Principal Investigator – Glenn R. Buttermann, M.D
Midwest Spine Institute, April 29, 2010
Challenges remain in the treatment of scoliosis and particularly in adults that may have more rigid deformities and pain related to additional degenerative spinal conditions. Future non-fusion devices may allow increased function by maintaining appropriately constrained mobility, decreasing pain and improving deformity. A large animal scoliosis model with the potential for producing a double major curve is proposed as a first step in the development of improved techniques and devices for this complex condition.
The current treatment for scoliosis for surgical candidates is spinal fusion. This halts curve progression and prevents the potential medical ill effects of severe curves. Modern techniques also may straighten the spine and enhance cosmesis and spinal balance. In adults, fusion may also decrease pain but the procedure is typically more extensive due to the need to include all the segments of the deformity. However, a fused spine cannot bend and in scoliosis fusions, a functional decrease typically occurs due to the many levels typically needed for fusing the entire scoliotic curve. The detrimental effect of fusion upon function is particularly notable when fusions include the lumbar spine where there is normally more motion than in the thoracic spine.
Due to the loss of mobility in the lumbar spine, and hence its detrimental effect on function of activities of daily living, spine surgeons when performing fusion for pediatric idiopathic scoliosis, will often perform a selective fusion. That is, the thoracic but not the lumbar spine will be fused and a moderate residual lumbar curve, if present, will be tolerated as a better option than fusing the entire spine. Unfortunately, during the middle age years, these lumbar curves often progress and become symptomatic. Long-term follow-up studies of the results of fusion surgery for adolescent scoliosis are few and were typically qualitative. Mid-term studies of pediatric scoliosis patients are just now becoming available and at >5years, the Principle Investigator and others have found a small decline (worsening) of outcomes (Buttermann 2008-a, Upasani 2008).
One of the most complex and challenging conditions encountered by the spinal surgeon is that of the patient who has a preexisting scoliosis and with aging has progression of their lumbar compensatory scoliosis. These patients will often have a stable thoracic scoliosis or have had a prior selective thoracic spinal fusion and have mild to moderate residual compensatory lumbar scoliosis throughout their young adult years. With aging and disc degeneration, many of these patients will have progression of their lumbar curvature. They may get a lateral listhesis near the apex of the lumbar curvature typically at L3-4 which is a sign of instability due to degenerative disc disease (Buttermann 2008-b, Schwab 2006).
Progressive low back pain may occur and some patients will also develop stenosis with secondary leg pain. Depending on the rigidity and number of degenerative discs involved, these patients may require extensive spinal fusion surgery down to L5 or S1 possibly with a decompression and possibly using anterior and posterior combined approaches. These types of surgeries, however, have more risk compared to that for patients who have degenerative disc disease of the lumbar spine without deformity. The outcomes of adult scoliosis surgery, as shown in multiple studies, leads to improved pain and a small improvement in function, but the function is never considered to be”normal” (Buttermann 2001, Smith 2009). A study by the PI found a 4 point improvement (0 to10 scale) in pain, and approximately a 15 point improvement in Oswestry Disability Index (function). This degree of improvement has been found in other studies of adult scoliosis (Bridwell 2009, Smith 2009).
We have also shown that over the last fifteen years, improved techniques in adult scoliosis surgery have led to lower pseudarthrosis rates, lower revision surgery rates and lower complication rates, however, when using the identical outcomes instruments of the above study, the current pain and functional outcomes improvement are similar to what they were 15 years ago (Buttermann 2008-a, Buttermann 2001).
One may conclude that fusion surgery for adolescent and adult scoliosis results in improved pain outcomes, but in the long-term there appears to be a slow gradual decline. Adult scoliosis surgery does not result in a functional spine even in the short term due to decreased spinal mobility.
The Principal Investigator contends that fusion for scoliosis has limits to improved pain and function and that nonfusion treatments, once developed, may lead to greater improvements in pain and function. Fusionless surgery for spinal deformity or in combination with selected fusion of specific spinal levels (hybrid techniques) may avoid the long-term decline in outcomes that are related to extensively fused spines. Current nonfusion devices and disc prosthesis result in instability in scoliosis patients, However, refined future generation devices, with constrained mobility, applied to the interbody and posterior elements (anterior and posterior spinal columns) are conceivable and hypothetically could result in function (spinal mobility and the patient’s ability to be more active) approaching that of a normal spine.
