Hak-Sun Kim

Reliability of Magnetic Resonance Imaging in Detecting Posterior Ligament Complex Injury in Thoracolumbar Spinal Fractures

Study Design. Prospective study of 34 patients with thoracolumbar spinal fractures. Objectives. To assess the reliability of magnetic resonance imaging (MRI) for posterior ligament complex injury in thoracolumbar spinal fractures. Summary of Background Data. Some researchers have studied posterior ligament complex injury in spinal fracture using MRI. However, most did not evaluate the findings of MRI compared with the operative findings. Methods. Thirty-four patients with thoracolumbar spinal fracture were evaluated by palpation of the interspinous gap, plain radiography, and MRI before operation. In addition to conventional MRI sequences, a fat-suppressed T2-weighted sagittal sequence was performed. Surgery was performed by a posterior approach. During the operation, posterior ligament complex injury was carefully examined. Results. A wide interspinous gap was palpated in 14 patients and was found in 21 patients on plain radiography. Magnetic resonance imaging raised suspicion of injury to the posterior ligament complex in 30 patients. According to interpretation of MRI, injury to the supraspinous ligament was suspected in 27 patients, the interspinous ligament in 30 patients, and the ligamentum flavum in 9 patients. There were 28 supraspinous ligament injuries, 29 interspinous ligament injuries, and 7 ligamentum flavum injuries in operative findings. There was a significant relation between MRI interpretation and operative findings. Conclusion. A fat-suppressed T2-weighted sagittal sequence of MRI was a highly sensitive, specific, and accurate method of evaluating posterior ligament complex injury. Based on the results of this study, a fat-suppressed T2-weighted sagittal sequence of MRIs is recommended for the accurate evaluation of posterior ligament complex injury and would be helpful in the selection of treatment options.

Delivery of Recombinant Human Bone Morphogenetic Protein-2 Using a Compression-Resistant Matrix in Posterolateral Spine Fusion in the Rabbit and in the Non-Human Primate

Study Design. A rabbit and rhesus monkey model of posterolateral intertransverse process spine arthrodesis was used. Objective. To test two new soft tissue compression resistant ceramic/collagen sponge carriers for recombinant human bone morphogenetic protein-2. Summary of Background Data. After determining that a plain collagen sponge was too compressible for large animals in a posterolateral fusion application, the authors demonstrated good bone induction using biphasic ceramic phosphate granules (60% hydroxyapatite/40% tricalcium phosphate) as the carrier matrix for recombinant human bone morphogenetic protein 2 in rhesus monkeys. A limitation of 60:40 biphasic ceramic phosphate was its slow resorption time caused by the high hydroxyapatite content, making radiographic detection of new bone formation very difficult. Methods. Adult New Zealand white rabbits (n = 14) underwent posterolateral spine arthrodesis at L5–L6 using 5:95 biphasic ceramic phosphate (5% hydroxyapatite/95% tricalcium phosphate) impregnated Type I collagen sponges (17 × 35 × 2.5 mm, two per side) loaded with 0.86 mg recombinant human bone morphogenetic protein 2. Additional rabbits (n = 14) received 60:40 hydroxyapatite-tricalcium phosphate granules as the carrier for bone morphogenetic protein 2. Adult rhesus monkeys (n = 6) underwent posterolateral arthrodesis at L4–L5 with ceramic/collagen sponge carrier loaded with 9 mg recombinant human bone morphogenetic protein 2 per side. Two monkeys received ceramic/collagen sponges containing 15:85 biphasic ceramic phosphate (15% hydroxyapatite/85% tricalcium phosphate) with two pieces per side; two received sponges containing 5:95 biphasic ceramic phosphate with two pieces per side, and two received sponges containing 5:95 biphasic ceramic phosphate with four pieces per side. The rabbits were killed after 5 weeks and the monkeys after 24 weeks; the spines were evaluated by manual palpation, radiographs, tensile mechanical testing (rabbits only), and histology. Results. The recombinant human bone morphogenetic protein 2 delivered in the 5:95 biphasic ceramic phosphate/collagen sponge achieved fusion in 100% of rabbits and had improved handling properties compared with the biphasic ceramic phosphate granules. Biomechanical results with 5:95 biphasic ceramic phosphate/collagen carrier were comparable to those obtained with the 60:40 biphasic ceramic phosphate granules and superior to those of autogenous bone graft (P < 0.05). The recombinant human bone morphogenetic protein 2 delivered in the 15:85 or the 5:95 biphasic ceramic phosphate/collagen sponge carrier (two pieces per side) induced fusion in nonhuman primates with normal bone histology, less residual ceramic, and more bone in the center of the carrier matrix in comparison with BCO granules alone. The 15:85 biphasic ceramic phosphate/collagen sponge resulted in fusion mass sizes closer to the original size of the matrix implanted than did the 5:95 biphasic ceramic phosphate/collagen sponge, which was considered a desirable feature. The monkeys with 9 mg recombinant human bone morphogenetic protein 2 spread over four sponges per side instead of two had half the effective recombinant human bone morphogenetic protein 2 concentration per sponge and inferior results. Conclusions. The new compression-resistant biphasic ceramic phosphate/collagen sponge matrices were biologically compatible with recombinant human bone morphogenetic protein 2 bone formation, resulted in biomechanically stiffer fusion masses than autograft, better space maintenance than plain collagen sponges, and improved handling and radiographic resorption properties over the ceramic carriers previously tested.

