Ane Simony

Mutation of the planar cell polarity gene VANGL1 in adolescent idiopathic scoliosis.

Study Design. Mutation analysis of a candidate disease gene in a cohort of patients with moderate to severe Adolescent idiopathic scoliosis (AIS). Objective. To investigate if damaging mutations in the planar cell polarity gene VANGL1 could be identified in AIS patients. Summary of Background Data. AIS is a spinal deformity which occurs in 1% to 3% of the population. The cause of AIS is often unknown, but genetic factors are important in the etiology. Rare variants in genes encoding regulators of WNT/planar cell polarity (PCP) signaling were recently identified in AIS patients. Methods. We analyzed the coding region of the VANGL1 gene for mutations using Sanger sequencing in 157 unrelated patients with moderate to severe AIS. The frequency of mutations in the patient cohort was compared with their frequency in a large cohort of controls. Functional effect of mutations were predicted in silico and analyzed in vitro by transfection of normal and mutant recombinant VANGL1 protein in Madin-Darby Canine Kidney (MDCK) cells. Cellular localization of recombinant proteins was analyzed by immunofluorescence microscopy analysis. Results. In the patient cohort, we identified two rare missense mutations in VANGL1, encoding a receptor involved in WNT/PCP signaling. The mutations, p.I136N and p.F440 V, are very rare in the normal population. Both mutations are predicted to be damaging, and to affect evolutionary conserved amino acid residues of VANGL1. Functional analysis in MDCK cells showed that the mutations abolished the normal translocation of VANGL1 to the cell membrane. Conclusion. Our data support that mutations in genes involved in WNT/PCP signaling may be associated with AIS, but replication in other patient cohorts and further analysis of the role of WNT/PCP signaling in AIS is needed. Level of Evidence: 4

Rate of Unsuspected Malignancy in Patients With Vertebral Compression Fracture Undergoing Percutaneous Vertebroplasty.

Study Design. Retrospective study. Objective. To determine the malignancy rate and histology in bone biopsies obtained during PVP for VCF. Summary of Background Data. Osteoporotic vertebral compression fractures (VCF) affect approximately 20% of postmenopausal women and can lead to long-term disability. Percutaneous vertebroplasty (PVP) is a minimally invasive procedure, primarily used in patients with severe pain after VCF. Even with a thorough clinical examination, magnetic resonance imaging (MRI) scans, and blood samples, some fractures maybe caused by an underlying malignant disease. Methods. 144 consecutive patients underwent PVP for painful VCF, at the Center for Spine Surgery and Research, Middelfart Hospital. All patients had bone biopsies obtained during the PVP, and these biopsies were sent to the Department for Pathology at Vejle Sygehus for histologic diagnosis. Results. About 144 patients were included in this study. The majority of the biopsy specimens (137, 95.1%) were acceptable for histological diagnosis. One hundred and twenty nine (89.6%) biopsies showed no signs of malignancy. Seven (4.9 %) were positive for malignancy. One biopsy was positive for MGUS. Seven (4.9 %) of the biopsies were unsuitable for histologic diagnosis. Conclusion. Our study shows an incidence of unsuspected malignancy in biopsies during PVP of 4.9%. Conservative treatment with analgesics and brace can potentially delay diagnosis and treatment of underlying malignant disease. We recommend biopsy during PVP as a standard procedure, to insure not to overlook any underlying malignancy despite the MRI-scan, blood analysis, and clinical examination being inconspicuous. Level of Evidence: 3

Reliability and Validity Testing of a Danish Translated Version of the Scoliosis Research Society Instrument–22 Revised (SRS-22R)

