Adam L. Shimer

Pelvic fixation for adult scoliosis

IntroductionObtaining a fusion, especially to the sacrum for adult deformity correction remains a challenge. Prior to modern fixation techniques, the reported fusion rates for adult scoliotic deformities were low. However sacropelvic fixation techniques for adult deformity continue to evolve. As a result, modern day pelvic fixation techniques have improved fusion rates at the base of long constructs. The purpose of this article is to discuss the history, indications, and modern fixation techniques for pelvic fixation in the surgical management of adult scoliosis patients.MethodsWe searched PUBMED using the search terms pelvic fixation, deformity, lumbopelvic, sacropelvic, and iliac fixation. Linkage or association studies published in English and available full-text were analyzed specifically regarding techniques and innovations in pelvic fixation.ResultsSacropelvic fixation should be considered in any patient with a long construct ending in the sacrum, those patients with associated risk factors for loss of distal fixation or high risk for pseudarthrosis at L5–S1, and those undergoing three column osteotomies or vertebral body resections in the low lumbar spine. Current pelvic fixation techniques with iliac screws, multiple screw/rod constructs, and S2-alar-iliac screws are all viable techniques for achieving pelvic fixation.ConclusionsThere is growing evidence that pelvic fixation may become the standard for obtaining long fusions in adult scoliosis. Although technically challenging, in selected cases the use of four pelvic screws and/or four rods across the lumbosacral pelvis can help address pseudarthroses, implant breakage, and screw pullout secondary to osteoporosis. Ultimately, indications and techniques should be individualized to the patient and based on surgeon preference and experience.

Gene therapy approaches for intervertebral disc degeneration.

Study Design. Review of the literature concerning the development of gene therapy approaches for the treatment of intervertebral disc degeneration. Objectives. To provide an overview of gene therapy principles, summarize the results of completed gene therapy studies, and discuss considerations for the direction of future research. Summary of Background Data. Intervertebral disc degeneration is characterized by progressive loss of the proteoglycan matrix in the nucleus pulposus. Exogenous growth factors have been shown to transiently increase matrix synthesis. Gene therapy offers exciting potential to induce and sustain endogenous production of growth factors within the intervertebral disc and thus possibly alter the degenerative course. Methods. Published and presented scientific literature was examined. Results/Conclusions. Several in vitro and in vivo studies have documented the capacity of gene therapy to favorably modify the biologic functions of intervertebral disc cells with the delivery of the cDNA for various growth factors. Currently, investigators are exploring the efficacy and safety of gene therapy in animal models of degeneration. With promising initial results and an immense potential clinical impact, gene therapy approaches for treatment of intervertebral disc degeneration will continue to receive dedicated research efforts.

Spinal reconstruction and bone morphogenetic proteins: Open questions

Spinal fusion is a proven surgical tool for the treatment of degenerative, traumatic, neoplastic, and infectious conditions of the spine. Traditional grafting techniques using autogenous bone graft or allograft have inherent drawbacks including varying pseudoarthrosis rates and well recognized bone graft harvest site complications. Bone morphogenetic proteins (BMPs) offer the exciting prospect of enhanced union rates equal to or greater than autograft and potentially eliminate graft harvest site complications. Many studies have clearly demonstrated the efficacy of BMP products for various applications in spine surgery. BMP has proven effective in achieving union in anterior and posterior lumbar surgery and recently in anterior cervical surgery. Despite the reported success, the universal adoption of BMP is tempered by high costs and lingering safety concerns with reported complications specific to BMP use including vertebral osteolysis, ectopic bone formation, radiculitis and cervical soft tissue swelling. Ongoing clinical and basic-science research is focused on clearly defining guidelines for BMP use in spine surgery and on developing more affordable BMP formulations with dosing that predictably results in spine fusion yet minimizes the possible side effect profile.

