Association Between Vertebral Endplate Defects and Patient-reported Symptoms: An Immunohistochemical Study Investigating the COX-2/PGE-2/EP-4 Axis.

BACKGROUND CONTEXT: Vertebral endplate defects are often implicated in degenerative disc disorders, yet their connection to patient-reported symptoms remains unclear. COX-2 and PGE-2 are known for their roles in inflammation and pain, with EP-4 receptor involvement in pain signaling. Examining their expression in vertebral endplate tissues may provide insights into pathomechanism of low back pain. PURPOSE: To investigate the association between endplate defects and patient-reported symptoms and to further clarify the role of the COX-2/PGE-2/EP-4 axis in the pathogenesis of chronic low back pain. STUDY DESIGN/SETTING: Retrospective study PATIENT SAMPLE: A total of 71 patients who had undergone single-level L4/5 or L5/S1 modified laminectomy decompression preserving proximal upper laminae and transforaminal lumbar interbody fusion surgery were included in this study, including 18 patients diagnosed with lumbar disc herniation, 19 with lumbar disc herniation accompanied by degenerative lumbar spinal stenosis, and 34 with degenerative spondylolisthesis. OUTCOME MEASURES: Demographic data, Pfirrmann grade, Modic changes, endplate defect score, visual analog scale (VAS) for back and leg pain, and Oswestry Disability Index (ODI) before surgery, 3-month and 6-month follow-up, and the percentage of immune-positive cells (COX-2, PGE-2, and EP-4) in endplate tissue sections. METHODS: Patients were divided into Defect and Non-defect groups according to endplate morphology on lumbar MR. All intraoperative endplate specimens were immediately fixed in 10% formaldehyde, and then embedded in paraffin 3 days later for tissue sections. The outcome measures were compared between the Defect group and Non-defect group. Data were analyzed using independent t-tests and χ² tests. Pearson's rank correlation test was used to assess correlations between patient-reported symptoms and the percentage of immune-positive cells in the groups. Multivariable logistic regression models using the forward stepwise likelihood ratio method were used to identify the factors that were independently associated with endplate defects. RESULTS: The age of Defect group was significantly higher than that of Non-defect group (52.5±7.7 vs. 57.2±9.1. P=0.024). There were no significant differences in gender, diagnosis, BMI, comorbidities, or surgical level between the two groups. Modic changes (Type Ⅱ/Type Ⅲ) were more common in patients of Defect group than Non-defect group (38.5% vs. 11.1%, P<0.001), and so was disc degeneration (Pfirrmann grade Ⅳ/Ⅴ) (69.2% vs. 33.3%, P<0.001). Defect group had significantly higher VAS-Back (6.5±2.0 vs. 4.9±1.6, P<0.001) and ODI scores (62.9±10.7 vs. 45.2±14.8, P<0.001) than Non-defect group, while there was no significant differences between the two groups during the 3 and 6-month follow-up after surgery. Histologically, Defect group was characterized by upregulation of COX-2, PGE-2, and EP-4 in endplate tissue sections. Both in Defect and Non-defect groups, VAS-Back showed moderate positive correlations with the expressions of COX-2 (r=0.643; r=0.558, p both<0.001), PGE-2 (r=0.611; r=0.640, p both<0.001), and EP-4 (r=0.643; r=0.563, p both<0.001). Multivariate regression analyses reveled that percentage of COX-2-positive cells was associated with endplate defects (OR=1.509, 95%CI [1.048∼2.171], P=0.027), as well as percentage of PGE-2-positive (OR=1.291, 95%CI [1.106∼1.508], P=0.001) and EP-4-positive cells (OR=1.284, 95%CI [1.048∼2.171], P=0.003). CONCLUSIONS: Patients with endplate defects had worse quality of life, more severe disc degeneration and Modic changes, and up-regulated COX-2/PGE-2/EP-4 axis expression in cartilage endplates in patients with defected endplates. Inflammatory factors may significantly contribute to the onset and progression of chronic low back pain in patients with endplate defects, consequently impacting patient-reported symptoms.

How Does the Slump Sitting Radiograph Increase Proportion of Segmental Instability and Kyphotic Alignment of Lumbar Degenerative Spondylolisthesis?

OBJECTIVE: Clinical and radiographic degenerative spondylolisthesis (CARDS) classification was proposed to differentiate homogenous lumbar degenerative spondylolisthesis (LDS) subgroups. The sitting radiograph exhibited lumbar malalignment with maximum lumbar kyphosis, intervertebral kyphosis, and spondylolisthesis.This study aimed to assess the sitting radiograph for distribution of clinical and radiographic degenerative spondylolisthesis classification, and to elucidate its significance for exhibiting kyphotic alignment (CARDS type D) and segmental instability. METHODS: A cohort of 101 patients with symptomatic lumbar degenerative spondylolisthesis (LDS) between September 2018 and December 2020 were recruited. The distribution and relibility of CARDS classification with or without sitting radiograph was assessed. The translational and angular range of motion and segmental instability was also evaluated. Univariate analysis of variance was used for multiple groups, and the least significant difference for two groups. Kappa consistency test of intrarater and interrater was evaluated for CARDS classification with or without sitting radiograph. Chi-square test was used to compare paried categorical data. RESULTS: Utility of sitting radiographs for CARDS classification revealed higher percentage of type D than that without the sitting radiograph (p < 0.001). The sitting radiograph revealed a larger slip distance than the flexion radiograph (p = 0.003), as well as a lower slip angle than flexion radiograph (p < 0.001). The sitting-supine modality demonstrated the largest translational range of motion compared to the sitting-extension (p < 0.001) and flexion-extension modalities (p < 0.001). The sitting-supine modality showed larger angular range of motion than the flexion-extension modality (p < 0.001). The percentage of flexion, extension, upright, supine, and sitting radiograph to identify translational instability was higher than that without sitting radiograph (p < 0.001), as well as taking angular motion ≥10° as an additional criterion for segmental instability (p < 0.001). CONCLUSION: The CARDS classification was reliable for LDS. The sitting radiograph showed maximal slip distance and kyphotic slip angle. Application of the sitting radiograph was necessary for evaluating segmental instability and kyphotic alignment of LDS.

