Seok Woo Kim

Interaction of human mesenchymal stem cells with disc cells : Changes in extracellular matrix biosynthesis

Study Design. To evaluate the in vitro interactions between human mesenchymal stem cells (MSCs) and degenerative disc cells. Objectives. To demonstrate the potential of MSCs in regulating the extracellular matrix synthesis of degenerative disc cells. Summary of Background Data. Culture of degenerative disc cells followed by their reinsertion into a disc can retard the degeneration process in an animal model. However, harvesting cells without accelerating degeneration is problematic. Autologous MSCs can be safely harvested from the bone marrow and transplanted into degenerative discs. Methods. Human degenerative nucleus pulposus (NP), anulus fibrosus (AF) cells, and MSCs were cultured as pellets, and coculture pellets were formed by addition of MSCs to disc cells (50:50 ratio). Glycosaminoglycan (GAG) and DNA content were measured. Proteoglycan synthesis was analyzed by RT-PCR and western blot. Type II collagen expression was assessed by immunohistochemistry. Results. Coculture pellets formed by the addition of MSCs to AF cells were superior in size to all other pellets. AF/MSC pellets showed higher experimental GAG content than the predicted values represented by the sum of individual control pellets, with 10.2 versus 5.6 &mgr;g/pellet at week 3, respectively. The effect was not observed in the NP/MSC coculture, or when chondrogenic medium was used. Close contact between cells was necessary to obtain this enhancement of GAG content. Proteoglycan and collagen expression in both individual and coculture pellets was confirmed by PCR analysis and western blot. Conclusion. Addition of MSCs to AF cells resulted in an up-regulation of the proteoglycans synthesis. This study provides the rationale for further investigation of the potential of MSC therapy in treating intervertebral disc degeneration.

Cervical disc replacement-porous coated motion prosthesis : a comparative biomechanical analysis showing the key role of the posterior longitudinal ligament

Study Design. Benchtop cadaveric biomechanical comparative testing and caprine animal model in vivo implantation. Objective. To evaluate the role of the posterior longitudinal ligament in cervical arthroplasty and to understand the relative contribution of this ligament in nonfusion applications. Summary of Background Data. Rauschning refers to the posterior longitudinal ligament as “The Kleenex Ligament” due to its apparent anatomic insignificance. White and Panjabi found the posterior longitudinal ligament ranked only fourth in importance in tensile load-to-failure biomechanical testing. In the postoperative situation following anterior cervical diskectomy fusion, posterior longitudinal ligament integrity is overlooked by physicians because the entire disc space usually fuses into a homogeneous block of bone. Purpose. This biomechanical study was undertaken to determine the relative importance of the posterior longitudinal ligament following two different degrees of anterior decompression, anterior disc replacement, and anterior arthrodesis procedures. Methods. A total of seven fresh frozen human cadaveric cervical spines (C3–C7) (mean age 68 ± 19 years) were used for biomechanical testing. Each vertebra was equipped with three non-colinear light emitting diodes designed for detection by an optoelectronic motion measurement system (3020 Optotract System). To determine the multidirectional flexibility, six pure moments (flexion, extension, right + left lateral bending, right + left axial rotation) and axial compression were applied using a servohydraulic 858 Bionix testing device configured with a six-degree-of-freedom spine simulator. Range of motion was defined as the peak displacement from the initial neutral position to the maximum load, whereas the neutral zone represents the motion from the initial neutral position to the unloaded position at the beginning of the third cycle. Seven groups of (N = 7 each) constructs at C5–C6 were: 1) intact “native” C5–C6 level; 2) anterior diskectomy (posterior longitudinal ligament intact); 3) a Low Profile Porous Coated Motion cervical disc replacement; 4) posterior longitudinal ligament resected; 5) Porous Coated Motion cervical disc replacement fixed with anterior flanges and screws; 6) tricortical structural allograft; and 7) an anterior cervical translational plate + allograft. The caprine model was evaluated for suitability as an animal model with 12 goats undergoing C3–C4 anterior cervical Porous Coated Motion disc replacement. Results. Group 2 (anterior diskectomy alone) was significantly more stable than Group 4 (anterior diskectomy + posterior longitudinal ligament resection) in flexion–extension, 18.7 ± 4.76°versus 24.8 ± 4.42° (P < 0.05) and in lateral bending, 5.9 ± 1.79°versus 10.7 ± 2.8° (P < 0.05). The comparison for the two conditions for axial rotation, 10.4 ± 13.9°versus 13.9 ± 2.7°, and axial compression, 1.19 ±.98°versus 1.52 ± 1.14°, showed the same trend. Twelve goats undergoing porous coated motion cervical disc replacement had no evidence of prosthesis loosening, neurologic complications, or experienced inflammatory reactions from particulate wear debris after 6 months of implantation. Discussion. This study confirms the pivotal role of the posterior longitudinal ligament in postsurgical stability of the cervical spine following anterior diskectomy. This is because the lateral anulus, uncovertebral ligaments, and lateral capsular ligaments are stretched and plastically deformed in the surgical distraction process of restoring the disc space height following anterior surgical decompression. There should be a separate determination of the range of motion of cervical disc replacements depending of the integrity and the amount of the posterior longitudinal ligament that has been resected. Clinical Relevance. There are two basic types of total knee replacements, posterior cruciate ligament-preserving and posterior cruciate ligament-sacrificing designs. In the cervical spine, an analogous situation exists biomechanically depending on whether the posterior longitudinal ligament needs to be removed in its entirety as part of the spinal cord decompression part of the procedure—it may be helpful to conceptually differentiate between posterior longitudinal ligament-preserving and posterior longitudinal ligament-sacrificing total cervical disc replacements.

