Details of a Researcher - Nakamura, Masaya

Papers - Nakamura, Masaya

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Major complications and sequelae after total en bloc spondylectomy for malignant spinal tumors

Matsumoto Morio, Hikata Tomohiro, Iwanami Akio, Hosogane Naobumi, Watanabe Kota, Ishii Ken, Nakamura Masaya, Toyama Yoshiaki

Neurosurgery Quarterly 2014.07

ISSN 1050-6438

This retrospective study looked at 33 consecutive patients with malignant, aggressive tumors in the thoracic and lumbar spine who underwent TES (24 men and 9 women; mean age 49.9 years; mean follow-up 3.6 years; 14 primary tumors and 19 metastatic tumors). TES was performed by a posterior-only approach in 15 patients and by a combined anterior and posterior approach in 18 patients. We classified complications as intraoperative, early (within 1 month after surgery), or late (>1 month after surgery), and examined the relationships between major complications and potentially related factors. Ten died of disease at 22.3 months after TES. Local recurrence was observed in 8 patients (24%) at an average of 15.4 months. Thirty-one major complications occurred in 24 patients (72.7%). There were 3 intraoperative, 17 early, and 11 late complications. Intraoperative complications included injury to the segmental artery, to the aorta, and to the spinal cord in 1 patient each. Early complications included prolonged chest tube drainage, cerebrospinal fluid leakage, and monoplegia due to the severing of nerve roots in 3 patients each, and pulmonary embolism, recurrent nerve palsy, pneumonia, endplate fracture, implant dislodgement, gastric ulcer, and ileus in 1 patient each. Late complications included implant failures in 8 patients and infection in 3 patients. Major complications were significantly associated with major blood loss (P=0.047). TES was frequently associated with major intraoperative, early, and late postoperative complications; most complications were managed successfully.

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Intramedullary cervicothoracic subependymoma

Wu Zhiwei, Iwanami Akio, Yasuda Akimasa, Mikami Shuji, Toyama Yoshiaki, Nakamura Masaya

Journal of Orthopaedic Science 20 ( 5 ) 927 - 934 2014.05

ISSN 0949-2658

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Surgeons' exposure to radiation in single- and multi- level minimally invasive transforaminal lumbar interbody fusion; a prospective study

Funao Haruki, Ishii Ken, Momoshima Suketaka, Iwanami Akio, Hosogane Naobumi, Watanabe Kota, Nakamura Masaya, Toyama Yoshiaki, Matsumoto Morio

PLoS ONE 9 ( 4 ) 2014.04

Although minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has widely been developed in patients with lumbar diseases, surgeons risk exposure to fluoroscopic radiation. However, to date, there is no studies quantifying the effective dose during MIS-TLIF procedure, and the radiation dose distribution is still unclear. In this study, the surgeons' radiation doses at 5 places on the bodies were measured and the effective doses were assessed during 31 consecutive 1- to 3-level MIS-TLIF surgeries. The operating surgeon, assisting surgeon, and radiological technologist wore thermoluminescent dosimeter on the unshielded thyroid, chest, genitals, right middle finger, and on the chest beneath a lead apron. The doses at the lens and the effective doses were also calculated. Mean fluoroscopy times were 38.7, 53.1, and 58.5 seconds for 1, 2, or 3 fusion levels, respectively. The operating surgeon's mean exposures at the lens, thyroid, chest, genitals, finger, and the chest beneath the shield, respectively, were 0.07, 0.07, 0.09, 0.14, 0.32, and 0.05 mSv in 1-level MIS-TLIF; 0.07, 0.08, 0.09, 0.18, 0.34, and 0.05 mSv in 2-level; 0.08, 0.09, 0.14, 0.15, 0.36, and 0.06 mSv in 3-level; and 0.07, 0.08, 0.10, 0.15, 0.33, and 0.05 mSv in all cases. Mean dose at the operating surgeon's right finger was significantly higher than other measurements parts (P,0.001). The operating surgeon's effective doses (0.06, 0.06, and 0.07 mSv for 1, 2, and 3 fusion levels) were low, and didn't differ significantly from those of the assisting surgeon or radiological technologist. Revision MIS-TLIF was not associated with higher surgeons' radiation doses compared to primary MIS-TLIF. There were significantly higher surgeons' radiation doses in over-weight than in normal-weight patients. The surgeons' radiation exposure during MIS-TLIF was within the safe level by the International Commission on Radiological Protection's guidelines. The accumulated radiation exposure, especially to surgeon's hands, should be carefully monitored. © 2014 Funao et al.

