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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.

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.

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.

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.

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.