Cilia length regulation and maintenance is the result of a precise balance between processes involved in its assembly and disassembly. Intraflagellar transport (IFT) is a tightly evolutionary conserved system, which is responsible for transferring molecules to and from the tip of the cilium as an organelle extended out of cytoplasm. The IFT system composed of two multi-protein complexes, IFT-A and IFT-B, localized at the cilia base, that are involved in retrograde and anterograde transportation respectively . The accumulation or increased activity of the anterograde IFT system leads to elongation of cilia whereas reduced mobility of them results in shorter cilia . Stimulation of cyclic AMP and subsequent increased activity of PKA has been shown to lengthen cilia in mammalian epithelial and mesenchymal cells, through increased trafficking of anterograde IFT complex . Fluid shear-mediated deflection of the longer primary cilia then stimulates cAMP reduction inside the cell creating a regulatory feedback loop which shortens the cilia again . Melatonin signalling dysfunction and the following disturbance of intracellular cAMP previously reported in AIS patients , ,  might explain ciliary length abnormalities observed in AIS osteoblasts. AIS osteoblasts failure to adjust their ciliary length in proportion to applied mechanical stimulation (i.e. short- or long-term fluid flow) indeed points towards the possibility of ciliary defects underlying AIS pathogenesis. Incapable of adjusting the length of their cilia accordingly, AIS osteoblasts are not able to transfer proper information about the type and scale of the introduced mechanical stimulation to the cell, compromising the adaptive nature of bone to surrounding forces and perhaps leading to structural abnormalities in the bone. There could be a causative link between cilia length miss-regulation and AIS, as is the case in some types of cancers .
It is well known that adolescentidiopathicscoliosis (AIS) is a three-dimensional deformity of the trunk and spine; characterized by a spinal curve or curves in the patient’s coronal plane. Nevertheless, the sagittal plane represents an important aspect of the patient’s balance . Proximal junctional kyphosis is a recently recognized phenomenon in adolescents after AIS surgery. As it has been reported by Yan et al. the incidence of the proximal junctional kyphosis in the adolescent patients was estimated at 11% with a range of 0–55% depending on the study; revision surgery was needed in 10% of these cases . Etiology of PJK is likely multifactorial, with risk factors including thoracoplasty, hybrid instrumentation (proximal hooks and distal pedicle screws, pelvic fixation), integrity of the posterior ligaments, and a preoperative large sagittal thoracic Cobb angle (T5–T12 > 40°) . Kim et al. reported that a greater immediate postoperative thoracic kyphosis angle decrease and male sex correlated significantly with PJK .
T.X. Haen 1,2 MD MSc, W. Skalli 2 PhD, R. Vialle 1 MD PhD
Purpose: Various spinal and rib cage parameters measured from complex exams were found to be correlated with preoperative pulmonary function tests (PFT). The aim was to investigate the relationship between preoperative rib cage parameters and PFT using biplanar stereoradiography in patients with severe adolescentidiopathicscoliosis (AIS). Methods: Fifty-four patients, 45 girls and nine boys, aged 13.8 ± 1.2 years, with Lenke 1 or 2 thoracic scoliosis (>50°) requiring surgical correction were prospectively included. All patients underwent preoperative PFT and low-dose biplanar X-rays. The following data were collected: forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), FEV1/FVC ratio, residual volume (RV), slow vital capacity (SVC), total lung capacity (TLC), rib cage volume (RCV), maximum rib hump (MRH), maximum width, mean thoracic index, spinal penetration index (SPI), apical vertebral rotation (AVR), main curve Cobb angle (MCCA), T4-T12 kyphosis. The primary outcome was the relationship between rib cage parameters and PFT. The secondary outcome was the relationship between rib cage parameters and spine parameters. Data were analyzed using Spearman’s rank test. A multivariable regression analysis was performed to compare PFTs and structural parameters. Significance was set at α = 0.05.
