John T. Braun

The search for idiopathic scoliosis genes

Study Design. A cohort of 145 patients with adolescent idiopathic scoliosis (AIS) were identified and contacted to determine whether they had a family history of scoliosis. These results were submitted to an internal genealogical database to screen for potential connections to other AIS families. The severity and incidence of AIS in extended family groups were also analyzed. Objectives. Our objectives were to quantify the genetic effect in AIS, determine the expressivity and penetrance of AIS in large family groupings, and examine larger scoliosis pedigrees for evidence of multiple genes. Summary of Background Data. Previous reports have suggested an 80% connectedness among scoliosis families, but no clear evidence of multiple genes. It is not known if there are major gene(s). Methods. A cohort of 145 AIS probands were identified and contacted to ascertain whether they had a family history of AIS. Their medical records and spine radiographs were reviewed to confirm the diagnosis and determine the disease severity. Using an internal genealogical database, the cases were screened for potential connections that would produce larger extended pedigrees. Results. Overall, 131 of the probands were in the database and 127 showed connections to other scoliosis families, a 97% connectedness. These results suggest a major scoliosis gene, as more than 50% of the probands were connected by founders that all resided in England in the mid 1500s. The differences in penetrance (41% vs. 34%) and expressivity (38% vs. 61%) between seemingly unrelated large family groupings might suggest that two different genes are a major influence for AIS in these families. Conclusions. Nearly all (97%) AIS patients have familial origins. There appears to be at least one major gene, and the differences in penetrance and expressivity in two large unconnected pedigrees might suggest the presence of more than one gene.

Mechanical modulation of vertebral growth in the fusionless treatment of progressive scoliosis in an experimental model.

Study Design. Wedging of apical spinal segments was measured during creation and correction of an experimental scoliosis in a goat model. Objectives. To create and correct apical vertebral wedge deformities in a progressive experimental scoliosis model by purely mechanical means. Summary of Background Data. The creation and correction of vertebral wedge deformities has been previously described in a rat tail model using external fixation. Methods. Experimental scoliosis was created in 14 goats using a posterior asymmetric tether with convex rib resection and concave rib tethering. After a period of up to 13 weeks, all tethers were removed and goats were randomized into treated (n = 8) and untreated (n = 6) groups. Treated goats underwent anterior thoracic stapling with four shape memory alloy staples along the convexity of the maximal curvature. Goats were followed for an additional 7 to 13 weeks during treatment. Serial radiographs were used to document progression or correction of the maximal scoliotic deformity as well as to measure the wedging of the apical spinal segment (two adjacent vertebrae and the intervening disc). Results. During the tethering period, all goats achieved a progressive, structural, lordoscoliotic curve of significant magnitude (mean: 61 degrees, range: 49 to 73 degrees). Wedging of the apical spinal segment measured 11.1 degrees at the beginning and 22.4 degrees at the end of the tethering period. The increase in apical spinal segment wedging of +11.3 degrees (10.7 degrees vertebral/0.6-degree disc) was significant (P = 0.001). During the treatment period, the scoliosis in the stapled goats measured 56.8 degrees at the beginning and 43.4 degrees at the end for an average correction of −13.4 degrees (range: 0 to−22 degrees) (P = 0.001), whereas the untreated goats measured 67.0 degrees at the beginning and 59.8 degrees at the end for an average correction of −7.2 degrees (range: +7 to −21 degrees) (P = 0.19). Additionally, wedging of the apical spinal segment in the stapled goats measured 22.5 degrees at the beginning and 20.3 degrees at the end for an average correction of −2.2 degrees (−0.6 degrees vertebral/−1.6-degree disc); wedging of the apical vertebral segment in the untreated goats measured 22.3 degrees at the beginning and 25.8 degrees at the end of the treatment period for an average progression of +3.5 degrees (3.5 degrees vertebral/0.0-degree disc). The difference in apical spinal segment correction versus progression in the stapled (−2.2 degrees) versus control (+3.5 degrees) goats was significant (P < 0.05). Conclusions. This study demonstrates the ability to create wedge deformities at the apex of an experimental scoliosis in a large animal model and to control the progression of these deformities using anterior thoracic staples.

