Core planar cell polarity genes VANGL1 and VANGL2 in predisposition to congenital vertebral malformations.

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2, many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder.

Proper positioning of mice for Cobb angle radiographic measurements.

BACKGROUND: There is no recommended standard for positioning of a mouse for radiographic assessment of the spine. This is necessary to have reproducible radiographic data and avoid false positive results. The objective of this study was to investigate the impact of various postures on Cobb angle measurements and to set up a positioning standard for imaging mouse spines. METHODS: This study was conducted in three parts. Firstly, we identified the problem of lack of posture standardization for radiographs. We collected 77 C57BL/6 J mice for spine radiographs and found a scoliosis prevalence of 28.6% with large variations in curve magnitude. Secondly, 24 C57BL/6 J mice underwent 4 consecutive weekly radiographs and observed high variations (relative standard deviation: 125.3%) between radiographs. Thirdly, we collected another 82 C57BL/6 J mice and designed 14 different postures that could take place during imaging. These postures were related to curling of the limbs, and head, pelvic and tail tilting. RESULTS: The results showed that head and pelvic tilting significantly affects the curve magnitude with effect size (Glass's delta) over 1.50. Avoiding these incorrect positions during radiographs is warranted. The standard recommended posture for mouse imaging entails positioning the snout, interorbital space, neck and whole spine in one line, and with the limbs placed symmetrical to the trunk, whilst avoiding stretching the body of the mouse. CONCLUSIONS: Our work exemplified the importance of standard protocol during imaging when using an animal model in the scoliosis study. We recommend utilizing this standard in studying various disorders of the spine to avoid technical causes for the appearance of a curve.

Multidisciplinary programme for rehabilitation of chronic low back pain - factors predicting successful return to work.

BACKGROUND: There are no clear indicators for predicting return to work for patients with chronic low back pain (LBP). We aim to report the outcomes of a 14-week multidisciplinary programme targeting patients with chronic LBP who failed conventional physiotherapy to provide functional rehabilitation. Also, this study will identify factors predicting successful return to work (RTW). METHODS: A collected cohort of patients with chronic LBP was consecutively enrolled into the programme from 1996 to 2014. All recruited patients failed to RTW despite at least 3 months of conservative treatment. Patient underwent weekly multidisciplinary sessions with physiotherapists, occupational therapists and clinical psychologists. Patient perceived function was considered the primary outcome of the programme. Patients were assessed for their sitting, standing and walking tolerance. Oswestry Disability Index (ODI) and Spinal Function Sort Score (SFSS) were used to assess patient perceived disability. RESULTS: One hundred and fifty-eight patients were recruited. After the programme, statistically significant improvement was found in ODI (47.5 to 45.0, p = 0.01) and SFSS (98.0 to 109.5, p <  0.001). There was statistically significant improvement (p <  0.01) in sitting, standing, walking tolerance and straight leg raise tests. 47.4% of the patients were able to meet their work demand. Multivariate logistic regression model (R2 = 59.5%, χ2 (9) = 85.640, p <  0.001) demonstrated that lower initial job demand level and higher patient-perceived back function correlated with greater likelihood of returning to work. CONCLUSION: The results of this study may support the use of this multidisciplinary programme to improve patient function and return to work.

When Should We Wean Bracing for Adolescent Idiopathic Scoliosis?

