Spinal Growth Modulation Research Articles

Biomechanical modeling and assessment of lumbar vertebral body tethering configurations.

Vertebral body tethering (VBT) is a fusionless spinal growth modulation technique, which shows promise for pediatric idiopathic scoliosis (IS) curve correction. This technique, mainly used for thoracic curves, is increasingly being used to treat lumbar curves in order to preserve spine flexibility. It remains necessary to adequately define the cord tension to be applied during the operation and the instrumented levels to biomechanically predict correction over time for the lumbar spine. Twelve pediatric patients with lumbar IS, treated with lumbar-only or lumbar and thoracic VBT, were selected for this study. Three independent variables were tested alternately using a patient-specific finite element model (FEM), which includes an algorithm modeling vertebra growth and spinecurvechanges due to growth modulation for 24months post-operatively according to the Hueter-Volkmann principle. Parameters included cable tensioning (150N/250N), upper instrumented level (actual UIV, UIV-1) and lower instrumented level (actual LIV, LIV + 1). Each FEM was personalized using 3D radiographic reconstruction and flexibility supine radiographs. An increase in cord tension (from 150 to 250N) had significant effects on main thoracic and thoraco-lumbar/lumbar Cobb angles, as well as on lumbar lordosis, after surgery (supplementary average correction of 3° and 8°, and increase of 1.4°, respectively) and after 24months (4°, 10° and 1.1°) (p < 0.05). Adding a level to the actual UIV or LIV did not improve correction. This parametric study showed that cord tension is the most important biomechanical parameter on the simulated immediate and 2-year increase in lumbar curve correction. Our preliminary model suggests that it is not advantageous to add additional instrumented levels. This computational study uses a retrospective validation cohort (level of evidence 3).

Prevalence of malnutrition and its associated outcomes in pediatric patients with scoliosis undergoing elective posterior spinal fusion or spine growth modulation - a retrospective review.

Recent attention within pediatric orthopedics focuses on the prevalence and prevention of post-operative complications, including surgical site infections (SSIs). While poor nutrition status has been noted as a risk factor, various definitions have been utilized. The aim of this retrospective chart review was to utilize the Academy of Nutrition and Dietetics (AND) and the American Society for Parenteral and Enteral Nutrition (ASPEN) diagnostic criteria to determine both the prevalence of malnutrition in pediatric patients undergoing spine deformity surgery and its influence on the prevalence of post-operative complications. A total of 2603 patients had a spine procedure between 2012 and 2018. Patients were excluded if they were less than 2 years of age or greater than 18 years of age and/or did not have their spine procedure completed at Children's Wisconsin. Patients who met inclusion criteria and had an irrigation and debridement (I&D) were selected for an I&D group. From the remaining charts, 127 patients were randomly selected for the non-I&D group. Patients in both groups were further divided into well-nourished and malnourished groups. T-tests and chi square tests were used to determine statistical significance. We found that 50% of patients who had an I&D had malnutrition during their clinical course. This is compared with 17% of patients who didn't require an I&D. Additionally, patients requiring multiple surgical interventions, had an increased prevalence of malnutrition. With the recent focus on reducing the prevalence of post-operative complications, the identification and treatment of malnutrition may be helpful in reducing post-operative complications.

Spine growth modulation with titanium implant: comparisons to observation and bracing in early adolescent idiopathic scoliosis.

Outcomes of a pilot study of spine growth modulation (GM) were compared to those of untreated and braced patients from a concurrent bracing effectiveness trial (BrAIST). The purpose of this study was to determine probabilities of progression (PP) to fusion indications (≥45°) in a cohort of subjects who underwent GM surgery, and to compare GM outcomes to those of matched BrAIST subjects. Secondary analyses were conducted comparing two prospective longitudinal studies. In one, a vertebral GM system was implanted in 6 highly skeletally immature AIS patients. The control group provided by BrAIST was comprised of a subset of untreated or braced subjects that fit the eligibility criteria of the GM study. GM outcomes were compared to predictions from two prognostic logistic regression models derived from BrAIST to estimate risk of curve progression to ≥45°. If the GM patients were untreated, PPs ranged from 68-98%. If braced for 18 hours/day, progression was expected in two of six, one with a PP of 71%. This latter patient not only did not progress, his curve decreased >20°. In the matched cohort, two were untreated and quickly progressed, whereas two were braced and did not progress. Therefore, the bracing models and matched cohort confirmed the initial assumption that all GM patients were at high risk if untreated. They also supported the probable benefit of the GM system, as 3 of 6 benefited from GM relative to predictions for untreated patients, and one of 6 benefited compared to predictions for highly compliant braced patients.

