牧 聡

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<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.

Dropped head syndrome (DHS) is characterized by apparent neck extensor muscle weakness and difficulty extending the neck to raise the head against gravity. The aim of the present study was to elucidate possible risk factors for DHS after cervical laminoplasty. Five patients who developed DHS after cervical laminoplasty (DHS group) and twenty age-matched patients who underwent laminoplasty without DHS after surgery (control group) were compared. The surgical procedure was single-door laminoplasty with strut grafting using resected spinous processes or hydroxyapatite spacers from C3 to C6 or C7. Analyses of preoperative images including the C2-C7 angle, C7-T1 kyphosis, T1 tilt, center of gravity line from the head-C7 sagittal vertical axis (CGH-C7 SVA) were performed on lateral plain cervical spine radiographs. Preoperative T2-weighted MRI at the C5 vertebral level was used to measure the cross-sectional area of the deep extensor muscles. Widths of the lateral gutters were assessed postoperatively using CT scans of the C5 vertebral body. The average preoperative C2-C7 angle was significantly smaller in the DHS group compared with the control group. The average preoperative C7-T1 angle was significantly larger in the DHS group compared with the control group. The average preoperative CGH-C7 SVA was significantly larger in the DHS group compared with the control group. In conclusion, patients with more pronounced preoperative C2-C7 kyphosis, C7-T1 kyphosis, and CGH-C7 SVA are more likely to develop DHS following laminoplasty.

We investigated the outcome of posterior decompression and instrumented fusion (PDF) surgery for patients with K-line (-) ossification of the posterior longitudinal ligament (OPLL) of the cervical spine, who may have a poor surgical prognosis. We retrospectively analyzed the outcome of a series of 27 patients who underwent PDF without correction of cervical alignment for K-line (-) OPLL and were followed-up for at least 1 year after surgery. We had performed double-door laminoplasty followed by posterior instrumented fusion without excessive correction of cervical spine alignment. The preoperative Japanese Orthopedic Association (JOA) score for cervical myelopathy was 8.0 points and postoperative JOA score was 11.9 points on average. The mean JOA score recovery rate was 43.6%. The average C2-C7 angle was 2.2° preoperatively and 3.1° postoperatively. The average maximum occupation ratio of OPLL was 56.7%. In conclusion, PDF without correcting cervical alignment for patients with K-line (-) OPLL showed moderate neurological recovery, which was acceptable considering K-line (-) predicts poor surgical outcomes. Thus, PDF is a surgical option for such patients with OPLL.

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 mid-to 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.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

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.

Granulocyte colony-stimulating factor (G-CSF) mobilizes peripheral blood stem cells (PBSCs) derived from bone marrow. We hypothesized that intraspinal transplantation of PBSCs mobilized by G-CSF could promote functional recovery after spinal cord injury. Spinal cords of adult nonobese diabetes/severe immunodeficiency mice were injured using an Infinite Horizon impactor (60 kdyn). One week after the injury, 3.0 µl of G-CSF-mobilized human mononuclear cells (MNCs; 0.5 × 10(5)/µl), G-CSF-mobilized human CD34-positive PBSCs (CD34; 0.5 × 10(5)/µl), or normal saline was injected to the lesion epicenter. We performed immunohistochemistry. Locomotor recovery was assessed by Basso Mouse Scale. The number of transplanted human cells decreased according to the time course. The CD31-positive area was significantly larger in the MNC and CD34 groups compared with the vehicle group. The number of serotonin-positive fibers was significantly larger in the MNC and CD34 groups than in the vehicle group. Immunohistochemistry revealed that the number of apoptotic oligodendrocytes was significantly smaller in cell-transplanted groups, and the areas of demyelination in the MNC- and CD34-transplanted mice were smaller than that in the vehicle group, indicating that cell transplantation suppressed oligodendrocyte apoptosis and demyelination. Both the MNC and CD34 groups showed significantly better hindlimb functional recovery compared with the vehicle group. There was no significant difference between the two types of transplanted cells. Intraspinal transplantation of G-CSF-mobilized MNCs or CD34-positive cells promoted angiogenesis, serotonergic fiber regeneration/sparing, and preservation of myelin, resulting in improved hindlimb function after spinal cord injury in comparison with vehicle-treated control mice. Transplantation of G-CSF-mobilized PBSCs has advantages for treatment of spinal cord injury in the ethical and immunological viewpoints, although further exploration is needed to move forward to clinical application.

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.

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

PURPOSE: 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). METHODS: In the G-CSF group (n = 28), patients were treated from August 2009 to July 2012 within 48 h of the injury, and G-CSF (10 μg/kg/day) was administered intravenously for five consecutive days. In the MPSS group (n = 34), patients underwent high-dose MPSS therapy from August 2003 to July 2005 following the NASCIS II protocol. We evaluated the ASIA motor score and the AIS grade elevation between the time of treatment and 3-month follow-up and adverse events. RESULTS: The ΔASIA 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). CONCLUSIONS: 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.

INTRODUCTION: Epidermoid cysts are known as embryonic or acquired ectopic aberrations of the ectoderm. To the best of our knowledge, there are only a few reports of elderly onset intramedullary epidermoid cysts. We report a case of elderly onset intramedullary epidermoid cyst at the conus medullaris. CASE PRESENTATION: A 63-year-old Japanese woman working as a farmer presented with slowly progressive gait disturbance and voiding dysfunction. A magnetic resonance imaging scan revealed an intramedullary mass lesion at L1 to L3. We diagnosed the lesion as an intramedullary spinal cord tumor. A laminectomy was performed at the level of Th12 to L3. Upon spinal cord dissection, a yellowish milky exudation erupted from the cystic lesion. We resected white cartilage-like pieces from the cystic cavity. Because the wall of the cystic lesion tightly adhered to the spinal cord parenchyma, we abandoned complete resection of the cyst wall. The pathological diagnosis was an epidermoid cyst. CONCLUSIONS: We propose that evacuation of the cyst contents is preferable, especially in cases with elderly onset and congenital origin.

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 μg/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 β 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 β 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. LEVEL OF EVIDENCE: N/A.

Nocardia cyriacigeorgica is a recently described species. During routine diagnostic testing of 121 clinical isolates, we found that about one fourth of the strains from Japan (19 isolates) and Thailand (8 isolates), which were identified in our laboratories as N. asteroides, in fact belong to N. cyriacigeorgica. To our knowledge, this is the first report of infection due to N. cyriacigeorgica in Japan and Thailand, and the third report of infection anywhere in the world. Although N. cyriacigeorgica is usually differentiated from other Nocardia species by utilization of glucose and gluconate, we found that it can also be differentiated by a characteristic synergistic effect between imipenem (IPM) and tobramycin (TOB).