STUDY DESIGN Cross-sectional Objectives: To present a reliable and valid Danish translation of the Scoliosis Research Society-22R (SRS-22R). SUMMARY OF BACKGROUND DATA The SRS22R was designed as a disease-specific measure of quality of life in surgically treated adolescent idiopathic scoliosis (AIS) patients. It has been translated and adapted into several languages. A reliable and valid Danish version is not available. METHODS A Danish version of the SRS-22R was developed using previously published and widely accepted guidelines. The final Danish SRS-22R and the Danish Short Form-36 were administered to 169 AIS patients and 45 healthy controls. Cronbachs α was computed as a measure of internal consistency. Concordant validity was determined by computing correlations of the SRS-22R Domains with the corresponding SF-36 domains and factor analysis. Discriminant validity was determined by comparing Domain scores between AIS patients treated surgically, AIS patients treated with a brace, and the healthy controls. RESULTS One hundred sixty-five (97.6%) AIS patients and 42 (93.3%) healthy controls returned their questionnaires. Moderate ceiling effects were observed in the AIS cohort for the Function and Satisfaction Domains. Cronbachs α for each Domain and the Total score were good to excellent. Pearson correlation coefficients were found to be high for the SRS-22R Domains that had similar latent variables as the SF-36 Domains. Factor analysis revealed an underlying factorial structure of the questionnaire accounting for 60% of the explained variance. The SRS-22R Domain scores were statistically significantly different between the AIS cohort that had surgery, the AIS cohort that was treated with a brace, and the healthy controls. CONCLUSIONS The Danish version of the SRS-22R is reliable, with content, concordant, and discriminant validity. The scores, the score distribution, and the ceiling and floor effects were similar to those of the original SRS-22R in English as well as other previous translations.

Reliability and Validity Testing of a Danish Translated Version of Spinal Appearance Questionnaire (SAQ) v 1.1.

STUDY DESIGN Cross-sectional. OBJECTIVE To develop a psychometrically reliable and valid Danish version of the Spinal Appearance Questionnaire (SAQ). The SAQ was developed as a disease-specific measure of quality of life in patients with adolescent idiopathic scoliosis (AIS), specifically for younger patients, as it has more visual cues than verbal questions. A reliable and valid Danish Version is not available. METHODS A Danish version of the SAQ was developed using previously published and widely accepted guidelines. The final Danish SAQ and the Danish SRS22-R were administered to 78 AIS patients two weeks apart. Baseline and follow-up scores were compared. Cronbachs α and intraclass correlations were used to determine reliability. Correlation of SAQ domains with SRS-22R domains was calculated. Discriminative properties were compared by computing effect size and standardized response mean. RESULTS Fifty-one patients returned both the baseline and follow-up questionnaires, with an average age 16 ± 3 years and 40.8 ± 28.8 days between baseline and follow-up. There were no floor or ceiling effects for SAQ Appearance. There was a low floor effect and moderate ceiling effect for SAQ Expectations. There was good to excellent internal consistency within each domain. CONCLUSION This purpose of this study was to translate and validate a Danish version of the SAQ. Although problems were identified with items 7 and 8, the Danish SAQ is reliable and valid.STUDY DESIGN Cross-sectional. OBJECTIVE To develop a psychometrically reliable and valid Danish version of the Spinal Appearance Questionnaire (SAQ). SUMMARY OF BACKGROUND DATA The SAQ was developed as a disease-specific measure of quality of life in patients with adolescent idiopathic scoliosis (AIS), specifically for younger patients, as it has more visual cues than verbal questions. A reliable and valid Danish Version is not available. METHODS A Danish version of the SAQ was developed using previously published and widely accepted guidelines. The final Danish SAQ and the Danish SRS22-R were administered to 78 AIS patients two weeks apart. Baseline and follow-up scores were compared. Cronbachs α and intraclass correlations were used to determine reliability. Correlation of SAQ domains with SRS-22R domains was calculated. Discriminative properties were compared by computing effect size and standardized response mean. RESULTS Fifty-one patients returned both the baseline and follow-up questionnaires, with an average age 16 ± 3 years and 40.8 ± 28.8 days between baseline and follow-up. There were no floor or ceiling effects for SAQ Appearance. There was a low floor effect and moderate ceiling effect for SAQ Expectations. There was good to excellent internal consistency within each domain. CONCLUSION This purpose of this study was to translate and validate a Danish version of the SAQ. Although problems were identified with items 7 and 8, the Danish SAQ is reliable and valid.

