古矢 丈雄

Background: We report on Japanese patients who showed neurological deterioration induced by sitting after cervicothoracic posterior decompression with instrumented fusion, but showed immediate neurological recovery after bed rest. Case Presentation: Patients showed incomplete paraparesis caused by the ossification of the posterior longitudinal ligament at uppermost thoracic spine. Cervicothoracic posterior decompression with instrumented fusion was performed. Postoperatively, the patients showed partial paraparesis when they were sitting. They showed rapid recovery from lower extremity paralysis upon lying down. After strict bed rest for one month, those patients showed no apparent development of paralysis during sitting. Conclusion: In patients with postoperative residual anterior spinal cord compression, micromotion might exacerbate neurological symptoms.

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.

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 LI to L3. We diagnosed the lesion as an intramedullary spinal cord tumor. A laminectomy was performed at the level of Th 12 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.

It is known that the severity of compression myelopathy sometimes worsens rapidly and results in poor functional recovery because of limited axonal regeneration. Levels of phosphorylated neurofilament subunit NF-H (pNF-H), which indicate axonal degeneration, are elevated in other neurological disorders. To our knowledge, there has been no examination of pNF-H levels in compression myelopathy. Therefore, we conducted a pilot cross-sectional study to evaluate pNF-H levels in the cerebrospinal fluid (CSF) of patients with worsening symptoms of cervical compression myelopathy. From January 2011 to March 2013, 51 samples of CSF were collected from patients at the time of myelography before spinal surgery. The indications for surgery were acutely worsening compression myelopathy (AM) in eight, chronic compression myelopathy (CM) in six, and lumbar canal stenosis (LCS) in 37 patients. The pNF-H levels were measured using a standard enzyme-linked immunosorbent assay. The mean +/- standard deviation pNF-H value was 2127.1 +/- 556.8 pg/ml in AM patients, 175.8 +/- 67.38 pg/ml in CM patients and 518.7 +/- 665.7 pg/ml in LCS patients. A significant increase in pNF-H levels was detected in the CSF of patients with AM compared with those with either CM or LCS. The clinical outcome of surgical treatment for patients with cervical myelopathy was satisfactory in both AM and CM patients. Despite the limitations of small sample size and lack of healthy CSF control data due to ethical considerations, our results suggest that pNF-H in CSF can act as a biomarker that reflects the severity of AM. (C) 2014 Published by Elsevier Ltd.

Background: Hemorrhage caused by spinal cord hemangioblastoma is rare, usually presenting as a subarachnoid hemorrhage. Intramedullary hemorrhage is an extremely rare manifestation of spinal cord hemangioblastoma. Case presentation: Forty-year-old Japanese male patient presented with acute paraplegia. Magnetic resonance (MR) imaging of the spinal cord revealed intramedullary hemorrhage. An intramedullary mass lesion was detected at the 8th thoracic vertebral level (T8) in a gadolinium enhanced-MR image. Spinal angiography revealed an intramedullary tumor stain at the level of T8. Therefore we diagnosed the problem as intramedullary hemorrhage caused by the hemangioblastoma. One month after the onset, extirpation of the intramedullary hemangioblastoma was performed. The tumor was completely removed. Pathological findings revealed a typical hemangioblastoma. At his final follow-up visit, the patient showed no apparent neurological recovery. Conclusion: Hemangioblastoma can be a cause of intramedullary hemorrhage should be considered in such cases.

Background: We report a rare case in which closed reduction was successfully obtained for iatrogenically displaced fracture-dislocation of the humeral anatomical neck with a favorable clinical outcome. Case presentation: A 53-year old postman suffered from shoulder dislocation with an undisplaced fracture of the humeral anatomical neck which was initially undiagnosed. After the first attempt to reduce the dislocation of the shoulder joint by Stimson's method, complete displacement of the fractured humeral anatomical neck occurred. By closed reduction under general anesthesia, the displaced humeral head was successfully reduced and was subsequently treated by conservative therapy using sling immobilization. Follow-up by MRI two years later showed no evidence of avascular necrosis of the humeral head. The patient showed a satisfactory range of motion of the affected shoulder joint. In the present case, the blood supply was partially preserved because a part of the lesser tubercle remained attached to the displaced humeral head. Conclusion: Based on this experience, we concluded that closed reduction might be attempted before deciding to perform an open reduction and internal fixation for displaced fracture-dislocation of the humeral anatomical neck.

