ISSLS PRIZE IN BASIC SCIENCE 2017: Intervertebral disc/bone marrow cross-talk with Modic changes.

STUDY DESIGN: Cross-sectional cohort analysis of patients with Modic Changes (MC). OBJECTIVE: Our goal was to characterize the molecular and cellular features of MC bone marrow and adjacent discs. We hypothesized that MC associate with biologic cross-talk between discs and bone marrow, the presence of which may have both diagnostic and therapeutic implications. BACKGROUND DATA: MC are vertebral bone marrow lesions that can be a diagnostic indicator for discogenic low back pain. Yet, the pathobiology of MC is largely unknown. METHODS: Patients with Modic type 1 or 2 changes (MC1, MC2) undergoing at least 2-level lumbar interbody fusion with one surgical level having MC and one without MC (control level). Two discs (MC, control) and two bone marrow aspirates (MC, control) were collected per patient. Marrow cellularity was analyzed using flow cytometry. Myelopoietic differentiation potential of bone marrow cells was quantified to gauge marrow function, as was the relative gene expression profiles of the marrow and disc cells. Disc/bone marrow cross-talk was assessed by comparing MC disc/bone marrow features relative to unaffected levels. RESULTS: Thirteen MC1 and eleven MC2 patients were included. We observed pro-osteoclastic changes in MC2 discs, an inflammatory dysmyelopoiesis with fibrogenic changes in MC1 and MC2 marrow, and up-regulation of neurotrophic receptors in MC1 and MC2 bone marrow and discs. CONCLUSION: Our data reveal a fibrogenic and pro-inflammatory cross-talk between MC bone marrow and adjacent discs. This provides insight into the pain generator at MC levels and informs novel therapeutic targets for treatment of MC-associated LBP.

Prior Lumbar Spinal Arthrodesis Increases Risk of Prosthetic-Related Complication in Total Hip Arthroplasty.

BACKGROUND: Degenerative hip disorders often coexist with degenerative changes of the lumbar spine. Limited data on this patient population suggest inferior functional improvement and pain relief after surgical management. The purpose of this study is to compare the rates of prosthetic-related complication after primary total hip arthroplasty (THA) in patients with and without prior lumbar spine arthrodesis (SA). METHODS: Medicare patients (n = 811,601) undergoing primary THA were identified and grouped by length of prior SA (no fusion, 1-2 levels fused [S-SAHA], and ≥3 levels fused [L-SAHA]). RESULTS: Compared with controls, patients with prior SA had significantly higher rates of complications including dislocation (control: 2.36%; S-SAHA: 4.26%; and L-SAHA: 7.51%), revision (control: 3.43%, S-SAHA: 5.55%, and L-SAHA: 7.77%), loosening (control: 1.33%, S-SAHA: 2.10%, and L-SAHA: 3.04%), and any prosthetic-related complication (control: 7.33%, S-SAHA: 11.15% [relative risk: 1.52], and L-SAHA: 14.16% [relative risk: 1.93]) within 24 months (P < .001). CONCLUSION: The interplay of coexisting degenerative hip and spine disease deserves further attention of both arthroplasty and spine surgeons.

Long fusion from sacrum to thoracic spine for adult spinal deformity with sagittal imbalance: upper versus lower thoracic spine as site of upper instrumented vertebra.

