Clinical and surgical results related to anterior-only multilevel cervical decompression and instrumented fusion for degenerative disease.

Introduction: Anterior-only multilevel cervical decompression and fusion surgery (AMCS) on 3-5-levels is challenging due to potential complications. Also, outcome predictors after AMCS are poorly understood. Research Question: We hypothesize that in patients with at most mild/moderate cervical kyphosis (CK) of the cervical spine, restoration of cervical lordosis (CL) positively influences clinical outcomes. Methods: Analysis of consecutive patients presenting with symptomatic degenerative cervical disease or non-union undergoing AMCS. We measured CL from C2 to C7, Cobb angle of fused levels (fusion angle, FA), C7-Slope, and sagittal vertical axis C2-7 (cSVA, stratified into ≤4cm∖>4cm). Patients with excellent outcome were grouped in BEST-outcomes and with moderate/poor outcomes in WORST-outcomes. Results: We included 244 patients. Fifty-four percent had 3-, 39% 4-level and 7% had 5-level fusion. At mean follow-up of 26 months, 41% of patients achieved BEST-outcome and 23% WORST-outcome. Complications and reoperation rates did not significantly differ. Non-union significantly influenced outcomes. The number of patients with non-union was significantly higher in patients with a preoperative cSVA>4cm (OR 13.1 (95%CI:1.8-96.8). Our model, based on the multivariable analysis with WORST-outcome as outcome variable showed a high accuracy (NPV=73%, PPV=77%, specificity=79%, sensitivity=71%). Discussion and Conclusion: In 3-5-level AMCS, improvement of FA and cSVA were independent predictors of clinical outcome. Improvement of CL positively influenced clinical outcomes and rates of non-union.

Surgical Realignment After Anterior Multilevel Decompression Using Cages and Plate for 3-level to 5-level Degenerative Fusions: Lessons Learned From the Analysis of Geometric Changes, Reciprocal Coupling, and Prediction of Sagittal Cervical Balance.

STUDY DESIGN: Retrospective, single-center case study. OBJECTIVE: Postoperative cervical imbalance with cervical sagittal vertical axis (cSVA) >4 cm can be predicted in 3-level to 5-level anterior-only cervical multilevel fusion surgery (ACMS). SUMMARY OF BACKGROUND DATA: Previous studies established correlations between cervical kyphosis (CK) correction and postoperative balance (cSVA ≤4 cm) with improved clinical outcomes. Understanding of what influences restoration of cervical lordosis (CL) in patients with degenerative disease with mild to moderate CK subjected to ACMS is important. To achieve a better understanding of geometric changes after ACMS, this study examines factors predicting perioperative alignment changes and regional interdependencies. MATERIALS AND METHODS: Analysis of patients with ACMS. Analysis included patient baseline characteristics, demographics and complications, and focused on radiographic measures including CL C2-7, fusion angle (FA), C7-Slope (C7S), T1-slope (T1S), T1-CL mismatch, and cSVA (cSVA ≤4 cm/>4 cm). We aimed to predict postoperative imbalance (cSVA >4 cm) and conducted a multivariable logistic regression analysis. RESULTS: Inclusion of 126 patients with 3-level to 5-level ACMS, mean age was 56 years and 4 fusion levels on average. Preoperative CK was present in 9%, mean FA-correction was 8 degrees, maximum 46 degrees. Postoperatively, 14 patients had cSVA >4 cm. A neural network model for prediction of cSVA >4 cm was established including preoperative cSVA, preoperative CL and correction of FA. The model achieved high performance (positive predictive value=100%, negative predictive value=94%, specificity=100%, sensitivity=20%). Also, variables such as nonunion, chronic lumbar pain or thoracolumbar multilevel fusion influenced the postoperative cSVA >4 cm rate. Alignment analysis highlighted strong correlations between C7S/T1S and cSVA/C2-tilt ( r =0.06/ r =0.7, P <0.0001). A formula was established to transfer cSVA data into C2-tilt data. CONCLUSION: This study identified independent variables predicting postoperative cSVA >4 cm including FA, which can be influenced by the surgeon. Our model supports the decision-making process targeting a postoperative cSVA ≤4 cm.

Center of rotation analysis for thoracic and lumbar 3-column osteotomies in patients with sagittal plane spinal deformity: insights in geometrical changes can improve understanding of correction mechanics.

