The aim of this study is to clarify the implication of ciliary pathway on the onset of the spinal curvature that occurs in Adolescent Idiopathic Scoliosis (AIS) patients through functional studies of two genes: POC5 and TTLL11. Since the genetic implication for AIS is accepted, many association and candidate gene analysis revealed the implication of ciliary genes. The characterisation of these two proteins was assessed by qPCR, WB and immunofluorescence in vitro using control cells and cells derived from AIS patients. The impact of genetic modification of these genes on the functionality of the proteins in vitro and in vivo was analysed in zebrafish model created by CRISPR/Cas9 using microCT and histologic analysis. Our study revealed that mutant cells, for both gene, were less ciliated and the primary cilia was significantly shorter compared to control cells. We also observed a default in cilia glutamylation by immunofluorescence and Western Blot. Moreover, we observed in both zebrafish model, a 3D spine curvature similar to the spinal deformation in AIS. Interestingly, our preliminary results of immunohistology showed a retinal defect, especially at the cone cell layer level. This study strongly supports the implication of the ciliary pathway in the onset of AIS and this is the first time that a mechanism is described for AIS. Indeed, we show that shorter cilia could be less sensitive to environmental factors due to lower glutamylation and result in altered signalling pathway. Identifying the biological mechanism involved is crucial for elucidating AIS pathogenesis

Aim. The aim of this study is to identify the incidence of the presence of an Inverted Radial Reflex (IRR) in asymptomatic subjects with Adolescent Idiopathic Scoliosis and determine its significance. Methods. Our study group consists of Adolescent Idiopathic Scoliosis patients who presented consecutively in our institution from June to September 2010. They were either seen in outpatient clinics or as elective admissions prior to operative correction of their spinal deformity. The presence of an idiopathic scoliosis deformity and the absence of any abnormal neurological symptoms were our inclusion criteria. They were examined by two clinicians for the presence of IRR using a tendon hammer. As part of their management all such patients routinely undergo an MRI scan in our Trust to investigate for the presence of intraspinal pathology. When the IRR was present we looked at their MRI scans to identify any relevant abnormalities. Results: We identified 100 subjects. There were 72 females and 28 males with an average age of 15 years. The IRR was present in 12 cases and in 6 of them the sign was present bilaterally. There were no further associated signs or symptoms. All cases had recently undergone MRI of their whole spine and their investigations did not demonstrate any abnormalities in the lower cervical spine. Conclusion. We have found an incidence of 12% for the presence of IRR in our study group. In all cases there were no abnormal cord signal changes in MRI scans and we can therefore conclude that in asymptomatic Adolescent Idiopathic Scoliosis patients the presence of IRR is of no clinical significance

There is a need for non-radiographic, objective outcome measures for children with Adolescent Idiopathic Scoliosis (AIS). Standing balance and stability is altered in children with AIS. The Margin of Stability (MoS) has been used to compare gait stability in clinical populations. Our objective was to compare the MoS in anterior-posterior (MoS. AP. ) and mediolateral (MoS. ML. ) directions in girls with AIS to Controls. Girls with AIS and healthy girls walked at three speeds on an instrumented treadmill wearing retroreflective markers, surrounded by motion capture cameras. The MoS. AP/ML. was calculated at left and right heel strike. Data was processed in Visual 3D. A two-way ANOVA was used to compare MoS. AP/ML. between group, speed and the interaction between group and speed. Pearson's correlation coefficient was used to compare the MoS to Cobb angle. Statistical significance was accepted when p > 0.05. A priori power analysis suggested 12 participants per group. Three Cases and four Controls were recruited. Girls with AIS all had right-sided main thoracic curves (Lenke type 1a, 61.3° ± 10.0°). MoS. AP. was significantly bigger for Cases compared to Controls on the left (p=0.038) and right foot (p=0.041). There was no significant difference between Cases and Controls for MoS. ML. , but there was a visual trend for a smaller MoS. ML. in Cases. There was no significant difference for speed or the interaction between group and speed for MoS. AP. or MoS. ML. In Cases, MoS. AP. increased with increasing Cobb angle on the left (r. 2. =0.687, p=0.054) and right (r. 2. =0.634, p=0.067) and MoS. ML. decreased with increasing Cobb angle on the left (r. 2. =-0.912, p=0.002). Further subjects are being recruited. Girls with Lenke type 1a AIS are more stable in the AP direction and less stable in the ML direction than Controls during treadmill walking. AP stability increases and ML stability decreases with increasing Cobb angle. This research suggests that the MoS could be used as an outcome measure for children with AIS. Continued work is required to increase the power of this study. Further work could consider these changes during walking overground, measuring an MoS or MoS-like measure using a wearable device, and in different curve types