We conducted a multicenter prospective controlled clinical trial to assess the feasibility of neuroprotective therapy using granulocyte colony-stimulating factor (G-CSF) for patients with acute spinal cord injury (SCI). The trial ran from August 2009 to March 2011 and included 45 SCI patients treated within 48 h of onset. Informed consent was obtained from all patients. After providing consent, patients were divided into two groups. In the G-CSF group (19 patients), G-CSF (10 μg/kg/day) was intravenously administered for five consecutive days, and in the control group (26 patients), patients were similarly treated except for the G-CSF administration. We evaluated motor functions using the American Spinal Cord Injury Association (ASIA) score 3 months after onset. The increase in ASIA motor score was significantly higher in the G-CSF group (26.1 ± 18.9) than in the control group (12.2 ± 14.7) (P &lt 0.01). In cases of incomplete paralysis (18 patients in the G-CSF group and 19 patients in the control group), the increase in motor score was also significantly higher (P &lt 0.05) in the G-CSF group (27.1 ± 18.9) than in the control group (15.1 ± 15.9). The present results suggest the possibility that G-CSF administration has beneficial effects on neurological recovery in patients with acute SCI. We believe that neuroprotection using G-CSF is an effective therapeutic strategy for acute SCI treatment.

To prove the efficacy of granulocyte colony-stimulating factor (G-CSF) for spinal cord injury (SCI), we performed several animal experiments in rodent SCI models. Through those experiments, we showed G-CSF's mechanisms of action for SCI. G-CSF showed efficacy for SCI through mobilization of bone marrow-derived cells. G-CSF attenuated neuronal cell death in vitro and in vivo, resulting in promotion of functional recovery after SCI. Expression of IL-1β and TNF-α was significantly suppressed by G-CSF in the acute phase of SCI. G-CSF promoted upregulation of anti-apoptotic protein Bcl-Xl on oligodendrocytes and suppressed apoptosis of oligodendrocytes after SCI. G-CSF exerted neuroprotective effects via promotion of angiogenesis after SCI. G-CSF's current use in the clinic for hematopoietic stimulation and its ongoing clinical trial for brain infarction make it an appealing molecule that could be rapidly placed into trials for acute SCI patients. G-CSF is one of the hopeful candidates for clinical application.

Study Design. Animal experimental study with intervention. Objective. The aim of this study was to elucidate therapeutic effects of delayed granulocyte colony-stimulating factor treatment for mechanical allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in rats. Summary of Background Data. Granulocyte colony-stimulating factor (G-CSF) is used clinically for patients with hematological disorders. Previous reports showed that immediate G-CSF attenuates neuropathic pain in CCI of the sciatic nerve. However, the acute treatment for neuropathic pain prior to accurate diagnosis is not realistic in clinical settings. Methods. Adult, female Sprague-Dawley rats were subjected to the CCI model. This model induces mechanical allodynia on the ipsilateral hind paw within the first week after the injury. One week after CCI, rats received intraperitoneal G-CSF (15.0 mu g/kg) for 5 consecutive days. Mechanical allodynia was assessed using the von Frey hair test. Immunohistochemistry for phosphorylated p38 mitogen-activated kinase (p-p38MAPK) and OX-42 (a marker for activated microglia) on tissue slides from a subset of rats 2 weeks after surgery. Western blot analyses were carried out to determine protein expression level of p-p38MAPK and interleukin-1 beta on spinal cord homogenates 2 weeks after CCI. Results. Results of the von Frey filament test showed that G-CSF significantly attenuates mechanical allodynia induced by the CCI model. Immunohistochemistry revealed that G-CSF reduced the number of p-p38MAPK-positive cells in the ipsilateral dorsal horn compared with that in the vehicle group rats. Immunofluorescent double staining revealed that p-p38MAPK-expressing cells in the spinal cord dorsal horn are mainly microglia. Western blot analysis indicated that G-CSF decreased the expression levels of both p-p38MAPK and interleukin-1 beta in the ipsilateral dorsal horn compared with that in the vehicle group rats. Conclusion. The present results indicate a beneficial effect of delayed G-CSF treatment in an animal model of peripheral nerve injury-induced neuropathic pain.

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 mu g/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.

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/SC1D) 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.

Study Design. Case report. Objective. We describe a case of osseous metaplastic meningioma in the thoracic spine that pathologically mimicked osteosarcoma. Summary of Background Data. As meningioma presents in many pathological forms, it is sometimes difficult to diagnose it pathologically. Methods. The patient's medical records, imaging results, and pathological findings were reviewed, as was the relevant literature. Results. A 20-year-old woman with a 6-month history of lumbago and right sciatica was referred to our hospital because magnetic resonance imaging (MRI) showed a tumor compressing her spinal cord at the T11 vertebra level. Computed tomography (CT) showed calcification of the tumor, and the preoperative diagnosis was meningioma. Surgery was performed and the tumor was entirely removed. The tumor was very hard, and pathological findings suggested atypical meningioma with massive ossification. Some parts of the tumor seemed malignant, as spindle cells with a high nucleocytoplasmic ratio were highly concentrated, which led to the possibility of osteosarcoma. The tumor was conclusively diagnosed as osseous metaplastic meningioma based not only on the pathology, but also on CT and MRI findings and the postoperative course. Conclusion. As meningioma presents in many pathological forms, it is sometimes difficult to diagnose it pathologically. Results of imaging studies including CT and MRI, as well as patients' postoperative course, should be considered when making a final diagnosis of meningioma.

