Published papers

STUDY DESIGN: Retrospective case series. OBJECTIVE: To determine the clinical significance and prognosis of idiopathic syringomyelia. SUMMARY OF BACKGROUND DATA: With the widespread use of magnetic resonance imaging, cases of syringomyelia are found occasionally. However, the clinical significance and optimum treatment strategy for idiopathic syringomyelia remain unclear, because there are few reports on details of this condition. METHODS: The clinical records and magnetic resonance images of 15 patients with idiopathic syringomyelia were reviewed to determine the changes in patient's neurologic status assessed by the Japanese Orthopedic Association scores for cervical myelopathy and the distribution of the syringomyelia on magnetic resonance imaging. Twelve cases were treated conservatively (conservative group) and syringo-subarachnoid shunt was performed in the remaining 3 cases (surgical group). The follow-up period ranged from 7 to 20 years (mean: 10.5 y). RESULTS: The localized type of idiopathic syringomyelia, which extended under 3 vertebras (mean: 2.1 vertebras), was observed in the 12 patients of the conservative group. There were no significant changes in either the size of the syringomyelia or the severity of the neurologic deficits during the follow-up period (mean: 10 y). In contrast, the extended type, which distributed over 4 or more vertebras (mean: 10.2 vertebras), was observed in the 3 patients of the surgical group. Because of severe and progressive neurologic deficits, syringo-subarachnoid shunt was performed and the surgery successfully prevented further neurologic deterioration. The mean Japanese Orthopedic Association score of the surgical group was significantly lower than that of the conservative group, both at the time of the initial examination and at the final follow-up. CONCLUSIONS: There are 2 types of idiopathic syringomyelia. One is a "localized" type, which might represents congenital enlargement of the central canal of the spinal cord, and can be managed conservatively. The other is an "extended" type, which causes progressive neurologic dysfunction, and should be treated surgically to prevent further neurologic deterioration. Further study should be needed to clarify the mechanism of the extended type of idiopathic syringomyelia. © 2009 Lippincott Williams & Wilkins, Inc.

STUDY DESIGN.: Questionnaire survey on leg cramps for patients with lumbar spinal canal stenosis (LCS). OBJECTIVE.: To evaluate the prevalence of leg cramps in patients with LCS treated surgically and the relationship between leg cramps and the surgical outcomes. SUMMARY OF BACKGROUND DATA.: Although it has been anecdotally reported that LCS patients have suffered from leg cramps, the true prevalence remains unknown. METHODS.: One hundred twenty LCS patients who underwent decompression surgery (men 85, women 35, mean age 73.5) and 370 elderly subjects from the general population (men 162, women 208, mean age 75.6) were enrolled in the study. The participants filled in a questionnaire regarding: (all participants) (1) experience of leg cramps, (2) frequency and time of the day of the cramp attacks; (for LCS patients only), (3) changes in cramps before and after surgery, (4) activities of daily living disturbance because of leg cramps, (5) satisfaction with surgery and walking ability, (6) the Roland-Morris Disability Questionnaire, and (7) the Oswestry Disability Index. RESULTS.: Eighty-five (70.8%) patients with LCS and 137 (37.2%) of the control population experienced leg cramps (age and sex adjusted odds ratio; 4.6, P < 0.01). Leg cramps occurred once or twice a week in 34.9% of the LCS group and once in several months in 44.5% of the control group, and occurred nocturnally in 73.3% of the LCS patients and in 91.6% of the control group. In LCS patients, leg cramps improved after surgery in 18.2%, remained unchanged in 45.5%, and worsened in 26.1%, and activities of daily living were disturbed in 47.6%. There was no significant difference in satisfaction with surgery, the Oswestry Disability Index, the Roland-Morris Disability Questionnaire scores, or walking ability between the LCS patients with or without leg cramps. CONCLUSION.: LCS patients had significantly more frequent attacks of nocturnal leg cramps than the control population, and leg cramps disturbed the quality of the patients' life, and they rarely improved after decompression surgery. Leg cramps should be recognized as one of the symptoms of LCS, which disturb the patients' quality of life. © 2009, Lippincott Williams & Wilkins.