OBJECT: Despite increasing numbers of patients with adult spinal deformity, it is unclear how to select the optimal upper instrumented vertebra (UIV) in long fusion surgery for these patients. The purpose of this study was to compare the use of vertebrae in the upper thoracic (UT) versus lower thoracic (LT) spine as the upper instrumented vertebra in long fusion surgery for adult spinal deformity. METHODS: Patients who underwent fusion from the sacrum to the thoracic spine for adult spinal deformity with sagittal imbalance at a single medical center were studied. The patients with a sagittal vertical axis (SVA) ≥ 40 mm who had radiographs and completed the 12-item Short-Form Health Survey (SF-12) preoperatively and at final follow-up (≥ 2 years postoperatively) were included. RESULTS: Eighty patients (mean age of 61.1 ± 10.9 years; 69 women and 11 men) met the inclusion criteria. There were 31 patients in the UT group and 49 patients in the LT group. The mean follow-up period was 3.6 ± 1.6 years. The physical component summary (PCS) score of the SF-12 significantly improved from the preoperative assessment to final follow-up in each group (UT, 34 to 41; LT, 29 to 37; p = 0.001). This improvement reached the minimum clinically important difference in both groups. There was no significant difference in PCS score improvement between the 2 groups (p = 0.8). The UT group had significantly greater preoperative lumbar lordosis (28° vs 18°, p = 0.03) and greater thoracic kyphosis (36° vs 18°, p = 0.001). After surgery, there was no significant difference in lumbar lordosis or thoracic kyphosis. The UT group had significantly greater postoperative cervicothoracic kyphosis (20° vs 11°, p = 0.009). The UT group tended to maintain a smaller positive SVA (51 vs 73 mm, p = 0.08) and smaller T-1 spinopelvic inclination (-2.6° vs 0.6°, p = 0.06). The LT group tended to have more proximal junctional kyphosis (PJK), although the difference did not reach statistical significance. Radiographic PJK was 32% in the UT group and 41% in the LT group (p = 0.4). Surgical PJK was 6.4% in the UT group and 10% in the LT group (p = 0.6). CONCLUSIONS: Both the UT and LT groups demonstrated significant improvement in clinical and radiographic outcomes. A significant difference was not observed in improvement of clinical outcomes between the 2 groups.

Immediate Voice and Swallowing Complaints Following Revision Anterior Cervical Spine Surgery.

OBJECTIVE: To report on the incidence of dysphagia, dysphonia, and acute vocal fold motion impairment (VFMI) following revision anterior cervical spine surgery, as well as to identify risk factors associated with acute VFMI in the immediate postoperative period. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care center. SUBJECTS AND METHODS: All patients who underwent 2-team reoperative anterior cervical discectomy and fusion (ACDF) were retrospectively reviewed. Incidence of dysphonia, dysphagia, and acute VFMI was noted. Patient and operative factors were evaluated for association with risk of acute VFMI. RESULTS: The incidence of postoperative dysphonia and dysphagia was 25% (18/72) and 52% (37/72), respectively. The incidence of immediate VFMI was 21% (15/72). Subjective postoperative dysphonia (odds ratio, [OR] 8; 95% CI, 2.2-28; P = .001) and dysphagia (OR, 22; 95% CI, 2.5-168; P = .005) were significantly associated with increased risk of VFMI. Three patients with VFMI required temporary injection medialization for voice complaints and/or aspiration. Infection (OR, 14; 95% CI, 1.4-147, P = .025) and level C7/T1 (OR, 5.5; 95% CI, 1.3-23, P = .02) were significantly associated with an increased risk of acute VFMI on multivariate logistic regression analysis. Number of prior surgeries, laterality of approach, side of approach relative to prior operations, and number of levels exposed were not significant. CONCLUSION: Early involvement of an otolaryngologist in the care of a patient undergoing revision ACDF can be helpful to the patient in anticipation of voice and swallowing changes in the postoperative period. This may be particularly important in those being treated at C7/T1 or those with spinal infections.

Relaxation of forces needed to distract cervical vertebrae after discectomy: a biomechanical study.

