研究者詳細 - 渡邉　航太

論文 - 渡邉　航太

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Potential involvement of semaphorin 3A in maintaining intervertebral disc tissue homeostasis

Mima Y., Suzuki S., Fujii T., Morikawa T., Tamaki S., Takubo K., Shimoda M., Miyamoto T., Watanabe K., Matsumoto M., Nakamura M., Fujita N.

Journal of Orthopaedic Research （Journal of Orthopaedic Research） 37 （ 4 ） 972 - 980 2019年04月

ISSN 07360266

© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. Intervertebral discs (IVDs) are avascular; however, ingrowth of blood vessels into their outer regions has been noted during the progression of degeneration. The mechanisms underlying vascularization in IVD degeneration are not completely understood. Semaphorin 3A (Sema3A), originally characterized as a chemorepulsive factor for growing axons in the developing nervous system, inhibits angiogenesis. This study aimed to elucidate the potential involvement of Sema3A in maintaining tissue homeostasis within the avascular IVD. We demonstrated that the mRNA expression of Sema3A was higher in rat annulus fibrosus (AF) than in nucleus pulposus (NP) and that its expression level decreased with age. Both mRNA and protein expression level of Sema3A was also markedly suppressed in AF tissues of a rat IVD degeneration model. Both real-time RT-PCR and Western blot clearly indicated that Sema3A expression significantly reduced by treating inflammatory cytokines in rat AF cells. In a gain- and loss-of-function study, we observed that Sema3A reduced the catabolic shift in rat AF cells. In addition, our results indicated that Sema3A potentially inhibited the IL-6/JAK/STAT pathway. Finally, BrdU assay and tube formation assay revealed that treatment of recombinant Sema3A significantly blocks both proliferation and tube formation of HUVEC. Our results indicate that Sema3A may help maintain IVD tissue homeostasis. Thus, although further studies are needed, Sema3A may be a potential molecular target for suppressing IVD degeneration. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

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Surgical outcomes of spinal fusion for osteoporotic thoracolumbar vertebral fractures in patients with Parkinson's disease: What is the impact of Parkinson's disease on surgical outcome?

Watanabe K., Katsumi K., Ohashi M., Shibuya Y., Izumi T., Hirano T., Endo N., Kaito T., Yamashita T., Fujiwara H., Nagamoto Y., Matsuoka Y., Suzuki H., Nishimura H., Terai H., Tamai K., Tagami A., Yamada S., Adachi S., Yoshii T., Ushio S., Harimaya K., Kawaguchi K., Yokoyama N., Oishi H., Doi T., Kimura A., Inoue H., Inoue G., Miyagi M., Saito W., Nakano A., Sakai D., Nukaga T., Ikegami S., Shimizu M., Futatsugi T., Ohtori S., Furuya T., Orita S., Imagama S., Ando K., Kobayashi K., Kiyasu K., Murakami H., Yoshioka K., Seki S., Hongo M., Kakutani K., Yurube T., Aoki Y., Oshima M., Takahata M., Iwata A., Endo H., Abe T., Tsukanishi T., Nakanishi K., Watanabe K., Hikata T., Suzuki S., Isogai N., Okada E., Funao H., Ueda S., Shiono Y., Nojiri K., Hosogane N., Ishii K.

BMC Musculoskeletal Disorders （BMC Musculoskeletal Disorders） 20 （ 1 ） 2019年03月

Background: To date, there have been little published data on surgical outcomes for patients with PD with thoracolumbar OVF. We conducted a retrospective multicenter study of registry data to investigate the outcomes of fusion surgery for patients with Parkinson's disease (PD) with osteoporotic vertebral fracture (OVF) in the thoracolumbar junction. Methods: Retrospectively registered data were collected from 27 universities and their affiliated hospitals in Japan. In total, 26 patients with PD (mean age, 76 years; 3 men and 23 women) with thoracolumbar OVF who underwent spinal fusion with a minimum of 2 years of follow-up were included (PD group). Surgical invasion, perioperative complications, radiographic sagittal alignment, mechanical failure (MF) related to instrumentation, and clinical outcomes were evaluated. A control group of 296 non-PD patients (non-PD group) matched for age, sex, distribution of surgical procedures, number of fused segments, and follow-up period were used for comparison. Results: The PD group showed higher rates of perioperative complications (p < 0.01) and frequency of delirium than the non-PD group (p < 0.01). There were no significant differences in the degree of kyphosis correction, frequency of MF, visual analog scale of the symptoms, and improvement according to the Japanese Orthopaedic Association scoring system between the two groups. However, the PD group showed a higher proportion of non-ambulators and dependent ambulators with walkers at the final follow-up (p < 0.01). Conclusions: A similar surgical strategy can be applicable to patients with PD with OVF in the thoracolumbar junction. However, physicians should pay extra attention to intensive perioperative care to prevent various adverse events and implement a rehabilitation regimen to regain walking ability.

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Spinal correction surgery improves asymmetrical trunk kinematics during gait in adolescent idiopathic scoliosis with thoracic major curve

Nishida M., Nagura T., Fujita N., Nakamura M., Matsumoto M., Watanabe K.

