Prognostic factors for neurological outcome after anterior decompression and fusion for proximal-type cervical spondylotic amyotrophy - A retrospective analysis of 77 cases.

BACKGROUND: Decompression through an anterior approach is theoretically effective for the surgical treatment of cervical spondylotic amyotrophy (CSA), because the pathology usually locates at the anterior side. However, most previous studies investigated posterior surgery or a mix of anterior surgery and posterior surgery in their investigation. Only a few small case series have investigated the surgical outcomes of anterior decompression and fusion (ADF). Therefore, we conducted a multicenter retrospective study that included patients who underwent ADF for proximal-type CSA. METHODS: We analyzed the outcomes of 77 consecutive spinal surgeries performed on proximal-type CSA patients who underwent ADF. Preoperative and postoperative manual muscle tests (MMT) and the patients' backgrounds, radiological findings, and complications were reviewed. We divided the cases into two groups, good-outcome group (MMT improvement â‰§ 2 or improved to MMT 5) and poor-outcome group (others) and evaluated the prognostic factors for outcomes. RESULTS: Of the 77 patients, 48 (62%) showed good neurological outcome. Multiple compressive lesions at anterior horn (AH) and/or ventral nerve roots (VNRs) were detected in 66 patients (85.7%) on the magnetic resonance images. The patients with a single compressive lesion at VNR or AH tended to show good neurological recovery when compare to those with multiple lesions. Age and duration of symptoms were related to the poor outcome in univariate analysis. Duration of symptoms was an independent factor associated with postoperative neurological outcome. The cut-off value for poor outcome was 7.0 months for the symptom duration (sensitivity: 79%, specificity: 54%, area under the curve: 0.69). CONCLUSIONS: Patients with proximal-CSA were more likely to have multiple compressive lesions at an AH and/or a VNR. The prognostic factor for poor neurological outcome was duration of symptoms of ≥7 months.

UV-Pre-Treated and Protein-Adsorbed Titanium Implants Exhibit Enhanced Osteoconductivity.

Titanium materials are essential treatment modalities in the medical field and serve as a tissue engineering scaffold and coating material for medical devices. Thus, there is a significant demand to improve the bioactivity of titanium for therapeutic and experimental purposes. We showed that ultraviolet light (UV)-pre-treatment changed the protein-adsorption ability and subsequent osteoconductivity of titanium. Fibronectin (FN) adsorption on UV-treated titanium was 20% and 30% greater after 1-min and 1-h incubation, respectively, than that of control titanium. After 3-h incubation, FN adsorption on UV-treated titanium remained 30% higher than that on the control. Osteoblasts were cultured on titanium disks after 1-h FN adsorption with or without UV-pre-treatment and on titanium disks without FN adsorption. The number of attached osteoblasts during the early stage of culture was 80% greater on UV-treated and FN-adsorbed (UV/FN) titanium than on FN-adsorbed (FN) titanium; osteoblasts attachment on UV/FN titanium was 2.6- and 2.1-fold greater than that on control- and UV-treated titanium, respectively. The alkaline phosphatase activity of osteoblasts on UV/FN titanium was increased 1.8-, 1.8-, and 2.4-fold compared with that on FN-adsorbed, UV-treated, and control titanium, respectively. The UV/FN implants exhibited 25% and 150% greater in vivo biomechanical strength of bone integration than the FN- and control implants, respectively. Bone morphogenetic protein-2 (BMP-2) adsorption on UV-treated titanium was 4.5-fold greater than that on control titanium after 1-min incubation, resulting in a 4-fold increase in osteoblast attachment. Thus, UV-pre-treatment of titanium accelerated its protein adsorptivity and osteoconductivity, providing a novel strategy for enhancing its bioactivity.

A Newly Created Meso-, Micro-, and Nano-Scale Rough Titanium Surface Promotes Bone-Implant Integration.

