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Introduction: For older adults, dysphagia is a serious problem that can occur after spinal cord injury (SCI), but its risk factors are unclear. This study aimed to identify risk factors for dysphagia in elderly patients (65 years) with cervical SCI. Methods: This multicenter study included 707 patients with cervical SCI (mean age 75.3 years). Univariate and multivariate analyses were conducted for patient characteristics and geriatric nutritional risk index (GNRI). Results: Dysphagia occurred in 69 patients (9.8%). The significant factors were as follows: male sex (odds ratio [OR] 3.43), GNRI

Study Design A retrospective study at a single academic institution. Purpose This study aimed to identify imaging risk factors for stenosis in extended neck positions undetectable in preoperative neutral magnetic resonance imaging (MRI) and improving decompression strategies for cervical spine disorders. Overview of Literature Cervical disorders are influenced by various dynamic factors, with spinal stenosis appearing during neck extension. Despite the diagnostic value of dynamic cervical MRI, standard practice often uses neutral-position MRI, potentially influencing surgical outcomes. Methods This study analyzed 143 patients who underwent decompression surgery between 2012 and 2014, who had symptomatic cervical disorders and MRI evidence of spinal cord or nerve compression but had no history of cervical spine surgery. Patient demographics, disease type, Japanese Orthopedic Association score, and follow-up periods were recorded. Spinal surgeons conducted radiological evaluations to determine stenosis levels using computed tomography myelography or MRI in neutral and extended positions. Measurements such as dural tube and spinal cord diameters, cervical alignment, range of motion, and various angles and distances were also analyzed. The residual space available for the spinal cord (SAC) was also calculated. Results During extension, new stenosis frequently appeared caudal to the stenosis site in a neutral position, particularly at C5/C6 and C6/C7. A low SAC was identified as a significant risk factor for the development of new stenosis in both the upper and lower adjacent disc levels. Each 1-mm decrease in SAC resulted in an 8.9- and 2.7-fold increased risk of new stenosis development in the upper and lower adjacent disc levels, respectively. A practical SAC cutoff of 1.0 mm was established as the threshold for new stenosis development. Conclusions The study identified SAC narrowing as the primary risk factor for new stenosis, with a clinically relevant cutoff of 1 mm. This study highlights the importance of local factors in stenosis development, advocating for further research to improve outcomes in patient with cervical spine disorders.

Introduction: Adolescent idiopathic scoliosis (AIS) with a major curve at the main thoracic (MT) area is classified as Lenke type 1, 2, or 3 depending on the flexibility of the proximal thoracic (PT) curve and lumbar curve. No definite classification has been established for a major curve at the PT spine. The purpose of this study is to investigate the radiographic characteristics before and after correction surgery for AIS with a major curve at the PT area. Methods: This is a retrospective cohort study at a single academic institution. Twelve patients with a major curve at the PT spine participated in our study and followed for at least two years after surgery. We evaluated the pre- and postoperative Cobb angles of the curve, curve range, location of the apex, sagittal parameters, and shoulder balance-related parameters. All patients were treated by posterior correction and fusion surgery using pedicle screw constructs. Results: The patients were classified as having a double-curve (DC) type, in which the MT curve was structural, or a single-curve (SC) type, in which the MT curve was corrected to less than 25° on supine side-bending films. The mean correction rates for the PT curve were favorable in both groups (DC, 65.7%±9.6%; SC, 39.2%±4.9%). The mean Cobb angle of the lumbar curve improved in the DC group (preoperative, 17.1°±4.0°; postoperative, 5.0°±4.2°) but deteriorated in the SC group (preoperative, 7.1°±1.2°; postoperative, 12.4°±4.4°) after surgery. Conclusions: We illustrated the postoperative radiographical changes of 12 consecutive patients with the major curve at the PT curve. Although posterior correction and fusion surgery corrected the PT curve satisfactorily in both DC and SC patients, the Cobb angle of the lumbar curve deteriorated after surgery in all SC patients. Surgeons need to pay attention to the fusion area, especially LIV, when operating the SC curve type.

