Diagnostic yield and clinical impact of exome sequencing in early-onset scoliosis (EOS).

BACKGROUND: Early-onset scoliosis (EOS), defined by an onset age of scoliosis less than 10 years, conveys significant health risk to affected children. Identification of the molecular aetiology underlying patients with EOS could provide valuable information for both clinical management and prenatal screening. METHODS: In this study, we consecutively recruited a cohort of 447 Chinese patients with operative EOS. We performed exome sequencing (ES) screening on these individuals and their available family members (totaling 670 subjects). Another cohort of 13 patients with idiopathic early-onset scoliosis (IEOS) from the USA who underwent ES was also recruited. RESULTS: After ES data processing and variant interpretation, we detected molecular diagnostic variants in 92 out of 447 (20.6%) Chinese patients with EOS, including 8 patients with molecular confirmation of their clinical diagnosis and 84 patients with molecular diagnoses of previously unrecognised diseases underlying scoliosis. One out of 13 patients with IEOS from the US cohort was molecularly diagnosed. The age at presentation, the number of organ systems involved and the Cobb angle were the three top features predictive of a molecular diagnosis. CONCLUSION: ES enabled the molecular diagnosis/classification of patients with EOS. Specific clinical features/feature pairs are able to indicate the likelihood of gaining a molecular diagnosis through ES.

Does the Use of Sanders Staging and Distal Radius and Ulna Classification Avoid Mismatches in Growth Assessment with Risser Staging Alone?

BACKGROUND: Although Risser stages are visible on the same radiograph of the spine, Risser staging is criticized for its insensitivity in estimating the remaining growth potential and its weak correlation with curve progression in patients with adolescent idiopathic scoliosis. Risser staging is frequently accompanied by other skeletal maturity indices to increase its precision for assessing pubertal growth. However, it remains unknown whether there is any discrepancy between various maturity parameters and the extent of this discrepancy when these indices are used concurrently to assess pubertal growth landmarks, which are important for the timing of brace initiation and weaning. QUESTIONS/PURPOSES: (1) What is the chronologic order of skeletal maturity grades based on the growth rate and curve progression rate in patients with adolescent idiopathic scoliosis? (2) What are the discrepancies among the grades of each maturity index for indicating the peak growth and start of the growth plateau, and how do these indices correspond to each other? (3) What is the effectiveness of Risser staging, Sanders staging, and the distal radius and ulna classification in assessing peak growth and the beginning of the growth plateau? METHODS: Between 2014 and 2017, a total of 13,536 patients diagnosed with adolescent idiopathic scoliosis were treated at our tertiary clinic. Of those, 3864 patients with a radiograph of the left hand and wrist and a posteroanterior radiograph of the spine at the same visits including initial presentation were considered potentially eligible for this study. Minimum follow-up was defined as 6 months from the first visit, and the follow-up duration was defined as 2 years since initial consultation. In all, 48% (1867 of 3864) of patients were eligible, of which 26% (485 of 1867) were excluded because they were prescribed bracing at the first consultation. These patients visited the subsequent clinics wearing the brace, which might have affected body height measurement. Six percent (117 of 1867) of eligible patients were also excluded as their major coronal Cobb angle reached the surgical threshold of 50° and had undergone surgery before skeletal maturity. Another 21% (387 of 1867) of patients were lost before minimum follow-up or had incomplete data, leaving 47% (878) for analysis. These 878 patients with 1139 skeletal maturity assessments were studied; 74% (648 of 878) were girls. Standing body height was measured in a standardized manner by a wall-mounted stadiometer. Several surgeons measured curve magnitude as per routine clinical consultation, skeletal maturity was measured according to the distal radius and ulna classification, and two raters measured Risser and Sanders stages. Reliability tests were performed with satisfaction. Data were collected for the included patients at multiple points when skeletal maturity was assessed, and only up to when brace wear started for those who eventually had bracing. The growth rate and curve progression rate were calculated by the change of body height and major coronal Cobb angle over the number of months elapsed between the initial visit and next follow-up. At each skeletal maturity grading, we examined the growth rate (in centimeters per month) and curve progression rate (in degrees per month) since the skeletal maturity assessment, as well as the mean age at which this maturity grading occurred. Each patient was then individually assessed for whether he or she was experiencing peak growth and the beginning of growth plateau at each timepoint by comparing the calculated growth rate with the previously defined peak growth rate of ≥ 0.7 cm per month and the beginning of growth plateau rate of ≤ 0.15 cm per month in this adolescent idiopathic scoliosis population. Among the timepoints at which the peak growth and the beginning of growth plateau occurred, the median maturity grade of each maturity index was identified as the benchmark grade for comparison between indices. We used the McNemar test to investigate whether pubertal growth landmarks were identified by specific maturity grades concurrently. We assessed the effectiveness of these skeletal maturity indices by the difference in proportions (%) between two benchmark grades in indicating peak growth and the growth plateau. RESULTS: For girls, the chronological order of maturity grades that indicated peak growth was the radius grade, ulna grade, Sanders stage, and Risser stage. Curve progression peaked between the age of 11.6 and 12.1 years at a similar timing by all maturity indices for girls but was inconsistent for boys. For both sexes, radius (R) grade 6, ulna (U) grade 5, Sanders stage (SS) 3, and Risser stage 0+ were the median grades for peak growth, whereas Risser stage 4, R8/9, U7/8, and SS6/7 indicated the beginning of the growth plateau. The largest discrepancy between maturity indices was represented by Risser stage 0+, which corresponded to six grades of the Sanders staging system (SS2 to SS7) and to R6 in only 41% (62 of 152) of girls in the whole cohort. Despite Risser stage 0+ corresponding to the wide range of Sanders and distal radius and ulna grades, none of the R6, U5, SS3, and Risser stage 0+ was found more effective than another grade in indicating the peak growth in girls. R6 most effectively indicated the peak growth in boys, and Risser stage 0+ was the least effective. For the beginning of the growth plateau in girls, SS6/7 was the most effective indicator, followed by U7/8. Risser stage 4 was the least effective because it indicated 29% (95% CI 21% to 36%; p < 0.001) fewer patients who reached the beginning of the growth plateau than did those with R8/9. Risser stage 4 also indicated 36% (95% CI 28% to 43%; p < 0.001) fewer patients who reached the beginning of the growth plateau than those indicated by U7/8, and it identified 39% fewer patients than SS6/7 (95% CI 32% to 47%; p < 0.001). For boys, similarly, R8/9, U7/8, and SS6/7 were all more effective than Risser stage 4 in identifying when the growth plateau began. CONCLUSION: Risser stage 0+ corresponds to a wide range of Sanders and distal radius and ulna grades. Risser stage 0+ is least effective in indicating the peak growth in boys, and Risser stage 4 is the least effective maturity grade for indicating when the growth plateau starts in both sexes. The concurrent use of R6 and SS3 can be useful for detecting the peak growth, and SS6/7 in conjunction with U7/8 is most effective in indicating the beginning of the growth plateau. Using a combination of specific grades of Sanders staging and the distal radius and ulna classification can indicate pubertal growth landmarks with reduced risk of underestimating or overestimating skeletal maturity. These findings may aid in refining clinical decision-making of brace initiation and weaning at a more precise timing. Among Risser stage 0, the appearance of R6, U5, and SS3 provide the most effective assessment of peak growth that can indicate the most effective bracing period within which curve progression occurs. For initiation of the growth plateau, Risser 4 is not useful, and SS6/7, R8/9 and U7/8 should be used instead. LEVEL OF EVIDENCE: Level III, diagnostic study.