The goal of adolescentidiopathicscoliosis (AIS) surgery is to achieve a 3D correction of the deformity and prevent curve progression of the unfused spine, while improving the overall cosmetic aspect of the trunk and preserving enough mobility for daily activities [ 1 ]. Correction has been reported with numerous systems, but the most popular technique currently relies on pedicle screws, with a recent emphasis on the axial correction of the deformity using direct vertebral derotation techniques [ 2 ]. How- ever, all-screw constructs have been associated with higher hospital charges (27.6% annually in the USA) and with a tendency to flatten the thoracic spine, not observed with hybrid constructs in matched patients [ 3 6 ]. Main- taining or restoring thoracic sagittal balance is essential not only to avoid future junctional degeneration (proxi- mal or distal), but also theoretically to improve pul- monary function, even if relevant clinical evidence is still lacking [ 7 9 ].
Adolescentidiopathicscoliosis (AIS) is the most com- mon form of the pathology, with risk of progression espe- cially during the pubertal growth spurt. The most common conservative treatment for progressive moderate to severe curves is bracing, which aims to stop or slow down the pro- gression to avoid surgery. Just like the assessment of scolio- sis severity, evaluation of brace effect on the spinal align- ment of AIS patients is often only focused on Cobb angle correction. Thanks to relatively recent technical advance- ments in 3D imaging of scoliosisin clinical routine [ 16 ], three-dimensional parameters started being included in the analysis of bracing [ 17 – 19 ]. This shows that bracing can have limited effects on the 3D deformity: it can leave the thoracic kyphosis and axial rotations unchanged or even worsened in up to 80% of cases [ 17 ]. This shows how the correction mechanisms of braces are still not completely understood. Several factors account for this: the complex shape of the deformity, the difficulty of planning and imple- menting an effective correction strategy, but also the com- pensating mechanisms that are usually not accounted for when planning a brace.
Adolescentidiopathicscoliosis (AIS) is a deformity of the spine, which is characterized by a typical three-dimen- sional pattern: a lateral displacement of the apical verte- bra, a torsion of the vertebral column and a flattening of the sagittal profile. This type of deformation is often com- pared to a buckling of the spine [ 7 , 9 , 12 , 13 ]: a mechani- cal phenomenon that may occur in slender structures under compressive loading and is characterized by a lateral dis- placement of parts of the structure. Buckling is due to a structural instability, and it can happen with low loads [ 27 ]. In this framework, spine stability and its tendency to buckle depend on its shape, its mechanical properties and its slenderness. The Scoliosis Research Society defines the vertebral slenderness as “the ratio of transverse vertebral diameters to vertebral height […] combined into various slenderness ratio” [ 23 ]. The slenderness ratio is higher in tall and thin structures and lower in short and stout ones.
One of the major revolutions in the field of adolescentidiopathicscoliosis (AIS) during the past 10 years is the develop- ment 3D imaging in standing position. The concept of AIS as a 3D deformity was brought for the first time in the early 80s by Perdriolle  and Dubousset and Graf  . Before them, AIS was a curve on a single AP view radiograph. From the concept to the routine use of 3D, we had to wait until the 21st cen- tury and the work of Georges Charpak, the 1992 Nobel Prize of physics, to see the development of standing position stereoradiography and its evolution in the actual EOS system (EOS Imag- ing)  . Accuracy and reproducibly of the system and its software for 3D reconstruction of the spine have been validated and are constantly improv- ing  . From now on, 3D analysis of the
This is an author-deposited version published in : http://oatao.univ-toulouse.fr/ Eprints ID : 10229
To cite this version : Swider, Pascal and Briot, Jérôme and Estivalèzes, Erik and Sales de Gauzy,
Jérôme. Disc volume properties from MRI inadolescentidiopathicscoliosis: correlation to surgical
AdolescentIdiopathicScoliosis (AIS) is a three-dimensional deviation of the spinal axis , which develops in most cases during adolescence and can lead to functional impairment. The scoliotic deformity is usually quantified radiographically using the Cobb angle  , a 2D parameter measured in the frontal plane that only suffices for a superficial description of the scoliosis. Surgery is often required at skeletal maturity in the case of severe scoliosis (Cobb angle higher than 45°), while conservative treatment (bracing or casting) is preferred when progressive scoliosis is diagnosed earlier (Cobb angle 20°-35°). The challenge of orthotic treatment is to stop or slow down the progression of the spinal curvature prior to skeletal maturity, in order to avoid surgery. Orthotic treatments are widely used for progressive curves; their effectiveness have often been questioned [3, 4], but a recent by Weinstein et al.  showed that bracing could significantly reduce scoliosis progression, especially in those patients with high level of compliance to brace wear.