BACKGROUND: Current brace weaning criteria for adolescents with idiopathic scoliosis (AIS) are not well defined. Risser Stage 4, ≥ 2 years since the onset of menarche, and no further increase in body height over 6 months are considered justifications for stopping bracing. However, despite adherence to such standards, curve progression still occurs in some patients, and so better criteria for brace discontinuation are needed. QUESTIONS/PURPOSES: (1) Is no change in height measurements over 6 months and Risser Stage 4 sufficient for initiating brace weaning? (2) What is the association between larger curves (45°) at brace weaning and the progression risk? (3) Are a more advanced Risser stage, Sanders stage, or distal radius and ulna classification associated with a decreased risk of curve progression? (4) When should we wean patients with AIS off bracing to reduce the time for brace wear while limiting the risk of postweaning curve progression? METHODS: All AIS patients who were weaned off their braces from June 2014 to March 2016 were prospectively recruited and followed up for at least 2 years after weaning. A total of 144 patients were recruited with mean followup of 36 ± 21 months. No patients were lost to followup. Patients were referred for brace weaning based on the following criteria: they were Risser Stage 4, did not grow in height in the past 6 months of followup, and were at least 2 years postmenarche. Skeletal maturity was assessed with Risser staging, Sanders staging, and the distal radius and ulna classification. Curve progression was determined as any > 5° increase in the Cobb angle between two measurements from any subsequent six monthly followup visits. All radiographic measurements were performed by spine surgeons independently as part of their routine consultations and without knowledge of this study. Statistical analyses included an intergroup comparison of patients with and without curve progression, binomial stepwise logistic regression analysis, odds ratios (ORs) with their 95% confidence intervals (CIs), and a risk-ratio calculation. A reasonable protective maturity stage would generate an OR < 1. RESULTS: Among patients braced until they had no change in height for 6 months, were 2 years postmenarche for girls, and Risser Stage 4, 29% experienced curve progression after brace weaning. Large curves (≥ 45°) were associated with greater curve progression (OR, 5.0; 95% CI, 1.7-14.8; p = 0.002) as an independent risk factor. Patients weaned at Sanders Stage 7 (OR, 4.7; 95% CI, 2.1-10.7; p < 0.001), radius Grade 9 (OR, 3.9; 95% CI, 1.75-8.51; p = 0.001), and ulna Grade 7 (OR, 3.1; 95% CI, 1.27-7.38; p = 0.013) were more likely to experience curve progression. The earliest maturity indices with a reasonable protective association were Sanders Stage 8 (OR, 0.21; 95% CI, 0.09-0.48; p < 0.001), and radius Grade 10 (OR, 0.42; 95% CI, 0.19-0.97; p = 0.042) with ulna Grade 9 (no patients with curve progression). CONCLUSION: Brace weaning indications using Risser staging are inadequate. Curve progression is expected in patients with large curves, irrespective of maturity status. Bone age measurement by either Sanders staging or the distal radius and ulna classification provides clearer guidelines for brace weaning, resulting in the least postweaning curve progression. Weaning in patients with Sanders Stage 8 and radius Grade 10/ulna Grade 9 provides the earliest and most protective timepoints for initiating brace weaning. LEVEL OF EVIDENCE: Level II, prognostic study.

The relevance of high-intensity zones in degenerative disc disease.

PURPOSE: The purpose of this study was to review the current understanding of high-intensity zones (HIZ) in the lumbar spine with particular attention to its imaging phenotype and clinical relevance. METHODS: A review was conducted of studies related to HIZ. Particular attention was made to imaging phenotypes and classification, and its relationship with discogenic low back pain (LBP). RESULTS: The most current classification system of HIZ is based on location (anterior and posterior), morphology (round, fissure, vertical, rim, or giant types), and its appearance on both T1- and T2-weighted magnetic resonance imaging (MRI). HIZ are commonly manifested with disc degeneration. Hence, both conditions share similar risk factors such as the effect of frequent and prolonged disc loading. The clinical significance of HIZ however is not conclusive. Provocative discography is not sensitive (~ 70%) for eliciting a concordant pain response. Population-based studies have conflicting results regarding the prevalence (14-63%) of HIZ and its correlation with LBP. CONCLUSIONS: HIZ are likely a risk factor for discogenic LBP. However, its etiology and pathophysiology are not well understood. Some clinical studies suggest a link between its occurrence and LBP. However, the results are not consistent as a result of studies which are underpowered and based on heterogeneous study populations, lacking control groups, and without standardized imaging phenotypes. HIZ may be an important pain biomarker that should be further studied. With more modern MRI technology and a detailed classification system, future large-scale population studies will improve our knowledge on its role in the disc degeneration cascade and development of LBP.

A randomized double-blinded clinical trial to evaluate the safety and efficacy of a novel superelastic nickel-titanium spinal rod in adolescent idiopathic scoliosis: 5-year follow-up.

PURPOSE: To evaluate the safety and efficacy of a superelastic shape-memory alloy (SNT) rod used in the treatment of adolescent idiopathic scoliosis (AIS). METHODS: AIS Patients with Lenke 1 curves undergoing fusion surgery were randomized (1:1) at the time of surgery to receive either the SNT or a conventional titanium alloy (CTA) rod. Radiographs were obtained preoperatively and postoperatively up to 5 years of follow-up. Parameters assessed included coronal and sagittal Cobb angles, and overall truncal and shoulder balance. Sagittal profiles were subcategorized into Types A (<20°), B (20-40°), and C (>40°). RESULTS: Twenty-four patients with mean age of 15 years were recruited. A total of 87.0% of subjects were followed up till postoperative 5 years, but all patients had minimum 2 years of follow-up. The fulcrum-bending correction index for the SNT group was 113% at postoperative day 4 and 127% at half-year, while the CTA group was 112% at postoperative day 4 and only 106% at half-year. In terms of sagittal profile, the SNT group moved toward type B profile at half-year follow-up with a mean correction of 7.6°, while no significant change was observed in the CTA group (-0.7°). Nickel levels remained normal, and there were no complications. CONCLUSIONS: This is the first randomized clinical trial of a novel SNT rod for treating patients with AIS, noting it to be safe and has potential to gradually correct scoliosis over time. This study serves as a pilot and platform to properly power future large-scale studies to demonstrate efficacy and superiority.