Low Preoperative Lung Functions in Children With Early Onset Scoliosis Predict Postoperative Length of Stay.

INTRODUCTION: Children with early onset scoliosis (EOS) undergoing spine surgery often have significant respiratory disease. Preoperative risk assessments that predict an increased length of hospital stay (LOS) for this group have not been previously evaluated. METHODS: A voluntary protocol using preoperative lung function studies began among participants of a multicenter registry in 2016. Preoperative assessments were standardized to include spirometry, blood hemoglobin levels, serum bicarbonate, albumin and prealbumin; radiographic parameters of the spine, C-EOS classification and need for preoperative pulmonary assistance before initial growth friendly device insertion or "definitive" spine fusion. Primary outcome was LOS postoperatively. Data, including age, diagnosis, and type of surgery, was collected prospectively. Secondary outcomes measured included intensive care unit LOS, requirement for new pulmonary assistance on discharge, and pulmonary complications. Groups were compared using the Fisher exact tests. RESULTS: Of 525 children enrolled, 101 (20%) had preoperative spirometry. Median age was 8.9 years [interquartile range (IQR): 4.27]. Etiologies for EOS included 29 neuromuscular (28%), 33 idiopathic (32%), 19 syndromic (19%), and 22 congenital (21%) scoliosis. Eighty (78%) had growing rod (GR) insertions; 23 (22%) had spine fusion SF. Eighteen subjects (17%) were hospitalized ≥7 days (median=9 d); 83 had a LOS <7 days (median=3 d). Percentage of forced vital capacity (FVC%) predicted was inversely associated with LOS ≥7 days with a median of 75.3% (IQR: 41.7) for LOS <7 days and 51.7% (IQR: 41.6) (P=0.02). There were no detectable differences in LOS for other preoperative values. CONCLUSION: FVC predicted ≤50% preoperatively in children undergoing initial growth friendly rod insertion or definitive fusion after growth friendly treatment is associated with an increased risk of postoperative hospital stays ≥7 days. As demonstrated in previous studies, severe restrictive lung disease (FVC% predicted at or below 50%) is associated with increased risk of poorer outcomes for EOS patients.

Expert Consensus for Early Onset Scoliosis Surgery.