Besides stimulating angiogenesis or cell survival, basic fibroblast growth factor (bFGF) has the potential for protecting neurons in the injured spinal cord. Objective: To investigate the effects of a sustained-release system of bFGF from gelatin hydrogel (GH) in a rat spinal cord contusion model. Methods: Adult female Sprague-Dawley rats were subjected to a spinal cord contusion injury at the T10 vertebral level using an IH impactor (200 kdyn). One week after contusion, GH containing bFGF (20 μg) was injected into the lesion epicenter (bFGF - GH group). The GH-only group was designated as the control. Locomotor recovery was assessed over 9 weeks by Basso, Beattie, Bresnahan rating scale, along with inclined plane and Rota-rod testing. Sensory abnormalities in the hind paws of all the rats were evaluated at 5, 7, and 9 weeks. Results: There were no significant differences in any of the motor assessments at any time point between the bFGF - GH group and the control GH group. The control GH group showed significantly more mechanical allodynia than did the group prior to injury. In contrast, the bFGF - GH group showed no statistically significant changes of mechanical withdrawal thresholds compared with pre-injury. Conclusion: Our findings suggest that bFGF-incorporated GH could have therapeutic potential for alleviating mechanical allodynia following spinal cord injury. © The Academy of Spinal Cord Injury Professionals, Inc. 2013.

STUDY DESIGN: Retrospective clinical study. OBJECTIVE: To report the surgical outcomes of patients with cervical myelopathy associated with athetoid cerebral palsy and to assess whether a halo vest is necessary for postoperative external immobilization. SUMMARY OF BACKGROUND DATA: Although a halo vest has remained the first choice for postoperative external immobilization of patients with cervical myelopathy associated with cerebral palsy, simplification of this method has been attempted in recent years. Studies focusing on postoperative external immobilization are rare. METHODS: Since 2001, 20 patients underwent surgery with posterior instrumented fusion or posterior fixation and anterior decompression with fusion with a year or longer follow-up. Before 2004, all patients were given a halo vest for postoperative external immobilization. After 2004, halo vests were not used, and when abnormal involuntary neck movements were severe, an intramuscular injection of botulinum toxin was administered before and after surgery. Surgical outcomes, surgical methods and complications were compared between the group that used a halo vest and the group that did not use a halo vest. RESULTS: In the halo vest group, the average Japanese Orthopedic Association score was 6.9 points before surgery and 9.3 points at 1-year follow-up. The average recovery rate was 25.0%. In the group without halo vest use, the average Japanese Orthopedic Association score was 5.8 points before surgery and 9.9 points at 1-year follow-up. The average recovery rate was 35.7%. The group without halo vest use achieved outcomes equal to those achieved in the group with halo vest use. The frequency of complications was less without halo vest use than with halo vest use. CONCLUSION: No inferiority in clinical outcomes was seen if postoperative halo vest use was omitted. Progress in surgical instrumentation and injection of botulinum toxin may explain this result.

Study Design. Retrospective clinical study.Objective. To report the surgical outcomes of patients with cervical myelopathy associated with athetoid cerebral palsy and to assess whether a halo vest is necessary for postoperative external immobilization.Summary of Background Data. Although a halo vest has remained the first choice for postoperative external immobilization of patients with cervical myelopathy associated with cerebral palsy, simplification of this method has been attempted in recent years. Studies focusing on postoperative external immobilization are rare.Methods. Since 2001, 20 patients underwent surgery with posterior instrumented fusion or posterior fixation and anterior decompression with fusion with a year or longer follow-up. Before 2004, all patients were given a halo vest for postoperative external immobilization. After 2004, halo vests were not used, and when abnormal involuntary neck movements were severe, an intramuscular injection of botulinum toxin was administered before and after surgery. Surgical outcomes, surgical methods and complications were compared between the group that used a halo vest and the group that did not use a halo vest.Results. In the halo vest group, the average Japanese Orthopedic Association score was 6.9 points before surgery and 9.3 points at 1-year follow-up. The average recovery rate was 25.0%. In the group without halo vest use, the average Japanese Orthopedic Association score was 5.8 points before surgery and 9.9 points at 1-year follow-up. The average recovery rate was 35.7%. The group without halo vest use achieved outcomes equal to those achieved in the group with halo vest use. The frequency of complications was less without halo vest use than with halo vest use.Conclusion. No inferiority in clinical outcomes was seen if postoperative halo vest use was omitted. Progress in surgical instrumentation and injection of botulinum toxin may explain this result.