T1 Slope as a Predictor of Kyphotic Alignment Change After Laminoplasty in Patients With Cervical Myelopathy

Study Design. Prospective study. Objective. To analyze the effect of T1 slope on kyphotic alignment change after cervical laminoplasty in patients with cervical myelopathy. Summary of Background Data. Laminoplasty is a posterior method, and maintenance of both preoperative and postoperative lordotic alignment is prerequisite for the successful surgery. Unfortunately, patients who underwent laminoplasty tend to have kyphotic alignment change after operation despite sufficient preoperative lordosis, and such kyphotic alignment change after cervical laminoplasty can reduce surgical outcome and require additional surgery. Methods. Consecutive patients who underwent cervical laminoplasty for cervical myelopathy were enrolled. Cervical spine lateral radiography in neutral, flexion, and extension were taken before surgery and at 2-year follow-up. Patients were divided into 2 groups according to the preoperative T1 slope, and postoperative cervical alignment change was compared according to the preoperative T1 slope. Results. A total of 51 patients were enrolled in this study. The mean age was 57.2 years (range, 39–88 yr). There were 39 male patients and 12 female patients. There were no differences in age, sex, the presence and type of ossification of posterior longitudinal ligament, and operation level between the patients with higher and lower preoperative T1 slope. Patients with higher preoperative T1 slope had more lordotic preoperative cervical alignment; however, they had more kyphotic alignment changes after laminoplasty (P< 0.001). After univariate logistic regression, only higher preoperative T1 slope was associated with significantly increased odds ratio for postoperative kyphotic alignment changes. Conclusion. We hypothesized that kyphotic alignment change by posterior structural injury after cervical laminoplasty would be more marked in patients with high T1 slope, and demonstrated that patients with cervical myelopathy with high T1 slope had more kyphotic alignment changes after cervical laminoplasty at 2-year follow-up. Level of Evidence: 4

T1 Slope and Cervical Sagittal Alignment on Cervical CT Radiographs of Asymptomatic Persons

