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Objective To determine the risk factors associated with radiographic changes and clinical outcomes following 3-level anterior cervical discectomy and fusion (ACDF) using rigidplate constructs and cortico-cancellous allograft. ACDF has demonstrated efficacy for treatment of multilevel degenerative cervical conditions, but current data exists in small heterogeneous forms. Methods A retrospective review included 98 patients with primary 3-level ACDF surgery at one institution from 2008 to 2013 with minimum 1-year follow-up. Cervical sagittal vertical axis (SVA), segmental height, fusion, and lordosis radiographs were measured preoperatively and at 2 postoperative periods. Results Rates of asymptomatic pseudarthroses and total reoperations were 18% and 4%, respectively. Results demonstrated immediate improvements in cervical lordosis (5.5°, p < 0.01) and segmental height (5.0-mm increase, p < 0.01) with little changes in the cervical SVA (3.2-mm increase, p < 0.01). The segmental height decreased from immediate postoperative period to final follow-up (1.7-mm decrease, p < 0.01). Older age was protective against radiolucent lines (p < 0.05). Patient-reported outcomes significantly improved following surgery (p < 0.01). Current smoking status and diagnosis of diabetes mellitus had no impact on radiographic or clinical outcomes. Risk factors were not identified for the 5 reoperations (4%). Conclusion Three-level ACDF with rigid-plating and cortico-cancellous allograft is an effective procedure for degenerative diseases of the cervical spine without the application of additional adjuncts or combined anteriorposterior cervical surgeries. Significant improvements in cervical lordosis, segmental height, and segmental alignment can be achieved with little change in cervical SVA and a low rate of reoperations over short-term follow-up. Similarly, patient-reported outcomes show significant improvements.

Background The rabbit lumbar spine is a commonly utilized model for studying intervertebral disc degeneration and for the pre‐clinical evaluation of regenerative therapies. Histopathology is the foundation for which alterations to disc morphology and cellularity with degeneration, or following repair or treatment are assessed. Despite this, no standardized histology grading scale has yet been established for the spine field for any of the frequently utilized animal models. Aims The purpose of this study was to establish a new standardized scoring system to assess disc degeneration and regeneration in the rabbit model. Materials and Methods The scoring system was formulated following a review of the literature and a survey of spine researchers. Validation of the scoring system was carried out using images provided by 4 independent laboratories, which were graded by 12 independent graders of varying experience levels. Reliability testing was performed via the computation of intra‐class correlation coefficients (ICC) for each category and the total score. The scoring system was then further refined based on the results of the ICC analysis and discussions amongst the authors. Results The final general scoring system involves scoring 7 features (nucleus pulposus shape, area, cellularity and matrix condensation, annulus fibrosus/nucleus pulposus border appearance, annulus fibrosus morphology, and endplate sclerosis/thickening) on a 0 (healthy) to 2 (severe degeneration) scale. ICCs demonstrated overall moderate to good agreement across graders. An addendum to the main scoring system is also included for use in studies evaluating regenerative therapeutics, which involves scoring cell cloning and morphology within the nucleus pulposus and inner annulus fibrosus. Discussion Overall, this new scoring system provides an avenue to improve standardization, allow a more accurate comparison between labs and more robust evaluation of pathophysiology and regenerative treatments across the field. Conclusion This study developed a histopathology scoring system for degeneration and regeneration in the rabbit model based on reported practice in the literature, a survey of spine researchers, and validation testing., The rabbit lumbar spine is a commonly utilized model for studying intervertebral disc degeneration and for the pre‐clinical evaluation of regenerative therapies, and histopathology is the foundation for which alterations to disc morphology and cellularity with degeneration, or following repair or treatment are assessed. Despite this, no standardized histology grading scale has yet been established for the spine field for any of the frequently utilized animal models. Therefore, the purpose of this study was to establish a new standardized scoring system to assess disc degeneration and regeneration in the rabbit model.