Background: Posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) has a potential risk for postoperative pleural effusion. Although pleural effusion at an early period after PSF for AIS occurs with a relatively high frequency and occasionally requires some treatments, the impact of postoperative pleural effusion on future pulmonary function or lung volume (LV) has not been clarified to date. The aim of this study was to evaluate the effect of pleural effusion after PSF for AIS on the postoperative pulmonary function and LV. Methods: A total of 114 consecutive patients who underwent PSF for AIS followed up greater than 2 years at our institute were retrospectively reviewed. We evaluated postoperative pleural effusion by computed tomography (CT) at the 1-week follow-up and divided patients into the pleural effusion (PF) and non-pleural effusion (NP) groups. We investigated spirometry parameters recorded for testing included vital capacity (VC), forced expiratory volume in the first second (FEV1), %VC, and FEV1% and measured the LV using CT images and a workstation at baseline and 2 years after surgery. Results: A total of 87 (76.3%) patients with postoperative pleural effusion were identified, but all patients were asymptomatic and did not require additional treatment for postoperative pleural effusion. All pulmonary function parameters at the 2-year follow-up exhibited no significant differences between the two groups. Although preoperative left LV (1.21±0.30 L vs. 1.36±0.34 L; p=.022) and total LV (2.68±0.62 L vs. 2.99±0.73 L; p=.031) were significantly lower in the PF group than in the NP group, all postoperative LV parameters were similar between the two groups. Conclusions: Pleural effusion at an early period after PSF for AIS was a postoperative occurrence without an impact on future pulmonary function and LV.

Introduction: Only a few reports have described the clinical features of recurrent spinal cord tumors. This study aimed to report the recurrence rates (RRs), radiographic imaging, and pathological features of various histopathological recurrent spinal cord tumors using a large sample size. Methods: This study adopted the retrospective observational study design using a single-center study setting. We retrospectively reviewed 818 consecutive individuals operated for spinal cord and cauda equina tumors between 2009 and 2018 in a university hospital. We first determined the number of surgeries and then the histopathology, duration to reoperation, number of surgeries, location, degree of tumor resection, and tumor configuration of the recurrent cases. Results: A total of 99 patients (46 men and 53 women) who underwent multiple surgeries were identified. The mean duration between the primary and second surgeries was 94.8 months. A total of 74 patients underwent surgery twice, 18 patients thrice, and 7 patients 4 or more times. The recurrence sites were broadly distributed over the spine, with mainly intramedullary (47.5%) and dumbbell-shaped (31.3%) tumors. The RRs for each histopathology were as follows: schwannoma, 6.8%; meningioma and ependymoma, 15.9%; hemangioblastoma, 15.8%; and astrocytoma, 38.9%. The RRs after total resection were significantly lower (4.4%) than that after partial resection. Neurofibromatosis-associated schwannomas had a higher RR than sporadic schwannomas (p

Study Design A retrospective study at a single academic institution. Purpose We aimed to understand the pathogenesis of cervical spondylolisthesis by analyzing whether narrowing of the disc height stabilizes the slipped disc level according to the degenerative cascade. Overview of Literature According to Kirkaldy-Willis’ degenerative cascade, the narrowing of the disc height at slipped level contributes to intervertebral stability in lumbar spondylolisthesis. Conversely, the pathogenesis of cervical spondylolisthesis is unknown due to a scarcity of reports on the condition. Methods The images of 83 patients with cervical single-level spondylolisthesis were studied. We looked at 52 slipped levels for anterior slippage and 31 for posterior slippage. The imaging parameters included slippage in the neutral, flexed, and extended positions, axial facet joint orientation, sagittal facet slope, global cervical alignment, C2–C7 angle, C2–C7 sagittal vertical axis, range of motion (ROM), and slipped disc angle ROM. Results With the narrowing of the intervertebral disc height, slippage in the flexed position of both anterior and posterior spondylolisthesis increased. However, in both anterior and posterior spondylolisthesis, disc height narrowing did not show stability. The narrowing of the intervertebral disc height was found to be a risk factor for a translation of slippage of 1.8 mm or more in flexion-extension motion in anterior spondylolisthesis in multivariate regression analysis. Conclusions Narrowing the intervertebral disc height did not stabilize the translation of slippage in flexion-extension motion in cervical spondylolisthesis. Instead, narrowing of the disc height was associated with a translation of slippage of 1.8 mm or more in flexion-extension motion in cases of anterior slippage. Therefore, we discovered that degenerative cascade stabilization for cervical spondylolisthesis was difficult to achieve.