Simple carrier matrix modifications can enhance delivery of recombinant human bone morphogenetic protein-2 for posterolateral spine fusion

Study Design. A nonhuman primate lumbar intertransverse process arthrodesis model was used to evaluate modifications to a plain collagen sponge to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2). Objectives. To evaluate the feasibility of enhancing the delivery of rhBMP-2 with the established collagen sponge carrier by adding biphasic ceramic phosphate (BCP) granules (15% hydroxyapatite, 85% tricalcium phosphate) or allograft chips to provide compression resistance for posterolateral spine arthrodesis. Summary of Background Data. Recombinant human bone morphogenetic protein-2 was successfully delivered with a resorbable collagen sponge in a rabbit intertransverse process fusion model. Success in nonhuman primates required a higher dose (6–9 mg) of rhBMP-2 and a more compression-resistant matrix (ceramic) than plain collagen. The limitation of the ceramic carrier was its radiopacity, which made radiographic detection of new bone formation difficult. Methods. Nine adult rhesus monkeys underwent bilateral posterolateral intertransverse process arthrodesis at L4-L5. The animals were divided into three groups (n = 3 each) based on the graft material implanted: 1) autogenous iliac crest bone (5 cm3/side); 2) collagen sponge and 15:85 BCP granules loaded with rhBMP-2 (3 mg/side); and, 3) collagen sponge and allograft chips loaded with rhBMP-2 (3 mg/side). The monkeys were killed 24 weeks after surgery. Inspection, manual palpation, radiography, computed tomographic scans, and histology were used to assess fusion. Results. All six monkeys with rhBMP-2 delivered in the collagen/15:85 BCP carrier and the collagen/allograft chips carrier achieved solid spine fusions, whereas only one of three animals fused with autogenous bone graft. Histologic analysis of the bone induced by rhBMP-2 showed normal trabecular bone and bone marrow elements. Conclusions. The addition of either 15:85 BCP granules or allograft bone chips to the existing resorbable collagen sponge matrix enhanced delivery of rhBMP-2 in the posterolateral spine. The combination matrices were more compression resistant and had improved radiographic resorption properties that permitted easy radiographic visualization of new bone. In addition, a lower dose of rhBMP-2 (3 mg/side) was successful compared with the dose previously used with the plain collagen sponge (6 mg/side).

rhBMP‐2 injected in a calcium phosphate paste (α‐BSM) accelerates healing in the rabbit ulnar osteotomy model