Experimental scoliosis in an immature goat model: A method that creates idiopathic-type deformity with minimal violation of the spinal elements along the curve

Study Design. Experimental scoliosis was created in an immature goat model. Objectives. To create a progressive, structural, idiopathic-type, lordoscoliotic curve convex to the right in the thoracic spine of the immature goat while maintaining the anterior and posterior elements of the spine along the maximal curve in a pristine state. Summary of Background Data. Progressive scoliotic curves in a small animal model have been created using a posterior asymmetric tether. However, attempts in larger animal models have had less success and typically required violation of the spinal elements. Methods. Scoliosis was created in 40 Spanish Cross X female goats (age 1–2 months, weight 8–12 kg) using a left posterior asymmetric tether from T5 to L1. Convex rib resection and concave rib tethering from T8 to T13 were performed before compression across the rigid construct. Goats were followed over a 6- to 15-week period with serial radiographs to document progression of the deformity. Results. Of the 40 goats that underwent posterior assymetric tethering with rib procedures, 7 (18%) encountered substantial complications (five deaths and two neurologic injuries). Of the 33 available for analysis, 27 goats (82%) developed progressive, structural, idiopathic-type, lordoscoliotic curves in convex to the right in the thoracic spine. All curves demonstrated characteristic radiographic features of idiopathic scoliosis including significant displacement of the apical vertebra from the midline, wedging of both the vertebral bodies and discs, rotation, and decreased flexibility. Initial scoliosis after posterior asymmetric tethering measured 42° on average (range 33–50°) and progressed to 60° on average (range 44–73°) over 6 to 15 weeks. The average progression of +18° (range 6–37°) was statistically significant (P < 0.001). Conclusions. This study establishes an experimental model for scoliosis that creates progressive, structural, idiopathic-type, lordoscoliotic curves convex to the right in the thoracic spine of the immature goat with high statistical significance (P < 0.001). In addition, this method of experimental scoliosis creation avoids violation of the spinal elements throughout the maximal portion of the curve providing an ideal opportunity subsequent study of the deformity.

Fusionless scoliosis correction using a shape memory alloy staple in the anterior thoracic spine of the immature goat.

Study Design. Experimental scoliosis was created in goats and then treated using anterior thoracic stapling. Objective. To correct, without fusion, a progressive idiopathic-type scoliotic deformity in an immature goat model using a shape memory alloy staple. Summary of Background Data. Fusionless scoliosis treatment techniques, using minimally invasive approaches to the anterior thoracic spine, provide theoretical advantages over currently available forms of treatment. Methods. Experimental scoliosis was created in 40 goats using a posterior asymmetric tether with convex rib resection and concave rib tethering for a period of up to 15 weeks. Twenty-seven goats with progressive deformities were used for subsequent study and randomized into 4 treatment groups: group I, anterior thoracic stapling with removal of the posterior tether; group II, removal of the posterior tether only; group III, anterior thoracic stapling with persistent posterior tethering; and group IV, persistent posterior tethering with no treatment. The treatment period lasted an additional 6 to 14 weeks. Staple backout was graded radiographically. After killing the goats, histology and disc biochemistry analyses were conducted. Results. The goats in group I corrected from an initial 57° of curvature to 43° over the duration of the treatment period. Group II goats, which served as a control for group I, corrected from 67° to 60° during the treatment period. Group III goats demonstrated a modest correction from 65° to 63° with the stapling procedure, whereas group IV goats (controls for group III) progressed from 55° to 67° with a persistent posterior tether during the treat ment period. The difference between the correction in group III and progression in group IV was statistically significant (P = 0.002). Complications were limited to partial staple backout in 27% of 56 staples. Conclusions. The results of this study support the efficacy of an anterior thoracic staple in correcting moderately severe scoliosis and halting the progression of more malignant scoliosis without fusion in a goat model.

