Reliable Magnetic Resonance Imaging Based Grading System for Cervical Intervertebral Disc Degeneration

STUDY DESIGN: Observational. PURPOSE: To develop a simple and comprehensive grading system for cervical discs that precisely, consistently and meaningfully presents radiologic and morphologic data. OVERVIEW OF LITERATURE: The Thompson grading system is commonly used to classify the severity of degenerative lumbar discs on magnetic resonance imaging (MRI). Inherent differences in the morphological and physiological characteristics of cervical discs have hindered development of precise classification systems. Other grading systems have been developed for degenerating cervical discs, but their versatility and feasibility in the clinical setting is suboptimal. METHODS: MRIs of 46 human cervical discs were de-identified and displayed in PowerPoint format. Each slide depicted a single disc with a normal (grade 0) disc displayed in the top right corner for reference. The presentation was given to 25 physicians comprising attending spine surgeons, spine fellows, orthopaedic residents, and two attending musculoskeletal radiologists. The grading system included Grade 0 (normal height compared to C2-3, mid cleft still visible), grade 1 (dark disc, normal height), grade 2 (collapsed disc, few osteophytes), and grade 3 (collapsed disc, many osteophytes). The ease of use of the system was gauged in the participants and the interobserver reliability was calculated. RESULTS: The intraclass correlation coefficient for interobserver reliability was 0.87, and 0.94 for intraobserver reliability, indicating excellent reliability. Ninety-five percent and 85 percent of the clinicians judged the grading system to be clinically feasible and useful in daily practice, respectively. CONCLUSIONS: The grading system is easy to use, has excellent reliability, and can be used for precise and consistent clinician communication.

Epidural Hematoma Presenting with Severe Neck Pain without Neurological Deficit - A Late Complication of Posterior Cervical Spine Surgery: Presentation of Three Unusual Cases

Postoperative epidural hematoma (EDH) usually present with neurological deficit. Massive EDH presenting with only severe pain without neurological deficit are rare. Atypical presentations of postoperative EDHs may lead to delayed diagnosis and treatment. We present three such cases after posterior cervical spine surgery. Three patients presented with severe neck pain and spasms without motor deficits several days after posterior cervical decompressive procedures. Imaging studies identified compressive EDHs at the surgical site with severe compression of the spinal cord. All were treated with emergent decompression, with resulting improvement of symptoms and pain relief without further neurological sequelae. In conclusion, postoperative EDHs after posterior cervical spine surgery may result in minimal neurological deficit. Our report reminds surgeons to keep this possibility in mind when patients complain of unusually severe neck pain and spasms after posterior cervical spine surgery.

Host Immune Responses to Intradiscal Gene Transfer / 대한척추외과학회지

PURPOSE: To elucidate host immune responses to intradiscal gene transfer. MATERIALS AND METHODS: Twenty rabbits were utilized. Ad/luciferase (adenovirus construct) were injected into nucleus pulposus of lumbar vertebrae. Group 1 received intradiscal injection of Ad/luciferase only, Group 2 received subcutaneous and intradiscal injection simultaneously, Group 3 received subcutaneous injection then intradiscal injection with 2 weeks interval. Blood samples were obtained serially after injection. Animals were sacrificed at 7 weeks. Antibody to adenovirus in peripheral blood was measured with ELISA and transgene expression was measured with standard luciferase kits. RESULTS: All rabbits in the Group 2 and 3 exhibited increased production of neutralizing antibody. There were clearly two subgroups in Group 1, three rabbits exhibited production of antibody but remaining three rabbits showed little or no production of antibody. All rabbits showed robust increase in transgene expression regardless of titer of neutralizing antibody. CONCLUSION: The intervertebral disc is favorable site for adenovirus-mediated gene transfer escaping from systemic immunity.