This study evaluated the ability of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) delivered in an injectable calcium phosphate carrier (α‐BSM) to accelerate healing in a rabbit ulna osteotomy model compared to untreated surgical controls. Healing was assessed by radiography, histology and biomechanics. Bilateral mid‐ulnar osteotomies were created in 16 skeletally mature rabbits. One limb in each animal was injected with either 0.1 mg rhBMP‐2/α‐BSM (BMP) (N = 8) or buffer/α‐BSM (BSM) (N = 8). Contralateral osteotomies served as untreated surgical controls (SXCT). Gamma scintigraphy showed 75%, 45% and 5% of the initial 125I‐rhBMP‐2 dose was retained at the osteotomy site at 3 h, 1 week and 3 weeks. The biological activity of rhBMP‐2 (alkaline phosphatase activity from bioassay) extracted from α‐BSM incubated in vitro up to 30 days at 37°C was unchanged. Radiographs demonstrated complete bridging of the BMP limbs at 4 weeks whereas none of the BSM or SXCT limbs were bridged. Post‐mortem peripheral quantitative computed tomography determined mineralized callus area was 62% greater in BMP limbs compared to SXCT limbs. Torsional stiffness and strength were 63% and 103% greater in BMP limbs compared to SXCT limbs. There was no difference in torsional properties between BSM and SXCT limbs. Failure occurred outside the osteotomy in four out of seven of the BMP limbs. All BSM and SXCT limbs failed through the osteotomy. Histology showed bony bridging of the osteotomy and no residual carrier in the BMP limbs. BSM and SXCT groups showed less mature calluses composed of primarily fibrocartilaginous tissue and immature bone in the osteotomy gap. These data indicate rhBMP‐2 delivered in α‐BSM accelerated healing in a rabbit ulna osteotomy model compared to BSM and SXCT groups.

Retention of 125I-labeled recombinant human bone morphogenetic protein-2 by biphasic calcium phosphate or a composite sponge in a rabbit posterolateral spine arthrodesis model.

The purpose of this study was to characterize the retention kinetics of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) applied to two calcium‐based delivery matrices. Biphasic calcium phosphate (BCP) and a composite containing BCP in an absorbable collagen sponge (BCP/ACS) were evaluated using a spinal fusion model in rabbits. rhBMP‐2 labeled with radioactive iodine (125I) was used as a tracer to assess in vivo retention of rhBMP‐2 in the presence of these materials (nine animals per material studied). Over a 36 day study period, animals were assessed for the following: percent administered dose retained at the implant site as measured by scintigraphic imaging (counting) with a gamma camera (all animals), radiography of the implant site (all animals), radioactivity in blood and plasma (all animals), and radioactivity in the urine and feces (three animals for each material). Radioactivity data were corrected for the decay of 125I and the attenuation between the implant in vivo and the gamma camera.

Overcoming the Immune Response to Permit Ex Vivo Gene Therapy for Spine Fusion With Human Type 5 Adenoviral Delivery of the LIM Mineralization Protein-1 cDNA

Study Design. An animal study in immune competent rabbits and athymic rats was conducted. Objectives. To develop an animal model for simulation of previous human Type 5 adenovirus (Ad5) exposure, to determine the impact of adenoviral pre-exposure on spine fusion induced with ex vivo Ad5-LMP-1, and to test strategies for overcoming any potential immune response. Summary of Background Data. Cells transduced with adenovirus containing the osteoinductive LMP-1 cDNA (Ad5-LMP-1) can induce spine fusion in rabbits. Because up to 80% of the human population has been exposed to adenovirus, immune responses to the vector may limit this strategy in humans. Few studies have modeled previous adenoviral exposure and tested strategies to circumvent it. Methods. Adult New Zealand white rabbits were injected with 108 or 109 viral particles of Ad5-LacZ. At 4 or 16 weeks after Ad5 injection, autologous buffy coats were prepared from peripheral blood, and 4 million cells per side were infected ex vivo for 10 minutes with Ad5-LMP-1 (multiplicity of infection = 4). Cells were implanted on a collagen matrix instead of an autograft for posterolateral lumbar arthrodesis. Unimmunized rabbits served as control subjects. Additional immunized rabbits underwent arthrodesis at 4 weeks with increased cell number (10 million) and viral dose (multiplicity of infection = 10), or with both parameters increased. The rabbits were killed at 4 weeks, and the spines were assessed by palpation and radiograph. A parallel study was performed in athymic rats using immunized rabbits for the donor cells. Results. All the unimmunized rabbits had solid spine fusions. None of the rabbits arthrodesed 4 weeks afterAd5 pre-exposure achieved fusion. At 4 weeks after Ad5 exposure, increasing the multiplicity of infection to 10 did not overcome the immune response (0/3 fused), but increasing the cell number to 10 million (2/3 fused) or increasing both cell number and multiplicity of infection (3/3 fused) did overcome the immune effects. Delaying arthrodesis until 16 weeks after Ad5 pre-exposure also overcame the immune response (3/3 fused). Similar results were seen in the athymic rat ectopic implant model, suggesting that the immune effect was mediated by humoral antibodies rather than a T-cell response. Conclusions. Two model systems were developed that simulate previous exposure to human Ad5 and could separate the cellular and humoral components of the response. There was a dose-dependent inhibition of ex vivo Ad5-LMP-1 gene transfer to cells from animals previously exposed to human Ad5. Data suggested that the inhibition of Ad5 infection was caused by humoral antibodies rather than a T-cell–based response. Minor modifications in the gene transfer protocol, such as doubling the viral dose or number of cells infected, or increasing the infection time, could overcome the immune response for an ex vivo approach.