BACKGROUND: Despite a validated classification system, high-quality multicenter research databases (CSSG/GSSG), and a recent proliferation in publications, early-onset scoliosis (EOS) surgeons have no consensus on standards for surgical treatment. The 21st-century revolution in EOS care has only accelerated, with the arrival of a classification system, magnetically controlled growing rod, nusinersen, and improved nonoperative care (Mehta or Risser casting and compliance-monitored braces). This dizzying pace of change may have outstripped our ability to develop best-practice standards for EOS surgical indications. To learn where consensus is best (and worst) at this moment, we surveyed EOS world thought-leaders on a collection of representative cases. METHODS: A 6-case survey was constructed and sent to 20 EOS world thought-leaders. The cases were selected to be representative of the major treatment categories: idiopathic, neuromuscular, syndromic, congenital, thoracic dysplasia, and spinal muscular atrophy (specifically to assess the impact of nusinersen and parasol deformity on surgical planning). Respondents were queried regarding treatment with specific attention to instrumentation and construct when surgery was selected. Responses regarding surgical timing and technique were analyzed for consensus (defined as >80%). χ analysis was performed to evaluate for differences in treatment preferences based on years of experience. RESULTS: The survey response was 100%. Clinical experience ranged from 8 to 40 years (average 23.9 y). There was no consensus on any case. The greatest variability was on the congenital case; the closest to consensus was on the spinal muscular atrophy case. Three or more approaches were selected for all 6 cases; >4 approaches were selected for 5 cases. There is a trend towards screw fixation for proximal anchors. The management of thoracic dysplasia and parasol deformity is far from consensus. CONCLUSION: The lack of consensus for surgical treatment of 6 representative EOS cases demands a renewed effort and commitment to develop best-practice guidelines based on multicenter outcome data. LEVEL OF EVIDENCE: Level V-Expert Opinion.

High Risk of Mismatch Between Sanders and Risser Staging in Adolescent Idiopathic Scoliosis: Are We Guiding Treatment Using the Wrong Classification?

BACKGROUND: Despite known limitations, Risser staging has traditionally been the primary marker of skeletal maturity utilized in decision-making for treatment of adolescent idiopathic scoliosis (AIS). The purpose of this study is to assess the incidence and factors associated with mismatch between Risser Staging and Sanders classification, and determine interobserver reliability. METHODS: We reviewed the medical records of consecutive patients aged 10 to 18 referred to our institution for evaluation of AIS from January to June 2016 with a closed triradiate cartilage. Data collected included sex, age, race, height, weight, body mass index percentile, menarchal status, Risser stage, Sanders classification, and major curve. Risser and Sanders stage was determined by 2 fellowship-trained pediatric spine surgeons and 1 pediatric orthopaedic nurse practitioner. Mismatch was defined as Risser stage 2 to 4 corresponding to Sanders 3 to 5, and Risser 0 to 1 corresponding to Sanders 6 to 7. RESULTS: A total of 165 consecutive patients were identified (mean age: 13.9±1.7 y, major curve 28.2±15.4 degrees, 76% female). The risk of skeletal maturity mismatch, based on the criteria of Risser 2 to 5 (limited growth remaining) corresponding to Sanders 3 to 5 (significant growth remaining) was 21.8%, indicating that 1 of 5 patients would be undertreated if managed by Risser criteria. Conversely, the mismatch risk for Risser 0 to 1 corresponding to Sanders 6 to 7 was 3.6%, leading such patients to be treated conservatively longer than necessary. Males and those of Hispanic ethnicity were at a higher risk of mismatch (23.1% vs. 11.9%, P=0.08; 33.3% vs. 8.8%, P=0.04, respectively). Body mass index percentile, race, and major curve were not associated with mismatch. The unweighted and weighted interobserver κ for Risser staging was 0.74 and 0.82, respectively, and 0.86 and 0.91 for Sanders classification, respectively. CONCLUSION: Given the limited sensitivity of Risser staging during peak growth velocity, high mismatch risk, and lower interobserver reliability, the Sanders classification should be utilized to guide treatment options in patients with AIS. Compared with Sanders, utilizing Risser staging results in mistreatment in a total of 1 of 4 patients, with the vast majority being undertreated. LEVEL OF EVIDENCE: Level II.

TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model.

PURPOSE: To characterize clinically measurable endophenotypes, implicating the TBX6 compound inheritance model. METHODS: Patients with congenital scoliosis (CS) from China(N = 345, cohort 1), Japan (N = 142, cohort 2), and the United States (N = 10, cohort 3) were studied. Clinically measurable endophenotypes were compared according to the TBX6 genotypes. A mouse model for Tbx6 compound inheritance (N = 52) was investigated by micro computed tomography (micro-CT). A clinical diagnostic algorithm (TACScore) was developed to assist in clinical recognition of TBX6-associated CS (TACS). RESULTS: In cohort 1, TACS patients (N = 33) were significantly younger at onset than the remaining CS patients (P = 0.02), presented with one or more hemivertebrae/butterfly vertebrae (P = 4.9 × 10‒8), and exhibited vertebral malformations involving the lower part of the spine (T8-S5, P = 4.4 × 10‒3); observations were confirmed in two replication cohorts. Simple rib anomalies were prevalent in TACS patients (P = 3.1 × 10‒7), while intraspinal anomalies were uncommon (P = 7.0 × 10‒7). A clinically usable TACScore was developed with an area under the curve (AUC) of 0.9 (P = 1.6 × 10‒15). A Tbx6-/mh (mild-hypomorphic) mouse model supported that a gene dosage effect underlies the TACS phenotype. CONCLUSION: TACS is a clinically distinguishable entity with consistent clinically measurable endophenotypes. The type and distribution of vertebral column abnormalities in TBX6/Tbx6 compound inheritance implicate subtle perturbations in gene dosage as a cause of spine developmental birth defects responsible for about 10% of CS.

Classification of coronal imbalance in adult scoliosis and spine deformity: a treatment-oriented guideline.