STUDY DESIGN: In vitro and in vivo biomechanical stress measurements are made of the intervertebral disc segment distraction force during anterior cervical discectomy. OBJECTIVE: The purpose of this study is to determine the short-term force relaxation of the native intervertebral disc segment and to determine the short-term force relaxation of the segment after removal of the intervertebral disc, as is commonly performed in anterior cervical discectomy with fusion and arthroplasty. SUMMARY OF BACKGROUND DATA: No published data examine the issue of intraoperative distraction force of the cervical intervertebral disc segment. This is a novel research in this area. METHODS: In vitro and in vivo studies under institutional review board approval were performed to determine the mechanical behavior of the normal and diseased cervical functional spinal unit. Seven in vitro and 11 in vivo spines were studied. Strain measurements between distracting Caspar-type pins were made before, at various points during, and after discectomy to assess how removal of the disc and other spinal components affects the force-displacement behavior of the spinal unit. RESULTS: The in vitro data show progressive reduction in force needed for distraction after discectomy and uncovertebral joint resection. Greatest reduction is noted after discectomy. The in vivo data indicate that, on average, the cervical functional spinal unit requires 20 N less force to achieve the same degree of distraction after removal of the intervertebral disc. CONCLUSIONS: A sharp reduction in the strain across the intervertebral space occurs after distraction. The removal of the cervical intervertebral disc significantly reduces the viscoelastic response of the cervical motion segment. The long-term force used to stabilize intervertebral grafts or implants is less than what is achieved at the time of distraction. The exact magnitude of the resultant force on graft or device at a given distraction force is unknown and would depend also upon fit.

Factors Associated With the Development of and Revision for Proximal Junctional Kyphosis in 440 Consecutive Adult Spinal Deformity Patients.

MINI: Proximal junctional kyphosis (PJK) is a common, yet incompletely understood, complication of surgery for adult spinal deformity. We analyzed 440 consecutive adult spinal deformity patients for trends in development of PJK and need for revision surgery. pelvic tilt and thoracic kyphosis were predictive for developing PJK, while radiographic evidence of proximal junctional failure was predictive for proceeding to revision. STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: The aim of this study was to examine which radiographic parameters and surgical strategies are most closely associated with proximal junctional kyphosis (PJK) after adult spinal deformity (ASD) surgery, the need for revision surgery for PJK, and whether these differ based on the upper instrumented vertebra (UIV). SUMMARY OF BACKGROUND DATA: Multiple parameters are considered when planning correction of ASD. Determining which of these factors contribute to the development of and need for revision surgery for PJK presents a challenging problem. METHODS: Consecutive patients undergoing long fusion to the pelvis with age >18 years, minimum 6-month follow-up, and adequate radiographs for analysis in a single institution between 2003 and 2011 were included. Along with chart review, measurement of proximal junctional angle (PJA), sagittal balance, and pelvic parameters was performed on preoperative, postoperative, and latest follow-up radiographs. Postoperative radiographs were also examined for signs of PJF. RESULTS: A total of 440 patients with a mean follow-up of 34 months met inclusion criteria, 159 of whom developed PJK (36%), with 65 requiring revision surgery (41%). Higher preoperative pelvic tilt (PT) (P = 0.018) and postoperative thoracic kyphosis (TK) (P ≤ 0.001) were predictive for development of PJK, whereas hooks at UIV were protective (odds ratio [OR] 0.049). In patients who developed PJK, revision was more frequent in younger patients (P = 0.005) with greater postoperative sagittal vertical axis and PJA (P = 0.029, P = 0.018). PJF with spondylolisthesis, fracture, or instrumentation failure at the UIV had the highest ORs for proceeding to a revision (5.1, 1.6, and 2.2, respectively). CONCLUSION: TK and PT are important indicators of overall rigidity and reference the ability of the spine to compensate for sagittal plane deformity. Special attention should be paid to these characteristics and to the choice of proximal instrumentation when attempting to prevent PJK. Prevention of radiographically evident PJF may hold the key to reducing the need for revision surgery. LEVEL OF EVIDENCE: 3.

A Comparison of Implants Used in Open-Door Laminoplasty: Structural Rib Allografts Versus Metallic Miniplates.

