木村 敦

Study design. Retrospective multi-center study. Objective. This study was conducted to clarify the incidence and neurological outcomes of fall-related deterioration of subjective symptoms in patients undergoing surgical treatment.Summary of Background Data.The evidence that minor trauma, including falls, increases the risk of worsening cervical myelopathy is insufficient. Methods. A retrospective analysis of patients who had undergone surgery for cervical myelopathy at 12 participating institutes was conducted. Patients who had undergone surgery for symptomatic cervical myelopathy from January 2012 to December 2013 and completed at least 1-year follow-up were included in this study. Data were collected by chart review and a questionnaire that included numbers of recalled falls during the last preoperative year and first postoperative year, circumstances of falls, and whether the patient had experienced fall-related deterioration of subjective symptoms. Results. A total of 360 eligible patients were recruited into the study. Of these, 177 (49%) reported at least one fall during the last preoperative year, and 105 (29%) experienced fall-related deterioration of subjective symptoms. Forty (11%) reported deterioration of numbness in the arms or legs, and 65 (18%) reported deterioration of motor deficits. Incidences of falls and fall-related deterioration of symptoms decreased significantly after surgery. Patients who experienced fall-related deterioration of motor deficits showed significantly worse surgical outcomes as assessed by Japanese Orthopaedic Association (JOA) score compared with those who did not experience deterioration. The optimal cut-off for preoperative JOA score in predicting an increased risk of fall-related deterioration in motor deficits was 8. Conclusion. Patients with cervical myelopathy commonly experienced preoperative fall-related deterioration of subjective symptoms, associated with significantly worse neurological outcomes. Surgical treatment significantly reduced the incidence of both falls and fall-related deterioration of subjective symptoms.

Background: Supra/interspinous ligaments connect adjacent spinous processes and act as a stabilizer of the spine. As with other spinal ligaments, it can become ossified. However, few report have discussed ossification supra/ interspinous ligaments (OSIL), so its epidemiology remains unknown. We therefore aimed to investigate the prevalence and distribution of OSIL in symptomatic patients with cervical ossification of the posterior longitudinal ligament (OPLL). Methods: The participants of our study were symptomatic patients with cervical OPLL who were diagnosed by standard radiographs of the cervical spine. The whole spine CT data as well as clinical parameters such as age and sex were obtained from 20 institutions belong to the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament (JOSL). The prevalence and distribution of OSIL and the association between OSIL and clinical parameters were reviewed. The sum of the levels involved by OPLL (OP-index) and OSIL (OSI-index) as well as the prevalence of ossification of the nuchal ligament (ONL) were also investigated. Results: A total of 234 patients with a mean age of 65 years was recruited. The CT-based evidence of OSIL was noted in 68 (54 males and 14 females) patients (29%). The distribution of OSIL showed a significant thoracic preponderance. In OSIL-positive patients, single-level involvement was noted in 19 cases (28%), whereas 49 cases (72%) presented multi-level involvement. We found a significant positive correlation between the OP-index grade and OSI-index. ONL was noted at a significantly higher rate in OSIL-positive patients compared to negative patients. Conclusions: The prevalence of OSIL in symptomatic patients with cervical OPLL was 29%. The distribution of OSIL showed a significant thoracic preponderance.

To determine whether the presence of intervertebral bridging ossifications is associated with intravertebral cleft (IVC) formation following a vertebral compression fracture (VCF). Patients with a VCF who received conservative treatment for a minimum of 3 months were recruited over a 3-year period. Baseline radiographs obtained within a month of onset were compared between 50 patients who developed an IVC at 3-month follow-up (IVC group) and 100 patients without an IVC (control group). Intervertebral bridging ossification was defined as complete bridging of the intervertebral space by ossification. The presence of bridging ossification was assessed at each intervertebral level from T9/10 to L5/S. In addition to the absolute levels of bridging ossifications, the level relative to a fresh VCF was recorded. The incidence of bridging ossification at levels T9/10 and T10/11 was significantly higher in the IVC group than in the control group. IVC group patients showed a significantly higher incidence of bridging ossification at the second proximal intervertebral segment than those in the control group. IVC group patients also had a significantly greater sagittal wedge angle and a greater local kyphosis angle than control group patients. A fresh VCF with bridging ossification at the second proximal intervertebral level is associated with increased risk of IVC formation. Careful observation and strict conservative treatment are recommended in such cases.