OBJECTIVE: Three-column osteotomy (3CO) is used for severe spinal deformities. Associated complications include sagittal translation (ST), which can lead to neurological symptoms. Mismatch between the surgical center of rotation (COR) and the concept of the ideal COR is a potential cause of ST. Matching surgical with conceptual COR is difficult with pedicle subtraction osteotomy (PSO) and vertebral column resection (VCR). This mismatch influences correction geometry, which can prevent maximum possible correction. The authors' objective was to examine the sagittal correction geometry and surgical COR of thoracic and lumbar 3CO. METHODS: In a retrospective study of patients with PSO or VCR for severe sagittal plane deformity, analysis of surgical COR was performed using pre- and postoperative CT scans in the PSO group and digital radiographs in the VCR group. Radiographic analysis included standard deformity measurements and regional kyphosis angle (RKA). All patients had 2-year follow-up, including neurological outcome. Preoperative CT scans were studied for rigid osteotomy sites versus mobile osteotomy sites. Additional radiographic analysis of surgical COR was based on established techniques superimposing pre- and postoperative images. Position of the COR was defined in a rectangular net layered onto the osteotomy vertebrae (OVs). RESULTS: The study included 34 patients undergoing PSO and 35 undergoing VCR, with mean ages of 57 and 29 years and mean RKA corrections of 31° and 49°, respectively. In the PSO group, COR was mainly in the anterior column, and surgical and conceptual COR matched in 22 patients (65%). Smaller RKA correction (27° vs 32°, p = 0.09) was seen in patients with anterior eccentric COR. Patients with rigid osteotomy sites were more likely to have an anterior eccentric COR (41% vs 11%, p = 0.05). In the VCR group, 20 patients (57%) had single-level VCR and 15 (43%) had multilevel VCR. COR was mainly located in the anterior or middle column. Mismatch between surgical and conceptual COR occurred in 24 (69%) patients. Larger RKA correction (63° vs 45°, p = 0.03) was seen in patients with anterior column COR. Patients with any posterior COR had a smaller RKA correction compared to the rest of the patients (42° vs 61°, p = 0.007). CONCLUSIONS: Matching the surgical with the conceptual COR is difficult and in this study failed in one- to two-thirds of all patients. In order to avoid ST during correction of severe deformities, temporary rods, tracking rods, or special instruments should be used for correction maneuvers.

Surgical outcomes with anatomic reduction of high-grade spondylolisthesis revisited: an analysis of 101 patients.

OBJECTIVE: The ideal strategy for high-grade L5-S1 isthmic spondylolisthesis (HGS) remains controversial. Critical questions include the impact of reduction on clinical outcomes, rate of pseudarthrosis, and postoperative foot drop. The scope of this study was to delineate predictors of radiographic and clinical outcome factors after surgery for HGS and to identify risk factors of foot drop. METHODS: This was a single-center analysis of patients who were admitted for HGS, defined as grade III or greater L5 translation according to the Meyerding (MD) classification. Complete postoperative reduction was defined as MD grade I or less and L5 slip < 20%. Forty-six patients completed health-related quality-of-life questionnaires (Oswestry Disability Index, Physical Component Summary of SF-36, and visual analog scale) and ≥ 2 years' follow-up (average 105 months). A 540° approach was used in 61 patients, a 360° approach was used in 40, and L5 corpectomy was used in 17. Radiographic analysis included measures of global spinopelvic balance (e.g., pelvic incidence [PI], lumbar lordosis) and measurement of lumbosacral kyphosis angle (LSA), L4 slope (L4S), L5 slip (%), and postoperative increase of L5-S1 height. RESULTS: The authors included 101 patients with > 1 year of clinical and radiographic follow-up. The mean age was 26 years. Average preoperative MD grade was 3.8 and average L5 slip was 81%; complete reduction was achieved in 55 and 42 patients, respectively, according to these criteria. At follow-up, LSA correlated with all clinical outcomes (r ≥ 0.4, p < 0.05). Forty patients experienced a major complication. Risk was increased in patients with greater preoperative deformity (i.e., LSA) (p = 0.04) and those who underwent L5 corpectomy (p < 0.01) and correlated with greater deformity correction. Thirty-one patients needed revision surgery, including 17 for pseudarthrosis. Patients who needed revision surgery had greater preoperative deformity (i.e., MD grade and L5 slip) (p < 0.01), greater PI (p = 0.02), and greater postoperative L4S (p < 0.01) and were older (p = 0.02), and these patients more often underwent L5 corpectomy (p < 0.01). Complete reduction was associated with lower likelihood of pseudarthrosis (p = 0.08) and resulted in better lumbar lordosis correction (p = 0.03). Thirty patients had foot drop, and these patients had greater MD grade and L5 slip (p < 0.01) and greater preoperative LSA (p < 0.01). These patients with foot drop more often required L5 corpectomy (p < 0.01). Change in preoperative L4S (p = 0.02), LSA (p < 0.01), and L5-S1 height (p = 0.02) were significantly different between patients with foot drop and those without foot drop. A significant risk model was established that included L4S change and PI as independent variables and foot drop as a dependent variable (82% negative predictive value and 71% positive predictive value, p < 0.01). CONCLUSIONS: Multivariable analysis identified factors associated with foot drop, major complications, and need for revision surgery, including degree of deformity (MD grade and L5 slip) and correction of LSA. Functional outcome correlated with LSA correction.

Temporary treatment with magnetically controlled growing rod for surgical correction of severe adolescent idiopathic thoracic scoliosis greater than 100°.

INTRODUCTION: Correction of severe idiopathic scoliosis poses surgical challenges. Treatment options entail anterior and/or posterior release, Halo-gravity traction (HGT) and three-column osteotomies (3CO). The authors report results with a novel technique of temporary short-term magnetically controlled growing rod (MCGR) as part of a posterior-only strategy to treat severe idiopathic major thoracic curves (MTC). METHODS: Seven patients with MTC > 100° treated with temporary MCGR were included. Mean age was 15 years. Preoperative MTC was av. 118° and TC-flexibility av. 19.8%. Patients underwent posterior instrumentation, periapical release using advanced Ponte osteotomies, segmental insertion of pedicle screws and a single MCGR. After av. 14 days, the second surgery was performed with removal of MCGR and final correction and fusion. The spinal height from lowest instrumented vertebra (LIV) to T1 was measured. MTC-correction and scoliosis correction index (SCI) were calculated. RESULTS: No patient suffered a major complication or neurologic deficit. Instrumentation was from T2 to L3 or L4. This kind of staged surgery achieved a correction of postop MTC to av. 39°, MTC-correction 67% and SCI of av. 4.3. Spinal height T1-LIV increased from preoperative av. 288 mm to postoperative av. 395 mm indicating an increase of > 10 cm. CONCLUSION: This is the first series of AIS patients that had temporary MCGR to treat severe thoracic scoliosis. A staged protocol including internal temporary distraction with MCGR after posterior release and definitive correction resulted in large MTC-correction and restoration of trunk height. Results indicate that technique has the potential to reduce the necessity for HGT and high-risk 3CO for the correction of severe scoliosis.

