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Background Intradural extramedullary spinal metastasis is a relatively rare condition. Furthermore, there are few reports with the initial presentation being a neurological symptom from an intradural metastasis. We report a case of a patient with metastasis to the cauda equina from breast cancer found due to neurological symptoms as the initial presentation. Case presentation A 76-year-old Japanese woman who was previously healthy presented to our hospital with bilateral severe buttock and lower extremity pain without any history of injury. A solitary intradural cauda equina mass was found by magnetic resonance imaging at the L2/3 level, and we suspected a schwannoma initially. The patient hoped to undergo surgery due to the severe pain. However, the chest computed tomographic scan obtained to assess the patient’s general status showed the suspected breast cancer of the left side and a lung metastasis. Hence, we considered the possibility of cauda equina tumor metastatic from the breast cancer. We performed an L1–3 laminectomy and tumor extirpation. The pathology revealed adenocarcinoma. After surgery, she had relief from pain, and her status remained satisfactory until she died 9 months after surgery. Conclusions It is difficult to clarify whether the cauda equina tumor is benign or malignant based only on Magnetic resonance imaging findings. Clinicians should consider the possibility of metastasis when planning the surgery for intradural cauda equina tumor extirpation.

Background Mayfield skull clamps are widely used and indispensable in current neurosurgery. Complications such as skull fractures or intracranial hematoma from using a Mayfield skull clamp have largely been reported in the pediatric population, are likely related to the relative thinness of the skull, such as in patients with hydrocephalus, and are extremely rare in adults. Here, we report a case of skull fracture and epidural hematoma caused by a Mayfield skull clamp used for posterior decompression surgery in an adult patient with chronic hemodialysis. Case presentation A 67-year-old Asian male patient with a history of dialysis-dependent chronic renal failure over 36 years suffered from severe cervical myelopathy. Neurological examination and radiographic images revealed cervical spondylotic myelopathy due to dialysis-related spondyloarthropathy. Laminoplasty was planned on patient consent. A Mayfield skull clamp was applied with the patient supine. Torque was applied to the screws with gentle care, but there was no resistance and it was not easy to reach the standard 60 lb (267 N) to 80 lb (356 N). Because a skull fracture was suspected, we canceled the surgery. Emergency head computed tomography showed depressed skull fractures underlying the single-pin sites with an associated epidural hematoma. The fractures and epidural hematoma were treated conservatively, and spontaneous resolution of the hematoma was confirmed. Cervical laminoplasty was performed successfully using a mask-type head holder on the subsequent day. Conclusions As a precaution for fractures and epidural hematoma in neurosurgical patients with bone fragility or a thin skull, use of a mask-type fixing device or halo ring is recommended.

We report two cases of restenosis caused by the progression of thickness of ossification of the posterior longitudinal ligament (OPLL) seven and more years after laminoplasty, resulting in neurological deterioration needed for revision anterior decompressive surgeries. Neurological recovery after revision anterior excision of OPLL was poor. In both cases, the patients had progressive OPLL, with a non-ossified segment of the ossification foci, in common. After laminoplasty, they also both exhibited osseous fusion of the elevated laminae, but there was discontinuity at the interlaminar space at the peak level of OPLL. Discontinuity of the osseous fusion in the elevated laminae might cause mechanical stress increases at the non-ossified segment of the OPLL and could lead to the progression of OPLL. The present cases showed that long-term progression of OPLL can induce neurological deterioration even after sufficient posterior decompression by laminoplasty. Therefore, when considering risk factors that may be predictive of the progression of OPLL after laminoplasty, it is important to perform strict follow-up examination to check for progression to reduce the risk of myelopathy symptoms that are indicative of neurological deterioration. Keywords: Ossification of the posterior longitudinal ligament, Laminoplasty, Cervical spine, revision surgery

We enrolled 100 patients who underwent preoperative CT angiography before cervical spine instrumentation and investigated the morphology of the C2 pedicle from the perspective of pedicle screw (PS) trajectory using volume rendering and multiplanar reconstruction. The narrowest portion of the pedicle was identified as the pedicle isthmus. Safe C2 PS insertion was regarded to be not feasible when the height of the medullary cavity of the pedicle isthmus and/or width of the medullary cavity of the pedicle isthmus was ⩽4mm. Forty-five (22.5%) pedicles were ⩽4mm in width, and safe insertion of a PS was determined to be not feasible. Among these, seven pedicles were ⩽4mm in both height and width. The remaining 38 pedicles were ⩽4mm in width with heights >4mm. There was no pedicle with a width >4mm and height

Spinal cord injury (SCI) can cause neuropathic pain (NeP), often reducing a patient's quality of life. We recently reported that granulocyte colony-stimulating factor (G-CSF) could attenuate NeP in several SCI patients. However, the mechanism of action underlying G-CSF-mediated attenuation of SCI-NeP remains to be elucidated. The purpose of the present study was to elucidate the therapeutic effect and mechanism of action of granulocyte colony-stimulating factor for SCI-induced NeP. T9 level contusive SCI was introduced to adult male Sprague Dawley rats. Three weeks after injury, rats received intraperitoneal recombinant human G-CSF (15.0 μg/kg) for 5 days. Mechanical allodynia was assessed using von Frey filaments. Immunohistochemistry and western blot analysis were performed in spinal cord lumbar enlargement samples. Testing with von Frey filaments showed significant increase in the paw withdrawal threshold in the G-CSF group compared with the vehicle group 4 weeks, 5 weeks, 6 weeks and 7 weeks after injury. Immunohistochemistry for CD11b (clone OX-42) revealed that the number of OX-42-positive activated microglia was significantly smaller in the G-CSF group than that in the vehicle rats. Western blot analysis indicated that phosphorylated-p38 mitogen-activated protein kinase (p38MAPK) and interleukin-1β expression in spinal cord lumbar enlargement were attenuated in the G-CSF-treated rats compared with that in the vehicle-treated rats. The present results demonstrate a therapeutic effect of G-CSF treatment for SCI-induced NeP, possibly through the inhibition of microglial activation and the suppression of p38MAPK phosphorylation and the upregulation of interleukin-1β.