Fulcrum flexibility of the main curve predicts postoperative shoulder imbalance in selective thoracic fusion of adolescent idiopathic scoliosis.

PURPOSE: To identify preoperative predictors for postoperative shoulder imbalance (PSI) after corrective surgery of adolescent idiopathic scoliosis (AIS) and using the fulcrum-bending radiograph to assess flexibility. METHODS: A consecutive surgical cohort of AIS patients undergoing selective thoracic fusion with alternate-level pedicle screw fixation was prospectively studied. Preoperative anteroposterior, lateral and fulcrum-bending radiographs were analysed. Postoperatively, a minimum of 2 years clinical and imaging follow-up was performed of all patients. PSI was defined as a radiographic shoulder height difference of more than 20 mm. RESULTS: A total of 80 patients were included, and 14 patients (18%) were confirmed with PSI at final follow-up. The flexibility of MT curve was an independent risk factor for PSI (odds ratio (OR) = 3.3 per 10% decrease, 95% confidence interval (CI) 1.6-8.2). Twenty-seven patients had a preoperative MT flexibility of < 55% (OR = 11.5, 95% CI 2.8-46.2). Postoperative T1 tilt was significantly higher in the PSI group (p < 0.001), and a T1 tilt of more than 9° resulted in 7.2 times higher odds of developing PSI (95% CI 2.0-26.0). Fulcrum-bending correction index (FBCI) was significantly higher in the PSI group at final follow-up, and 25 patients had a final postoperative MT FBCI above 120% (OR = 8.5 (95% CI 2.3-31.0). CONCLUSIONS: A low preoperative curve flexibility is a significant predictor for PSI. The surgical strategy should consider proximal fusion in presence of low-flexibility MT curves and consider less aggressive MT curve correction. Achieving a level T1 should be a main priority during intraoperative correction and may require fusion of the PT curve. LEVEL OF EVIDENCE: III. These slides can be retrieved under Electronic Supplementary Material.

Curve Progression in Adolescent Idiopathic Scoliosis Does Not Match Skeletal Growth.

BACKGROUND: Determining the peak growth velocity of a patient with adolescent idiopathic scoliosis (AIS) is important for timely treatment to prevent curve progression. It is important to be able to predict when the curve-progression risk is greatest to maximize the benefits of any intervention for AIS. The distal radius and ulna (DRU) classification has been shown to accurately predict skeletal growth. However, its utility in predicting curve progression and the rate of progression in AIS is unknown. QUESTIONS/PURPOSES: (1) What is the relationship between radius and ulna grades to growth rate (body height and arm span) and curve progression rate? (2) When does peak curve progression occur in relation to peak growth rate as measured by months and by DRU grades? (3) How many months and how many DRU grades elapse between peak curve progression and plateau? METHODS: This was a retrospective analysis of a longitudinally maintained dataset of growth and Cobb angle data of patients with AIS who presented with Risser Stages 0 to 3 and were followed to maturity at Risser Stage 5 at a single institute with territory-wide school screening service. From June 2014 to March 2016, a total of 513 patients with AIS fulfilled study inclusion criteria. Of these, 195 were treated with bracing at the initial presentation and were excluded. A total of 318 patients with AIS (74% girls) with a mean age of 12 ± 1.5 years were studied. For analysis, only data from initial presentation to commencement of intervention were recorded. Data for patients during the period of bracing or after surgery were not used for analysis to eliminate potential interventional confounders. Of these 318 patients, 192 were observed, 119 were braced, and seven underwent surgery. Therefore 192 patients (60.4%) who were observed were followed up until skeletal maturity at Risser Stage 5; no patients were lost to followup. The mean curve magnitude at baseline was 21.6 ± 4.8. Mean followup before commencing intervention or skeletal maturity was 4.3 ± 2.3 years. Standing body height, arm span, curve magnitude, Risser stage, and DRU classification were studied. A subgroup analysis of 83 patients inclusive of acceleration, peak, and deceleration progression phases for growth and curve progression was studied to determine any time lag between growth and curve progression. Results were described in mean ± SD. RESULTS: There was positive correlation between growth rate and curve progression rate for body height (r = 0.26; p < 0.001) and arm span (r = 0.26; p < 0.001). Peak growth for body height occurred at radius grade (R) 6 (0.56 ± 0.29 cm/month) and ulna grade (U) 4 (0.65 ± 0.31 cm/month); peak change in arm span occurred at R5 (0.67 ± 0.33 cm/month) and U3 (0.67 ± 0.22 cm/month); and peak curve progression matched with R7 (0.80 ± 0.89 cm/month) and U5 (0.84 ± 0.78 cm/month). Subgroup analysis confirmed that peak curve progression lagged behind peak growth rate by approximately 7 months or one DRU grade. The mean time elapsed between the peak curve progression rate and the plateau phase at R9 U7 was approximately 16 months, corresponding to two DRU grades. CONCLUSIONS: By using a standard skeletal maturity parameter in the DRU classification, this study showed that the maximal curve progression occurs after the peak growth spurt, suggesting that the curve should be monitored closely even after peak growth. In addition, the period of potential curve continuing progression extends nearly 1.5 years beyond the peak growth phase until skeletal maturity. Future studies may evaluate whether by observing the trend of growth and curve progression rates, we can improve the outcomes of interventions like bracing for AIS. LEVEL OF EVIDENCE: Level II, prognostic study.