Abstract Although the incidence of cervical spinal cord injury (CSCI) with ossification of the posterior longitudinal ligament (OPLL) has increased in older adults, its etiology and neurological outcomes remain unknown. We identified OPLL characteristics and determined whether they influence neurological severity and improvement of CSCI in older patients. This multicenter retrospective cohort study identified 1512 patients aged ≥ 65 years diagnosed with CSCI on admission during 2010–2020. We analyzed CSCI etiology in OPLL patients. We performed propensity score-adjusted analyses to compare neurological outcomes between patients with and without OPLL. Cases were matched based on variables influencing neurological prognosis. The primary neurological outcome was rated according to the American Spine Injury Association (ASIA) impairment scale (AIS) and ASIA motor score (AMS). In 332 OPLL patients, the male-to-female ratio was approximately 4:1. Half of all patients displayed low-energy trauma-induced injury and one-third had CSCI without a bony injury. Propensity score matching created 279 pairs. There was no significant difference in the AIS grade and AMS between patients with and without OPLL during hospitalization, 6 months, and 12 months following injury. OPLL patients tended to exhibit worse neurological findings during injury; nevertheless, OPLL was not associated with poor neurological improvement in older CSCI patients.

Study Design A retrospective study conducted at a single academic institution. Purpose This study compared the postoperative alignment of consecutive double laminectomies according to their decompression levels and investigated the influence of the extension unit of the spinous process and its attached muscles on postoperative alignment. Overview of Literature Many reports have investigated bony and soft tissue factors as the causes of postoperative cervical alignment disorders. To-this-date, no other article has clarified the importance of the attached muscles between the spinous processes of C3 and C6 to maintain local cervical alignment. Methods In total, 155 consecutive patients who underwent muscle-preserving consecutive double laminectomies for cervical spondylotic myelopathy from 2005 to 2013 were included in this study. The imaging parameters included the C2–C7 angle, range of motion, C2–C7 sagittal vertical axis (SVA), C7 slope, C2–C5 angle, C5–C7 angle, local disk angle caudal to the decompression level, and the disk height between C2/C3 and C7/Th1. Results The caudal disk angle of the decompression level decreased after consecutive double laminectomies, thus suggesting that the extension unit maintained the local lordosis at the lower disk of the decompression level. Postoperatively, in the C3–4 decompression cases, the C2–C7 angle decreased by 7.3°, and the C2–C7 SVA increased by 8.6 mm, thus indicating the appearance of an alignment disorder. Multivariate logistic regression analysis showed that cephalad laminectomy was a risk factor for C2–C7 angle decreases >10°. However, the postoperative recovery rate of Japanese Orthopedic Association scores after consecutive double laminectomies was reasonable, and the overall cervical alignment was well maintained in all decompression levels except C3–C4. Conclusions The cervical extension unit maintained lordosis at the disk caudal to it. The extension unit was found to contribute more to the maintenance of lordosis of the entire cervical spine at the cephalad side.

Abstract Although traumatic cervical spine injuries in older adults are commonly caused by minor traumas, such as ground-level falls, their prognosis is often unfavorable. Studies examining the clinical characteristics of cervical spine injuries in older adults according to the external cause of injury are lacking. This study included 1512 patients of ≥ 65 years of age with traumatic cervical spine injuries registered in a Japanese nationwide multicenter database. The relationship between the external causes and clinical characteristics, as well as factors causing unfavorable outcomes at the ground-level falls, were retrospectively reviewed and examined. When fall-induced cervical spine injuries were categorized and compared based on fall height, the patients’ backgrounds and injury statuses differed significantly. Of note, patients injured from ground-level falls tended to have poorer pre-injury health conditions, such as medical comorbidities and frailty, compared with those who fell from higher heights. For ground-level falls, the mortality, walking independence, and home-discharge rates at 6 months post-injury were 9%, 67%, and 80%, respectively, with preexisting medical comorbidities and frailty associated with unfavorable outcomes, independent of age or severity of neurological impairment at the time of injury.