STUDY DESIGN: A retrospective case-controlled study. SUMMARY OF BACKGROUND DATA: Open-door laminoplasty has been successfully used to address cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament. Two common implants include rib allograft struts and metallic miniplates. OBJECTIVE: The goals of this study were to compare outcomes, complications, and costs associated with these 2 implants. METHODS: A retrospective review was done on 51 patients with allograft struts and 55 patients with miniplates. Primary outcomes were neck visual analog scale (VAS) pain scores and Nurick scores. Secondary outcomes included length of the procedure, estimated blood loss, rates of complications, and the direct costs associated with the surgery and inpatient hospitalization. RESULTS: There were no differences in demographic characteristics, diagnoses, comorbidities, and preoperative outcome scores between the 2 treatment groups. Mean follow-up was 27 months. The postoperative neck VAS scores and Nurick scores improved significantly from baseline to final follow-up for both groups, but there was no difference between the 2 groups. The average length of operation (161 vs. 136 min) and number of foraminotomies (2.7 vs. 1.3) were higher for the allograft group (P=0.007 and 0.0001, respectively). Among the miniplate group, there was no difference in complications but a trend for less neck pain for patients treated without hard collar at final follow-up (1.8 vs. 2.3, P=0.52). The mean direct costs of hospitalization for the miniplate group were 15% higher. CONCLUSIONS: Structural rib allograft struts and metallic miniplates result in similar improvements in pain and functional outcome scores with no difference in the rate of complications in short-term follow-up. Potential benefits of using a plate include shorter procedure length and less need for postoperative immobilization. When costs of bracing and operative time are included, the difference in cost between miniplates and allograft struts is negligible.

Ossification of the posterior longitudinal ligament of the cervical spine in 3161 patients: a CT-based study.

STUDY DESIGN: A cross-sectional study. OBJECTIVE: To examine the prevalence of ossification of the posterior longitudinal ligament (OPLL) and ossification of the nuchal ligament (ONL) of the cervical spine in the San Francisco area. SUMMARY OF BACKGROUND DATA: The prevalence of OPLL and ONL is unknown in the non-Asian population. METHODS: This computed tomography-based cross-sectional study assessed the prevalence of OPLL and ONL within the cervical spine of patients treated at a level 1 trauma center between 2009 and 2012. The prevalence of both OPLL and ONL was compared between racial groups. RESULTS: Of the 3161 patients (mean age, 51.2 ± 21.6 yr; 66.1% male), there were 1593 Caucasians (50.4%), 624 Asians (19.7%), 472 Hispanics (14.9%), 326 African Americans (10.3%), 62 Native Americans (2.0%), and 84 Others (2.7%). The prevalence of cervical OPLL was 2.2% (95% confidence interval [CI]: 1.7-2.8). The adjusted prevalence was 1.3% in Caucasian Americans (95% CI: 0.7-2.3), 4.8% in Asian Americans (95% CI: 2.8-8.1), 1.9% in Hispanic Americans (95% CI: 0.9-4.0), 2.1% in African Americans (95% CI: 0.9-4.8), and 3.2% in Native Americans (95% CI: 0.8-12.3). The prevalence of OPLL in Asian Americans was significantly higher than that in Caucasian Americans (P = 0.005). ONL was detected in 346 patients and the prevalence was 10.9% (95% CI: 10.0-12.0). The adjusted prevalence of ONL was 7.3% in Caucasian Americans (95% CI: 5.8-9.3), 26.4% in Asian Americans (95% CI: 21.9-31.5), 7.4% in Hispanic Americans (95% CI: 5.2-10.5), 2.5% in African Americans (95% CI: 1.2-4.9), and 25.8% in Native Americans (95% CI: 16.5-37.5). ONL was significantly more common in Asian Americans than in Caucasian Americans, Hispanic Americans, and African Americans (P = 0.001). CONCLUSION: This study also demonstrated that OPLL and ONL were significantly more common in Asian Americans than in Caucasian Americans. LEVEL OF EVIDENCE: 3.

Percutaneous plasma decompression alters cytokine expression in injured porcine intervertebral discs.