Radiological Outcomes in Adolescent Idiopathic Scoliosis Patients More Than 22 Years After Treatment

STUDY DESIGN Longitudinal cohort. OBJECTIVES To evaluate the long-term radiologic outcomes in adolescent idiopathic scoliosis (AIS) patients more than 22 years after treatment. SUMMARY OF BACKGROUND DATA Although treatment for AIS is prophylactic and is aimed at preventing curve progression, very few studies report long-term outcomes of treatment. METHODS AIS patients treated with Boston brace or posterior spinal fusion (PSF) with Harrington-dorso-transverse traction (DTT) instrumentation from 1983 to 1990 were requested to return to clinic. Subsequently, 36-inch standing radiographs were obtained after patient consent. Cobb angles were compared with pretreatment and immediate posttreatment radiographs. Any evidence of adjacent-level disease or local kyphosis was also noted. RESULTS One hundred fifty-nine (78%) of 219 patients were available for follow-up, 66 braced and 93 surgical. There were 85 females with an average age at surgery of 14.3 years and an average age at follow-up of 37.6 years. The mean length of follow-up was 24.5 years (range, 22-30 years). There was a statistically significant curve progression of 2.9° in the PSF group. There was a greater degree of curve progression in the braced group (5.5°), but this was not statistically significant. Proximal segment degeneration was seen in 8 (5%), 2 in the brace cohort and 6 in the PSF cohort. Distal segment degeneration was seen in 26 (16%) patients, 4 treated with brace and 22 treated with PSF. No patient developed proximal junction kyphosis. Three patients in the PSF cohort required additional surgery for distal adding-on. Four patients had a noncontiguous L5-S1 fusion, three from the PSF cohort and one from the braced cohort. CONCLUSION In this cohort with an average follow-up of 24.5 years, with 78% available for follow-up, both the braced and surgically treated patients had a very small degree of curve progression, with a small incidence of distal segment degeneration and reoperation. LEVEL OF EVIDENCE III.

Wednesday, September 26, 2018 7:35 AM–9:00 AM ePosters: P178. Coccydynia, outcome one-year after surgical treatment of 138 consecutive patients

BACKGROUND CONTEXT Coccydynia caused by trauma or giving birth is mostly reported in females in the age 30-60years. Many treatment modalities have been suggested including special pillows, steroid injections, special physiotherapy and pain medication. Patients suffering from coccydynia reports severe pain and reduced Health related quality of life. Surgical treatment, can relieve persistent pain in patients suffering from coccydynia.This study reports the outcome, after surgical removal of coccyx in 138 consecutive patients. PURPOSE The purpose of this study is to report the outcome and rate of complications, 1 year after surgical treatment with partial or complete removal of the coccyx. STUDY DESIGN/SETTING A prospective cohort study. PATIENT SAMPLE Patients suffering from persistent coccydynia, for at least 12 months, after a blunt trauma. OUTCOME MEASURES Patient Reported Outcome Measures, SF- 36PCS/MCS, ODI, EQ5D, VAS Back/VAS Leg. METHODS Patients are evaluated by examination with bimanual palpation of the coccyx, and examination of the pelvic ligaments. If abnormal movement is present and the pain mechanism can be activated during examination of the coccyx, surgery with full or partially removal of the coccyx bone is suggested. All patients are treated with steroid injections prior to surgery, with only short term relief. RESULTS A total of 138 consecutive patients was treated at the Sector for Spine Surgery, Middelfart Hospital and evaluated 3 and 12 months after surgery. Three months after surgery, 40% of the patients are pain free in sitting position, 47% of the patients are experiencing some degree of discomfort in sitting position but are improved and 13% of the patients are still experiencing pain while sitting. A total of 99 patients are satisfied, 1 year after the surgery. A total of 22 patients have hoped to have a bigger improvement and 17 patients are not satisfied. A total of 32 patients developed infections after surgery and received antibiotics, 5 reoperations was performed, 3 due to infections and 2 due to rupture of the skin after return to normal daily living 3 months after surgery. CONCLUSIONS Pain in the coccyx after trauma or birth, are a quite common condition in women. Patients with severe symptoms and a history of pain duration of more than 12-18 months, should be referred for spine surgical evaluation. Partial or complete resection of the coccyx, is a safe procedure with in most patients will relieve the pain and restore the ability to sit.