The bone healing environment in the posterolateral spine following arthrodesis surgery is one of the most challenging in all of orthopedics and our understanding of the molecular signaling pathways mediating osteogenesis during spinal fusion is limited. In this study, the spatial and temporal expression pattern of Wnt signaling factors and inhibitors during spinal fusion was assessed for the first time. Bilateral posterolateral spine arthrodesis with autologous iliac crest bone graft was performed on 21 New Zealand White rabbits. At 1‐, 2‐, 3‐, 4‐, and 6‐weeks, the expression of sclerostin and a variety of canonical and noncanonical Wnts signaling factors was measured by qRT‐PCR from tissue separately collected from the transverse processes, the Outer and Inner Zones of the fusion mass, and the adjancent paraspinal muscle. Immunohistochemistry for sclerostin protein was also performed. Sclerostin and many Wnt factors, especially Wnt3a and Wnt5a, were found to have distinct spatial and temporal expression patterns. For example, harvesting ICBG caused a significant increase in sclerostin expression. Furthermore, the paraspinal muscle immediately adjacent to the transplanted ICBG also had significant increases in sclerostin expression at 3 weeks, suggesting new potential mechanisms for pseudarthroses following spinal arthrodesis. The presented work is the first description of the spatial and temporal expression of sclerostin and Wnt signaling factors in the developing spine fusion, filling an important knowledge gap in the basic biology of spinal fusion and potentially aiding in the development of novel biologics to increase spinal fusion rates., In this study, the temporal and spatial expression of sclerostin and Wnt signaling factors during a developing posterolateral spine fusion was determined for the first time. Most of the canonical and noncanonical Wnt factors and inhibitors that were assessed were found to have distinct spatial and temporal expression patterns and those patterns were found to differ between successful fusions and nonunions, suggesting new molecular mechanisms for the development of pseudarthroses following spinal arthrodesis. This fills an important knowledge gap in the basic biology of spinal fusion and may aid in the development of novel biologics to increase spinal fusion rates.

Background Context Anterior cervical discectomy and fusion (ACDF) is a very common operative intervention for the treatment of cervical spine degenerative disease in those who have failed non-operative measures. However, studies examining long-term follow-up on patients who underwent ACDF reveal evidence of radiographic and clinical degenerative disc disease at the levels adjacent to the fusion construct. Consistent with other junctional regions of the spine, the cervicothoracic junction (CTJ) has significant morphologic variations. As a result, the CTJ undergoes significant static and dynamic stress. Given these findings, there has been some thought that ACDF down to C7 may experience additional risks for adjacent segment degeneration/disease (ASD) when compared with ASDFs that are cephalad to C7. Purpose The goal of this study is to evaluate the rate of radiographic and clinical ASD in patients who have undergone single- or multilevel ACDF, down to C7. Study Design This is a retrospective cohort study. Patient Sample The sample included consecutive patients from a single orthopedic surgeon at one quaternary referral medical center who underwent an ACDF between January 2008 and November 2014. Indications for surgery included radiculopathy, myelopathy, or myeloradiculopathy in the setting of failed conservative treatments. Patients were excluded if they had an ACDF of which the caudal level was cephalad to C7 or if they had undergone a previous cervical fusion. Outcome Measures Radiographic diagnosis of ASD was determined by the presence of disc space narrowing >50%, new or enlarged osteophytes, end plate sclerosis, or increased calcification of the anterior longitudinal ligament (ALL). Postoperatively, data were collected on the presence of new radicular or myelopathic symptoms indicative of pathology at C7–T1, indicating a diagnosis of clinical ASD. Methods Demographic information was collected for all patients, which included age, sex, body mass index, smoking status, and Charleston Comorbidity Index (CCI). Several radiographic parameters were measured preoperatively, immediately postoperatively, and at the last follow-up: C2–C7 lordosis, sagittal vertical axis (SVA), thoracic inlet angle (TIA), and T1 slope C2–C7 lordosis were measured using the Cobb angle between the inferior end plate of C2 to the inferior end plate of C7. Radiographic and clinical factors associated with ASD were analyzed postoperatively. Results Four patients (4.8%) presented with clinical evidence of ASD, all of whom also showed signs of radiographic ASD and improved with conservative measures. No patients underwent reoperation for ASD at the C7–T1 junction. Thirty patients (36.1%) presented radiographic evidence of ASD. These were generally older (54.4 vs. 48.4 years; p=.014). There were neither significant differences in radiographic parameters nor between single- versus multilevel ACDFs and the development of ASD. Conclusions The cervicothoracic junction may present with vulnerability to ASD given the junctional biomechanics. However, this study provides evidence that an ACDF with the caudal level of C7 does not incur additional risk of ASD, showing similar outcomes to ACDFs at other levels.