A rare postoperative complication of anterior lower thoracic instrumentation: diaphragmatic laceration with hemothorax.

PURPOSE: To highlight the importance of preventing visceral injury due to prominent anterior implants at the spinal column. METHODS: A 52-year-old man with cord compression was treated with a T9/10 discectomy and instrumented fusion via a right thoracotomy and trans-pleural approach. Postoperatively, he had improved lower limb numbness. However, after a bout of coughing, there was sudden increase in chest drain output, hemodynamic instability and massive fluid collection in the right chest cavity. RESULTS: Emergency re-exploration of the thoracotomy was performed and a 6 cm laceration of the right postero-medial diaphragm was identified as the bleeding source and was found to be in close proximity with the locking nut of the anterior implants. The laceration was repaired and a soft synthetic patch was used to cover the implants. Postoperatively, the hemothorax resolved and the patient recovered from the neurological deficit. CONCLUSIONS: Prevention of diaphragmatic injury can be performed using lower profile and less sharp-edged implants. Implant coverage with a soft synthetic material is necessary if unable to perform direct repair of the parietal pleura over the implants.

Predictive factors for neurological deterioration after surgical decompression for thoracic ossified yellow ligament.

PURPOSE: To investigate the rate and predictive factors of post-operative neurological deterioration in ossified yellow ligament (OYL) surgery. METHODS: A retrospective review was conducted for all patients with thoracic OYL causing myelopathy requiring surgical decompression from January 1998 to December 2012. Clinical parameters under study included clinical presentation, distribution of OYL, pre-operative walking score, pre- and post-operative neurological status, status of intra-operative neurophysiological monitoring, and modified Japanese Orthopaedic Association (mJOA) score. Any complications were also recorded. All outcomes were measured at post-operative 1 week and at 2 years. RESULTS: A total of 26 patients were included in this study. Most patients (92.3%) had Frankel grade D pre-operatively. The rate of neurological deterioration was 15.4% and was correlated with the presence of dural tear, extra-dural hematoma and spinal cord injury. Pre-operative walking score was prognostic of patients' walking ability in the post-operative period. Intra-operative monitoring of Somatosensory Evoked Potentials (SSEP) was found to be useful for monitoring spinal cord injury in OYL surgery, with a positive predictive value of 100% and a negative predictive value of 92.3%. The false negative rate of a SSEP signal drop was only 7.7% CONCLUSIONS: This is the first study exploring risk factors for post-operative neurological deterioration after surgery for thoracic OYL. The rate of neurological deficit is not small and prognostic factors for poor outcome include poor pre-operative walking score, presence of intra-operative dural tear, extra-dural hematoma and spinal cord injury, and intra-operative drop of SSEP signal.

Preventing Fusion Mass Shift Avoids Postoperative Distal Curve Adding-on in Adolescent Idiopathic Scoliosis.