L4/5 Disc Herniation: Not Unusually Accompanied with L5/S1 Low-Grade Spondylolytic Spondylolisthesis.

OBJECTIVE: Isthmic spondylolisthesis (IS) is distinguished by a congenital defect or acquired fracture of the pars interarticularis. Numerous studies on L5 low-grade IS have been carried out; however, there is a paucity of data regarding the condition of L5 IS concomitant with L4/5 disc herniation. This study aimed to identify the incidence rate and to illustrate the possible risk factors for L4/5 disc herniation in L5 low-grade IS patients. METHODS: A total of 268 consecutive patients diagnosed as L5/S1 low-grade IS between May 2017 and May 2022 were retrospectively enrolled in this study. Depending on the presence of L4/5 disc herniation or not, patients were divided into an L4/5 disc herniation group (L4/5 DH) and an L4/5 non-disc herniation group (L4/5 non-DH). Radiographic parameters were measured, and the ratios of L4-S1 segmental lordosis (SL) to lumbar lordosis (LDI), L4 inferior endplate (IEP) to L5 superior endplate (SEP) (L4 IEP/L5 SEP), and L5 IEP to S1 SEP (L5 IEP/S1 SEP) were compared between groups. The Pfirrmann grade of the L4/5 disc and the L5/S1 disc, and Roussouly classifications of each patient were also recorded. Univariate analysis (including independent-samples t-test and χ2 -test) and multiple logistic regression analysis were performed to analyze the data. RESULTS: There were 40 patients (14.9%) in the L4/5 DH group. The Roussouly classification differed significantly between groups. As demonstrated by the Pfirrmann grade, the L4/5 DH group showed more advanced disc degeneration at L4/5 than the L4/5 non-DH group. In contrast to the L4/5 non-DH group, the L4/5 DH group had a significantly larger L4 IEP, L4 IEP/L5 SEP, S1 SEP, and LDI while smaller L4/5 disc angle, L4/5 disc height, slip percentage, lumbar lordosis, and sacral slope. Multivariate logistic regression analysis revealed that higher L4/5 disc Pfirrmann grade (p = 0.004), decreased L4/5 disc height (p < 0.001), and lower L5 slip percentage (p = 0.022) were significantly associated with the occurrence of L4/5 DH. CONCLUSIONS: L4/5 disc herniation is not unusually accompanied by L5/S1 low-grade IS. Advanced L4/5 disc degeneration, decreased L4/5 disc height, and lower L5 slip percentage might be significantly associated with L4/5 disc herniation.

Utility of MRI-based vertebral bone quality scores and CT-based Hounsfield unit values in vertebral bone mineral density assessment for patients with diffuse idiopathic skeletal hyperostosis.

This study investigated bone mineral density assessment for patients with DISH. DXA-based T-scores overestimated bone quality, while MRI-based VBQ scores and CT-based HU values provided accurate assessments, particularly for advanced degenerative cases. This enhances accurate evaluation of BMD, crucial for clinical decision-making. PURPOSE: To investigate the diagnostic effectiveness of DXA, MRI, and CT in assessing bone mineral density (BMD) for diffuse idiopathic skeletal hyperostosis (DISH) patients. METHODS: Retrospective analysis of 105 DISH patients and 116 age-matched controls with lumbar spinal stenosis was conducted. BMD was evaluated using DXA-based T-scores, MRI-based vertebral bone quality (VBQ) scores, and CT-based Hounsfield unit (HU) values. Patients were categorized into three BMD subgroups. Lumbar osteophyte categories were determined by Mata score. Demographics, clinical data, T-scores, VBQ scores, and HU values were collected. Receiver operating characteristic (ROC) analysis identified VBQ and HU thresholds for diagnosing normal BMD using DXA in controls. Correlations between VBQ, HU, and lumbar T-score were analyzed. RESULTS: Age, gender, and BMI showed no significant differences between DISH and control groups. DISH patients had higher T-score (L1-4), the lowest T-score, and Mata scores. VBQ and HU did not significantly differ between groups. In controls, VBQ and HU effectively diagnosed normal BMD (AUC = 0.857 and 0.910, respectively) with cutoffs of 3.0 for VBQ and 104.3 for HU. DISH had higher normal BMD prevalence using T-scores (69.5% vs. 58.6%, P < 0.05), but no significant differences using VBQ (57.1% vs. 56.2%, P > 0.05) and HU (58.1% vs. 57.8%, P > 0.05). Correlations revealed moderate correlations between HU and T-scores (L1-4) in DISH (r = 0.642, P < 0.001) and strong in controls (r = 0.846, P < 0.001). Moderate negative correlations were observed between VBQ and T-scores (L1-4) in DISH (r = - 0.450, P < 0.001) and strong in controls (r = - 0.813, P < 0.001). CONCLUSION: DXA-based T-scores may overestimate BMD in DISH. VBQ scores and HU values could effectively complement BMD assessment, particularly in DISH patients or those with advanced lumbar degeneration.

Not All Osteophytes Are Located on the Right Side of the Vertebrae in Diffuse Idiopathic Skeletal Hyperostosis: A Quantitative Analysis in Relation to the Position of Aorta.

OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by osteophytes in the anterior vertebrae, and the presence of aorta may have an impact on their formation. However, the anatomical positional relationship between the aorta and osteophytes in patients with DISH remains controversial. This study aimed to evaluate the position of osteophytes in relation to aorta in DISH, and the influence of aortic pulsation on the formation of osteophytes from the perspective of morphology. METHODS: We conducted a retrospective review of 101 patients diagnosed with DISH and symptomatic lumbar spinal stenosis between June 2018 and December 2021. A total of 637 segments with heterotopic ossification in DISH were used for quantitative measurements on CT scans. The Cartesian coordinate system was built up on the axial CT scans to reflect the relative position between aorta and osteophytes. Osteophytes were divided into adjacent aorta group (AD group) and non-adjacent aorta group (N-AD group). In terms of the morphology, osteophytes in the AD group were further divided into convex, flat, and concave types. The relative position between aorta and osteophytes, and the aorta-osteophyte distance and morphology of osteophytes were compared. Univariate analysis of variance was performed for multiple groups, and two independent-samples t-tests were used for two groups. RESULTS: From T5 to L4, aorta gradually descended from left side to middle of vertebrae, and osteophytes gradually shifted from right side of vertebrae (T5-T10) to bilateral sides (T11-L4). Of 637 osteophytes in DISH, 60.1% (383/637) were in AD group, including convex type 0.6% (4/637), flat type 34.7% (221/637), and concave type 24.8% (158/637). The N-AD group accounted for 39.9% (254/637). Flat osteophytes were concentrated in T5-T12, while concave osteophytes in T11-L4. Overall, the aorta-osteophyte distance of concave type was significantly smaller than that of flat type. CONCLUSION: Osteophytes are not always located on the right side of vertebrae, but move with the position of the descending aorta. Furthermore, the morphology of osteophytes varies by vertebral segment in DISH, which is related to aorta descending anteriorly in the spine.

Halo-gravity traction combined with growing rod treatment: an effective preoperative management for severe early-onset scoliosis.

OBJECTIVE: The aim of this study was to investigate the effectiveness of preoperative halo-gravity traction (HGT) with subsequent growing rod (GR) treatment in patients with severe early-onset scoliosis (EOS). METHODS: The authors retrospectively reviewed a cohort of patients with severe EOS who had received preoperative HGT with subsequent GR treatment at their center between January 2008 and January 2020. Patients with a Cobb angle in the coronal or sagittal plane that was > 90° were included. All patients received at least 6 weeks of HGT before GR placement. Results of pulmonary function tests (PFTs) and blood gas tests were compared before and after HGT. Radiological parameters were compared pre-HGT, post-HGT, postindex surgery, and at the latest follow-up. RESULTS: A total of 28 patients (17 boys and 11 girls, mean age 6.1 ± 2.3 years) were included in this study. After a mean of 65.2 ± 22.9 days of traction, the Cobb angle decreased from 101.4° ± 12.5° to 74.5° ± 19.3° (change rate 26.5%), and the kyphosis angle decreased from 71.1° ± 21.2° to 42.7° ± 9.5° (change rate 39.9%). There was a significant improvement in BMI but a decrease in hemoglobin levels following HGT. No HGT-related complications were recorded except pin site infections in 2 patients. Statistically significant improvements in PFTs after HGT were observed in forced vital capacity (FVC) (p = 0.011), the percentage predicted FVC (p = 0.007), FEV1 (p = 0.015), and the percentage predicted forced expiratory volume in 1 second (FEV1) (p = 0.005). Fourteen patients received assisted ventilation due to preoperative hypoxia, alveolar hypoventilation, or hypercapnia. Significant improvement was seen in PaCO2 (p = 0.008), PaO2 (p = 0.005), actual bicarbonate (p = 0.005), and oxygen saturation (p = 0.012) in these patients. After the index surgery, the Cobb angle decreased to 49.5° ± 18.9° and the kyphosis angle decreased to 36.2° ± 25.8°. After a mean of 4.3 ± 1.4 lengthening procedures, the Cobb angle was 56.5° ± 15.8°, and the kyphosis angle was 38.8° ± 19.7°. Surgical complications occurred in 14 (50%) patients, but none of these patients required revision surgery at the latest follow-up. CONCLUSIONS: Preoperative HGT notably improved both spinal deformity and pulmonary function in patients with severe EOS. GR treatment after HGT is a safe and effective strategy for these patients.

Junctional Kyphosis after Correction with Long Instrumentation for Late Posttraumatic Thoracolumbar Kyphosis: Characteristics and Risk Factors.

OBJECTIVE: Junctional kyphosis is a common complication after corrective long spinal fusion for adult spinal deformity. Whereas there is still a paucity of data on junctional kyphosis, specifically among late posttraumatic thoracolumbar kyphosis (LPTK) patients. Thus, the aim of this study was to investigate the characteristics and risk factors of junctional kyphosis in LPTK patients receiving long segmental instrumented fusion. METHODS: We retrospectively reviewed a cohort of LPTK patients who had received long segmental instrumented fusion (>4 segments) in our center between January 2012 and January 2019. Radiographic assessments included the sagittal alignment, pelvic parameters, bone quality on CT images, and measurements of the cross-sectional area (CSA, cross-sectional area of muscle-vertebral body ratio × 100) and fat saturation fraction (FSF, cross-sectional area of fat-muscle body ratio × 100) of paraspinal muscles. Patients in this study were divided into those with junctional kyphosis or failure (Group J) and those without (Group NJ) during follow-up. Group J included patients with junctional kyphosis (Group JK) and patients with junctional failure (Group JF). RESULTS: A total of 65 patients (16 males and 49 females, average age 56.5 ± 23.4 years) were enrolled in this study. After (32.7 ± 8.5) months follow-up, 15 patients (23.1%) experienced junctional kyphosis, and four of them deteriorated into junctional failure. Eighty percent (12/15) of junctional kyphosis was identified within 6 months after surgery. In comparison with Group NJ, Group J were older (P = 0.026), longer fusion levels (P < 0.001), greater thoracic kyphosis (P = 0.01), greater global kyphosis (P = 0.023), lower bone quality (P < 0.001), less CSA (P = 0.005) and higher FSF (P <0.001) of paraspinal muscles. Preoperative global kyphosis more than 48.5° (P = 0.001, odds ratio 1.793) and FSF more than 48.4 (P = 0.010, odds ratio 2.916) were identified as independent risk factors of junctional kyphosis. Based on the statistical differences among Group NJ, Group JK and Group JF (P < 0.001), Group JF had lower bone quality than Group NJ (P < 0.001) and Group JK (P = 0.015). In terms of patient-reported outcomes, patients in Group JF had worse outcomes in ODI and VAS scores, and PCS and MCS of SF-36 than Group NJ and group JK CONCLUSION: The prevalence of junctional kyphosis was 23.1% in LPTK patients after long segmental instrumented fusion. Preoperative hyperkyphosis and advanced fatty degeneration of paraspinal muscles were independent risk factors of junctional kyphosis. Patients with lower bone quality were more likely to develop junctional failure.

