古矢 丈雄

Chronic intractable neuropathic pain after central or peripheral nervous system injury remains refractory to therapeutic intervention. Using microarray and RT-qPCR methods, we found that Noggin mRNA is downregulated in the lumbar enlargement 2 weeks after chronic constriction injury (CCI) in rats. Eight-week-old female Sprague Dawley rats were used for the CCI model. Two weeks after CCI, rats underwent a laminectomy at L5 under halothane anesthesia, and a silicone tube connected to an osmotic minipump was inserted intrathecally for 14 days. Rats were administered Noggin ranging from 10 ng/ml to 10 μg/ml. Phosphate buffered saline (PBS) was used as a control. The time course of mechanical allodynia was assessed for 5 weeks using von Frey filaments. An ANOVA showed that rats administered Noggin at 2 μg/ml had significantly less mechanical allodynia compared with controls. We next compared the effect of intrathecal administration (14 days) of Noggin (2 μg/ml), bone morphogenetic protein 4 (BMP4 2 μg/ml), or BMP4 (μg/ml) + Noggin (μg/ml) with controls. Only Noggin administration significantly reduced mechanical allodynia in the CCI model. Fluorescence immunohistochemistry indicated that Noggin administration decreased astrocyte accumulation in the dorsal horn compared with PBS after administration for one week. BMP4-driven conversion of oligodendrocyte progenitor cells (OPCs) to type 2 astrocytes is inhibited by Noggin Hampton et al. (2007). We speculated that Noggin administration inhibits the conversion of OPCs to astrocytes, and decreases glial fibrillar acidic protein expression. This histological condition could decrease neuropathic pain.

The K-line, which is a virtual line that connects the midpoints of the anteroposterior diameter of the spinal canal at C2 and C7 in a plain lateral radiogram, is a useful preoperative predictive indicator for sufficient decompression by laminoplasty (LMP) for ossification of the posterior longitudinal ligament (OPLL). K-line is defined as (+) when the peak of OPLL does not exceed the K-line, and is defined as (-) when the peak of OPLL exceeds the K-line. For patients with K-line (-) OPLL, LMP often results in poor outcome. The aim of the present study was to compare the clinical outcome of LMP, posterior decompression with instrumented fusion (PDF) and anterior decompression and fusion (ADF) for patients with K-line (-) OPLL. The present study included patients who underwent surgical treatment including LMP, PDF and ADF for K-line (-) cervical OPLL. We retrospectively compared the clinical outcome of those patients in terms of Japanese Orthopedic Association score (JOA score) recovery rate. JOA score recovery rate was significantly higher in the ADF group compared with that in the LMP group and the PDF group. The JOA score recovery rate in the PDF group was significantly higher than that in the LMP group. LMP should not be used for K-line (-) cervical OPLL. ADF is one of the suitable surgical treatments for K-line (-) OPLL. Both ADF and PDF are applicable for K-line (-) OPLL according to indications set by each institute and surgical decisions.

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 <= 4 mm. Forty-five (22.5%) pedicles were <= 4 mm in width, and safe insertion of a PS was determined to be not feasible. Among these, seven pedicles were <= 4 mm in both height and width. The remaining 38 pedicles were <= 4 mm in width with heights >4 mm. There was no pedicle with a width >4 mm and height <4 mm. In other words, short pedicles were always concomitantly narrow. Therefore, the seven pedicles <= 4 mm in both height and width were considered to be morphologically narrow. The heights of the pedicle isthmus were not limited by the vertebral artery groove (VAG) and safe C2 PS insertion can be considered feasible where the VAG is marginally cranial, whereas the widths of the pedicle isthmus are limited by the VAG. Therefore, safe C2 PS insertion is precluded only when the VAG courses cranially and medially. It is a medially-shifted, rather than a high-riding, vertebral artery that precludes safe C2 PS insertion. Therefore to avoid vertebral artery injury an axial CT scan, parallel to the pedicle axis, should be evaluated before C2 PS insertion. (c) 2016 Elsevier Ltd. All rights reserved.

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 5 years. 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 9 months 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. (C) 2015 Elsevier Ltd. All rights reserved.