We performed a phase I/IIa clinical trial and confirmed the safety and feasibility of granulocyte colony-stimulating factor (G-CSF) as neuroprotective therapy in patients with acute spinal cord injury (SCI). In this study, we retrospectively analyzed the clinical outcome in SCI patients treated with G-CSF and compared these results to a historical cohort of SCI patients treated with high-dose methylprednisolone sodium succinate (MPSS). In the G-CSF group (n = 28), patients were treated from August 2009 to July 2012 within 48 h of the injury, and G-CSF (10 μg/kg/day) was administered intravenously for five consecutive days. In the MPSS group (n = 34), patients underwent high-dose MPSS therapy from August 2003 to July 2005 following the NASCIS II protocol. We evaluated the ASIA motor score and the AIS grade elevation between the time of treatment and 3-month follow-up and adverse events. The ΔASIA motor score was significantly higher in the G-CSF group than in the MPSS group (p

Study design An open-labeled multicenter prospective nonrandomized controlled clinical trial. Objective To confirm the feasibility of using granulocyte colony-stimulating factor (G-CSF) for treatment of acute spinal cord injury (SCI). Summary of background data We previously reported that G-CSF promotes functional recovery after compression-induced SCI in mice. On the basis of these findings, we conducted a multicenter prospective controlled clinical trial to assess the feasibility of G-CSF therapy for patients with acute SCI. Methods The trial ran from August 2009 to March 2011, and included 41 patients with SCI treated within 48 hours of onset. Informed consent was obtained from all patients. After providing consent, patients were divided into 2 groups. In the G-CSF group (17 patients), G-CSF (10 μg/kg/d) was intravenously administered for 5 consecutive days, and in the control group (24 patients), patients were similarly treated except for the G-CSF administration. We evaluated motor and sensory functions using the American Spinal Cord Injury Association score and American Spinal Cord Injury Association impairment scale at 1 week, 3 months, 6 months, and 1 year after onset. Results Only 2 patients did not experience American Spinal Cord Injury Association impairment scale improvement in the G-CSF group. In contrast, 15 patients in the control group did not experience American Spinal Cord Injury Association impairment scale improvement. In the analysis of increased American Spinal Cord Injury Association motor score, a significant increase in G-CSF group was detected from 1 week after the administration compared with the control group. After that, some spontaneous increase of motor score was detected in control group, but the significant increase in G-CSF group was maintained until 1 year of follow-up. Conclusion Despite the limitation that patient selection was not randomized, the present results suggest the possibility that G-CSF administration has beneficial effects on neurological recovery in patients with acute SCI. Level of evidence 3.

Object Clinical use of autologous induced pluripotent stem cells (iPSCs) could circumvent immune rejection and bioethical issues associated with embryonic stem cells. Spinal cord injury (SCI) is a devastating trauma with long-lasting disability, and current therapeutic approaches are not satisfactory. In the present study, the authors used the neural stem sphere (NSS) method to differentiate iPSCs into astrocytes, which were evaluated after their transplantation into injured rat spinal cords. Methods Induced pluripotent stem cell–derived astrocytes were differentiated using the NSS method and injected 3 and 7 days after spinal contusion–based SCI. Control rats were injected with DMEM in the same manner. Locomotor recovery was assessed for 8 weeks, and sensory and locomotion tests were evaluated at 8 weeks. Immunohistological parameters were then assessed. Results Transplant recipients lived for 8 weeks without tumor formation. Transplanted cells stretched their processes along the longitudinal axis, but they did not merge with the processes of host GFAP-positive astrocytes. Locomotion was assessed in 3 ways, but none of the tests detected statistically significant improvements compared with DMEM-treated control rats after 8 weeks. Rather, iPSC transplantation caused even greater sensitivity to mechanical stimulus than DMEM treatment. Conclusions Astrocytes can be generated by serum treatment of NSS-generated cells derived from iPSCs. However, transplantation of such cells is poorly suited for repairing SCI.

Object Granulocyte colony-stimulating factor (G-CSF) has neuroprotective effects on the CNS. The authors have previously demonstrated that G-CSF also exerts neuroprotective effects in experimental spinal cord injury (SCI) by enhancing migration of bone marrow–derived cells into the damaged spinal cord, increasing glial differentiation of bone marrow–derived cells, enhancing antiapoptotic effects on both neurons and oligodendrocytes, and by reducing demyelination and expression of inflammatory cytokines. Because the degree of angiogenesis in the subacute phase after SCI correlates with regenerative responses, it is possible that G-CSF's neuroprotective effects after SCI are due to enhancement of angiogenesis. The aim of this study was to assess the effects of G-CSF on the vascular system after SCI. Methods A contusive SCI rat model was used and the animals were randomly allocated to either a G-CSF–treated group or a control group. Integrity of the blood–spinal cord barrier was evaluated by measuring the degree of edema in the cord and the volume of extravasation. For histological evaluation, cryosections were immunostained with anti–von Willebrand factor and the number of vessels was counted to assess revascularization. Real-time reverse transcriptase polymerase chain reaction was performed to assess expression of angiogenic cytokines, and recovery of motor function was assessed with function tests. Results In the G-CSF–treated rats, the total number of vessels with a diameter > 20 μm was significantly larger and expression of angiogenic cytokines was significantly higher than those in the control group. The G-CSF–treated group showed significantly greater recovery of hindlimb function than the control group. Conclusions These results suggest that G-CSF exerts neuroprotective effects via promotion of angiogenesis after SCI.

Context We report the autopsy of a 65-year-old woman who underwent a C3–C7 laminoplasty 4 years after the diagnosis of cervical spondylotic myelopathy (CSM). Her sensory disturbance, spasticity, and vesicorectal disturbance, which corresponded to long tract sign, had improved after surgery. Findings Cross sections at the C4–C5 level showed a triangular shape because of atrophied ventral gray matter. Moreover, despite the scarce glial scar formation around the cystic cavity, regeneration of gray matter had not occurred. In the white matter, the posterior and lateral funiculi were shrunken including three to four segments. Conclusion Pathological change of white matter did not coincide with relief of clinical symptoms in this case. These findings indicate that it may be better to operate earlier in cases of CSM, because delay may lead to irreversible histological change.

The aim of this study was to evaluate whether transplantation of human bone marrow stromal cell-derived Schwann cells (hBMSC-SC) promotes functional recovery after contusive spinal cord injury of adult rats. Human bone marrow stromal cells (hBMSC) were cultured from bone marrow of adult human patients and induced into Schwann cells (hBMSC-SC) in vitro. Schwann cell phenotype was confirmed by immunocytochemistry. Growth factors secreted from hBMSC-SC were detected using cytokine antibody array. Immunosuppressed rats were laminectomized and their spinal cords were contused using NYU impactor (10 g, 25 mm). Nine days after injury, a mixture of Matrigel and hBMSC-SC (hBMSC-SC group) was injected into the lesioned site. Five weeks after transplantation, cresyl-violet staining revealed that the area of cystic cavity was smaller in the hBMSC-SC group than that in the control group. Immunohistochemistry revealed that the number of anti-growth-associated protein-43-positive nerve fibers was significantly larger in the hBMSC-SC group than that in the control group. At the same time, the number of tyrosine hydroxylase- or serotonin-positive fibers was significantly larger at the lesion epicenter and caudal level in the hBMSC-SC group than that in the control group. In electron microscopy, formation of peripheral-type myelin was recognized near the lesion epicenter in the hBMSC-SC group. Hind limb function recovered significantly in the hBMSC-SC group compared with the control group. In conclusion, the functions of hBMSC-SC are comparable to original Schwann cells in rat spinal cord injury models, and are thus potentially useful treatments for patients with spinal cord injury.