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Rewiring of regenerated axons by combining treadmill training with semaphorin3A inhibition

Zhang Liang, Kaneko Shinjiro, Kikuchi Kaoru, Sano Akihiko, Maeda Miho, Kishino Akiyoshi, Shibata Shinsuke, Mukaino Masahiko, Toyama Yoshiaki, Liu Meigen, Kimura Toru, Okano Hideyuki, Nakamura Masaya

Molecular Brain 7 ( 1 ) 2014.03

Background: Rats exhibit extremely limited motor function recovery after total transection of the spinal cord (SCT). We previously reported that SM-216289, a semaphorin3A inhibitor, enhanced axon regeneration and motor function recovery in SCT adult rats. However, these effects were limited because most regenerated axons likely do not connect to the right targets. Thus, rebuilding the appropriate connections for regenerated axons may enhance recovery. In this study, we combined semaphorin3A inhibitor treatment with extensive treadmill training to determine whether combined treatment would further enhance the "rewiring" of regenerated axons. In this study, which aimed for clinical applicability, we administered a newly developed, potent semaphorin3A inhibitor, SM-345431 (Vinaxanthone), using a novel drug delivery system that enables continuous drug delivery over the period of the experiment. Results: Treatment with SM-345431 using this delivery system enhanced axon regeneration and produced significant, but limited, hindlimb motor function recovery. Although extensive treadmill training combined with SM-345431 administration did not further improve axon regeneration, hindlimb motor performance was restored, as evidenced by the significant improvement in the execution of plantar steps on a treadmill. In contrast, control SCT rats could not execute plantar steps at any point during the experimental period. Further analyses suggested that this strategy reinforced the wiring of central pattern generators in lumbar spinal circuits, which, in turn, led to enhanced motor function recovery (especially in extensor muscles). Conclusions: This study highlights the importance of combining treatments that promote axon regeneration with specific and appropriate rehabilitations that promote rewiring for the treatment of spinal cord injury. © 2014 Zhang et al.; licensee BioMed Central Ltd.

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Inflammatory cascades mediate synapse elimination in spinal cord compression

Takano Morito, Kawabata Soya, Komaki Yuji, Shibata Shinsuke, Hikishima Keigo, Toyama Yoshiaki, Okano Hideyuki, Nakamura Masaya

Journal of Neuroinflammation 11 2014.03

Background: Cervical compressive myelopathy (CCM) is caused by chronic spinal cord compression due to spondylosis, a degenerative disc disease, and ossification of the ligaments. Tip-toe walking Yoshimura (twy) mice are reported to be an ideal animal model for CCM-related neuronal dysfunction, because they develop spontaneous spinal cord compression without any artificial manipulation. Previous histological studies showed that neurons are lost due to apoptosis in CCM, but the mechanism underlying this neurodegeneration was not fully elucidated. The purpose of this study was to investigate the pathophysiology of CCM by evaluating the global gene expression of the compressed spinal cord and comparing the transcriptome analysis with the physical and histological findings in twy mice. Methods: Twenty-week-old twy mice were divided into two groups according to the magnetic resonance imaging (MRI) findings: a severe compression (S) group and a mild compression (M) group. The transcriptome was analyzed by microarray and RT-PCR. The cellular pathophysiology was examined by immunohistological analysis and immuno-electron microscopy. Motor function was assessed by Rotarod treadmill latency and stride-length tests. Results: Severe cervical calcification caused spinal canal stenosis and low functional capacity in twy mice. The microarray analysis revealed 215 genes that showed significantly different expression levels between the S and the M groups. Pathway analysis revealed that genes expressed at higher levels in the S group were enriched for terms related to the regulation of inflammation in the compressed spinal cord. M1 macrophage-dominant inflammation was present in the S group, and cysteine-rich protein 61 (Cyr61), an inducer of M1 macrophages, was markedly upregulated in these spinal cords. Furthermore, C1q, which initiates the classical complement cascade, was more upregulated in the S group than in the M group. The confocal and electron microscopy observations indicated that classically activated microglia/macrophages had migrated to the compressed spinal cord and eliminated synaptic terminals. Conclusions: We revealed the detailed pathophysiology of the inflammatory response in an animal model of chronic spinal cord compression. Our findings suggest that complement-mediated synapse elimination is a central mechanism underlying the neurodegeneration in CCM. © 2014 Takano et al.; licensee BioMed Central Ltd.