BACKGROUND CONTEXT: Discectomy is a surgical technique commonly used to treat bulging or herniated discs causing nerve root compression. Clinical data suggest discectomy may also help patients with contained discs and no clear neural compromise. However, the mechanisms of clinical efficacy are uncertain, and consequently bases for treatment optimization are limited. PURPOSE: To determine the effect of percutaneous plasma decompression on the histologic, morphologic, biochemical and biomechanical features of degenerating intervertebral discs. STUDY DESIGN: An adult porcine model of disc degeneration was used to establish a degenerative baseline against which to evaluate discectomy efficacy. OUTCOME MEASURES: Cytokines interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha were measured from tissue samples using enzyme-linked immunosorbent assay. Histology and morphology images were rated for degenerative findings (of cells and matrix) in both the nucleus and annulus. Proteoglycan content was determined, and intact specimen stiffness and flexibility were measured biomechanically. Magnetic resonance images were collected for biomechanical specimens. METHODS: Using a retroperitoneal surgical approach, stab incisions were made in four or five lumbar discs per spine in 12 minipigs. Animals were allocated into one of three groups: 6-week recovery, 12-week recovery and percutaneous plasma decompression using an electrosurgical device at 6 weeks with recovery for 6 additional weeks. Four additional animals served as controls. RESULTS: Discs treated with discectomy had a significant increase in IL-8 and a decrease in IL-1 as compared with the 12-week, nontreated discs. There were no significant differences in morphologic and biomechanical parameters or proteoglycan content between treated discs and time-matched, nontreated discs. CONCLUSIONS: Our results demonstrate that percutaneous plasma discectomy alters the expression of inflammatory cytokines in degenerated discs, leading to a decrease in IL-1 and an increase in IL-8. Whereas both IL-1 and IL-8 have hyperalgesic properties, IL-1 is likely to be a more important pathophysiologic factor in painful disc disorders than IL-8. Therefore, the alteration in cytokine expression that we observed is consistent with this effect as a mechanism of pain relief after discectomy. In addition, given that IL-1 is catabolic in injured tissue and IL-8 is anabolic, our results suggest that a percutaneous plasma discectomy may be capable of initiating a repair response in the disc.

Spinal infections.

Spinal infections can occur in a variety of clinical situations. Their presentation ranges from the infant with diskitis who is unwilling to crawl or walk to the adult who develops an infection after a spinal procedure. The most common types of spinal infections are hematogenous bacterial or fungal infections, pediatric diskitis, epidural abscess, and postoperative infections. Prompt and accurate diagnosis of spinal infections, the cornerstone of treatment, requires a high index of suspicion in at-risk patients and the appropriate evaluation to identify the organism and determine the extent of infection. Neurologic function and spinal stability also should be carefully evaluated. The goals of therapy should include eradicating the infection, relieving pain, preserving or restoring neurologic function, improving nutrition, and maintaining spinal stability.

Adjacent segment motion after anterior cervical discectomy and fusion versus Prodisc-c cervical total disk arthroplasty: analysis from a randomized, controlled trial.

STUDY DESIGN: Post hoc analysis of data acquired in a prospective, randomized, controlled trial. OBJECTIVE: To compare adjacent segment motion after anterior cervical discectomy and fusion (ACDF) versus cervical total disc arthroplasty (TDA). SUMMARY OF BACKGROUND DATA: TDA has been designed to be a motion-preserving device, thus theoretically normalizing adjacent segment kinematics. Clinical studies with short-term follow-up have yet to demonstrate a consistent significant difference in the incidence of adjacent segment disease. METHODS: Two hundred nine patients at 13 sites were treated in a prospective, randomized, controlled trial of ACDF versus TDA for single-level symptomatic cervical degenerative disc disease (SCDD). Flexion and extension radiographs were obtained at all follow-up visits. Changes in ROM were compared using the Wilcoxon signed-rank test and the Mann-Whitney U test. Predictors of postoperative ROM were determined by multivariate analysis using mixed effects linear regression. RESULTS: Data for 199 patients were available with 24-month follow-up. The groups were similar with respect to baseline demographics. A significant increase in motion at the cranial and caudal adjacent segments after surgery was observed in the ACDF group only (cranial: ACDF: +1.4° (0.4, 2.4), P = 0.01; TDA: +0.8°, (-0.1, +1.7), P = 0.166; caudal: ACDF: +2.6° (1.3, 3.9), P < 0.0001; TDA: +1.3, (-0.2, +2.8), P = 0.359). No significant difference in adjacent segment ROM was observed between ACDF and TDA. Only time was a significant predictor of postoperative ROM at both the cranial and caudal adjacent segments. CONCLUSION: Adjacent segment kinematics may be altered after ACDF and TDA. Multivariate analysis showed time to be a significant predictor of changes in adjacent segment ROM. No association between the treatment chosen (ACDF vs. TDA) and ROM was observed. Furthermore clinical follow-up is needed to determine whether possible differences in adjacent segment motion affect the prevalence of adjacent segment disease in the two groups.