Glial cells, including astrocytes and macrophages/microglia, are thought to modulate pathological states following spinal cord injury (SCI). In the present study, we evaluated the therapeutic effects of interferon-γ (IFN-γ), which is one of the cytokines regulating glial function, in a mouse contusive SCI model. We found that intraperitoneal injection of IFN-γ significantly facilitated locomotor improvement following SCI. Immunohistochemistry demonstrated that IFN-γ decreased the accumulation of chondroitin sulfate proteoglycans (CSPGs), which are critical axon outgrowth inhibitors produced by reactive astrocytes in the injured central nervous system (CNS). Quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting demonstrated that neurocan, one of several CSPGs, was reduced in the spinal cords of IFN-γ-treated mice compared to vehicle-treated mice. Consistently, IFN-γ inhibited the production of neurocan from activated astrocytes in vitro. In addition, IFN-γ treatment enhanced the number of serotonin-positive nerve fibers and myelinated nerve fibers around the lesion epicenter. We also found that glial cell line-derived neurotrophic factor (GDNF) and insulin-like growth factor-1 (IGF-1) were upregulated post-SCI following IFN-γ treatment. Our results indicate that IFN-γ exhibits therapeutic effects in mouse contusive SCI, presumably by reducing CSPG expression from reactive astrocytes and increasing the expression of neurotrophic factors.

We evaluated the feasibility and reliability of open source Digital Imaging and COmmunication in Medicine (DICOM) imaging software, OsiriX (Antoine Rosset, 2003-2009), in spine surgery. CT data were used and processed with OsiriX and with commercial software for comparison. Images were reconstructed and compared in volume rendering (VR) and multi-planar reconstruction (MPR) mode. When all images were compared, the three-dimensional (3D) reconstructed images from both software packages showed considerable consistency in VR mode. Measurements in MPR mode also showed similar values with no statistically significant difference. These results demonstrate that OsiriX has approximately equivalent values to commercial software and provides reliable preoperative 3D information for the surgical field. In addition, any clinician, can obtain information using OsiriX at any time. Thus, OsiriX is a helpful tool in preoperative planning for spine surgery.

Postoperative C5 palsy is a common complication after cervical spine decompression surgery. However, the incidence, prognosis, and etiology of C5 palsy after anterior decompression with spinal fusion (ASF) have not yet been fully established. In the present study, we analyzed the clinical and radiological characteristics of patients who developed C5 palsy after ASF for cervical degenerative diseases. The cases of 199 consecutive patients who underwent ASF were analyzed to clarify the incidence of postoperative C5 palsy. We also evaluated the onset and prognosis of C5 palsy. The presence of high signal changes (HSCs) in the spinal cord was analyzed using T2-weighted magnetic resonance images. C5 palsy occurred in 17 patients (8.5%), and in 15 of them, the palsy developed after ASF of 3 or more levels. Among ten patients who had a manual muscle test (MMT) grade ≤2 at the onset, five patients showed incomplete or no recovery. Sixteen of the 17 C5 palsy patients presented neck and shoulder pain prior to the onset of muscle weakness. In the ten patients with a MMT grade ≤2 at the onset, nine patients showed HSCs at the C3-C4 and C4-C5 levels. The present findings demonstrate that, in most patients with severe C5 palsy after ASF, pre-existing asymptomatic damage of the anterior horn cells at C3-C4 and C4-C5 levels may participate in the development of motor weakness in combination with the nerve root lesions that occur subsequent to ASF. Thus, when patients with spinal cord lesions at C3-C4 and C4-C5 levels undergo multilevel ASF, we should be alert to the possible occurrence of postoperative C5 palsy.

Study design Case report. Objective To describe the usefulness of simulated surgery for evaluation of a patient with neurofibromatosis type-1 (NF-1) who had severe cervicothoracic kyphoscoliosis and an anomalous vertebral artery (VA). Summary of background data Several surgical procedures have been used in the treatment of cervicothoracic kyphoscoliosis associated with myelopathy in patients with NF-1. However, to our knowledge, there has been no report that describes a surgical procedure for NF-1 patients with anomalous VA at the cervical spine. Methods A 45-year-old man with NF-1 developed cervical myelopathy. Preoperative examinations revealed severe cervicothoracic kyphoscoliosis, dystrophic changes of the cervical vertebrae, and the anomalous course of a VA and VA aneurysms. To assist in the preoperative planning and intraoperative navigation, we created 3-dimensional (3D) full-scale models of the patient's spine. Using a model, we performed a simulation of the planned surgery for spinal cord decompression with spinal fusion through both anterior and posterior approaches. Results Through the simulation, we could evaluate the risk of VA injury at the process of corpectomy, and altered the surgical procedure for the spinal cord decompression with spinal fusion from a posterior approach and a bone graft alone from an anterior approach. We accomplished the surgery successfully without any neurovascular complications. After surgery, the patient experienced relief from myelopathy. Conclusion Preoperative surgical simulation using a 3D full-scale model was useful for improving the accuracy and safety of the surgery for cervicothoracic kyphoscoliosis with NF-1.

We studied 27 patients with cervical ossification of the posterior longitudinal ligament (OPLL) but no clinical symptoms of myelopathy. We investigated the occupation ratio of the spinal canal by OPLL with cervical radiographs, assessed the morphological types of OPLL, and measured the segmental range of motion (ROM) at the level of maximum cord compression on flexion and extension radiographs. Patients were classified as having continuous-type OPLL (17 patients), mixed-type OPLL (seven patients), or segmental-type OPLL (three patients). The segmental ROM was negatively correlated with the OPLL occupation ratio (r=-0.49, p

We evaluated the clinical results of posterior decompression with instrumented fusion (PDF) for thoracic myelopathy due to ossification of the posterior longitudinal ligament (OPLL). A total of 24 patients underwent PDF, and their surgical outcomes were evaluated by the Japanese Orthopaedic Association (JOA) scores (0–11 points) and by recovery rates calculated at 3, 6, 9 and 12 months after surgery and at a mean final follow-up of 4 years and 5 months. The mean JOA score before surgery was 3.7 points. Although transient paralysis occurred immediately after surgery in one patient (3.8%), all patients showed neurological recovery at the final follow-up with a mean JOA score of 8.0 points and a mean recovery rate of 58.1%. The mean recovery rate at 3, 6, 9 and 12 months after surgery was 36.7, 48.8, 54.0 and 56.8%, respectively. The median time point that the JOA score reached its peak value was 9 months after surgery. No patient chose additional anterior decompression surgery via thoracotomy. The present findings demonstrate that despite persistent anterior impingement of the spinal cord by residual OPLL, PDF can result in considerable neurological recovery with a low risk of postoperative paralysis. Since neurological recovery progresses slowly after PDF, we suggest that additional anterior decompression surgery is not desirable during the early stage of recovery.