It is expected that human neural stem/progenitor cells (hNS/PCs) will some day be used in cell replacement therapies. However, their availability is limited because of ethical issues, so they have to be expanded to obtain sufficient amounts for clinical application. Moreover, in-vitro-maintained hNS/PCs may have a potential for tumorigenicity that could be manifested after transplantation in vivo. In the present study, we demonstrate the in vitro and in vivo properties of long-term-expanded hNS/PCs, including a 6-month bioluminescence imaging (BLI) study of their in vivo tumorigenicity. hNS/PCs cultured for approximately 250 days in vitro (hNS/PCs-250) exhibited a higher growth rate and greater neurogenic potential than those cultured for approximately 500 days in vitro (hNS/PCs-500), which showed greater gliogenic potential. In vivo, both hNS/PCs-250 and -500 differentiated into neurons and astrocytes 4 weeks after being transplanted into the striatum of immunodeficient mice, and hNS/PCs-250 exhibited better survival than hNS/PCs-500 at this time point. We also found that the grafted hNS/PCs-250 survived stably and differentiated properly into neurons and astrocytes even 6 months after the surgery. Moreover, during the 6-month observation period by BLI, we did not detect any evidence of rapid tumorigenic growth of the grafted hNS/PCs, and neither PCNA/ Ki67-positive proliferating cells nor significant malignant invasive features were detected histologically. These findings support the idea that hNS/PCs may represent a nontumorigenic, safe, and appropriate cell source for regenerative therapies for neurological disorders. © 2008 Wiley-Liss, Inc.

We applied diffusion tensor tractography (DTT), a recently developed MRI technique that reveals the microstructures of tissues based on its ability to monitor the random movements of water molecules, to the visualization of peripheral nerves after injury. The rat sciatic nerve was subjected to contusive injury, and the data obtained from diffusion tensor imaging (DTI) were used to determine the tracks of nerve fibers (DTT). The DTT images obtained using the fractional anisotropy (FA) threshold value of 0.4 clearly revealed the recovery process of the contused nerves. Immediately after the injury, fiber tracking from the designated proximal site could not be continued beyond the lesion epicenter, but the intensity improved thereafter, returning to its pre-injury level by 3 weeks later. We compared the FA value, a parameter computed from the DTT data, with the results of histological and functional examinations of the injured nerves, during recovery. The FA values of the peripheral nerves were more strongly correlated with axon-related (axon density and diameter) than with myelin-related (myelin density and thickness) parameters, supporting the theories that axonal membranes play a major role in anisotropic water diffusion and that myelination can modulate the degree of anisotropy. Moreover, restoration of the FA value at the lesion epicenter was strongly correlated with parameters of motor and sensory functional recovery. These correlations of the FA values with both the histological and functional changes demonstrate the potential usefulness of DTT for evaluating clinical events associated with Wallerian degeneration and the regeneration of peripheral nerves. © 2008 Elsevier Inc. All rights reserved.

Spinal cord injury (SCI), despite considerable progress in palliative care, has currently no satisfying therapeutic leading to functional recovery. Inability of central nervous system severed axons to regenerate after injury is considered to originate from both limited intrinsic capabilities of neurons and inhibitory effect of the local environment. Precisely, the so-called "glial scar" formed by reactive astrocytes in response to injury exerts a well-known axon-outgrowth inhibitory effect. However, recent studies revealed that role of reactive astrocytes after SCI is more complex. During the first weeks after injury, reactive astrocytes indeed protect the tissue and contribute to a spontaneous relative functional recovery. Compaction of the lesion center and seclusion of inflammatory cells by migrating reactive astrocytes seem to underlie this beneficial effect. Stimulation of reactive astrocytes migration in the sub-acute phase of SCI might thus represent a new approach to improve the functional outcome of patients. © 2008 Elsevier Ltd. All rights reserved.