INTRODUCTION: In adult spinal deformity (ASD), sagittal imbalance and sagittal malalignment have been extensively described in the literature during the past decade, whereas coronal imbalance and coronal malalignment (CM) have been given little attention. CM can cause severe impairment in adult scoliosis and ASD patients, as compensatory mechanisms are limited. The aim of this paper is to develop a comprehensive classification of coronal spinopelvic malalignment and to suggest a treatment algorithm for this condition. METHODS: This is an expert's opinion consensus based on a retrospective review of CM cases where different patterns of CM were identified, in addition to treatment modifiers. After the identification of the subgroups for each category, surgical planning for each subgroup could be specified. RESULTS: Two main CM patterns were defined: concave CM (type 1) and convex CM (type 2), and the following modifiers were identified as potentially influencing the choice of surgical strategy: stiffness of the main coronal curve, coronal mobility of the lumbosacral junction and degeneration of the lumbosacral junction. A surgical algorithm was proposed to deal with each situation combining the different patterns and their modifiers. CONCLUSION: Coronal malalignment is a frequent condition, usually associated to sagittal malalignment, but it is often misunderstood. Its classification should help the spine surgeon to better understand the full spinal alignment of ASD patients. In concave CM, the correction should be obtained at the apex of the main curve. In convex CM, the correction should be obtained at the lumbosacral junction. These slides can be retrieved under Electronic Supplementary Material.

Surgical outcome differences between the 3D subtypes of right thoracic adolescent idiopathic scoliosis.

BACKGROUND: The current classifications of adolescent idiopathic scoliosis (AIS) aim to guide surgical decision making. However, variance exists within treatment recommendations and suboptimal outcomes have been observed while following these guidelines based on two-dimensional images. We used previously developed 3D classification for right thoracic AIS patients and aimed to determine the variation in surgical decision making and the risk of suboptimal outcomes in each subtype according to our classification. METHODS: Seventy-six right thoracic AIS patients with 2-year follow-up were included retrospectively. Five 3D preoperative subgroups were determined based on a previous classification system. The upper and lower instrumented vertebrae (UIV and LIV) and the radiographic surgical outcomes at 2-year [frontal balance (FB), proximal junctional kyphosis (PJK), and adding on] were compared between the subtypes. RESULTS: The fusion length and the rate of radiographic suboptimal outcomes were statistically different between the five groups. LIV at T12 in Type 1 and UIV at T2 in Type 2 were associated with improved FB and lower PJK, respectively. Type 3 had the highest rate of suboptimal FB and developing PJK. Type 4 had the longest fusion, and suboptimal FB was observed in 42% of the patients independent from the LIV level. Type 5 had the lowest rate of unsatisfactory radiographic outcomes at 2 years. CONCLUSION: Following the preoperative 3D classification of the AIS patients, we showed that the UIV and LIV selection has a different impact on the surgical outcomes in each of the five subtypes. The proposed 3D classification has the potential for risk stratification following a posterior spinal surgery in right thoracic AIS. These slides can be retrieved under Electronic Supplementary Material.

Clinical photography in severe idiopathic scoliosis candidate for surgery: is it a useful tool to differentiate among Lenke patterns?

PURPOSE: Clinical photography has proven to be reliable for posture assessment in adolescents and young adults with idiopathic scoliosis. This paper attempts to elucidate whether clinical photography is capable of distinguishing the distinctive characteristics in trunk deformity of the different Lenke patterns in patients with severe scoliosis candidate for surgery. METHODS: One hundred and seventy-three patients (82% women), average age of 20.8 years and average largest curve magnitude of 58.7° were included. PA standing full-spine X-rays and digital photographs from the back of the trunk were measured. RADIOLOGICAL MEASUREMENTS: It is used to measure magnitude of the proximal thoracic (PTC), main thoracic (MTC) and thoracolumbar/lumbar (TL/LC) curves, T1 tilt and the clavicle-rib intersection angle. PHOTOGRAPHIC MEASUREMENTS: It is used to measure shoulder height angle, axilla height angle, waist height angle (WHA), right and left waist angles and trunk areas. STATISTICAL ANALYSIS: One-way ANOVA to test mean differences among Lenke types for radiological and photographic measurements was performed. ROC curve analysis was conducted to find out cutoff values in photographic measurements to differentiate among curve patterns. RESULTS: Most radiological and photographic measurements differ among curve patterns. On ROC curve analysis, solid cutoff values were found for WHA (AUC = 0.8), left waist angle (AUC = 0.81), right waist angle (AUC = 0.81) and the difference between left and right waist angles (AUC = 0.86) to differentiate between types 1 and 2 and the other three types (3, 5 and 6). CONCLUSIONS: Clinical photography is a valid method for assessing trunk asymmetry in severe idiopathic scoliosis. Specifically, for waist area measurements, robust cutoff values can be determined to discriminate among different curve patterns according to Lenke classification. These slides can be retrieved under Electronic Supplementary Material.

Immediate postoperative coronal imbalance in Lenke 5 and Lenke 6 adolescent idiopathic scoliosis: Is it predictable?

