascular ingrowth occurs, in part, because of the changing degenerative phenotype.nnnCONCLUSIONSnA detailed understanding of the biology of IVD degeneration is essential to the design of therapeutic solutions to treat degenerative discs. Although significant advances have been made in explaining the biologic mediators of disc degeneration, the inhospitable biochemical environment of the IVD remains a challenging environment for biological therapies.

Does Lumbar Facet Fluid Detected on Magnetic Resonance Imaging Correlate With Radiographic Instability in Patients With Degenerative Lumbar Disease

Study Design. Retrospective radiographic/imaging study. Objective. The purpose of this study was to analyze the association between lumbar facet fluid on MRI and sagittal instability on flexion lumbar radiographs in patients with degenerative disease at L4–L5. We hypothesized that the amount of facet fluid on MRI correlates with instability on the flexion radiograph. Summary of Background Data. Although never formally studied, it has been suggested that lumbar facet fluid detected on MRI is indicative of spinal segment instability. Methods. Patients who underwent laminectomy or laminectomy and fusion for the treatment of degenerative lumbar disease at L4–L5 at our institution between 2002 and 2004 and who had preoperative lumbar MRI and anteroposterior and flexion-extension radiographs available for review were study eligible. Axial T2 MRI images through the L4–L5 facets were analyzed for facet fluid. The facet fluid index was calculated, i.e., the ratio of the sum of the width of fluid in each facet (bilateral) to the sum of the width of each facet (bilateral). Instability on the flexion radiograph was measured as percent anterior slip at L4–L5. Results. Fifty-one patients were included in the study, 28 (55%) of whom had facet fluid noted on MRI. Of those patients who did have facet fluid on the MRI, 23 of 28 had instability on the flexion lumbar radiograph and 5 of 28 had no instability. The mean facet fluid index and percent anterior slip for the 28 patients with MRI facet fluid was 0.12% and 11.1%, respectively. There was a positive linear association between these values (Pearson correlation coefficient of 0.90, P < 0.001). The positive predictive value of L4–L5 facet fluid on MRI as an indicator of radiographic instability was 82%. Conclusions. There is a close linear association between the facet fluid index and the amount of radiographic instability at L4–L5. Facet fluid on MRI should raise high suspicion of lumbar instability.

Cellular Therapy for Disc Degeneration

Study Design. Review article regarding the developing field of cellular therapies for symptomatic disc degeneration. Objective. To review the rationale and discuss the results of cellular strategies that have been proposed or investigated for disc degeneration. Summary of Background Data. Disc degeneration is a substantial clinical problem. Disc degeneration begins with a loss of disc cells and alterations in the extracellular matrix of the disc. One promising approach for this problem involves the use of cells transplanted to the degenerative disc to achieve functional tissue repair. Methods. The rationale for using cellular therapy for disc degeneration is discussed. The basic science studies involving cellular transplantation to the disc are reviewed and future directions of this line of research are discussed. Results. Although substantial work remains, the future of cellular therapies for symptomatic disc degeneration appears promising. Conclusion. Continued research is warranted to further define the optimal cell type, scaffolds, and adjuvants that will allow successful disc repair in human patients.

Intervertebral disk degeneration and emerging biologic treatments.

&NA; Although understanding of the biologic basis of intervertebral disk (IVD) degeneration is rapidly advancing, the unique IVD environment presents challenges to the development and delivery of biologic treatments. Acceleration of cellular senescence and apoptosis in degenerative IVDs and the depletion of matrix proteins have prompted the development of treatments based on replacing IVD cells using various cell sources. However, this strategy has not been tested in animal models. IVD degeneration and associated pain have led to interest in pathologic innervation of the IVD and ultimately to the development of percutaneous devices to ablate afferent nerve endings in the posterior annulus. Degeneration leads to changes in the expression of matrix protein, cytokines, and proteinases. Injection of growth factors and mitogens may help overcome these degenerative changes in IVD phenotype, and these potential treatments are being explored in animal studies. Gene therapy is an elegant method to address changes in protein expression, but efforts to apply this technology to IVD degeneration are still at early stages.

Sensory neurons and fibers from multiple spinal cord levels innervate the rabbit lumbar disc.