What Is the Role of Anterior Vertebral Tethering?: Commentary on an article by Peter O. Newton, MD, et al.: "Anterior Spinal Growth Modulation in Skeletally Immature Patients with Idiopathic Scoliosis. A Comparison with Posterior Spinal Fusion at 2 to 5 Years Postoperatively".

Commentary The article by Newton et al. addresses a timely and important question. It is important in that it compares a relatively new and relatively untested procedure, anterior vertebral tethering, with a long-established one, posterior fusion and instrumentation for idiopathic scoliosis. It is timely in that many centers are very interested in this newer surgical procedure. It is also especially important in that it reports on outcomes at least 2 years postoperatively. The data, which are honestly reported in detail, are not favorable to vertebral tethering. Indeed, some of the data contradict portions of the authors’ earlier reports. The discussion of the results presents a more favorable interpretation than is deserved, an opinion noted by each reviewer prior to publication. Although the initial patient selection for tethering is not presented, the study group and the control group are well-matched as to severity and maturity. The tethering group achieved significantly less reduction of deformity and had more complications and revisions. The proposed advantages of tethering, progressive postoperative correction and maintenance of spinal motion, were not demonstrated. The lack of progressive correction with growth is unexpected and worthy of note. In a 2014 article, Samdani et al. reported significant gradual correction from 44° preoperatively to 20° immediately postoperatively and 13.5° at 2 years after vertebral tethering1. The frequency of breakage of the tethers, 52%, is alarming. It is alarming because it represents failure of the construct and especially because we do not know what will happen to the spine in the future. Will the untethered segment(s) allow continued progression, and will the patient have pain? It is also concerning because, in this study, with longer follow-up, the incidence of breakage of tethers has increased. I noted in a prior commentary that we simply do not have enough follow-up of this surgical procedure to promote wider usage, and this article by Newton et al. reinforces my conclusion2. For certain, we need development of a more durable, fatigue-resistant cable prior to generalized use. It is interesting that, although we should congratulate the authors for openly publishing these unfavorable results, we also have to be critical of some of their statements. Newton et al. state that they were able to prevent or delay posterior spinal fusion in a majority of patients. They note that 52% of patients were successful in having curves of <35° and 74% were successful in having curves of <50°. This is not good enough. We have to ask what did the patients gain in that transaction? They had more subsequent surgical procedures, more than half with broken tethers, and no demonstrated advantage in mobility. They paid a price in terms of greater residual spinal rotation and coronal deformity. Nine of 23 patients had a revision surgical procedure, with 3 patients who underwent spinal fusion and 3 patients who were scheduled to undergo spinal fusion. In their earlier work, Newton et al. and others showed proof of the concept that anterior tethering of vertebrae can alter spinal growth to correct deformity with continued growth. This an important finding and will certainly be of use in the future. To get a real benefit from the technology, we must perform studies that identify the circumstances of deformity and maturity in which the advantages of gradual correction and lack of fusion can be appreciated. Can we achieve gradual correction without overcorrection? Should this technique replace brace management of smaller curves in younger patients? Surely, we can come up with more fatigue-resistant cable materials, and continuing to use current models with >50% failure is not wise.

Spine Growth Modulation in Early Adolescent Idiopathic Scoliosis: Prospective US FDA IDE Pilot Study of Titanium Clip-Screw Implant at Two to Five Years