Resolution of the lumbosacral fractional curve and evaluation of the risk for adding on in 101 patients with posterior correction of Lenke 3, 4, and 6 curves.

OBJECTIVE: In double and triple major adolescent idiopathic scoliosis curves it is still controversial whether the lowest instrumented vertebra (LIV) should be L3 or L4. Too short a fusion can impede postoperative distal curve compensation and promote adding on (AON). Longer fusions lower the chance of compensation by alignment changes of the lumbosacral curve (LSC). This study sought to improve prediction accuracy for AON and surgical outcomes in Lenke type 3, 4, and 6 curves. METHODS: This was a retrospective multicenter analysis of patients with adolescent idiopathic scoliosis who had Lenke 3, 4, and 6 curves and ≥ 1 year of follow-up after posterior correction. Resolution of the LSC was studied by changes of LIV tilt, L3 tilt, and L4 tilt, with the variables resembling surrogate measures for the LSC. AON was defined as a disc angle below LIV > 5° at follow-up. A matched-pairs analysis was done of differences between LIV at L3 and at L4. A multivariate prediction analysis evaluated the AON risk in patients with LIV at L3. Clinical outcomes were assessed by the Scoliosis Research Society 22-item questionnaire (SRS-22). RESULTS: The sample comprised 101 patients (average age 16 years). The LIV was L3 in 54%, and it was L4 in 39%. At follow-up, 87% of patients showed shoulder balance, 86% had trunk balance, and 64% had a lumbar curve (LC) ≤ 20°. With an LC ≤ 20° (p = 0.01), SRS-22 scores were better and AON was less common (26% vs 59%, p = 0.001). Distal extension of the fusion (e.g., LIV at L4) did not have a significant influence on achieving an LSC < 20°; however, higher screw density allowed better LC correction and resulted in better spontaneous LSC correction. AON occurred in 34% of patients, or 40% if the LIV was L3. Patients with AON had a larger residual LSC, worse LC correction, and worse thoracic curve (TC) correction. A total of 44 patients could be included in the matched-pairs analysis. LC correction and TC correction were comparable, but AON was 50% for LIV at L3 and 18% for LIV at L4. Patients without AON had a significantly better LC correction and TC correction (p < 0.01). For patients with LIV at L3, a significant prediction model for AON was established including variables addressed by surgeons: postoperative LC and TC (negative predictive value 78%, positive predictive value 79%, sensitivity 79%, specificity 81%). CONCLUSIONS: An analysis of 101 patients with Lenke 3, 4, and 6 curves showed that TC and LC correction had significant influence on LSC resolution and the risk for AON. Improving LC correction and achieving an LC < 20° offers the potential to lower the risk for AON, particularly in patients with LIV at L3.

Diagnostic accuracy of CT scan-based criteria compared with surgical exploration for the analysis of cervical fusion and nonunion.

OBJECTIVE: Computed tomography (CT) scans are accepted as the imaging standard of reference to define union after anterior cervical discectomy and fusion (ACDF). However, ideal CT criteria to diagnose union have not been identified or validated. The objective of this study was to analyze the diagnostic value of 9 CT-based criteria and identify the ideal criteria among them to assess cervical fusion after ACDF using surgical exploration as the standard of reference. METHODS: The authors performed a retrospective radiographic study of a single surgeon's prospective assessment of osseous fusion during cervical revision surgery by analyzing complete radiographic data in 44 patients who underwent anterior cervical revision surgery due to symptomatic suspected nonunion or adjacent level disease. All patients received standard preoperative CT scans, which were assessed by an independent radiologist to evaluate 9 diagnostic criteria for osseous union. During revision surgery, scar tissue was removed and manual segmental translation tests were performed. Nonunion was defined by visualized motion at the treated ACDF level. RESULTS: In total, 44 patients were included in the study (30 men; patient age 54 ± 6 years, BMI 28 ± 5 kg/m2). For analysis of fusion, 75 cervical levels were explored, of which 61 levels (81%) showed intraoperative movement indicating nonunion. Statistical analysis showed that of the 9 parameters used to diagnose bone union, "bridging bone on ≥ 3 CT slices" yielded the highest sensitivity (100%) and specificity (58%). Multivariate analysis revealed that prediction accuracy was not increased if several criteria were combined to determine fusion. CONCLUSIONS: The authors found that the best indicator of bone union was the item bridging bone on ≥ 3 CT slices. Combining the scoring of more than one criterion did not increase the diagnostic accuracy.

Flexibility of thoracic kyphosis affects postoperative sagittal alignment in adult patients with spinal deformity.