Zhang Y, Kerns JM, Anderson DG, Lee YS, Chen E-Y, Tannoury C, An HS: Sensory neurons and fibers from multiple spinal cord levels innervate the rabbit lumbar disc. Am J Phys Med Rehabil 2006;85:865–871. Objective:To establish the neurotransmission pathway from the lumbar L5/6 intervertebral disc (IVD) to the spinal cord in the rabbit. Design:Fluorogold particles injected into the posterior portion of the rabbit L5/6 IVD were traced by examining gold-positive neurons and fibers in the dorsal root ganglion (DRG) and spinal cord at various root levels. Results:Fluorogold-labeled neurons were observed bilaterally in primary afferent DRG neurons from the L3 through L5 segments; a small number of gold-labeled neurons were found at the L1 level. Fluorogold-labeled neurons were predominantly present in the ipsilateral DRG (the side of the injection) at the L5 level, but they were more equally distributed (on both sides) at the L4 and L3 levels. In the posterior horn of the spinal cord, Fluorogold particles were found in nerve fibers as rostral as the T12 level. Conclusions:Our study has shown that Fluorogold particles injected into the rabbit L5/6 IVD are taken up by primary sensory neurons in the DRGs and primary sensory fibers in the posterior horn of the spinal cord at multiple levels. This diffuse innervation pattern of the lumbar disc may help explain why discogenic back pain in humans is often poorly localized.

Aberrant right subclavian artery encountered during debridement of T2 osteomyelitis and associated phlegmon.

BACKGROUND CONTEXTnAn aberrant right subclavian artery is a rare congenital abnormality of the aortic arch. The anomalous origin for the right subclavian artery arises as the last branch of the thoracic aorta. In the most common anomalous form, the right subclavian artery passes posterior to both the esophagus and trachea as it crosses midline to supply the right upper extremity. The aberrant right subclavian artery is often not symptomatic, but it can cause dysphagia.nnnPURPOSEnTo describe a case of an aberrant right subclavian artery discovered during debridement of T2 osteomyelitis.nnnSTUDY DESIGNnCase report.nnnMETHODSnA 49-year-old woman with diabetes was transferred to our institution with bilateral lower extremity weakness and incontinence of bowel and bladder function. Examination revealed no motor function in quadriceps, hamstrings, tibialis anterior, extensor hallucis longus, or gastrocsoleus complex of her bilateral lower extremities.nnnRESULTSnSpinal computed tomography scan showed pathologic collapse of the T2 vertebra. Magnetic resonance (MR) demonstrated an abscess and a phlegmon anterior to T2. Magnetic resonance also demonstrated spinal cord compression at the T2 vertebral level, and T2-weighted MR demonstrated the presence of spinal cord signal changes.nnnCONCLUSIONSnWe report a rare case where an aberrant right subclavian artery was associated with a T2 osteomyelitis and paravertebral abscess. The intraoperative injury to this aberrant artery led to the eventual death of the patient. When planning an anterior approach to the upper thoracic region, surgeons should be aware of this anatomic variant of the subclavian artery and its associated aberrant recurrent laryngeal nerve.

Clinical and Finite Element Analysis of Acute Whiplash

Study Design: A prospective 1-year follow-up study of whiplash patients presenting with neurological signs/or symptoms (WADIII), and whiplash patients with neck pain but no neurologic findings (WADI/II). Objective: We hypothesize that WADI/II and WADIII are distinct entities, with regards to clinical presentation, pathoanatomy, and prognosis. Summary of Background Data: symptoms associated with whiplash injury range from mild neck pain (WADI/II), to injuries associated with neurologic sequellae (WADIII). To date, literature considers whiplash associated disorders (WAD) a single clinical and pathologic entity, with different grades of severity (WADI-IV). Methods: Thirty one subjects were divided into a WADIII study group and a WADI/II comparison group. All subjects underwent H&P, radiographic evaluations, and clinical outcome measures (collected at 3, 6, and 12 months). Statistical analysis was performed (Student T-test, Wilcoxon Signed-Rank test) with significance set at p=0.05. A finite element analysis (FEA) technology (SCOSIA©) was used to predict stresses within the neuraxis. Results: At day 0: Better neurologic assessments, functional performances, and higher quality-of-life measurements were noted in WADI/II compared to WADIII. VAS scores were comparable. At 12 months: Both groups reported improvements in neurologic status and disability symptoms. However functional recovery and quality-of-life measures significantly improved in WADIII, and conversely deteriorated in WADI/II along with notable worsening of pain symptoms. Litigation claims were comparable. FEA predicted higher stress within the neuraxis of WADIII, notably in subjects with preexisting stenosis and odontoid retroflexion. Conclusion: WADI/II and WADIII are distinct entities. Musculoskeletal injury precipitates WADI/II pain symptoms while neuronal stretching leads to WADIII neurologic injuries, which are mostly recoverable.