Purpose: To investigate whether diffusion-tensor tractography (DTT) of neuronal fibers is useful for delineating the configuration of the neuronal fiber trajectories in the primate visual pathway, including the well-developed optic chiasm, in comparison with tract tracing at manganese-enhanced magnetic resonance (MR) imaging. Materials and Methods: The handling methods used for all the animals in this study were approved by the institutional committee for animal experiments. Diffusion-tensor MR imaging was performed in four healthy common marmosets, and in two of these animals, manganese-enhanced MR imaging tract tracing was performed by using a 7.0-T MR imaging unit. The visual pathways were quantitatively investigated in terms of the manganese distribution observed on the manganese- enhanced MR images. The images obtained with DTT and manganese-enhanced MR imaging tract tracing were qualitatively compared, and the features of the visual pathway were verified through fusion of the reconstructed images obtained by using these two modalities. Results: DTT provided information regarding the neuroanatomic features of the marmoset visual pathway and revealed the bilateral branching patterns of the typical primate retino-geniculate pathways, although several incorrectly tracked fibers were noted. The distribution of manganese on the manganese-enhanced MR images revealed bilateral innervation of the retinal projections and depicted the layered internal structure of the lateral geniculate nuclei bilaterally, depending on the ocularity of each layer. These morphologic findings were consistent with those of previous histopathologic studies. Conclusion: The findings of this preliminary study raise the possibility that DTT is useful for visualizing the neuronal fiber trajectories in primate visual pathways. © RSNA, 2008.

Object. This retrospective study was conducted to evaluate the prevalence and clinical consequences of postoperative lamina closure after open-door laminoplasty and to identify the risk factors. Methods. Eighty-two consecutive patients with cervical myelopathy who underwent open-door laminoplasty without plates or spacers in the open side (Hirabayashi's original method) were included (62 men and 20 women with a mean age of 62 years and a mean follow-up of 1.8 years). In 67 patients the cause of cervical myelopathy was spondylotic myelopathy, and in 15 it was caused by ossification of posterior longitudinal ligament. Radiographic measurements were made of the anteroposterior diameters of the spinal canal and vertebral bodies from C3-6, and the presence of kyphosis were assessed. Lamina closure was defined as ≥ 10% decrease in the canal-to-body ratio at the final follow-up compared with that immediately after surgery at ≥ 1 vertebral level. The impact of lamina closure on neck pain, patient satisfaction, Japanese Orthopaedic Association scores, and recovery rates were also evaluated. Results. The mean canal-to-body ratio at C3-6 was 0.69-0.72 preoperatively, 1.25-1.28 immediately after surgery, and 1.18-1.24 at the final follow-up examination. Lamina closure was observed in 34% of patients and was not associated with sex, age, or cause of myelopathy, but was significantly associated with the presence of preoperative kyphosis (p = 0.014). Between patients with and without lamina closure, there was no significant difference in preoperative (9.7 ± 3.1 vs 10.6 ± 2.5) and postoperative (13.7 ± 2.4 vs 13.1 ± 2.7) Japanese Orthopaedic Association scores, recovery rates (53.9 ± 29.9% vs 44.3 ± 29.5%), neck pain scores (3.5 ± 0.7 vs 3.3 ± 1.0), or patient satisfaction level (4.0 ± 1.4 vs 4.8 ± 1.0). Conclusions. Lamina closure at ≥ 1 vertebral level occurred in 34% of patients. Although patients with lamina closure obtained equivalent recovery from myelopathy in a short-term follow-up, they tended to be less satisfied with surgery compared with those who did not have closure. The only significant risk factor identified was the presence of preoperative cervical kyphosis, and preventative methods for lamina closure, therefore, should be considered for patients with preoperative kyphosis.