Objective We performed a retrospective analysis of medical records and radiographic images of patients who never underwent spinal treatment including diagnosis. The objective of this study is to explain the biomechanical and physiologic characteristics of cervical alignment related to thoracic inlet angle including T1 slope changes in each individual. Methods We reviewed the cervical CT radiographs of 80 patients who visited ENT outpatient clinic without any symptom, diagnosis and treatment of cervical spine from January 2011 to September 2012. All targeted people were randomized without any prejudice. We assessed the data-T1 slope, Cobbs angle C2-7, neck tilt, sagittal vertical axis (SVA) C2-7 and thoracic inlet angle by the CT radiographs. Results The relationships between each value were analyzed and we concluded that Cobbs angle C2-7 gets higher as the T1 slope gets higher, while the SVA C2-7 value decreases. Conclusion We propose that the T1 slope is background information in deciding how much angle can be made in the cervical spinal angle of surgical lordotic curvature, especially severe cervical deformity.

Is It Possible to Evaluate the Parameters of Cervical Sagittal Alignment on Cervical Computed Tomographic Scans

Study Design. Retrospective study. Objective. The purpose of this study was to analyze the relationship of the parameters of cervical sagittal alignment between those obtained from cervical CT and those obtained from radiography, as well as to determine which parameter would help predict physiological lordosis of the cervical spine. Summary of Background Data. Sagittal balance in the cervical spine is as important as the pelvic incidence and is related to the concept of T1 slope. However, many articles including this article based on unclear cervical x-ray radiographs could weakly explain the parameters. To overcome the fundamental limitation of x-ray radiographs, Hallym University Sacred Heart Hospital reported the strong correlation between T1 slope and cervical lordosis on the cervical dimensional CT scans like result by checking by the cervical x-ray radiographs. Methods. A retrospective analysis of data from 50 asymptomatic adults in whom both cervical CT scans and cervical radiograph were obtained at the same time. The T1 slope, Cobb angle C2–C7, neck tilt, and thoracic inlet angle (TIA) obtained from the CT scans and radiographs were assessed. Results. The T1 slope on x-ray was significantly correlated with the T1 slope on CT. The mean of the T1 slope on x-ray was larger than the mean of the T1 slope on CT (3.3° ± 6.1°). More cervical spine lordosis was evident on the cervical radiograph than on the cervical CT scan (5.93° ± 9.0°). No significant difference was seen between the TIA on x-ray and the TIA on CT (TIA on x-ray − TIA on CT, −0.1 ± 7.6, P = 0.959). Conclusion. This difference may be due to the differing effect of gravity upon the spine between the upright versus the supine position. Accordingly, TIA and T1 slope may be used as a guide for the assessment of sagittal balance of the cervical spine. Level of Evidence: N/A

Porous coated motion cervical disc replacement: a biomechanical, histomorphometric, and biologic wear analysis in a caprine model.

Study Design. The biomechanical, histopathologic, and histomorphometric characteristics of cervical disc replacement were assessed in a caprine animal model. Objective. To investigate the biomechanical, porous ingrowth, and histopathologic characteristics of the Porous Coated Motion (PCM) Cervical Disc replacement (Cervitech, Inc., Rockaway, NJ). Summary of Background Data. As an alternative to anterior cervical interbody arthrodesis, an artificial cervical disc serves to replace the symptomatic degenerated disc, restore the functional biomechanical properties of the motion segment, and preserve neurologic function. Methods. There were 12 mature Nubian goats divided into 2 groups based on postoperative survival periods of 6 (n = 6) and 12 months (n = 6). Using an anterior surgical approach, a complete discectomy was performed at the C3–C4, followed by implantation of the PCM device. Functional outcomes of the disc prosthesis were based on computerized tomography (CT), multidirectional flexibility testing, undecalcified histology, histomorphometric, and immunocytochemical analyses. Results. There was no evidence of prosthesis loosening, or neurologic or vascular complications. CT showed the ability to image and assess the cervical spinal canal for the presence of compressive pathology in the area of the CoCrMo prosthesis. Multidirectional flexibility testing under axial rotation and lateral bending indicated no differences in the full range of intervertebral motion between the disc prosthesis and nonoperative controls (P > 0.05). Based on immunohistochemical and histologic analysis, there was no evidence of particulate debris, cytokines, or cellular apoptosis within the local or systemic tissues. Moreover, review of the spinal cord at the operative levels indicated no evidence of cord lesions, inflammatory reaction, wear particles, or significant pathologic changes in any treatment. Histomorphometric analysis at the metal-bone interface indicated the mean trabecular ingrowth of 40.5% ± 24.4% and 58.65% ± 28.04% for the 6 and 12-month treatments, respectively. Conclusion. To our knowledge, this serves as the first in vivo time-course study investigating the use of the PCM device for cervical arthroplasty. All 12 animals undergoing cervical disc replacement had no evidence of implant loosening, subluxation, or inflammatory reactions. PCM cervical arthroplasty permits unobstructed visualization of the spinal canal based on CT imaging. Segmental intervertebral motion was preserved under axial rotation and lateral bending loading conditions, while at the same time permitting porous osseointegration at the prosthesis-bone interface. Based on histopathologic review of all local and systemic tissues, there was no evidence of particulate wear debris, cytokines, cellular apoptosis, or significant pathologic changes in any treatment.