Breast asymmetry is a common complaint among girls with adolescentidiopathicscoliosis (AIS). AIS is a complex tridimensional deformity of the spine that arises in 1-3% of otherwise healthy children between 10 years of age and skeletal maturity . Patients with scoliosis are generally screened, evaluated and if necessary, surgically corrected using a posterior approach. However, it is the anterior aspect of the deformity that often concerns girls with AIS, in particular, the asymmetry of their breasts. It is commonly believed that the breast asymmetry is secondary to the chest wall deformity (e.g. left breast larger in a right thoracic scoliosis) . Breast asymmetry is defined as a difference in shape, position and/or volume of the breast or the nipple-areola complex, and may be primary or secondary to a thoracic deformity. Some patients with scoliosis experience breast asymmetry, but its relationship with the thoracic deformity remains unknown [3,4]. Most women have some degree of minor physiological asymmetry (as high as 88% in some studies) [5,6] but this has not been previously described in the adolescent population.
Purpose To evaluate the 3D deformity of the acetabula and lower limbs in subjects with adolescentidiopathicscoliosis (AIS) and their relationship with spino-pelvic alignment.
Methods Two hundred and seventy-four subjects with AIS (frontal Cobb: 33.5° ± 18° [10°–110°]) and 84 controls were enrolled. All subjects underwent full-body biplanar X-rays with subsequent 3D reconstructions. Classic spino-pelvic and lower limb parameters were collected as well as acetabular parameters: acetabular orientation in the 3 planes (tilt, antever- sion and abduction), center–edge angle (CEA) and anterior and posterior sector angles. Subjects with AIS were represented by both lower limb sides and classified by elevated (ES) or lowered (LS), depending on the frontal pelvic obliquity. Param- eters were then compared between groups. Determinants of acetabular and lower limb alterations were investigated among spino-pelvic parameters.
A. L. Simon 1 • J. Sales de Gauzy 3 • K. Mazda 1
Purpose Recent literature has reported that the ]progres- sion risk of Lenke 5 adolescentidiopathicscoliosis (AIS) during adulthood had been underestimated. Surgery is, therefore, proposed more to young patients with progres- sive curves. However, choice of the approach and fusion levels remains controversial. The aim of this study was to analyze the influence of the length of posterior fusion on clinical and radiological outcomes in Lenke 5 AIS. Methods All Lenke 5 AIS operated between 2008 and 2012 were included with a minimum 2-year follow-up. Patients were divided into two groups according to the length of fusion. In the first group (selective), the upper instrumented level (UIV) was the upper end vertebra of the main structural curve and distally the fusion was extended to the stable and neutral vertebra, according to Lenke’s classification. In the second group (hyperselective), shorter fusions were performed and the number of levels fused depended on the location of the apex of the curve (at maximum, 2 levels above and below, according to Hall’s criteria). Apart from the fusion level selection, the surgical procedure was similar in both groups. Radiological out- comes and SRS-22 scores were reported.