The objective of this review article is to summarize the rationale and the literature on the use of small molecules in spine fusion. As opposed to recombinant proteins or even antibodies, the small size of pharmacologic small molecules affords them many unique advantages. Although the literature remains sparse on this subject as it pertains to spinal fusion, there is mounting evidence that small molecules can be effective at increasing bone formation by modulating a variety of biologic signaling cascades in bone. While there is still much work to be done in this field before it is ready to make a clinical impact, pharmacologic small molecules remain a very promising strategy for achieving consistently successful spine fusions.

Degeneration of the intervertebral disc (IVD) results in deterioration of the spinal motion segment and can lead to debilitating back pain. Given the established mitotic and anti-apoptotic effects of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in a variety of cell types we postulated that rhPDGF-BB might delay disc cell degeneration through inhibition of apoptosis. To address this hypothesis, we treated human IVD cells isolated from five independent patients with rhPDGF-BB in monolayer and 3D pellet cultures. The anti-apoptotic potential, cell proliferative capacity, morphology/pellet differentiation, and gene expression of PDGF-treated IVD cells were evaluated via flow cytometry/immunohistochemistry, MTT assays, histology, and quantitative RT-PCR, respectively. We found that rhPDGF-BB treatment significantly inhibited cell apoptosis, increased cell proliferation and matrix production, and maintained mRNA expression of critical extracellular matrix genes. This study suggests two possible mechanisms for the anti-degenerative effects of rhPDGF-BB on human IVD cells. First, PDGF treatment strongly inhibited IVD cell apoptosis in 3D cultures. Second, rhPDGF-BB acts as an anabolic agent, promoting maintenance of IVD cell phenotype in 3D culture, based on the molecular and protein expression analysis. We speculate that rhPDGF-BB may be used as a biologic treatment to target early degenerative IVD disease in the future.

BACKGROUND CONTEXT Anterior cervical discectomy and fusion (ACDF) has been associated with successful outcomes for a variety of degenerative conditions of the cervical spine via neural decompression and stabilization. ACDF for one or two levels using allograft and rigid plating gives a high union rate with good clinical outcome. However, concerns regarding the potential stress-shielding associated with rigid plating, the lack of healing potential with allograft, pseudarthrosis, subsidence, loss of lordosis and reoperation have previously been discussed, particularly for multilevel cases. PURPOSE The purpose of the current study is to detail the radiographic and clinical outcomes of a series of three-level primary ACDF procedures using a rigid construction with cortico-cancellous allograft at a single institution. STUDY DESIGN/SETTING Retrospective cohort series. PATIENT SAMPLE A retrospective review was performed on 98 patients who underwent a primary three-level ACDF with rigid plating and cortico-cancellous allograft by a single-surgeon from 2008 to 2014 with a minimum of 1-year follow-up. Exclusion criteria included revision surgeries, infections, anterior or posterior surgeries, and follow-up of less than 12 months. OUTCOME MEASURES Demographics, perioperative data, and complications were recorded. Preoperative, 2-week postoperative, and final follow-up images were reviewed to evaluate cervical sagittal vertical axis (SVA), segmental height, fusion, cervical lordosis, and fusion. Patient reported outcomes were obtained in the form of Neck Disability Index (NDI) scores and Visual Analog Scales (VAS) scores for the neck and arm. METHODS Radiographic measurements from preoperative, immediate postoperative, and final follow-up were compared using Student's t-tests. Bivariate and multivariate analyses were used to identify risk factors for patient report and radiographic outcomes such as: reoperations, graft lucencies, loss of lordosis, loss of segmental height, and progressive cervical SVA. RESULTS Average follow-up was 24.7±13.2 months. Rates of asymptomatic radiographic lucencies and total reoperations were 18% (17 patients) and 4% (4 patients) respectively. Immediate improvements in cervical lordosis (5.5°, p CONCLUSIONS Three-level ACDF with rigid-plating and cortico-cancellous allograft is an effective procedure for degenerative diseases of the cervical spine without the application of additional adjuncts or combined anterior-posterior cervical surgeries. Significant improvements in cervical lordosis, segmental height, and segmental alignment can be achieved with little change in cervical SVA and a low rate of reoperations over short-term follow-up. Similarly, patient reported outcomes show significant improvements following these three-level ACDF procedures.