Titanium implants are the standard therapeutic option when restoring missing teeth and reconstructing fractured and/or diseased bone. However, in the 30 years since the advent of micro-rough surfaces, titanium's ability to integrate with bone has not improved significantly. We developed a method to create a unique titanium surface with distinct roughness features at meso-, micro-, and nano-scales. We sought to determine the biological ability of the surface and optimize it for better osseointegration. Commercially pure titanium was acid-etched with sulfuric acid at different temperatures (120, 130, 140, and 150 °C). Although only the typical micro-scale compartmental structure was formed during acid-etching at 120 and 130 °C, meso-scale spikes (20-50 µm wide) and nano-scale polymorphic structures as well as micro-scale compartmental structures formed exclusively at 140 and 150 °C. The average surface roughness (Ra) of the three-scale rough surface was 6-12 times greater than that with micro-roughness only, and did not compromise the initial attachment and spreading of osteoblasts despite its considerably increased surface roughness. The new surface promoted osteoblast differentiation and in vivo osseointegration significantly; regression analysis between osteoconductivity and surface variables revealed these effects were highly correlated with the size and density of meso-scale spikes. The overall strength of osseointegration was the greatest when the acid-etching was performed at 140 °C. Thus, we demonstrated that our meso-, micro-, and nano-scale rough titanium surface generates substantially increased osteoconductive and osseointegrative ability over the well-established micro-rough titanium surface. This novel surface is expected to be utilized in dental and various types of orthopedic surgical implants, as well as titanium-based bone engineering scaffolds.

UV-Photofunctionalization of Titanium Promotes Mechanical Anchorage in A Rat Osteoporosis Model.

Effects of UV-photofunctionalization on bone-to-titanium integration under challenging systemic conditions remain unclear. We examined the behavior and response of osteoblasts from sham-operated and ovariectomized (OVX) rats on titanium surfaces with or without UV light pre-treatment and the strength of bone-implant integration. Osteoblasts from OVX rats showed significantly lower alkaline phosphatase, osteogenic gene expression, and mineralization activities than those from sham rats. Bone density variables in the spine were consistently lower in OVX rats. UV-treated titanium was superhydrophilic and the contact angle of ddH2O was ≤5°. Titanium without UV treatment was hydrophobic with a contact angle of ≥80°. Initial attachment to titanium, proliferation, alkaline phosphatase activity, and gene expression were significantly increased on UV-treated titanium compared to that on control titanium in osteoblasts from sham and OVX rats. Osteoblastic functions compromised by OVX were elevated to levels equivalent to or higher than those of sham-operated osteoblasts following culture on UV-treated titanium. The strength of in vivo bone-implant integration for UV-treated titanium was 80% higher than that of control titanium in OVX rats and even higher than that of control implants in sham-operated rats. Thus, UV-photofunctionalization effectively enhanced bone-implant integration in OVX rats to overcome post-menopausal osteoporosis-like conditions.

Novel Osteogenic Behaviors around Hydrophilic and Radical-Free 4-META/MMA-TBB: Implications of an Osseointegrating Bone Cement.

Poly(methyl methacrylate) (PMMA)-based bone cement, which is widely used to affix orthopedic metallic implants, is considered bio-tolerant but lacks osteoconductivity and is cytotoxic. Implant loosening and toxic complications are significant and recognized problems. Here we devised two strategies to improve PMMA-based bone cement: (1) adding 4-methacryloyloxylethyl trimellitate anhydride (4-META) to MMA monomer to render it hydrophilic; and (2) using tri-n-butyl borane (TBB) as a polymerization initiator instead of benzoyl peroxide (BPO) to reduce free radical production. Rat bone marrow-derived osteoblasts were cultured on PMMA-BPO, common bone cement ingredients, and 4-META/MMA-TBB, newly formulated ingredients. After 24 h of incubation, more cells survived on 4-META/MMA-TBB than on PMMA-BPO. The mineralized area was 20-times greater on 4-META/MMA-TBB than PMMA-BPO at the later culture stage and was accompanied by upregulated osteogenic gene expression. The strength of bone-to-cement integration in rat femurs was 4- and 7-times greater for 4-META/MMA-TBB than PMMA-BPO during early- and late-stage healing, respectively. MicroCT and histomorphometric analyses revealed contact osteogenesis exclusively around 4-META/MMA-TBB, with minimal soft tissue interposition. Hydrophilicity of 4-META/MMA-TBB was sustained for 24 h, particularly under wet conditions, whereas PMMA-BPO was hydrophobic immediately after mixing and was unaffected by time or condition. Electron spin resonance (ESR) spectroscopy revealed that the free radical production for 4-META/MMA-TBB was 1/10 to 1/20 that of PMMA-BPO within 24 h, and the substantial difference persisted for at least 10 days. The compromised ability of PMMA-BPO in recruiting cells was substantially alleviated by adding free radical-scavenging amino-acid N-acetyl cysteine (NAC) into the material, whereas adding NAC did not affect the ability of 4-META/MMA-TBB. These results suggest that 4-META/MMA-TBB shows significantly reduced cytotoxicity compared to PMMA-BPO and induces osteoconductivity due to uniquely created hydrophilic and radical-free interface. Further pre-clinical and clinical validations are warranted.