To confirm the feasibility and safety of granulocyte colony-stimulating factor (G-CSF) for treating spinal neuropathic pain associated with compression myelopathy, we have initiated an open-label single-center prospective clinical trial. Between January 2009 and February 2011, 17 patients were accrued and were divided into two groups. One group included 7 patients who complained of pain associated with worsening symptoms of myelopathy (progressing myelopathy-related pain group). The other group included 10 patients who complained of pain that persisted after surgery for compression myelopathy (post-operative persistent pain group). All patients underwent intravenous administration of G-CSF (10 mu g/kg/day) for 5 consecutive days. Pain severity was evaluated using a visual analog scale (VAS) before and after G-CSF administration. In 14 of the 17 patients, pain was relieved within several days after G-CSF administration. Pain disappeared completely in 3 patients. In the progressing myelopathy-related pain group, the mean VAS score was 71.4/100 before G-CSF administration, and decreased to 35.9/100 at 1 week after G-CSF administration (p < 0.05). In the post-operative persistent pain group, the mean VAS score was 72.0/100 before G-CSF administration, and decreased to 51.7/100 at 1 week after G-CSF administration (p < 0.05). No severe adverse events occurred during or after G-CSF administration. The present results provide us with the possibility that G-CSF has a pain-relieving effect for neuropathic pain in patients with compression myelopathy.

Context: A clinical trial was conducted to evaluate the safety and efficacy of neuroprotective therapy using granulocyte colony-stimulating factor (G-CSF) for patients with worsening symptoms of compression myelopathy. During this trial, we found that neuropathic pain associated with thoracic myelopathy was dramatically reduced after G-CSF administration in two cases.Findings: A 32-year-old man with compression of the spinal cord at levels T7-T10 complained of spastic gait associated with spontaneous severe pain from his back to his chest. G-CSF 10 mu g/kg/day was administered for 5 consecutive days; his pain was reduced 1 day after the initial G-CSF administration. One month after administration, he underwent spinal fusion surgery for decompression of the spinal cord. Six months after G-CSF administration, he showed recovery from myelopathy and no recurrence of pain. A 68-year-old man with spastic gait and bilateral thigh pain caused by ossified ligamentum flavum at T11-T12 was treated with G-CSF 10 mu g/kg/day for 5 days; his pain was reduced 1 day after initial administration. One month later, he underwent a T10-T12 laminectomy. Three months after G-CSF administration, his thigh pain began to attenuate. At 6 months after administration, he showed recovery from myelopathy, and his pain was still improved compared with that before administration.Conclusion: G-CSF may have a therapeutic effect on spinal neuropathic pain.

Granulocyte colony-stimulating factor (G-CSF) is a cytokine that is clinically used to treat neutropenia. G-CSF also has non-hematopoietic functions and could potentially be used to treat neuronal injury. To confirm the safety and feasibility of G-CSF administration for acute spinal cord injury (SCI), we have initiated a phase I/IIa clinical trial of neuroprotective therapy using G-CSF.The trial included a total of 16 SCI patients within 48 h of onset. In the first step, G-CSF (5 mu g/kg/day) was intravenously administered for 5 consecutive days to 5 patients. In the second step, G-CSF (10 mu g/kg/day) was similarly administered to 11 patients. We evaluated motor and sensory functions of patients using the American Spinal Cord Injury Association (ASIA) score and ASIA impairment scale (AIS) grade.In all 16 patients, neurological improvement was obtained after G-CSF administration. AIS grade increased by one step in 9 of 16 patients. A significant increase in ASIA motor scores was detected 1 day after injection (P < 0.01), and both light touch and pin prick scores improved 2 days after injection (P < 0.05) in the 10 mu g group. No severe adverse effects were observed after G-CSF injection.These results indicate that intravenous administration of G-CSF (10 mu g/kg/day) for 5 days is essentially safe, and suggest that some neurological recovery may occur in most patients. We suggest that G-CSF administration could be therapeutic for patients with acute SCI.

Background: Granulocyte colony-stimulating factor (G-CSF) is a protein that stimulates differentiation, proliferation, and survival of cells in the granulocytic lineage. Recently, a neuroprotective effect of G-CSF was reported in a model of cerebral infarction and we previously reported the same effect in studies of murine spinal cord injury (SCI). The aim of the present study was to elucidate the potential therapeutic effect of G-CSF for SCI in rats. Methods: Adult female Sprague-Dawley rats were used in the present study. Contusive SCI was introduced using the Infinite Horizon Impactor (magnitude: 200 kilodyne). Recombinant human G-CSF (15.0 mu g/kg) was administered by tail vein injection at 1 h after surgery and daily the next four days. The vehicle control rats received equal volumes of normal saline at the same time points. Results: Using a contusive SCI model to examine the neuroprotective potential of G-CSF, we found that G-CSF suppressed the expression of pro-inflammatory cytokine (IL-1 beta and TNF-alpha) in mRNA and protein levels. Histological assessment with luxol fast blue staining revealed that the area of white matter spared in the injured spinal cord was significantly larger in G-CSF-treated rats. Immunohistochemical analysis showed that G-CSF promoted up-regulation of anti-apoptotic protein Bcl-Xl on oligpodendrocytes and suppressed apoptosis of oligodendrocytes after SCI. Moreover, administration of G-CSF promoted better functional recovery of hind limbs. Conclusions: G-CSF protects oligodendrocyte from SCI-induced cell death via the suppression of inflammatory cytokines and up-regulation of anti-apoptotic protein. As a result, G-CSF attenuates white matter loss and promotes hindlimb functional recovery.