PURPOSE: Proximal junctional kyphosis (PJK) in adult spinal deformity (ASD) surgery patients is a severe complication with potential need for revision surgery. While thoracic kyphosis (TK) is known to influence PJK, the role of TK flexibility is still unknown. We analyzed the influence of TK flexibility to predict postoperative sagittal alignment. METHODS: Patients with ASD, ≥ 2-year follow-up, and upper-most instrumented vertebra (UIV) including and below T10 were included in this retrospective study. TK flexibility, defined as > 10° difference of the TK in standing and supine imaging, was analyzed. Patient characteristics like age, sex, weight, total hip arthroplasty, and sagittal alignment parameters were studied. RESULTS: Sixty-five patients aged 66 ± 8 years were included in the study. Lowest instrumented vertebra was S1 or the ilium in 85% of them; the number of levels being fused averaged 7. Flexible TK was present in 31% (n = 20). These patients had a larger preoperative TK (p < 0.01), but no PJK was found (p = 0.04). In contrast, patients who underwent revision surgery had a decreased TK flexibility (p = 0.04) and increased PJK angle at follow-up (p = 0.01). In the non-flexible patients, the PJK was found in 14% of patients. CONCLUSIONS: Based on our retrospective data, TK flexibility influences the outcome of ASD surgery. In patients demonstrating no TK flexibility, a more cephalad UIV-level should be considered because spontaneous curve correction in the sagittal plane might be low in these patients. This new parameter should be included in future prediction models. These slides can be retrieved under Electronic Supplementary Material.

Osteotomies in ankylosing spondylitis: where, how many, and how much?

INTRODUCTION: This article presents the current concepts of correction of spinal deformity in ankylosing spondylitis (AS) patients. Untreated AS can be a debilitating disease. In a few patients, disease progression results in severe spinal deformity affecting not only the thoracolumbar, but also the cervical spine. Surgery for correction in AS patients has a long history. With the advent of modern instrumentation, standardization of surgical and anesthesiologic techniques, surgical safety and corrective results could be improved and experiences from lumbar osteotomies could be transferred to the cervical spine. METHODS: This article presents the current concepts of correction of spinal deformity in AS patients. In particular, questions regarding the localization and number of osteotomies, the optimal surgical target angle as well as planning and prediction of postoperative alignment are discussed. RESULTS: Insight into recent technical developments, current challenges with correction and geometric analysis of center of rotation (COR) in cervical 3-column osteotomies (3CO) will be presented. CONCLUSION: The article should encourage readers to improve surgical correction efficacy and provide a better understanding of correction geometry in 3CO for thoracolumbar and cervical spinal deformities.

Posterior vertebral column resection with 360-degree osteosynthesis in osteoporotic kyphotic deformity and spinal cord compression.

Osteoporotic fractures with severe kyphosis and neurologic deficits often require decompression and stabilisation. To reduce the risk of procedure-related complications, single-stage posterolateral vertebrectomy and a 360-degree fusion can be performed. An adequate reduction of kyphotic deformity through this approach has not been reported. The aim of this study is to investigate the efficacy of kyphotic deformity reduction by this approach in osteoporotic situation. A retrospective analysis and chart review was performed for 10 consecutive patients who underwent posterolateral decompression and posterior vertebrectomy with dorsal mesh stabilisation and reduction of kyphotic deformity. Preoperative back pain was 8.6 on a visual analogue scale; it was reduced to 5.5 at discharge and 3.7 at the latest follow-up (18 months). The Frankel score improved from D to E (three patients) or was equal (E). Radiological segmental kyphosis was corrected from a mean of 25° to 5° (p < 0.008) postoperatively with a loss of 3° at follow-up (p < 0.005). Single-stage posterolateral vertebrectomy allow for a fast and safe reconstitution/preservation of neurological function in patients with osteoporotic fracture and kyphotic deformity. A significant correction of often-accompanied hyperkyphosis is possible without neurological deterioration and with an improved sagittal profile and good pain reduction.

Granulation Tissue Eroding the Subchondral Bone Also Promotes New Bone Formation in Ankylosing Spondylitis.

OBJECTIVE: We previously suggested that fibroblast-rich granulation tissue eroding the subchondral bone is instrumental in the joint remodeling that occurs in ankylosing spondylitis (AS). The purpose of this study was to determine if this granulation tissue also carries bone-forming capabilities, which we approached by searching for bone-forming cells (hypertrophic chondrocytes, osteoblasts) in its vicinity. We also assessed adipogenic tissue transformation, which has been suggested to be an intermediate feature in AS bone formation based on imaging studies. METHODS: The facet joints of AS patients, osteoarthritis (OA) patients, and autopsy subjects (controls) were screened for subchondral granulation tissue. We searched for hypertrophic chondrocytes by assessing RUNX-2, type X collagen, and matrix metalloproteinase 13 (MMP-13) expression, for osteoblasts by analyzing RUNX-2, CD56, and type I collagen expression, as well as for signs of new bone formation. Adipocytes and lipid accumulation were assessed in Safranin O-stained sections. RESULTS: In the joints of AS and OA patients, RUNX-2-positive cells were found to be lining the granulation tissue. These cells coexpressed type I collagen but lacked type X collagen and MMP-13 expression, confirming their osteoblastic nature. In 91% of AS joints and in 20% of OA joints (P < 0.05), we observed foci of new bone formation at contact zones between the granulation tissue and the cartilage. Joints containing bony spots showed greater replacement of the adjacent bone marrow by granulation tissue than did joints without bone formation (P < 0.05). The granulation tissue often contained adipocytes and lipid accumulations. Replacement of the subchondral bone marrow by fat tissue was also frequently found but was not associated with new bone formation. CONCLUSION: The subchondral granulation tissue carries osteoblasts, which promote new bone formation, leading to intraarticular ankylosis of the facet joints in AS.