Surgical outcomes for distal-type cervical spondylotic amyotrophy: a multicenter retrospective analysis of 43 cases.

PURPOSE: Distal-type cervical spondylotic amyotrophy (CSA) is a rare form of cervical spondylosis that causes muscle weakness of upper extremities. The pathophysiology and appropriate surgical method for the treatment of CSA are still controversial. We investigated clinical outcomes in surgically treated distal-type CSA. METHODS: The authors executed an analysis of the outcomes of 43 consecutive spinal surgeries performed in distal-type CSA patients. The duration of symptoms, perioperative manual muscle test (MMT) results, radiological findings, and perioperative complications were reviewed. We compared surgical outcomes between different approaches and examined the factors related to poor outcomes (MMT improvement ≤ 0) after surgery. RESULTS: The pathophysiology of CSA was mostly caused by a combination of multiple lesions in the anterior horn and/or nerve root. Nineteen of 29 patients (65.5%) who received anterior approach methods were included in the good outcome group (MMT improvement ≥ 1), whereas 7 of 14 patients (50.0%) in the posterior group were classified as good. In the anterior group, the mean MMT grade significantly improved from 2.6 to 3.4 (p = 0.0035) despite the higher rate of complications. The duration of symptoms was substantially associated with poor outcomes. The MMT grade significantly improved from 2.2 to 3.2 (p = 0.0118) in the < 6 months group. Cervical alignments and preoperative MMT grade were not statistically associated with poor outcomes. CONCLUSIONS: Patients with poor outcomes had symptoms for a longer duration. We found tolerable clinical outcomes within 6 months from onset. The anterior approaches might be recommended because this procedure significantly improved MMT levels in the hands. These slides can be retrieved under Electronic Supplementary Material.

Repair of osteochondral defects in a rabbit model using a porous hydroxyapatite collagen composite impregnated with bone morphogenetic protein-2.

Articular cartilage has a limited capacity for spontaneous repair, and an effective method to repair damaged articular cartilage has not yet been established. The purpose of this study was to evaluate the effect of transplantation of porous hydroxyapatite collagen (HAp/Col) impregnated with bone morphogenetic protein-2 (BMP-2). To evaluate the characteristics of porous HAp/Col as a drug delivery carrier of recombinant human BMP-2 (rhBMP-2), the rhBMP-2 adsorption capacity and release kinetics of porous HAp/Col were analyzed. Porous HAp/Col impregnated with different amounts of rhBMP-2 (0, 5, and 25 µg) was implanted into osteochondral defects generated in the patellar groove of Japanese white rabbits to evaluate the effect on osteochondral defect regeneration. At 3, 6, 12, and 24 weeks after operation, samples were harvested and subjected to micro-computed tomography analysis and histological evaluation of articular cartilage and subchondral bone repair. The adsorption capacity was 329.4 µg of rhBMP-2 per cm(3) of porous HAp/Col. Although 36% of rhBMP-2 was released within 24 h, more than 50% of the rhBMP-2 was retained in the porous HAp/Col through the course of the experiment. Defects treated with 5 µg of rhBMP-2 showed the most extensive subchondral bone repair and the highest histological regeneration score, and differences against the untreated defect group were significant. The histological regeneration score of defects treated with 25 µg of rhBMP-2 increased up to 6 weeks after implantation, but then decreased. Porous HAp/Col, therefore, is an appropriate carrier for rhBMP-2. Implantation of porous HAp/Col impregnated with rhBMP-2 is effective for rigid subchondral bone repair, which is important for the repair of the smooth articular surface.

Clinical Outcomes of Surgical Treatment for Arachnoid Web: A Case Series.

INTRODUCTION: We describe 5 patients who underwent operative treatment for arachnoid web (AW) and discuss the postoperative clinical outcome in each case. AW is an extremely rare disease that causes cord compression and syringomyelia in the thoracic spine. To date, 14 cases only of AW have been reported, and the effect of surgical intervention on clinical and radiologic outcomes is unknown. METHODS: Five patients who underwent surgical treatment for AW were retrospectively reviewed. The clinical outcomes were evaluated using the thoracic Japanese Orthopaedic Association (T-JOA) score. Preoperative and postoperative images were reviewed. RESULTS: All the patients presented with spastic gait and numbness in the lower extremities. Two patients also presented with bladder-bowel dysfunction (BBD). AW, or the so-called "scalpel" sign, was seen dorsally in the thoracic spine on magnetic resonance imaging in all the patients. Syringomyelia adjacent to the web was observed in 4 patients. Fenestration and web resection without instrumentation was performed in all the cases. Overall, significant improvement was seen in locomotion and the total T-JOA score postoperatively. However, numbness in the lower extremities improved in 2 patients but was unchanged in 3 cases. BBD was ameliorated in 1 patient but remained unchanged in the other patient. CONCLUSIONS: Our experience suggests that surgical treatment, including the another patient and resection of the web, can correct the flow dynamics of cerebrospinal fluid and allow neurologic recovery, in particular locomotion, in patients with AW.