The Efficacy and Integrity of Shape Memory Alloy Staples and Bone Anchors with Ligament Tethers in the Fusionless Treatment of Experimental Scoliosis

BACKGROUND Scoliosis is a complex three-dimensional deformity with limited treatment options. Current treatments present potential problems that may be addressed with use of fusionless techniques for the correction of scoliosis. However, there are few data comparing the efficacy of different fusionless implant strategies in controlling scoliosis or on the integrity of rigid compared with flexible devices in an in vivo setting over time. The objective of this study was to compare the efficacy and integrity of rigid and flexible anterior thoracic tethers used to treat experimental scoliosis. METHODS Experimental scoliosis was created in twenty-four Spanish Cross-X female goats and was subsequently treated with either anterior shape memory alloy staples or anterior ligament tethers attached to bone anchors. Serial radiographs were analyzed to determine the efficacy of the implants in controlling scoliosis progression as well as the integrity of the implants at study completion. After the goats were killed, the implants were analyzed with use of three quantitative indices of implant integrity and implant pullout testing. RESULTS Over the treatment period, scoliosis progressed from 77.3 degrees to 94.3 degrees in the goats treated with staples and was corrected from 73.4 degrees to 69.9 degrees in the goats treated with bone anchors, with loosening of eighteen of forty-two staples (two of the eighteen dislodged) and evidence of drift in two of forty-nine anchors. Histologic sections revealed a consistent halo of fibrous tissue around the staple tines but well-fixed bone anchors at all sites. Pullout testing demonstrated that bone anchors had greater strength than staples initially and at the study completion, with an increase in bone anchor fixation over the course of the study. CONCLUSIONS In this scoliosis model, the flexible ligament tethers attached to bone anchors demonstrated greater efficacy and integrity than the more rigid shape memory alloy staples.

Three-Dimensional Analysis of 2 Fusionless Scoliosis Treatments : A Flexible Ligament Tether Versus a Rigid-Shape Memory Alloy Staple

Study Design. Experimental scoliosis was created and subsequently corrected in goats. The 3-dimensional (3-D) effects of the treatments were analyzed. Objective. To analyze the 3-D effect of 2 different fusionless scoliosis treatment techniques on an experimental idiopathic-type scoliosis using plain radiographs and computerized tomography. Summary of Background Data. Scoliosis is a complex 3-D spinal deformity with limited treatment options. By preserving growth, motion, and function of the spine, fusionless scoliosis surgery provides theoretical advantages over current forms of treatment. Methods. Scoliosis was created in 24 Spanish cross-X female goats using a flexible, left posterior asymmetric tether from the T5 to L1 laminae, with convex rib resection and concave rib tethering from T8 to T13. After 8 weeks of posterior tethering, goats were randomized into 3 treatment groups: group 1, no treatment; group 2, anterior-shape memory alloy staple; and group 3, anterior ligament tether with bone anchor. The 6 levels of maximal curvature were instrumented in groups 2 and 3. All goats were observed for an additional 12–16 weeks. Serial radiographs and computerized tomography were used to document progression/correction of coronal, sagittal, and transverse plane deformities throughout the study. Results. There were 20 goats that had progressive, structural, idiopathic-type, lordoscoliotic curves convex to the right in the thoracic spine over the 8-week tethering period. An overall deformity score equaling the sum of the scoliosis, lordosis, and axial rotation measurements was calculated for each goat at 3 times. Conclusion. The data in this study show the ability of a ligament tether attached to a bone anchor to correct scoliosis modestly in the coronal plane, but not in the sagittal or transverse plane. In addition, although a significant decrease in the deformity score was shown initially in this group (P < 0.001), the effect was lost over time. The final deformity in the bone anchor/ligament tether group wassignificantly less than either the stapled or untreated groups (P < 0.03). Further study is warranted to provide a better understanding of the 3-D effects of fusionless scoliosis treatments.