Correlation of magnetic resonance diffusion tensor imaging and clinical findings of cervical myelopathy

BACKGROUND CONTEXT Despite significant advances in the development of diagnostic technology, the diagnosis of cervical myelopathy (CM) still remains based on the clinical findings, which do not provide the means for a sufficiently accurate diagnosis. Furthermore, conventional magnetic resonance imaging (MRI) using T1- and T2-weighted sequences lacks sensitivity to detect and characterize spinal cord lesions. Considering these uncertainties, several investigators have assessed the diagnostic value of diffusion tensor imaging (DTI), an advanced MRI technique that measures the diffusion of water molecules. PURPOSE To determine the diagnostic value of DTI in CM in reliably characterizing spinal lesions and in associating them with the clinical findings. STUDY DESIGN/SETTING Prospective cohort study. PATIENT SAMPLE Fifteen CM patients and five healthy volunteers without a history of neurological disorders or of symptoms as controls. OUTCOME MEASURES Symptoms and signs of CM were evaluated by the use of a modified Japanese Orthopedic Score and the other clinical findings. T2-weighed MRI was used to note the number of compressed levels. Diffusion tensor imaging results were measured according to two parameters, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), at anterior, lateral, and posterior regions of interest (ROIs) in each of five cervical vertebrae, C3-C7. METHODS On diagnosis of CM by clinical evaluation and findings from T2-weighted MRI, the 15 subjects were assigned to two subgroups based on complaints, symptoms, and signs. The nine subjects who had typical CM symptoms such as motor weakness, gait disturbance, clumsiness of the hands, and unilateral hypesthesia were assigned to the paralysis subgroup. The other six subjects, whose main symptom was pain and who had vague signs of upper motor neuron injury despite a definitive finding of CM by T2-weighted MRI, were assigned to the pain subgroup. Once assignments had been made, subjects underwent DTI done by the use of the same scanner as for T2-weighted MRI. Results of DTI for each subgroup and controls were averaged, and the mean was used for comparisons. Diffusion tensor imaging results from the paralysis subgroup were sorted into affected and unaffected sides according to the presence or the absence of symptoms. RESULTS The paralysis subgroup and the pain subgroup had similar findings from T2-weighted MRI on presentation. The paralysis subgroup had statistically significantly decreased FA values in the anterior and lateral ROIs on the affected side and in the anterior ROIs on the unaffected side, compared with controls. The paralysis subgroup also had statistically significantly increased ADC values in the anterior ROIs of the affected side, compared with controls. The pain subgroup showed significantly increased ADC values in anterior, lateral, and posterior ROIs. CONCLUSIONS Use of DTI to quantitatively compare compression in the cervical spinal cords of CM subjects and healthy controls explained individual differences in the clinical findings in the subjects. These findings even applied to CM subjects whose compressed spinal cords looked similar on conventional T2-weighted MRI. Therefore, DTI provided more accurate and reliable information than did conventional T2-weighted MRI about the relationship between spinal cord structure and clinical presentation of CM. Based on our DTI findings, we hypothesized that different clinical findings in CM are attributable to the stage of progression and the severity of pathologic change at presentation. We anticipate that the use of DTI to quantify the extent of myelopathological changes in CM could be more reliable than any other existing diagnostic tools and might provide invaluable information about selecting the optimal treatment for CM and predicting surgical outcomes and prognosis.