Pedicle Subtraction Osteotomy for Kyphosis Following Lumbar Fusion Surgery.

INTRODUCTION: Pedicle subtraction osteotomy (PSO) is performed to correct sagittal plane deformity. This procedure is useful with revision cases in which the number of intact discs for correction is limited. METHODS: Forty-four patients (10 male and 34 female) with minimum follow-up of 2 years were reviewed; all had undergone PSO revision surgery for kyphosis following previous lumbar fusion surgery. The average age at operation was 72.8 years (range 42-85 years), and the average follow-up period was 4.1 years (2-9 years). The average fusion level was 7.5 (4-13 level), and the average previously fused level was 2.4 (1-7 level). RESULTS: The average operation time was 424 min, and average blood loss was 2880 g. The average JOA score of 14.0 before operation changed to 21.8 at 1-year follow-up and to 20.7 at final follow-up. The average recovery rate at final follow-up was 45.7%. Four patients underwent re-operations for proximal junctional kyphosis and 3 patients for rod fracture. The fusion rate was 88.6%, and 13 patients (29.5%) developed subsequent vertebral fracture. The average PI-LL (Pelvic incidence minus Lumbar lordosis) at pre-op of 52.9 degrees changed to 3.8 degrees at post-op, to 13.4 degrees at 1-year follow-up, and to 14.8 degrees at final follow-up. The average correction at the PSO site was 36.0 degrees at post-op, 36.7 degrees at 1-year follow-up, and 37.0 degrees at final follow-up. The average sagittal vertical axis at pre-op of 145.0 mm decreased to 51.2 mm at 1-year follow-up; however, it increased to 75.3 mm at final follow-up. CONCLUSION: PSO for correction of kyphosis following previous lumbar fusion surgery was an effective procedure without correction loss at the local osteotomy site; however, its surgical invasiveness and complication rate were high. Subsequent vertebral fracture, adjacent segment degeneration, and rod fracture contribute to deterioration of outcome that is evident at long-term follow-up.

Ultraviolet treatment restores bioactivity of titanium mesh plate degraded by contact with medical gloves.

Titanium mesh plate (Ti mesh) used for bone augmentation inadvertently comes into contact with medical gloves during trimming and bending. We tested the hypotheses that glove contact degrades the biological capability of Ti mesh and that ultraviolet treatment (UV) can restore this capability. Three groups of Ti mesh specimens were prepared: as-received (AR), after glove contact (GC), and after glove contact followed by UV treatment. The AR and GC meshes were hydrophobic, but GC mesh was more hydrophobic. AR and GC meshes had significant amounts of surface carbon, and Si content was higher for GC mesh than for AR mesh. UV mesh was hydrophilic, and carbon and silicon content values were significantly lower in this group than in the AR and GC groups. The number, alkaline phosphatase activity, and mineralization ability of attached osteoblasts were significantly lower in the GC group than in the AR group and markedly higher in the UV group than in the AR group. In conclusion, glove contact caused chemical contamination of Ti mesh, which significantly reduced its bioactivity. UV treatment restored bioactivity in contaminated Ti mesh, which outperformed even the baseline Ti mesh.

Biological and osseointegration capabilities of hierarchically (meso-/micro-/nano-scale) roughened zirconia.