Background: The authors have developed a screening tool, the 25-Geriatric Locomotive Function Scale (GLFS-25), for the early detection of locomotive syndrome (LS). However, few studies have examined the prevalence of LS in the general population. This study estimated the prevalence of LS in Japan using the GLSF-25 and investigated age specific mean values for this scale. Methods: A nationwide cross-sectional questionnaire survey was conducted to reveal standard values for the GLFS-25 and to estimate the total number of individuals with LS in Japan. Subjects were individuals selected from residents aged 40-79 years in Japan by a stratified, two-stage random sampling method in 2014. The survey period was from February to March 2014. A total of 9028 subjects were invited to participate. The GLFS-25 was used to estimate the prevalence of LS. We also investigated the degree of recognition of LS. Results: Answers for the questionnaire were obtained from 5162 subjects (57.2%); 22.1% of responders had heard of LS. According to the GLSF-25, 614 subjects were regarded as having LS, representing a prevalence of 11.9%. When standardizing this value with the age distribution of the Japanese population, the total number of individuals with LS between the 40s and 70s in Japan was estimated to be approximately 7.5 million. Age specific standard values on the GLFS-25 were 4.4 in the 40s, 5.5 in the 50s, 7.1 in the 60s, and 12.7 in the 70s. The prevalence of LS increased with age and was particularly high in subjects aged 70-79. Conclusions: The degree of recognition of LS was 22%. This study demonstrated sex- and age specific standard values of the GLFS-25 and estimated the total number of individuals with LS in Japan based on a representative population. (C) 2015 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Study Design. A prospective study. Objective. The aim of this study was to elucidate the impact of axial pain following cervical laminoplasty on health-related quality of life (HRQOL). Summary of Background Data. Axial neck pain is a frequently encountered complication after laminoplasty. However, limited information is available regarding the time-dependent changes in axial pain and the impact of this pain on clinical outcomes, including HRQOL. Methods. One hundred sixty-two consecutive patients with cervical myelopathy underwent double-door laminoplasty using hydroxyapatite spacers from 2008 to 2012. The outcome measures included the Japanese Orthopaedic Association score (JOA score), the EuroQol 5 Dimension Questionnaire (EQ-5D), and the Short Form-36 survey (SF-36). The intensity of axial pain was assessed using an 11-point numerical rating scale (NRS). These assessments were conducted preoperatively and at 6-month, 1-year, and 2-year follow-ups. Patient satisfaction with outcome was graded using a 7-point NRS at the 2-year follow-up. Result. One hundred twenty-one patients completed the 2-year follow-up. The mean axial pain intensity decreased slightly over time; however, the decrease was not significant. The JOA score, EQ-5D score, and all SF-36 domains, excluding general health perceptions, improved significantly compared with baseline levels at the 6-month follow-up or later. Baseline axial pain intensity showed a significant negative correlation with baseline HRQOL only in the SF-36 bodily pain domain. In contrast, axial pain intensity showed significant negative correlations with all HRQOL measures at the 6-month follow-up. At the 2-year follow-up, patients with an axial pain intensity >= 3 showed significantly worse outcomes than did patients with a pain intensity <3 in the EQ-5D score, SF-36 score, and patient satisfaction grades, but not in the JOA score. Conclusion. Axial neck pain has a significant negative impact on clinical outcomes, including a wide range of HRQOL measures and patient satisfaction with outcome, in patients undergoing conventional double-door laminoplasty.