Results at 24 months from the prospective, randomized, multicenter Investigational Device Exemption trial of ProDisc-C versus anterior cervical discectomy and fusion with 4-year follow-up and continued access patients.

BACKGROUND: Cervical total disk replacement (TDR) is intended to address pain and preserve motion between vertebral bodies in patients with symptomatic cervical disk disease. Two-year follow-up for the ProDisc-C (Synthes USA Products, LLC, West Chester, Pennsylvania) TDR clinical trial showed non-inferiority versus anterior cervical discectomy and fusion (ACDF), showing superiority in many clinical outcomes. We present the 4-year interim follow-up results. METHODS: Patients were randomized (1:1) to ProDisc-C (PDC-R) or ACDF. Patients were assessed preoperatively, and postoperatively at 6 weeks and 3, 6, 12, 18, 24, 36, and 48 months. After the randomized portion, continued access (CA) patients also underwent ProDisc-C implantation, with follow-up visits up to 24 months. Evaluations included Neck Disability Index (NDI), Visual Analog Scale (VAS) for pain/satisfaction, and radiographic and physical/neurologic examinations. RESULTS: Randomized patients (103 PDC-R and 106 ACDF) and 136 CA patients were treated at 13 sites. VAS pain and NDI score improvements from baseline were significant for all patients (P < .0001) but did not differ among groups. VAS satisfaction was higher at all time points for PDC-R versus ACDF patients (P = .0499 at 48 months). The percentage of patients who responded yes to surgery again was 85.6% at 24 months and 88.9% at 48 months in the PDC-R group, 80.9% at 24 months and 81.0% at 48 months in the ACDF group, and 86.3% at 24 months in the CA group. Five PDC-R patients (48 months) and no CA patients (24 months) had index-level bridging bone. By 48 months, approximately 4-fold more ACDF patients required secondary surgery (3 of 103 PDC-R patients [2.9%] vs 12 of 106 ACDF patients [11.3%], P = .0292). Of these, 6 ACDF patients (5.6%) required procedures at adjacent levels. Three CA patients required secondary procedures (24 months). CONCLUSIONS: Our 4-year data support that ProDisc-C TDR and ACDF are viable surgical options for symptomatic cervical disk disease. Although ACDF patients may be at higher risk for additional surgical intervention, patients in both groups show good clinical results at longer-term follow-up.

Biomechanics of the anterior longitudinal ligament during 8 g whiplash simulation following single- and contiguous two-level fusion: a finite element study.

STUDY DESIGN: A computational study of anterior longitudinal ligament (ALL) strain in the cervical spine following single- and 2-level fusion during simulated whiplash. OBJECTIVE: To evaluate how cervical fusion alters the peak strain of the ALL in the adjacent motion segments. SUMMARY OF BACKGROUND DATA: Although an in vitro study of ALL strain during whiplash has been conducted in healthy cervical spines, no such study has been performed in a cervical spine with fused segments. It has been demonstrated that the loss of motion following fusion results in increased strain in the adjacent motion segments. However, the biomechanics of the adjacent motion segments during high energy acceleration-deceleration simulations have not been widely reported. Accordingly, we investigated the peak strain of the ALL following single- and 2-level fusion during simulated whiplash. METHODS: A detailed finite element (FE) model of the human body in the driver-occupant position was used to investigate cervical hyperextension injury. The cervical spine was subjected to simulated whiplash at 8 g acceleration and peak ALL strains were computed. The results were validated against published experimental data. This validated FE model was then modified to simulate single- and 2-level fusion and tested under identical loading conditions. RESULTS: The mean increase in peak ALL strain at the motion segment immediately adjacent to the level of fusion was 15.5% for single-level fusion when compared with 40.8% in 2-level contiguous fusion (P = 0.019). CONCLUSION: Cervical arthrodesis increases peak ALL strain in the adjacent motion segments. Two-level fusion increased ALL strain in the adjacent motion segments, on average, greater than single-level fusion did. Disc arthroplasty and other techniques that provide stability without loss of flexibility may be beneficial in patients undergoing multiple-level fusion. Detailed FE models such as ours can provide strong correlation with experimentally determined data.