PURPOSE: Zirconia is a potential alternative to titanium for dental and orthopedic implants. Here we report the biological and bone integration capabilities of a new zirconia surface with distinct morphology at the meso-, micro-, and nano-scales. METHODS: Machine-smooth and roughened zirconia disks were prepared from yttria-stabilized tetragonal zirconia polycrystal (Y-TZP), with rough zirconia created by solid-state laser sculpting. Morphology of the surfaces was analyzed by three-dimensional imaging and profiling. Rat femur-derived bone marrow cells were cultured on zirconia disks. Zirconia implants were placed in rat femurs and the strength of osseointegration was evaluated by biomechanical push-in test. RESULTS: The rough zirconia surface was characterized by meso-scale (50 µm wide, 6-8 µm deep) grooves, micro-scale (1-10 µm wide, 0.1-3 µm deep) valleys, and nano-scale (10-400 nm wide, 10-300 nm high) nodules, whereas the machined surface was flat and uniform. The average roughness (Ra) of rough zirconia was five times greater than that of machined zirconia. The expression of bone-related genes such as collagen I, osteopontin, osteocalcin, and BMP-2 was 7-25 times upregulated in osteoblasts on rough zirconia at the early stage of culture. The number of attached cells and rate of proliferation were similar between machined and rough zirconia. The strength of osseointegration for rough zirconia was twice that of machined zirconia at weeks two and four of healing, with evidence of mineralized tissue persisting around rough zirconia implants as visualized by electron microscopy and elemental analysis. CONCLUSION: This unique meso-/micro-/nano-scale rough zirconia showed a remarkable increase in osseointegration compared to machine-smooth zirconia associated with accelerated differentiation of osteoblasts. Cell attachment and proliferation were not compromised on rough zirconia unlike on rough titanium. This is the first report introducing a rough zirconia surface with distinct hierarchical morphology and providing an effective strategy to improve and develop zirconia implants.

A Comparative Study of Anterior Decompression With Fusion and Posterior Decompression With Laminoplasty for the Treatment of Cervical Spondylotic Myelopathy Patients With Large Anterior Compression of the Spinal Cord.

STUDY DESIGN: This is a retrospective observational single-center study. OBJECTIVES: To compare anterior decompression and fusion (ADF) and laminoplasty (LAMP) for the treatment of cervical spondylotic myelopathy (CSM) patients with large anterior compression in terms of clinical and radiologic outcomes. SUMMARY OF BACKGROUND DATA: We have reported that insufficient posterior decompression could be often seen after laminoplasty for CSM patients with preoperative anterior clearance of the spinal cord, defined as an interval <4 mm between the preoperative the modified K-line and anterior structure of the spinal canal at most compressive segment on sagittal T1-weighted magnetic resonance imaging. Here we conduct a study comparing ADF and LAMP for the treatment of CSM patients with such a risk factor. MATERIALS AND METHODS: Of the 221 consecutive CSM patients treated with either ADF or LAMP between 2008 and 2012 at our hospital, 79 patients in whom the interval was <4 mm with age ranged from 50 to 79 years were enrolled. Patients with myelopathy caused by single-level disk herniation, tumor or ossification of posterior longitudinal ligament, or patients with a history of cervical spine injury were excluded. The Japanese Orthopedic Association (JOA) scoring system for cervical myelopathy, recovery rate of the JOA score at the time of 2 years after surgery were investigated as clinical outcomes to compare these 2 groups. RESULTS: Demographics were almost similar between ADF and LAMP groups. The mean preoperative and postoperative JOA scores were 10.9 and 13.8 points for ADF group and 10.1 and 12.4 points for LAMP group, indicating that the recovery rate of JOA score was significantly greater in ADF group (49.6%) than that in LAMP group (38.2%; P=0.047). In LAMP group, spinal cord deformity was a significant predictive factor for unsatisfactory clinical outcome. CONCLUSION: ADF provided better surgical treatment for the patients with absence of preoperative anterior clearance of the spinal cord.

Bone Defect Regeneration by a Combination of a ß-Tricalcium Phosphate Scaffold and Bone Marrow Stromal Cells in a Non-Human Primate Model.

BACKGROUND: Reconstruction of large bone defects is a great challenge in orthopedic research. In the present study, we prepared composites of bone marrow-derived stromal cells (BMSCs) and ß-tricalcium phosphate (ß-TCP) with three novel aspects: proliferation of BMSCs with continuous dexamethasone treatment, cell loading under low pressure, and use of autologous plasma as the cell loading medium. The effectiveness of the resulting composite for large bone-defect reconstruction was tested in a non-human primate model, and the bone union capability of the regenerated bones was examined. MATERIALS AND METHODS: Primary surgery: Bone defects (5 cm long) were created in the left femurs of nine cynomolgus monkeys with resection of the periosteum (five cases) or without resection (four cases), and porous ß-TCP blocks were transplanted into the defects. Secondary surgery: Bone marrow aspirates harvested from seven of the nine monkeys were cultured with dexamethasone, and BMSCs were obtained. BMSCs were suspended in autologous plasma and introduced into a porous ß-TCP block under low-pressure conditions. The BMSC/ß-TCP composites were transplanted into bone defects created at the same sites as the primary surgery. Bone union evaluation: Five regenerated femurs were shortened by osteotomy surgery 8 to 15 months after transplantation of the ß-TCP/BMSC composites, and bone union was evaluated radiographically. RESULTS: After the primary surgery and treatment with ß-TCP alone, one of the five periosteum-resected monkeys and two of the four periosteum-preserved monkeys exhibited successful bone reconstruction. In contrast, five of the seven cases treated with the ß-TCP/MSC composite showed successful bone regeneration. In four of the five osteotomy cases, bone union was confirmed. CONCLUSION: We validated the effectiveness of a novel ß-TCP/BMSC composite for large bone defect regeneration and confirmed the bone union capability of the regenerated bone.