European Spine Journal （European Spine Journal） 28 （ 3 ） 619 - 626 2019年03月

ISSN 09406719

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: To clarify the effect of posterior correction and fusion surgery on the trunk–pelvic kinematics during gait in adolescent idiopathic scoliosis (AIS) patients with single thoracic major curve. Methods: Among preoperative AIS patients who planned correction surgery, 18 patients with Lenke type 1A or B were selected for this study. All patients were female. The patients’ trunk and pelvic kinematics during gait were measured three-dimensionally and dynamically using reflective markers, optoelectronic motion capture system. The gait analysis was performed before and 1–2 years after surgery. The trunk and pelvic symmetry during gait was evaluated at coronal, sagittal, and transverse planes between concave and convex sides. Results: The trunk and pelvic angles in sagittal and coronal planes were equivalent between concave and convex sides before and after surgery. Preoperatively, transverse trunk rotation angles were significantly deviated toward the concave (left) side during both static standing (4.3 ± 2.0°) and gait (8.8 ± 0.6°, p < 0.01). Preoperative transverse pelvic rotation angles were significantly deviated toward the convex side during static standing (4.0 ± 3.8°). However, pelvis displayed with symmetric rotational kinematics during gait. Postoperatively, the deviated transverse trunk rotation angle significantly decreased (1.6 ± 0.3°), and the transverse rotational kinematics of both trunk and pelvis improved to symmetric. Conclusions: Posterior correction and fusion surgery have improved preoperative asymmetric global rotational kinematics of trunk and pelvis in transverse plane to symmetric postoperatively in AIS patients with thoracic single major curve. Graphical abstract: These slides can be retrieved under Electronic Supplementary Material.[Figure not available: see fulltext.].

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Identification of novel LFNG mutations in spondylocostal dysostosis

Otomo N., Mizumoto S., Lu H., Takeda K., Campos-Xavier B., Mittaz-Crettol L., Guo L., Takikawa K., Nakamura M., Yamada S., Matsumoto M., Watanabe K., Ikegawa S.

Journal of Human Genetics （Journal of Human Genetics） 64 （ 3 ） 261 - 264 2019年03月

ISSN 14345161

Spondylocostal dysostosis (SCDO) is a heterogeneous group of skeletal disorders characterized by multiple segmentation defects involving vertebrae and ribs. Seven disease genes have been reported as causal genes for SCDO: DLL3, MESP2, TBX6, HES7, RIPPLY2, DMRT2, and LFNG. Here we report a Japanese SCDO case with multiple severe vertebral anomalies from cervical to sacral spine. The patient was a compound heterozygote for c.372delG (p.K124Nfs*) and c.601G>A (p.D201N) variants of LFNG, which encodes a glycosyltransferase (O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase). The missense variant was in the DxD motif, an active-site motif of the glycosyltransferase, and its loss of the enzyme function was confirmed by an in vitro enzyme assay. This is the second report of LFNG mutations in SCDO.

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Spinal epidural lipomatosis is a previously unrecognized manifestation of metabolic syndrome

Ishihara S., Fujita N., Azuma K., Michikawa T., Yagi M., Tsuji T., Takayama M., Matsumoto H., Nakamura M., Matsumoto M., Watanabe K.

Spine Journal （Spine Journal） 19 （ 3 ） 493 - 500 2019年03月

ISSN 15299430

© 2018 Elsevier Inc. BACKGROUND CONTEXT: Spinal epidural lipomatosis (SEL) is a condition in which excess lumbar epidural fat (EF) deposition often leads to compression of the cauda equina or nerve root. Although SEL is often observed in obese adults, no systematic research investigating the potential association between SEL and metabolic syndrome has been conducted. PURPOSE: To elucidate potential association between SEL and metabolic syndrome. STUDY DESIGN: An observational study used data of a medical checkup. PATIENT SAMPLE: We retrospectively reviewed data from consecutive subjects undergoing medical checkups. A total of 324 subjects (174 men and 150 women) were enrolled in this study. OUTCOME MEASURES: The correlation of EF accumulation with demographic data and metabolic-related factors was evaluated. METHODS: The degree of EF accumulation was evaluated based on the axial views of lumbar magnetic resonance imaging. Visceral and subcutaneous fat areas were measured at the navel level using abdominal computed tomography. Metabolic syndrome was diagnosed according to the criteria of the Japanese Society of Internal Medicine. The correlation of SEL with metabolic syndrome and metabolic-related conditions was statistically evaluated. RESULTS: The degree of EF accumulation demonstrated a significant correlation to body mass index, abdominal circumference, and visceral fat area. However, age, body fat percentage, and subcutaneous fat area showed no correlation with the degree of EF accumulation. Logistic regression analysis revealed that metabolic syndrome (odds ratio [OR]=3.8, 95% confidence interval [CI]=1.5–9.6) was significantly associated with SEL. Among the diagnostic criteria for metabolic syndrome, visceral fat area ≥100 cm 2 (OR=4.8, 95% CI=1.5–15.3) and hypertension (OR=3.5, 95% CI=1.1–11.8) were observed to be independently associated with SEL. CONCLUSION: This is the first study to demonstrate that metabolic syndrome is associated with SEL in a relatively large, unbiased population. Our data suggest that metabolic-related conditions are potentially related to EF deposition and that SEL could be a previously unrecognized manifestation of metabolic syndrome.

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Myelopathy due to human T-cell leukemia virus type-1 from the donor after ABO-incompatible liver transplantation

Wakabayashi T., Obara H., Seki M., Shinoda M., Kitago M., Yagi H., Abe Y., Matsubara K., Yamada Y., Oshima G., Oki K., Nagoshi N., Watanabe K., Hibi T., Itano O., Hoshino K., Suzuki N., Kuroda T., Kitagawa Y.