Study DesignProspective longitudinal study of growth modulation system for early adolescent idiopathic scoliosis (AIS), consecutive case series from first human use to skeletal maturity, fusion, or five years postoperation. ObjectivesDetermine adverse events and curvature changes to end of study; examine factors most likely to explain variability in curve changes. Summary of BackgroundPilot clinical safety study was performed under US Food and Drug Administration (FDA) Investigational Device Exemption (IDE). Safety and radiographic results were previously reported to 24 months postoperation. MethodsSubjects with early AIS underwent thoracoscopic placement of titanium clip-screw devices designed to modify growth asymmetrically. Eligibility was based on high risk of progression to 50°: single major thoracic curve 25°–40°, Risser 0, open triradiate cartilages, and premenarchal if female. Six subjects, the maximum allowed, enrolled. Adverse events (AEs), clinical outcomes, and curvatures were systematically collected. Disc heights, vertebral heights, and implant-bone contact areas were assessed. ResultsConsecutive subjects enrolled, aged 12.1 years (±1.7), three were female. AEs from two to five years postoperation included deformity changes leading to a second surgery in three patients: two for posterior spinal fusion, and one for thoracoscopic removal of half the implants for overcorrection. In the latter case, overcorrection appeared halted for duration of study. One patient, whose curve exceeded 50° at age 18 years, did not choose fusion. Major thoracic curves were 34° (±3°) preoperatively and 42° (±20°) at end of study. ConclusionsIn a study of spine growth modulation in patients with early AIS with high risk of progression, at skeletal maturity or five years postoperation, major thoracic curves of half progressed to >50°, whereas curves of the other half remained <40°, below fusion indications. Removal of selected implants may halt overcorrection. The next, pivotal, study phase was approved by FDA. Level of EvidenceLevel IV, prospective case series under stringent regulatory controls.

What's New in Pediatric Spine Growth Modulation and Implant Technology for Early-Onset Scoliosis?

Early-onset scoliosis (EOS) affects roughly 1 to 2 out of 10,000 live births per year. Because this subset of patients has a yet to achieve a majority of their skeletal growth, a number of treatment challenges need to be addressed before surgical intervention. If left untreated, EOS can cause a number of problems throughout the patient's lifespan, particularly in regards to the growth of the thorax and pulmonary development. A wide variety of surgical systems and techniques are available to the treating surgeon. A review of the orthopaedic literature from 2010 to 2015 relating to pediatric spine growth modulation was performed. Ninety-eight papers were identified and, following exclusion criteria, a total of 31 papers were selected for further review. This paper summarizes the recently published literature regarding growth-friendly spinal implants, the status of their Food and Drug Administration approval labeling as well as the indications, applications, and complications associated with their implementation. There are a growing number of options at the surgeon's disposal when treating patients with EOS. As surgeons, we must continue to be vigilant in our demand for sound clinical evidence as we strive to provide optimal care for our patients. The rapidly advancing field of spinal growth modulation is exciting. More work must be done to further enhance our ability to predictably modulate growth in the pediatric spine.

Lumbar Scoliosis Induction in Juvenile Dogs by Three-dimensional Modulation of Spinal Growth Using Nickel-Titanium Coil Springs.

Background:Current treatments for scoliosis have some defects and complications. To study spinal deformities and test novel scoliosis treatments, many animal models of scoliosis have been developed. These models applied a single load to the spine and could not precisely modulate the spinal growth in different dimensions. In this study, we applied posterior tethering in various directions with the application of nickel-titanium (NT) coil springs in dog's spine to modulate spinal growth in the coronal, sagittal, and transverse planes and create a scoliosis model possess curves that mimic adolescent idiopathic scoliosis (AIS) three dimensionally.Methods:Scoliosis was surgically induced in eight 8-week-old female dogs (weight: 1.95–2.30 kg) using bone screws and NT coil springs. The deformity was induced through the placement of posterior NT coil springs that tethered the spine by bone screw fixation. All dogs were monitored with serial radiographs to document changes in deformities.Results:All experimental animals developed scoliotic curves convex to the left in the lumbar segment. The mean coronal Cobb angle was 18.0° immediately postoperatively and 54.5° at 22 weeks. The mean lordosis increased from 6.2° postoperatively to 35.0° at final follow-up. Apical axial rotation increased from 4.5° postoperatively to 31.2° at 22 weeks.Conclusions:With the application of NT springs in dogs that allowed posterior tethering in various directions, lumbar spinal deformity was achieved in three planes: coronal, sagittal, and transverse planes. Notably, the lumbar spine in surgically treated dogs developed lordoscoliosis with obvious rotation and the curves mimic AIS three dimensionally well. This method allows lumbar scoliosis to develop without deep dissection of muscle and maintains the essential anatomical elements along the spinal curve. Moreover, the spinal growth modulation technique could yield information that would provide a basis for developing novel early-stage treatments for children with scoliosis.

