Biomechanical analysis and modeling of different vertebral growth patterns in adolescent idiopathic scoliosis and healthy subjects

<p>Abstract</p> <p>Background</p> <p>The etiology of AIS remains unclear, thus various hypotheses concerning its pathomechanism have been proposed. To date, biomechanical modeling has not been used to thoroughly study the influence of the abnormal growth profile (i.e., the growth rate of the vertebral body during the growth period) on the pathomechanism of curve progression in AIS. This study investigated the hypothesis that AIS progression is associated with the abnormal growth profiles of the anterior column of the spine.</p> <p>Methods</p> <p>A finite element model of the spinal column including growth dynamics was utilized. The initial geometric models were constructed from the bi-planar radiographs of a normal subject. Based on this model, five other geometric models were generated to emulate different coronal and sagittal curves. The detailed modeling integrated vertebral body growth plates and growth modulation spinal biomechanics. Ten years of spinal growth was simulated using AIS and normal growth profiles. Sequential measures of spinal alignments were compared.</p> <p>Results</p> <p>(1) Given the initial lateral deformity, the AIS growth profile induced a significant Cobb angle increase, which was roughly between three to five times larger compared to measures utilizing a normal growth profile. (2) Lateral deformities were absent in the models containing no initial coronal curvature. (3) The presence of a smaller kyphosis did not produce an increase lateral deformity on its own. (4) Significant reduction of the kyphosis was found in simulation results of AIS but not when using the growth profile of normal subjects.</p> <p>Conclusion</p> <p>Results from this analysis suggest that accelerated growth profiles may encourage supplementary scoliotic progression and, thus, may pose as a progressive risk factor.</p

FEM Simulation of Non-Progressive Growth from Asymmetric Loading and Vicious Cycle Theory: Scoliosis Study Proof of Concept

Scoliosis affects about 1-3% of the adolescent population, with 80% of cases being idiopathic. There is currently a lack of understanding regarding the biomechanics of scoliosis, current treatment methods can be further improved with a greater understanding of scoliosis growth patterns. The objective of this study is to develop a finite element model that can respond to loads in a similar fashion as current spine biomechanics models and apply it to scoliosis growth. Using CT images of a non-scoliotic individual, a finite element model of the L3-L4 vertebra was created. By applying asymmetric loading in accordance to the ‘vicious cycle’ theory and through the use of a growth modulation equation it is possible to determine the amount of growth each region of the vertebra will undergo; therefore predict scoliosis growth over a period of time. This study seeks to demonstrate how improved anatomy can expand researchers current knowledge of scoliosis

Biomechanical simulations of the scoliotic deformation process in the pinealectomized chicken: a preliminary study

<p>Abstract</p> <p>Background</p> <p>The basic mechanisms whereby mechanical factors modulate the metabolism of the growing spine remain poorly understood, especially the role of growth adaptation in spinal disorders like in adolescent idiopathic scoliosis (AIS). This paper presents a finite element model (FEM) that was developed to simulate early stages of scoliotic deformities progression using a pinealectomized chicken as animal model.</p> <p>Methods</p> <p>The FEM includes basic growth and growth modulation created by the muscle force imbalance. The experimental data were used to adapt a FEM previously developed to simulate the scoliosis deformation process in human. The simulations of the spine deformation process are compared with the results of an experimental study including a group of pinealectomized chickens.</p> <p>Results</p> <p>The comparison of the simulation results of the spine deformation process (Cobb angle of 37°) is in agreement with experimental scoliotic deformities of two representative cases (Cobb angle of 41° and 30°). For the vertebral wedging, a good agreement is also observed between the calculated (28°) and the observed (25° – 30°) values.</p> <p>Conclusion</p> <p>The proposed biomechanical model presents a novel approach to realistically simulate the scoliotic deformation process in pinealectomized chickens and investigate different parameters influencing the progression of scoliosis.</p

EEG-triggered functional MRI in patients with pharmacoresistant epilepsy

Functional magnetic resonance imaging (fMRI) triggered by scalp electroencephalography (EEG) recordings has become a promising new tool for noninvasive epileptic focus localization. Studies to date have shown that it can be used safely and that highly localized information can be obtained. So far, no reports using comprehensive clinical information and/or long-term follow-up after epilepsy surgery in a larger patient group have been given that would allow a valuable judgment of the utility of this technique. Here, the results of 11 patients with EEG-triggered fMRI exams who also underwent presurgical evaluation of their epilepsy are given. In most patients we were able to record good quality EEG inside the magnet, allowing us to trigger fMRI acquisition by interictal discharges. The fMRI consisted of echoplanar multislice acquisition permitting a large anatomical coverage of the patient's brain. In 8 of the 11 patients the exam confirmed clinical diagnosis, either by the presence (n = 7) or absence (n = 1) of focal signal enhancement. In six patients, intracranial recordings were carried out, and in five of them, the epileptogenic zone as determined by fMRI was confirmed. Limitations were encountered a) when the focus was too close to air cavities; b) if an active epileptogenic focus was absent; and c) if only reduced cooperation with respect to body movements was provided by the patient. We conclude that EEG-triggered fMRI is a safe and powerful noninvasive tool that improves the diagnostic value of MRI by localizing the epileptic focus precisely

EMSY overexpression disrupts the BRCA2/RAD51 pathway in the DNA-damage response: implications for chromosomal instability/recombination syndromes as checkpoint diseases