INTRODUCTION: Interleukin-6 (IL-6) is thought to play a crucial role in the radicular pain caused by lumbar spinal stenosis. However, efficacy of inhibition of IL-6 for sciatica in patients with lumbar spinal stenosis has not been clarified. The purpose of the current study was to examine the effect of the anti-IL-6 receptor monoclonal antibody, tocilizumab, on radicular pain by its epidural administration onto spinal nerves in patients with lumbar spinal stenosis. METHODS: Sixty patients with low back and radicular leg pain caused by spinal stenosis were investigated. In 30 patients, we infiltrated 2.0 mL of lidocaine and 80 mg of tocilizumab onto the affected spinal nerve, and 2.0 mL of lidocaine and 3.3 mg of dexamethasone were used in 30 patients. Low back pain, leg pain, and leg numbness were evaluated during 1 month after spinal nerve infiltration. RESULTS: Infiltration of tocilizumab was more effective than dexamethasone for leg pain (3 days, 1, 2, and 4 weeks), low back pain (3 days, 1, 2 and 4 weeks), and leg numbness (3 days, 1 and 2 weeks). No adverse event was observed in either group. CONCLUSION: Our results indicate that the epidural administration of an anti-IL-6 receptor monoclonal antibody, tocilizumab, onto the spinal nerve produced reduction of radicular leg pain, numbness, and low back pain without adverse event. IL-6 may be one of the inducers of pain caused by spinal stenosis in humans.

A 72-year-old man with a history of fall was admitted to our institute. Neurological testing demonstrated motor weakness of left upper limbs, showing grade 3/5 muscle strength for wrist and fingers. He had no sensory loss in his trunk or bilateral upper and lower extremities. Deep tendon reflexes were normal in both upper and lower extremities. Babinski signs were positive bilaterally. Radiologic examination showed fractures of cervical spine at the C3 and C6 levels which we classified as stage 3 compressive flexion fractures under the Allen classification system. Magnetic resonance imaging (MRI) showed a space-occupying lesion in the vertebral canal at the C3/4 level. We initially diagnosed the mass as a traumatic spinal subdural or subarachnoid hematoma. Diachronic MRI evaluation and enhanced-MRI and CT myelogram established the diagnosis of an intradural extramedullary tumor. To the best of our knowledge, no report has previously described finding an intradural extramedullary tumor incidentally during imaging studies of a traumatic injury at the same spinal level. Our experience suggests that the presence of atypical findings, such as oval shape, in a posttraumatic space-occupying spinal lesion should lead clinicians to consider the possibility that the lesion may be a tumor rather than a hematoma.

Study Design. Consecutive case series and literature review.Objective. To describe the utility of 3-dimensional computed tomographic angiography (3D CTA) for evaluating vertebral artery (VA) anomalies before surgery.Summary of Background Data. Recent advances in instrumentation surgery at the craniovertebral junction (CVJ) enable us to perform rigid internal fixation. However, the risk of VA injury as a complication of the surgery has become a major problem. Thus, the importance of preoperative evaluation of the VA course has been emphasized.Methods. Cases of 100 consecutive patients who underwent CVJ instrumentation surgery since July 1998 were analyzed. Occipitocervical/ thoracic or C1-C2 posterior fusion was performed for atlantoaxial subluxation (AAS) in 59 patients and cervical fixation including C2 was required for middle-to-lower cervical lesions in 41 patients. Twenty-seven patients with AAS had a congenital skeletal anomaly (CSA) at the CVJ including os odontoideum and occipitalization of C1 (AAS-CSA[+] group). Anomalous VAs at the extra- and intraosseous regions were evaluated by 3D CTA.Results. No neurovascular injury occurred during surgery. Abnormal courses of the VA at the extraosseous region were detected in 10 cases: 2 had fenestration and 8 had a persistent first intersegmental artery. All 10 cases were in the AAS-CSA(+) group. A high-riding VA was detected in 31 cases. Fourteen out of the 31 cases were in the AAS-CSA(+) group, indicating 51.9% of the AAS-CSA(+) group had high-riding VA. In the AAS-CSA(+) group, a C1-C2 transarticular screw and C2 pedicle screw were actually inserted in 58% and 31% of the planned insertions, respectively.Conclusion. The present findings suggest that the frequency of an abnormal VA at the extra- and intraosseous regions is increased when patients have AAS and CSA at the CVJ. Using preoperative 3D CTA, we can precisely identify anomalous VAs and thereby reduce the risk of their intraoperative injury.