For preoperative evaluation of the vertebral artery (VA) at the craniovertebral junction, 3-dimensional (3-D) computed tomography (CT) angiography can simultaneously and precisely depict the location of the VA and the circumferential osseous tissues. However, this procedure has the risk of contrast-induced nephropathy, especially when patients have pre-existing renal impairment. We report the case of a 73-year-old woman with rheumatoid arthritis and concomitant chronic renal failure in whom severe myelopathy developed due to atlantoaxial vertical subluxation and subaxial subluxation. We planned to perform C1 laminectomy and C3-C7 laminoplasty, but to avoid the risk of intraoperative VA injury, we applied a fusion image technique of 3-D magnetic resonance (MR) angiography and co-registered 3-D CT that allowed for virtual assessment preoperatively of the VA courses, instead of 3-D CT angiography. Through the 3-D hybrid MR angiography-CT images, we could predict, in detail, the VA courses and the surrounding bony structures. At surgery, we found that the locations of the VAs were identical to that predicted on the preoperative image fusion analysis. We conclude that our image fusion techniques possess accurate diagnostic value for detecting arterial course, and could be applicable for patients in whom administration of contrast media should be avoided due to specific conditions, such as drug allergy and chronic renal failure.

Study design Gene expression and protein localization of osteopontin (OPN) in spinal hyperostosis of the twy mouse by means of in situ hybridization, immunohistochemistry, and Northern blot analysis. Objective To verify the involvement of OPN in spinal hyperostosis in the twy mouse and elucidate its ossification pattern at molecular levels. Summary of background data OPN is a molecule that consistently colocalizes with ectopic calcification in human pathologic conditions. The twy mouse, which shows ectopic calcification of the spinal ligament resulting in hind limb paralysis, is considered to be a model for human ossification of the posterior longitudinal ligament of the spine. Methods Twenty-eight each of age-matched twy, heterozygote, and wild-type mice were killed at 2, 4, 8, 12, and 16 weeks old and subject to histologic and/or molecular analyses. Sections were hybridized with RNA probes for OPN and also stained with anti-OPN antibodies. Total cellular RNA was extracted from the cervicothoracic spine of each genotype at 2- and 16-week-old, and gene expression for OPN and COL10A1 was quantified by Northern blot analysis. Results Enhanced expression of OPN mRNA was observed in spinal hyperostotic lesions of the twy mouse, specifically in cells of the spinal ligament and chondrogenic cells in the outer layer of the anulus fibrosus. These trends were also confirmed by immunohistochemical analyses. Northern blot analysis showed that a considerable amount of OPN transcripts was detected in all genotypes at 2 weeks old, but the robust expression of OPN mRNA was maintained only in twy mice at 16 weeks old. COL10A1 transcripts were hardly detected regardless of the genotype at 16 weeks old. Conclusion OPN was overexpressed in the hyperostotic spinal lesions of twy mice, and the hyperostosis was induced mainly by ectopic ossification of the spinal ligament. Because OPN is considered to be an inhibitor of calcification, further studies will be necessary to verify whether OPN overexpressed in the twy mouse is functional.

The spontaneous dominant mouse mutant, Elbow knee synostosis (Eks), shows elbow and knee joint synosotsis, and premature fusion of cranial sutures. Here we identify a missense mutation in the Fgf9 gene that is responsible for the Eks mutation. Through investigation of the pathogenic mechanisms of joint and suture synostosis in Eks mice, we identify a key molecular mechanism that regulates FGF9 signaling in developing tissues. We show that the Eks mutation prevents homodimerization of the FGF9 protein and that monomeric FGF9 binds to heparin with a lower affinity than dimeric FGF9. These biochemical defects result in increased diffusion of the altered FGF9 protein (FGF9(Eks)) through developing tissues, leading to ectopic FGF9 signaling and repression of joint and suture development. We propose a mechanism in which the range of FGF9 signaling in developing tissues is limited by its ability to homodimerize and its affinity for extracellular matrix heparan sulfate proteoglycans.

Macrophage migration inhibitory factor (MIF) is a multipotential protein that acts as a proinflammatory cytokine, a pituitary hormone, and a cell proliferation and migration factor. The objective of this study was to elucidate the role of MIF in spinal cord injury (SCI) using female MIF knockout (KO) mice. Mouse spinal cord compression injury was produced by application of a static load (T8 level, 20 g, 5 min). We analyzed the motor function of the hind limbs and performed histological examinations. Hind-limb function recovered significantly in the KO mice starting from three weeks after injury. Cresyl-violet staining revealed that the number of surviving neurons in the KO mice was significantly larger than that of WT mice six weeks after injury. Immunohistochemical analysis revealed that the number of NeuN/caspase-3-active, double-positive, apoptotic neurons in the KO mice was significantly smaller than that of the WT mice 24 and 72 h after SCI. These results were related to in-vitro studies showing increased resistance of cerebellar granular neurons from MIF-KO animals to glutamate neurotoxicity. These results suggest that MIF existence hinders neuronal survival after SCI. Suppression of MIF may attenuate detrimental secondary molecular responses of the injured spinal cord.

Object The authors previously reported that Schwann cells (SCs) could be derived from bone marrow stromal cells (BMSCs) in vitro and that they promoted axonal regeneration of completely transected rat spinal cords in vivo. The aim of the present study is to evaluate the efficacy of transplanted BMSC-derived SCs (BMSC-SCs) in a rat model of spinal cord contusion, which is relevant to clinical spinal cord injury. Methods Bone marrow stromal cells were cultured as plastic-adherent cells from the bone marrow of GFPtransgenic rats. The BMSC-SCs were derived from BMSCs in vitro with sequential treatment using beta-mercaptoethanol, all-trans-retinoic acid, forskolin, basic fibroblast growth factor, platelet derived–growth factor, and heregulin. Schwann cells were cultured from the sciatic nerve of neonatal, GFP-transgenic rats. Immunocytochemical analysis and the reverse transcriptase–polymerase chain reaction were performed to characterize the BMSC-SCs. For transplantation, contusions with the New York University impactor were delivered at T-9 in 10- to 11-week-old male Wistar rats. Four groups of rats received injections at the injury site 7 days postinjury: the first received BMSCSCs and matrigel, a second received peripheral SCs and matrigel, a third group received BMSCs and matrigel, and a fourth group received matrigel alone. Histological and immunohistochemical studies, electron microscopy, and functional assessments were performed to evaluate the therapeutic effects of BMSC-SC transplantation. Results Immunohistochemical analysis and reverse transcriptase–polymerase chain reaction revealed that BMSC-SCs have characteristics similar to SCs not only in their morphological characteristics but also in their immunocytochemical phenotype and genotype. Histological examination revealed that the area of the cystic cavity was significantly reduced in the BMSC-SC and SC groups compared with the control rats. Immunohistochemical analysis showed that transplanted BMSCs, BMSC-SCs, and SCs all maintained their original phenotypes. The BMSC-SC and SC groups had a larger number of tyrosine hydroxilase–positive fibers than the control group, and the BMSC-SC group had more serotonin-positive fibers than the BMSC or control group. The BMSC-SC group showed significantly better hindlimb functional recovery than in the BMSC and control group. Electron microscopy revealed that transplanted BMSC-SCs existed in association with the host axons. Conclusions Based on their findings, the authors concluded that BMSC-SC transplantation reduces the size of the cystic cavity, promotes axonal regeneration and sparing, results in hindlimb functional recovery, and can be a useful tool for spinal cord injury as a substitute for SCs.