Relook into the Risk Factors of Proximal Junctional Kyphosis in Early Onset Scoliosis Patients: Does the Location of Upper Instrumented Vertebra in Relation to the Sagittal Apex Matter?

OBJECTIVE: Growing rods surgery is the mainstay of treatment for early-onset scoliosis (EOS) while proximal junctional kyphosis (PJK) is one of the most commonly reported postoperative complications. We sought to investigate the impact of the location of upper instrumented vertebra (UIV) in relation to the sagittal apex on proximal junctional kyphosis in EOS after traditional growing rods (GRs) treatment. METHODS: A total of 102 EOS patients who received traditional growing rods treatment with a follow-up of at least 2 years between 2009 and 2020 were retrospectively reviewed. Radiographic measurements were performed before and after the index surgery and at the latest follow-up. We investigated the coronal Cobb angle and spinopelvic parameters of the whole spine. The location of the UIV, apex, lower instrumented vertebra (LIV), inflection vertebra (IV), the number and distance of UIV-apex, LIV-apex and IV-apex were also recorded. Risk factors for PJK were analyzed by logistic regression analysis. RESULTS: PJK was observed in 21 patients (20.6%) during the follow-up period. The PJK group showed a younger age at the index surgery (5.9 vs. 7.1 years, P = 0.042), more lengthening procedure times (5.0 vs. 4.0, P = 0.032), larger preoperative coronal Cobb angle (82.0 vs. 75.6°, P = 0.038), higher correction rate (51.2% vs. 44.4%, P = 0.047) and larger postoperative proximal junctional angle (PJA) (13.9 vs. 5.5°, P < 0.001) than the non-PJK group. The ratio of the number and distance from UIV-apex to IV-apex also differed significantly between the two groups. The logistic regression revealed that age at the index surgery ≤ 7 years, the ratio of the number from UIV- apex to IV- apex ≤ 0.6 and the ratio of the distance from UIV- apex to IV- apex ≤ 0.6 were independent risk factors for postoperative PJK. CONCLUSION: Besides younger age, a closer location of UIV relative to the sagittal apex is identified to be an independent risk factor of postoperative PJK. Selection of UIV at a relatively farther location away from the sagittal apex might help prevent occurrence of PJK.

Utility of the decubitus or the supine rather than the extension lateral radiograph in evaluating lumbar segmental instability.

OBJECTIVE: To determine the superiority of decubitus and supine radiographs for the reduction of olisthesis instead of the extension radiograph, and the inconsistency of the CT scout view, 3D-reconstruction and MR image in evaluating segmental instability. METHODS: A cohort of 154 low-grade lumbar degenerative spondylolisthesis patients with the average age of (60.9 ± 8.6) years were enrolled. Slip percentage was measured on the flexion, upright and extension radiographs, the decubitus lateral radiograph, CT scout view, the supine median sagittal 3D-reconstruction and MR image. The translational range of motion was calculated, and segmental instability was defined as translational motion ≥ 8%. RESULTS: The flexion radiograph showed higher slip percentage than upright radiograph (p < 0.001). The slip percentage of the MR image was lower than CT scout view (p = 0.003) and CT sagittal radiograph (p = 0.001) on the basis of statistical differences among three groups (p = 0.002). The slip percentage of the CT scout view, decubitus radiograph, and extension radiograph was statistically different (p = 0.01). The CT scout view and sagittal reconstruction had lower slip percentage than the extension radiograph (p = 0.042; p = 0.003, respectively). Both the flexion-supine and flexion-decubitus modality had larger translational motion than the flexion-extension modality (p = 0.007; p < 0.001, respectively). CONCLUSION: Many modalities and techniques are used to show the vertebral displacement and its possible change and any cane used in the daily practice. In this study, supine and decubitus lateral radiography have larger reduction of olisthesis than the extension radiograph. The flexion radiograph coupled with a supine or decubitus radiograph reveals greater mobility than the flexion-extension modality.

Galectin-3 Enhances Osteogenic Differentiation of Precursor Cells From Patients With Diffuse Idiopathic Skeletal Hyperostosis via Wnt/ß-Catenin Signaling.

Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory skeletal disease characterized by the progressive ectopic ossification and calcification of ligaments and enthuses. However, specific pathogenesis remains unknown. Bone marrow mesenchymal stem cells (BMSCs) are a major source of osteoblasts and play vital roles in bone metabolism and ectopic osteogenesis. However, it is unclear whether BMSCs are involved in ectopic calcification and ossification in DISH. The current study aimed to explore the osteogenic differentiation abilities of BMSCs from DISH patients (DISH-BMSCs). Our results showed that DISH-BMSCs exhibited stronger osteogenic differentiation abilities than normal control (NC)-BMSCs. Human cytokine array kit analysis showed significantly increased secretion of Galectin-3 in DISH-BMSCs. Furthermore, Galectin-3 downregulation inhibited the increased osteogenic differentiation ability of DISH-BMSCs, whereas exogenous Galectin-3 significantly enhanced the osteogenic differentiation ability of NC-BMSCs. Notably, the increased Galectin-3 in DISH-BMSCs enhanced the expression of ß-catenin as well as TCF-4, whereas attenuation of Wnt/ß-catenin signaling partially alleviated Galectin-3-induced osteogenic differentiation and activity in DISH-BMSCs. In addition, our results noted that Galectin-3 interacted with ß-catenin and enhanced its nuclear accumulation. Further in vivo studies showed that exogenous Galectin-3 enhanced ectopic bone formation in the Achilles tendon in trauma-induced rats by activating Wnt/ß-catenin signaling. The current study indicated that enhanced osteogenic differentiation of DISH-BMSCs was mainly attributed to the increased secretion of Galectin-3 by DISH-BMSCs, which enhanced ß-catenin expression and its nuclear accumulation. Our study helps illuminate the mechanisms of pathological osteogenesis and sheds light on the possible development of potential therapeutic strategies for DISH treatment. © 2022 American Society for Bone and Mineral Research (ASBMR).