Evaluation of complications and neurological deficits with three-column spine reconstructions for complex spinal deformity: a retrospective Scoli-RISK-1 study

OBJECT The goal in this study was to evaluate the risk factors for complications, including new neurological deficits, in the largest cohort of patients with adult spinal deformity to date. METHODS The Scoli-RISK-1 inclusion criteria were used to identify eligible patients from 5 centers who were treated between June 1, 2009, and June 1, 2011. Records were reviewed for patient demographic information, surgical data, and reports of perioperative complications. Neurological deficits were recorded as preexisting or as new deficits. Patients who underwent 3-column osteotomies (3COs) were compared with those who did not (posterior spinal fusion [PSF]). Between-group comparisons were performed using independent samples t-tests and chi-square analyses. RESULTS Two hundred seven patients were identified-75 who underwent PSF and 132 treated with 3CO. In the latter group, patients were older (58.9 vs 49.4 years, p < 0.001), had a higher body mass index (29.0 vs 25.8, p = 0.029), smaller preoperative coronal Cobb measurements (33.8° vs 56.4°, p < 0.001), more preoperative sagittal malalignment (11.7 cm vs 5.4 cm, p < 0.001), and similar sagittal Cobb measurements (45.8° vs 57.7°, p = 0.113). Operating times were similar (393 vs 423 minutes, p = 0.130), although patients in the 3CO group sustained higher estimated blood loss (2120 vs 1700 ml, p = 0.066). Rates of new neurological deficits were similar (PSF: 6.7% vs 3CO: 9.9%, p = 0.389), and rates of any perioperative medical complication were similar (PSF: 46.7% vs 3CO: 50.8%, p = 0.571). Patients who underwent vertebral column resection (VCR) were more likely to sustain medical complications than those treated with pedicle subtraction osteotomy (73.7% vs 46.9%, p = 0.031), although new neurological deficits were similar (15.8% vs 8.8%, p = 0.348). Regression analysis did not reveal significant predictors of neurological injury or complication from collected data. CONCLUSIONS Despite higher estimated blood loss, rates of all complications (49.3%) and new neurological deficits (8.7%) did not vary for patients who underwent complex reconstruction, whether or not a 3CO was performed. Patients who underwent VCR sustained more medical complications without an increase in new neurological deficits. Prospective studies of patient factors, provider factors, and refined surgical data are needed to define and optimize risk factors for complication and neurological deficits.

Correlation of posterior ligamentous complex injury and neurological injury to loss of vertebral body height, kyphosis, and canal compromise.

Study Design. Retrospective, case-control study. Objective. The purpose of this study was to determine if thoracolumbar vertebral body collapse, translation, or canal compromise (CC) is associated with injury to the posterior ligamentous complex (PLC) or neurological elements. Summary of Background Data. Radiographical parameters, including loss of vertebral body height (LOVBH), vertebral body translation, local kyphosis (LK), and CC, are often used as indicators of spinal instability. The hypothesis of this study was that LOVBH greater than 50%, LK greater than 20°, translation greater than 3.5 mm, or CC greater than 50% is associated with ligamentous and neurological injury. Methods. Retrospective review of prospectively collected spinal cord injury database was performed. Inclusion criteria include consecutive patients with thoracolumbar burst fractures. Exclusion criteria include flexion-distraction injuries and pathological fractures. Computed tomographic scan measurements of the spine were performed by 2 experienced spine surgeons blinded to magnetic resonance imaging results. On magnetic resonance imaging, the supraspinous ligament, interspinous ligament, ligamentum flavum, facet joints, and disc were graded as intact, indeterminate, or disrupted. American Spinal Injury Association (ASIA) score and Frankel Scale score were recorded. Spearman correlation coefficients were calculated to evaluate relationships between vertebral body measurements, ligamentous injury, and neurological injury. Results. Forty-six patients were included in the study. Ten patients had kyphosis greater than 20°, 1 patient had kyphosis greater than 30°, and 9 patients had LOVBH greater than 50%. There were 34 patients with vertebral body translation greater than 3.5 mm and 15 patients with CC greater than 50%. Sixteen patients had ligamentous injury. There was a significant correlation between subjacent segment translation greater than 3.5 mm and ligamentous injury (R = 0.323, P = 0.029) and ASIA motor score (R = −0.379, P = 0.009). There was no significant correlation between ligamentous injury or neurological injury and the following threshold parameters: LOVBH greater than 50%, vertebral body kyphosis greater than 20°, caudal or cephalad interspinous widening greater than 7 mm, CC greater than 50%, and sagittal transverse ratio less than 0.48. Conclusion. The results of this study indicate that LOVBH greater than 50% and LK greater than 20° are not predictive of PLC injury in thoracolumbar burst fractures. Translation greater than 3.5 mm was associated with PLC injury. The PLC and neural elements should be directly assessed with magnetic resonance imaging if there is clinical concern.