situations leads to the use of postural strategies based more on the hip than on the ankle joint. Indeed, as using proprioceptive information becomes more difficult, the central nervous system has to rely on other information, i.e. vestibular and visual. This increased weighting of head sensory cues leads to an inversion of muscular activation sequences with a less appropriate top-down strategy, characterised by more hip joint input, as opposed to a more stable bottom-up strategy based on the ankle joint (inverted pendulum). 10 These results should be considered in conjunction with the results of dynamic posturographic tests, which show that patients with greater spine deformation tended to fall more and used more reactional than anticipatory strategies. Traditionally, good performances in dynamic posturographic tests are conveyed by the use of an anticipatory strategy, involving the ankle joint more than the hip joint. 8,10 The mechanisms related to the planning and programming of postural responses lead to reactional postural adjustments being favoured over anticipatory postural adjustments. This strategy reflects the increased difficulty for patients with bigger curves to devise postural strategies from movement-related parameters. It follows that AIS may represent a specific impairment of higher cortical function, as suggested by Machida. 59
in turn, protects the nerves that span from the spinal cord form being compressed between adjoining vertebrae. The intervertebral discs are composed of two distinguishable structures. The inner structure, named the nucleus pulposus, is responsible for resisting compression via hydrostatic forces. Such important near incompressibility is achieved by the constraints offered by the surrounding annulus fibrosus combined with the inferior and superior endplates. The nucleus makes up roughly 45% of the discs cross sectional area upon analysis in the transverse plane . In contrast to the disorderly composition of the nucleus, the outer annulus is a highly organized dense structure of collagen fibrils. The intervertebral discs are considered avascular and they must derive their nutrients via diffusion through the enclosing endplates or surrounding solution. These discs play an essential role in maintaining the integrity of the spinal column. Conversely, under a distorted environment, they may become paralysing and problematic . Degeneration of the intervertebral disc can be induced in two ways: by overloading or through immobilization. The development and the associated biological alterations that arise from these two criteria are well defined in a review performed by Stokes . In short, degenerative alterations within the disc may be linked to cell mediated changes that occur in relation to mechanical stimulus. More specifically the chondrocytes, who are responsible for producing the extracellular matrix along with proteoglycans and collagen, are less likely to proliferate under altered or non-optimal mechanical conditions (overloading or immobilization). While the intervertebral discs are responsible for providing compression resistance to the spine, the ligaments and passive spinal musculature (fascia) are responsible for maintaining stability and resisting tensional forces.
Shear wave elastography is a rapid and non-invasive mea- surement which can be performed at bedside; potentially, it could play a key role in helping the surgeon choosing the last instrumented level. Moreover, it could be potentially employed to detect early a degeneration of the adjacent disc postoperatively. Future work should aim at including larger cohorts to analyze more in detail those discs adjacent to the lower junctional vertebra (defining the lower end of the scoli- otic curve), to the stable vertebra (the most closely bisected by a vertically directed central sacral line) and the neutral disc (vertebra with the least axial rotation) [ 14 ]. These vertebrae are critical in the assessment of spinal deformities, and there- fore, their adjacent discs could present specific characteristics. Future work could also assess the feasibility of standing disc elastography, which could be informative on disc changes when loaded, while intraoperative elastography could provide a strong validation of the measurement, which would not be affected by the surrounding soft tissues, although anterior ap- proach is rare inscoliosis surgery.
could not be predicted if mechanical factors were taken into account independently. In order to carry out the complex growth process, energy physically integrates multi-axial stresses and implements the transformation of mechanical stimuli into the mechanochemical transduction, which regulates the biological growth, maintenance and remodeling (Carter D.R., Fyhrie D.R. et al. 1987; Silver F.H. and Bradica G. 2002; Silver F.H. and Siperko L.M. 2003). In addition, other stimuli, e.g. heat, electric/magnetic field, may also play similar roles on the regulation of bone cell activities (Madreperla S. A. et al. 1985; Ciombor D. M. et al. 2002), but this was not addressed in our study. Unlike the stress especially for mechanical environment, energy is a basic component existing in any kinds of processes including physical and biological process, and furthermore, energy can be considered as an equivalent that is generated from different stimuli but with similar effects. This comprehensive property makes it possible to explain how mechanical stimuli trigger biological modification (Carter D.R., Fyhrie D.R. et al. 1987). In addition, for the mechanical consideration, the energy concept logically integrates the multi-axial loads for comprehensively describing mechanobiological influences and further predicting the vertebra or other bone deformities.