STUDY DESIGN: Retrospective study of patients who underwent laminectomy for unification. OBJECTIVE: To identify radiographic predictors of residual low back pain (LBP) after laminectomy for lumbar spinal canal stenosis (LCS). SUMMARY OF BACKGROUND DATA: Residual LBP is a common complication of laminectomy and no radiographic predictors of its occurrence have been identified previously. METHODS: Clinical results and radiographic findings in 49 patients (21 males and 28 females, minimum 5-year follow-up) who underwent single level laminectomy for LCS were retrospectively reviewed. Patients who had an improvement in LBP scores in the Japanese Orthopedic Association (JOA) scoring system during the follow-up periods were classified as the recovery group, whereas those without improvements were classified as the nonrecovery group. Patients' clinical data (sex, duration of symptoms, age at surgery, JOA scores) and radiographic parameters (including lumbar lordotic angle, lumbar range of motion (ROM) and the intervertebral rotational angle) were analyzed to detect the factors significantly related with the occurrence of residual LBP. RESULTS: The average preoperative JOA score of 14.8±5.1 points improved to 21.6±5.5 points at the final follow-up providing an average recovery rate of 48.1±36.8%. Thirty-four and 15 patients were classified into the recovery and the nonrecovery groups, respectively. Binary logistic regression analysis revealed that significant predictors of residual LBP were preoperative lumbar lordosis angle and lumbar ROM. The mean preoperative lumbar lordosis and ROM in the nonrecovery group were significantly smaller than those in the recovery group (lordosis: 25.3±15.8 degrees vs. 37.8±13.6 degrees, P=0.006 and ROM: 22.1±10.6 degrees vs. 31.2±9.9 degrees, P=0.006). In addition, increase of the postoperative lumbar ROM was significantly larger in the nonrecovery than that in the recovery group (P=0.009). CONCLUSIONS: Our results indicate that preoperative lordosis angle and lumbar ROM were the significant radiographic predictors for residual LBP after laminectomy for LCS. Patient with flatback and limited lumbar mobility before surgery are prone to suffer residual LBP. It is suggested that these sagittal radiographic parameters should be taken into account when choosing laminectomy as the surgical option for LCS. © 2008 Lippincott Williams & Wilkins, Inc.

Dendritic cells (DCs) have important functions as modulators of immune responses, and their ability to activate T cells is of great value in cancer immunotherapy. The isolation of DCs from the peripheral blood of rhesus and African green monkeys has been reported, but the immune system in the common marmoset remains poorly characterized, although it offers many potential advantages for preclinical studies. In the present study, we devised methods, based on techniques developed for mouse and human DC preparation, for isolating DCs from three major tissue sources in the common marmoset: bone marrow (BM), spleen and peripheral blood. Each set of separated cells was analysed using the cell surface DC-associated markers CD11c, CD80, CD83, CD86 and human leucocyte antigen (HLA)-DR, all of which are antibodies against human antigens, and the cells were further characterized both functionally and morphologically as antigen-presenting cells. BM proved to be an excellent cell source for the isolation of DCs intended for preclinical studies on cell therapy, for which large quantities of cells are required. In the BM-derived CD11c+ cell population, cells exhibiting the characteristic features of DCs were enriched, with the typical DC morphology and the abilities to undergo endocytosis, to secrete interleukin (IL)-12, and to stimulate Xenogenic T cells. Moreover, BM-derived DCs produced the neurotrophic factor NT-3, which is also found in murine splenic DCs. These results suggest that BM-derived DCs from the common marmoset may be useful for biological analysis and for preclinical studies on cell therapy for central nervous system diseases and cancer. © 2007 Blackwell Publishing Ltd.