Aims

Scoliosis is a lateral curvature of the spine with associated rotation, often causing distress due to appearance. For some curves, there is good evidence to support the use of a spinal brace, worn for 20 to 24 hours a day to minimize the curve, making it as straight as possible during growth, preventing progression. Compliance can be poor due to appearance and comfort. A night-time brace, worn for eight to 12 hours, can achieve higher levels of curve correction while patients are supine, and could be preferable for patients, but evidence of efficacy is limited. This is the protocol for a randomized controlled trial of ‘full-time bracing’ versus ‘night-time bracing’ in adolescent idiopathic scoliosis (AIS).

Aim:. To Determine Whether Maximal Rib Prominence Measured On Lateral Radiographs Can Be Used As A Surrogate To Rib Rotation Determined By Surface Tomography (Quantecscanning) In Assessment Of Spinal Rotation. Method:. Patients With Adolescent Idiopathic Scoliosis Underwent Plain Lateral Radiographs And Quantec Scans. Maximal Rib Prominence On The Lateral Radiograph Was Defined Pre- And Post-Operatively By Distance From Most Posterior Aspect Of The Rib To The Facet Joint And Instrumented Rod, Respectively. Rib Rotation Was Measured By Surface Tomography Quantec Scan Using The Suzuki Method. This Was Then Repeated At A Later Time And By An Additional Investigator To Assess Intra- Observer And Inter-Observer Variability. The Correlation Between Maximal Rib Prominence And The Suzuki Ratio Was Determined. Results:. 20 Patients, Median Age 15 Years, Were Evaluated. The Correlation Coefficient Between Radiograph Determined Maximal Rib Prominence And Quantec Derived Suzuki Ratio Was 0.68, R2=0.46 (See Figure). Discussion:. There Was A Weak Positive Correlation Between Radiograph Determined Maximal Rib Prominence And Quantec Derived Suzuki Ratio. Further Investigation In A Larger Cohort Is Warranted. Conflict Of Interest Statement: No conflict of interest

Adolescent Idiopathic Scoliosis (AIS) patients were subjected to four weeks of Physiotherapy Scoliosis Specific Exercise (PSSE). 124 (Exclusion = 3) Patients were enrolled and assigned to either complete their treatment in one 4-week bout (4WC) (63 patients, M. age. = 14.52), or to complete their treatment in two separate fortnightly bouts (2X2WC) (63 patients, M. age. = 14.26). Clinical exam, surface topography and Scoliometer readings were compared. The SRS-30 questionnaire before and after treatment was conducted at 6, 12, 18 and 24 months. Group 1 (4WC) showed significant improvements from baseline (Pre-3.73 – Post 3.9; p=0.026) after the course of treatment, and showed significant improvements at 12 months follow up in Mental Health (p=0.006), Aggregate score (p= 0.005) and Satisfaction score (p=0.011). Satisfaction score remained statistically significant at 18 months follow up (p=0.016). Group 2 (2X2WC) did not record a significant improvement from baseline (p=0.058); however, showed significant improvements in self-image (p=0.013). There was no statically significant difference in SRS scores with respect to follow up time. We conclude that Physiotherapy Scoliosis Specific Exercise (PSSE) is a successful non-invasive therapy for AIS. The modified Schroth technique (ScolioGold) shows significant improvement in SRS30 scores with the 4-week intensive course that are sustained at a 2 year follow up

Background

Scoliosis is described as a lateral spinal curvature exceeding ten degrees on radiograph with vertebral rotation. Approximately 80% of scoliosis presentations are adolescent idiopathic scoliosis (AIS). Current management for AIS in the UK occurs in Surgeon or Paediatrician-led clinics and can be conservative or surgical. The musculoskeletal assessment and triage of AIS appears well-suited to an advanced physiotherapist practitioner (APP) skill set. The aim of this service evaluation was to scope, develop, implement and evaluate a four-month pilot of an APP-led AIS triage pathway.