PURPOSE: Immediate postoperative coronal imbalance (IPCIB) is a common reason for worse postoperative appearance in adolescent idiopathic scoliosis (AIS) patients and rarely improves on its own at follow-up, thereby greatly influencing the patients' health-related quality of life. However, no studies have been performed to detect the primary risk factors for IPCIB and it remains unclear whether the condition can be predicted preoperatively. The purpose of this study is to detect the primary risk factors for IPCIB in Lenke 5 and Lenke 6 AIS patients and to explore whether IPCIB can be predicted preoperatively. METHODS: Medical records of Lenke 5 and Lenke 6 AIS patients who underwent correction surgery in our hospital from June 2017 to October 2018 were analyzed. Anteroposterior films were evaluated before and after surgery. Patients were divided into two groups, i.e., occurrence and non-occurrence of IPCIB. The risk factors for IPCIB were analyzed, and an IPCIB index was proposed and verified. RESULTS: Thirty-seven Lenke 5/Lenke 6 AIS patients with IPCIB and 48 patients without IPCIB were recruited. Univariate analysis showed that there were significant differences between the two groups in the number of unfused vertebrae, preoperative thoracic Cobb angle, preoperative lumbar Cobb angle, preoperative translation of lumbar apex, preoperative coronal balance, preoperative L5 tilt, preoperative bending L5 tilt, postoperative translation of thoracic apex, postoperative lumbar Cobb angle, postoperative translation of lumbar apex, postoperative radiographic shoulder height, and postoperative L5 tilt. Logistic regression analysis showed that the preoperative bending L5 tilt, postoperative translation of the thoracic apex, and postoperative lumbar Cobb angle were the primary risk factors for IPCIB. The IPCIB index was defined as 1.3 * preoperative bending L5 tilt + 1.5 * postoperative translation of thoracic apex - 0.8 * postoperative lumbar Cobb angle. The receiver operating characteristics curve indicated that the occurrence rate of IPCIB was 88% and the non-occurrence rate was 90% when the IPCIB index was greater than 16. CONCLUSION: The preoperative bending L5 tilt, postoperative translation of the thoracic apex, and the postoperative lumbar Cobb angle were the primary risk factors for IPCIB in Lenke 5 and Lenke 6 AIS patients. The IPCIB index can be used to predict the occurrence of IPCIB with high accuracy. Our results indicate that the thoracic curve should be adequately corrected during surgery; however, moderate correction of the lumbar curve is recommended. These slides can be retrieved under Electronic Supplementary Material.

A novel radiographic classification of severe spinal curvatures exceeding 100°: the Omega (Ω), gamma (γ) and alpha (α) deformities.

PURPOSE: For spine curvatures with Cobb angles > 100°, curve classification and characterization become more difficult with conventional radiographs. 3-D computerized axial tomography scans add relevant information to categorize and describe a new classification to aid preoperative assessment in communication and patient evaluation. The purpose of this study is to describe a radiographic classification system of curves exceeding 100°. METHODS: A consecutive series of patients with curves exceeding 100° underwent a full spine radiographic review using conventional radiographs and 3-D CT. A descriptive analysis was performed to categorize curves into 4 main types (1, 2, 3 and 4) and 6 subtypes (1C, 1S, 1CS, 2P, 2D and 2PD) based on the location of the Cobb angle of the major scoliotic and kyphotic deformity as well as the location of the upper/lower end vertebra relative to the apical vertebra. RESULTS: A total of 98 patients met the inclusion criteria. There were 51 males and 47 females with an average age of 17.8 ± 4.5 years. The diagnosis included idiopathic (48); congenital (24); neuromuscular (4); and neurofibromatosis (2). The mean major coronal and sagittal Cobb (kyphosis) were 131.2° ± 23.4° and 154 ± 45.6, respectively. The classification scheme yielded 4 main types (1, 2, 3 and 4) and 6 subtypes under types 1 and 2 (1C, 1S, 1CS, 2P, 2D and 2PD). CONCLUSIONS: Our study describes a novel method of classifying severe spinal curvatures exceeding 100° using erect AP/lateral radiographs and 3-D CT reconstructive images. We hope that the descriptive analysis and classification will expand our understanding of these complex deformities. These slides can be retrieved under Electronic Supplementary Material.

The Association Between the Classification of Early-onset Scoliosis and Smith Complications After Initiation of Growth-friendly Spine Surgery: A Preliminary Study.

BACKGROUND: Early-onset scoliosis (EOS) is a complex, heterogeneous condition involving multiple etiologies, genetic associations, and treatment plans. In 2014, Williams and colleagues proposed a classification system of EOS (C-EOS) that categorizes patients by etiology, Cobb angle, and kyphosis. Shortly after, Smith and colleagues validated a classification system to report complications of growth-friendly spine instrumentation. Severity refers to the level of care and urgency required to treat the complication, and can be classified as device-related or disease-related complications. The purpose of this study was to investigate if C-EOS can be used as a reliable predictor of Smith complications to better risk stratify these young, surgical patients. METHODS: This study queried retrospective data from a large multicenter registry with regard to growth-friendly spine instrumentation in the EOS population. One-hundred sixteen patients were included in final data analysis to investigate the outcomes of their growth-friendly procedures according to the Smith complication classification system. RESULTS: There were 245 Smith complications distributed among 116 patients included in this study (2.1 complications per patient). The majority of the complications were device related requiring at least one unplanned trip to the operating room (Smith Device Complication IIA or IIB; 111 complications). There were no complications that caused abandonment of growth-friendly instrumentation (Smith Complication III) and no mortalities (Smith Complication IV). The most severely affected EOS group was the hyperkyphotic syndromic group with a major curve angle >50 degrees (S3+), with 3.4 complications per patient. The least affect EOS group was the hyperkyphotic congenital group with a major curve angle between 20 and 50 degrees, with 0.3 complications per patient. CONCLUSIONS: The C-EOS simplifies a complex pathology and the Smith complication classification scheme creates a language to discuss treatment of known complications of growth-friendly spine surgery. Although there is an association between more advanced C-EOS and Smith complications, there does not appear to be a correlation that can satisfy a risk stratification at this time. LEVEL OF EVIDENCE: Level II.