BACKGROUND: Surgery for adolescent idiopathic scoliosis (AIS) is only complete after achieving fusion to maintain the correction obtained intraoperatively. The instrumented or fused segments can be referred to as the "fusion mass". In patients with AIS, the ideal fusion mass strategy has been established based on fulcrum-bending radiographs for main thoracic curves. Ideally, the fusion mass should achieve parallel endplates of the upper and lower instrumented vertebra and correct any "shift" for truncal balance. Distal adding-on is an important element to consider in AIS surgery. This phenomenon represents a progressive increase in the number of vertebrae included distally in the primary curvature and it should be avoided as it is associated with unsatisfactory cosmesis and an increased risk of revision surgery. However, it remains unknown whether any fusion mass shift, or shift in the fusion mass or instrumented segments, affects global spinal balance and distal adding-on after curve correction surgery in patients with AIS. QUESTIONS/PURPOSES: (1) To investigate the relationship among postoperative fusion mass shift, global balance, and distal adding-on phenomenon in patients with AIS; and (2) to identify a cutoff value of fusion mass shift that will lead to distal adding-on. METHODS: This was a retrospective study of patients with AIS from a single institution. Between 2006 and 2011 we performed 69 selective thoracic fusions for patients with main thoracic AIS. All patients were evaluated preoperatively and at 2 years postoperatively. The Cobb angle between the cranial and caudal endplates of the fusion mass and the coronal shift between them, which was defined as "fusion mass shift", were measured. Patients with a fusion mass Cobb angle greater than 20° were excluded to specifically determine the effect of fusion mass shift on distal adding-on phenomenon. Fusion mass shift was empirically set as 20 mm for analysis. Therefore, of the 69 patients who underwent selective thoracic fusion, only 52 with a fusion mass Cobb angle of 20° or less were recruited for study. We defined patients with a fusion mass shift of 20 mm or less as the balanced group and those with a fusion mass shift greater than 20 mm as the unbalanced group. A receiver operating characteristic (ROC) curve was used to determine the cutoff point of fusion mass shift for adding-on. RESULTS: Of the 52 patients studied, fusion mass shift (> 20 mm) was noted in 11 (21%), and six of those patients had distal adding-on at final followup. Although global spinal balance did not differ significantly between patients with or without fusion mass shift, the occurrence of adding-on phenomenon was significantly higher in the unbalanced group (55% (six of 11 patients), odds ratio [OR], 8.6; 95% CI, 2-39; p < 0.002) than the balanced group (12% [five of 41 patients]). Based on the ROC curve analysis, a fusion mass shift more than 18 mm was observed as the cutoff point for distal adding-on phenomenon (area under the curve, 0.70; 95% CI, 0.5-0.9; likelihood ratio, 5.0; sensitivity, 0.64; specificity, 0.73; positive predictive value, 39% [seven of 18 patients]; negative predictive value, 88% [30 of 34 patients]; OR, 4.8; 95% CI, 1-20; p = 0.02). CONCLUSIONS: Our study illustrates the substantial utility of the fulcrum-bending radiograph in determining fusion levels that can avoid fusion mass shift; thereby, underlining its importance in designing personalized surgical strategies for patients with scoliosis. Preoperatively, determining fusion levels by fulcrum-bending radiographs to avoid residual fusion mass shift is imperative. Intraoperatively, any fusion mass shift should be corrected to avoid distal adding-on, reoperation, and elevated healthcare costs. LEVEL OF EVIDENCE: Level II, prognostic study.

Antimicrobial prophylaxis to prevent surgical site infection in adolescent idiopathic scoliosis patients undergoing posterior spinal fusion: 2 doses versus antibiotics till drain removal.

PURPOSE: There is much variation in the choice, timing and duration of antimicrobial prophylaxis for preventing surgical site infections (SSI) but no guideline exists for scoliosis surgery. The aim of study was to compare the efficacy of two antimicrobial prophylaxis (AMP) protocols with cephazolin in preventing SSI in adolescent idiopathic scoliosis (AIS). METHODS: A retrospective comparative analysis of two post-operative AMP protocols (two postoperative doses versus continued antibiotics till drain removal) was performed. Patient characteristics, pre-operative, intra- and post-operative risk factors for infection, drain use, generic drug name and number of doses administered were recorded from 226 patients with AIS who had undergone posterior spinal fusion. Details of superficial or deep SSI and wound healing aberrations, and serious adverse events were recorded. Analysis was performed to evaluate differences in the pre-, intra- and post-operative variables between the two groups. RESULTS: 155 patients received 2 postoperative doses of AMP and 71 patients had antibiotics till drain removal. The average follow-up was 43 months. The overall rate of SSI was 1.7 % for the spine wound and 1.3 % for the iliac crest wound. 1.9 % of patients with 2 doses of AMP and 1.4 % of patients with antibiotics till drain removal had SSI. No adverse reactions attributable to cephazolin were observed. CONCLUSIONS: This is the first study on the AMP protocol in scoliosis surgery for SSI prevention. Results suggest that two doses of AMP are as effective as continued antimicrobial use until drain removal. Cephazolin appears to be effective and safe for prophylaxis.

Quantitative assessment of column-specific degeneration in cervical spondylotic myelopathy based on diffusion tensor tractography.