Use of ultrasonic bone scalpel (UBS) is becoming popular in spinal surgery. This study presents the safety profile of UBS for posterior release in surgical correction of adolescent idiopathic scoliosis (AIS).

From 2016 to 2018, UBS (Misonix) was used by the senior author in a variety of spinal operations. Data for intraoperative complications when this devise was used for posterior correction of AIS were collected. Revision cases were excluded.

UBS was used for posterior release of AIS in 65 patients (58 female, seven male) with an average age of 15.6 years (range 11–23). Average length of posterior instrumentation was 12 levels (range 6–14). Instrumentation was exclusively from T2 to L4. To achieve adequate release for correction, UBS was used to perform a total of 644 modified in-situ chevron osteotomies (average ten, range six to 12) and 31 rib osteotomies. Overall, three complications (4.6 %) were directly related to the use of UBS: one haemopneumothorax, which was successfully treated with a chest drain; and two loss of motor-evoked potentials during monitoring, which led to the postponement of the final correction. These two patients did not have any neurological problems and their surgery was completed successfully within 1 week of the initial surgery. One late deep infection was reported. This was not thought to be directly related to the use of UBS.

Use of UBS in the posterior surgical treatment of AIS appears to be relatively safe with a low level of acceptable complications. However, appropriate training is required for the use of UBS.

To determine whether spinal facet osteoblasts at the curve apex display a different phenotype to osteoblasts from outside the curve in patients with adolescent idiopathic scoliosis (AIS). Intrinsic differences in the phenotype of spinal facet bone tissue and in spinal osteoblasts have been implicated in the pathogenesis of AIS. However, no study has compared the phenotype of facet osteoblasts at the curve apex with the facet osteoblasts from outside the curve in patients with AIS.

Facet bone tissue was collected from three sites, the concave and convex side at the curve apex and from outside the curve from three female patients with AIS (aged 13–16 years). Micro-CT analysis was used to determine the density and trabecular structure. Osteoblasts were then cultured from the sampled bone. Osteoblast phenotype was investigated by assessing cellular proliferation (MTS assay), cellular metabolism (alkaline phosphatase and Seahorse Analyser), bone nodule mineralisation (Alizarin red assay), and the mRNA expression of Wnt signalling genes (quantitative RT-PCR).

Convex bone showed greater bone mineral density and trabecular thickness than did concave bone. The convex side of the curve apex exhibited a significantly higher proliferative and metabolic phenotype and a greater capacity to form mineralised bone nodules than did concave osteoblasts. mRNA expression of SKP2 was significantly greater in both concave and convex osteoblasts than in non-curve osteoblasts. The expression of SFRP1 was significantly downregulated in convex osteoblasts compared with either concave or non-curve.

Intrinsic differences that affect osteoblast function are exhibited by spinal facet osteoblasts at the curve apex in patients with AIS.

A Core Outcome Set (COS) for treatment of adolescent idiopathic scoliosis (AIS) is essential to ensure that the most meaningful outcomes are evaluated and used consistently. Measuring the same outcomes ensures evidence from clinical trials and routine clinical practice of different treatments can be more easily compared and combined, therefore increasing the quality of the evidence base. The SPINE-COS-AYA project aims to develop a gold standard COS which can be used internationally in research and routine clinical practice to evaluate the treatment (surgical and bracing) of AIS.

In this qualitative study, the views of adolescents and young adults with AIS (10-25 years of age), their family members and healthcare professionals in a UK region were sought, via interviews, on treatment outcomes. Participants were purposively recruited from a variety of sources including NHS outpatient clinics and social media. Semi-structured interviews were analysed using thematic analysis.

Key findings will be presented, to include potential core outcome domains identified by the different subgroups.

The core outcome domains identified in this research programme will subsequently form part of an international consensus survey to agree a COS. In future, if the COS is used by healthcare staff and researchers, it will be easier for everyone, including patients and their families, to assess which treatment works best.

Introduction

Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity. It occurs mainly in girls and progresses during pre-pubertal and pubertal growth, which is a crucial period for bone mass acquisition. The cause and molecular mechanisms of AIS are not clear; at present the consensus is that AIS has a multifactor cause, with many genetic factors. During the past 5 years, considerable effort has been devoted to identify a gene or genes that cause a predisposition to AIS. Many loci for this disorder have been mapped to different chromosome regions, but no genes have been clearly identified as being responsible for AIS, and, most importantly, the resulting protein defects remain to be shown. We aimed to identify the gene(s) that could be involved in AIS and to validate their involvement by both genetic and functional analyses.