Objective Ossification of the ligamentum flavum (OLF) is rarely identified in cervical spine and its pathogenesis has not been established. We report a case of multiple-level OLF, combined with the calcification of the cervical ligamentum flavum and posterior atlanto-axial membrane. Clinical presentation A 42-year-old man without any systemic background presented with one month history of pain from the neck to the right shoulder and right leg numbness. Cervical computed tomography demonstrated OLF from C2 to C5, a small area of calcification of the ligamentum flavum (CLF) from C5/6 to C7/T1 and extensive calcification of the posterior atlanto-axial membrane, resulting in spinal canal stenosis. Magnetic resonance imaging showed spinal canal stenosis and severe spinal cord compression from C2 to C5. Thoracic X-ray also showed ossification of the posterior longitudinal ligament (OPLL). We performed laminectomy from C1 to C5 and resected the calcified posterior atlanto-axial membrane and OLF. Histopathological examination demonstrated calcified granules within degenerated fibrous tissue in the posterior atlanto-axial membrane and mature bony trabeculae, bone marrow and residual ligament tissue in the OLF. Conclusions Simultaneous development of cervical OLF and CLF in this case seems unlikely to have occurred coincidentally and suggests that the pathogenesis of OLF and CLF may share a common initiation factor. © Springer-Verlag Berlin Heidelberg 2012.

Purpose: To test the usefulness of a novel performance test, the tally counter test (counter test), which uses a hand tally counter to objectively assess the severity of cervical myelopathy. Methods: Eighty-three patients with compressive cervical myelopathy (mean age 64 ± 13 years) who were undergoing cervical laminoplasty and 280 healthy control subjects (aged 20-89 years) were tested. The subjects were instructed to push the button of a tally counter as many times as possible in 10 s. The average of the right- and left-sided values in each patient was used for analysis. In the patient group, counter test values were compared with Japanese Orthopaedic Association (JOA) and Japanese version of the 36-Item Short Form Health Survey scores preoperatively and 12 months postoperatively. Results: The average counter test value was significantly lower in patients with myelopathy than age- and gender-matched controls (32.9 ± 10.9 vs. 46.9 ± 8.5, P &lt 0.0001). The counter test value was significantly higher at 2 weeks postoperatively than preoperatively (P = 0.0014). Counter test values showed a moderate correlation with JOA scores and a weak to moderate correlation with SF-36 physical functioning, role functioning, and role-emotional scores both pre- and postoperatively. The intraclass correlation coefficient of counter test values was high both pre- and postoperatively. Conclusion: The tally counter test is objective and quantitative assessment method for patients with cervical myelopathy. The test is simple, reliable, and capable of detecting small functional changes. © 2012 Springer-Verlag Berlin Heidelberg.

Pulsatile movements of the dura mater have been interpreted as a sign that the cord is free within the subarachnoid space, with no extrinsic compression. However, the association between restoration of pulsation and adequate decompression of the spinal cord has not been established. The present study investigated the relationship between the extent of spinal cord decompression and spinal cord and dural pulsations based on quantitative analysis of intraoperative ultrasonography (US). Eighty-five consecutive patients (55 males, 30 females; mean age, 64 +/- A 13 years) who underwent cervical double-door laminoplasty to relieve compressive myelopathy were enrolled. Spinal cord decompression status was classified as: Type 1 (non-contact), the subarachnoid space was retained on the ventral side of the cord, Type 2 (contact and apart), the cord showed both contact with and separation from the anterior element of the cervical spine, or Type 3 (contact), the cord showed continuous contact with the anterior element of the cervical spine. Spinal cord and dura mater dynamics were quantitatively analyzed using automatic video-tracking software. Furthermore, the intensity of spinal and dural pulsation was compared with the recovery of motor function at 1 year after surgery as measured by increase in the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). Spinal cord pulsation amplitude ranged from 0.01 to 0.84 mm (mean 0.30 +/- A 0.16 mm) and dural pulsation amplitude ranged from 0.01 to 0.38 mm (mean 0.14 +/- A 0.08 mm). Average spinal cord pulsation amplitude in Type 2 patients was significantly larger than that in the other groups, whereas, average dural pulsation amplitudes were similar for all three groups. There was a significant correlation between spinal cord and dural pulsation amplitudes in Type 1 patients, but not in Type 2 or Type 3 patients. Type 3 patients showed a particularly poor correlation between spinal cord and dural pulsations. Spinal cord pulsation amplitude was moderately correlated with the recovery of motor function evaluated by JOACMEQ. The present results suggest that restoration of dural pulsation is not an adequate indicator of sufficient decompression of the spinal cord following a surgical procedure.