PURPOSE: Cervical spondylotic myelopathy (CSM) is a common spinal cord disorder in the elderly. Diffusion tensor imaging (DTI) has been shown to be of great value for evaluating the microstructure of nerve tracts in the spinal cord. Currently, the quantitative assessment of the degeneration on the specific tracts in CSM is still rare. The aim of the present study was to use tractography-based quantification to investigate the column-specific degeneration in CSM. METHODS: A total of 43 volunteers were recruited with written informed consent, including 20 healthy subjects and 23 CSM patients. Diffusion MRI was taken by 3T MRI scanner. Fiber tractography was performed using TrackVis to reconstruct the white matter tracts of the anterior, lateral and posterior column on the bilateral sides. The DTI metrics acquired from tractography, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD), were compared between healthy subjects and CSM patients. RESULTS: Compared to healthy subjects, FA was found significantly lower in the lateral (Healthy 0.64 ± 0.07 vs. CSM 0.53 ± 0.08) and posterior column (Healthy 0.67 ± 0.08 vs. CSM 0.47 ± 0.08) (p < 0.001), while MD, AD and RD were significantly higher in the anterior, lateral and posterior column in CSM (p < 0.05). CONCLUSION: Loss of microstructural integrity was detected in the lateral and posterior column in CSM. Tractography-based quantification was capable of evaluating the subtle pathological insult within white matter on a column-specific basis, which exhibited potential clinical value for in vivo evaluation of the severity of CSM.

Normal values of cervical spinal cord diffusion tensor in young and middle-aged healthy Chinese.

PURPOSE: Lack of normal reference value of diffusion tensor imaging parameters hinders its application in clinical practice. In this study, we aim to establish a comprehensive normal DTI database of Chinese subjects. METHODS: Sixty-five healthy subjects aged 21-61 years were recruited and underwent 3T DTI scan of cervical spine. DTI parameters were measured in whole cord, ventral, lateral and dorsal column from C2 to C7 segments. Regions, segments, gender and age-related changes of DTI parameters were analyzed. RESULTS: No significant difference was found between genders (p > 0.05). DTI parameters significantly differed among different cord levels (p < 0.05). FA value in whole cord, grey matter, dorsal and ventral column showed significant but weak correlation with age (p < 0.05). CONCLUSION: A comprehensive normal database of DTI parameters of cervical spinal cord was established. The effect of gender and age-related changes is negligible in DTI analysis of cervical spinal cord disorders.

Using the Proximal Femur Maturity Index at Brace Initiation for Adolescent Idiopathic Scoliosis Predicts Curve Progression Risk.

BACKGROUND: The Proximal Femur Maturity Index (PFMI) can be used to assess skeletal maturity on existing whole-spine radiographs without additional radiation. However, the relationship between the PFMI at the initiation of bracing for adolescent idiopathic scoliosis (AIS) and subsequent curve progression remains unknown. This study aimed to investigate the relationship between the PFMI and curve progression, and the predictability of risks to adulthood curve progression and surgical thresholds based on the PFMI grade at brace initiation. METHODS: This was a prospective study of 202 patients with AIS who were prescribed underarm bracing according to the Scoliosis Research Society criteria and had good brace-wear compliance. The patients were followed from brace initiation until complete skeletal maturity. Longitudinal data on the coronal Cobb angle and skeletal maturity assessments using Risser staging, Sanders staging, the distal radius and ulna classification, and the PFMI were collected. Each patient was assessed on whether the major curve progressed to ≥40° (adulthood deterioration) and ≥50° (the surgical threshold). Logistic regressions were used to predict probabilities of curve progression to the 2 thresholds, adjusted for factors that were significant in univariate analyses. RESULTS: The PFMI correlated with the other skeletal maturity indices (r s [Spearman rank correlation] = 0.60 to 0.72, p < 0.001 for all). The pre-brace PFMI grade correlated with progression to ≥40° (r rb [rank-biserial correlation] = -0.30, p < 0.001) and to ≥50° (r rb = -0.20, p = 0.005). Based on regression models (p < 0.001) adjusted for the pre-brace major Cobb angle and curve type, brace initiation at PFMI grades 2 and 3 for a curve of ≥30° had predicted risks of 30% (95% confidence interval [CI], 4% to 55%) and 12% (95% CI, 7% to 17%), respectively, for progression to the surgical threshold. Brace initiation at PFMI grade 5 had 0% progression risk. CONCLUSIONS: The PFMI can be used for predicting curve progression and prognosticating brace outcomes in AIS. Patients with brace initiation at PFMI grade 4 for a curve of <30° or at grade 5 were unlikely to progress to the adulthood deterioration or surgical threshold. In comparison, skeletally immature patients initiating bracing at a PFMI grade of ≤3 for a major curve of ≥30° had a higher risk of progression despite compliant brace wear. LEVEL OF EVIDENCE: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Impaired glycine neurotransmission causes adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity, affecting millions of adolescents worldwide, but it lacks a defined theory of etiopathogenesis. Because of this, treatment of AIS is limited to bracing and/or invasive surgery after onset. Preonset diagnosis or preventive treatment remains unavailable. Here, we performed a genetic analysis of a large multicenter AIS cohort and identified disease-causing and predisposing variants of SLC6A9 in multigeneration families, trios, and sporadic patients. Variants of SLC6A9, which encodes glycine transporter 1 (GLYT1), reduced glycine-uptake activity in cells, leading to increased extracellular glycine levels and aberrant glycinergic neurotransmission. Slc6a9 mutant zebrafish exhibited discoordination of spinal neural activities and pronounced lateral spinal curvature, a phenotype resembling human patients. The penetrance and severity of curvature were sensitive to the dosage of functional glyt1. Administration of a glycine receptor antagonist or a clinically used glycine neutralizer (sodium benzoate) partially rescued the phenotype. Our results indicate a neuropathic origin for "idiopathic" scoliosis, involving the dysfunction of synaptic neurotransmission and central pattern generators (CPGs), potentially a common cause of AIS. Our work further suggests avenues for early diagnosis and intervention of AIS in preadolescents.