Preclinical evaluation of the Dynesys posterior spinal stabilization system: a nonhuman primate model

BACKGROUND CONTEXT Posterior dynamic spinal stabilization systems are intended to restore near-normal biomechanical function of the spine without inducing unnatural stresses to the spinal elements or eliciting a histopathological response. These devices must resist loosening within the challenging biomechanical environment of the lumbar spine. PURPOSE To determine the biomechanical effects of the Dynesys dynamic stabilization system (Zimmer, Inc., Warsaw, IN, USA) in the acute postoperative period and after 6 and 12 months in vivo; to examine the facet joints at the same postoperative intervals for signs of degeneration; and to measure the incidence of screw loosening after in vivo loading. STUDY DESIGN/SETTING This was an in vitro and in vivo animal survival study. METHODS Fourteen baboons were used. Eight animals underwent survival surgery to implant a posterior dynamic stabilization system spanning two lumbar levels. Six animals were sacrificed acutely, and their spines were biomechanically tested in the intact condition and with instrumentation implanted as described above. Six animals in the survival group were sacrificed at 6 months postoperatively and two animals at 12 months postoperatively. Their spines were biomechanically tested with instrumentation in situ and explanted. The facets were then processed using undecalcified technique. Microradiographs of the facets were examined for signs of arthrosis, inflammation, and degenerative changes. RESULTS The range of flexion-extension motion for the acute group of instrumented spines was 27% of the intact condition. After 6 months with instrumentation in situ, flexion-extension was 56% of the intact condition. After 12 months with instrumentation in situ, flexion-extension was 70% of the intact condition. With instrumentation explanted, flexion-extension at 6 and 12 months was not different from the intact condition (p>.05). Similar results were observed for lateral bending. There were no significant differences in axial rotation between any groups at any time point (p>.05). The facet joints at the operative and adjacent levels exhibited normal articular cartilage at both the 6- and 12-month postoperative time points. There was no evidence of facet arthrosis in any animal. At 6 months postoperatively, 0 of 36 screws exhibited radiolucency at the bone-metal interface. At 12 months postoperatively, 3 of 12 screws exhibited radiolucency. CONCLUSIONS After 12 months in vivo, spinal motions were stabilized by the dynamic instrumentation system. No facet arthrosis was observed at 6 and 12 months postoperatively. Explantation of the instrumentation restored motion to intact levels. A 25% rate of screw loosening (3 of 12 screws) was observed at the 12-month postoperative time point.

Biomechanical comparison of iliac screws versus interbody femoral ring allograft on lumbosacral kinematics and sacral screw strain.