BACKGROUND CONTEXT The optimal method of addressing the positive sagittal imbalance often present in degenerative scoliosis (DS) is controversial. An important distinction is whether or not the etiology of the loss of lumbar lordosis (LL) and positive sagittal imbalance often seen on preoperative radiographs, is truly structural, or whether it is more positional in nature given that spinal stenosis is almost always present in DS patients who require surgery. This distinction directly affects the decision about whether or not, in addition to decompression, the entire curve needs to be addressed (regional or global fusion), or if a lesser local fusion of only the symptomatic levels can be performed with a satisfactory radiographic result. PURPOSE This study aims to determine (1) if the loss of LL often associated with DS is structural or rather largely due to positional factors secondary to spinal stenosis, and (2) if the entire DS curve or a lesser local fusion of only the neurologically symptomatic levels need to be addressed. STUDY DESIGN/SETTING Retrospective case series. PATIENT SAMPLE We obtained radiographic and clinical data on 114 consecutive patients. We included patients if they had loss of normal LL (positive sagittal imbalance) observed on preoperative radiographs and underwent a decompression and instrumented posterolateral inter-transverse process arthrodesis of only their neurologically symptomatic levels in the setting of DS. We excluded patients if they had undergone a previous fusion, concomitant osteotomy procedure, or any type of interbody arthrodesis, or had less than 6 months follow-up. Of the original 114 patients identified, 68 fulfilled the above criteria. OUTCOME MEASURES Pre- and postoperative radiographs were reviewed to measure lumbar lordosis, pelvic incidence, pelvic tilt, and sacral slope. Postoperative radiographs were also measured against preoperative extension lumbar radiographs and lumbar magnetic resonance imaging (MRI) to compare changes in radiographic pelvic parameters. METHODS Three independent members of the research team performed all measurements. Inter-rater reliability was calculated using a Pearson coefficient test and a strong correlation was considered if R>0.8. The three sets of measurements were then averaged for final statistical analysis. Relationships were considered significant at p RESULTS Average follow-up was 22 months. In addition to decompression, instrumented fusion was most commonly performed from L4 to S1 (N=17), followed by L3-S1 (N=12). The average PI found preop and postop was 52° and 53°, respectively. The average PT found preop and postop was 24° and 27°, respectively. Preoperative LL had a mean Cobb angle of 32° (range 2°–60°). Preop MRIs and lumbar extension radiographs revealed an average LL of 42° (range 10°–66°) and 48° (range 20°–74°), respectively. Initial postop radiographs (average 3 weeks) revealed that LL was corrected to a mean of 44° (range 14°–68°, p CONCLUSIONS We were able to correct LL to within 10° of the PI in this cohort of symptomatic DS patients with decompression and local instrumented fusion of symptomatic levels only. Loss of LL in symptomatic DS patients has a large positional component likely due to stenosis. Preoperative MRI and extension radiographs can be used to predict achievable postoperative LL correction.