PURPOSE: Pain from osteoarthritis (OA) is generally classified as nociceptive (inflammatory). Animal models of knee OA have shown that sensory nerve fibers innervating the knee are significantly damaged with destruction of subchondral bone junction, and induce neuropathic pain (NP). Our objective was to examine NP in the knees of OA patients using painDETECT (an NP questionnaire) and to evaluate the relationship between NP, pain intensity, and stage of OA. MATERIALS AND METHODS: Ninety-two knee OA patients were evaluated in this study. Pain scores using Visual Analogue Scales (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), painDETECT, duration of symptoms, severity of OA using the Kellgren-Lawrence (KL) system, and amount of joint fluid were evaluated and compared using a Spearman's correlation coefficient by rank test. RESULTS: Our study identified at least 5.4% of our knee OA patients as likely to have NP and 15.2% as possibly having NP. The painDETECT score was significantly correlated with the VAS and WOMAC pain severity. Compared with the painDETECT score, there was a tendency for positive correlation with the KL grade, and tendency for negative correlation with the existence and amount of joint fluid, but these correlations were not significant. CONCLUSION: PainDETECT scores classified 5.4% of pain from knee OA as NP. NP tended to be seen in patients with less joint fluid and increased KL grade, both of which corresponded to late stages of OA. It is important to consider the existence of NP in the treatment of knee OA pain.

STUDY DESIGN: Case report. OBJECTIVE: Diagnosis of symptomatic extra-foraminal lumbosacral stenosis using diffusion tensor imaging (DTI). SUMMARY OF BACKGROUND DATA: Conventional magnetic resonance imaging (MRI) has sometimes proved inadequate for evaluating symptomatic spinal nerve lesions. DTI has been developed to visualize anisotropy of nerve-fiber tracts to evaluate nerve degeneration. We report a case of nerve compression causing a far-out lesion diagnosed using DTI. METHODS: A 68-year-old patient presented with an 8-month history of severe right-sided sciatica. Computed tomography and MRI showed right L5-S1 foraminal stenosis and contact of the L5 transverse process and S1 ala without canal stenosis at the L4-L5 level. We evaluated the fractional anisotropy (FA) of the right L5 spinal nerve and compared it with bilateral L3-S1 spinal nerves to determine the L5 spinal nerve compression site. RESULTS: DTI revealed narrowing of the right L5 spinal nerve between the L5 transverse process and S1 ala. FA was significantly decreased in the right L5 spinal nerve between the L5 transverse process and S1 ala. There was no significant difference in the FA of spinal nerves between the right and left sides at L3, L4, or S1. The right L5 spinal nerve from the central spinal canal to the extra-foraminal lumbosacral lesion was exposed during surgery and found to be severely compressed by the L5 transverse process and S1 ala. Postoperatively, the patient's symptoms disappeared immediately. CONCLUSION: We used DTI to diagnose a symptomatic lesion as an extra-foraminal lumbosacral lesion caused by compression of the L5 spinal nerve at the foramina. Because DTI can quantitatively measure damage to nerve fibers, it may be advantageous for the diagnosis of far-out syndrome.

Based on the neuroprotective effects of granulocyte colony-stimulating factor (G-CSF) on experimental spinal cord injury, we initiated a clinical trial that evaluated the safety and efficacy of neuroprotective therapy using G-CSF for patients with worsening symptoms of compression myelopathy. We obtained informed consent from 15 patients, in whom the Japanese Orthopaedic Association (JOA) score for cervical myelopathy decreased two points or more during a recent 1-month period. G-CSF (5 or 10 mu g/kg/day) was intravenously administered for five consecutive days. We evaluated motor and sensory functions of the patients and the presence of adverse events related to G-CSF therapy. G-CSF administration suppressed the progression of myelopathy in all 15 patients. Neurological improvements in motor and sensory functions were obtained in all patients after the administration, although the degree of improvement differed among the patients. Nine patients in the 10-mu g group (n = 10) underwent surgical treatment at 1 month or later after G-CSF administration. In the 10-mu g group, the mean JOA recovery rates 1 and 6 months after administration were 49.9 +/- A 15.1 and 59.1 +/- A 16.3%, respectively. On the day following the start of G-CSF therapy, the white blood cell count increased to more than 22,700 cells/mm(3). It varied from 12,000 to 50,000 and returned to preadministration levels 3 days after completing G-CSF treatment. No serious adverse events occurred during or after treatment. The results indicate that G-CSF administration at 10 mu g/kg/day is safe for patients with worsening symptoms of compression myelopathy and may be effective for their neurological improvement.

STUDY DESIGN: Prospective trial. OBJECTIVE: To examine the bone union and clinical results after unilateral or bilateral instrumented posterolateral fusion surgery using a local bone graft. SUMMARY OF BACKGROUND DATA: The iliac crest bone graft technique for lumbar posterolateral fusion surgery is widely used; however, donor site problems such as pain and sensory disturbance have been reported. Local bone has been used for bilateral multisegment fusion surgery; however, outcomes have been poor because of insufficient amounts of local bone used. This study evaluated unilateral and bilateral posterolateral fusion at 3 levels using a local bone graft. METHODS: Sixty-two patients diagnosed with degenerated spondylolisthesis at 3 levels were divided into 2 groups. All underwent decompression and bilateral instrumented posterolateral fusion. However, a unilateral local bone graft was used in 32 patients and bilateral local bone graft was used in 30 patients. The amount of bone grafting, proportion of patients with bone union, duration of bone union, visual analog scale score, Japanese Orthopedic Association score, and Oswestry Disability Index were evaluated before and 2 years after surgery. RESULTS: Visual analog scale score, Japanese Orthopedic Association score, and Oswestry Disability Index were not significantly different between the 2 groups before and after surgery (P > 0.05). The amount of local bone graft used for each segment was significantly less in the bilateral group (P < 0.05). The proportion of patients with rates of bone union and instability were 86% and 9%, respectively, in the unilateral group, but significantly poorer at 60% and 34% in the bilateral group. CONCLUSION: If multisegment fusion (3-level fusion) is performed, bilateral local bone grafting results in a poor rate of bone union because of an insufficiency of local bone. Unilateral bone grafting is recommended because better rates of bone union and stability are achieved.