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Distinct roles of endogenous vascular endothelial factor receptor 1 and 2 in neural protection after spinal cord injury

Shinozaki Munehisa, Nakamura Masaya, Konomi Tsunehiko, Kobayashi Yoshiomi, Takano Morito, Saito Nobuhito, Toyama Yoshiaki, Okano Hideyuki

Neuroscience Research 78 ( 1 ) 55 - 64 2014.01

ISSN 0168-0102

Secondary degeneration after spinal cord injury (SCI) is caused by increased vascular permeability, infiltration of inflammatory cells, and subsequent focal edema. Therapeutic interventions using neurotrophic factors have focused on the prevention of such reactions to reduce cell death and promote tissue regeneration. Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor. However, the effect of VEGF on SCI remains controversial. VEGF signaling is primarily regulated through two primary receptors, VEGF receptor 1 (VEGF-R1) and VEGF receptor 2 (VEGF-R2). The purpose of this study was to examine the effects of intraperitoneal administration of VEGF-R1- and VEGF-R2-neutralizing antibodies on a mouse model of SCI. VEGF-R1 blockade, but not VEGF-R2 blockade, decreased the permeability and infiltration of inflammatory cells, and VEGF-R2 blockade caused a significant increase in neuronal apoptosis in the acute phase of SCI. VEGF-R2 blockade decreased the residual tissue area and the number of neural fibers in the chronic phase of SCI. VEGF-R2 blockade worsened the functional recovery and prolonged the latency of motor evoked potentials. These data suggest that endogenous VEGF-R2 plays a crucial role in neuronal protection after SCI. © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society.

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Perioperative factors affecting the occurrence of acute complex regional pain syndrome following limb bone fracture surgery

Sumitani Masahiko, Yasunaga Hideo, Uchida Kanji, Horiguchi Hiromasa, Nakamura Masaya, Ohe Kazuhiko, Fushimi Kiyohide, Matsuda Shinya, Yamada Yoshitsugu

Rheumatology (United Kingdom) 53 ( 7 ) 1186 - 1193 2014

ISSN 1462-0324

Objective: Complex regional pain syndrome (CRPS) describes a broad spectrum of symptoms that predominantly localize to the extremities. Although limb fracture is one of the most frequently reported triggering events, few large-scale studies have shown the occurrence of and factors associated with CRPS following limb fracture. This study aimed to show the occurrence and identify of those factors. Methods: Using the Japanese Diagnosis Procedure Combination database, we identified 39 patients diagnosed with CRPS immediately after open reduction and internal fixation (ORIF) for limb fracture from a cohort of 185 378 inpatients treated with ORIF between 1 July and 31 December of each year between 2007 and 2010. Patient and clinical characteristics such as age, gender, fracture site, duration of anaesthesia and use of regional anaesthesia were investigated by logistic regression analyses to examine associations between these factors and the in-hospital occurrence of CRPS after ORIF. Results: The occurrence of CRPS was relatively high in fractures of the distal forearm, but low in fractures of the lower limb and in patients with multiple fractures. Generally females are considered to be at high risk of CRPS; however, we found a comparable number of male and female patients suffering from CRPS after ORIF for limb fracture. In terms of perioperative factors, a longer duration of anaesthesia, but not regional anaesthesia, was significantly associated with a higher incidence of CRPS. Conclusion: Although a limited number of CRPS patients were analysed in this study, reduced operative time might help to prevent the development of acute CRPS following limb fracture. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

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Pediatric myxopapillary ependymoma treated with subtotal resection and radiation therapy

Shirasawa H., Ishii K., Iwanami A., Mikami S., Toyama Y., Matsumoto M., Nakamura M.