Cartilage in facet joints of patients with ankylosing spondylitis (AS) shows signs of cartilage degeneration rather than chondrocyte hypertrophy: implications for joint remodeling in AS.

INTRODUCTION: In ankylosing spondylitis (AS), joint remodeling leading to joint ankylosis involves cartilage fusion. Here, we analyzed whether chondrocyte hypertrophy is involved in cartilage fusion and subsequent joint remodeling in AS. METHODS: We assessed the expression of chondrocyte hypertrophy markers runt-related transcription factor 2 (Runx2), type X collagen (COL10), matrix metalloproteinase 13 (MMP13), osteocalcin and beta-catenin and the expression of positive bone morphogenic proteins (BMPs) and negative regulators (dickkopf-1 (DKK-1)), sclerostin, (wingless inhibitory factor 1 (wif-1)) of chondrocyte hypertrophy in the cartilage of facet joints from patients with AS or osteoarthritis (OA) and from autopsy controls (CO) by immunohistochemistry. Sex determining region Y (SRY)-box 9 (Sox9) and type II collagen (COL2) expression was assessed as indicators of chondrocyte integrity and function. RESULTS: The percentage of hypertrophic chondrocytes expressing Runx2, COL10, MMP13, osteocalcin or beta-catenin was significantly increased in OA but not in AS joints compared to CO joints. Frequencies of sclerostin-positive and DKK-1-positive chondrocytes were similar in AS and CO. In contrast, wif-1- but also BMP-2- and BMP-7-expressing and Sox9-expressing chondrocytes were drastically reduced in AS joints compared to CO as well as OA joints whereas the percentage of COL2-expressing chondrocytes was significantly higher in AS joints compared to CO joints. CONCLUSIONS: We found no evidence for chondrocyte hypertrophy within hyaline cartilage of AS joints even in the presence of reduced expression of the wnt inhibitor wif-1 suggesting that chondrocyte hypertrophy is not a predominant pathway involved in joint fusion and remodeling in AS. In contrast, the reduced expression of Sox9, BMP-2 and BMP-7 concomitantly with induced COL2 expression rather point to disturbed cartilage homeostasis promoting cartilage degeneration in AS.

Comparison of Anteroposterior to Posterior-Only Correction of Scheuermann's Kyphosis: A Matched-Pair Radiographic Analysis of 92 Patients.

STUDY DESIGN: Retrospective radiographic benchmark study. OBJECTIVE: To evaluate the amount of instrumented correction obtained from a combined anterior/posterior (A/P) versus posterior-only (post-only) approach for Scheuermann's kyphosis. SUMMARY OF BACKGROUND DATA: An A/P approach was thought to optimize correction; however, instrumentation advances using pedicle screws allow treatment through an all-posterior approach. METHODS: A total of 166 Scheuermann's kyphosis patients were treated between 2 centers: 90 by combined A/P approach at 1 center and 76 by post-only at the second center. From the 166 patients, a matched cohort of 92 (46 from each) was established according to preoperative sagittal (±10°) and hyperextension (HE) Cobb (±10°) measurements and matched for age and gender. RESULTS: In the matched-pair group, average preoperative sagittal Cobb angles were 75.9° for the A/P group versus 78.8° for the post-only group (p = .2). The HE Cobb angles were similar (52.4° vs. 51.1°; p = .6). They showed similar corrections (33.7° vs. 30.6°; p = .3) and postoperative Cobb measurements (43.4° vs. 47.1°; p = .2) as well. The number of fusion levels was 9 in the A/P group and 12 in the post-only group; the difference yielded significance (p = .02). CONCLUSIONS: The A/P and post-only approaches averaged similar degrees of correction. The A/P patients were likely to correct more than their preoperative HE sagittal Cobb measurement, whereas the post-only group corrected close to their preoperative HE measurement. The number of fusion levels was larger with the post-only group.

Histomorphologic and histomorphometric characteristics of zygapophyseal joint remodeling in ankylosing spondylitis.

OBJECTIVE: To unravel the mechanisms that control bony ankylosis in ankylosing spondylitis (AS). METHODS: Histomorphologic and histomorphometric analyses were performed on zygapophyseal joints obtained from 18 patients with AS, 9 patients with osteoarthritis (OA), and 10 cadaver donors without a rheumatic disease (controls). The proteoglycan content of the cartilage was determined by Safranin O staining and the chondrocyte apoptosis according to caspase 3 expression. RESULTS: AS joints were categorized into 3 groups according to the morphology of the joint surfaces and joint space: group 1 were joints with an open joint space, group 2 were joints with cartilaginous fusion, and group 3 were joints with bony fusion of the joint surfaces. Progressive loss of the joint space from group 1 joints to group 3 joints suggests that this grouping corresponds to sequential stages of joint remodeling. Cartilage thickness and subchondral bone plate thickness declined from group 1 to group 3 (P < 0.01). Increased chondrocyte apoptosis rates were found in groups 1 and 2 (P < 0.05), while in group 3, a reduction in the proteoglycan content was found (P < 0.001). Bone marrow replacement and invasion of the subchondral bone plate by fibrous tissue was found predominantly in AS joints in group 2. CONCLUSION: Cartilage degeneration, indicated by cartilage thinning, enhanced chondrocyte apoptosis, and proteoglycan loss, and subchondral bone thinning, promoted by invasion of the subchondral bone plate by a fibrous tissue originating from the bone marrow, are hallmarks of joint remodeling in AS.