Magnetically controlled growing rods for severe spinal curvature in young children: a prospective case series.

BACKGROUND: Scoliosis in skeletally immature children is often treated by implantation of a rod to straighten the spine. Rods can be distracted (lengthened) as the spine grows, but patients need many invasive operations under general anaesthesia. Such operations are costly and associated with negative psychosocial outcomes. We assessed the effectiveness and safety of a new magnetically controlled growing rod (MCGR) for non-invasive outpatient distractions. METHODS: We implanted the MCGR in five patients, two of whom have now reached 24 months' follow-up. Each patient underwent monthly outpatient distractions. We used radiography to measure the magnitude of the spinal curvature, rod distraction length, and spinal length. We assessed clinical outcome by measuring the degree of pain, function, mental health, satisfaction with treatment, and procedure-related complications. FINDINGS: In the two patients with 24 months' follow-up, the mean degree of scoliosis, measured by Cobb angle, was 67° (SD 10°) before implantation and 29° (4°) at 24 months. Length of the instrumented segment of the spine increased by a mean of 1·9 mm (0·4 mm) with each distraction. Mean predicted versus actual rod distraction lengths were 2·3 mm (1·2 mm) versus 1·4 mm (0·7 mm) for patient 1, and 2·0 mm (0·2 mm) and 2·1 mm (0·7 mm) versus 1·9 mm (0·6 mm) and 1·7 mm (0·8 mm) for patient 2's right and left rods, respectively. Throughout follow-up, both patients had no pain, had good functional outcome, and were satisfied with the procedure. No MCGR-related complications were noted. INTERPRETATION: The MCGR procedure can be safely and effectively used in outpatient settings, and minimises surgical scarring and psychological distress, improves quality of life, and is more cost-effective than is the traditional growing rod procedure. The technique could be used for non-invasive correction of abnormalities in other disorders. FUNDING: Ellipse Technologies.

Cervical spine complications after treatment of nasopharyngeal carcinoma.

PURPOSE: Radiotherapy has been the mainstay treatment for nasopharyngeal carcinoma (NPC) and has achieved good disease control. However, irradiation is associated with potential complications such as osteoradionecrosis (ORN) and infection. There is sparse description in the literature of such complications and how they are best managed. The objectives of the study are: (1) to describe the complications at the cervical spine after surgical and radiotherapy treatment for NPC (2) to identify key principles in the diagnosis and treatment of these complications. METHODS: A retrospective review of all patients with cervical spine complications after radiation treatment and surgery for NPC treated in a tertiary referral center, since 1990. RESULTS: Fourteen patients with cervical spine ORN and infections were found with an average duration to diagnosis of 8.6 years. All 14 patients had mucosal and deep biopsies and none had tumor recurrence. Four patients had ORN, eight had osteomyelitis and two patients had both ORN and osteomyelitis. CONCLUSIONS: Radiotherapy complications usually have delayed and subtle presentations. ORN progresses slowly and can often be treated conservatively. Infections should be treated aggressively with surgical debridement and the results are generally good. Patients should be regularly followed-up with transoral examination to assess the integrity of the posterior pharyngeal wall and imaging to assess for ORN. Pharyngeal defects raise concern for cervical spine infections. Coverage of pharyngeal defects in these patients is important to prevent recurrent infection.