Abstract Background The 1-year mortality and functional prognoses of patients who received surgery for cervical trauma in the elderly remains unclear. The aim of this study is to investigate the rates of, and factors associated with mortality and the deterioration in walking capacity occurring 1 year after spinal fusion surgery for cervical fractures in patients 65 years of age or older. Methods Three hundred thirteen patients aged 65 years or more with a traumatic cervical fracture who received spinal fusion surgery were enrolled. The patients were divided into a survival group and a mortality group, or a maintained walking capacity group and a deteriorated walking capacity group. We compared patients’ backgrounds, trauma, and surgical parameters between the two groups. To identify factors associated with mortality or a deteriorated walking capacity 1 year postoperatively, a multivariate logistic regression analysis was conducted. Results One year postoperatively, the rate of mortality was 8%. A higher Charlson comorbidity index (CCI) score, a more severe the American Spinal Cord Injury Association impairment scale (AIS), and longer surgical time were identified as independent factors associated with an increase in 1-year mortality. The rate of deterioration in walking capacity between pre-trauma and 1 year postoperatively was 33%. A more severe AIS, lower albumin (Alb) and hemoglobin (Hb) values, and a larger number of fused segments were identified as independent factors associated with the increased risk of deteriorated walking capacity 1 year postoperatively. Conclusions The 1-year rate of mortality after spinal fusion surgery for cervical fracture in patients 65 years of age or older was 8%, and its associated factors were a higher CCI score, a more severe AIS, and a longer surgical time. The rate of deterioration in walking capacity was 33%, and its associated factors were a more severe AIS, lower Alb, lower Hb values, and a larger number of fused segments.

Introduction: In elderly patients with cervical spinal cord injury, comorbidities such as cardiovascular and cerebrovascular diseases are common, with frequent administration of antiplatelet/anticoagulant (APAC) drugs. Such patients may bleed easily or unexpectedly during surgery despite prior withdrawal of APAC medication. Few reports have examined the precise relationship between intraoperative blood loss and history of APAC use regarding surgery for cervical spine injury in the elderly. The present multicenter database survey aimed to answer the question of whether the use of APAC drugs affected the amount of intraoperative blood loss in elderly patients with cervical spinal cord trauma. Methods: The case histories of 1512 patients with cervical spine injury at 33 institutes were retrospectively reviewed. After excluding cases without spinal surgery or known blood loss volume, 797 patients were enrolled. Blood volume loss was the outcome of interest. We calculated propensity scores using the inverse probability of treatment weighting (IPTW) method. As an alternative sensitivity analysis, linear mixed model analyses were conducted as well. Results: Of the 776 patients (mean age: 75.1±6.4 years) eligible for IPTW calculation, 157 (20.2%) were taking APAC medications before the injury. After weighting, mean estimated blood loss was 204 mL for non-APAC patients and 215 mL for APAC patients. APAC use in elderly patients was not significantly associated with surgical blood loss according to the IPTW method with propensity scoring or linear mixed model analyses. Thus, it appeared possible to perform surgery expecting comparable blood loss in APAC and non-APAC cases. Conclusions: This multicenter study revealed no significant increase in surgical blood loss in elderly patients with cervical trauma taking APAC drugs. Surgeons may be able to prioritize patient background, complications, and preexisting conditions over APAC use before injury when examining the surgical indications for cervical spine trauma in the elderly.

Study Design This is a retrospective study. Purpose This study aims to evaluate the risk factor associated with pseudoarthrosis after placement of lateral interbody fusion (LIF) cages for adult spinal deformity (ASD) treatment. Overview of Literature LIF technique is widely used for ASD correction. Furthermore, pseudoarthrosis is a major complication of fusion surgery required for revision surgery. Methods This study included 42 patients with ASD (two men and 40 women; 112 segments; mean, 68.5±8.4 years; and mean follow-up, 31.6±17.0 months) who underwent LIF and posterior correction surgery. The concave slot of the LIF cage was filled with an autologous iliac crest bone graft (IBG), and the convex slot with a porous hydroxyapatite/collagen (HAp/Col) composite was soaked with bone marrow aspirate. Endplate injury, the gap between vertebral endplate and cage in the coronal or sagittal plane, and fusion status were evaluated using computed tomography multiplanar reconstruction at 12 months after surgery. Moreover, the associated risk factors for pseudoarthrosis were analyzed. Results Fusion at LIF segments were observed in 71.4% segments at 12 months after surgery. Fusion on the concave slot (autologous IBG side), convex slot (porous HAp/Col composite side), and both concave and convex slots were observed in 66.1%, 37.5%, and 36.6% of patients, respectively. Moreover, pseudoarthrosis was observed in 28.6% at 12 months after surgery. Consequently, logistic regression analysis of the fusion at the LIF segment revealed that the gap between the LIF cage and endplate in the coronal plane (p=0.030; odds ratio, 0.183; 95% confidence interval, 0.030–0.183) was significantly associated with pseudoarthrosis at the LIF segments. Conclusions ASD surgery fusion rate using LIF cages was 71.4% at 12 months after surgery. The fusion rate was higher on the concave slot filled with autologous IBG than on the convex slot filled with a porous HAp/Col composite. The gap in the coronal plane was a risk factor for pseudoarthrosis at the LIF segment.