A multiplex analysis for profiling the expression of candidate genes along with epigenetic modification may lead to a better understanding of the complex machinery of neuropathic pain. In the present study, we found that partial sciatic nerve ligation most remarkably increased the expression of monocyte chemotactic protein 3 (MCP-3, known as CCL7) a total of 33 541 genes in the spinal cord, which lasted for 4 weeks. This increase in MCP-3 gene transcription was accompanied by the decreased trimethylation of histone H3 at Lys27 at the MCP-3 promoter. The increased MCP-3 expression associated with its epigenetic modification observed in the spinal cord was almost abolished in interleukin 6 knockout mice with partial sciatic nerve ligation. Consistent with these findings, a single intrathecal injection of recombinant proteins of interleukin 6 significantly increased MCP-3 messenger RNA with a decrease in the level of Lys27 trimethylation of histone H3 at the MCP-3 promoter in the spinal cord of mice. Furthermore, deletion of the C-C chemokine receptor type 2 (CCR2) gene, which encodes a receptor for MCP-3, failed to affect the acceleration of MCP-3 expression in the spinal cord after partial sciatic nerve ligation. A robust increase in MCP-3 protein, which lasted for up to 2 weeks after surgery, in the dorsal horn of the spinal cord of mice with partial sciatic nerve ligation was seen mostly in astrocytes, but not microglia or neurons. On the other hand, the increases in both microglia and astrocytes in the spinal cord by partial sciatic nerve ligation were mostly abolished in interleukin 6 knockout mice. Moreover, this increase in microglia was almost abolished by CCR2 gene deletion, whereas the increase in astrocytes was not affected in nerve-ligated mice that lacked the CCR2 gene. We also found that either in vivo or in vitro treatment with MCP-3 caused robust microglia activation. Under these conditions, intrathecal administration of MCP-3 antibody suppressed the increase in microglia within the mouse spinal cord and neuropathic pain-like behaviours after nerve injury. With the use of a functional magnetic resonance imaging analysis, we demonstrated that a single intrathecal injection of MCP-3 induced dramatic increases in signal intensity in pain-related brain regions. These findings suggest that increased MCP-3 expression associated with interleukin 6 dependent epigenetic modification at the MCP-3 promoter after nerve injury, mostly in spinal astrocytes, may serve to facilitate astrocyte-microglia interaction in the spinal cord and could play a critical role in the neuropathic pain-like state. © 2013 The Author (2013). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.

Severe cervical kyphosis requiring surgical treatment is rare in patients with neurofibromatosis Type 1 (NF1). When it occurs, however, dystrophic changes in the vertebrae make surgical correction and fusion of the deformity extremely difficult. The authors report on 3 cases of severe cervical kyphosis associated with NF1 that were successfully treated with combined anterior and posterior correction and fusion. All patients underwent halo-gravity traction for approximately 1 month prior to surgery to correct the deformity gradually. Posterior correction and fusion were performed with segmental spinal instrumentation consisting of lateral mass screws, lamina screws, pedicle screws, and polyethylene tape for sublaminar wiring. Anterior spinal fusion was performed using a fibula strut to induce solid bone fusion. All patients used a halo vest for postoperative external fixation. Preoperative CT scans showed dystrophic cervical spine changes, and MR images demonstrated extensive neurofibromas outside the cervical spine in all 3 patients. The preoperative kyphotic angles were as follows: Case 1, 140°; Case 2, 81°; and Case 3, 72°; after halo-gravity traction, the kyphosis angles improved to 50°, 55°, and 51°, respectively; and after surgery, they were 50°, 15°, and 27°, respectively. Solid bone union was observed in all patients at the latest follow-up. All three patients experienced postoperative complications consisting of superficial infection, severe pneumonia, and partial dislocation of the distal fibula graft after removing the halo vest, in one patient each. Although dystrophic cervical vertebral changes in these patients with NF1 complicated the correction of severe cervical kyphosis, the use of preoperative halo-gravity traction, a combination of spinal instrumentations, an anterior strut bone graft, and postoperative halo-vest fixation made it possible to correct the kyphosis, maintain the correction, and achieve solid bone fusion. © 2013 AANS.