Purpose of the study

We propose a simple classification for adolescent idiopathic scoliosis (AIS) based on two components which include the curve type and shoulder level and suggest a treatment algorithm for AIS.

We previously reported that osteoblasts at the curve apex in adolescent idiopathic scoliosis (AIS) exhibit a differential phenotype, compared to non-curve osteoblasts(1). However, the Hueter-Volkmann principle on vertebral body growth in spinal deformities (2) suggests this could be secondary to altered biomechanics. This study examined whether non-curve osteoblasts subjected to mechanical strain resemble the transcriptomic phenotype of curve apex osteoblasts.

Facet spinal tissue was collected perioperatively from three sites, (i) the concave and (ii) convex side at the curve apex and (iii) from outside the curve (non-curve) from six AIS female patients (age 13–18 years; NRES 19/WM/0083). Non-curve osteoblasts were subjected to strain using a 4-point bending device. Osteoblast phenotype was determined by RNA sequencing and bioinformatic pathway analysis.

RNAseq revealed that curve apex osteoblasts exhibited a differential transcriptome, with 1014 and 1301 differentially expressed genes (DEGs; p<0.05, fold-change >1.5) between convex/non-curve and concave/non-curve sites respectively. Non-curve osteoblasts subjected to strain showed increased protein expression of the mechanoresponsive biomarkers COX2 and C-Fos. Comparing unstimulated vs strain-induced non-curve osteoblasts, 423 DEGs were identified (p<0.05, fold-change >1.5). Of these DEGs, only 5% and 6% were common to the DEGs found at either side of the curve apex, compared to non-curve cells. Bioinformatic analysis of these strain-induced DEGs revealed a different array of canonical signalling pathways and cellular processes, to those significantly affected in cells at the curve apex.

Mechanical strain of AIS osteoblasts in vitro did not induce the differential transcriptomic phenotype of AIS osteoblasts at the curve apex.

Introduction

Despite extensive research, the cause of adolescent idiopathic scoliosis (AIS) is still largely unclear. Girls with AIS tend to be taller and leaner, and have a lower body-mass index (BMI) and lower bone mass, than do healthy girls. Recent MRI studies have shown the presence of relative anterior spinal overgrowth in girls with AIS. The lower bone mineral status and BMI could be related to dysfunctional central regulation pathway of growth, bodyweight, and bone metabolism. Following several interesting reports on the role of leptin in regulation of the above pathway in animals and human beings, our recent study has shown a low leptin concentration in girls with AIS girls compared with healthy adolescents. This finding leads to our new hypothesis that abnormal leptin bioavailability could be associated with the lower bodyweight, lower bone mineral density, and relatively disproportional endochondral skeletal growth in AIS. This study aimed to investigate the leptin bioavailability in girls with AIS.

Background

Surgical treatment of AIS includes several purposes such as arrest deformity progression through a solid fusion, obtain a permanent correction of the deformity and others.

Introduction

Different subclinical neurological dysfunction has been reported in adolescent idiopathic scoliosis (AIS), including poor postural control and asymmetric otolith vestibulo-ocular responses when compared with normal controls. The objective of this pilot study is to establish whether abnormal MRI morphoanatomical changes arise in the CNS (brain and vestibular system), among left-thoracic versus right-thoracic AIS when compared with normal adolescent controls, with use of advanced computerised statistical morphometry techniques.

Introduction

Autonomic nerve system (ANS) regulates intercostal vascular nutrition (internal mammary artery), and its pathological status leads to developmental asymmetry of the trunk and rib cage, and consequently producing scoliotic deformity of the spine. The aim of this study is to investigate the possible causation of idiopathic scoliosis in development abnormalities of ANS.

Introduction

The cause of adolescent idiopathic scoliosis (AIS) is still not known. Although several candidate gene studies and linkage analyses have been done, no causal relationship has yet been established. To our knowledge, we report the first case-control based genome-wide association study (GWAS) for this trait.

Introduction

A common question posed by adolescents undergoing corrective scoliosis surgery is, “How much taller will I be after my operation?” This study aims to help answer this question, and quantify the gain in height that might be expected.

Aim

To evaluate the effect of corrective surgery for adolescent idiopathic scoliosis on pelvic morphology.