Study Design. This study evaluates the effect of iliac screw fixation versus interbody femoral ring allograft (FRA) on lumbosacral kinematics and sacral screw strain in long segment instrumentations. Objective. (1) Quantify kinematic properties of 3 lumbosacral fixation techniques; (2) Evaluate sacral screw strain as instrumented levels extend cephalad; and (3) Determine whether iliac screws or FRA biomechanically protect sacral screws. Summary of Background Data. High failure rates at the lumbosacral junction have been reported with long posterior instrumentation ending with S1 pedicle screws. Achieving lumbosacral arthrodesis remains a clinical challenge. Methods. Seven human cadavaric lumbosacral spines were biomechanically evaluated intact and in 3 instrumented conditions: pedicle screw fixation alone (pedicle screw group), pedicle screw fixation supplemented with iliac screws (iliac screw group), and pedicle screw fixation supplemented with FRA (allograft group). Each condition was tested spanning L5–S1, L4–S1, L3–S1, L2–S1, and L1–S1. Testing included pure unconstrained moments (±10 Nm) in axial rotation, flexion/extension, and lateral bending, with quantification of S1 screw strain and lumbosacral range of motion (ROM). Results. Testing revealed decreasing lumbosacral ROM as instrumentation extended cephalad (P < 0.05). In axial rotation, ROM was markedly higher for the allograft group compared to pedicle screw and iliac screw groups with instrumentation to L4 (P < 0.05). In flexion/extension, length of instrumentation in each group correlated with ROM. As length of instrumentation increased, ROM decreased, particularly for the iliac screw group. In lateral bending, ROM decreased in all groups as instrumentation lengthened (P < 0.05). Strain on unprotected sacral screws increased in flexion, extension, and lateral bending as instrumentation extended to L3 (P < 0.05). Iliac screws reduced strain in constructs to L3 and above (P < 0.05). Allograft reduced strain when fixation reached L2, but was not as effective as iliac screws overall. Neither iliac screws nor allograft reduced strain in constructs terminating at L5 or L4. (P > 0.05) Conclusion. For instrumented fusions extending above L3, sacral screws should be protected with supplemental iliac screws or FRA at L5–S1. Of the two, iliac screws appear more effective.

Is cervical lordosis relevant in laminoplasty

BACKGROUND CONTEXT Laminoplasty aims to decompress the spinal cord and stabilize the cervical spine in patients with multilevel cervical lesions. Not every patient with cervical compressive myelopathy is a good candidate for laminoplasty. Most studies recommend that neutral or kyphotic alignments are contraindications for laminoplasty. However, cervical sagittal alignment does not have a strong and consistent effect on the clinical outcomes of laminoplasty. Moreover, many reports on the effect of cervical sagittal alignment did not designate the ideal definition of alignment and used different definitions of lordosis. PURPOSE To identify the effect of preoperative cervical alignment according to two different definitions after midline splitting double-door laminoplasty. STUDY DESIGN Retrospective cohort study. PATIENT SAMPLE From August 2008 to September 2010, 58 patients were diagnosed with cervical myelopathy and treated with midline splitting double-door laminoplasty. OUTCOME MEASURES The clinical results were assessed with the modified Japanese Orthopedic Association (JOA) score, neck disability index (NDI), and visual analog scale (VAS) and were compared to analyze the rate of change between preoperative and postoperative values. Postoperative radiological results at the final follow-up examinations were compared between groups to obtain the change in range of motion and sagittal alignment. METHOD The effect of cervical alignment on JOA, NDI, and VAS scales and also on change of alignment and change of range of motion (ROM) at the final follow-up examinations was analyzed statistically between two groups according to two different definitions such as Toyama classification and Cobb angle. RESULTS No difference was found between the two groups according to Toyama classification in terms of the postoperative improvement rate of the modified JOA score (p=.086), decreasing rate of the VAS (p=.940) or NDI (p=.211), postoperatively. Additionally, no difference was found for the decreasing rate of ROM (p=.427) or sagittal alignment (p=.864) based on the radiological evaluation results. Also, there was no difference between two groups according to Cobb angle in terms of the modified JOA score (p=.743), VAS (p=.548), or NDI (p=.32), postoperatively. Additionally, no difference was found for the ROM (p=1.000) or sagittal alignment (p=.440) based on the radiological evaluation results. CONCLUSIONS Despite nonlordosis cervical sagittal alignment, double-door laminoplasty would be effective for patients with cervical myelopathy because of cervical spondylotic myelopathy or ossification of the posterior longitudinal ligament. Furthermore, sagittal alignment is not the absolute and sole factor that surgeons should consider when determining the optimal treatment strategy.