Annals of Hepatology （Annals of Hepatology） 18 （ 2 ） 397 - 401 2019年03月

ISSN 16652681

We report the case of a 53-year-old-man who developed human T-cell leukemia virus type-1-associated myelopathy (HAM) after ABO-incompatible liver transplantation for alcoholic liver cirrhosis. The living donor was seropositive for human T-cell leukemia virus type-1 (HTLV-1) and the recipient was seronegative for HTLV-1 before transplantation. After transplantation, the recipient developed steroid-resistant acute cellular rejection, which was successfully treated using anti-thymocyte globulin, and he was eventually discharged. He underwent spinal surgery twice after the transplantation for the treatment of cervical spondylosis that had been present for a period of 9 months before the transplantation. The surgery improved his gait impairment temporarily. However, his gait impairment progressed, and magnetic resonance imaging revealed multiple sites of myelopathy. He was diagnosed with HAM 16 months after the transplantation. Pulse steroid therapy (1000 mg) was administered over a period of 3 days, and his limb paresis improved. Presently, steroid therapy is being continued, with a plan to eventually taper the dose, and he is being carefully followed up at our institution. Our case suggests that liver transplantation involving an HTLV-1-positive living donor carries the risk of virus transmission and short-term development of HAM after transplantation.

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Does Posterior Cervical Decompression Conducted by Junior Surgeons Affect Clinical Outcomes in the Treatment of Cervical Spondylotic Myelopathy? Results From a Multicenter Study

Nagoshi N., Iwanami A., Isogai N., Ishikawa M., Nojiri K., Tsuji T., Daimon K., Takeuchi A., Tsuji O., Okada E., Fujita N., Yagi M., Watanabe K., Nakamura M., Matsumoto M., Ishii K., Yamane J.

Global Spine Journal （Global Spine Journal） 9 （ 1 ） 25 - 31 2019年02月

ISSN 21925682

© The Author(s) 2018. Study Design: Retrospective multicenter study. Objectives: To evaluate the outcomes of posterior cervical decompression for cervical spondylotic myelopathy (CSM) when performed by board-certified spine (BCS) or non-BCS (NBCS) surgeons. Methods: We reviewed outcomes for 675 patients who underwent surgery for CSM, were followed at least 1 year after surgery, and were assessed preoperatively and at final follow-up by Japanese Orthopaedic Association (JOA) scores and by the visual analog scale (VAS) for the neck. Cervical alignment was assessed on radiographs by C2-C7 angles, and range of motion (ROM) by extension minus flexion C2-C7 angles. We compared outcomes for BCS surgeons, who must meet several requirements, including experience in more than 300 spinal surgeries, and for NBCS surgeons. Results: BCS surgeons performed 432 of 675 laminoplasties. NBCS surgeons were primary in 243 surgeries, of which 187 were directly supervised by a BCS surgeon. BCS surgeons required significantly less time in surgery (98.0 ± 39.5 vs 108.1 ± 49.7 min; P <.01). BCS and NBCS surgeons had comparable perioperative complications rates, and preoperative-to-postoperative changes in JOA scores (2.9 ± 2.1 vs 3.1 ± 2.3; P =.40) and VAS (−1.5 ± 2.9 vs −1.4 ± 2.5; P =.96). Lordotic cervical alignment and ROM were maintained after operations by both groups. Conclusions: Surgical outcomes such as functional recovery, complication rates, and cervical dynamics were comparable between the BCS and NBCS groups. Thus, posterior cervical decompression for CSM is safe and effective when performed by junior surgeons who have been trained and supervised by experienced spine surgeons.

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Impact of lumbar hypolordosis on the incidence of symptomatic postoperative spinal epidural hematoma after decompression surgery for lumbar spinal canal stenosis

Fujita N., Michikawa T., Yagi M., Suzuki S., Tsuji O., Nagoshi N., Okada E., Tsuji T., Nakamura M., Matsumoto M., Watanabe K.

European Spine Journal （European Spine Journal） 28 （ 1 ） 87 - 93 2019年01月

ISSN 09406719

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: Potential associations between radiographic parameters and the incidence of symptomatic postoperative spinal epidural hematoma (PSEH) have not been identified. This study aimed to identify risk factors including radiographic parameters for symptomatic PSEH after posterior decompression surgery for lumbar spinal canal stenosis (LSS). Methods: We retrospectively reviewed 1007 consecutive patients who underwent lumbar decompression surgery for lumbar spinal canal stenosis (LSS) at our institution. We identified 35 cases of symptomatic PSEH, defined by clinical symptoms and MRI findings, and selected 3 or 4 age- and sex-matched control subjects for each PSEH subject (124 controls). We compared radiographic parameters and previously reported risk factors between PSEH and control subjects. Results: Compared to the control group, PSEH patients had significantly higher preoperative systolic (p =.020) and diastolic (p =.048) blood pressure, and more levels of decompression (p =.001). PSEH and control subjects had significant differences in lumbar lordosis (PSEH 24.8° ± 14.6°, control 34.8° ± 14.5°), pelvic tilt (25.1° ± 11.7° vs. 20.8° ± 8.4°), sacral slope (23.4° ± 9.4° vs. 27.6° ± 8.3°), and pelvic incidence minus lumbar lordosis (23.7° ± 15.0° vs. 13.7° ± 14.6°). Multivariate analysis revealed two significant risk factors for PSEH: decompression of two or more levels and lumbar lordosis < 25°. Conclusions: Multilevel decompression and hypolordosis are significant risk factors for symptomatic PSEH after decompression surgery for LSS. LSS patients with lumbar hypolordosis or multilevel stenosis should be carefully observed for PSEH after decompression surgery. Graphical abstract: These slides can be retrieved under Electronic Supplementary Material.[Figure not available: see fulltext.].