Dexamethasone enhances osteogenic differentiation of bone marrow- and muscle-derived stromal cells and augments ectopic bone formation induced by bone morphogenetic protein-2.

UNLABELLED: We evaluated whether dexamethasone augments the osteogenic capability of bone marrow-derived stromal cells (BMSCs) and muscle tissue-derived stromal cells (MuSCs), both of which are thought to contribute to ectopic bone formation induced by bone morphogenetic protein-2 (BMP-2), and determined the underlying mechanisms. Rat BMSCs and MuSCs were cultured in growth media with or without 10-7 M dexamethasone and then differentiated under osteogenic conditions with dexamethasone and BMP-2. The effects of dexamethasone on cell proliferation and osteogenic differentiation, and also on ectopic bone formation induced by BMP-2, were analyzed. Dexamethasone affected not only the proliferation rate but also the subpopulation composition of BMSCs and MuSCs, and subsequently augmented their osteogenic capacity during osteogenic differentiation. During osteogenic induction by BMP-2, dexamethasone also markedly affected cell proliferation in both BMSCs and MuSCs. In an in vivo ectopic bone formation model, bone formation in muscle-implanted scaffolds containing dexamethasone and BMP-2 was more than two fold higher than that in scaffolds containing BMP-2 alone. Our results suggest that dexamethasone potently enhances the osteogenic capability of BMP-2 and may thus decrease the quantity of BMP-2 required for clinical application, thereby reducing the complications caused by excessive doses of BMP-2. HIGHLIGHTS: 1. Dexamethasone induced selective proliferation of bone marrow- and muscle-derived cells with higher differentiation potential. 2. Dexamethasone enhanced the osteogenic capability of bone marrow- and muscle-derived cells by altering the subpopulation composition. 3. Dexamethasone augmented ectopic bone formation induced by bone morphogenetic protein-2.

Modified K-line in magnetic resonance imaging predicts clinical outcome in patients with nonlordotic alignment after laminoplasty for cervical spondylotic myelopathy.

STUDY DESIGN: Retrospective single-center study. OBJECTIVE: To investigate whether a preoperative index predicts clinical outcome after laminoplasty for cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: This is the first study using the modified K-line, which connects the midpoints of the spinal cord at the C2 and C7 levels on midsagittal magnetic resonance imaging, to assess the relationship between postoperative clinical outcome and anticipated degree of spinal cord shifting. METHODS: Sixty-one consecutive patients who underwent laminoplasty for the treatment of cervical spondylotic myelopathy between 2000 and 2011 at our hospital were retrospectively reviewed. The interval between the preoperative mK-line and the anterior structure of the spinal canal at each segment of the C3 to C6 levels (INTn, n = 3-6) were measured on sagittal T1-weighted magnetic resonance imaging, and the sum of the INTn (INTsum) was then calculated. The degree of posterior cord shift was defined as follows: %Csum = ΣCn; Cn = (Bn-An) × 100/An (n = 3-6; An and Bn represent the preoperative and postoperative intervals between the midpoint of the spinal cord and the anterior impingement at each segment on sagittal T1-weighted magnetic resonance imaging, respectively). In addition, we defined INTmin as the minimum interval of the INTn in each patient. All patients were divided into lordotic and nonlordotic groups on the basis of lateral neutral radiography. The Japanese Orthopaedic Association (JOA) scoring system and recovery rate of the JOA score for cervical myelopathy was evaluated as clinical outcomes. RESULTS: The recovery rate of the JOA score was 48.1%. The lordotic and nonlordotic groups contained 38 and 23 patients, respectively. Linear regression analysis revealed that INTmin was significantly correlated with the recovery rate of the patients in the nonlordotic group, whereas INTsum was not associated with recovery of the JOA score. CONCLUSION: We identified INTmin as a predictive factor for clinical outcomes in patients with nonlordotic alignment after laminoplasty. LEVEL OF EVIDENCE: 4.