Antioxidative nanofullerol prevents intervertebral disk degeneration

Compelling evidence suggests that reactive oxygen species (ROS) play a pivotal role in disk degeneration. Fullerol nanoparticles prepared in aqueous solution have been demonstrated to have outstanding ability to scavenge ROS. In this report, in vitro and in vivo models were used to study the efficacy of fullerol in preventing disk degeneration. For in vitro experiments, a pro-oxidant H2O2 or an inflammatory cytokine interleukin (IL)-1β was employed to induce degenerated phenotypes in human nucleus pulposus cells encapsulated in alginate beads, and fullerol was added in the culture medium. For the animal study, an annulus-puncture model with rabbit was created, and fullerol was injected into disks. It was shown that cytotoxicity and cellular ROS level induced by H2O2 were significantly diminished by fullerol. IL-1β-induced nitric oxide generation in culture medium was suppressed by fullerol as well. Gene-profile and biochemical assays showed that fullerol effectively reversed the matrix degradation caused by either H2O2 or IL-1β. The animal study delineated that intradiskal injection of fullerol prevented disk degeneration, increasing water and proteoglycan content and inhibiting ectopic bone formation. These results suggest that antioxidative fullerol may have a potential therapeutic application for disk degeneration.

Use of a bioactive scaffold for the repair of bone defects in a novel reproducible vertebral body defect model.

Bone defects in vertebral bodies (VB) usually occur after the reduction of fractures or are caused by bone disease. Besides the treatment of original disease, repair of the bone defect can restore the structure of VB and improve stabilization of the spine to protect the spinal cord nerves. To aid studies of the efficacy of bioengineering techniques for repair of VB, we developed a rat model with a critical size bone defect in VB. Air-motivated burrs were used to create two sizes of bone defect (2 x 3 x 1.5 mm; 2 x 3 x 3 mm) in the anterior part of VB in 6-month-old Fischer 344 rats. Quantitative CT analyses and histological assays demonstrated that neither defects self-repaired by 8 weeks post surgery. Moreover, the tendency of bone formation was monitored in the same animal by serial CT image evaluations, allowing us to demonstrate that there was significant bone growth during the 4- to 6-week period after the creation of the bone defect. We then implanted sintered poly(lactic-co-glycolic acid) (PLGA) microsphere scaffolds loaded with Matrigel with or without recombinant human bone morphogenetic protein 2 (rhBMP2; 2.0 microg rhBMP2/10 microL Matrigel/scaffold) into the bone defect (2 x 3 x 3 mm) in the VB. Bone formation was detected by quantitative analyses of serial CT images, which demonstrated bone growth in rats that received the rhBMP2 implant, in both surrounding areas and inside area of the scaffold. In addition to a rapid increase within 2 weeks of the operation, another significant bone formation period was found between 4 and 8 weeks after the implantation. By contrast, the control group that received the implant without rhBMP2 did not show similar bone formation tendencies. The results of CT analyses were confirmed by histological studies. This study suggests that a critical size bone defect of the anterior VB can be developed in a rat model. Characterization of this model demonstrated that 4 to 6 weeks after creation of the defect was a significant bone growth period for VB bone repair in rats. This animal model has further utility for the study of different biomaterials for VB bone repair. Implantation of a bioactive PLGA scaffold carrying rhBMP2 allowed more successful repair of the VB defect. Although further characterization studies are needed, the bioactive PLGA scaffold developed in this study will likely adapt easily to other in vivo osteogenesis applications.

The effects of simulated microgravity on intervertebral disc degeneration.