Study Design. Observational anatomic study. Objective. To give precise information on the surgical anatomy of the medial branches of the cervical dorsal rami. Summary of Background Data. The anatomy of the medial branches has not been sufficiently described. Methods. We recorded the location of the medial branches in 94 consecutive patients who underwent laminoplasty for cervical compression myelopathy. A posterior cervical approach was made along the edge of the nuchal ligament, and, after carefully detaching the trapezius muscle from the nuchal ligament; we identified the right-side branches around the semispinalis capitis muscle. We recorded the location of the branches with reference to the spinous processes and the semispinalis capitis and trapezius muscles. In 52 patients, we electrically stimulated the branches and observed the contraction of these muscles. Results. Branches were identified between C3 and C6 spinous process levels in 92 patients. A single branch was identified in 56 patients, 2 branches were identified in 35 patients, and 3 branches were identified in the remaining 1 patient. Branches were located between C3 and C4 (n = 12), between C4 and C5 (n = 80), between C5 and C6 (n = 2), and at C6 (n = 35). There were 4 patterns of final course: 52 branches passed through the medial side of the semispinalis capitis and trapezius muscles and terminated in a subcutaneous area; 50 branches penetrated the semispinalis capitis and trapezius muscles and terminated in a subcutaneous area; 12 branches terminated in the semispinalis capitis muscle; and 15 branches penetrated the semispinalis capitis and terminated at the nuchal ligament. In 19 of 52 patients tested, the semispinalis capitis muscle contracted after electrical stimulation. Conclusion. Medial branches of the cervical dorsal rami were discernible in cervical posterior approach laminoplasty and were frequently found adjacent to C4 and C5 spinous processes. The medial branches sometimes supplied motor fibers to the semispinalis capitis muscle. Knowledge of the course of these branches might be helpful for avoiding injury during laminoplasty.

Anterior decompression with fusion (ADF) for patients with cervical ossification of the posterior longitudinal ligament (OPLL) is reportedly associated with a higher incidence of complications than is laminoplasty. However, the frequency of perioperative complications associated with ADF for cervical OPLL has not been fully established. The purpose of this study was to investigate the incidence of perioperative complications, especially neurological complications, following ADF performed to relieve compressive cervical myelopathy due to cervical OPLL. Study participants comprised 150 patients who had undergone ADF for cervical OPLL at 27 institutions between 2005 and 2008. Perioperative-especially neurological-complications occurring within 2 weeks after ADF were analyzed. Preoperative imaging findings, including Cobb angle, between C2 and C7 and occupying ratio of OPLL were investigated. Multivariate analysis with logistic regression was performed to identify independent risk factors for neurological complications. Three patients (2.0 %) showed deterioration of lower-extremity function after ADF. One of the three patients had not regained their preoperative level of function 6 months after surgery. Upper-extremity paresis occurred in 20 patients (13.3 %), five of whom had not returned to preoperative levels 6 months after surgery. Patients with upper-extremity paresis showed significantly higher occupying ratios of OPLL, greater blood loss, longer operation times, fusion of more segments, and higher rates of cerebrospinal fluid leakage than those without paresis. Independent risk factors for upper-extremity paresis were a high occupying ratio of OPLL and large blood loss during surgery. The incidences of deterioration in upper- and lower-extremity functions were 13.3 % and 2.0 %, respectively. Patients with a high occupying ratio of OPLL are at higher risk of developing neurological deterioration.