Spinal Cord 52 ( SUPPL. 2 ) 2014

ISSN 1362-4393

Study design:Case report and review of the literature.Objectives: Myxopapillary ependymoma (MPE) is a relatively rare glioma that develops from the spinal part of the filum terminale, usually in adulthood. While it is generally benign, MPE can disseminate intraspinally, and this malignant behavior requires a multidisciplinary response with surgery and radiotherapy. We report here a case of MPE occurring in the lumbosacral spine area of an 8-year-old boy.Setting:Japan, Tokyo.Methods:We report here a case of MPE, treated with subtotal surgical resection followed by craniospinal irradiation (CSI), in an 8-year-old boy. The patient was referred to our hospital with a 6-month history of severe pain in the lower back and legs, paralysis of the legs and dysuria. Magnetic resonance imaging images showed a large tumor that filled the entire spinal canal below L1. After subtotal resection of the tumor, the pathological findings established a diagnosis of MPE. Since the tumor had perforated its capsule, increasing the risk of intraspinal dissemination, the patient underwent radiotherapy and CSI after surgery.Results:Magnetic resonance images obtained 3 years after the surgery did not show any recurrence of MPE.Conclusion:Although tumor resection followed by CSI can be considered an effective strategy for treating a child with MPE, long-term follow-up is necessary to ensure early detection of any local recurrence or dissemination of the tumor, or of post-radiotherapy scoliosis. © 2014 International Spinal Cord Society All rights reserved.

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Prevalence and characteristics of chronic musculoskeletal pain in Japan

Nakamura Masaya, Nishiwaki Yuji, Ushida Takahiro, Toyama Yoshiaki

Journal of Orthopaedic Science 19 ( 2 ) 339 - 350 2014

ISSN 0949-2658

Background: An epidemiological survey conducted in Japan in fiscal year 2010 revealed a high prevalence of chronic musculoskeletal pain, low patient satisfaction with treatment, a high incidence of protracted treatment lasting a year or more, and reduced quality of life. To improve the current system for treating chronic musculoskeletal pain, it is important to identify risk factors, including patient characteristics, for developing chronic pain. Thus, we sought to determine the incidence of new chronic pain in the Japanese population, as well as the persistence rate, associated factors, and current state of treatment of chronic pain, by repeating a postal survey in a nationwide representative sample group first surveyed in 2010. Methods: Among 11,507 participants in the 2010 epidemiological survey, 1,717 reported chronic pain and 6,283 reported no chronic pain. A repeat questionnaire, mailed to subjects in these 2 groups in fiscal year 2011, received replies from 85 % of those who reported pain and 76 % of those without pain in 2010. Results: The incidence of new chronic pain was 11.1 %. Risk factors for developing chronic pain included working in a professional, managerial, or clerical/specialist occupation, being female, having a BMI ≥25; currently using alcohol or cigarettes; and having completed an education level of vocational school or higher. Persistent chronic pain was reported by 45.2 % of respondents. Those with severe (VAS score ≥7) and constant lower-back pain lasting more than 5 years had the highest risk of the pain persisting. More than 80 % respondents with persistent chronic pain had a history of treatment, and while about 30 % were still receiving treatment at the time of the survey, the other 50 % had discontinued treatment despite the persistence of pain because of a low degree of satisfaction with treatment. Discussion: We identified risk factors related to the development of new chronic pain and the persistence of chronic pain. Countermeasures to prevent chronic pain could be especially important for the high-risk populations for understanding the pathology of chronic pain. © 2014 The Author(s).

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Factors contributing to improvement of syringomyelia after foramen magnum decompression for Chiari type I malformation

Nagoshi Narihito, Iwanami Akio, Toyama Yoshiaki, Nakamura Masaya

Journal of Orthopaedic Science 19 ( 3 ) 418 - 423 2014

ISSN 0949-2658

Background: Although various surgical approaches have been proposed for treating syringomyelia associated with Chiari type I malformation, a standard method has yet to be established. we prospectively investigated the results of our surgical method: foramen magnum decompression combined with C1 laminectomy and excision of the outer layer of the dura mater. Methods: Twenty patients underwent surgery between 2000 and 2010 at our hospital. After surgery, the size of the syrinx decreased in 11 patients (decreased group) but remained unchanged in nine patients (unchanged group). The following parameters were compared: age at the time of surgery, duration of morbidity, improvement of preoperative symptoms, morphological type and length of the syrinx, presence or absence of scoliosis, cervical alignment, basal and clivo-axial angles, and postoperative subarachnoid space at the foramen magnum level. Results: Preoperative symptoms improved in all patients in the decreased group but in only one patient in the unchanged group. The average duration of morbidity was significantly shorter in the decreased group. Morphological examination revealed that the size of all central-type syrinxes decreased after surgery, whereas in all cases of deviated-type syrinx, size was unchanged. The average length of preoperative syrinx was significantly shorter in the decreased group. The postoperative subarachnoid space at the foramen magnum was enlarged in the entire decreased group, whereas residual narrowing of the space was observed in 44 % of patients in the unchanged group. No significant intergroup differences were observed in the other factors. Conclusions: In patients with syringomyelia, a longer and deviated type of syrinx, a longer duration of morbidity, and postoperative residual narrowing of the subarachnoid space are associated with a poor prognosis after the surgical procedure. The pathogenesis of syringomyelia is inconsistent, and the choice of surgical technique for each pathological condition is important. © 2014 The Japanese Orthopaedic Association.