Spine Growth Modulation in Early Adolescent Idiopathic Scoliosis: Two-Year Results of Prospective US FDA IDE Pilot Clinical Safety Study of Titanium Clip-Screw Implant

Study DesignProspective pilot clinical safety study of novel treatment, consecutive case series from first human use in patients with early adolescent idiopathic scoliosis (AIS). ObjectiveThe primary purpose was to determine the initial safety of a titanium clip-screw implant system for spine growth modulation. The secondary aim was to document curvatures to 2 years postoperatively. Summary of Background DataSpinal growth modulation was documented in preclinical studies. A prospective pilot clinical safety study was then performed under a Food and Drug Administration (FDA) Investigational Device Exemption (IDE) (www.clinicaltrials.gov Identifier: NCT01465295). MethodsSix subjects with early AIS underwent thoracoscopic placement of titanium clip-screw devices. Eligibility criteria included only patients at high risk for progression to 50°: single major thoracic curve 25°–40°, age ≥10 years, skeletally immature (Risser 0 plus open triradiate cartilages), and if female, premenarchal. Adverse events (AEs), clinical outcomes, and radiographic measures were documented using Good Clinical Practices. ResultsSix consecutive subjects were enrolled, three females and three males aged 12.1 years (±1.7). AEs included one that was device related—mild device migration at 18 months in the most rapidly progressive curve. Procedure-related AEs were mostly pulmonary. A chylous effusion that met the clinical protocol definition of a serious AE resolved after minimally invasive interventions. Major thoracic curves were 34° (±3°) preoperatively and 38° (±18°) at two years (intrasubject change, 4° ± 18°). At 24 months, curves in 3 patients were >45° and 3 were <40°. ConclusionsA spine growth modulation system undergoing study under an FDA IDE was determined to be safe. Variability in curve response to the implant was high, ranging from progression to correction. Investigational approval was granted by the US FDA for the next cohort of 30 subjects.

Early outcomes of spinal growth tethering for idiopathic scoliosis with a novel device: a prospective study with 2 years of follow-up.

Adolescent idiopathic scoliosis is a 3D spine deformity that worsens during the whole growth. New methods for spinal growth modulation with flexible spinal implants have been described to avoid progression of the deformity during growth spurt. The main limitations are that no specific ancillaries and devices are available, which makes the surgery technically demanding. We have developed a new method of spinal growth tethering using minimal invasive videothoracoscopic approach. Fixation is performed with staples and synthetic ligament on the lateral aspect of vertebral bodies on main curvature convexity. Patients with progressive thoracic idiopathic scoliosis despite the brace treatment were included. The clinical and radiological examinations were compared before and 2years after surgery. Six patients with flexible thoracic curves with a mean age 11.2±1.2years and a mean Cobb angle 45°±10° (35-60) were operated. All were skeletally immature. At last follow-up, the Cobb angle was stable. None of the patient underwent fusion. The procedure allowed a stabilization of the deformity during growth spurt. Validated devices and further studies with longer term follow-up are needed to confirm the efficiency of this technique. This small cohort of patients is a source of reflection for further medical devices developments. Level 4 case series comparing to not randomized studies.

Novel Hemi-Staple for the Fusionless Correction of Pediatric Scoliosis: Influence on Intervertebral Disks and Growth Plates in a Porcine Model.

In vivo porcine model utilized to evaluate the influence of an intravertebral fusionless growth modulating device (hemi-staple) on intervertebral disks and growth plates. To evaluate the radiographic and histologic changes in disks and growth plates with the purpose of measuring influence of the explored hemi-staple. Fusionless growth modulation for the early treatment of scoliosis should insure the long-term viability of the intervertebral disk and successfully reduce or arrest local growth. A novel hemi-staple that proved effective in the control of coronal spinal alignment warranted further analyses of its influence on the disk health and growth-plate morphology. A hemi-staple that inhibited local vertebral growth exclusive of the disk was introduced over T5-T8 in 4 immature pigs (16 vertebrae; experimental), whereas 3 underwent surgery without instrumentation (sham) and 2 had no intervention (control). Three-month follow-up before animal euthanasia provided radiographic (disk height and health) and histologic (growth plate morphology, disk health, and type X collagen distribution) analyses. No postoperative complications were experienced. Radiographic data returned inverse disk wedging (greater disk height adjacent to device, 2.6±0.7 mm compared with the noninstrumented side, 1.8±0.5 mm) in experimental segments and suggested disk viability. Histologic data confirmed device growth modulation through significant local reduction of growth plate hypertrophic zone (125.64±16.61 μm and 61.16±8.25 μm in noninstrumented and instrumented sections, respectively) and cell height (16.14±1.87 μm and 9.22±1.57 μm in noninstrumented and instrumented sections, respectively). A variability of disk health, dependant of device insertion location, was observed. Type X collagen was consistently identified in experimental growth plates and absent from intervertebral disks. Hemi-staples decreased growth plate hypertrophic zone and cell height, and, depending on device insertion site, showed positive signs of disk health sustainability. Spinal growth modulation achieved exclusive of disk compression, as practiced by this method, offers unique advantages over other fusionless techniques. This technique may provide a suitable and attractive alternative for the early treatment of idiopathic scoliosis.