Study Design. Histological observational study of patients with spinal meningioma. Objective. To clarify the status of tumor cell invasion into the dura mater and to provide fundamental information for appropriate management of dural attachment. Summary of Background Data. Histological appearance of the dura attached to spinal meningioma has not been sufficiently evaluated. Methods. Dura mater resected in a Simpson Grade 1 manner from 25 consecutive patients with spinal meningiomas (World Health Organization grade 1) was histologically observed to determine the status of tumor cell invasion. As no clear borders such as a tumor capsule between tumor and dura mater were observed, histological findings of the dura mater were classified into the following 3 categories: grade 1, no dural invasion, with only inflammation of the dura; grade 2: dural invasion below the zone between the inner and outer layers; and grade 3, dural invasion into or over the zone between the inner and outer layers (full-thickness invasion). Results. In our microscopic study, 19 of the 25 cases of spinal meningioma showed evidence of dural invasion and 15 cases showed full-thickness invasion. Conclusion. This histological investigation of resected dura mater attached to spinal meningioma showed a high rate of full-thickness tumor invasion into the dura mater.

Spinal cord injury (SCI) is an incapacitating injury that can result in limited functional recovery. We have previously shown increases in the lysophospholipid mediator, sphingosine-1-phosphate (SIP), in the spinal cord after contusion injury. To apply S1P receptor modulation to the treatment of SCI, we examined the therapeutic effects of FTY720, an S1P receptor agonist, on locomotor recovery after SCI in mice. Oral administration of FTY720 shortly after contusion SCI significantly improved motor function recovery, as assessed by both Basso Mouse Scale scores and Rotarod Performance test results. FTY720 induced lymphopenia and reduced T-cell infiltration in the spinal cord after SCI but did not affect the early infiltration of neutrophils and the activation of microglia. In addition, plasma levels and mRNA expression of inflammatory cytokines in the spinal cord after SCI were not attenuated by FTY720. Vascular permeability and astrocyte accumulation were both decreased by FTY720 in the injured spinal cord. The therapeutic effects of FTY720 were not solely dependent on immune modulation, as confirmed by the demonstration that FTY720 also ameliorated motor function after SCI in mice with severe combined immunodeficiency. Finally, the S1P(1) receptor agonist, SEW2871, partly mimicked the therapeutic effect of FTY720. Our data highlight the Importance of immune-independent functions of FTY720 in decreasing vascular permeability and astrogliosis in the injured spinal cord and promoting locomotor function recovery after SCI. (Am J Pathol 2012, 180:1625-1635; DOI: 10.1016/j.ajpath.2011.12.012)

Spontaneous spinal epidural hematoma without discernable underlying conditions is a rare complication during pregnancy. We report a pregnant woman who developed the hematoma at 16 weeks of pregnancy; the earliest occurrence ever reported. A 36-year-old Japanese primipara with twins felt shoulder, neck and back pain at 16(+1) weeks with progressive quadriplegia. Magnetic resonance imaging revealed a mass in the C3-7 epidural space, compatible with a spinal epidural hematoma, and decompression was performed 9 h after symptom onset. Rehabilitation started and she gave birth abdominally to healthy twin infants at the 29th week. Motor, sensory and sphincter disturbances remained. This case demonstrates that spinal epidural hematoma can occur even without known underlying conditions and even at an early gestational age.

No previous studies have reported 10-year follow-up results for double-door laminoplasty using hydroxyapatite (HA) spacers. The purpose of this study was therefore to explore the long-term results of double-door laminoplasty using HA spacers and to determine if non-union or breakage of HA spacers is related to restenosis of the enlarged cervical canal. The study group consisted of 68 patients with a minimum of 10 years of follow-up after double-door laminoplasty using HA spacers. The average postoperative Japanese Orthopaedic Association score improved significantly after surgery and was maintained until the final follow-up. The average range of motion decreased by 42.6% in patients with cervical spondylotic myelopathy (CSM) and 65.8% in patients with ossification of the posterior longitudinal ligament (OPLL). The enlarged cervical canal area was preserved almost until the final follow-up. The average non-union rates of HA spacers were 21% in CSM and 17% in OPLL, and the average breakage rates were 24 in CSM and 21% in OPLL at the final follow-up. Although non-union and breakage of HA spacers were common, neither of these factors were correlated with restenosis of the enlarged cervical canal.