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Investigation of chronic musculoskeletal pain (third report)

Nakamura Masaya, Nishiwaki Yuji, Sumitani Masahiko, Ushida Takahiro, Yamashita Toshihiko, Konno Shinichi, Taguchi Toshihiko, Toyama Yoshiaki

Journal of Orthopaedic Science 19 ( 4 ) 667 - 675 2014

ISSN 0949-2658

Background: The previous epidemiological surveys conducted in Japan revealed that once the vicious cycle of chronic musculoskeletal pain begins, it is difficult to disrupt the cycle. This finding suggests the existence of problems with the conventional approaches to treatment of chronic musculoskeletal pain. The purpose of this study was to investigate the characteristics of patients with chronic musculoskeletal pain focusing on neuropathic and psychogenic pain. Methods: The questionnaire was sent again to the 660 subjects found to have persistent chronic pain in the epidemiological surveys conducted in 2011. Responses were collected from 588 subjects (response rate 90 %). Results: Of the 588 responders, 365 (62 %) complained of persistent chronic pain. Among them, 128 (35 %) were still receiving treatment and 193 (53 %) had discontinued treatment. The degree of satisfaction with the treatment was low, and 66 % of the patients had switched the medical facility that they visited to receive treatment. The cited reasons for the change in the medical facility visited and discontinuation of treatment were "treatment was ineffective," "I did not have sufficient time," "I thought I could take care of it myself," and "Treatment seemed to be unnecessary". Involvement of neuropathic pain was suggested in 20 % of all the patients with chronic pain. As the PainDETECT Score rose, the Visual Analog Scale (VAS) score became higher and the change of medical facility for treatment also increased. The Pain Catastrophizing Scale score was correlated positively with the VAS score. The Hospital Anxiety and Depression Scale score was significantly correlated with the VAS score and the duration of pain. Discussion: The results of this survey indicated that the chronic course of musculoskeletal pain may be attributable to the following factors: (1) lack of appropriate treatment of neuropathic pain and psychogenic pain, and (2) insufficient awareness/knowledge among patients about chronic musculoskeletal pain. © 2014 The Author(s).

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Dumbbell mesenchymal chondrosarcoma

Iida Tsuyoshi, Nakamura Masaya, Tsuji Osahiko, Iwanami Akio, Mikami Shuji, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Journal of Orthopaedic Science 19 ( 1 ) 190 - 193 2014

ISSN 0949-2658

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Global gene expression analysis following spinal cord injury in non-human primates

Nishimura Soraya, Sasaki Takashi, Shimizu Atsushi, Yoshida Kenji, Iwai Hiroki, Koya Ikuko, Kobayashi Yoshiomi, Itakura Go, Shibata Shinsuke, Ebise Hayao, Horiuchi Keisuke, Kudoh Jun, Toyama Yoshiaki, Anderson Aileen J., Okano Hideyuki, Nakamura Masaya

Experimental Neurology 261 171 - 179 2014

ISSN 0014-4886

Spinal cord injury (SCI) is a devastating condition with no established treatment. To better understand the pathology and develop a treatment modality for SCI, an understanding of the physiological changes following SCI at the molecular level is essential. However, studies on SCI have primarily used rodent models, and few studies have examined SCI in non-human primates. In this study, we analyzed the temporal changes in gene expression patterns following SCI in common marmosets (Callithrix jacchus) using microarray analysis and mRNA deep sequencing. This analysis revealed that, although the sequence of events is comparable between primates and rodents, the inflammatory response following SCI is significantly prolonged and the onset of glial scar formation is temporally delayed in primates compared with rodents. These observations indicate that the optimal time window to treat SCI significantly differs among different species. This study provides the first extensive analysis of gene expression following SCI in non-human primates and will serve as a valuable resource in understanding the pathology of SCI. © 2014 Elsevier Inc.