Objective The purpose of our study was to investigate the risk factors of remnant tumor growth after incomplete resection (IR) of cervical dumbbell-shaped schwannomas (DS). Methods Twenty-one patients with IR of cervical DS with at least 2 years of follow-up were included and were divided into 2 groups: the remnant tumor growth (G) (n = 10) and no growth (NG) (n = 11) groups. The tumor location in the axial plane according to Toyama classification, the location of the remnant tumor margin, and the tumor growth rate (MIB-1 index) index were compared. Results No significant differences in Toyama classification and MIB-1 index were found. Age was significantly higher in the G group (61.4 years vs. 47.6 years; p=0.030), but univariate logistic regression analysis revealed little correlation to the growth (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.001–1.166; p=0.047). Seventeen patients (9 in the G and 8 in the NG group) underwent the posterior one-way approach, and significant differences in the location of the remnant tumor margin were confirmed: within the spinal canal in 1 and 0 case, at the entrance of the intervertebral foramen in 7 and 1 cases, and in the foramen distal from the entrance in 1 and 7 cases, in the G and NG groups, respectively (p=0.007). The proximal margin was identified as a significant predictor of the growth (OR, 56.0; 95% CI, 2.93–1,072; p=0.008). Conclusion Remnant tumors with margins distally away from the entrance of the foramen were less likely to grow after IR of cervical DS.

Introduction: The present study aimed to understand the characteristics of adjacent segment stenosis post-surgery by examining the status of adjacent segment stenosis in patients with long-term follow-up after muscle-preserving selective laminectomy (SL). Methods: We examined 43 patients who underwent muscle-preserving SL at a single academic institution and were followed up for >10 years. The C2-C7 angle, C2-C7 sagittal vertical axis, range of motion, and C7 slope were measured using an X-ray lateral view. The anterior-posterior diameter of the spinal cord (AP of SC) and anterior-posterior diameter of the dural tube (AP of dura) at adjacent segment were measured using magnetic resonance imaging T2-weighted sagittal section. Residual space for the spinal cord at the adjacent segment (SAC) was calculated as the difference between AP of SC and AP of dura. Results: Four cases had cephalad adjacent segment stenosis at the last follow-up (upper stenosis (US) group), 9 cases had caudal adjacent segment stenosis ( lower stenosis (LS) group), and 30 cases had no stenosis (none (N) group). AP of SC, AP of dura, and SAC at the upper adjacent segment were significantly lower in the US group. AP of dura and SAC at the lower adjacent segment were significantly lower in the LS group. Multivariate logistic regression analysis revealed that the small AP of dura in the upper adjacent segment and small SAC in the lower adjacent segment were risk factors for developing a new stenosis. Conclusions: Decompression should be considered beforehand in adjacent segments with small AP of SC and small AP of dura when performing cervical decompression.

Body weight-supported treadmill training with the voluntary driven exoskeleton (VDE-BWSTT) has been shown to improve the gait function of patients with chronic spinal cord injury. However, little is known whether VDE-BWSTT can effectively improve the trunk function of patients with chronic spinal cord injury. In this open-label, single-arm study, nine patients with chronic spinal cord injury at the cervical or thoracic level (six males and three females, aged 37.8 ± 15.6 years, and time since injury 51.1 ± 31.8 months) who underwent outpatient VDE-BWSTT training program at Keio University Hospital, Japan from September 2017 to March 2019 were included. All patients underwent twenty 60-minute gait training sessions using VDE. Trunk muscular strength, i.e., the maximum force against which patient could maintain a sitting posture without any support, was evaluated in four directions: anterior, posterior, and lateral (right and left) after 10 and 20 training sessions. After intervention, lateral muscular strength significantly improved. In addition, a significant positive correlation was detected between the change in lateral trunk muscular strength after 20 training sessions relative to baseline and gait speed. The change in trunk muscular strength after 20 training sessions relative to baseline was greatly correlated with patient age. This suggests that older adult patients with chronic spinal cord injury achieved a greater improvement in trunk muscle strength following VDE-BWSTT. All these findings suggest that VDE-BWSTT can improve the trunk function of patients with chronic spinal cord injury and the effect might be greater in older adult patients. The study was approved by the Keio University of Medicine Ethics Committee (IRB No. 20150355-3) on September 26, 2017.