CELSR2 is a candidate susceptibility gene in idiopathic scoliosis

A Swedish pedigree with an autosomal dominant inheritance of idiopathic scoliosis was initially studied by genetic linkage analysis, prioritising genomic regions for further analysis. This revealed a locus on chromosome 1 with a putative risk haplotype shared by all affected individuals. Two affected individuals were subsequently exome-sequenced, identifying a rare, non-synonymous variant in the CELSR2 gene. This variant is rs141489111, a c.G6859A change in exon 21 (NM_001408), leading to a predicted p.V2287I (NP_001399.1) change. This variant was found in all affected members of the pedigree, but showed reduced penetrance. Analysis of tagging variants in CELSR1-3 in a set of 1739 Swedish-Danish scoliosis cases and 1812 controls revealed significant association (p = 0.0001) to rs2281894, a common synonymous variant in CELSR2. This association was not replicated in case-control cohorts from Japan and the US. No association was found to variants in CELSR1 or CELSR3. Our findings suggest a rare variant in CELSR2 as causative for idiopathic scoliosis in a family with dominant segregation and further highlight common variation in CELSR2 in general susceptibility to idiopathic scoliosis in the Swedish-Danish population. Both variants are located in the highly conserved GAIN protein domain, which is necessary for the auto-proteolysis of CELSR2, suggesting its functional importance.

Concordance Rates of Adolescent Idiopathic Scoliosis in a Danish Twin Population

Study Design. Clinical, radiological, and genetic determination of zygosity of twin pairs from the Danish Twin Registry who self-reported having adolescent idiopathic scoliosis (AIS). Objective. To establish concordance rates of AIS. Summary of Background Data. The etiology of and the true mode of inheritance of AIS remain unclear. Studies on concordance in twin pairs provide a basis for analyzing the influence of genetic versus environmental factors. In 2007, using self-report of AIS from the Danish Twin Registry, concordance rates of 0.13 in monozygotic twins and 0.00 in dizygotic twins were reported. Methods. All 46,418 twins registered in the Danish Twin Registry born from 1931 to 1982 were sent a survey, which included questions about scoliosis. The survey was returned by 34,944 individuals (75.3%) representing 23,204 pairs. From the present study, 548 individuals representing 274 complete twin pairs in which at least one twin self-reported having scoliosis were invited to a clinical and radiological examination. Zygosity was established by genetic testing. Results. A total of 182 individuals (33.2%) of the original cohort agreed to participate, 128 of whom had scoliosis by self-report. There were 91 twin pairs, in which one or both twins had reported scoliosis and 36 individuals whose twin did not want to participate. Only 35 (27%) of the 128 participants with self-reported scoliosis had a clinically and radiologically confirmed curve. Calculating concordance in twins with Cobb angles greater than 10°, we found that the pairwise concordance rate was 0.4 (0.10–0.70) for monozygotic and 0.05 (−0.05–0.15) for dizygotic twins, P = 0.05, probandwise concordance was 0.45 (0.16–0.74) for monozygotic and 0.1 (−0.03–0.23) for dizygotic pairs. Conclusion. Concordance rates in a Danish twin population using genetic testing for zygosity are higher than previously reported using self-report. Although not statistically significant, the differences in monozygotic and dizygotic pairs indicate that genetic factors may be of importance for scoliosis. Level of Evidence: 3

Prevalence of Unsuspected Malignancy in Patients with Vertebral Compression Fracture undergoing Percutaneous Vertebroplasty