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High preoperative hemoglobin A1c is a risk factor for surgical site infection after posterior thoracic and lumbar spinal instrumentation surgery

Hikata Tomohiro, Iwanami Akio, Hosogane Naobumi, Watanabe Kota, Ishii Ken, Nakamura Masaya, Kamata Michihiro, Toyama Yoshiaki, Matsumoto Morio

Journal of Orthopaedic Science 19 ( 2 ) 223 - 228 2014

ISSN 0949-2658

Background: Diabetes mellitus (DM) is reported to be a risk factor for surgical site infection (SSI), which is a serious complication after spinal surgery. The effect of DM on SSI after instrumented spinal surgery remains to be clarified. The aim was to elucidate perioperative risk factors for infection at the surgical site after posterior thoracic and lumbar spinal arthrodesis with instrumentation in patients with DM. Methods: Consecutive patients who underwent posterior instrumented thoracic and lumbar spinal arthrodesis during the years 2005-2011, who could be followed for at least 1 year after surgery, were included. These included 36 patients with DM (19 males and 17 females; mean age 64.3 years). The patients' medical records were retrospectively reviewed to determine the SSI rate. The characteristics of the DM patients were examined in detail, including the levels of serum glucose and HbA1c, which indicate the level of diabetes control. Results: Patients with DM had a higher rate of SSI (6 of 36 patients, 16.7 %) than patients without DM (10 of 309 patients, 3.2 %). Although the perioperative serum glucose level did not differ between DM patients that did or did not develop SSI, the preoperative HbA1c value was significantly higher in the patients who developed SSI (7.6 %) than in those who did not (6.9 %). SSI developed in 0.0 % of the patients with controlled diabetes (HbA1c <7.0 %) and in 35.3 % of the patients with uncontrolled diabetes (HbA1c ≥7.0 %). Conclusions: DM patients whose blood glucose levels were poorly controlled before surgery were at high risk for SSI. To prevent SSI in DM patients, we recommend lowering the HbA1c to <7.0 % before performing surgery. © 2013 The Japanese Orthopaedic Association.

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C1 posterior arch screw as an auxiliary anchor in posterior reconstruction for atlantoaxial dislocation associated with type II odontoid fracture

Nagoshi Narihito, Suda Kota, Morita Tomonori, Matsumoto Satoko, Iimoto Seiji, Yasui Keigo, Komatsu Miki, Kobayashi Yosuke, Minami Akio, Toyama Yoshiaki, Matsumoto Morio, Nakamura Masaya

SpringerPlus 3 ( 1 ) 2014

Introduction: Although pedicle or lateral mass screws are usually chosen to fix atlantoaxial (C1-C2) instability, there is an increased risk for vertebral artery (VA) injury when used in patients with bone or arterial anomalies or osteoporotic bone. Here we report the C1 posterior arch screw as a new technique for upper cervical fixation.Case description: A 90-year-old man complained of upper cervical pain after falling in his house. The initial computed tomography (CT) scan showed C1-C2 posterior dislocation with a type II odontoid fracture. The patient underwent C2 fracture reduction and posterior C1-C2 fixation. On the right side of C1, because lateral mass screw placement could cause injury to the dominant VA considering a risk in oldest-old osteoporotic patients, a posterior arch screw was chosen instead as an auxiliary anchor. An intralaminar screw was placed on the right side of C2 because a high-riding VA was observed. A lateral mass screw and a pars interarticularis screw were placed on the left side of C1 and C2, respectively. Ten months later, the odontoid fracture had healed, with normal anatomical alignment. Although the patient experienced slight weakness when spreading his bilateral fingers, his overall condition was good.Discussion and evaluation: We have presented a novel technique using C1 posterior arch screws for the fixation of a C1-C2 dislocation. Such a screw is an alternative to the C1 lateral mass screw in patients who are at risk for a VA injury because of anomalous bone and arterial structures or poor bone quality.Conclusions: Although there have been few comparable studies, and the long-term outcome is unknown, fixation with a posterior arch screw could be a beneficial choice for surgeries involving the upper cervical region.