Background: Dropped head syndrome (DHS) is defined as weakness of the neck extensor muscles causing a correctable chin-on-the-chest deformity. Here we report the case of a patient with severe pain from lower leg ischemia showing DHS whose symptoms were attenuated by pain relief after amputation of the severely ischemic lower leg. To our knowledge this is the first report indicating that severe pain can cause DHS. Case presentation: A 64-year-old Asian woman was referred to our department with a 1-month history of DHS. She also suffered from severe right foot pain because of limb ischemia. She began to complain of DHS as her gangrenous foot pain worsened. She had neck pain and difficulty with forward gaze. We found no clinical or laboratory findings of neuromuscular disorder or isolated neck extensor myopathy. We amputated her leg below the knee because of progressive foot gangrene. Her severe foot pain resolved after the surgery and her DHS was attenuated. Conclusion: Severe pain can cause DHS. If a patient with DHS has severe pain in another part of the body, we recommend considering aggressive pain relief as a treatment option.

Study Design: Retrospective case-control study. Purpose: To determine whether kissing spine is a risk factor for recurrence of sciatica after lumbar posterior decompression using a spinous process floating approach. Overview of Literature: Kissing spine is defined by apposition and sclerotic change of the facing spinous processes as shown in X-ray images, and is often accompanied by marked disc degeneration and decrement of disc height. If kissing spine significantly contributes to weight bearing and the stability of the lumbar spine, trauma to the spinous process might induce a breakdown of lumbar spine stability after posterior decompression surgery in cases of kissing spine. Methods: The present study included 161 patients who had undergone posterior decompression surgery for lumbar canal stenosis using a spinous process floating approaches. We defined recurrence of sciatica as that resolved after initial surgery and then recurred. Kissing spine was defined as sclerotic change and the apposition of the spinous process in a plain radiogram. Preoperative foraminal stenosis was determined by the decrease of perineural fat intensity detected by parasagittal T1-weighted magnetic resonance imaging. Preoperative percentage slip, segmental range of motion, and segmental scoliosis were analyzed in preoperative radiographs. Univariate analysis followed by stepwise logistic regression analysis determined factors independently associated with recurrence of sciatica. Results: Stepwise logistic regression revealed kissing spine (p =0.024 odds ratio, 3.80) and foraminal stenosis (p &lt 0.01 odds ratio, 17.89) as independent risk factors for the recurrence of sciatica after posterior lumbar spinal decompression with spinous process floating procedures for lumbar spinal canal stenosis. Conclusions: When a patient shows kissing spine and concomitant subclinical foraminal stenosis at the affected level, we should sufficiently discuss the selection of an appropriate surgical procedure.

Study Design: Retrospective case series. Purpose: To elucidate the impact of postoperative occiput-C2 (O-C2) angle change on subaxial cervical alignment. Overview of Literature: In the case of occipito-upper cervical fixation surgery, it is recommended that the O-C2 angle should be set larger than the preoperative value postoperatively. Methods: The present study included 17 patients who underwent occipito-upper cervical spine (above C4) posterior fixation surgery for atlantoaxial subluxation of various etiologies. Plain lateral cervical radiographs in a neutral position at standing were obtained and the O-C2 angle and subaxial lordosis angle (the angle between the endplates of the lowest instrumented vertebra (LIV) and C7 vertebrae) were measured preoperatively and postoperatively soon after surgery and ambulation and at the final follow-up visit. Results: There was a significant negative correlation between the average postoperative alteration of O-C2 angle (DO-C2) and the average postoperative alteration of subaxial lordosis angle (Dsubaxial lordosis angle) (r=-0.47, p=0.03). Conclusions: There was a negative correlation between DO-C2 and Dsubaxial lordosis angles. This suggests that decrease of midto lower-cervical lordosis acts as a compensatory mechanism for lordotic correction between the occiput and C2. In occipito-cervical fusion surgery, care must be taken to avoid excessive O-C2 angle correction because it might induce mid-to-lower cervical compensatory decrease of lordosis.

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 mu l of G-CSF-mobilized human mononuclear cells (MNCs; 0.5 x 10(5)/mu l), G-CSF-mobilized human CD34-positive PBSCs (CD34; 0.5 x 10(5)/mu l), 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.