Introduction: Our group has conducted extensive basic and preclinical studies of the use of human induced pluripotent cell (iPSC)-derived neural stem/progenitor cell (hiPSC-NS/PC) grafts in models of spinal cord injury (SCI). Evidence from animal experiments suggests this approach is safe and effective. We are preparing to initiate a first-in-human clinical study of hiPSC-NS/PC transplantation in subacute SCI. Setting: NS/PCs were prepared at a Good Manufacturing Practice-grade cell processing facility at Osaka National Hospital using a clinical-grade integration-free hiPSC line established by the iPSC Stock Project organized by the Kyoto University Center for iPS Cell Research and Application. After performing all quality checks, the long-term safety and efficacy of cells were confirmed using immunodeficient mouse models. Methods: The forthcoming clinical study uses an open-label, single-arm design. The initial follow-up period is 1 year. The primary objective is to assess the safety of hiPSC-NS/PC transplantation in patients with subacute SCI. The secondary objective is to obtain preliminary evidence of its impact on neurological function and quality-of-life outcomes. Four patients with C3/4-Th10 level, complete subacute (within 24 days post-injury) SCI will be recruited. After obtaining consent, cryopreserved cells will be thawed and prepared following a multi-step process including treatment with a γ-secretase inhibitor to promote cell differentiation. A total of 2 × 106 cells will be transplanted into the injured spinal cord parenchyma 14–28 days post-injury. Patients will also receive transient immunosuppression. This study protocol has been reviewed and approved by the Certified Committee for Regenerative Medicine and the Japanese Ministry of Health, Labor and Welfare (University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000035074; Japan Registry of Clinical Trials [jRCT] number, jRCTa031190228). Discussion/conclusion: We plan to start recruiting a patient as soon as the COVID-19 epidemic subsides. The primary focus of this clinical study is safety, and the number of transplanted cells may be too low to confirm efficacy. After confirming safety, a dose-escalation study is planned.

Objective To evaluate the cervical dynamics, neurological function, pain, and quality of life in patients with mild cervical kyphotic alignment who underwent expansive unilateral open-door laminoplasty (ELAP). Methods In this retrospective single-center study, we reviewed the surgical outcomes of 80 patients with cervical spondylotic myelopathy who were followed for at least 2 years. The patients were categorized into the preoperative kyphotic group (C2–7 angle < 0°) and nonkyphotic group (angle ≥ 0°). We compared clinical information, radiographic parameters, Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) scores, and cervical Japanese Orthopaedic Association (JOA) scores between the groups. Results The kyphotic and nonkyphotic groups comprised 17 and 63 patients, respectively. The preoperative C2–7 angles were -3.7° in the kyphotic group and 15.4° in the nonkyphotic group (p

Background: Few studies have examined the changes in cervical sagittal alignment (CSA) and its relationship with other sagittal alignments in AIS patients with major thoracolumbar/lumbar (TL/L) curve who underwent correction surgery. This study investigated the radiographical changes in CSA after correction surgery in patients with Lenke type 6 adolescent idiopathic scoliosis (AIS) and assess any possible factors affecting postoperative CSA. Methods: Forty-four patients with Lenke type 6 AIS (3 males and 41 females, mean age at surgery of 15.6 ± 2.8 years) who could be followed up for 3 years after correction surgery were included in this study. Variations of outcome variables were analyzed in various spinal sagittal parameters using radiographic outcomes. Univariate correlation analyses were used to evaluate possible factors influencing the postoperative CSA. The Scoliosis Research Society (SRS)-22 questionnaires and the Oswestry Disability Index (ODI) were used for clinical evaluation, and the changes between pre- and 3-year post-operation were compared. Results: The Cobb angle of the major and minor curve was significantly improved after correction surgery. Furthermore, CSA, such as C2-7 angle and T1 slope, changed significantly postoperatively. The magnitude of coronal curve correction did not affect CSA postoperatively, while the postoperative TK, T10-L2 kyphosis and LL were significantly correlated with the postoperative C2-7 angle, respectively. None of the patients in this study complained of neck or low back pain during the period up 3 years after the operation. Comparing each domain of SRS-22 or ODI score, these were unchanged between pre-, 1-year, and 3-year post-operation, with no statistically significant differences. Conclusions: CSA changed significantly after correction surgery, and cervical kyphosis indicated a tendency to decrease in Lenke type 6 AIS patients, which was associated with an improvement in thoracic and lumbar sagittal alignment, not correction for coronal deformity.