Adolescent idiopathic scoliosis (AIS) patients treated before the 1990s have a 1% to 2% increased lifetime risk of developing breast and thyroid cancer as a result of ionizing radiation from plain radiographs. Although present plain radiographic techniques have been able to reduce some of the radiation exposure, modern treatment algorithms for scoliosis often include computed tomography (CT) and intraoperative fluoroscopy. The exact magnitude of exposure to ionizing radiation in adolescents during modern scoliosis treatment is therefore unclear.To determine the difference in radiation exposures in patients undergoing various forms of treatment for AIS.Retrospective cohort.Patients aged 9 to 18 years with a diagnosis of AIS, followed and/or treated with nonoperative or operative management for a minimum of 2 years.Number of radiographs and total radiation exposure calculated.The charts and radiographs of patients managed for AIS at a single institution between September 2007 and January 2012 were reviewed. Patients were divided into three groups: operative group, braced group, and observation group. Patient demographics, Cobb angles, and curve types were recorded. The number of radiographs per year that each patient received and the total radiation dose were recorded. The plain radiographic radiation exposure was then combined with the direct exposure recording from ancillary tests, such as fluoroscopy and CT, and a radiation exposure rate was calculated (mrad/y). A single-factor analysis of variance (α=0.01) with a Tukey honest significant difference post hoc analysis was used to test significance between groups.Two hundred sixty-seven patients were evaluated: 86 operative, 80 brace, and 101 observation. All groups had similar demographics and curve type distribution. The mean initial Cobb angle at presentation was significantly different between the groups: operative (57°±11°), brace (24°±7.9°), and observation (18°±9.4°) (p.01). There was a significant difference among the groups in terms of the mean number of radiographs received per year; operative group, 12.2 (95% confidence interval [CI]: 10.8-13.5; p.001); braced group, 5.7 (95% CI: 5.2-6.2; p.001), and observed group, 3.5 (95% CI: 3.160-3.864; p.001). The operative group received 1,400 mrad per year (95% CI: 1,350-1,844; p.001), braced group received 700 mrad per year (95% CI: 598-716; p.001), and observed group received 400 mrad per year (95% CI: 363-444; p.001). Importantly, 78% of radiation in the operative group was attributable to the operative fluoroscopy exposure.Significant differences exist in the total radiation exposure in scoliosis patients with different treatment regimens, with operative patients receiving approximately 8 to 14 times more radiation than braced patients or those undergoing observation alone, respectively. Operative patients also receive more than twice the radiation per year than braced or observed patients. Almost 78% of the annual radiation exposure for operative patients occurs intraoperatively. Because children are notably more sensitive to the carcinogenic effects of ionizing radiation, judicious use of present imaging methods and a search for newer imaging methods with limited ionizing radiation should be undertaken.

Object The chronic stinger syndrome is a distinct entity from acute stingers and has been shown to have its own pathophysiology that, unlike acute stingers, may reflect long-standing geometrical changes of the subaxial spinal canal and chronic irritation/degeneration of the exiting nerve root complex. There is no method available, however, to accurately predict these symptoms in athletes. The mean subaxial cervical space available for the cord (MSCSAC) is a novel alternative to the Torg ratio for predicting neurological symptoms caused by cervical spondylosis in elite athletes. It is the goal of this study to determine critical values for this measurement index and to retrospectively correlate those values to neurological symptoms. Methods Magnetic resonance images obtained in 103 male athletes participating in the 2005 and 2006 National Football League Scouting Combine and a control group of 42 age-matched male nonathletes were retrospectively reviewed. The Torg ratio and SAC values were calculated in triplicate at each cervical level from C3–6 by using lateral radiographs and midsagittal T2-weighted MR images of the cervical spine, respectively. These values were then averaged for each individual to produce mean subaxial cervical Torg ratio (MSCTR) and MSCSAC values. Receiver operating characteristic curves were constructed for each measurement technique and were compared based on their respective area under the curves (AUCs). Results The MSCSAC difference between athletes with and without chronic stingers was statistically significant (p < 0.01). The difference between athletes with and without chronic stingers compared with controls was also statistically significant (p < 0.001 and p < 0.001, respectively). The AUC for the MSCSAC was 0.813, which was significantly greater than the AUC for both the MSCTR (p = 0.0475) and the individual Torg ratio (p = 0.0277). The MSCTR had the second largest AUC (0.676) and the conventional method of measuring individual Torg ratio values produced the lowest AUC (0.661). It was found that using the MSCSAC with a critical value of 5.0 mm produced a sensitivity of 80% and a negative likelihood ratio of 0.23 for predicting chronic stingers. Lowering the cutoff value to 4.3 mm for the MSCSAC resulted in a possible confirmatory test with a specificity of 96% and a positive likelihood ratio of 13.25. Conclusions A critical value of 5.0 mm for the MSCSAC provides the clinician with a screening test for chronic stingers and anything < 4.3 mm adds additional confidence as a confirmatory test. These results are ~ 20% more accurate than the classic Torg ratio based on our AUC analysis. It was found that measuring the spinal geometry throughout the length of the subaxial cervical spine produced a more reliable method by which to predict neurological symptoms than the traditional approach of measuring individual levels. This shows that the underlying pathogenesis of the chronic stinger syndrome is best characterized as a process that involves the entire subaxial region uniformly.