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Predictive model for major complications 2 years after corrective spine surgery for adult spinal deformity

Yagi M., Hosogane N., Fujita N., Okada E., Tsuji O., Nagoshi N., Asazuma T., Tsuji T., Nakamura M., Matsumoto M., Watanabe K.

European Spine Journal （European Spine Journal） 28 （ 1 ） 180 - 187 2019年01月

ISSN 09406719

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: ASD surgery improves a patient’s health-related quality of life, but it has a high complication rate. The aim of this study was to create a predictive model for complications after surgical treatment for adult spinal deformity (ASD), using spinal alignment, demographic data, and surgical invasiveness. Methods: This study included 195 surgically treated ASD patients who were > 50 years old and had 2-year follow-up from multicenter database. Variables which included age, gender, BMI, BMD, frailty, fusion level, UIV and LIV, primary or revision surgery, pedicle subtraction osteotomy, spinal alignment, Schwab-SRS type, surgical time, and blood loss were recorded and analyzed at least 2 years after surgery. Decision-making trees for 2-year postoperative complications were constructed and validated by a 7:3 data split for training and testing. External validation was performed for 25 ASD patients who had surgery at a different hospital. Results: Complications developed in 48% of the training samples. Almost half of the complications developed in late post-op period, and implant-related complications were the most common complication at 2 years after surgery. Univariate analyses showed that BMD, frailty, PSO, LIV, PI-LL, and EBL were risk factors for complications. Multivariate analysis showed that low BMD, PI-LL > 30°, and frailty were independent risk factors for complications. In the testing samples, our predictive model was 92% accurate with an area under the receiver operating characteristic curve of 0.963 and 84% accurate in the external validation. Conclusion: A successful model was developed for predicting surgical complications. Our model could inform physicians about the risk of complications in ASD patients in the 2-year postoperative period. Graphical abstract: These slides can be retrieved under Electronic Supplementary Material.[Figure not available: see fulltext.].

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Acute Paraparesis Due to Protrusion of a Disc Following Lateral Interbody Fusion for Degenerative Kyphoscoliosis: A Case Report

Ruchirawan S., Fujita N., Yagi M., Tsuji O., Okada E., Nagoshi N., Ishii K., Nakamura M., Matsumoto M., Watanabe K.

JBJS case connector （JBJS case connector） 9 （ 1 ） 1 - 5 2019年01月

ISSN 21603251

CASE: A 74-year-old woman presented with severe trunk deformity. Radiographs revealed severe sagittal and coronal imbalance with spinal canal stenosis at L4 to L5. Anterior cages were placed at L2 to L3, L3 to L4, and L4 to L5. Three days later, posterior correction surgery from T5 to the ilium with decompression at L4 to L5 was performed. At 30 minutes after surgery, leg muscle strength severely deteriorated. Emergency surgery revealed disc fragments protruding into the spinal canal at L2 to L3. CONCLUSION: Because posteriorly placed extreme lateral interbody fusion (XLIF) cages can be a risk factor for disc protrusion into the spinal canal, computed tomographic evaluation or prophylactic posterior decompression should be considered before the correction procedure.

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Early surgical intervention may facilitate recovery of cervical spinal cord injury in DISH

Tsuji O., Suda K., Takahata M., Matsumoto-Harmon S., Komatsu M., Menjo Y., Watanabe K., Ishii K., Nakamura M., Matsumoto M., Minami A., Iwasaki N.

Journal of Orthopaedic Surgery （Journal of Orthopaedic Surgery） 27 （ 1 ） 2019年01月

ISSN 10225536

© The Author(s) 2019. Study design: A retrospective study of consecutive surgically managed cases of cervical spinal fractures and diffuse idiopathic skeletal hyperostosis (DISH) at our hospital from October 2006 to April 2016. Summary of background data: Prognostic factors have not been determined for cervical fractures in DISH. Objectives: To assess demographics, surgical techniques, and complications in cervical spinal cord injury with DISH and to evaluate factors affecting neurological prognosis. Methods: Patients’ medical records and radiographs were reviewed and analyzed for demographics, injury characteristics, surgical outcomes, perioperative complications, additional surgeries, and neurological prognosis. Neurological status was assessed by the American Spinal Injury Association (ASIA) grade at admission and discharge. Results: Of 38 patients (mean age 71.9 ± 8.8), 20 had type 1 fractures (through the disc space), 8 had type 2 (through the vertebral body), and 10 had type 3 (through disc and vertebral body). ASIA grades at admission included 14 ASIA-A, 4 ASIA-B, 7 ASIA-C, 8 ASIA-D, and 5 ASIA-E. All patients underwent posterior fusion with an average of 4.5 ± 2.5 instrumented vertebrae (range, 2–7) and six patients required secondary halo-vest fixation. Of 14 ASIA-A patients, 12 developed serious postsurgical pulmonary complications and 4 of these died within 6 months of surgery. Of the 38 patients, 13 improved more than one grade after treatment, 24 did not improve, and 1 deteriorated. In the 18 ASIA-A/B cases (complete motor paralysis), neither fracture type nor injury mechanism (e.g. a ground-level fall or high-energy trauma) correlated with neurological prognosis, but a time of 8 h or less from injury to surgery correlated significantly with an improvement from ASIA A/B to C/D (p < 0.01, Pearson’s χ 2 test). Conclusion: Patients with complete motor paralysis after a cervical fracture with DISH may recover to partial paralysis if surgically treated within 8 h of injury.