In situ analysis of interleukin-23- and interleukin-12-positive cells in the spine of patients with ankylosing spondylitis.

OBJECTIVE: The interleukin-12 (IL-12) family of cytokines has been suggested to play a critical role in inflammatory autoimmune diseases, and recent studies analyzing peripheral blood and synovial fluid from patients with spondyloarthritides suggest that IL-23 might be a proinflammatory factor in these disorders. This study was undertaken to investigate the presence and source of IL-23 in the spines of patients with ankylosing spondylitis (AS). METHODS: The frequency of IL-23-positive and IL-12-positive cells within the subchondral bone marrow and within fibrous tissue replacing normal bone marrow in facet joints of patients with AS was analyzed by immunohistochemistry. The origin of IL-23-positive cells was determined by double staining of CD163+ macrophages, CD68+ macrophages, CD1a+ dendritic cells, tryptase-positive mast cells, myeloperoxidase-positive cells, CD20+ B cells, and CD3+ T cells. Findings in 28 facet joints from 22 AS patients were compared with those in 20 facet joints from 13 patients with osteoarthritis (OA) and 10 normal control specimens. RESULTS: The frequency of IL-23-positive cells in subchondral bone marrow from the joints of AS patients (mean ± SD 42.50 ± 32.81/high-power field [hpf]) was significantly increased compared to that in subchondral bone marrow from OA patients (OA 15.63 ± 29.90/hpf) (P = 0.0017) or controls (19.36 ± 16.8/hpf) (P = 0.03). Myeloperoxidase-positive cells and, to a lesser extent, macrophages and dendritic cells were found to be the origin of IL-23 in the bone marrow. In AS and OA patients, the frequency of IL-23-positive cells was significantly higher than that of IL-12-positive cells (P < 0.001 in both patient groups). Within fibrous tissue from AS and OA facet joints, IL-23 was predominantly produced by CD163+ macrophages (mean ± SD 0.64 ± 0.59/hpf and 4.36 ± 3.4/hpf, respectively) and CD68+ macrophages (2.3 ± 0.65/hpf and 6.54 ± 4.1/hpf, respectively). CONCLUSION: IL-23 is expressed in the subchondral bone marrow and in fibrous tissue replacing bone marrow in facet joints of patients with AS. It might have a role in inflammatory processes and in chronic changes in AS joints, which makes it an interesting potential therapeutic target in this disease.

Analysis of IL-17(+) cells in facet joints of patients with spondyloarthritis suggests that the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response.

INTRODUCTION: In this study, we analysed the number of IL-17(+) cells in facet joints, in the peripheral blood (PB) and synovial fluid (SF) of spondyloarthritis (SpA) patients and compared these results with those of patients with other rheumatic diseases and controls. METHODS: Immunohistochemical analysis of IL-17(+) cells was performed in facet joints of 33 ankylosing spondylitis (AS) patients and compared with data from 20 osteoarthritis (OA) patients. The frequency of IL-17(+)CD4(+) T cells in PB and SF of SpA patients (PB n = 30, SF n = 11), rheumatoid arthritis (RA) patients (PB n = 14, SF n = 7), OA patients (PB n = 10) and healthy controls (PB n = 12) was analysed after stimulation with Staphylococcus aureus Enterotoxin B and phorbol 12-myristate 13-acetate/ionomycin and quantified by flow cytometry. RESULTS: In AS facet joints, the frequency of IL-17-secreting cells was significantly higher than in samples obtained from OA patients (P < 0.001), with a slight predominance of IL-17(+) cells among the mononuclear cells (61.5% ± 14.9%) compared to cells with polysegmental nuclei. Immunofluorescence microscopy revealed that the majority of IL-17(+) cells were myeloperoxidase-positive (35.84 ± 13.06/high-power field (HPF) and CD15(+) neutrophils (24.25 ± 10.36/HPF), while CD3(+) T cells (0.51 ± 0.49/HPF) and AA-1(+) mast cells (2.28 ± 1.96/HPF) were less often IL-17-positive. The frequency of IL-17(+)CD4(+) T cells in the PB and SF of SpA patients did not differ significantly compared to RA patients, OA patients or healthy controls. CONCLUSIONS: Our data suggest an important role for IL-17 in the inflammatory processes in AS. However, the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response.

The morbidity of open transthoracic approach for anterior scoliosis correction.