BACKGROUND CONTEXT Astronauts experience back pain, particularly low back pain, during and after spaceflight. Recent studies have described histologic and biochemical changes in rat intervertebral discs after space travel, but there is still no in vitro model to investigate the effects of microgravity on disc metabolism. PURPOSE To study the effects of microgravity on disc degeneration and establish an in vitro simulated microgravity study model. STUDY DESIGN Discs were cultured in static and rotating conditions in bioreactor, and the characteristics of disc degeneration were evaluated. METHODS The mice discs were cultured in a rotating wall vessel bioreactor where the microgravity condition was simulated. Intervertebral discs were cultured in static and microgravity condition. Histology, biochemistry, and immunohistochemical assays were performed to evaluate the characteristics of the discs in microgravity condition. RESULTS Intervertebral discs cultured in rotating bioreactors were found to develop changes of disc degeneration manifested by reduced red Safranin-O staining within the annulus fibrosus, downregulated glycosaminoglycan (GAG) content and GAG/hydroxyproline ratio, increased matrix metalloproteinase 3 expression, and upregulated apoptosis. CONCLUSIONS We conclude that simulated microgravity induces the molecular changes of disc degeneration. The rotating bioreactor model will provide a foundation to investigate the effects of microgravity on disc metabolism.

Obesity Is Associated with an Increased Rate of Incidental Durotomy in Lumbar Spine Surgery

Study Design. Retrospective database analysis. Objective. To determine the impact of obesity on the rate of incidental durotomy in lumbar spine surgery. Summary of Background Data. There is a paucity of data on the overall impact of obesity on the rate of incidental durotomy in lumbar spine surgery, specifically with regard to the type of procedure performed. Methods. A large administrative database was queried for all patients who underwent lumbar spine surgery for decompression and/or fusion. They were then stratified into separate cohorts on the basis of body mass index and by procedural codes. Documentation of incidental durotomy was noted. Patient demographics and associated comorbidities were assessed. Odds ratios and 95% confidence intervals were calculated and &khgr;2 test was used to assess for statistical significance. Results. The incidental durotomy ranged from 0.5% to 2.6%, with the highest rates observed in multilevel laminectomies and revision decompressions in the obese and morbidly obese groups. For patients who underwent decompression only procedures, nonobese patients had a significantly lower rate of durotomy than the obese and morbidly obese cohorts. For patients who underwent fusion with or without decompression, there was a significantly increased rate of durotomy in obese patients compared with nonobese patients. The morbidly obese cohort also had significantly higher rates of incidental durotomy than the nonobese cohort in both revision decompression and revision fusion procedures. Conclusion. This analysis of a large administrative database demonstrates that obesity is associated with increased rates of incidental durotomy in lumbar spine surgery. Furthermore, obesity, in association with increasing complexity of the procedure, increases the rate of incidental durotomy in lumbar spine surgery. Surgeons must be aware of these increased risks as the rate of obesity increases in the population. Level of Evidence: 3

Intervertebral disk-like biphasic scaffold—demineralized bone matrix cylinder and poly(polycaprolactone triol malate)—for interbody spine fusion

Interbody fusion is an established procedure to preserve disk height and anterior fusion, but fusion with autografts, allografts, and metallic cages has its endogenous shortcomings. The objective of this study is to investigate whether a biphasic scaffold model, the native demineralized bone matrix cylinder in conjunction with degradable biomaterial poly(polycaprolactone triol malate), can be employed as a biological graft for interbody fusion. The poly(polycaprolactone triol malate) was synthesized by polycondensing malic acid and polycaprolactone and then the concentric sheet of poly(polycaprolactone triol malate) was fabricated into the demineralized bone matrix cylinder derived from rabbit femurs. Rabbit chondrocytes were loaded onto the three-dimensional constructs with 1-day in vitro culture and implanted into the subcutaneous dorsal pocket of nude mice. The chondrocytes/scaffold constructs are approximately two folds bigger than the scaffold-alone constructs after 12 weeks of implantation. X-ray and micro-computed tomography imaging showed endochondral bone formation in the chondrocytes/scaffold constructs as early as 4 weeks and showed that the bone intensity increased over time. Histological staining confirmed the above observation. By week 8, lamellar bone tissues were formed inside the demineralized bone matrix cylinder. In addition, the compression biomechanical test showed that the chondrocytes/scaffold constructs produced a significant higher compressive strength compared to the scaffold group. These results demonstrated that the inner-phase poly(polycaprolactone triol malate) degraded over time and was replaced by new bone in an in vivo environment.