Polygenic inheritance of adolescent idiopathic scoliosis: A study of extended families in Utah

A heritability study of 69 extended Utah families with a history of adolescent idiopathic scoliosis (AIS) indicates that AIS is a polygenic, multifactorial condition. Each family reported a history of AIS within four generations; a total of 247 individuals were confirmed via X‐rays and medical records to have AIS. Coefficient of kinship was more than 25 standard deviations higher for these 69 families than for the general population. Excluding all probands and assuming autosomal dominant inheritance, 1,260 individuals over the age of 16 were determined to be at risk for AIS because they have a parent with AIS. Assuming 50% of these individuals carry the allele, estimated penetrance in at‐risk males is approximately 9%, and estimated penetrance in at‐risk females is approximately 29%. Recurrence risk in relatives decreases as the degree of relationship to the affected individual becomes more distant; however, the lowest recurrence risk calculated, for third‐degree relatives, is still an average of 9%, well above the general populations risk. Onset of AIS appears to be inherited separate from curve pattern and severity. In a study of phenotypes in 36 of the families, the affected individuals were consistent in either curve severity or curve pattern, but not both. It is unclear whether severity or pattern is more heritable, but it is possible that the location of the curve on the spine is the most heritable trait of the phenotype. The study demonstrates the genetic complexity of AIS, including the low penetrance of its cumulative alleles and variable expression.

Anterior cervical fixation: analysis of load-sharing and stability with use of static and dynamic plates.

BACKGROUND Anterior plates provide stability following decompression and fusion of the cervical spine. Various plate designs have emerged, and they include static plates with fixed-angle screws, rotationally dynamic plates that allow the screws to toggle in the plate, and translationally dynamic plates that allow the screws to both toggle and translate vertically. The goal of this study was to document the effects of plate design following a single-level corpectomy and placement of a full-length strut graft and the effects following 10% subsidence of the graft. METHODS A total of twenty-one cadaveric cervical spines (C2-T1) were randomized into three treatment groups and were tested for initial range of motion. A C5 corpectomy was performed, reconstruction was done with a full-length interbody spacer containing a load-cell, and an anterior cervical plate was applied. Load-sharing data were recorded with incremental axial loads. The range of motion was measured with +/- 2.5 Nm of torque in flexion-extension, lateral bending, and axial rotation. Then, the total length of the interbody spacer was reduced by 10% to simulate subsidence, and load-sharing and the range of motion were retested. RESULTS With the full-length interbody spacer, there were no significant differences in the abilities of the constructs to share load or limit motion. Following shortening of the interbody spacer, the static plate construct lost nearly 70% of its load-sharing capability, while neither of the dynamic plate constructs lost load-sharing capabilities. Also, the static plate construct allowed significantly more motion in flexion-extension following simulated subsidence than did either of the dynamic plate constructs (p < 0.05). CONCLUSIONS Although all of the tested anterior cervical plating systems provide similar load-sharing and stiffness following initial placement of the interbody spacer, the static plate system lost its ability to share load and limit motion following simulated subsidence of the interbody spacer. Both dynamic plate systems maintained load-sharing and stiffness despite simulated subsidence. CLINICAL RELEVANCE This study provides an improved understanding of the immediate performance of anterior cervical fusion surgery with plate fixation.

Creation of an experimental idiopathic-type scoliosis in an immature goat model using a flexible posterior asymmetric tether