STUDY DESIGN: Retrospective study. OBJECTIVE: To analyze the patient satisfaction and the patients' perceived approach-related morbidity (ArM) after open thoracotomy (OTC) for instrumented anterior scoliosis surgery. SUMMARY OF BACKGROUND DATA: There is no mid- to long-term data on the patients' perceived ArM concerning chest wall dissection for open anterior scoliosis correction. METHODS: A specific questionnaire was used to retrospectively evaluate mid- to long-term follow-up data concerning ArM after OTC of patients younger than 30 years (range, 11-28 years) who underwent anterior open transthoracic scoliosis surgery. The questionnaire was comprised of detailed scar-related questions. Applying strict inclusion criteria, we could analyze outcomes in terms of percentage morbidity (morbidity [%]) of 40 patients who underwent OTC for instrumented scoliosis correction. RESULTS: Mean age of the patients was 16 ± 3.8 years, follow-up was 61.5 ± 72.6 months on average, and mean incision length was 25.7 ± 3.1 cm. Mean number of levels fused was 5.9 ± 1.5. Single thoracotomy was performed in 25 patients and a thoracoabdominal approach in 15 patients. Mean morbidity (0%, not delineating no ArM; 100%, delineating highest ArM) was 5.4% ± 11.3%; 47.5% of patients had no morbidity; 12.5% had morbidity >10% (mean: 28.5%). Signs of intercostal neuralgia (ICN) were present in 10%. Patients judged their clinical outcome as "good" in 20% and "excellent" in 80%. Statistical analysis did not reveal differences in outcomes and percentage morbidity concerning age of patients, extent of approach (thoracotomy vs. thoracoabdominal approach) and incision length, gender, or follow-up length. However, the presence of ICN had a significant effect on the outcome, showing high correlation with increased morbidity (P < 0.0001). In the clinical judgment of outcomes, the severity of the ArM after OTC was mild, except for 2 patients who had moderate approach and scar-related morbidity. CONCLUSION: ArM after open thoracic spinal surgery or thoracoscopic procedures can be assessed using the questionnaire. The current study showed that ArM in young patients who underwent OTC for anterior instrumented scoliosis correction was low. Patients with increased signs of ICN did worse in terms of the questionnaire survey. The study showed that neither cosmesis nor scar-related problems were a concern for patients undergoing OTC.

Approach-related morbidity in transthoracic anterior spine surgery: a clinical study and review of literature / Morbidade relacionada à abordagem transtorácica anterior da coluna: estudo clínico e revisão da literatura / Morbilidad relacionada con el abordaje torácico anterior de la columna: estudio clínico y revisión de la literatura

BACKGROUND: Anterior access to the thoracic spine is done by open thoracotomy (OTC) or video-assisted thoracoscopic surgery (VATS). VATS is known as the method which results in lower morbidity rates, but there is little evidence of its less invasiveness. Objective: The current study yielded for outcome data concerning patients' perception of approach-related morbidity (ArM) following OTC for spinal surgery and that of a control group having a chest tube thoracotomy (CTT). METHODS: We performed a questionnaire assessment of ArM after OTC and CTT. Applying strict inclusion criteria, we compared outcomes in terms of percentage morbidity (Morbidity percent) of 43 patients that underwent OTC for instrumented scoliosis correction to 30 patients that had CTT for minor thoracic pathologies (e.g., pneumothorax). RESULTS: Mean age in CTT and OTC Group was 50.2 and 16.5 years old, follow-up was of 32.2 and 58.4 months, and mean incision length was 2.5 and 25.5 cm, respectively. Mean number of levels fused in the OTC Group was 5.8. Mean morbidity (0 percent delineating no cases, 100 percent delineating highest morbidity) for the CTT Group was 10.8±15.4 percent (0-59.5 percent), 42 percent of patients had no morbidity. Signs of intercostal neuralgia (ICN) were present in 16.7 percent. A total of 35.5 percent had a morbidity >10 percent (mean: 27.5 percent), and 10 percent of morbidity cases were defined as having a chronic post-thoracotomy pain (CPP). In the OTC Group, mean morbidity was 7.0±12.7 percent (0-52.1 percent), 44 percent had no morbidity. Out of the sample, 18.6 percent had morbidity >10 percent (mean: 28.6 percent). Signs of ICN were present in 14 percent. In both groups, the presence of ICN had a significant impact on and showed correlation with morbidity (p<0.0001). In terms of clinical judgement, the severity of the ArM after a CTT or OTC was generally mild except for one patient in each group. Age and follow-up were significantly ...

INTRODUÇÃO: A abordagem anterior da coluna torácica tem sido utilizada por meio da toracotomia aberta (TA) ou vídeo-assistida (TVA). A abordagem vídeo-assistida tem sido mencionada como a de menor morbidade do procedimento, apesar de não existir evidência científica que confirme essa observação. OBJETIVO: Observar os resultados relacionados à morbidade da toracotomia aberta para a correção de deformidade da coluna vertebral e toracotomia para a colocação de tubo de drenagem torácica, utilizando um grupo de pacientes como controle. MÉTODOS: Com base em questionário relacionado com a avaliação da morbidade da abordagem anterior da coluna torácica respondido pelos pacientes, e utilizando critérios estritos de inclusão dos pacientes, foram avaliados, em termos de porcentagem (morbidade por cento), 43 pacientes submetidos à toracotomia aberta para tratamento da escoliose (Grupo OTC) e 30 pacientes portadores de outras doenças de menor gravidade submetidos à toracotomia para a colocação de dreno de tórax após o procedimento (por exemplo, pneumotórax) (Grupo CTT). RESULTADOS: A média de idade dos pacientes de ambos os grupos foi 50,2 e 16,5 anos; seguimento clínico médio foi de 32,2 e 58,4 meses; e a extensão da incisão da pele 2,5 e 25,5 cm, respectivamente. A média do número de vértebras artrodesadas foi 5,8 no grupo submetido à toracotomia aberta para a correção de deformidade. A morbidade média (variando de 0 por cento, nenhuma morbidade, a 100 por cento, alta morbidade) no grupo de pacientes submetidos à toracotomia para colocação de dreno de tórax foi 10,8±15,4 (0-59,5 por cento), e 42 por cento dos pacientes não apresentavam morbidade. No grupo submetido à toracotomia aberta para a colocação do dreno de tórax, foi observada neuralgia intercostal em 16,7 por cento, e 35,5 por cento dos pacientes apresentavam morbidade maior que 10 por cento (média 27,5 por cento). A morbidade foi definida como a presença de dor crônica após toracotomia. ...