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Transplantation of neural stem/progenitor cells at different locations in mice with spinal cord injury

Iwai Hiroki, Nori Satoshi, Nishimura Soraya, Yasuda Akimasa, Takano Morito, Tsuji Osahiko, Fujiyoshi Kanehiro, Toyama Yoshiaki, Okano Hideyuki, Nakamura Masaya

Cell Transplantation 23 ( 11 ) 1415 - 1464 2014

ISSN 0963-6897

Transplantation of neural stem/progenitor cells (NS/PCs) promotes functional recovery after spinal cord injury (SCI); however, few studies have examined the optimal site of NS/PC transplantation in the spinal cord. The purpose of this study was to determine the optimal transplantation site of NS/PCs for the treatment of SCI. Wild-type mice were generated with contusive SCI at the T10 level, and NS/PCs were derived from fetal transgenic mice. These NS/PCs ubiquitously expressed ffLuc-cp156 protein (Venus and luciferase fusion protein) and so could be detected by in vivo bioluminescence imaging 9 days postinjury. NS/PCs (low: 250,000 cells per mouse; high: 1 million cells per mouse) were grafted into the spinal cord at the lesion epicenter (E) or at rostral and caudal (RC) sites. Phosphate-buffered saline was injected into E as a control. Motor functional recovery was better in each of the transplantation groups (E-Low, E-High, RC-Low, and RC-High) than in the control group. The photon counts of the grafted NS/PCs were similar in each of the four transplantation groups, suggesting that the survival of NS/PCs was fairly uniform when more than a certain threshold number of cells were transplanted. Quantitative RT-PCR analyses demonstrated that brain-derived neurotropic factor expression was higher in the RC segment than in the E segment, and this may underlie why NS/PCs more readily differentiated into neurons than into astrocytes in the RC group. The location of the transplantation site did not affect the area of spared fibers, angiogenesis, or the expression of any other mediators. These findings indicated that the microenvironments of the E and RC sites are able to support NS/PCs transplanted during the subacute phase of SCI similarly. Optimally, a certain threshold number of NS/PCs should be grafted into the E segment to avoid damaging sites adjacent to the lesion during the injection procedure.

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Surgeons' exposure to radiation in single- and multi-level minimally invasive transforaminal lumbar interbody fusion; a prospective study

Funao Haruki, Ishii Ken, Momoshima Suketaka, Iwanami Akio, Hosogane Naobumi, Watanabe Kota, Nakamura Masaya, Toyama Yoshiaki, Matsumoto Morio

PLoS ONE 9 ( 4 ) e95233 2014

Although minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has widely been developed in patients with lumbar diseases, surgeons risk exposure to fluoroscopic radiation. However, to date, there is no studies quantifying the effective dose during MIS-TLIF procedure, and the radiation dose distribution is still unclear. In this study, the surgeons' radiation doses at 5 places on the bodies were measured and the effective doses were assessed during 31 consecutive 1- to 3-level MIS-TLIF surgeries. The operating surgeon, assisting surgeon, and radiological technologist wore thermoluminescent dosimeter on the unshielded thyroid, chest, genitals, right middle finger, and on the chest beneath a lead apron. The doses at the lens and the effective doses were also calculated. Mean fluoroscopy times were 38.7, 53.1, and 58.5 seconds for 1, 2, or 3 fusion levels, respectively. The operating surgeon's mean exposures at the lens, thyroid, chest, genitals, finger, and the chest beneath the shield, respectively, were 0.07, 0.07, 0.09, 0.14, 0.32, and 0.05 mSv in 1-level MIS-TLIF; 0.07, 0.08, 0.09, 0.18, 0.34, and 0.05 mSv in 2-level; 0.08, 0.09, 0.14, 0.15, 0.36, and 0.06 mSv in 3-level; and 0.07, 0.08, 0.10, 0.15, 0.33, and 0.05 mSv in all cases. Mean dose at the operating surgeon's right finger was significantly higher than other measurements parts (P<0.001). The operating surgeon's effective doses (0.06, 0.06, and 0.07 mSv for 1, 2, and 3 fusion levels) were low, and didn't differ significantly from those of the assisting surgeon or radiological technologist. Revision MIS-TLIF was not associated with higher surgeons' radiation doses compared to primary MIS-TLIF. There were significantly higher surgeons' radiation doses in over-weight than in normal-weight patients. The surgeons' radiation exposure during MIS-TLIF was within the safe level by the International Commission on Radiological Protection's guidelines. The accumulated radiation exposure, especially to surgeon's hands, should be carefully monitored.