Surgical outcome of lumbar fusion surgery in patients with Parkinson disease.

Study Design Retrospective study. Objectives To investigate the overall surgical outcome of lumbar fusion surgery in patients with Parkinson disease (PD). Summary of Back ground Data Poor bone quality and muscular dysfunction are important clinical manifestations connected with musculoskeletal diseases in PD patients. These secondary changes caused by PD often result in spinal pathology, indicating spine operations for some patients with scoliosis, kyphosis, osteoporotic fracture, or degenerative spondylosis. However, little is known about the surgical outcome or prognosis of spine surgery in PD patients. Methods Lumbar fusion surgery was performed on 20 patients who had PD and degenerative spinal diseases. At the time of lumbar fusion surgery, the mean duration of PD, age, sex, the preoperative visual analog pain scale (VAS, 0 to 100 mm) for low back pain, Hoehn and Yahr staging, and other comorbidities were evaluated. Patients postoperative clinical outcome was measured using the criteria of Kim and Kim and VAS for back pain. Radiographic assessment was made using plain films and a dynamogram. Results At the time of the spine surgery, Hoehn and Yahr staging of PD was from 1 to 2 in all patients. Only 1 patient had a satisfactory outcome; a good result according to Kim and Kims criteria. The average postoperative VAS (mm) was 55.2, whereas the mean preoperative VAS (mm) was 53.9. Radiological assessment showed fusion status in 15 patients and probably no solid fusion mass in 5 patients. Conclusions A poor surgical outcome would be inevitable because of the worsening of symptoms owing to the natural history of PD. Therefore, our current study suggested surgical indication should be exercised cautiously in the patients with PD and spinal stenosis.

The Accuracy of Computed Tomography in Assessing Cervical Pedicle Screw Placement

Study Design. A blinded, prospective comparison of computed tomography scan accuracy for determining the location of cervical pedicle screw position in human cadavers. Objectives. To establish recommended computed tomography technique guidelines for assessing location of cervical pedicle screws. Summary of Background Data. A small number of studies have described the accuracy of roentgenography regarding the assessment of pedicle screw position. However, a few studies have investigated the accuracy of computed tomography in this respect. Ebraheim et al evaluated the relation of lateral mass screws to the nerve roots within the intervertebral foramen on oblique radiographs. No study has been undertaken, to our knowledge, to specifically define the reliability and validity of computed tomography scans in the case of cervical pedicle screw placement. Methods. As a pilot study, 10 cadaveric cervical spines from another study with bilateral 3.5 mm titanium pedicle screws were scanned with 1.0 mm axial slices. After the scans were interpreted by three blinded readers, each panel member was “trained” with regard to individual accuracy. Ten more cadaveric cervical spines were instrumented with 3.5 mm titanium screws in each pedicle (C2–C7). The specimens were then scanned with a variety of computed tomography techniques, including spiral acquisitions at 1.0 mm, 1.0 mm + reconstruction, 2.5 mm, 5.0 mm slices, and the three-dimensional Stealth Station™ recipes. The specimens were dissected, and malpositioned screws were recorded and photographed by independent raters. The same three readers from the pilot study then read each new scan in random order. Results. Reader accuracies in the pretraining pilot study were 74%, 68%, and 52%, with kappa coefficients of 0.49, 0.37, and 0.07, respectively, and significant intrarater variances (P = 0.014). After training, the accuracy rate improved significantly to 89%, 88%, and 85% in posttraining study, and the kappa coefficients were 0.81, 0.78, and 0.73, respectively. Kappa statistical analysis showed negligible interreader variance on the entire pivotal study except by the three-dimensional StealthStation™ format. The overall mean kappa coefficients were 0.77, 0.75, and 0.73. Assessment of pedicle screw position was statistically inferior with 5.0 mm axial slices, in contrast to slices <3.0 mm. Conclusions. We demonstrated that reliance on computed tomography scan data in determining the misplacement of a pedicle screw is usually accurate given proper scan acquisition, presentation windows, and adequate reader training, but a clinically significant error rate remains. A conventional computed tomography scan should not be treated as a gold standard, particularly without regard to the readers’ training.