Dynamic changes in spinal cord compression by cervical ossification of the posterior longitudinal ligament evaluated by kinematic computed tomography myelography.

STUDY DESIGN: A prospective clinical study. OBJECTIVE: To investigate the dynamic causative factor in the pathogenesis of myelopathy in patients with cervical ossification of the posterior longitudinal ligament (OPLL) using kinematic computed tomography (CT) myelography. SUMMARY OF BACKGROUND DATA: Kinematic CT myelography is useful for dynamically evaluating the cervical spine with high-resolution images, particularly in bony compressive lesions. However, no studies have evaluated the dynamic factors in patients with OPLL using kinematic CT myelography. METHODS: From 2008 to 2013, 51 consecutive patients with OPLL who presented with myelopathy were prospectively enrolled in this study. The patients were examined with kinematic (flexion-extension) CT myelography using a multidetector CT scanner. The range of motion at C2-C7 from flexion to extension was measured in the sagittal view. The segmental range of motion, anterior-posterior diameter and cross-sectional area (CSA) of the spinal cord were measured at the level where the spinal cord was most compressed by OPLL. RESULTS: The neurological condition of the patients evaluated by Japanese Orthopaedic Association scores were 10.8 ± 2.4 points. The mean range of motion at C2-C7 and at the most compressed segment were 23.1 ± 11.7 and 7.0 ± 4.4°, respectively. Both the anterior-posterior diameter and the CSA at the most compressed levels were significantly decreased during neck extension compared with flexion. Interestingly, the anterior-posterior diameter and the CSA were decreased during neck flexion in 13.7% (7/51) of the patients. All 7 of these patients had massive OPLL with an occupying rate 60% or more. The dynamic change rate of CSA (flexion/extension) was significantly smaller in patients with an OPLL occupying rate 60% or more compared with patients with an occupying rate less than 60%. CONCLUSION: Although spinal cord compression was increased during neck extension in most of the patients, greater levels of compression could be placed on the spinal cord during neck flexion when the patients had OPLL with a high occupying rate. LEVEL OF EVIDENCE: 4.

Modified K-line in magnetic resonance imaging predicts insufficient decompression of cervical laminoplasty.

STUDY DESIGN: A retrospective single-center study. OBJECTIVE: To clarify preoperative factors predicting unsatisfactory indirect decompression after laminoplasty in patients with cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: Many authors have shown that inadequate indirect decompression after laminoplasty can inhibit neural recovery and should be considered a complication. We previously demonstrated that residual anterior compression of the spinal cord (ACS) impaired recovery of upper extremity motor function. Although the K-line has been established as a predictive index indicating that laminoplasty is required in patients with ossification of the posterior longitudinal ligament, it remains unclear what preoperative factors can predict insufficient posterior cord decompression in patients with cervical spondylotic myelopathy. METHODS: Forty-six consecutive patients who underwent laminoplasty for the treatment of cervical spondylotic myelopathy at our hospital were reviewed. A modified K-line was defined as the line connecting the midpoints of the spinal cord at C2 and C7 on a T1-weighted sagittal magnetic resonance image. We also determined the minimum interval between the tip of local kyphosis and a line connecting the midpoint of the cord at the level of the inferior endplates of C2 and C7 (INTmin) on the midsagittal image. Data analysis involved logistic regression and receiver operating characteristic curve analysis to select the most valuable index for predicting postoperative ACS. RESULTS: Ten patients had ACS immediately after laminoplasty. Logistic regression analysis showed that INTmin was a significant predictive factor for the occurrence of postoperative ACS (odds ratio = 0.485; 95% confidence interval = 0.29-0.81; P = 0.02). Receiver operating characteristic curve analysis showed an area under the curve of 0.871. A cutoff of 4.0 mm had a sensitivity of 80% and a specificity of 80.6% for prediction of postoperative ACS. CONCLUSION: The parameter INTmin correlated with the occurrence of postoperative ACS. A cutoff point of 4.0 mm is most appropriate for alerting spine surgeons to a high likelihood of postoperative ACS.

After repeated division, bone marrow stromal cells express inhibitory factors with osteogenic capabilities, and EphA5 is a primary candidate.