The Utility of a Novel Proximal Femur Maturity Index for Staging Skeletal Growth in Patients with Idiopathic Scoliosis.

BACKGROUND: For growing patients, it is ideal to have a growth plate visible in routine radiographs for skeletal maturity assessment without additional radiation. The proximal femoral epiphyseal ossification is in proximity to the spine; however, whether it can be used for assessing a patient's growth status remains unknown. METHODS: Two hundred and twenty sets of radiographs of the spine and the left hand and wrist of patients with idiopathic scoliosis were assessed for skeletal maturity and reliability testing. Risser staging, Sanders staging (SS), distal radius and ulna (DRU) classification, the proximal humeral ossification system (PHOS), and the novel proximal femur maturity index (PFMI) were used. The PFMI was newly developed on the basis of the radiographic appearances of the femoral head, greater trochanter, and triradiate cartilage. It consists of 7 grades (0 to 6) associated with increasing skeletal maturity. The PFMI was evaluated through its relationship with pubertal growth (i.e., the rate of changes of standing and sitting body height [BH] and arm span [AS]) and with established skeletal maturity indices. Longitudinal growth data and 780 corresponding spine radiographs were assessed to detect peak growth using receiver operating characteristic (ROC) curve analysis. RESULTS: The PFMI was found to be correlated with chronological age (τ b = 0.522), growth rates based on standing BH (τ b = -0.303), and AS (τ b = -0.266) (p < 0.001 for all). The largest growth rate occurred at PFMI grade 3, with mean standing BH growth rates (and standard deviations) of 0.79 ± 0.44 cm/month for girls and 1.06 ± 0.67 cm/mo for boys. Growth rates of 0.12 ± 0.23 cm/mo (girls) and 0 ± 0 cm/mo (boys) occurred at PFMI grade 6, indicating growth cessation. Strong correlations were found between PFMI gradings and Risser staging (τ b = 0.743 and 0.774 for girls and boys), Sanders staging (τ b = 0.722 and 0.736, respectively), and radius (τ b = 0.792 and 0.820) and ulnar gradings (τ b = 0.777 and 0.821), and moderate correlations were found with PHOS stages (τ b = 0.613 and 0.675) (p < 0.001 for all). PFMI gradings corresponded to as young as SS1, R4, U1, and PHOS stage 1. Fair to excellent interrater and intrarater reliabilities were observed. PFMI grade 3 was most prevalent and predictive for peak growth based on ROC results. CONCLUSIONS: The PFMI demonstrated clear pubertal growth phases with satisfactory reliability. Grade 3 indicates peak growth and grade 6 indicates growth cessation. CLINICAL RELEVANCE: The use of PFMI can benefit patients by avoiding additional radiation in skeletal maturity assessment and can impact current clinical protocol of patient visits. PFMI gradings had strong correlations with SS, DRU gradings, and Risser staging, and they cross-referenced to their established grades at peak growth and growth cessation. PFMI may aid in clinical decision making.

Entropy-based analysis for diffusion anisotropy mapping of healthy and myelopathic spinal cord.

The present study utilized diffusion MR imaging and fractional anisotropy (FA) mapping to delineate the microstructure of spinal cord. The concept of Shannon entropy was introduced to analyze the complex microstructure of healthy and injured spinal cords based on FA map. A total of 30 volunteers were recruited in this study with informed consent, including 13 healthy adult subjects (group A, 25±3 years), 12 healthy elderly subjects (group B, 53±7 years) and 5 cervical spondylotic myelopathy (CSM) patients (group C, 53±15 years). Diffusion MRI images of cervical spinal cord were taken using pulsed gradient spin-echo-echo-planar imaging (SE-EPI) sequence with a 3T MR system. The region of interest was defined to cover the spinal cord in FA maps. The Shannon entropy of FA values of voxels in the cord was calculated as well as the average FA values. The significant differences were determined among three groups using one-way ANOVA and post-hoc test. As compared with adult and elderly healthy subjects, the entropy of whole spinal cord was significantly lower in CSM patients (group A: 6.07±0.18; B: 6.01±0.23; C: 5.32±0.44; p<0.05). Whereas there were no significant difference in FA values among groups (group A: 0.62±0.08; B: 0.64±0.09; C: 0.64±0.12). In CSM patients, there was a loss of architectural structural complexity in the cervical spinal cord tissue as noted by the lower Shannon entropy value. It indicated the potential application of entropy-based analysis for the diagnosis of the severity of chronic compressive spinal cord injuries, i.e. CSM.