Complication Severity Score for Growth-friendly Surgery Has Strong Interrater and Intrarater Agreement.

BACKGROUND: Growth-friendly surgery has high complication rates. The Complication Severity Score for growth-friendly surgery was developed to maintain consistency while reporting complications as part of research in this rapidly evolving field. This study evaluates the interrater and intrarater reliability of this complication classification system. METHODS: After Institutional Review Board approval, complications during treatment for early onset scoliosis were identified from a prospectively collected database. Previous validation studies and a 10-case pilot survey determined that 60 cases were needed to represent a minimum of substantial agreement. In total, 63 of 496 cases were selected randomly to evenly represent each severity classification. The cases comprised an internet survey for classification sent to faculty and research coordinators involved in early onset scoliosis research, 3 weeks apart, with questions shuffled between iterations. Fleiss Kappa and Cohen Kappa were used to assess interrater and intrarater agreement, respectively. RESULTS: A total of 20 participants, 12 faculty and 8 research assistants, completed the survey twice. The overall Fleiss Kappa coefficient for interrater agreement from the second round of the survey was 0.86 (95% confidence interval, 0.86-87), which represents substantial agreement. Reviewers agreed almost perfectly on categorizing complications as Device I (0.85), Disease I (0.91), Disease II (0.94), Device IIB (0.92), and Disease IV (0.98). There was substantial agreement for categorizing Device IIA (0.73) and Device III (0.76) complications. Disease III and Device IV were not evaluated in this survey since none of these occurred in the database. There was almost perfect intrarater agreement among faculty (0.87), research coordinators (0.85), and overall (0.86). CONCLUSIONS: There is strong interrater and intrarater agreement for the published complications classification scheme for growing spine surgery. The complication classification system is a reliable tool for standardizing reports of complications with growth-friendly surgery. Adoption of this classification when reporting on growth-friendly surgery is recommended to allow for comparison of complications between treatment modalities. LEVEL OF EVIDENCE: Level I-diagnostic study.

Does Reoperation Risk Vary for Different Types of Pediatric Scoliosis?

STUDY DESIGN: Retrospective cohort study of spine fusion surgery utilizing the New York State Inpatient Database. OBJECTIVE: The objective was to determine whether there were differences in reoperation rates among pediatric scoliosis associated with various etiologies compared with idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: The incidence of postoperative complications and reoperations is known to vary among patients with diverse scoliosis pathologies. As these are heterogeneous conditions and often with rare occurrence, it is difficult to compare them in a single study. We aimed to assess reoperation events after fusion for several etiologies of pediatric scoliosis. METHODS: The 2008 to 2011 New York State Inpatient Database was queried using International Classification of Diseases (ICD-9-CM) codes for patients with in-hospital stays including a spine arthrodesis for scoliosis. All approaches, all fusion lengths, and ages 10 to 21 were included. Patient identifiers and linkage variables were used to identify revisits. The relative risk of reoperation was calculated for several rare conditions associated with scoliosis. RESULTS: Two thousand three hundred fifty-six pediatric scoliosis fusion surgeries were identified in 2008 in the state of New York. The 1- and 4-year reoperation rate for idiopathic scoliosis was 0.9% and 1.6%, respectively. For nonidiopathic scoliosis, the 1- and 4-year rates were 4.2% and 20.4%, respectively. Of the nonidiopathic scoliosis subtypes, congenital scoliosis (4.7% risk at 1 y, 41.6% at 4 y), the neuromuscular disease arthrogryposis (7.3% risk at 1 y, 28.6% at 4 y), and syndrome neurofibromatosis (9.1% at 1 y, 32.3% at 4 y) showed the highest risk for reoperation. Length of stay and hospital charges were higher for reoperations. CONCLUSIONS: Using a large administrative database, we identified neuromuscular, syndromic, and congenital forms of scoliosis that have the highest relative risk for a reoperation within 1 year. At-risk populations should be identified and resources allocated and preventative measures instituted accordingly to prevent these costly events. LEVEL OF EVIDENCE: Level III.

Three-Dimensional Analysis of Hemimetameric Segmental Shift in Congenital Scoliosis.