Background. Prevention of graft dislodgement in multilevel cervical corpectomy and fusion has been an unresolved problem. Anterior plate fixation has a significant failure rate. External support with a halo-vest is uncomfortable for patients. In the present study, we report a new surgical technique of anterior pedicle screw (APS) fixation for multilevel cervical corpectomy and spinal fusion, and describe the safety and utility of the system. Method. After cervical corpectomy, the pedicles on the right side were visualised under oblique fluoroscopy. Guide wires were inserted into the pedicles from the inner wall of the excavated vertebral body until they were hidden in the pedicles. After a fibula autograft was placed, the graft was penetrated in the reverse direction by the guide wires. After drilling and tapping, cannulated screws were inserted into the pedicles through the grafted fibula along the guide wires. Findings. In 9 patients with cervical myelopathy, the surgery was accomplished with a fibula autograft using APS fixation. A total of 22 APSs were inserted, and 21 screws were placed precisely in the pedicles. There were no neurovascular complications. Patients were allowed to ambulate without a halo-vest on the second day after the surgery. Post-operatively, no dislodgement of the grated fibula occurred, and all patients improved neurologically. Conclusions. The insertion of APSs is feasible and safe. APS fixation enables us to obtain rigid fixation anteriorly, and we propose that APS fixation is an attractive option for multilevel cervical corpectomy and fusion.

Introduction We determined the incidence of vertebral artery (VA) anomalies at the craniovertebral junction (CVJ) in patients with Down syndrome, and characterized the VA anomalies. Methods The course of the VA in 46 consecutive patients who were due to undergo posterior arthrodesis surgery at the CVJ were evaluated by three-dimensional CT angiography (3DCTA). Included were five patients with Down syndrome who suffered from myelopathy due to atlantoaxial subluxation. All five patients with Down syndrome also had a simultaneous congenital skeletal anomaly, either os odontoideum or ossiculum terminale. Results Of the five patients with Down syndrome, three had VA anomalies at the CVJ, two had fenestration and one had a persistent first intersegmental artery. Of the other 41 patients without Down syndrome, five had VA anomalies at the CVJ. The incidence of VA anomalies at the CVJ was much higher in patients with Down syndrome than in those without Down syndrome. Conclusion In planning surgery in patients with Down syndrome with symptomatic atlantoaxial subluxation and a congenital skeletal anomaly at the CVJ, we should consider the possible presence of VA anomalies. Preoperative 3DCTA allows us to precisely identify an anomalous VA and evaluate the possible risk of intraoperative VA injury in advance.

Granulocyte colony-stimulating factor (G-CSF) is a protein that stimulates differentiation, proliferation, and survival of granulocytic lineage cells. Recently, a neuroprotective effect of G-CSF was reported in a model of cerebral infarction. The aim of the present study was to elucidate the potential therapeutic effect of G-CSF for spinal cord injury (SCI) in mice. We found that G-CSF is neuroprotective against glutamate-induced cell death of cerebellar granule neurons in vitro. Moreover, we used a mouse model of compressive SCI to examine the neuroprotective potential of G-CSF in vivo. Histologic assessment with cresyl violet staining revealed that the number of surviving neurons in the injured spinal cord was significantly increased in G-CSF-treated mice. Immunohistochemistry for neuronal apoptosis revealed that G-CSF suppressed neuronal apoptosis after SCI. Moreover, administration of G-CSF promoted hindlimb functional recovery. Examination of signaling pathways downstream of the G-CSF receptor suggests that G-CSF might promote functional recovery by inhibiting neuronal apoptosis after SCI. G-CSF is currently used in the clinic for hematopoietic stimulation, and its ongoing clinical trial for brain infarction makes it an appealing molecule that could be rapidly placed into trials for patients with acute SCI.

✓ The authors report the case of a 62-year-old woman who suffered an accidental fall and complained of severe neck pain and right C-7 radiculopathy. A right C6–7 facet fracture–subluxation was diagnosed. Bone fragments impinged on the right C-7 nerve root at the neural foramen. The bilateral vertebral arteries (VAs) ascended at the anterior aspect of C-6 and C-5 and entered the transverse foramen at the C-4 level. Based on findings of anomalous VAs, the authors applied a pedicle screw (PS)/rod system to effect surgical correction of the deformity. Intraoperatively, they successfully performed reduction of the subluxation, decompression of the impinged nerve root, and minimum single-segment fusion involving the placement of a PS/rod system. After surgery, the patient's neurological deficit dramatically improved and spinal fusion was completed without any loss of deformity correction. Prior to surgery for cervical injuries, the possible presence of an abnormal VA course should be considered. Preoperative detection of anomalous VAs will affect decisions on the appropriate corrective surgery option in cases of cervical spine injuries.

The aim of the present study was to elucidate the effects of granulocyte colony-stimulating factor (G-CSF)-mediated mobilization of bone marrow-derived stem cells on the injured spinal cord. Bone marrow cells of green fluorescent protein (GFP) transgenic mice were transplanted into lethally irradiated C57BL/6 mice. Four weeks after bone marrow transplantation, spinal cord injury was produced by a static load (20 g, 5 min) at T8 level. G-CSF (200 microg/kg/day) was injected subcutaneously for 5 days. Immunohistochemistry for GFP and cell lineage markers was performed to evaluate G-CSF-mediated mobilization of bone marrow-derived cells into injured spinal cord. Hind limb locomotor recovery was assessed for 6 weeks. Immunohistochemistry revealed that G-CSF increased the number of GFP-positive cells in injured spinal cord, indicating that bone marrow-derived cells were mobilized and migrated into injured spinal cord. The numbers of double positive cells for GFP and glial markers were larger in the G-CSF treated mice than in the control mice. Luxol Fast Blue staining revealed that G-CSF promoted white matter sparing. G-CSF treated mice showed significant recovery of hind limb function compared to that of the control mice. In conclusion, G-CSF showed efficacy for spinal cord injury treatment through mobilization of bone marrow-derived cells.

Cerebellar hemorrhage remote from the site of surgery can complicate neurosurgical procedures. However, this complication after lumbar surgery is rare. Furthermore, hemorrhage in both the cerebellum and the temporal lobe after spine surgery is rarer still. Herein we present a case of remote hemorrhage in both the cerebellum and the temporal lobe after lumbar spine surgery. A 79-year-old woman with a Schwannoma at the L4 level presented with low back and bilateral leg pain refractory to conservative management. Surgery was undertaken to remove the Schwannoma and to perform posterior fusion. During the surgery, the dura mater was removed in order to excise the Schwannoma. Reconstruction of the dura mater was performed; postoperatively the patient had a cerebrospinal fluid leak. Five days after surgery, clouding of consciousness started gradually, and hemorrhage in the cerebellum and the temporal lobe was revealed by computed tomography. Emergent evacuation of the hemorrhage was performed and the patient recovered consciousness after the surgery. Leakage of cerebrospinal fluid may have induced this hemorrhage. While rare, intracranial hemorrhage after spine surgery can occur, sometimes requiring emergent intervention.