Only eight cases of intraosseous schwannoma of the mobile spine have been reported in the English literature. We report herein a rare case of intraosseous schwannoma mimicking benign osteoblastoma originating from the posterior column of the thoracic spine. A 60-year-old man presented with a history of back pain for several months. The patient subsequently developed gait disturbance and numbness on bilateral lower limbs. Preoperative computed tomography and magnetic resonance imaging showed a neoplastic lesion occupying the posterior column of the ninth thoracic vertebra. The most likely preoperative diagnosis was osteoblastoma. The patient underwent tumor excision and posterior fusion with instrumentation. No nerve involvement of the tumor was identified intraoperatively. Histological diagnosis was schwannoma. To the best of our knowledge, this represents the first report of intraosseous schwannoma originating from the posterior column of the mobile spine.

Study Design. Retrospective multi-institutional study. Objective. To investigate the incidence of neurological deficits after cervical laminoplasty for ossification of the posterior longitudinal ligament (OPLL). Summary of Background Data. According to analysis of long-term results, laminoplasty for cervical OPLL has been reported as a safe and effective alternative procedure with few complications. However, perioperative neurological complication rates of laminoplasty for cervical OPLL have not been well described. Methods. Subjects comprised 581 patients (458 men and 123 women; mean age: 62 + 10 years; range: 30-86 years) who had undergone laminoplasty for cervical OPLL at 27 institutions between 2005 and 2008. Continuous-type OPLL was seen in 114, segmental-type in 146, mixed-type in 265, local-type in 24, and not judged in 32 patients. Postoperative neurological complications within 2 weeks after laminoplasty were analyzed in detail. Cobb angle between C2 and C7 (C2/C7 angle), maximal thickness, and occupying rate of OPLL were investigated. Pre- and postoperative magnetic resonance imaging was performed on patients with postoperative neurological complications. Results. Open-door laminoplasty was conducted in 237, double-door laminoplasty in 311, and other types of laminoplasty in 33 patients. Deterioration of lower-extremity function occurred after laminoplasty in 18 patients (3.1%). Causes of deterioration were epidural hematoma in 3, spinal cord herniation through injured dura mater in 1, incomplete laminoplasty due to vertebral artery injury while making a trough in 1, and unidentified in 13 patients. Prevalence of unsatisfactory recovery not reaching preoperative level by 6-month follow-up was 7/581 (1.2%). Mean occupying rate of OPLL for patients with deteriorated lower-extremity function was 51.2 +/- 13.6% (range, 21.0%-73.3%), significantly higher than the 42.3 +/- 13.0% for patients without deterioration. OPLL thickness was also higher in patients with deterioration (mean, 6.6 +/- 2.2 mm) than in those without deterioration (mean, 5.7 +/- 2.0 mm). No significant difference in C2/C7 lordotic angle was seen between groups. Conclusion. Although most neurological deterioration can be expected to recover to some extent, the frequency of short-term neurological complications was higher than the authors expected.

Adult cases with isolated juvenile xanthogranuloma of the central nervous system are very rare. We report a case with dumbbell-type juvenile xanthogranuloma in the cervical spine. A 38-year-old man presented with moderate numbness of the right ring finger and right little finger and weakness of the right grip. Magnetic resonance imaging (MRI) showed an intra-spinal mass extending into the paravertebral area. The spinal cord was compressed by the lesion, which was isointense with the spinal cord on both T1- and T2-weighted imaging. Homogenous enhancement was observed after gadolinium administration. These findings favored a preoperative diagnosis of a rare tumor, rather than tumor of the nervous system. Complete surgical removal of the tumor was performed through hemilaminectomy combined with facetectomy between C7 and T1. Histological examination and immunohistochemical testing led to a diagnosis of juvenile xanthogranuloma. Two years after complete resection, MRI showed no recurrence. This appears to represent the first report of dumbbell-type juvenile xanthogranuloma in the cervical spine. Total removal of such lesions is recommended because of the high potential risk of tumor recurrence around the central nervous system.