Impact of lumbar fusion on sitting spinopelvic balance: Multisegmental versus monosegmental.

OBJECTIVES: To compare the differences in sagittal spinopelvic parameters between patients receiving monosegmental or multisegmental lumbar fusion and to assess the impact of fusion length on sitting balance. METHODS: The current study recruited 41 patients who had undergone lumbar fusion, consisting of 18 in the monosegmental group and 23 in the multisegmental group. And the control group included 50 lumbar degenerative patients who had no previous spinal fusion surgery. Spinopelvic parameters of patients were assessed: sagittal vertical axis, pelvic tilt, sacral slope, pelvic incidence, thoracic kyphosis, lumbar lordosis, and proximal femur angles. RESULTS: We observed significant differences in sitting TK (P = 0.031), LL (P = 0.012), PT (P = 0.009) and SVA (P = 0.009) among the three groups. When transitioning from standing to sitting, the multisegmental group had the least change in SVA (P = 0.016), PT (P = 0.043), and LL (P = 0.009), with a compensatory increase in TK (P = 0.021). Moderate to strong correlations were found between the change in the LL and those in the SVA (r = -0.548, P = 0.001), PT (r = -0.600, P = 0.001), and SS (r = 0.623, P = 0.001). CONCLUSION: Multisegmental lumbar fusion significantly limits the lumbar mobility and affects the ability to compensate postural changes. Reducing the fusion segments as much as possible is of particular value in preserving lumbar mobility and maintaining the compensatory mechanism of spinopelvis.

Abnormal causal connectivity of left superior temporal gyrus in drug-naïve first- episode adolescent-onset schizophrenia: A resting-state fMRI study.

This study aimed to investigate the alterations of causal connectivity between the brain regions in Adolescent-onset schizophrenia (AOS) patients. Thirty-two first-episode drug-naïve AOS patients and 27 healthy controls (HC) were recruited for resting-state functional MRI scanning. The brain region with the between-group difference in regional homogeneity (ReHo) values was chosen as a seed to perform the Granger causality analysis (GCA) and further detect the alterations of causal connectivity in AOS. AOS patients exhibited increased ReHo values in left superior temporal gyrus (STG) compared with HCs. Significantly decreased values of outgoing Granger causality from left STG to right superior frontal gyrus and right angular gyrus were observed in GC mapping for AOS. Significantly stronger causal outflow from left STG to right insula and stronger causal inflow from right middle occipital gyrus (MOG) to left STG were also observed in AOS patients. Based on assessments of the two strengthened causal connectivity of the left STG with insula and MOG, a discriminant model could identify all patients from controls with 94.9% accuracy. This study indicated that alterations of directional connections in left STG may play an important role in the pathogenesis of AOS and serve as potential biomarkers for the disease.

Coronal imbalance after growing rod treatment in early-onset scoliosis: a minimum of 5 years' follow-up.

OBJECTIVE: The objective of this study was to investigate the incidence and risk factors of coronal imbalance (CI) in patients with early-onset scoliosis (EOS) who underwent growing rod (GR) treatment. METHODS: A consecutive series of 61 patients with EOS (25 boys and 36 girls, mean age 5.8 ± 1.7 years) who underwent GR treatment was retrospectively reviewed. Postoperative CI was defined as postoperative C7 translation on either side ≥ 20 mm. Patients were divided into an imbalanced and a balanced group. Coronal patterns were classified into three types: type A (C7 translation < 20 mm), type B (C7 translation ≥ 20 mm with C7 plumb line [C7PL] shifted to the concave side of the curve), and type C (C7 translation ≥ 20 mm and a C7PL shifted to the convex side of the curve). RESULTS: Each patient had an average of 5.3 ± 1.0 lengthening procedures and was followed for an average of 6.2 ± 1.3 years. Eleven patients (18%) were diagnosed with CI at the latest distraction, 5 of whom graduated from GRs and underwent definitive fusion. However, these patients continued to present with CI at the last follow-up evaluation. The proportion of preoperative type C pattern (54.5% vs 16.0%, p = 0.018), immediate postoperative apical vertebral translation (30.4 ± 13.5 mm vs 21.2 ± 11.7 mm, p = 0.025), lowest instrumented vertebra tilt (11.4° ± 8.2° vs 7.3° ± 3.3°, p = 0.008), and spanned obliquity angle (SOA) (9.7° ± 10.5° vs 4.1° ± 4.5°, p = 0.006) values in the imbalanced group were significantly higher than in the balanced group. Multiple logistic regression demonstrated that a preoperative type C pattern and immediate postoperative SOA > 11° were independent risk factors for postoperative CI. CONCLUSIONS: The incidence of CI in patients with EOS who underwent GR treatment was 18%. This complication could only be slightly improved after definitive spinal fusion because of the autofusion phenomenon. A preoperative type C pattern and immediate postoperative SOA > 11° were found to be the risk factors for CI occurrence at the latest follow-up.