STUDY DESIGN: This is a retrospective cohort study. BACKGROUND: Hemimetameric segmental shift (HMMS) is defined as a hemivertebral deformation in which 2 or more hemivertebrae exist on both sides of the spine and are separated by at least 1 normal vertebra. Reports of HMMS are rare and based on simple anterior x-ray images. No reports have used 3-dimensional computed tomography (3D-CT) to analyze both the anterior and posterior elements. The objective of this study was to analyze the morphology and clinical features of HMMS 3 dimensionally. METHODS: HMMS was confirmed in 32 (6.6%, 16 males and 16 females) of 483 patients diagnosed with congenital scoliosis at the study institution between 1998 and 2013. The average age at the first visit was 6 years and 3 months. 3D-CT imaging was performed for 30 patients older than 2 years (average age: 9 y and 8 mo) and used to classify cases according to posterior elements. RESULTS: With regard to the number of hemivertebrae present, 21 patients had 2 hemivertebrae, 7 patients had 3 hemivertebrae, and 2 patients had 4 hemivertebrae. Patients with 2 hemivertebrae predominantly had hemivertebrae in the thoracolumbar spine. Patients were classified into 2 categories: malformation existing at an equal level in anterior and posterior sides (unison HMMS) and malformation existing at nonequal levels (discordant HMMS). Nine patients had unison HMMS and all of them had 2 hemivertebrae (average: 4.6 vertebrae). Twenty-one patients had discordant HMMS, with 12 having 2 hemivertebrae, 7 having 3 hemivertebrae, and 2 having 4 hemivertebrae. CONCLUSIONS: Through 3D-CT analysis, HMMS was categorized as unison or discordant. Discordant HMMS was observed in 21 of 30 (70%) patients and in all patients with >3 hemivertebrae. Diagnosing HMMS, whether unison or discordant, is clinically important and should be done with careful analysis of bone models and/or radiologic images to determine the correct spinal levels. LEVEL OF EVIDENCE: Level IV-diagnostic study.

Evaluation of the efficiency of the Chêneau brace on scoliosis deformity : A systematic review of the literature.

BACKGROUND: Scoliosis is a three-dimensional deformity of the spine and rib cage. Depending on the severity of this disease, various kinds of treatment methods have been used and bracing is among the most common. One of the braces which has been used for subjects with scoliosis is the Chêneau brace. The aim of this review was to evaluate the efficiency of the Chêneau brace on the scoliosis curve progression and control based on the available literature. METHOD: We conducted a Medline search via PubMed, Google Scholar, ISI Web of Sciences, Ebsco and Scopus. Keywords such as Chêneau brace, Chêneau light and CAD/CAM spinal brace were used in combination with scoliosis. The quality of the studies was evaluated by the Down and Black tool. RESULTS: Based on the aforementioned keywords, 55 papers were found. Finally based on the mentioned criteria 14 papers were selected for final analysis. The quality of the studies varied between scores of 13 and 25 using the Down and Black tool. The results of the selected studies confirmed that a good scoliotic curve correction can be achieved with the Chêneau brace. CONCLUSION: The Chêneau brace provides a 3-dimensional correction of the spinal deformity which not only influences the progression of scoliotic curve but also influences its natural history. It cannot be concluded that the Chêneau brace is superior to other available braces; however, it has been shown that this brace is effective to control the scoliotic curve progression especially in the lumbar and thoracolumbar regions.

Quantifying Anesthesia Exposure in Growing Rod Treatment for Early Onset Scoliosis.

BACKGROUND: Growing rod (GR) treatment for early-onset scoliosis requires repeated anesthesia exposure (AE). At a minimum, GR treatment requires AE for diagnostic imaging, index GR surgery, periodic lengthenings, and final fusion. Adjunct procedures and complication-related procedures also increase AE. To our knowledge, this is the first study to quantify AE in GR treatment and to establish preoperative expectations. METHODS: A single-center retrospective review of 16 patients who completed GR treatment and underwent final fusion. Duration of all AE related to GR treatment for "standard" care procedures (ie, advanced imaging, index surgery, lengthenings, final fusion) and "associated" care procedures (ie, revisions, adjunctive surgical procedures, wound-related complications) were reviewed. Etiologies were classified per the classification of early-onset scoliosis. Mean total anesthesia time (TAT) was tallied and analyzed for standard care and associated care procedures. RESULTS: There were 5 syndromic, 8 neuromuscular, and 3 idiopathic patients. The mean age at the first AE event related to GR treatment was 7.4 years (range, 3.8 to 11 y). Mean age at the index GR surgery and final fusion was 8.1 years (range, 3.9 to 14.4 y) and 12.8 years (range, 9.7 to 19 y), respectively. The percentage of TAT for each procedural category was 7% for advanced imaging, 14% for index GR, 14% for lengthenings, 21% for final fusion, 27% for revisions, 9% for adjunct surgery, and 9% for wound complications. Standard care procedures accounted for 55% of TAT, whereas associated care procedures accounted for 45%. CONCLUSIONS: This study quantified expected duration of AE in GR treatment. Revisions and final fusion contributed most to TAT. Given the recent controversy of repeated AE in young children, efficiency measures should be implemented to reduce AE and avoid duplication without compromising the goals of surgical treatment. Associated care procedures accounted for 45% of the total AE. LEVEL OF EVIDENCE: Level IV.

The Classification for Early-onset Scoliosis (C-EOS) Correlates With the Speed of Vertical Expandable Prosthetic Titanium Rib (VEPTR) Proximal Anchor Failure.