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Lumbar spinal canal stenosis leads to locomotive syndrome in elderly patients

Fujita N., Sakurai A., Miyamoto A., Michikawa T., Tsuji O., Nagoshi N., Okada E., Yagi M., Otaka Y., Tsuji T., Kono H., Ishii K., Nakamura M., Matsumoto M., Watanabe K.

Journal of Orthopaedic Science （Journal of Orthopaedic Science） 24 （ 1 ） 19 - 23 2019年01月

ISSN 09492658

© 2018 The Japanese Orthopaedic Association Background: Locomotive syndrome is a condition in which the ability to lead a normal life is restricted owing to a dysfunction in one or more of the parts of the musculoskeletal system. Although lumbar spinal canal stenosis (LSS) is considered to cause locomotive syndrome, a detailed assessment of the association between two pathologies has not yet been reported. Methods: The clinical data of patients aged > 65 years old who planned to undergo surgery for LSS at multiple institutions were prospectively collected from April 2016 to August 2017. A total of 200 participants comprising 120 men and 80 women were enrolled in this study. Association of severity of LSS evaluated by Zurich Claudication Questionnaire scores with three locomotive syndrome risk tests (Stand-up Test, the Two-step Test, and a 25-question risk assessment) and Timed Up-and-Go Test were evaluated. Results: In the total assessment of locomotive syndrome, 96.5% of the participants were diagnosed as grade 2, and the remaining 3.5% were diagnosed as grade 1. When the participants were divided into 3 groups according to the LSS severity, the scores of all locomotive syndrome risk tests were significantly worse with increasing LSS severity. Logistic regression analysis revealed that LSS severity was positively correlated with the risk level of locomotive syndrome evaluated by the Two-step Test (OR = 3.45, CI = 1.33–8.96). Conclusions: All LSS patients with surgical indications were diagnosed as having locomotive syndrome. In addition, our results indicated that LSS severity is potentially associated with the progression of locomotive syndrome. The treatment of LSS may be beneficial in alleviating the risk for locomotive syndrome.

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Surgical treatment of osteoporotic vertebral fracture with neurological deficit - A nationwide multicenter study in Japan

Hosogane N., Nojiri K., Suzuki S., Funao H., Okada E., Isogai N., Ueda S., Hikata T., Shiono Y., Watanabe K., Watanabe K., Kaito T., Yamashita T., Fujiwara H., Nagamoto Y., Terai H., Tamai K., Matsuoka Y., Suzuki H., Nishimura H., Tagami A., Yamada S., Adachi S., Ohtori S., Orita S., Furuya T., Yoshii T., Ushio S., Inoue G., Miyagi M., Saito W., Imagama S., Ando K., Sakai D., Nukaga T., Kiyasu K., Kimura A., Inoue H., Nakano A., Harimaya K., Kawaguchi K., Yokoyama N., Oishi H., Doi T., Ikegami S., Shimizu M., Futatsugi T., Kakutani K., Yurube T., Oshima M., Uei H., Aoki Y., Takahata M., Iwata A., Seki S., Murakami H., Yoshioka K., Endo H., Hongo M., Nakanishi K., Abe T., Tsukanishi T., Ishii K.

Spine Surgery and Related Research （Spine Surgery and Related Research） 3 （ 4 ） 361 - 367 2019年

Introduction: The prevalence of patients with osteoporosis continues to increase in aging societies, including Japan. The first choice for managing osteoporotic vertebral compression fracture (OVF) is conservative treatment. Failure in conservative treatment for OVF may lead to non-union or vertebral collapse, resulting in neurological deficit and subsequently requiring surgical intervention. This multicenter nationwide study in Japan was conducted to comprehensively understand the outcomes of surgical treatments for OVF non-union. Methods: This multicenter, retrospective study included 403 patients (89 males, 314 females, mean age 73.8 ± 7.8 years, mean follow-up 3.9 ± 1.7 years) with neurological deficit due to vertebral collapse or non-union after OVF at T10-L5 who underwent fusion surgery with a minimum 1-year follow-up. Radiological and clinical outcomes at baseline and at the final follow-up (FU) were evaluated. Results: OVF was present at a thoracolumbar junction such as T12 (124 patients) and L1 (117 patients). A majority of OVF occurred after a minor trauma, such as falling down (55.3%) or lifting objects (8.4%). Short segment fusion, including affected vertebra, was conducted (mean 4.0 ± 2.0 vertebrae) with 256.8 minutes of surgery and 676.1 g of blood loss. A posterior approach was employed in 86.6% of the patients, followed by a combined anterior and posterior (8.7%), and an anterior (4.7%) approach. Perioperative complications and implant failures were observed in 18.1% and 41.2%, respectively. VAS scores of low back pain (74.7 to 30.8 mm) and leg pain (56.8 to 20.7 mm) improved significantly at FU. Preoperatively, 52.6% of the patients were unable to walk and the rate of non-ambulatory patients decreased to 7.5% at FU. Conclusions: This study demonstrated that substantial improvement in activity of daily living (ADL) was achieved by fusion surgery. Although there was a considerable rate of complications, fusion surgery is beneficial for elderly OVF patients with non-union.