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 (SO) 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&apos;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 &gt; 20 mu m 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. (DOI: 10.3171/2011.5.SPINE10421)

BACKGROUND: Surgery for lumbar spondylolisthesis is widely performed. However, there have been no reports comparing posterolateral and anterior interbody fusion prospectively. We compared instrumented posterolateral fusion with anterior interbody fusion for L4 spondylolisthesis in a prospective study. METHODS: Forty-six patients diagnosed with L4 degenerated spondylolisthesis were divided into two groups. Twenty-two consecutive patients underwent non-instrumented anterior interbody fusion using an iliac bone graft (ALIF; L4-L5 level), and 24 consecutive patients underwent instrumented posterolateral fusion with local bone (PLF; L4-L5 level). The rates of bone union, visual analog scale (VAS) score, Japanese Orthopedic Association (JOA) score, Oswestry Disability Index (ODI), surgical invasion, and complications were evaluated before and 2 years after surgery. RESULTS: Age, VAS score, JOA score, and ODI were not significantly different between the two groups before surgery (P > 0.05). Success of bone union between the two groups was not significantly different (P > 0.05). Blood loss during surgery was significantly less; however, periods of bed rest and hospital stay were significantly longer in the ALIF group (P < 0.05). Overall patient satisfaction, and low back and leg pain in both groups were significantly improved after surgery; however, low back pain showed greater improvement in the ALIF group compared with the PLF group (P < 0.05). Complications such as donor site pain (4 patients in the ALIF group) and dural tearing (3 patients in the PLF group) were observed. CONCLUSIONS: If single level fusion for L4 spondylolisthesis is performed, both anterior and posterior methods reduce patients' low back and leg pain. Improvement of low back pain was significantly greater after ALIF; however, periods of hospital stay and of bed rest were significantly longer.

A 60-year-old man presented with thoracic myelopathy due to ossification of the posterior longitudinal ligament (OPLL). His spinal cord was severely impinged anteriorly by a beak-type OPLL and posteriorly by ossification of the ligamentum flavum at T4/5. He underwent surgical posterior decompression with instrumented fusion (PDF). Immediately after surgery, he developed a Brown-Sequard-type paralysis, which spontaneously resolved without requiring the addition of OPLL extirpation. This example highlights that the risk of postoperative neurological deterioration cannot be eliminated even when PDF is selected as the surgical procedure for thoracic OPLL, especially in instances in which the spinal cord is severely compressed. (C) 2010 Elsevier Ltd. All rights reserved.

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. (C) 2009 Elsevier Ltd. All rights reserved.

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.

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. Case report.Objective. To report a surgically treated case of cervical ossification of the posterior longitudinal ligament (OPLL), in which a spinal subarachnoid hematoma (SSAH) developed intraoperatively but was successfully treated.Summary of Background Data. Previous reports have indicated that trauma, lumbar puncture, vascular lesions such as arteriovenous malformation, neoplastic lesions, and coagulopathy can cause SSAH. To the best of our knowledge, there has been no report that describes the occurrence of SSAH during anterior decompression surgery of the cervical spine.Methods. A 52-year-old man with cervical myelopathy caused by OPLL underwent surgery for anterior decompression from C2/3 to C6/7. Immediately after the OPLL floating procedure, cerebrospinal fluid leakage and massive bleeding occurred at right edge of the OPLL at the C3-C4 level. After hemostasis, the dura mater at the C5-C6 levels bulged rapidly and became cyanotic. Intraoperative ultrasonographic images showed a high-intensity mass lesion on the ventral side of the spinal cord, indicating an intrathecal hematoma.Results. We incised the dura, found the hematoma under the intact arachnoid, and removed it. We then found that the bleeding occurred from the radicular artery along the right C4 root. After hemostasis, we performed anterior spine fusion from C2-C7. After surgery, the patient's myelopathy was improved, and no neurologic deficit related to the subarachnoid hematoma was found.Conclusion. This experience suggests that when anterior decompression surgery is performed for cervical OPLL patients, we should consider the possible occurrence of an SSAH. Intraoperative ultrasonography is a useful tool for detecting SSAHs.