Despite their nearly universal activation of mammalian target of rapamycin (mTOR) signaling, glioblastomas (GBMs) are strikingly resistant to mTOR-targeted therapy. We analyzed GBM cell lines, patient-derived tumor cell cultures, and clinical samples from patients in phase 1 clinical trials, and find that the promyelocytic leukemia (PML) gene mediates resistance to mTOR-targeted therapies. Direct mTOR inhibitors and EGF receptor (EGFR) inhibitors that block downstreammTOR signaling promote nuclear PML expression in GBMs, and genetic overexpression and knockdown approaches demonstrate that PML prevents mTOR and EGFR inhibitor-dependent cell death. Low doses of the PML inhibitor, arsenic trioxide, abrogate PML expression and reverse mTOR kinase inhibitor resistance in vivo, thus markedly inhibiting tumor growth and promoting tumor cell death in mice. These results identify a unique role for PML in mTOR and EGFR inhibitor resistance and provide a strong rationale for a combination therapeutic strategy to overcome it.

Solitary bone cysts of the lumbar vertebrae are extremely rare. We report a 20-year-old man, who presented with a 5-year history of persistent low back pain. Radiographic examination, magnetic resonance imaging, and subsequent computed tomography revealed a well-circumscribed osteolytic and cystic lesion at the right pedicle of the L3 vertebra. On the basis of the radiologic findings, a simple bone cyst was considered the most probable diagnosis. The patient underwent a minimally invasive operation with the assistance of an endoscope. The gross total curettage resection of the lesion including the cyst walls was accomplished, followed by a combined graft consisting of granulated β-tricalcium phosphate and autologous iliac crest cancellous bone. At the 1-year follow-up, the patient's symptoms were resolved, bone union at the lesion site had been achieved, and he had returned to his previous level of physical activity. Copyright © 2013 by Lippincott Williams & Wilkins.

The enthusiasm for producing patient-specific human embryonic stem cells using somatic nuclear transfer has somewhat abated in recent years because of ethical, technical, and political concerns. However, the interest in generating induced pluripotent stem cells (iPSCs), in which pluripotency can be obtained by transcription factor transduction of various somatic cells, has rapidly increased. Human iPSCs are anticipated to open enormous opportunities in the biomedical sciences in terms of cell therapies for regenerative medicine and stem cell modeling of human disease. On the other hand, recent reports have emphasized the pitfalls of iPSC technology, including the potential for genetic and epigenetic abnormalities, tumorigenicity, and immunogenicity of transplanted cells. These constitute serious safety-related concerns for iPSC-based cell therapy. However, preclinical data supporting the safety and efficacy of iPSCs are also accumulating. In this Review, recent achievements and future tasks for safe iPSC-based cell therapy are summarized, using regenerative medicine for repair strategies in the damaged central nervous system (CNS) as a model. Insights on safety and preclinical use of iPSCs in cardiovascular repair model are also discussed. © 2013 American Heart Association, Inc.

Stimulated by the 2012 Nobel Prize in Physiology or Medicine awarded for Shinya Yamanaka and Sir John Gurdon, there is an increasing interest in the induced pluripotent stem (iPS) cells and reprograming technologies in medical science. While iPS cells are expected to open a new era providing enormous opportunities in biomedical sciences in terms of cell therapies and regenerative medicine, safety-related concerns for iPS cell-based cell therapy should be resolved prior to the clinical application of iPS cells. In this review, the pre-clinical investigations of cell therapy for spinal cord injury (SCI) using neural stem/progenitor cells derived from iPS cells, and their safety issues in vivo, are outlined. We also wish to discuss the strategy for the first human trails of iPS cell-based cell therapy for SCI patients. © 2013 IBCB, SIBS, CAS All rights reserved.