Development of fusionless treatment systems for scoliosis will require an in vivo large animal model. The characteristics of large animals allow the use of spinal implants which are sized for treating human conditions. This large animal model should induce a scoliosis, preferably with a double major curve pattern such as a primary thoracic with a compensatory lumbar scoliosis. The animal model should not violate the spinal tissues (including the muscles and ligaments) or ribs. Prior studies have evaluated subcutaneous posterior tethers in small animals and were able to successfully induce scoliosis (Tsuang 1992). Preliminary work by the Principal Investigator includes establishing and validating this posterior tethering model in a small animal, rabbit, model (Kallemeier 2006). The model we produced had a scoliosis with wedging of both the discs and vertebrae which is similar to the human condition. This model was unique since it did not disturb the spine or ribs which was a deficiency in prior large animal models (Braun 2006, Newton 2005, Schwab 2009). Furthermore, our model is the only one reported to have the ability to produce double-major curves. We would apply this specific tethering technique to the large animal model and analyze the deformity in detail including high resolution CT scan to assess morphological changes such as vertebral wedging and lung volumes (Mehta 2006).
Once the large animal model is refined, potential fusionless treatments could be applied for the treatment of the scoliosis. These could include devices such as currently available”growth rods” or preferable other devices that do not require multiple reoperations. If only the deformity is of concern, the author contends that a posterior (or anterior only) segmental expanding device should be developed. Segmental fixation remains a challenge for dynamic devices and additional development is required. For patients with pain in addition to deformity, an interbody (elastic) device may be required in addition to the dynamic segmental fixation. Biological treatments could also be tested. Recently, certain growth factors have been shown to have local effects when applied to the intervertebral disc and growth plates (An 2005, Miyamoto 2006, Thomas 2005). Potentially, local application of growth factors to the concave vertebral growth plate and annulus could correct disc and vertebral wedging and thus correct scoliosis.
The objective of this study is to develop a large animal model of scoliosis. Inducing the scoliosis should not violate any of the tissues directly associated with the spine or ribs. It is desirable that a primary thoracic curve with a compensatory-like lumbar curve is obtained. Such a model should allow for future studies of nonfusion scoliosis treatments. Specifically, the aim of this study is that an oblique posterior subcutaneous tethering from the scapula to the contralateral pelvis in an immature goat will produce scoliosis.
The experimental design will compare control (N=4) and experimental (N=6) groups. Six week-old immature domestic goats will be obtained after IUCAC approval and after confirming that the animals are healthy, they will undergo a general anesthetic. After prepping and drapping, small incisions are made and, a flexible cable (1.1 mm stainless steel cable) will be passed subcutaneously from the left scapula to the right ilium. At the ilium, the cable will be passed through a fenestrated plate to prevent the cable cutting through the bony structure. Proximally the cable will be passed around the acromial process. The cable will then be tensioned to two kilograms. The skin wounds will be closed, and the animals will then be allowed to recover with unrestricted activity in a pen. The control group will have the identical surgery performed as a sham procedure. In the control group, the tether will not be tightened and the loop will remain opened to prevent tethering during growth.
All animals will undergo a plain radiograph at the time of their procedure to record spinal alignment in sagittal and coronal planes before and after intraoperative tether tensioning. At 3 months after their original procedure all animals will undergo a general anesthetic, have repeat radiographs obtained, and then percutaneous release of the cable tethers. The animals will then be allowed to return to unrestricted activity. At 6 and 9 months after implantation, the animals will have repeat general anesthetic and repeat plain x-rays obtained. At 12 months after implantation, the animals will have repeat general anesthetic and be euthanized after which repeat plain x-rays will be obtained. At this time, a high resolution CT scan of the vertebra will be obtained to allow for assessment of vertebral morphology (vertebral body wedging) as well as generalized chest CT with algorithms used to determine lung volume. The vertebral bodies and intervening discs at the apex of the curvatures will be isolated and then processed for decalcified histology. Histology will assess the health of the intervertebral discs between the scoliosis and control groups. Unpaired T tests will be used to assess for any statistical differences of the scoliosis Cobb angle, the magnitude of vertebral body wedging, and lung volumes between the control and experimental groups.
PILOT STUDY DATA
A pair of 7 week old goats underwent the tethering procedure described above without complications which induced a double major curve (10 – 30 degree range for both thoracic and lumbar curves).
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