Life expectancy after lumbar spine surgery: one- to eleven-year follow-up of 1015 patients.

Study Design. Retrospective study. Objectives. To investigate the 10-year survival of a large number of elderly patients who underwent spine surgery for lumbar spinal stenosis, and to identify significant risk factors and compare them with age- and gender-matched controls from the general population. Summary of Background Data. There have been many studies on treatment options and surgical outcomes for lumbar spinal stenosis. However, survival outcomes after lumbar spinal stenosis surgery have not previously been studied. Because these operations are usually performed for elderly patients, we consider patient survival or life expectancy to be a significant outcome measure. Methods. Between January 1997 and June 2006, patients underwent spine surgery for lumbar spinal stenosis. The date of death was verified using records from the National Health Insurance Corporation. Cumulative 10-year survival was calculated using the Kaplan-Meier method, and the survival of patients who had undergone spine surgery was compared to that of age- and sex-matched members of the general population. A Cox multivariate regression analysis was used in order to compare the survival rates for different covariates. Results. Using Kaplan-Meier curves, the overall 10-year survival was 87.8% in patients 60 to 70 years old at surgery, and 83.8% in patients 70 to 85 years old at surgery. The 10-year survival rate of female patients and patients who underwent fusion surgery were higher than those of male patients and patients with nonfusion surgery. Compared to the adjusted corresponding portion in general population, the standardized mortality ratios were 0.21, 0.53, and 0.45 in patients aged 50 to 59, 60 to 69, and 70 to 85, respectively. Conclusion. Elderly patients who underwent spine surgery for spinal stenosis had reduced mortality compared to the corresponding portion of the general population. Therefore, surgery for spinal stenosis is a justifiable procedure even in elderly patients.

The Biomechanical Effect of Pedicle Screws' Insertion Angle and Position on the Superior Adjacent Segment in 1 Segment Lumbar Fusion

Study Design. A finite element analysis. Objective. To investigate the association between the position of an inserted pedicle screw and the corresponding facet contact force or intradiscal pressure. Summary of Background Data. Although superior facet joint violation by pedicle screws is not an uncommon occurrence in instrumented lumbar fusion surgery, its actual biomechanical significance is not well understood. Furthermore, the association between the position of the pedicle screw and the stress on the corresponding disc/facet joint has yet to be investigated. Methods. According to the positions of pedicle screws in L4 of the L4–L5 lumbar fusion, 4 L4–L5 fusion models were simulated. These models included the violation of both L3–L4 superior facet joints by pedicle screws (facet joint violation [FV] model), the nonencroachment of both L3–L4 superior facet joints by pedicle screws (facet joint preservation [FP] model), and the removal state of pedicle screws in the FV model (removal of violated pedicle screws [rFV] model). The facet joint contact [FC] model represented the scenario in which the pedicle screws did not encroach upon either facet joint but were inserted close to the L3–L4 facet joint surface. Moreover, the uninstrumented fusion [UF] model represented the uninstrumented L4–L5 fusion. In each scenario, the intradiscal pressures and facet contact forces at the L2–L3 and L3–L4 segments were analyzed under extension and torsion moments. Results. The FV model yielded the greatest increases in facet contact force and intradiscal pressure at the L3–L4 segment under extension and torsion moments. Following the FV model, the increases in intradiscal pressure and facet contact force were the second highest in the FC model followed by the FP model. Furthermore, the rFV model represented prominent reductions of previously increased facet contact force and intradiscal pressure at the L3–L4 segment. Conclusion. In models of 1-segment lumbar fusion surgery, the positions of pedicle screws were closely linked with corresponding disc stresses and facet contact forces. However, even in cases of facet violation by pedicle screws, removal of the pedicle screw after fusion completion can reduce facet contract forces and disc stresses under both extension and torsional moments.