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Bi-allelic loss of function variants of TBX6 causes a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis

Otomo N., Takeda K., Kawai S., Kou I., Guo L., Osawa M., Alev C., Kawakami N., Miyake N., Matsumoto N., Yasuhiko Y., Kotani T., Suzuki T., Uno K., Sudo H., Inami S., Taneichi H., Shigematsu H., Watanabe K., Yonezawa I., Sugawara R., Taniguchi Y., Minami S., Kaneko K., Nakamura M., Matsumoto M., Toguchida J., Watanabe K., Ikegawa S.

Journal of Medical Genetics （Journal of Medical Genetics） 56 （ 9 ） 622 - 628 2019年

ISSN 00222593

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ. Background: Congenital scoliosis (CS) is a common vertebral malformation. Spondylocostal dysostosis (SCD) is a rare skeletal dysplasia characterised by multiple vertebral malformations and rib anomalies. In a previous study, a compound heterozygosity for a null mutation and a risk haplotype composed by three single-nucleotide polymorphisms in TBX6 have been reported as a disease-causing model of CS. Another study identified bi-allelic missense variants in a SCD patient. The purpose of our study is to identify TBX6 variants in CS and SCD and examine their pathogenicity. Methods: We recruited 200 patients with CS or SCD and investigated TBX6 variants. We evaluated the pathogenicity of the variants by in silico prediction and in vitro experiments. Results: We identified five 16p11.2 deletions, one splice-site variant and five missense variants in 10 patients. In vitro functional assays for missense variants identified in the previous and present studies demonstrated that most of the variants caused abnormal localisation of TBX6 proteins. We confirmed mislocalisation of TBX6 proteins in presomitic mesoderm cells induced from SCD patient-derived iPS cells. In induced cells, we found decreased mRNA expressions of TBX6 and its downstream genes were involved in somite formation. All CS patients with missense variants had the risk haplotype in the opposite allele, while a SCD patient with bi-allelic missense variants did not have the haplotype. Conclusions: Our study suggests that bi-allelic loss of function variants of TBX6 cause a spectrum of phenotypes including CS and SCD, depending on the severity of the loss of TBX6 function.

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Stride length of elderly patients with lumbar spinal stenosis: Multi-center study using the Two-Step test

Fujita N., Sakurai A., Miyamoto A., Michikawa T., Otaka Y., Suzuki S., Tsuji O., Nagoshi N., Okada E., Yagi M., Tsuji T., Kono H., Ishii K., Nakamura M., Matsumoto M., Watanabe K.

Journal of Orthopaedic Science （Journal of Orthopaedic Science） 24 （ 5 ） 787 - 792 2019年

ISSN 09492658

© 2019 Background: Short stride length is one of clinical symptoms associated with lumbar spinal stenosis (LSS). Short stride is a risk factor for falls; therefore, identification of factors associated with short stride is critical for fall prevention in LSS patients. Although the Two-Step test can conveniently assess maximal stride length, it has not become widely used; therefore, its data are limited. We identified the potential factors associated with short stride of elderly LSS patients using Two-Step test. Methods: Clinical data of patients aged >65 years who planned to undergo surgery for LSS were prospectively collected at multiple institutions. Patients were assessed with the Two-Step test and Timed Up-and-Go Test prior to surgery; 357 consecutive patients were enrolled. We determined the cut-off value of the Two-Step test score for short stride, referring to the Timed Up-and-Go Test score of 13.5 s, used to indicate high risk of falls in elderly individuals. Logistic regression model was constructed to identify factors associated with short stride. Results: The Two-Step test score showed moderate-to-strong inverse correlation with that of Timed Up-and-Go Test (r = −0.65, p < 0.001). Using the tentative Two-Step test cut-off value (0.93) for short stride, multivariable analysis showed that age ≥80 years (OR = 2.3, 95% CI:1.1–4.8), a score of <60 for lumbar function in Japanese Orthopedic Association Back Pain Evaluation Questionnaire (OR = 2.7, 95% CI:1.5–4.7), motor deficit (OR = 2.7, 95% CI:1.2–6.1), and sagittal vertical axis ≥50 mm (OR = 2.1, 95% CI:1.2–3.5) were factors significantly associated with short stride in elderly patients with LSS. Conclusions: Using the Two-Step test, we found that 80 years old and over, lumbar dysfunction, motor deficit of the lower extremities, and forward-bent posture were associated with short stride in LSS patients. Therefore, elderly LSS patients with these conditions may have a higher risk for falls.

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Lumbar spinal surgery improves locomotive syndrome in elderly patients with lumbar spinal canal stenosis: A multicenter prospective study

Fujita N., Michikawa T., Miyamoto A., Sakurai A., Otaka Y., Suzuki S., Tsuji O., Nagoshi N., Okada E., Yagi M., Tsuji T., Kono H., Ishii K., Nakamura M., Matsumoto M., Watanabe K.