Granulocyte colony-stimulating factor (G-CSF) mobilizes peripheral blood stem cells (PBSCs) derived from bone marrow. We hypothesized that intraspinal transplantation of PBSCs mobilized by G-CSF could promote functional recovery after spinal cord injury. Spinal cords of adult nonobese diabetes/severe immunodeficiency mice were injured using an Infinite Horizon impactor (60 kdyn). One week after the injury, 3.0 μl of G-CSF-mobilized human mononuclear cells (MNCs; 0.5 × 105/μl), G-CSF-mobilized human CD34-positive PBSCs (CD34; 0.5 × 105/μl), or normal saline was injected to the lesion epicenter. We performed immunohistochemistry. Locomotor recovery was assessed by Basso Mouse Scale. The number of transplanted human cells decreased according to the time course. The CD31-positive area was significantly larger in the MNC and CD34 groups compared with the vehicle group. The number of serotonin-positive fibers was significantly larger in the MNC and CD34 groups than in the vehicle group. Immunohistochemistry revealed that the number of apoptotic oligodendrocytes was significantly smaller in cell-transplanted groups, and the areas of demyelination in the MNC- and CD34-transplanted mice were smaller than that in the vehicle group, indicating that cell transplantation suppressed oligodendrocyte apoptosis and demyelination. Both the MNC and CD34 groups showed significantly better hindlimb functional recovery compared with the vehicle group. There was no significant difference between the two types of transplanted cells. Intraspinal transplantation of G-CSF-mobilized MNCs or CD34-positive cells promoted angiogenesis, serotonergic fiber regeneration/sparing, and preservation of myelin, resulting in improved hindlimb function after spinal cord injury in comparison with vehicle-treated control mice. Transplantation of G-CSF-mobilized PBSCs has advantages for treatment of spinal cord injury in the ethical and immunological viewpoints, although further exploration is needed to move forward to clinical application.

Background Symptom of herpes zoster is sometimes difficult to distinguish from sciatica induced by spinal diseases, including lumbar disc herniation and spinal canal stenosis. Here we report a case of sciatica mimicking lumbar canal stenosis. Case presentation A 74-year-old Chinese male patient visited our hospital for left-sided sciatic pain upon standing or walking for 5 min of approximately 1 month’s duration. At the first visit to our hospital, there were no skin lesions. A magnetic resonance imaging showed spinal canal stenosis between the 4th and 5th lumbar spine. Thus, we diagnosed the patient with sciatica induced by spinal canal stenosis. We considered decompression surgery for the stenosis of 4th and 5th lumbar spine because conservative therapy failed to relieve the patient’s symptom. At that time, the patient complained of a skin rash involving his left foot for several days. A vesicular rash and erythema were observed on the dorsal and plantar surfaces of the great toe and lateral malleolus. The patient was diagnosed with herpes zoster in the left 5th lumbar spinal nerve area based on clinical findings, including the characteristics of the pain and vesicular rash and erythema in the 5th lumbar spinal dermatome. The patient was treated with famciclovir (1,500 mg/day) and non-steroidal anti-inflammatory drugs. After 1 week of medication, the skin rash resolved and pain relief was obtained. Conclusion In conclusion, spinal surgeons should keep in mind herpes zoster infection as one of the possible differential diagnoses of sciatica, even if there is no typical skin rash. Electronic supplementary material The online version of this article (doi:10.1186/s13104-015-1272-z) contains supplementary material, which is available to authorized users.

Posterior decompression with instrumented fusion (PDF) surgery has been previously reported as a relatively safe surgical procedure for any type of thoracic ossification of the longitudinal ligament (OPLL). However, mid- to long-term outcomes are still unclear. The aim of the present study was to elucidate the mid- to long-term clinical outcome of PDF surgery for thoracic OPLL patients. The present study included 20 patients who had undergone PDF for thoracic OPLL and were followed for at least 5years. Increment change and recovery rate of the Japanese Orthopaedic Association (JOA) score were assessed. Revision surgery during the follow-up period was also recorded. Average JOA scores were 3.5 preoperatively and 7.1 at final follow-up. The average improvement in JOA score was 3.8 points and the average recovery rate was 47.0%. The JOA score showed gradual increase after surgery, and took 9months to reach peak recovery. As for neurological complications, two patients suffered postoperative paralysis, but both recovered without intervention. Six revision surgeries in four patients were related to OPLL. Additional anterior thoracic decompression for remaining ossification at the same level of PDF surgery was performed in one patient. Decompression surgery for deterioration of symptoms of pre-existing cervical OPLL was performed in three patients. One patient had undergone lumbar and cervical PDF surgery for de novo ossification foci of the lumbar and cervical spine. PDF surgery for thoracic OPLL is thus considered a relatively safe and stable surgical procedure considering the mid- to long-term outcomes.

Introduction Epidermoid cysts are known as embryonic or acquired ectopic aberrations of the ectoderm. To the best of our knowledge, there are only a few reports of elderly onset intramedullary epidermoid cysts. We report a case of elderly onset intramedullary epidermoid cyst at the conus medullaris. Case presentation A 63-year-old Japanese woman working as a farmer presented with slowly progressive gait disturbance and voiding dysfunction. A magnetic resonance imaging scan revealed an intramedullary mass lesion at L1 to L3. We diagnosed the lesion as an intramedullary spinal cord tumor. A laminectomy was performed at the level of Th12 to L3. Upon spinal cord dissection, a yellowish milky exudation erupted from the cystic lesion. We resected white cartilage-like pieces from the cystic cavity. Because the wall of the cystic lesion tightly adhered to the spinal cord parenchyma, we abandoned complete resection of the cyst wall. The pathological diagnosis was an epidermoid cyst. Conclusions We propose that evacuation of the cyst contents is preferable, especially in cases with elderly onset and congenital origin. Electronic supplementary material The online version of this article (doi:10.1186/1752-1947-9-7) contains supplementary material, which is available to authorized users.