Metamorphosis of human lumbar vertebrae induced by VEPTR growth modulation and stress shielding.

IntroductionDistraction-based spinal growth modulation by growing rods or vertical expandable prosthetic titanium ribs (VEPTRs) is the mainstay of instrumented operative strategies to correct early onset spinal deformities. In order to objectify the benefits, it has become common sense to measure the gain in spine height by assessing T1-S1 distance on anteroposterior (AP) radiographs. However, by ignoring growth changes on vertebral levels and by limiting measurement to one plane, valuable data is missed regarding the three-dimensional (3D) effects of growth modulation. This information might be interesting when it comes to final fusion or, even more so, when the protective growing implants are removed and the spine re-exposed to physiologic forces at the end of growth.MethodsThe goal of this retrospective radiographic study was to assess the growth modulating impact of year-long, distraction-based VEPTR treatment on the morphology of single vertebral bodies. We digitally measured lumbar vertebral body height (VBH) and upper endplate depth (VBD) at the time of the index procedure and at follow-up in nine patients with rib-to-ileum constructs (G1) spanning an anatomically normal lumbar spine. Nine patients with congenital thoracic scoliosis and VEPTR rib-to-rib constructs, but uninstrumented lumbar spines, served as controls (G2). All had undergone more than eight half-yearly VEPTR expansions. A Wilcoxon signed-rank test was used for statistical comparison of initial and follow-up VBH, VBD and height/depth (H/D) ratio (significance level 0.05).ResultsThe average age was 7.1 years (G1) and 5.2 year (G2, p > 0.05) at initial surgery; the average overall follow-up time was 5.5 years (p = 1). In both groups, VBH increased significantly without a significant intergroup difference. Group 1 did not show significant growth in depth, whereas VBD increased significantly in the control group. As a consequence, the H/D ratio increased significantly in group 1 whereas it remained unchanged in group 2. The growth rate for height in mm/year was 1.4 (group 1) and 1.1 (group 2, p = 0.45), and for depth, it was −0.3 and 1.1 (p < 0.05), respectively.ConclusionsVEPTR growth modulating treatment alters the geometry of vertebral bodies by increasing the H/D ratio. We hypothesize that the implant-related deprivation from axial loads (stress-shielding) impairs anteroposterior growth. The biomechanical consequence of such slender vertebrae when exposed to unprotected loads in case of definitive VEPTR removal at the end of growth is uncertain.

Surgical management of moderate adolescent idiopathic scoliosis with ApiFix®: a short peri- apical fixation followed by post-operative curve reduction with exercises.