Inhibition of MMP2/MMP9 after spinal cord trauma reduces apoptosis.

STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To characterize the increase in gelatinase A (MMP2) activity after spinal cord injury (SCI) in the mouse model, and the effects of MMP2/MMP9 inhibition on apoptotic cells. SUMMARY OF BACKGROUND DATA: Clinical consequences of SCI are due to a series of secondary injury cascades. Matrix metalloproteinases are thought play a key role in this, leading to apoptotic cell death. METHODS: SCI via a drop tower in mice was used. MMP2 beta-gal reporter mice were used to quantify the level of MMP2 after SCI. In a follow-up experiment, mice which underwent SCI were randomized to daily SQ injections of MMP2/MMP9 inhibitor versus placebo. MMP2 levels were quantified and histology was performed with TUNEL and Luxol fast blue staining. RESULTS: MMP2 transcription was significantly upregulated after SCI, by the beta-gal assay. Inhibition of MMP2/MMP9 activity after SCI led to statistically significant decreases in apoptosis within the zone of injury. There was a trend towards preservation of myelin by preserved luxol fast blue staining. CONCLUSION: After SCI, MMP2 is upregulated along with neuron and glial cells apoptosis. The level of apoptosis could be reduced with MMP2/MMP9 inhibition. This supports MMP2 as cause for apoptosis after SCI with the potential for therapeutic intervention as apoptosis can be reduced with MMP2 inhibition.

Intervertebral disc replacement maintains cervical spine kinetics.

STUDY DESIGN: An in vitro biomechanical study of C4-C5 intervertebral disc replacement using a cadaveric model. OBJECTIVES: To investigate the degree of motion afforded by a ball-and-socket cervical intervertebral disc prosthesis design. SUMMARY OF BACKGROUND DATA: Intervertebral disc prostheses designs attempt to restore or maintain cervical disc motion after anterior cervical discectomy and reduce the likelihood of accelerated degeneration in adjacent discs by maintaining normal motion at the affected disc level. Surprisingly, the actual kinetic and biomechanical effects that cervical disc arthroplasty imparts on the spine have not been widely reported. Accordingly, we investigated what effect implanting a cervical disc prosthesis has on the range of motion at the affected level as well as how it changes the coupled motion patterns at the level of implantation. METHODS: Six fresh-frozen human cadaveric cervical spines (C2-C7) were used in this study. We evaluated two different spinal conditions: intact and after disc replacement at C4-C5. Compression (using the follower load concept) and pure moment loading were applied to the specimen. Range of motion was measured using an optical tracking system. Statistical differences between the intact and replaced condition range of motion was determined using analysis of variance with post hoc comparisons (alpha = 0.05). RESULTS: The data indicate that the intervertebral disc prosthesis approximated the intact motion in all three rotation planes at the affected level. Finally, changes in cervical coupled rotations, specifically lateral bending during axial rotation loading and axial rotation during lateral bending loading, were not statistically significant between the two tested conditions. CONCLUSIONS: Our data demonstrate that a ball-and-socket design can replicate physiologic motion at the affected and adjacent levels. More importantly, the data indicate that motion coupling, which is most dramatic in the cervical spine and plays an important biomechanical role, is maintained.