Transplantation of bone marrow stromal cells (BMSCs) for spinal cord injury (SCI) has been shown to improve functional outcome. BMSCs can be easily obtained from bone marrow aspirate and have fewer problems in the clinical application for human SCI from the ethical and legal points of view. Recently, we produced cells with neural stem and/or progenitor cell property and neural regeneration supporting capacity from human bone marrow stromal cells (human bone marrow stromal cell-derived neuroregenerative cells: hBMSC-NRs). The aim of the present study was to clarify the effectiveness of transplantation of hBMSC-NRs to injured spinal cord of severe combined immunodeficiency (NOD/SCID) mice. Neurite outgrowth assay of PC-12 cells was performed. One week after a T9-level contusion SCI, hBMSCs or hBMSC-NRs were transplanted into the spinal cord. After the transplantation, functional and histological examinations were performed. Conditioned media of hBMSC-NRs significantly promoted the neurite outgrowth of PC-12 cells in vitro. Transplanted hBMSC-NRs survived in the injured spinal cord 8 weeks after SCI. Immunohistochemistry revealed that the density of serotonin-positive fibers of the transplanted group was significantly higher than that of the control group at the epicenter and caudal segment to the injured site. The recovery of hind limb function of the hBMSC-NRs group was significantly better than that of the control group. In conclusion, hBMSC-NRs can be one of the realistic candidates for cell transplantation therapy for human SCI.

Object The use of human umbilical cord blood (HUCB) cells has been reported to improve functional recovery in cases of central nervous system injuries such as stroke, traumatic brain injury, and spinal cord injury (SCI). The authors investigated the effects of hemopoietic stem cells that were derived from HUCB and transplanted into the injured spinal cords of rats. Methods One week after injury, an HUCB fraction enriched in CD34-positive cells was transplanted into the experimental group. In control animals, vehicle (Matrigel) was transplanted. Recovery of motor functions was assessed using the Basso, Beattie, and Bresnahan Locomotor Scale, and immunohistochemical examinations were performed. Cells from HUCB that were CD34 positive improved functional recovery, reduced the area of the cystic cavity at the site of injury, increased the volume of residual white matter, and promoted the regeneration or sparing of axons in the injured spinal cord. Immunohistochemical examination revealed that transplanted CD34-positive cells survived in the host spinal cord for at least 3 weeks after transplantation but had disappeared by 5 weeks. The transplanted cells were not positive for neural markers, but they were positive for hemopoietic markers. There was no evidence of an immune reaction at the site of injury in either group. Conclusions These results suggest that transplantation of a CD34-positive fraction from HUCB may have therapeutic effects for SCI. The results of this study provide important preclinical data regarding HUCB stem cell–based therapy for SCI.

Case report. To report a case with giant cell tumor (GCT) of C6 vertebra, in which three-dimensional (3-D) full-scale modeling of the cervical spine was useful for preoperative planning and intraoperative navigation. A university hospital in Japan. A 27-year-old man with a GCT involving the C6 vertebra presented with severe neck pain. The C6 vertebra was collapsed and the tumor had infiltrated around both vertebral arteries (VAs). A single-stage operation combining anterior and posterior surgical procedures was scheduled to resect the tumor and stabilize the spine. To evaluate the anatomic structures within the surgical fields, we produced a 3-D full-scale model from the computed tomography angiography data. The 3-D full-scale model clearly showed the relationships between the destroyed C6 vertebra and the deviations in the courses of both VAs. Using the model, we were able to identify the anatomic landmarks around the VAs during anterior surgery and to successfully resect the tumor. During the posterior surgery, we were able to determine accurate starting points for the pedicle screws. Anterior iliac bone graft from C5 to C7 and posterior fixation with a rod and screw system from C4 to T2 were performed without any complications. Postoperatively, the patient experienced relief of his neck pain. The 3-D full-scale model was useful for simultaneously evaluating the destruction of the vertebral bony structures and the deviations in the courses of the VAs during surgery for GCT involving the cervical spine.

Study design This retrospective study was conducted to investigate the clinical outcomes of several surgical procedures for thoracic myelopathy caused by ossification of the posterior longitudinal ligament (OPLL). Objective To evaluate the effect of myelopathy treatment and safety of posterior decompression with instrumented fusion. Summary of background data Many different surgical procedures have been used for the treatment of thoracic OPLL. However, the possibility of postoperative paraplegia remains a major risk, and consistent protocols and procedures for surgical treatment of thoracic OPLL have also not been established. Methods A total of 51 patients who underwent surgery for thoracic OPLL were classified into 3 groups: (1) posterior decompression group (18 patients), which included 12 who underwent laminectomy and 6 who underwent cervicothoracic laminoplasty; (2) OPLL extirpation group (16 patients), which included 4 who underwent anterior decompression through thoracotomy and 12 who underwent anterior decompression through the posterior approach; and (3) posterior decompression and fusion group (17 patients), all of whom underwent laminectomy with posterior instrumented fusion. In each group, the Japanese Orthopedic Association score was used to evaluate thoracic myelopathy, and the recovery rate calculated 1 year after surgery and at final examination. Results Mean recovery rate at final follow-up was 41.9% in the posterior decompression group, 62.1% in the OPLL extirpation group, and 59.3% in the posterior decompression and fusion group. Postoperative paralysis occurred in 3 patients in the posterior decompression group and in 3 in the OPLL extirpation group. In the OPLL extirpation group, leakage of cerebrospinal fluid occurred in 8 patients and hydrothorax in 2. Late neurologic deterioration occurred in 7 patients in the posterior decompression group. There were no cases of postoperative paralysis or late neurologic deterioration in the posterior decompression and fusion group. Conclusions A considerable degree of neurologic recovery was obtained by posterior decompression with instrumented fusion, despite the anterior impingement of the spinal cord by OPLL remaining. In addition, the rate of postoperative complications was extremely low with this procedure. We recommend that 1-stage posterior decompression and instrumented fusion be selected for patients in whom the spinal cord is severely damaged before surgery and/or when extirpation of OPLL is associated with increased risk.

Study Design. This study examined the extraosseous and intraosseous anomalies of vertebral arteries in patients who underwent surgery of the craniovertebral junction. Objectives. To describe the usefulness of three-dimensional computed tomography angiography for evaluating vertebral artery anomalies before surgery. Summary of Background Data. Previous studies using catheter angiograms have identified anomalous courses of the vertebral artery at the craniovertebral junction. Studies using computed tomography reconstruction also showed deviation of the vertebral artery groove at the C2 isthmus, demonstrating a risk of vertebral artery injury for C1–C2 transarticular screw placement. These analyses provided us with useful information for identifying anomalies of the vertebral artery, but they could not visualize the artery and its circumferential osseous tissue simultaneously, nor could they analyze the reciprocal anatomy of both tissues. Methods. Thirty-one consecutive patients who submitted to surgery at the craniovertebral junction were evaluated before surgery by three-dimensional computed tomography angiography. Eleven of the patients had congenital osseous anomalies at the craniovertebral junction including os odontoideum and ossiculum terminale. Anomalous vertebral arteries at the extraosseous region were visualized by three-dimensional reconstruction images, and the intraosseous deviation of the vertebral artery at the C2 isthmus was evaluated by multiplanar reconstruction images. Results. Extraosseous and/or intraosseous vertebral artery anomalies were detected in 9 cases. Eight of the 9 cases had osseous anomalies at the craniovertebral junction. Abnormal courses of the vertebral artery at the extraosseous region were detected in 4 cases: 2 had fenestration and 2 had persistent first intersegmental artery. Asymmetry of bilateral vertebral arteries was found in 5 cases: the right was dominant in 3 cases and the left in 2 cases. A high-riding vertebral artery at the C2 isthmus was detected in 5 cases. Based on these findings, we modified our surgical approach and the screw placement; consequently, no vertebral artery injury occurred. Conclusions. In patients having osseous anomalies at the craniovertebral junction, the frequency of vertebral artery anomalies at the extraosseous and intraosseous regions is increased. With preoperative three-dimensional computed tomography angiography, we can precisely identify the anomalous vertebral artery and reduce the risk of intraoperative injury to the vertebral artery, in advance.