Object. The aim in this prospective study was to determine the morphological limitations of laminoplasty for cervical ossification of the posterior longitudinal ligament (OPLL) by using intraoperative ultrasonography and to investigate correlations between ultrasonographic findings and 2-year follow-up results. Methods. Included in this study were 40 patients who underwent double-door laminoplasty for cervical myelopathy due to OPLL. Intraoperative ultrasonography was used to evaluate posterior shift of the spinal cord after the posterior decompression procedure. To determine the decompression status of the cord, the authors classified ultrasonographic findings into 3 types on the basis of the presence or absence of spinal cord contact with OPLL after decompression: Type 1, noncontact; Type 2, contact and apart; and Type 3, contact. Patients were divided accordingly into Group 1, showing Type I or 2 findings, representing sufficient decompression; and Group 2, showing Type 3 findings with insufficient decompression. Preoperative sagittal alignment of the cervical spine (C2-7 angle) and preoperative maximal thickness of OPLL were compared between groups. The authors also investigated the morphological limitations of laminoplasty and 2-year follow-up results by using the Japanese Orthopedic Association (JOA) scoring system. Results. According to receiver operating characteristic curve analysis, an OPLL maximal thickness > 7.2 mm was a cutoff value for insufficient decompression. However, sufficient or insufficient decompression did not correlate with 2-year results, as determined by JOA scores. The C2-7 angle had no impact on ultrasonographic findings. Conclusions. Laminoplasty has a morphological limitation for thick OPLLs, and a thickness > 7.2 mm represents a theoretical cutoff for residual cord compression after laminoplasty. According to 2-year results, however, laminoplasty can remain the first choice for any type of multiple-level OPLL. (DOI: 10.3171/2010.3.SPINE09680)

Objective: Spinal cord injury (SCI) is accompanied by disruption of the blood-spinal cord barrier and subsequent extravasation of fluid and proteins, which results in edema (increased water content) at the site of injury. However, the mechanisms that control edema and the extent to which edema impacts outcome after SCI are not well elucidated. Methods: Here, we examined the role of aquaporin-4 (AQP4) water channels after experimental contusion injury in mice, a clinically relevant animal model of SCI. Results: Mice lacking AQP4 (AQP4(-/-) mice) exhibited significantly impaired locomotor function and prolonged bladder dysfunction compared with wild-type (WT) littermates after contusion SCI. Consistent with a greater extent of functional deterioration, AQP4(-/-) mice showed greater neuronal loss and demyelination, with prominent cyst formation, which is generally absent in mouse SCI. The extent of spinal cord edema, as expressed by percentage water content, was persistently increased above control levels in AQP4(-/-) mice but not WT mice at 14 and 28 days after injury. Immunohistochemical analysis indicated that blood vessels in the vicinity of the lesion core had incomplete barrier function because of sparse tight junctions. Interpretation: These results suggest that AQP4 plays a protective role after contusion SCI by facilitating the clearance of excess water, and that targeting edema after SCI may be a novel therapeutic strategy. ANN NEUROL 2010;67:794-801