Study Design. Longitudinal follow-up of animals after a surgically initiated scoliosis. Objective. To create a progressive, structural, idiopathic-type, lordoscoliotic curve convex to the right in the thoracic spine of the immature goat using a flexible posterior asymmetric tether with minimal disruption of the spinal elements along the curve. Summary of Background Data. Our previous work created an experimental scoliosis model using a rigid posterior asymmetric tether to study the safety and efficacy of fusionless scoliosis treatments. Posterior asymmetric tethers, whether rigid or flexible, represent the most reliable method of creating an experimental deformity that approximates idiopathic scoliosis. Although our initial rigid model was unique in creating progressive structural scolioses without violation of the essential spinal elements along the curve, there were a number of shortcomings associated with the model. These included substantially stiff curves and unpredictability of curve progression. Methods. Scoliosis was created in 24 Spanish Cross X female goats (age, 6–8 weeks; weight, 8–12 kg) using a braided synthetic ligament as a left posterior asymmetric tether from T5 to L1. Convex rib resection and concave rib tethering from ribs 8 to 13 were performed without disruption of the spinal elements before tensioning of the posterior tether. All goats were followed over an 8-week period with serial radiographs to document progression of the deformity. At the end of 8 weeks, the 20 goats with progressive curves were randomized into treatment groups for a separate study. However, 6 of these 20 remained untreated in the subsequent study and, therefore, were followed for an additional 12 to 16 weeks. Results. There were two deaths in the early postoperative period due to pulmonary complications. Of the remaining 22 goats, 20 (91%) developed progressive, structural, idiopathic-type, lordoscoliotic curves convex to the right in the thoracic spine. Initial scoliosis after tethering measured 55.4° on average (range, 37°–75°) and progressed to 74.4° on average (range, 42°–93°) over 8 weeks. The average progression of 19.0° (range, 5°–33°) was statistically significant (P < 0.001). The average initial lordosis after tethering measured −18.9° (range, −13° to −27°) and progressed to −40.7° on average (range, −28° to −56°) over 8 weeks. The average progression in lordosis of −21.8° (range, −5° to −43°) was significant (P < 0.001). Conclusions. This study demonstrated the effectiveness of a flexible posterior asymmetric tether in creating idiopathic-type deformities in a shorter tethering period than previously described. With substantial remaining spinal growth after the 8-week tethering period and preservation of the essential spinal elements in an undisturbed state, this model is suitable for the study of scoliosis progression and various fusionless scoliosis treatment methods.

Relative versus absolute modulation of growth in the fusionless treatment of experimental scoliosis.

Study Design. Absolute and relative growth modulation of apical spinal segments were measured during creation and correction of an experimental scoliosis in a goat model. Objective. To differentiate relative and absolute changes in growth on the concavity and convexity of an experimental scoliosis treated with anterior vertebral stapling. Summary of Background Data. The creation and correction of vertebral wedge deformities have been previously described in a rat tail model using external fixation as well as in a goat model using anterior vertebral body stapling. Methods. Progressive, structural, scoliotic curves convex to the right in the thoracic spine were created in 14 Spanish Cross-X female goats using a posterior asymmetric tether. After 7–13 weeks, all tethers were removed, and goats were randomized into stapled (n = 8) and untreated (n = 6) groups. Stapled goats underwent anterior vertebral stapling with 4 shape memory alloy staples (Medtronic Sofamor Danek, Memphis, TN) along the convexity of the maximal curvature. All goats were observed for an additional 7–13 weeks. There were 12 additional goats matched for age, sex, and weight used as growth controls throughout the study. Serial radiographs were used to document progression or correction of the maximal scoliotic deformity, and changes in relative and absolute growth at the apical spinal segment T9–10 (2 adjacent vertebrae and the intervening disc). Results. All tethered goats had progressive, structural, scoliotic curves of significant magnitude during the tethering period (average 61.4°, range 49° to 73°) (P = 0.001). There was 1 goat from each group eliminated from the study because its apical spinal segment did not match the T9–10 level used to establish normal growth in controls. During the treatment period, stapled goats had a correction of −6.9° (P = 0.03), whereas untreated goats had little change (−1.4°). Apical spinal segment wedging progressed in all tethered goats, from 11.1° to 22.4°, duringthe tethering period (P = 0.001). During the treatment period, wedging corrected −2.2° (range 22.5° to 20.3°) in the stapled goats but progressed +3.5° (range 22.3° to 25.8°) in the untreated goats (P < 0.05). Apical spinal segment growth in all tethered goats was decreased on the concavity by 78% and increased on the convexity by 33% when compared to growth controls (P < 0.001). During the treatment period, growth on the concavity of the apical spinal segment of the stapled goats was decreased by 10% but increased in the untreated goats by 37% when compared to growth controls. On the convexity, apical spinal segment growth at T9–10 was decreased in the stapled goats by 18% and increased in the untreated goats by 29% when compared to growth controls (P < 0.04). Conclusions. Data in this study show the ability to modulate relative and absolute growth, according to the Hueter-Volkmann law, at the apical spinal segment of a progressive experimental scoliosis. However, anterior vertebral stapling, although able to control progressive wedging and scoliosis at the apical spinal segment, was not able to reverse fully the Hueter-Volkmann effect.