To investigate the mechano-transduction system of cells, we identified genes responsive to a cyclic mechanical stimulus. MC3T3.E1 cells were cultured on a computer-controlled vacuum-pump-operated device designed to provide a cyclic mechanical stimulus. A maximum elongation of 15% of membrane at 10 cycles/min (3 s extension followed by 3 s relax per cycle) was repeated for 48 h. By means of a differential display, the gene expression pattern of cells exposed to the stimulus was compared with that of unexposed cells. As a result, a gene fragment that was exclusively expressed in mechanically stressed cells was identified. By using expressed sequence tag walking together with the oligo-capping method, this gene was identified as phosphatidylinositol 4-phosphate 5-kinase type II beta (initially known as Pip5k2beta but now reclassified as Pip4k2beta). The specific up-regulation of Pip4k2beta upon mechanical stimulus was also confirmed by using another apparatus, viz. a computer-controlled linearized-stepping motor system. To examine the involvement of the cyclic mechanical stimulus in the regulation of Pip4k2beta expression in musculoskeletal tissue, we created an Achilles tendon transection model in rabbits. The temporal expression of Pip4k2beta was assessed by means of a quantitative reverse-transcribed polymerase chain reaction. In the gastrocnemius muscle, expression of Pip4k2beta rapidly decreased 1 week after transection but was restored to normal levels at 4 weeks. In the Achilles tendon, however, expression remained decreased until 4 weeks after transection. We suggest that the expression of Pip4k2beta can be used as a marker for cells receiving a suitable mechanical stimulus.

Case report. To report a case with thoracic myelopathy caused by ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF), in which postoperative paralysis occurred after laminectomy and was reversed after an additional posterior instrumented fusion. A University Hospital in Japan. A 71-year-old woman, with a spastic palsy of both lower extremities, had OPLL and OLF at T10–T11, which pinched the spinal cord anteriorly and posteriorly. She underwent a laminectomy at T10–T11, and no further neurological deterioration was seen immediately after surgery. Over the next 18 h, however, myelopathy worsened, showing severe paraparesis. An additional posterior instrumented fusion at T7–L1 was performed without correction of the kyphosis. After fusion, neurological deficits gradually recovered, despite the presence of residual anterior impingement of spinal cord by the OPLL. The present case provides evidence for the possibility that laminectomy alone produces postoperative paralysis for combined thoracic OPLL and OLF, and we recommend that a posterior instrumented fusion should be added when posterior decompression is performed for this disorder.

Study design Case report of a Down syndrome patient with right vertebral artery fenestration and abnormalities of the craniovertebral junction. Objectives Describe the utility of 3-dimensional computed tomography angiography for evaluating vertebral artery anomalies before surgery. Summary of background data Previous reviews evaluating catheter angiograms identified various anomalies of vertebral artery at the craniovertebral junction. The frequency of vertebral artery anomalies is increased in patients having osseous anomalies at the craniovertebral junction. Down syndrome is associated with a high incidence of bone abnormalities at the craniovertebral junction, but there have been no published reports of vertebral artery anomalies per se at the craniovertebral junction. Methods A 16-year-old woman with trisomy 21 presented with gait abnormalities and myelopathy in association with bone abnormalities at the craniovertebral junction, including hypoplastic odontoid and ossiculum terminale. Computed tomography angiography showed that right vertebral artery bifurcated after exiting the C2 transverse foramen with one branch passing through the C1 transverse foramen, whereas the other turned posteromedially and entered the spinal canal between C1 and C2. Results Occipito-C2 posterior fusion was performed with a rod and screw system. Intraoperatively, the course of the anomalous right vertebral artery was identified by Doppler angiography, and the surgical approach was modified to allow safe pedicle screw insertion while avoiding vertebral artery injury. After surgery, myelopathy resolved within 3 months. Conclusions Before corrective surgery of craniovertebral junction anomalies in patients with Down syndrome, the possibility of vertebral artery anomalies associated with abnormal craniovertebral junction anatomy should be considered. With preoperative 3-dimensional computed tomography angiography, we can precisely identify the anomalous vertebral artery and modify the surgical approach to reduce the possible risk of intraoperative vertebral artery injury in advance.

To comprehensively evaluate gene expression in the early stage of fracture healing, we used a cDNA microarray with 2304 cDNA clones derived from an oligo-capped mouse embryo library. Closed mid-diaphyseal fractures were created in mouse tibiae and expression profiles were analyzed 3 days after fracture. Six genes were up-regulated in comparison to those in unfractured bones and these included three genes previously identified but never shown to be present in fractures, periostin, calumenin, and FHL-1. Cloning of these genes has been completed but their expression pattern and function during fracture healing and bone formation remain to be elucidated. Up-regulation of the six genes was reconfirmed by semi-quantitative RT-PCR analysis. Spatial and temporal expression of one of the newly identified fracture-induced genes, periostin, was analyzed using in situ hybridization, because it displayed the highest up-regulation ratio. A signal for periostin was detected in undifferentiated mesenchymal cells and immature preosteoblastic cells in the periosteal tissues between days 3 and 14 after fracture. Northern analysis showed that periostin gene expression rapidly increased by day 3, reached a peak on day 7, and declined by day 14. These findings suggest that periostin is a specific marker for preosteoblasts and may play an important role in periosteal callus formation during the early stage of fracture healing.

Recovery in central nervous system disorders is hindered by the limited ability of the vertebrate central nervous system to regenerate lost cells, replace damaged myelin, and re-establish functional neural connections. Cell transplantation to repair central nervous system disorders is an active area of research, with the goal of reducing functional deficits. Recent animal studies showed that cells of the hematopoietic stem cell (HSC) fraction of bone marrow transdifferentiated into various nonhematopoietic cell lineages. We employed a mouse model of spinal cord injury and directly transplanted HSCs into the spinal cord 1 week after injury. We evaluated functional recovery using the hindlimb motor function score weekly for 5 weeks after transplantation. The data demonstrated a significant improvement in the functional outcome of mice transplanted with hematopoietic stem cells compared with control mice in which only medium was injected. Fluorescent in situ hybridization for the Y chromosome and double immunohistochemistry showed that transplanted cells survived 5 weeks after transplantation and expressed specific markers for astrocytes, oligodendrocytes, and neural precursors, but not for neurons. These results suggest that transplantation of HSCs from bone marrow is an effective strategy for the treatment of spinal cord injury.