Journal of Orthopaedic Science （Journal of Orthopaedic Science） 25 （ 2 ） 213 - 218 2019年

ISSN 09492658

© 2019 The Japanese Orthopaedic Association Background: Owing to musculoskeletal dysfunction, locomotive syndrome elevates the risk of requiring nursing care. Among degenerative musculoskeletal disorders, lumbar spinal canal stenosis (LSS) associates with locomotive syndrome; however, whether lumbar spinal surgery for LSS improves locomotive syndrome remains unclear. Hence, this study aimed to identify the efficacy of lumbar spinal surgery on locomotive syndrome among elderly patients with LSS. Methods: We prospectively collected the clinical data from multiple institutions of patients (age >65 years) who underwent lumbar spinal surgery. Patients were examined for the locomotive syndrome risk test, including the stand-up Test, the two-step Test, and the 25-question risk assessment, 1-day preoperatively and 6-month and 1-year postoperatively. Using a logistic regression model, we identified factors associated with improvement of locomotive syndrome in the total assessment. Results: Overall, we examined the data of 166 patients in this study. Upon converting each score of three tests to the stage of locomotive syndrome, the two-step test and the 25-question risk assessment revealed marked improvement in the postoperative distribution of stages. However, the stand-up test revealed a comparable distribution of stages pre- and postoperatively. In the total assessment, the postoperative distribution of stages was significantly improved than that preoperatively. The multivariable analysis revealed that failed back surgery syndrome [odds ratio (OR), 0.2; 95% confidence interval (CI): 0.04–1.05; P = 0.057)] and preoperative stage of 2 in stand-up test (OR, 0.2; 95% CI: 0.05–1.02; P = 0.054) tended to have inverse association with postoperative improvement of locomotive syndrome in the total assessment. Conclusions: Lumbar spinal surgery improved the stage of locomotive syndrome among elderly patients with LSS. This study suggests that lumbar spinal surgery for LSS could be beneficial in alleviating locomotive syndrome.

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Clinical outcomes and prognostic factors for cavernous hemangiomas of the spinal cord: A retrospective cohort study

Nagoshi N., Tsuji O., Nakashima D., Takeuchi A., Kameyama K., Okada E., Fujita N., Yagi M., Matsumoto M., Nakamura M., Watanabe K.

Journal of Neurosurgery: Spine （Journal of Neurosurgery: Spine） 31 （ 2 ） 271 - 278 2019年

ISSN 15475654

OBJECTIVE Intramedullary cavernous hemangioma (CH) is a rare vascular lesion that is mainly characterized by the sudden onset of hemorrhage in young, asymptomatic patients, who then experience serious neurological deterioration. Despite the severity of this condition, the therapeutic approach and timing of intervention for CH remain matters of debate. The aim of this study was to evaluate the clinical characteristics of CH patients before and after surgery and to identify prognostic indicators that affect neurological function in these patients. METHODS This single-center retrospective study included 66 patients who were treated for intramedullary CH. Among them, 57 underwent surgery and 9 patients received conservative treatment. The authors collected demographic, symptomology, imaging, neurological, and surgical data. Univariate and multivariate logistic regression analyses were performed to identify the prognostic indicators for neurological function. RESULTS When comparing patients with stable and unstable gait prior to surgery, patients with unstable gait had a higher frequency of hemorrhagic episodes (52.4% vs 19.4%, p = 0.010), as assessed by the modified McCormick Scale. The lesion was significantly smaller in patients who underwent conservative treatment compared with surgery (2.5 ± 1.5 mm vs 5.9 ± 4.1 mm, respectively; p = 0.024). Overall, the patients experienced significant neurological recovery after surgery, but a worse preoperative neurological status was identified as an indicator affecting surgical outcomes by multivariate analysis (OR 10.77, 95% CI 2.88–40.36, p < 0.001). In addition, a larger lesion size was significantly associated with poor functional recovery in patients who had an unstable gait prior to surgery (8.6 ± 4.5 mm vs 3.5 ± 1.6 mm, p = 0.011). CONCLUSIONS Once a hemorrhage occurs, surgical intervention should be considered to avoid recurrence of the bleeding and further neurological injury. In contrast, if the patients with larger lesion presented with worse preoperative functional status, surgical intervention could have a risk for aggravating the functional deficiencies by damaging the thinning cord parenchyma. Conservative treatment may be selected if the lesion is small, but regular neurological examination by MRI is needed for assessment of a change in lesion size and for detection of functional deterioration.

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Risk factors for proximal junctional fracture following fusion surgery for osteoporotic vertebral collapse with delayed neurological deficits: A retrospective cohort study of 403 patients

Tamai K., Terai H., Suzuki A., Nakamura H., Watanabe K., Katsumi K., Ohashi M., Shibuya Y., Izumi T., Hirano T., Kaito T., Yamashita T., Fujiwara H., Nagamoto Y., Matsuoka Y., Suzuki H., Nishimura H., Tagami A., Yamada S., Adachi S., Yoshii T., Ushio S., Harimaya K., Kawaguchi K., Yokoyama N., Oishi H., Doi T., Kimura A., Inoue H., Inoue G., Miyagi M., Saito W., Nakano A., Sakai D., Nukaga T., Ikegami S., Shimizu M., Futatsugi T., Ohtori S., Furuya T., Orita S., Imagama S., Ando K., Kobayashi K., Kiyasu K., Murakami H., Yoshioka K., Seki S., Hongo M., Kakutani K., Yurube T., Aoki Y., Oshima M., Takahata M., Iwata A., Endo H., Abe T., Tsukanishi T., Nakanishi K., Watanabe K., Hikata T., Suzuki S., Isogai N., Okada E., Funao H., Ueda S., Shiono Y., Nojiri K., Hosogane N., Ishii K.