INTRODUCCIÓN: el abordaje anterior de la columna torácica ha sido utilizado por medio de la toracotomía abierta o vídeo asistida. El abordaje video asistida ha sido mencionada como la menor morbilidad del procedimiento, a pesar de existir poca evidencia científica confirmando esa observación. OBJETIVO: el objetivo del presente estudio fue observar los resultados relacionados con la morbilidad de la toracotomía abierta para la corrección de la deformidad de la columna vertebral y toracotomía para la colocación de tubo de drenaje torácica, utilizando ese grupo como Control. MÉTODOS: con base en un cuestionario respondido por los pacientes; y relacionado con la evaluación de la morbilidad del abordaje anterior de la columna torácica y utilizando criterios estrictos de inclusión de los pacientes, fueron evaluados 43 pacientes sometidos a toracotomía abierta para tratamiento de la escoliosis; y 30 pacientes portadores de otras enfermedades de menor gravedad, que fueron sometidos a la toracotomía para la colocación de dreno de tórax después del procedimiento. RESULTADOS: el promedio de edad de los pacientes sometidos al procedimiento en el tórax y a la toracotomía para la colocación de dreno o toracotomía abierta para tratamiento de escoliosis fue, respectivamente: 50.2 años y 16.5 años; el seguimiento clínico fue de 32.2 meses y 54.8 meses; y la extensión de la incisión de la piel 2.5 cm y 25 cm. El promedio del número de vértebras artrosadas fue 5.8 en el grupo sometido a la toracotomía abierta para la corrección de deformidad. La morbilidad promedio (variando de 0 por ciento - ninguna morbilidad a 100 por ciento - alta morbilidad) en el grupo de pacientes sometidos a la toracotomía para colocación de dreno de tórax fue de 10.8±15.4 (0-59.5 por ciento), y un 42 por ciento de los pacientes no presentaron morbilidad. En el grupo sometido a la toracotomía abierta para la colocación del dreno de tórax fue observada neuralgia intercostal en 16.7 ...

Immunohistochemical analysis of osteoblasts in zygapophyseal joints of patients with ankylosing spondylitis reveal repair mechanisms similar to osteoarthritis.

OBJECTIVE: New bone formation of the spine is a typical feature of ankylosing spondylitis (AS). It is unknown whether new bone formation is part of a physiological repair process or a unique pathological entity of the disease. METHODS: We analyzed zygapophyseal joints from patients with AS and osteoarthritis (OA) undergoing spinal surgery for rigid hyperkyphosis (AS) or radiculopathy caused by severe OA. In 17 patients with AS, 11 with OA, and 5 controls we performed immunohistochemical analysis of osteoprotegerin (OPG), nuclear factor-kappaB ligand (RANKL), and osteocalcin (OC) expression in osteoblasts and determined the trabecular thickness in AS and OA patients and controls. Osteoclasts were detected by tartrate-resistant alkaline phosphatase (TRAP) staining. RESULTS: Trabecular thickness was significantly lower in patients with AS compared to OA (p = 0.01). The absolute number of CD56+ osteoblasts (p < 0.001) and OC+ (p = 0.002), OPG+ (p = 0.003), and RANKL+ osteoblasts (p = 0.03) in AS patients was also significantly lower than in OA patients. The percentages of OC+, OPG+, and RANKL+ osteoblasts did not differ between AS and OA (p > 0.05 in all cases). In controls, the percentages of OPG+ (p = 0.013) and OC+ (p = 0.034) but not RANKL+ (p > 0.05) osteoblasts were significantly lower compared to AS patients. The frequency of TRAP+ osteoclasts in AS patients was significantly lower compared to OA (p < 0.001), but higher compared to controls. CONCLUSION: Immunohistochemical analysis of zygapophyseal joints suggested that osteoblast activity is similar in AS and OA, indicating that new bone formation is possibly a physiological function of repair in both diseases.

Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis.

OBJECTIVE: Osteocytes are considered to be sensors of bone damage and regulators of bone mass by specifically expressing sclerostin, an inhibitor of bone formation. The contribution of osteocytes in regulating local bone remodeling in arthritis is unknown. The aim of this study was to investigate the role of osteocytes as contributors to bone remodeling in ankylosing spondylitis (AS). METHODS: Sclerostin expression and osteocyte death were assessed by immunohistochemistry in joints derived from patients with AS, patients with rheumatoid arthritis (RA), and patients with osteoarthritis (OA), as well as from control subjects. In addition, the serum level of sclerostin was assessed by enzyme-linked immunosorbent assay in healthy subjects and patients with AS; this assessment included the longitudinal correlation of sclerostin serum levels and radiographic progression in the spine of patients with AS. RESULTS: Sclerostin expression was confined exclusively to osteocytes. Whereas the majority of osteocytes in healthy individuals and patients with RA were sclerostin positive, expression was significantly reduced in patients with OA and was virtually absent in patients with AS. Moreover, serum levels of sclerostin were significantly lower in patients with AS than in healthy individuals. Importantly, low serum sclerostin levels in patients with AS were significantly associated with the formation of new syndesmophytes (P = 0.007). CONCLUSION: Sclerostin expression is impaired in patients with AS, suggesting a specific alteration of osteocyte function in this disease. A low serum level of sclerostin in the setting of AS is linked to increased structural damage, emphasizing the role of sclerostin in the suppression of bone formation.