3.2 Identification of a single nucleotide polymorphism in the Pitx1 promoter
determine if this occurs due to inactivating mutations or other genetic alterations within the regulatory regions of the gene. Approximately 10 kb of the human Pitx1 promoter was analyzed in genomic DNA obtained from AIS (n=92) and control subjects (n=88) using Fluorescence Polarization–Single Base Extension (FP-SBE) technology, at McGill University and Genome Quebec Innovation Centre. We identified a G to A polymorphism (rs6867012) located at nucleotide position -3727, upstream of the transcriptional initiation site. Statistical analysis revealed that the heterozygous variant AG had a significant association with AIS (30.6%) than controls (18.4%), p=0.057 (Table 3.1). The occurrence of the homozygous variant AA was rare in AIS (3.4%) and controls (1.2%), with p=0.61. Interestingly, the SNP is located within an E2F-like binding site, which is of interest since E2Fs can stimulate Pitx1 expression . E2F is a family of transcription factors.
Two main limitations affect the FEM evaluated in the present study; first, gravitational forces  and muscle contributions [9,33] were not explicitly implemented in the model. Therefore, the agreement between radiologic indices and simulation is only related to the passive me- chanical response of the spine-ribcage complex. This lim- itation, however, only affects the realism of the interaction between the brace and the patient’s voluntary response, which is beyond the scope of this article. Viscoelastic behavior of soft tissues was neglected as well, but this aspect probably does not play an important role in brace action, which is slow and the effects of which are measured after long delays.
3.1 Numerical test case of a 34 elements simplified spine
The direct problem was geometrically under-constrained and several admissible equilibria for 11eq have been obtained from energy minimization. Four solutions or deformation modes, Üe q l• lleq2, u eq 3, lleq4, have been selected in Fig. 2 b. The convergence criterion of energy balance minimization was lower than 10- 12• Calculations lasted between 0.2 s and 1 min CPU rime on a desk computer (Intel Xeon ® 3.6GHz). The inverse problem algorithm was applied using u eq1 as the targeted kinematic mode. It also played the role of uc previously introduced in paragraph 2.3.2 . The initial vector of effective properties p, i.e., K i , B i and uf, was randomly generated with values between 0.5 X Pre f and 1.5 X P ref ·
movement three trials were recorded and the average of the marker motion was calculated to reduce the effect of the marker place ment and measurement errors on the results. More over although the pelvic orientations during the course of the movement were registered, this study focused on the spine and pelvis parameters at the maximum range of movement. Subsequently only the ROMs exceeding 10 degrees were considered in the analysis. Consideration of the pelvic markers errors due to the skin movement artifact does not adversely affect the results and general conclusions of the study. Statistically significant differences between the scoliotic subgroups in terms of the pelvic ROM in the three anatomical planes showed the relationship between the spinal deformities and pelvic motion in AIS subgroups. Another limitation of this study was the selected sample; the studied subjects mostly had moderate spinal deformities. The spino-pelvic kinematic interaction in subjects with moderate (<40°) and severe curves (>40°), such as pre- surgery subjects, can be compared to better identify the impact of the curve severity on the pelvic motion in isolated scoliotic subgroups. However the results of the current study showed the significant impact of the thoracic and lumbar deformities on the spine and pelvic ROM and suggested the importance of the pelvic orientation in postural assessment of the patient.