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 &lt; 0.01). No patient developed myelopathy during the study period. Three patients with massive OPLL did not develop myelopathy and the mobility of their cervical spine was highly suggesting that dynamic factors such as the segmental ROM preferentially contribute to the restricted, development of myelopathy in patients with cervical OPLL. Thus, by controlling the dynamic factors (hypermobility), we might be able to reduce neurological deterioration in patients with cervical OPLL. (C) 2009 Elsevier Ltd. All rights reserved.

We have started a Phase I and IIa clinical trial to assess the safety and feasibility of neuroprotective therapy using granulocyte colony-stimulating factor (G-CSF) for patients with acute spinal cord injury (SCI). Six patients with acute SCI were received intravenous G-CSF injection (5μg/kg per day) for 5 days. After injection, we had neurological evaluations with American Spinal Cord Injury Association (ASIA) score, and confirmed side effects for medication with physical findings and laboratory data. In all 6 patients, some neurological improvement was obtained after medication. Mean white blood cell (WBC) counts were 25.2 to 38.4 (&amp times 103/μl) 1 days after medication that was higher than previous counts. From 1 day to 5 days after the medication, during the administration, WBC counts kept higher than previous counts, and 1 days after the end of medication, WBC counts returned to the previous rate. No severe adverse effects were seen in all patients after G-CSF injection.

In light of reports that the administration of fasudil, a Rho-kinase inhibitor, improved rats locomotor abilities following spinal cord injury, we hypothesized that combining fasudil with another type of therapy, such as stem cell transplantation, might further improve the level of locomotor recovery. Bone marrow stromal cells (BMSCs) are readily available for stem cell therapy. in the present study, we examined whether fasudil combined with BMSC transplantation would produce synergistic effects on recovery. Adult female Sprague-Dawley rats were subjected to spinal cord contusion injury at the T10 vertebral level using an IH impactor (200 Kdyn). Immediately after contusion, they were administrated fasudil intrathecally for 4 weeks. GFP rat-derived BMSCs (2.5x10(6)) were injected into the lesion site 14 days after contusion. Locomotor recovery was assessed for 9 weeks with BBB scoring. Sensory tests were conducted at 8 weeks. Biotinylated dextran amine (BDA) was injected into the sensory-motor cortex at 9 weeks. In addition to an untreated control group, the study also included a fasudil-only group and a BMSC-only group in order to compare the effects of combined therapy vs. single-agent therapy. Animals were perfused transcardially 11 weeks after contusion, and histological examinations were performed. The combined therapy group showed statistically better locomotor recovery than the untreated control group at 8 and 9 weeks after contusion. Neither of the two single-agent treatments improved open field locomotor function. Sensory tests showed no statistically significant difference by treatment. Histological and immunohistochemical studies provided some supporting evidence for better locomotor recovery following combined therapy. The average area of the cystic cavity was significantly smaller in the fasudil+BMSC group than in the control group. The number of 5-HT nerve fibers was significantly higher in the fasudil+BMSC group than in the control group on the rostral side of the lesion site. BDA-labeled fibers on the caudal side of the lesion epicenter were observed only in the fasudil+BMSC group. on the other hand, only small numbers of GFP-labeled grafted cells remained 9 weeks after transplantation, and these were mainly localized at the site of injection. Double immunofluorescence studies showed no evidence of differentiation of grafted BMSCs into glial cells or neurons. The Rho-kinase inhibitor fasudil combined with BMSC transplantation resulted in better locomotor recovery than occurred in the untreated control group. However, the data failed to demonstrate significant synergism from combined therapy compared with the levels of recovery following single-agent treatment. (C) 2009 Elsevier B.V. All rights reserved.

Study Design. To report a new index, the K-line, for deciding the surgical approach for cervical ossification of the posterior longitudinal ligament (OPLL). Objective. To analyze the correlation between the K-line-based classification of cervical OPLL patients and their surgical outcome. Summary of Background Data. Previous studies showed that kyphotic alignment of the cervical spine and a large OPLL are major factors causing poor surgical outcome after laminoplasty for cervical OPLL patients. However, no report has evaluated these 2 factors in 1 parameter. Methods. The K-line was defined as a line that connects the midpoints of the spinal canal at C2 and C7. Twenty-seven patients who had cervical OPLL and underwent posterior decompression surgery were classified into 2 groups according to their K-line classification. OPLL did not exceed the K-line in the K-line (+) group and did exceed it in the K-line (+) group. By intraoperative ultrasonography, we evaluated the posterior shift of the spinal cord after the posterior decompression procedure. The Japanese Orthopedic Association scores before surgery and 1 year after surgery were evaluated, and the recovery rate was calculated. Results. Eight patients were classified as K-line (+), and 19 patients were classified as K-line (+). The mean recovery rate was 13.9% in the K-line (+) group and 66.0% in the K-line (+) group (P &lt; 0.01). Ultrasonography showed that the posterior shift of the spinal cord was insufficient in the K-line (+) group. Conclusion. The present results demonstrate that a sufficient posterior shift of the spinal cord and neurologic improvement will not be obtained after posterior decompression surgery in the K-line (+) group. Our new index, the K-line, is a simple and practical tool for making decisions regarding the surgical approach for cervical OPLL patients.