Surgery in adolescent idiopathic scoliosis (AIS) is a major operative intervention where 10–12 vertebrae are instrumented and fused. A smaller motion preserving surgery would be more desirable for these otherwise healthy adolescents. The ApiFix® system is a novel less invasive short segment pedicle screw based instrumentation inserted around the apex of the main curve. The system has a ratchet mechanism that enables gradual postoperative device elongation and curve correction. The ratchet is activated by performing specific spinal exercises. The unique features of the device allow curve correction without fusion. The system which has a CE approval was employed in adolescents with main thoracic curves.More than a dozen of ApiFix surgeries have been performed so far. The preoperative Cobb angle was 45° ± 8, and 25° ± 8 at final follow up. The following is a report on three adolescent females aged 13–16 years with curves between 43°-53° and Risser sign of 1–4 who underwent surgery with ApiFix®. Two pedicle screws were inserted around the curve apex and the ratchet based device with polyaxial ring connectors was attached to the screws. No fusion attempt was made. Operative time was around one hour. Two weeks after surgery the patients were instructed to perform Schroth like daily exercises with the aim of rod elongation and gradual curve correction. Patients were followed between 6 months to 2 years. Curves were reduced and maintained between 22- 33°. Patients were pain free and were able to perform their spinal exercises. Postoperative gradual elongation of the device was observed. No screw loosening or rod breakage were observed. No adding on or curve progression was seen.Three factors may contribute to the ApiFix® success: polyaxial connections that prevent mechanical failure, gradual curve correction by spinal motion and spinal growth modulation. The ApiFix® system allows managing moderate AIS with a simple and minor surgical intervention. Recovery is rapid with negligible motion loss. It allows gradual and safe curve correction with high patient satisfaction. It may also serve as an internal brace for AIS.

Paper #22: Spine Growth Modulation Using Titanium Clip/Screw Device: Vertebral and Disc Height Changes at 1 Year

Paper #22: Spine Growth Modulation Using Titanium Clip/Screw Device: Vertebral and Disc Height Changes at 1 Year

Spinal growth modulation with posterior unilateral elastic tether in immature swine model

Background contextFusionless scoliosis surgery is frequently performed in children. Many studies have analyzed the effects of spinal growth modulation by tethering the anterior and anterolateral aspects of the spine in animal models. However, few studies have reported the disc health and spinal motion in spines with posterior unilateral elastic tethering. PurposeTo analyze the regional radiography, biochemistry, and histology of spinal motion segments fixed by posterior unilateral elastic tethering. Study designA randomized controlled trial. Outcome measuresPreoperative and postoperative radiographs of the spines were taken. After an 8-week recovery period, the spines were harvested en bloc and underwent radiographic, biochemical, and histologic analyses. MethodsFifteen 3-month-old swine were randomly divided into three groups. Instrumentation was performed posteriorly in the swine. In the elastic fixation (EF) group, five swine were instrumented on the left side of the lumbar vertebrae from L1 to L5 with pedicle screws that were connected with a unilateral elastic tether with tension to produce a curve on the spine. The same surgery was performed in the five animals of the metal rod fixation (MF) group, in which the screws were connected with metal rods and curves were established. In the control group, five animals were instrumented with five screws with no connecting cable. ResultsScoliosis and lordosis were created in the coronal and sagittal planes in both the EF and MF groups. On average, the Cobb angles were 12.16°±1.37° and 9.10°±2.02° (p=.023) in the coronal plane and 17.44°±11.29° and 5.32°±3.06° (p=.049) in the sagittal plane in the two groups, respectively. The vertebrae and discs wedged on the tethered side in the two groups showed no significant differences (p>.05). The thickness of end-plate epiphysis on the fixed side was significantly decreased in the two groups (p=.032 and p=.024). No apparent change was found in the gross morphology of the discs in the two groups. The distribution of collagen types I and II decreased and that of matrix metalloprotease-3 (MMP-3) increased in both the EF and MF groups. Additionally, the proteoglycan synthesis decreased in the two groups. ConclusionsUnilateral elastic tethering resulted in vertebral wedging and scoliosis. Although changes in collagen and MMP-3 distribution, proteoglycan synthesis, end-plate epiphysis, and disc thickness were observed, the tethered discs and end plates did not demonstrate gross morphologic signs of degeneration.

Spinal growth modulation using a novel intravertebral epiphyseal device in an immature porcine model

Fusionless growth modulation is an attractive alternative to conventional treatments of idiopathic scoliosis. To date, fusionless devices achieve unilateral growth modulation by compressing the intervertebral disc. This study explores a device to control spinal alignment and vertebral morphology via growth modulation while excluding the disc in a porcine model. A device that locally encloses the vertebral growth plate exclusive of the disc was introduced anteriorly over T5-T8 in four immature pigs (experimental) while three underwent surgery without instrumentation (sham) and two were selected as controls. Bi-weekly coronal and lateral radiographs were taken over the 12-week follow-up to document vertebral morphology and spinal alignment modifications via an inverse approach (creation of deformity). All animals completed the experiment with no postoperative complications. Control and sham groups showed no significant changes in spinal alignment. Experimental group achieved a final coronal Cobb angle of 6.5°±3.5° (constrained to the four instrumented levels) and no alteration to the sagittal profile was observed. Solely the experimental group ended with consistent vertebral wedging of 4.1°±3.6° amounting to a cumulative wedging of up to 25° and a concurring difference in left/right vertebral height of 1.24±1.86mm in the coronal plane. The proposed intravertebral epiphyseal device, for the early treatment of progressive idiopathic scoliosis, demonstrated its feasibility by manipulating spinal alignment through the realization of local growth modulation exclusive of the intervertebral disc.