Introduction Osteoporotic vertebral compression fractures (VCF) affect ~20% of postmenopausal women and can lead to long-term disability. Percutaneous Vertebroplasty (PVP) is a minimally invasive procedure, primarily used in patients with severe pain after VCF. Even with a thorough clinical examination, MRI scans and blood samples, some fractures maybe caused by an underlying malignant disease. Objectives were to determine the prevalence of malignancy and histology in bone biopsies obtained during PVP for osteoporotic VCF. Material and Methods Study design - Retrospective study of a prospective collected cohort. 144 consecutive patients underwent PVP for painful VCF, at the Center for Spine Surgery and Research, Middelfart Hospital. All patients had bone biopsies obtained during the PVP, and these biopsies were sent to the Department for Pathology at Vejle Sygehus for histologic diagnosis. Results 144 patients were included in this study. The majority of the biopsy specimens (137, 95,1%) were acceptable for histological diagnosis. 129 (89.6%) of the biopsies showed no signs of malignancy. Seven (4,9%) were positive for malignancy. 1 biopsy was positive for MGUS. Seven (4.9%) of the biopsies were unsuitable for histologic diagnosis. Conclusion Our study shows a prevalence of unsuspected malignancy in biopsies during PVP of 4.9%. Conservative treatment with analgesics and brace can potentially delay diagnosis and treatment of underlying malignant disease. We recommend biopsy during PVP as a standard-procedure, to insure not to overlook any underlying malignancy despite the MRI-scan, blood analysis and clinical examination being inconspicuous.

Radiological Outcome in Adolescent Idiopathic Scoliosis Patients 20 Years after Treatment

Introduction The purpose of this study was to evaluate the long-term radiological outcome, curve progression, and adjacent level degeneration 20 years after idiopathic scoliosis treatment with Boston brace or Harrington rods. Materials and Methods A total of 219 patients treated with Boston brace or posterior spinal fusion a.m. Harrington were invited to participate in a long-term evaluation with clinical examination and X-ray evaluation. The old medical charts and X-ray descriptions were available. Standing X-ray was examined, the Cobb angle measured and compared with the patients previous X-ray and the adjacent levels were evaluated for any signs of adjacent level disease or local kyphosis. Results A total of 159 patients (78%) participated. Of them, 66 patients were treated with Boston brace and 92 patients were treated with posterior spinal fusion a.m. Harrington. In the brace group, the Cobb angle before treatment was 37.5 degrees (35.1–40.0 degrees) and after treatment was 34.7 degrees (31.9–37.5 degrees). Cobb angle after 20 years was 40.2 degrees (36.7–43.6 degrees). In the surgical group, the Cobb angle before treatment was 54.5 degrees (50.4–58.8 degrees), 1-year postoperatively was 29.5 degrees (25.7–33.9 degrees). Cobb angle after 20 years was 32.35 degrees (27.9–39.5 degrees). A total of 26 patients had distal segment degeneration in X-ray (16.5%), 4 patients were treated with brace and 22 patients with posterior spinal fusion. A total of 8 patients had proximal segment degeneration (5%), 2 patients were treated with brace and 6 patients with posterior spinal fusion. A total of 4 patients were treated with posterior fusion of the distal adjacent segment (2.6%), 1 was treated with brace and 3 were treated with posterior spinal fusion. Conclusion The average follow-up was 24.5 years (range, 15–35 years). The brace group had a small reduction in the spinal deformity during the treatment period, and X-rays show a small progression of the deformity, with the Cobb angle increasing by 5.5 degrees within 20 years. The surgically treated patients had a large correction during surgery and there is no statistical significant progression or loss of correction over a 20-year period. Only 4 patients in the brace group have distal segment degeneration and only 1 patient was treated with a one-level spinal fusion. The surgically treated groups had a significant deformity correction during surgery and have maintained the correction after 20 years. A total of 22 patients have distal degeneration and 3 patients were treated with distal adding on surgery.