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FOXC2 mutations in familial and sporadic spinal extradural arachnoid cyst

Ogura Yoji, Yabuki Shoji, Iida Aritoshi, Kou Ikuyo, Nakajima Masahiro, Kano Hiroki, Shiina Masaaki, Kikuchi Shinichi, Toyama Yoshiaki, Ogata Kazuhiro, Nakamura Masaya, Matsumoto Morio, Ikegawa Shiro

PLoS ONE 8 ( 11 ) 2013.11

Spinal extradural arachnoid cyst (SEDAC) is a cyst in the spinal canal that protrudes into the epidural space from a defect in the dura mater. Most cases are sporadic; however, three familial SEDAC cases have been reported, suggesting genetic etiological factors. All familial cases are associated with lymphedema-distichiasis syndrome (LDS), whose causal gene is FOXC2. However, FOXC2 mutation analysis has been performed in only 1 family, and no mutation analysis has been performed on sporadic (non-familial) SEDACs. We recruited 17 SEDAC subjects consisting of 2 familial and 7 sporadic cases and examined FOXC2 mutations by Sanger sequencing and structural abnormalities by TaqMan copy number assay. We identified 2 novel FOXC2 mutations in 2 familial cases. Incomplete LDS penetrance was noted in both families. Four subjects presented with SEDACs only. Thus, SEDAC caused by the heterozygous FOXC2 loss-of-function mutation should be considered a feature of LDS, although it often manifests as the sole symptom. Seven sporadic SEDAC subjects had no FOXC2 mutations, no symptoms of LDS, and showed differing clinical characteristics from those who had FOXC2 mutations, suggesting that other gene(s) besides FOXC2 are likely to be involved in SEDAC. © 2013 Ogura et al.

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In vivo tracing of neural tracts in tiptoe-walking yoshimura mice by diffusion tensor tractography

Takano Morito, Komaki Yuji, Hikishima Keigo, Konomi Tsunehiko, Fujiyoshi Kanehiro, Tsuji Osahiko, Okano Hideyuki, Toyama Yoshiaki, Nakamura Masaya

107 - 117 2013.11

In ossification of the posterior longitudinal ligaments (OPLL), axonal disruption results in motor and sensory function impairment. Twy (tiptoe-walking Yoshimura) mice develop spontaneous calcification in the cervical ligaments, thereby causing chronic compression of the spinal cords. To determine whether in vivo diffusion tensor tractography (DTT) can evaluate the axonal disruption of the chronic compressive spinal cords in twy mice, 6-, 15-, and 20-week-old twy mice were chronologically subjected to DTT. MRI was performed using a 7.0-Tesla magnet with a surface coil (CryoProbe). Diffusion tensor images were analyzed using TrackVis (Massachusetts General Hospital, MA, USA). We succeeded in depicting in vivo high-resolution DTT of the twy mice. The progress of the ligamentous calcification was observed at C2-3 level in each twy mouse, and the number of RT-97 or SMI31 positive fibers was decreased depending on the severity of the compression of the spinal cord. Quantitative analysis of sequential DTT enabled to detect subtle damage of the compressed spinal cord prior to the deterioration of neurological function in twy mice. Thus, in a clinical setting, DTT could be a new effective imaging modality in patients with cervical OPLL.

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Regenerative medicine for spinal cord injury utilizing iPS cells

Tsuji Osahiko, Nori Satoshi, Kobayashi Yoshiomi, Fujiyoshi Kanehiro, Okano Hideyuki, Toyama Yoshiaki, Nakamura Masaya

229 - 245 2013.11

Reports of functional recovery from spinal cord injury (SCI) after the transplantation of rat-fetus-derived neural stem/precursor cells (NS/PCs) and murine embryonic stem cells (ES cells) have raised great expectations for the successful clinical trial of stem cell transplantation therapy. However, the ethical issues concerning about destroying human embryos or fertilized oocytes to obtain such stem cells have been a major impediment to developing clinically useful stem cell sources and to use them in clinical applications. Recently, induced pluripotent stem cells (iPS cells), which can serve as a source of autologous cell transplantation, have been attracting a lot of attention as a clinically practical alternative to stem cells obtained directly from tissues. In this chapter, we outline the neural induction of murine and human iPS cells, their therapeutic efficacy in mouse and primate SCI models, and their safety in vivo.

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