Optimal Reconstruction of Sagittal Alignment According to Global Alignment And Proportion Score Can Reduce Adjacent Segment Degeneration After Lumbar Fusion.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study was to investigate the ability of Global Alignment and Proportion (GAP) score to predict the occurrence of adjacent segment degeneration (ASD) after fusion surgery for lumbar degenerative diseases. SUMMARY OF BACKGROUND DATA: The recently developed GAP score was applied to predict postoperative complications for adult spinal deformity, as well as to facilitate future outcome-based research on optimal treatment for various spinal conditions. However, it remains unclear whether reconstruction of alignment according to GAP score can reduce the ASD rates. METHODS: This study retrospectively reviewed 126 consecutive patients who had undergone lumbar fusion and had been followed over 2 years. Pre- and postoperative radiographs and MRI were analyzed for ASD. GAP scores were calculated based on the early postoperative spinopelvic parameters. Cochran-Armitage test of trend was performed to investigate the association between GAP score and the occurrence of ASD. Receiver-operating characteristic curves were used to analyze the predictive accuracy of the GAP score for ASD. RESULTS: Radiographical ASD (R-ASD) and symptomatic ASD (S-ASD) were diagnosed in 44 (34.9%) patients and in 13 (10.3%) patients, respectively. The patients with a proportioned spinopelvic state according to the GAP score had significantly lower rates of ASD (R-ASD and S-ASD) or S-ASD than those with a moderately or severely disproportioned spinopelvic state. The area under curve for the GAP score predicting ASD and S-ASD was 0.691 (95% confidence interval [CI]: 0.596∼0.785, P < 0.01) and 0.865 (95% CI: 0.771∼0.958, P < 0.01), respectively. CONCLUSION: Our study revealed a significant association between postoperative GAP score and occurrence of ASD after lumbar fusion surgery. Setting surgical goals according to the GAP score may help reduce the occurrence of ASD, especially for S-ASD.Level of Evidence: 4.

Utility of Natural Sitting Lateral Radiograph in the Diagnosis of Segmental Instability for Patients with Degenerative Lumbar Spondylolisthesis.

BACKGROUND: Segmental instability in patients with degenerative lumbar spondylolisthesis is an indication for surgical intervention. The most common method to evaluate segmental mobility is lumbar standing flexion-extension radiographs. Meanwhile, other simple radiographs, such as standing upright radiograph, a supine sagittal magnetic resonance imaging (MRI) or supine lateral radiograph, or a slump or natural sitting lateral radiograph, have been reported to diagnose segmental instability. However, those common posture radiographs have not been well characterized in one group of patients. Therefore, we measured slip percentage in a group of patients with degenerative lumbar spondylolisthesis using radiographs of patients in standing upright, natural sitting, standing flexion, and standing extension positions as well as supine MRI. QUESTIONS/PURPOSES: We asked: (1) Does the natural sitting radiograph have a larger slip percentage than the standing upright or standing flexion radiograph? (2) Does the supine sagittal MRI reveal a lower slip percentage than the standing extension radiograph? (3) Does the combination of the natural sitting radiograph and the supine sagittal MRI have a higher translational range of motion (ROM) and positive detection rate of translational instability than traditional flexion-extension mobility using translational instability criteria of greater than or equal to 8%? METHODS: We retrospectively performed a study of 62 patients (18 men and 44 women) with symptomatic degenerative lumbar spondylolisthesis at L4 who planned to undergo a surgical intervention at our institution between September 2018 and June 2019. Each patient underwent radiography in the standing upright, standing flexion, standing extension, and natural sitting positions, as well as MRI in the supine position. The slip percentage was measured three times by single observer on these five radiographs using Meyerding's technique (intraclass correlation coefficient 0.88 [95% CI 0.86 to 0.90]). Translational ROM was calculated by absolute values of difference between two radiograph positions. Based on the results of comparison of slip percentage and translational ROM, we developed the diagnostic algorithm to evaluate segmental instability. Also, the positive rate of translational instability using our diagnostic algorithms was compared with traditional flexion-extension radiographs. RESULTS: The natural sitting radiograph revealed a larger mean slip percentage than the standing upright radiograph (21% ± 7.4% versus 17.7% ± 8.2%; p < 0.001) and the standing flexion radiograph (21% ±7.4% versus 18% ± 8.4%; p = 0.002). The supine sagittal MRI revealed a lower slip percentage than the standing extension radiograph (95% CI 0.49% to 2.8%; p = 0.006). The combination of natural sitting radiograph and the supine sagittal MRI had higher translational ROM than the standing flexion and extension radiographs (10% ± 4.8% versus 5.4% ± 3.7%; p < 0.001). More patients were diagnosed with translational instability using the combination of natural sitting radiograph and supine sagittal MRI than the standing flexion and extension radiographs (61% [38 of 62] versus 19% [12 of 62]; odds ratio 3.9; p < 0.001). CONCLUSION: Our results indicate that a sitting radiograph reveals high slip percentage, and supine sagittal MRI demonstrated a reduction in anterolisthesis. The combination of natural sitting and supine sagittal MRI was suitable to the traditional flexion-extension modality for assessing translational instability in patients with degenerative lumbar spondylolisthesis. LEVEL OF EVIDENCE: Level III, diagnostic study.

Is Growth-friendly Surgical Treatment Superior to One-stage Posterior Spinal Fusion in 9- to 11-year-old Children with Congenital Scoliosis?