Background and Purpose: We have previously shown that the sphingosine 1-phosphate (S1P)/S1P receptor-1 (S1P1R) axis contributes to the migration of transplanted neural progenitor cells (NPCs) toward areas of spinal cord injury. In the current study, we examined a strategy to increase endogenous NPC migration toward the injured central nervous system to modify S1PR. Methods: S1P concentration in the ischemic brain was measured in a mouse thrombosis model of the middle cerebral artery. NPC migration in vitro was assessed by a Boyden chamber assay. Endogenous NPC migration toward the insult was evaluated after ventricular administration of the S1P2R antagonist JTE-013. Results: The concentration of S1P in the brain was increased after ischemia and was maximal 14 days after the insult. The increase in S1P in the infarcted brain was primarily caused by accumulation of microglia at the insult. Mouse NPCs mainly expressed S1P1R and S1P2R as S1PRs, and S1P significantly induced the migration of NPCs in vitro through activation of S1P1R. However, an S1P1R agonist failed to have any synergistic effect on S1P-mediated NPC migration, whereas pharmacologic or genetic inhibition of S1P2R by JTE-013 or short hairpin RNA expression enhanced S1P-mediated NPC migration but did not affect proliferation and differentiation. Interestingly, administration of JTE-013 into a brain ventricle significantly enhanced endogenous NPC migration toward the area of ischemia. Conclusions: Our findings suggest that S1P is a chemoattractant for NPCs released from an infarcted area and regulation of S1P2R function further enhances the migration of NPCs toward a brain infarction. © 2008 American Heart Association, Inc.

Neural stem/progenitor cells (NSPCs) migrate toward a damaged area of the central nervous system (CNS) for the purpose of limiting and/or repairing the damage. Although this migratory property of NSPCs could theoretically be exploited for cell-based therapeutics of CNS diseases, little is known of the mechanisms responsible for migratory responses of NSPCs. Here, we found that sphingosine 1-phosphate (Sph-1-P), a physiological lysophospholipid mediator, had a potent chemoattractant activity for NSPCs, in which, of Sph-1-P receptors, S1P(1) was abundantly expressed. Sph-1-P-induced NSPC migration was inhibited by the pretreatment with pertussis toxin, Y-27632 (a Rho kinase inhibitor), and VPC23019 (a competitive inhibitor of S1P(1) and S1P(3)). Sph-1-P does not act as intracellular mediator or in an autocrine manner, because [H-3] sphingosine, incorporated into NSPCs, was mainly converted to ceramide and sphingomyeline intracellularly, and the stimulation-dependent formation and extracellular release of Sph-1-P were not observed. Further, Sph-1-P concentration in the spinal cord was significantly increased at 7 days after a contusion injury, due to accumulation of microglia and reactive astrocytes in the injured area. This locally increased Sph1-P concentration contributed to the migration of in vivo transplanted NSPCs through its receptor S1P(1), given that lentiviral transduction of NSPCs with a short hairpin RNA interference for S1P(1) abolished in vivo NSPC migration toward the injured area. This is the first report to identify a physiological role for a lipid mediator in NSPC migration toward a pathological area of the CNS and further indicates that the Sph-1-P/S1P(1) pathway may have therapeutic potential for CNS injuries.

The ideal goal of regeneration medicine is to restore form and function to damaged tissues. While stem cell transplantation is considered a promising therapeutic approach, knowing the fate of transplanted cells using appropriate markers is essential. We developed new inbred transgenic rat strains with lacZ and GFP based on the transgenic (Tg) animal technique in rats. These Tg animals expressed most of their marker genes ubiquitously, compared to previous Tg rats. Immunological antigenicity against marker proteins was evaluated using conventional skin grafting, and results suggested lacZ-Tg-derived skin was much less immunogenic than that of GFP-Tg. However, GFP-positive cells from parental transgenic rats were still potential candidates for the study of cellular fate in immune privilege sites, such as the brain. Taking advantage of less immunogenic lacZ, we also examined the role of bone marrow-derived cells (BMDCs) in skin wound healing using an in vivo biological imaging system. Although transplantation of BMDCs enhanced wound healing at the injection site, BMDCs were detected only for a short time, suggesting a transient contribution of autologous BMDC-transplantation in wound healing. Our Tg-rat system may provide great benefits for the elucidation of the cellular process of regenerative medicine, including cell and tissue transplantation. (C) 2005 Elsevier Inc. All rights reserved.