EMSY links the BRCA2 pathway to sporadic breast/ovarian cancer. It encodes a nuclear protein that binds to the BRCA2 N-terminal domain implicated in chromatin/transcription regulation, but when sporadically amplified/overexpressed, increased EMSY level represses BRCA2 transactivation potential and induces chromosomal instability, mimicking the activity of BRCA2 mutations in the development of hereditary breast/ovarian cancer. In addition to chromatin/transcription regulation, EMSY may also play a role in the DNA-damage response, suggested by its ability to localize at chromatin sites of DNA damage/repair. This implies that EMSY overexpression may also repress BRCA2 in DNA-damage replication/checkpoint and recombination/repair, coordinated processes that also require its interacting proteins: PALB2, the partner and localizer of BRCA2; RPA, replication/checkpoint protein A; and RAD51, the inseparable recombination/repair enzyme. Here, using a well-characterized recombination/repair assay system, we demonstrate that a slight increase in EMSY level can indeed repress these two processes independently of transcriptional interference/repression. Since EMSY, RPA and PALB2 all bind to the same BRCA2 region, these findings further support a scenario wherein: (a) EMSY amplification may mimic BRCA2 deficiency, at least by overriding RPA and PALB2, crippling the BRCA2/RAD51 complex at DNA-damage and replication/transcription sites; and (b) BRCA2/RAD51 may coordinate these processes by employing at least EMSY, PALB2 and RPA. We extensively discuss the molecular details of how this can happen to ascertain its implications for a novel recombination mechanism apparently conceived as checkpoint rather than a DNA repair system for cell division, survival, death, and human diseases, including the tissue specificity of cancer predisposition, which may renew our thinking about targeted therapy and prevention

"Rehabilitation schools for scoliosis" thematic series: describing the methods and results

The Scoliosis Rehabilitation model begins with the correct diagnosis and evaluation of the patient, to make treatment decisions oriented to the patient. The treatment is based on observation, education, scoliosis specific exercises, and bracing. The state of research in the field of conservative treatment is insufficient. There is some evidence supporting scoliosis specific exercises as a part of the rehabilitation treatment, however, the evidence is poor and the different methods are not known by most of the scientific community. The only way to improve the knowledge and understanding of the different physiotherapy methodologies (specific exercises), integrated into the whole rehabilitation program, is to establish a single and comprehensive source of information about it. This is what the SCOLIOSIS Journal is going to do through the "Rehabilitation Schools for Scoliosis" Thematic Series, where technical papers coming from the different schools will be published

Histomorphological study of the spinal growth plates from the convex side and the concave side in adolescent idiopathic scoliosis

Asymmetrical growth of the vertebrae has been implicated as one possible etiologic factor in the pathogenesis of adolescent idiopathic scoliosis. The longitudinal vertebral growth derives from the endochondral ossification of the vertebral growth plate. In the present study, the growth plates from the convex and concave side of the vertebrae were characterized by the method of histology and immunohistochemistry to evaluate the growth activity, cell proliferation, and apoptosis. Normal zoned architectures were observed in the convex side of the growth plate and disorganized architectures in the concave side. The histological grades were significantly different between the convex and the concave side of the growth plate in the apex vertebrae (P < 0.05). The histological difference was also found significant statistically between end vertebrae and apex vertebrae in the concave side of vertebral growth plates (P < 0.05). The proliferative potential indexes and apoptosis indexes of chondrocytes in the proliferative and hypertrophic zone in the convex side were significantly higher than that in the concave side in the apex vertebral growth plate (P < 0.05). There was a significant difference of the proliferative potential index (proliferating cell nuclear antigen, PCNA index) between convex side and concave side at the upper end vertebra (P < 0.05). The difference of the proliferative potential index and apoptosis index were found significant statistically in the concave side of the vertebral growth plate between end vertebrae and apex vertebrae (P < 0.05). The same result was also found for the apoptosis index (terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labeling assay, TUNEL index) in the convex side of vertebral growth plate between end vertebrae and apex vertebrae (P < 0.05). Some correlation were found between radiographic measurements and proliferation and apoptosis indexes. The difference in histological grades and cellular activity between the convex and concave side indicated that the bilateral growth plate of the vertebrae in AIS patients have different growth kinetics which may affect the curve progression

Conservative treatment of idiopathic scoliosis according to FITS concept: presentation of the method and preliminary, short term radiological and clinical results based on SOSORT and SRS criteria

<p>Abstract</p> <p>Background</p> <p>Conservative scoliosis therapy according to the FITS Concept is applied as a unique treatment or in combination with corrective bracing. The aim of the study was to present author's method of diagnosis and therapy for idiopathic scoliosis FITS-Functional Individual Therapy of Scoliosis and to analyze the early results of FITS therapy in a series of consecutive patients.</p> <p>Methods</p> <p>The analysis comprised separately: (1) single structural thoracic, thoracolumbar or lumbar curves and (2) double structural scoliosis-thoracic and thoracolumbar or lumbar curves. The Cobb angle and Risser sign were analyzed at the initial stage and at the 2.8-year follow-up. The percentage of patients improved (defined as decrease of Cobb angle of more than 5 degrees), stable (+/- 5 degrees), and progressed (increase of Cobb angle of more than 5 degrees) was calculated. The clinical assessment comprised: the Angle of Trunk Rotation (ATR) initial and follow-up value, the plumb line imbalance, the scapulae level and the distance from the apical spinous process of the primary curve to the plumb line.</p> <p>Results</p> <p>In the Group A: (1) in single structural scoliosis 50,0% of patients improved, 46,2% were stable and 3,8% progressed, while (2) in double scoliosis 50,0% of patients improved, 30,8% were stable and 19,2% progressed. In the Group B: (1) in single scoliosis 20,0% of patients improved, 80,0% were stable, no patient progressed, while (2) in double scoliosis 28,1% of patients improved, 46,9% were stable and 25,0% progressed.</p> <p>Conclusion</p> <p>Best results were obtained in 10-25 degrees scoliosis which is a good indication to start therapy before more structural changes within the spine establish.</p