Matrix Synthesis of Human Intervertebral Disc Cells: Effect of Gene Transfer, Exogenous Growth Factor, Incubation Period, and Culture Methods / 대한척추외과학회지

STUDY DESIGN: In vitro experiment to determine the matrix synthesis of intervertebral disc (IVD) cell to various biologic interventions and conditions. OBJECTIVES: To elucidate biologic responses in terms of matrix synthesis of human IVD cells in vitro to various factors i.e. concentration of adenoviral vector and exogenous growth factor, duration of incubation, and type of culture methods. SUMMARY OF LITERATURE REVIEW: Sophisticated method to delivery of growth factors, in continuous manner, is the genetic modification of disc cells through gene transfer. Direct comparison of gene transfer and exogenous growth factor on matrix synthesis has not been reported. MATERIALS AND METHODS: IVD tissue was obtained from twenty three patients. Isolation and preparation of disc cells in monolayer (D) and alginate beads (3D) culture were performed. Disc cells in 2D and 3D were treated with either Ad/TGF-beta1 or exogenous TGF-beta1. Control cultures were treated with either saline or Ad/luciferase. Matrix synthesis (newly synthesized proteoglycan) was measured in various conditions (concentration of adenoviral vector and exogenous growth factor, duration of incubation, and type of culture methods). Newly synthesized proteoglycan were analyzed using chromatography on Sephadex G-25 in PD-10 columns after S35-sulfate incorporation. RESULTS: Ad/TGF-beta1 showed increase in proteoglycan synthesis (plateau at 75MOI) in 3D culture, (plateau at 25MOI) in 2D culture. In 3D culture, Ad/TGF-beta1 showed significant increase in proteoglycan synthesis on day 1, 2, and 3 of incubation. In 2D culture, Ad/TGF-beta1 showed significant increase in proteoglycan synthesis on day 2 of incubation with significant loss of anabolic effect on day 3. In 3D culture, exogenous TGF-beta1 showed increase in proteoglycan synthesis (plateau at 2ng/ml) while in 2D culture, there is no synthetic response to exogenous TGF-beta1 CONCLUSION: Therapeutic gene transfer provided sustained and increased anabolic responses than exogenous growth factor.

Intradiscal Gene Therapy: Therapeutic Implications in Degenerative Disc Disease / 대한척추외과학회지

STUDY DESIGN: In vitro and in vivo studies to determine the anabolic effects of intervertebral disc (IVD) to adenovirus-mediated therapeutic gene transfer. OBJECTIVES: To quantify the anabolic effect of human IVD cells in vitro and rabbit IVD in vivo to therapeutic gene transfer. SUMMARY OF LITERATURE REVIEW: An alternative possibility to delivery of growth factors, in continuous manner, is the genetic modification of disc cells through gene transfer. Contemplating to extend this approach to treatment of disc degeneration, it is necessary to demonstrate anabolic effect of human IVD cells and rabbit disc to therapeutic gene transfer. MATERIALS AND METHODS: In vitro: IVD tissue was obtained from twelve patients. IVD cells were then isolated, cultured, and transduced with Ad/TGF-beta1. Genetically modified disc cells were incorporated into alginate beads and cultured. In vivo: Fifteen skeletally mature New Zealand white rabbit were used. 15ul of saline containing Ad/TGF-beta1 were injected into the nucleus pulposus of the disc in six rabbits. All rabbits were sacrificed 6 weeks after surgery. Nucleus pulposus tissues were harvested, weighted, and cultured. Conditioned medium of alginate bead and rabbit disc tissue cultures were subjected to ELISA to detect TGF-beta1 production. Newly synthesized proteoglycan were analyzed using chromatography on Sephadex G-25 in PD-10 columns after S35-sulfate incorporation. RESULTS: Concentration of TGF-beta1 increased over time in alginate beads cultures transduced with Ad/TGF- beta1. At 6 weeks nucleus pulposus tissue from the disc injected with Ad/TGF-beta1 exhibited 200% (p<0.05) increase in TGF- beta1 production. There was statistically significant 290% increase in newly synthesized proteoglycan in alginate cultures transduced with Ad/TGF- beta1 (p<0.05) compared to control. At 6 weeks nucleus pulposus tissue from the disc injected with Ad/TGF- beta1 exhibited 85% increase in proteoglycan synthesis (p<0.05) over that of intact control. CONCLUSION: In this study, we observed the robust upregulation of proteoglycan synthesis in gene transferred disc cells in vitro and in vivo - indicating good prospects for biologic effects of therapeutic gene therapy in the disc using adenovirus-mediated approach.