Study design: Retrospective case series. Objective: To evaluate our treatment strategy for cervical dumbbell neurinoma. Summary of background data: In treating cervical dumbbell neurinoma, possible difficulties include reoperation due to recurrent tumor, denervation due to nerve root resection, and postoperative spinal deformity due to extensive bony removal. Methods: We reviewed 75 cases of cervical dumbbell neurinoma that were treated surgically between 1985 and 2006. Postoperative neurological deficits, effects of surgical margins on tumor recurrence, and surgical complications were investigated retrospectively. Results: Sensory and motor deficits due to resection of specific nerve roots appeared temporarily in 33 and 23 % of all cases, and persisted in 8 and 8 % at final evaluation, respectively. Total, subtotal, and partial resection was performed in 57, 13, and 5 cases, respectively. The total resection rate was low in the tumors that had large extraforaminal components. Of the subtotally resected 13 cases, only two cases of high tumor-growth rate required re-operation or showed tumor growth. Among the five partially resected cases, re-operation was necessary in two cases 13 and 15 years later because of aggravated neurological symptoms due to tumor growth. Two patients who underwent C2 laminectomy developed kyphosis, and three patients who underwent facet joint resection and curettage of vertebral body lesions developed scoliosis. Conclusion: Total resection should be attempted for cervical dumbbell tumors. In cases where total resection was potentially of high risk, however, subtotal resection (within the capsule) was found to be a practical choice yielding favorable long-term outcome when the tumor growth rate (MIB-1 index) was low. © 2012 The Japanese Orthopaedic Association.

STUDY DESIGN.: Basic imaging experiment. OBJECTIVE.: To determine whether in vivo diffusion tensor tractography (DTT) can be used to evaluate the axonal disruption of the chronically compressed spinal cord in tiptoe walking Yoshimura (twy) mice. SUMMARY OF BACKGROUND DATA.: In cervical ossification of the posterior longitudinal ligament, axonal disruption results in motor and sensory functional impairment. Twy mice develop spontaneous calcification in the cervical ligaments, which causes chronic compression of the spinal cord. DTT is emerging as a powerful tool for tracing axonal fibers in vivo. METHODS.: Five twy mice were subjected to DTT at 6, 15, and 20 weeks of age. Magnetic resonance imaging was performed using a 7.0-Tesla magnet (Biospec 70/16; Billerica, MA) with a CryoProbe. Diffusion tensor images were analyzed using TrackVis (Massachusetts General Hospital, MA). Motor performance was evaluated by Rotarod treadmill test and Digigait analysis. Histological analysis was performed by hematoxylin-eosin staining and immunostaining for RT-97 and SMI-31. RESULTS.: High resolution DTT of twy mice in vivo was successful. A lower number of RT-97- or SMI-31-positive fibers were associated with more severe spinal cord compression, which was determined by observing the ligamentous calcification at the C2-C3 level in each twy mouse. The severity of canal stenosis based on magnetic resonance images was strongly correlated with the axial area of the spinal cord. The tract fiber (TF) ratio (the number of TFs at the C2-C3 level/the number of TFs at the C0-C1 level) was strongly correlated with the RT-97/SMI-31-positive area and with motor function (rotarod latency, stride length). Furthermore, a two-part linear regression analysis showed that canal stenosis around 50% to 60% caused a sharp decrease in the TF ratio before the deterioration of motor function. CONCLUSION.: We conclude that DTT could be useful for detecting the early changes associated with the compressed spinal cord in cervical ossification of the posterior longitudinal ligament. Copyright © 2013 Lippincott Williams & Wilkins.

We describe the clinical features of limbic encephalitis that developed after palliative spinal cordotomy in 2 patients with malignant thoracic astrocytoma. Both patients showed short-term memory loss, hallucinations of smells and psychiatric symptoms. Brain MRI on T2-weighted and fluid-attenuated inversion recovery sequences revealed high intensity lesions in bilateral temporal lobe areas. We considered that both patients had paraneoplastic limbic encephalitis associated with astrocytoma because of various clinical and radiological features. But the possibility of intracranial dissemination of astrocytoma could not be fully excluded. The differential diagnosis between intracranial dissemination of spinal cord astrocytoma and paraneoplastic limbic encephalitis may be sometimes difficult. © 2012 The Japanese Society of Internal Medicine.