Spine Surgery and Related Research （Spine Surgery and Related Research） 3 （ 2 ） 171 - 177 2019年

Introduction: Approximately 3% of osteoporotic vertebral fractures develop osteoporotic vertebral collapse (OVC) with neurological deficits, and such patients are recommended to be treated surgically. However, a proximal junctional fracture (PJFr) following surgery for OVC can be a serious concern. Therefore, the aim of this study is to identify the incidence and risk factors of PJFr following fusion surgery for OVC. Methods: This study retrospectively analyzed registry data collected from facilities belonging to the Japan Association of Spine Surgeons with Ambition (JASA) in 2016. We retrospectively analyzed 403 patients who suffered neurological deficits due to OVC below T10 and underwent corrective surgery; only those followed up for !2 years were included. Potential risk factors related to the PJFr and their cut-off values were calculated using multivariate logistic regression analysis and receiver operating characteristic (ROC) analysis. Results: Sixty-three patients (15.6%) suffered PJFr during the follow-up (mean 45.7 months). In multivariate analysis, the grade of osteoporosis (grade 2, 3: adjusted odds ratio (aOR) 2.92; p=0.001) and lower instrumented vertebra (LIV) level (sacrum: aOR 6.75; p=0.003) were independent factors. ROC analysis demonstrated that lumbar bone mineral density (BMD) was a predictive factor (area under curve: 0.72, p=0.035) with optimal cut-off value of 0.61 g/cm2 (sensitivity, 76.5%; specificity, 58.3%), but that of the hip was not (p=0.228). Conclusions: PJFr was found in 16% cases within 4 years after surgery; independent risk factors were severe osteoporosis and extended fusion to the sacrum. The lumbar BMD with cut-off value 0.61 g/cm2 may potentially predict PJFr. Our findings can help surgeons select perioperative adjuvant therapy, as well as a surgical strategy to prevent PJFr following surgery.

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Surgical Treatment of Cervical Spondylotic Myelopathy in the Elderly: Outcomes in Patients Aged 80 Years or Older

Isogai N., Nagoshi N., Iwanami A., Kono H., Kobayashi Y., Tsuji T., Fujita N., Yagi M., Watanabe K., Kitamura K., Shiono Y., Nakamura M., Matsumoto M., Ishii K., Yamane J.

Spine （Spine） 43 （ 24 ） E1430 - E1436 2018年12月

ISSN 03622436

STUDY DESIGN: Retrospective multicenter study. OBJECTIVE: We aimed to assess the outcomes following posterior cervical decompression for cervical spondylotic myelopathy (CSM) in a large sample of patients older than 80 years. SUMMARY OF BACKGROUND DATA: Although age is a predictor of surgical outcomes for CSM, most previous studies have only investigated the effect of age for patients aged 65 to 75 years, and surgical outcomes remain unclear for older patients. METHODS: Patients older than 50 years who underwent posterior cervical decompression for CSM were enrolled from 17 institutions. The patients were grouped into a young-old group (<80 yrs old) and an old-old group (≥80 yrs). Clinical information, comorbidities, perioperative complications, Japanese Orthopaedic Association (JOA) scores, Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), visual analog scale (VAS) scores, and radiographic parameters were compared between the two groups. All patients were followed for at least 1 year after surgery. RESULTS: The young-old and old-old groups included 491 and 77 patients, respectively. The JOA score and quality of life measured by JOACMEQ improved significantly after surgery in both groups. Compared with the young-old group, the old-old group had lower preoperative JOA scores (9.6 vs. 11.0), lower final JOA scores (12.6 vs. 14.0), and lower recovery rates (42% vs. 50%). However, there were no significant differences in perioperative complications or in the VAS scores at the final assessments. The old-old group had a higher mean preoperative sagittal Cobb angle at C2-C5, though this was not statistically significant postoperatively. CONCLUSION: Posterior decompression surgery is safe and beneficial for patients older than 80 years with CSM, despite having a more limited neurological recovery compared with younger patients.3.

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A multi-ethnic meta-analysis confirms the association of rs6570507 with adolescent idiopathic scoliosis

Kou I., Watanabe K., Takahashi Y., Momozawa Y., Khanshour A., Grauers A., Zhou H., Liu G., Fan Y., Takeda K., Ogura Y., Zhou T., Iwasaki Y., Kubo M., Wu Z., Matsumoto M., Kawakami N., Uno K., Suzuki T., Sudo H., Minami S., Kotani T., Ito M., Yanagida H., Taneichi H., Yonezawa I., Chiba K., Hosogane N., Fujita N., Yagi M., Kono K., Okada E., Nishida K., Kakutani K., Sakuma T., Harimaya K., Kaito T., Watanabe K., Taniguchi Y., Tsuji T., Akazawa T., Karol L., Rathjen K., Sucato D., Birch J., Johnston C., Richards B., Ramo B., McIntosh A., Herring J., Einarsdottir E., Kere J., Huang D., Qiu G., Qiu Y., Wise C., Song Y., Wu N., Su P., Gerdhem P., Ikegawa S.

Scientific Reports （Scientific Reports） 8 （ 1 ） 2018年12月

© 2018, The Author(s). Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity and has a significant genetic background. Genome-wide association studies (GWASs) identified several susceptibility loci associated with AIS. Among them is a locus on chromosome 6q24.1 that we identified by a GWAS in a Japanese cohort. The locus is represented by rs6570507 located within GPR126. To ensure the association of rs6570507 with AIS, we conducted a meta-analysis using eight cohorts from East Asia, Northern Europe and USA. The analysis included a total of 6,873 cases and 38,916 controls and yielded significant association (combined P = 2.95 × 10 −20 ; odds ratio = 1.22), providing convincing evidence of the worldwide association between rs6570507 and AIS susceptibility. In silico analyses strongly suggested that GPR126 is a susceptibility gene at this locus.

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