The differentiation capability of human bone marrow stromal cells (hBMSCs) is thought to deteriorate over multiple doubling processes. To clarify the deterioration mechanisms, the multilineage differentiation capabilities of short- and long-term passaged BMSCs were compared. Predictably, long-term passaged BMSCs showed reduced differentiation capacities compared to short-term passaged cells. Furthermore, a non-human primate heterotopic bone formation model demonstrated that long-term passaged BMSCs have bone formation capabilities but also exert inhibitory effects on bone formation. This finding indicated that long-term passaged BMSCs express higher levels of inhibitory factors than short-term passaged BMSCs do. Co-culture assays of short- and long-term passaged BMSCs suggested that the inhibitory signals required cell-cell contact and would therefore be expressed on the cell membrane. A microarray analysis of BMSCs identified ephrin type-A receptor 5 (EphA5) as an inhibitory factor candidate. Quantitative PCR revealed that among all members of the ephrin and Eph receptor families, only the expression of EphA5 was increased by BMSC proliferation. A gene knockdown analysis using siRNAs demonstrated that knockdown of EphA5 gene expression in long-term passaged BMSCs led to an increase in ALP mRNA expression. These results indicate that EphA5 may be a negative regulator of bone formation. A better understanding of the roles of the ephrin and Eph receptor families in hBMSCs may lead to alternative approaches for manipulating hBMSC fate. In addition, this avenue of discovery may provide new therapeutic targets and quality-control markers of the osteogenic differentiation capabilities of hBMSCs.

Massive bone reconstruction with heat-treated bone graft loaded autologous bone marrow-derived stromal cells and ß-tricalcium phosphate composites in canine models.

Bone marrow-derived stromal cells (BMSCs) contain mesenchymal stem cells that are capable of forming various mesenchymal tissues. We hypothesized that BMSCs and ß-tricalcium phosphate (ß-TCP) composites would promote the remodeling of large-sized autologous devitalized bone grafts; therefore, the aim of this study was to evaluate the effects of the composites on the remodeling of autologous devitalized bone grafts. Autologous BMSCs cultured in culture medium containing dexamethasone (10(-7) M) were loaded into porous ß-TCP granules under low-pressure. Theses BMSC/TCP composites were put into the bone marrow cavity of autologous heat-treated bone (femoral diaphysis, 65-mm long, 100°C, 30 min) and put back to the harvest site. In the contralateral side, ß-TCP without BMSC were used in the same manner as the opposite side as the control. Treatment with the BMSC/TCP composites resulted in a significant increase in thickness, bone mineral density, and matured bone volume of the cortical bone at the center of the graft compared to the control. Histological analysis showed matured regenerated bone in the BMSC loaded group. These results indicate that BMSC/TCP composites facilitated bone regeneration and maturation at the graft site of large-sized devitalized bone. This method could potentially be applied for clinical use in the reconstruction of large bone defects such as those associated with bone tumors.

Porous/dense composite hydroxyapatite for anterior cervical discectomy and fusion.

STUDY DESIGN: A prospective analysis OBJECTIVE: Our aim was to investigate the efficacy of new synthetic porous/dense composite hydroxyapatite (HA) for use in anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Iliac crest bone graft (ICBG) has been traditionally used as the "gold standard" for ACDF. The significant complication rate associated with harvesting tricortical ICBG, however, has encouraged development of alternative graft substitutes. METHODS: The morphology of the porous/dense HA was observed by scanning electron microscopy (SEM), and the in vitro compressive strength of the composite HA was measured. From April 2005, 51 consecutive patients underwent 81 levels of ACDF using the composite HA with percutaneously harvested trephine bone chips. Clinical and radiological evaluation was performed during the postoperative hospital stay and at follow-up. Furthermore, the outcomes in ACDF using the composite HA were compared with those using tricortical ICBG. RESULTS: The SEM images demonstrated 100- to 300-µm pores (approximately 40% of porosity) in the porous layers of the HA. The compressive strength of the composite HA was 203.1 ± 4.1 MPa. In the clinical study, the demographic data of the patients were similar in HA and ICBG groups. The fusion rates in HA group were comparable with those in ICBG group. The cervical lordosis was enhanced postoperatively in both groups and well preserved at 2-year follow-up without significant differences between the groups. The intraoperative blood loss in HA group was significantly lesser than that in ICBG group. Donor site complications were found in 29.2% of the patients in ICBG group, whereas no donor site morbidity was found in HA group. No major collapse or fragmentation of the composite HA was found. CONCLUSION: The hybrid graft of composite HA and percutaneously harvested trephine chips seemed promising as a graft substitute for ACDF. LEVEL OF EVIDENCE: 4.