BACKGROUND: The distraction-based growth-friendly technique has become a mainstay of treatment for young children with long-spanned congenital scoliosis. However, in patients who are 9 years to 11 years old, the choice is much less clear, and posterior spinal fusion is also a potential option. QUESTIONS/PURPOSES: Comparing growth-friendly scoliosis surgery and posterior spinal fusion, which technique (1) provides greater correction of spinal deformity, (2) is associated with more surgical complications, and (3) results in greater improvement in pulmonary function tests, health-related quality of life scores, other patient-reported outcomes? METHODS: Between 2009 and 2017, one spinal center performed 212 spinal interventions for scoliosis in patients aged between 9 years and 11 years old and who had open triradiate cartilage, including 40 patients with growth-friendly approaches (34 with growing-rod technique and six with a vertical expandable prosthetic titanium rib) and 172 with one-stage posterior spinal fusion, respectively. During this period, our general indications for using growth-friendly surgery were patients with open triradiate cartilage, major curve higher than 40°, and upper and lower end vertebrae involving at least eight segments. Twelve patients with a median (range) age of 9.3 years (9 to 11) treated with growth-friendly surgery met the following inclusion criteria: (1) had at least two lengthening procedures before definitive spinal fusion along with 2 years of follow-up after definitive spinal fusion; (2) had been followed until skeletal maturity (Risser grade ≥ 4); and (3) with complete radiographic and clinical data (health-related quality of life (HRQoL) and pulmonary function test results) preoperatively and at the latest follow-up. A group of patients between 9 years and 11 years old and underwent one-stage posterior spinal fusion was selected from our database of patients with congenital scoliosis. Our general indications for using one-stage posterior spinal fusion were patients with a major curve greater than 40°, and with thoracic height higher than 18 cm. Sixty-two patients who had open triradiate cartilage and had been followed until skeletal maturity (Risser grade ≥ 4) were accounted for. In this retrospective, controlled study, we matched patients in the posterior spinal fusion group to those 12 patients who had growth-friendly surgery by age, sex, pathologic findings, major curve size, and location of the apex of the major curve (2:1 matching provided 24 patients in the control group). The median (range) age was 9.8 years (9 to 11). We then compared the groups in terms of magnitude of correction and postoperative complications. Surgical complications, including infection, implant-related complications, and alignment-related complications were evaluated and classified using the surgical complications grading system. Pulmonary function tests and HRQoL were also compared between groups. Pulmonary function tests were performed at the same center with a spirometer. HRQoL were assessed by questionnaire, including the 24-item Early-onset Scoliosis questionnaire for parent-reported outcomes and the Scoliosis Research Society-22 questionnaire for patient-reported outcomes. All patients involved in this study gave their informed consent. RESULTS: The posterior spinal fusion group achieved a greater correction magnitude at the latest follow-up (median [range] 46% [28 to 70] versus median 34% [9 to 58], difference of medians = 11%; p < 0.001) than the growth-friendly group. A higher proportion of patients in the growth-friendly group had complications than in the posterior spinal fusion group (7 of 12 versus 4 of 24; p = 0.03). There were no between-group differences in terms of pulmonary function tests. Few differences were found between the groups in terms of 24-item Early-onset Scoliosis parental impact (median [range] 60 [44 to 83] for the growth-friendly group versus median 71 [55 to 87] for the posterior spinal fusion group, difference of medians = 13; p = 0.001), financial burden (median 44 [30 to 55] for the growth-friendly group versus median 62 [53 to 75] for the posterior spinal fusion group, difference of medians = 16; p < 0.001) and the Scoliosis Research Society-22 self-image scores (median 3.8 [3.2 to 4.3] for the growth-friendly group versus median 4.4 [4.1 to 4.6] for the posterior spinal fusion group, difference of medians = 0.5; p = 0.006) at the latest follow-up, and those differences that were observed all favored the posterior spinal fusion group. CONCLUSIONS: In light of the superior deformity correction and fewer observed complications with posterior spinal fusion, and the absence of important differences in validated outcomes scores or pulmonary function tests, posterior spinal fusion might be a better choice for 9- to 11-year-old children with long-spanned congenital scoliosis and limited growth potential in the intended instrumentation area. LEVEL OF EVIDENCE: Level III, therapeutic study.

How does sagittal spinopelvic alignment of lumbar multisegmental spondylolysis differ from monosegmental spondylolysis?

OBJECTIVE: The aim of this study was to investigate sagittal alignment and compensatory mechanisms in patients with monosegmental spondylolysis (mono_lysis) and multisegmental spondylolysis (multi_lysis). METHODS: A total of 453 adult patients treated for symptomatic low-grade spondylolytic spondylolisthesis were retrospectively studied at a single center. Patients were divided into 2 subgroups, the mono_lysis group and the multi_lysis group, based on the number of spondylolysis segments. A total of 158 asymptomatic healthy volunteers were enrolled in this study as the control group. Radiographic parameters measured on standing sagittal radiographs and the ratios of L4-S1 segmental lordosis (SL) to lumbar lordosis (L4-S1 SL/LL) and pelvic tilt to pelvic incidence (PT/PI) were compared between all experimental groups. RESULTS: There were 51 patients (11.3%) with a diagnosis of multi_lysis in the spondylolysis group. When compared with the control group, the spondylolysis group exhibited larger PI (p < 0.001), PT (p < 0.001), LL (p < 0.001), and L4-S1 SL (p = 0.025) and a smaller L4-S1 SL/LL ratio (p < 0.001). When analyzing the specific spondylolysis subgroups, there were no significant differences in PI, but the multi_lysis group had a higher L5 incidence (p = 0.004), PT (p = 0.018), and PT/PI ratio (p = 0.039). The multi_lysis group also had a smaller L4-S1 SL/LL ratio (p = 0.012) and greater sagittal vertical axis (p < 0.001). CONCLUSIONS: A high-PI spinopelvic pattern was involved in the development of spondylolytic spondylolisthesis, and a larger L5 incidence might be associated with the occurrence of consecutive multi_lysis. Unlike patients with mono_lysis, individuals with multi_lysis were characterized by an anterior trunk, insufficiency of L4-S1 SL, and pelvic retroversion.

Does Vertebral End Plate Morphology Affect Cage Subsidence After Transforaminal Lumbar Interbody Fusion?