To elucidate neuroprotective effect of granulocyte colony-stimulating factor (G-CSF) for acute spinal cord injury (SCI), we performed experimental studies and early phase of clinical trials. The results of experimental studies showed that G-CSF exerts neuroprotective effects for acute SCI via mobilization of bone marrow-derived cells into injured spinal cord, suppression of neuronal apoptosis, suppression of inflammatory cytokine up-regulation, suppression of oligodendrocyte apoptosis and promotion of angiogenesis. Next we moved to clinical trial. In a phase I/IIa trial, no adverse events were observed. Then, we conducted a non-randomized, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. We are now preparing a phase III trial to confirm G-CSF treatment efficacy for acute SCI. The current trial will include cervical SCI within 48 hours after injury. Patients will be randomly assigned to G-CSF and placebo groups and evaluated by double blinded manner. Our primary endpoint is changes in American Spinal Injury Association motor scores from baseline to 3 months. Each group will include 44 patients (88 total patients). After completion of this clinical trial, pharmaceutical approval will be applied for health insurance publication. G-CSF-mediated neuroprotection is a promising candidate for a novel therapeutic approach for SCI.

The motion at the non-ossified segment of the ossification of the posterior longitudinal ligament (OPLL) is thought to be highly correlated to aggravation of symptoms of myelopathy. The rationale for posterior decompression with instrumented fusion (PDF) surgery is to limit the motion of the non-ossified segment of OPLL by stabilization. The purpose of the present study was to elucidate the course of bone union and remodelling of the non-ossified segment of thoracic OPLL (T-OPLL) after PDF surgery. A total of 29 patients who underwent PDF surgery for T-OPLL were included in this study. We measured the thickness of the OPLLs by determining the thickest part of the OPLL in the sagittal multi-planer reconstruction CT images pre- and post-operatively. Five experienced spine surgeons independently performed CT measurements of OPLL thickness twice. Japanese Orthopaedic Association score for thoracic myelopathy was measured as clinical outcome measure. Non-ossified segment of OPLLs fused in 24 out of 29 (82.8 %) patients. The average thickness of the OPLL at its thickest segment was 8.0 mm and decreased to 7.3 mm at final follow-up. The decrease in ossification thickness was significantly larger in the patients who showed fusion of non-ossified segments of OPLL compared with that in the patients did not show fusion. There was no significant correlation between the clinical outcome and the decrease in thickness of the OPLLs. The results of this study showed that remodelling of the OPLLs, following fusion of non-ossified segment of OPLLs, resulted in a decreased OPLL thickness, with potential for a reduction of spinal cord compression.

Background: Cervical deformity can influence global sagittal balance. We report two cases of severe low back pain and lower extremity radicular pain associated with dropped-head syndrome. Symptoms were relieved by cervical corrective surgery. Case presentation: Two Japanese women with dropped head syndrome complained of severe low back pain and lower extremity radicular pain on walking. Radiographs showed marked cervical spine kyphosis and lumbar spine hyperlordosis. After cervicothoracic posterior corrective fusion was performed, cervical kyphosis was corrected and lumbar lordosis decreased, and low back pain and leg pain were relieved in both patients. Conclusions: Cervical deformity can influence global sagittal balance. Marked cervical kyphosis in patients with dropped-head syndrome can induce compensatory thoracolumbar hyperlordosis. Low back symptoms in patients with dropped-head syndrome are attributable to this compensatory lumbar hyperlordosis. Symptoms of lumbar canal stenosis may result from cervical deformity and can be improved with cervical corrective surgery.

Spinal cord injury (SCI) can cause neuropathic pain (NO), 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 mu g/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 (p381VIAPK) and interleukin-1 beta 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 SG-induced NeP, possibly through the inhibition of microglial activation and the suppression of p38MAPK phosphorylation and the upregulation of interleukin-1 beta. (C) 2015 Elsevier B.V. All rights reserved.

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.

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 mu g/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 Delta ASIA motor score was significantly higher in the G-CSF group than in the MPSS group (p < 0.01). When we compared AIS grade elevation in patients with AIS grades B/C incomplete paralysis, 17.9 % of patients in the G-CSF group had an AIS grade elevation of two steps compared to 0 % of patients in the MPSS group (p < 0.05), and the incidence of pneumonia was significantly higher in the MPSS group (42.9 %) compared to the G-CSF group (8.3 %) (p < 0.05). These results suggest that G-CSF administration is safe and effective, but a prospective randomized controlled clinical trial is needed to compare the efficacy of MPSS versus G-CSF treatment in patients with SCI.

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.

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.