BACKGROUND: The Classification for Early-onset Scoliosis (C-EOS) was developed by a consortium of early-onset scoliosis (EOS) surgeons. This study aims to examine if the C-EOS classification correlates with the speed (failure/unit time) of proximal anchor failure in EOS surgery patients. METHODS: A total of 106 EOS patients were retrospectively queried from an EOS database. All patients were treated with vertical expandable prosthetic titanium rib and experienced proximal anchor failure. Patients were classified by the C-EOS, which includes a term for etiology [C: Congenital (54.2%), M: Neuromuscular (32.3%), S: Syndromic (8.3%), I: Idiopathic (5.2%)], major curve angle [1: ≤20 degrees (0%), 2: 21 to 50 degrees (15.6%), 3: 51 to 90 degrees (66.7%), 4: >90 degrees (17.7%)], and kyphosis ["-": ≤20 (13.5%), "N": 21 to 50 (42.7%), "+": >50 (43.8%)]. Outcome was measured by time and number of lengthenings to failure. RESULTS: Analyzing C-EOS classes with >3 subjects, survival analysis demonstrates that the C-EOS discriminates low, medium, and high speed of failure. The low speed of failure group consisted of congenital/51-90/hypokyphosis (C3-) class. The medium-speed group consisted of congenital/51-90/normal and hyperkyphosis (C3N, C3+), and neuromuscular/51-90/hyperkyphosis (M3+) classes. The high-speed group consisted of neuromuscular/51-90/normal kyphosis (M3N), and neuromuscular/>90/normal and hyperkyphosis (M4N, M4+) classes. Significant differences were found in time (P<0.05) and number of expansions (P<0.05) before failure between congenital and neuromuscular classes.As isolated variables, neuromuscular etiology experienced a significantly faster time to failure compared with patients with idiopathic (P<0.001) and congenital (P=0.026) etiology. Patients with a major curve angle >90 degrees demonstrated significantly faster speed of failure compared with patients with major curve angle 21 to 50 degrees (P=0.011). CONCLUSIONS: The ability of the C-EOS to discriminate the speeds of failure of the various classification subgroups supports its validity and demonstrates its potential use in guiding decision making. Further experience with the C-EOS may allow more tailored treatment, and perhaps better outcomes of patients with EOS. LEVEL OF EVIDENCE: Level III.

Classification of Early Onset Scoliosis has Excellent Interobserver and Intraobserver Reliability.

BACKGROUND: Classification systems can be useful tools for clinical care and research but must be proven as reliable. The purpose of this study was to evaluate the interobserver and intraobserver reliability of the Classification of Early Onset Scoliosis (C-EOS) scheme. METHODS: After IRB approval, 50 cases were drawn from a prospectively collected database of patients with EOS. Cases were selected using a stratified randomization scheme based on etiology. These cases were used to create an internet survey that was sent to pediatric orthopaedic faculty, research coordinators, and fellows involved in EOS care and research. Participants were asked to classify each case and were provided with a written C-EOS scheme that could be referenced while they completed the survey. Surveys were sent to participants twice, 3 weeks apart, to assess both intraobserver and interobserver reliability. Fleiss κ and Cohen κ were used to assess interobserver and intraobserver reliability, respectively. RESULTS: There were 36 total participants, 29 who completed the survey twice (21 faculty, 13 research coordinators, and 2 fellows). Overall Fleiss κ coefficient for interobserver reliability was excellent across the major categories of etiology (0.84), major curve (0.93), and kyphosis (0.96). Overall intraobserver reliability was excellent with Cohen κ values for etiology (0.92), major curve (0.96), and kyphosis (0.98). Faculty members had excellent agreement for etiology (0.90), major curve (0.91), and kyphosis (0.96). Research coordinators had high levels of agreement for etiology (0.78), and excellent for major curve (0.95) and kyphosis (0.96). Intraobserver reliability was excellent across all major categories for all groups: faculty, research coordinators, and fellows. CONCLUSIONS: The study shows high levels of interobserver and intraobserver agreement of the C-EOS scheme. The C-EOS scheme can be used as a reliable tool for classifying EOS patients for clinical communication and research. LEVEL OF EVIDENCE: Level II-diagnostic study.

The Interobserver and Intraobserver Reliability of the Sanders Classification Versus the Risser Stage.

BACKGROUND: Estimation of skeletal maturity, classically performed using Risser sign, plays a crucial role in the treatment of AIS. Recent data, however, has shown the simplified Tanner-Whitehouse (Sanders) classification, based on an anteriorposterior (AP) hand radiographs, to correlate more closely to the rapid growth phase and thus curve progression. This study evaluated the interobserver and intraobserver reliability of the Sanders and Risser classifications among clinicians at different levels of training. METHODS: Twenty AP scoliosis radiographs and 20 AP hand radiographs were randomized and distributed to 11 graders. The graders consisted of 3 orthopaedic residents, 3 spine fellows, 3 spine surgeons, and 1 radiologist. The graders were then asked to classify the radiographs according to the Sanders and Risser classifications. There were 3 rounds of grading, each done 3 weeks apart. The overall κ coefficient was then calculated for each system to evaluate the interobserver and intraobserver reliability. RESULTS: For all graders the average κ coefficient for the interobserver and intraobserver reliability of the Sanders classification was 0.54 and 0.62, respectively, and 0.46 and 0.49 for the Risser classification. With respect to spine attendings alone, the average κ coefficient for the interobserver and intraobserver reliability of Sanders classification was 0.72 and 0.77, respectively, and 0.46 and 0.67 for the Risser classification. CONCLUSIONS: Our study demonstrated that the Sanders classification had moderate reliability with respect to physicians at various levels of training and had good reliability with respect to attending spine surgeons. Interestingly, the Risser staging was found to have less interobserver and intraobserver reliability overall. The Sanders classification is a reliable and reproducible system and should be in the armamentarium of surgeons who treat adolescent idiopathic scoliosis. LEVEL OF EVIDENCE: Level III.