OBJECTIVE: To investigate the effect of end plate morphology on cage subsidence and to compare the surgical outcomes among patients with different vertebral end plate morphologies. METHODS: We reviewed a series of consecutive patients from January 2009 to January 2016 who had undergone monosegment L4/5 transforaminal lumbar interbody fusion (TLIF) with a follow-up >2 years. The enrolled patients were divided into 3 groups based on the preoperative vertebral end plate morphology on T1-weighed sagittal magnetic resonance scans: concave group (C group), flat group (F group), and irregular group (Ir group). Lumbar lordosis (LL), segmental lordosis (SL), and disc height (DH) were measured on the plain image at each follow-up, and three-dimensional computed tomography (3D-CT) was obtained at 1 year follow-up to evaluate the cage subsidence and solid fusion. RESULTS: A total of 145 consecutive patients (41 males and 104 females) were included in this study, with a mean follow-up of 33.8 ± 12.3 months. The age was significantly older in the Ir group than in the C group or F group (P < 0.05). Cage subsidence was detected in 23 patients (15.9%) at 1 year follow-up through 3D-CT. The incidence of cage subsidence was significantly higher in the Ir group than in the F group or C group (P < 0.05). Patients in the Ir group had significant loss of DH, SL, and LL at the latest follow-up, compared with those in the C group and F group (P < 0.05). Patients with cage subsidence had a significantly older age (P < 0.05). The presence of cage subsidence was associated with end plate morphology as shown by logistic regression analysis (P < 0.05). Before surgery, Oswestry Disability Index and visual analog scale back pain scores were significantly higher in the Ir group than in the C and F groups (P < 0.05). After surgery and until the latest follow-up, each group experienced significant improvement in contrast to preoperative scores regardless of end plate morphology (P < 0.05). CONCLUSIONS: Morphology of the end plate plays an important role in the development of cage subsidence after TLIF surgery. Fused segments with irregular end plates are prone to cage subsidence. Although cage subsidence does not affect short-term clinical outcomes, measures should be taken to prevent cage subsidence-related loss of SL and total LL.

How does the cervical spine respond to hyperkyphosis correction in Scheuermann's disease?

OBJECTIVE: This study aimed to quantify the response of the cervical spine to the surgical correction of Scheuermann's kyphosis (SK) and to postoperative proximal junctional kyphosis (PJK). METHODS: Fifty-nine patients (mean age 14.6 ± 2.3 years) were enrolled in the study: 35 patients in a thoracic SK (T-SK) group and 24 in a thoracolumbar SK (TL-SK) group. The mean follow-up period was 47.2 ± 17.6 months. Radiographic data, PJK-related complications, and patient-reported outcomes were compared between groups. RESULTS: The global kyphosis significantly decreased postoperatively, and similar correction rates were observed between the two groups (mean 47.1% ± 8.6% [T-SK] vs 45.8% ± 9.4% [TL-SK], p = 0.585). The cervical lordosis (CL) in the T-SK group notably decreased from 21.4° ± 13.3° to 13.1° ± 12.4° after surgery and was maintained at 14.9° ± 10.7° at the latest follow-up, whereas in the TL-SK group, CL considerably increased from 7.2° ± 10.7° to 11.7° ± 11.1° after surgery and to 13.8° ± 8.9° at the latest follow-up. PJK was identified in 16 patients (27.1%). Its incidence in the TL-SK group was notably higher than it was in the T-SK group (41.6% [n = 10] vs 17.1% [n = 6], p = 0.037). Compared with non-PJK patients, PJK patients had greater CL and lower pain scores on the Scoliosis Research Society-22 questionnaire (p < 0.05). CONCLUSIONS: Hyperkyphosis correction eventually resulted in reciprocal changes in the cervical spine, with CL notably decreased in the T-SK group but significantly increased in the TL-SK group. Patients developing PJK have increased CL, which seems to have a negative effect on patients' health-related quality of life.

Sagittal reconstruction of lumbosacral contiguous double-level spondylolytic spondylolisthesis: a comparison of double-level and single-level transforaminal lumbar interbody fusion.

BACKGROUND: Contiguous double-level lumbar spondylolytic spondylolisthesis is an extremely rare condition. There is a paucity of data of lumbosacral deformity and sagittal spino-pelvic malalignment among these patients. Moreover, the effect of transforaminal lumbar interbody fusion (TLIF) on sagittal realignment still remains largely unknown. The aim of the study is to investigate the reconstruction of sagittal alignment and the improvement of clinical outcomes after posterior instrumented double-level or single-level TLIF. METHODS: From January 2010 to September 2018, the records of patients with contiguous L4/5 and L5/S1 double-level spondylolytic spondylolisthesis were retrospectively reviewed. Patients who had undergone double-level or single-level TLIF and a minimum of 2 years' follow-up were included. The slippage parameters and spino-pelvic parameters were measured preoperatively, postoperatively, and at the latest follow-up. RESULTS: A total of 58 patients (21 males and 37 females, mean age of 57.1 ± 6.9 years) were enrolled. Thirty-eight patients were treated with double-level TLIF and the remaining 20 with single-level TLIF (L4/5 in 14; L5/S1 in 6). After surgery, the spondylolisthesis was significantly reduced at both L4/5 and L5/S1 level (all P < 0.001). There was a significant reduction in pelvic tilt (P < 0.001) and a significant increase in sacral slope (P < 0.001). Significant increase in L4-S1 height (P < 0.001) and L4-S1 lordosis (P = 0.012) and decrease in L5 slope (P = 0.004) and L5 incidence (P = 0.001) were also observed. Compared to single-level TLIF, double-level TLIF increased L4-S1 height (P < 0.001) and L4-S1 lordosis (P < 0.001) and reduced L4-SVA (P = 0.007) and L5 incidence (P = 0.013) more obviously, and the sagittal balance was better corrected in double-level TLIF group (P = 0.006). Double-level TLIF group showed larger increase in VAS scores for low back pain. The incidence of implant-related complications was lower in the double-level group. CONCLUSION: Posterior short-segment instrumented TLIF can bring favorable radiographic and clinical outcomes in patients with lumbosacral contiguous double-level spondylolytic spondylolisthesis. Double-level TLIF is more efficient to improve L4-S1 height, regional lumbar lordosis, and global sagittal balance.