Intervertebral Disc Health Preservation After Six Months of Spinal Growth Modulation

Spinal growth modulation has been proposed as a non-fusion strategy for treatment of idiopathic scoliosis, although the effect of this treatment modality on intervertebral disc health has not been evaluated in detail. The objectives of this in vivo study were to assess the creation of three-dimensional spinal deformity during six months of growth modulation compared with that in sham-surgery controls, and to compare, with use of magnetic resonance imaging (MRI), gross morphological, histological, and biochemical analyses, disc health between control animals and animals treated with a spinal tether. Six immature Yucatan mini-pigs underwent anterior spinal instrumentation with vertebral screws connected by a polyethylene tether over four consecutive thoracic vertebrae (T8-T11). An additional six animals underwent sham surgery (screw placement only [the control group]). Radiographs were obtained preoperatively, postoperatively, and monthly thereafter during six months of growth. Computed tomography (CT) and MRI studies were performed ex vivo, and the spines were sectioned for histological and biochemical analyses. Multivariate analysis of variance (MANOVA) was used to compare six-month postoperative data between the control and tethered animals, with the alpha level of significance set at 0.05. Radiographs and CT images demonstrated the creation of significant three-dimensional deformity (p < 0.013) in the tethered animals compared with the controls. Macroscopic, MRI, and histological evaluation revealed no signs of disc degeneration, with a bulging gelatinous nucleus pulposus, discrete fibrous anular lamellae, and uniformly hyperintense T2-signal intensity within the nuclei pulposi. Biochemical analysis demonstrated no significant difference in the nuclei pulposus between the tethered and control vertebrae; however, the water content (p < 0.001) of both sides of the anulus fibrosus and the glycosaminoglycan content (p < 0.001) of the left side of the anulus fibrosus differed significantly between the two groups. Six months of spinal growth modulation created significant spinal deformity in all three planes compared with what was found in the sham-surgery controls. Although disc health was qualitatively maintained, quantitative changes in the anulus fibrosus water content and the disc height were observed on the side opposite to the tether. These changes likely represent metabolic responses of the discs to compressive loads generated by the flexible tether.

Effects of Intraoperative Tensioning of an Anterolateral Spinal Tether on Spinal Growth Modulation in a Porcine Model

in vivo analysis in an immature porcine model. to evaluate the effect of intraoperative tensioning of an anterolateral flexible spinal tether on growth modulation manifested as deformity creation, disc response, spinal motion, and screw fixation using radiographs, computed tomography, magnetic resonance imaging, biomechanical testing, and histology. spinal growth modulation using an anterolateral flexible tether has been proposed as a nonfusion surgical deformity correction strategy for idiopathic scoliosis and has been successfully demonstrated in a porcine model to create spinal deformity while maintaining disc viability. twelve 7-month-old mini-pigs were instrumented with a screw-staple and polyethylene tether construct over 4 consecutive thoracic vertebrae (T8-T11). Intraoperative tensioning of the tether (250 N) was performed in alternate pigs (Pretensioned and Untensioned groups, n = 6 per group). Screws were coated with hydroxyapatite in half of the animals in each surgical group. Preoperative, postoperative, and monthly radiographs were evaluated, comparing deformity creation, vertebral body wedging, and disc wedging between the groups. Vertebral body shape was evaluated by computed tomography. Magnetic resonance and histology evaluated disc health. Biomechanical testing was performed to determine the effect of tensioning the tether on spinal motion and screw fixation. intraoperative tensioning produced immediate coronal deformity (8° ± 4° vs. 2° ± 1° in untensioned spines; P = 0.01) and apical disc (T9-T10) wedging, vertex on tethered side, (5° ± 2° vs. 2° ± 1°; P = 0.01). After 12 months, the groups were similar in coronal deformity (28° ± 18° pretensioned, 27° ± 11° untensioned, P = 0.88), sagittal deformity (25° ± 3° vs. 22° ± 3°; P = 0.14), vertebral body wedging (10° ± 5° vs. 8° ± 3°; P = 0.45), and disc wedging (-4° ± 1° vs. -4° ± 3°; P = 0.88). There was no radiographic evidence of screw loosening. One of the discs from each group had diminished T2 signal after 12 months of tethering. Tether pretensioning did not affect spinal stiffness or motion. Interestingly, screw fixation increased with pretensioning; however, there was no significant advantage with hydroxyapatite coating. Histology demonstrated normal-appearing discs. pretensioning of the tether created immediate deformity without effecting ultimate vertebral or disc deformity creation. Spinal motion and stiffness were not altered by pretensioning; however, pretensioning increased the torque required for screw extraction.

Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy.

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans.

Growth modulation in the management of growing spine deformities.

The Hueter-Volkmann law explains the physiological response of the growth plate under mechanical loading. This law mainly explains the pathological mechanism for growing long-bone deformities. Vertebral endplates also show a similar response under mechanical loading. Experimental studies have provided information about spinal growth modulation and, now, it is possible to explain the mechanism of the curvature progression. Convex growth arrest is shown to successfully treat deformities of the growing spine and unnecessary growth arrest of the whole spine is prevented. Both anterior and posterior parts of the convexity should be addressed to achieve a satisfactory improvement in the deformity, albeit epiphysiodesis effect cannot be stipulated at all times. Anterior vertebral body stapling without fusion yielded better results with new shape memory alloys and techniques. This method can be used with minimally invasive techniques and has the potential advantage of producing reversible physeal arrest. Instrumented posterior hemiepiphysiodesis seems to be as effective as classical combined anterior and posterior arthrodesis, where it is less invasive and morbid. Convex hemiepiphysiodesis with concave-side distraction through growing rod techniques provide a better control of the curve immediately after surgery. This method has the advantages of posterior instrumented hemiepiphysiodesis, but necessitates additional surgeries. Concave-side rib shortening and/or convex-side lengthening is an experimental method with an indirect effect on spinal growth. To conclude, whatever the cause of the spinal deformity, growth modulation can be used to manage the growing spine deformities with no or shorter segment fusions.

Spinal Growth Modulation with Use of a Tether in an Immature Porcine Model

Spinal growth modulation by tethering the anterolateral aspect of the spine, as previously demonstrated in a nonscoliotic calf model, may be a viable fusionless treatment method for idiopathic scoliosis. The purpose of the present study was to evaluate the radiographic, histologic, and biomechanical results after six and twelve months of spinal growth modulation in a porcine model with a growth rate similar to that of adolescent patients. Twelve seven-month-old mini-pigs underwent instrumentation with a vertebral staple-screw construct connected by a polyethylene tether over four consecutive thoracic vertebrae. The spines were harvested after six (n = 6) or twelve months (n = 6) of growth. Monthly radiographs, computed tomography and magnetic resonance imaging scans (made after the spines were harvested), histologic findings, and biomechanical findings were evaluated. Analysis of variance was used to compare preoperative, six-month postoperative, and twelve-month postoperative data. Radiographs demonstrated 14 degrees +/- 4 degrees of coronal deformity after six months and 30 degrees +/- 13 degrees after twelve months of growth. Coronal vertebral wedging was observed in all four tethered vertebrae and progressed throughout each animal's survival period. Disc wedging was also created; however, in contrast to the findings associated with vertebral wedging, the tethered side was taller than the untethered side. Magnetic resonance images revealed no evidence of disc degeneration; however, the nucleus pulposus had shifted toward the side of the tethering. Midcoronal undecalcified histologic sections showed intact bone-screw interfaces with no evidence of implant failure or loosening. With the tether cut, stiffness decreased and range of motion increased in lateral bending away from the tether at both time-points (p < 0.05). In this porcine model, mechanical tethering during growth altered spinal morphology in the coronal and sagittal planes, leading to vertebral and disc wedging proportional to the duration of tethering. The resulting concave thickening of the disc in response to the tether was not anticipated and may suggest a capacity for the nucleus pulposus to respond to the compressive loads created by growth against the tether.