Objective: Although syringomyelia is considered a risk factor for neurological complications of correction surgery for scoliosis, only a few reports on the surgical results of the correction surgery complicated with associated syringomyelia are available. The purpose of this study is to verify the potential risk of neurological complications due to the presence of syringomyelia and explore the factors affecting the surgical outcomes of posterior correction surgery for scoliosis associated with syringomyelia. Methods: This is a retrospective observational study in a single university hospital setting. Among 754 consecutive patients who underwent posterior correction and fusion surgery for scoliosis from 2009 through 2018 in our institution, we identified 28 patients presenting with spinal syringomyelia on preoperative whole spine MRI. The identified cases comprised 14 males and 14 females aged 11 years to 23 years (14.0 ± 2.9 years), and those with wide-type syrinx within fused spinal levels had undergone surgery for syringomyelia beforehand. First, we investigated the occurrence rate of peri- and postoperative neurological complications. Then we explored the factors affecting the correction rate of the Cobb angle and the incidence of coronal decompensation. Results: Neurological complication (transient sensory deficits in bilateral legs) occurred in one case with thoracic single curve and narrow-type syrinx, disappearing spontaneously within several weeks postoperatively. The cases with an L4 long curve (n = 3, including L4 in thoracolumbar long C-shaped curve) showed a significantly poor correction rate (38.7%, p = 0.003) and developed postoperative coronal decompensation. Conclusions: Prior treatment for wide-type syrinx located within the spinal fusion level effectively prevented severe neurological complications, and when treating cases with long-curve L4 scoliosis associated with syringomyelia, the surgeons should note the occurrence of postoperative coronal decompensation.

Abstract Stem cell-based regenerative therapy has opened an avenue for functional recovery of patients with spinal cord injury (SCI). Regenerative rehabilitation is attracting wide attention owing to its synergistic effects, feasibility, non-invasiveness, and diverse and systemic properties. In this review article, we summarize the features of rehabilitation, describe the mechanism of combinatorial treatment, and discuss regenerative rehabilitation in the context of SCI. Although conventional rehabilitative methods have commonly been implemented alone, especially in studies of acute-to-subacute SCI, the combinatorial effects of intensive and advanced methods, including various neurorehabilitative approaches, have also been reported. Separating the concept of combined rehabilitation from regenerative rehabilitation, we suggest that the main roles of regenerative rehabilitation can be categorized as conditioning/reconditioning, functional training, and physical exercise, all of which are indispensable for enhancing functional recovery achieved using stem cell therapies.

Study Design This is a retrospective observational study with an outpatient setting. Purpose This study aimed to describe the effects of duloxetine (DLX) administration for postsurgical chronic neuropathic disorders (both pain and numbness) following spinal surgery in patients without depression. Overview of Literature Although several reports indicated the potential of DLX to effectively treat postoperative symptoms as a perioperative intervention, there have been no reports of its positive effect on postsurgical chronic neuropathic disorders. Methods A total of 24 patients with postsurgical chronic pain and/or numbness Numeric Rating Scale (NRS) scores of ≥4 were enrolled. All patients underwent spine or spinal cord surgery at Keio University Hospital and received daily administration of DLX for more than 3 months. The mean postoperative period before the first administration of DLX was 35.5±57.0 months. DLX was administered for more than 3 months at a dose of 20, 40, or 60 mg/day, and the degree of pain and numbness was evaluated using the NRS before administration and 3 months after administration. Effectiveness was defined as more than a 2-point decrease in the NRS score following administration. Results In terms of the type of symptoms, 15 patients experienced only numbness, eight experienced both pain and numbness, and one experienced only pain. Of the 24 patients, 19 achieved effective relief with DLX. DLX was effective for all patients with postsurgical chronic pain (n=9), and it reduced postsurgical chronic numbness in 18 of 23 patients. No significant difference was observed in background spinal disorders. DLX was not effective for five patients who complained only of postsurgical chronic numbness. Conclusions This study reports the effectiveness of DLX for postsurgical chronic neuropathic disorders. Although DLX reduced postsurgical chronic pain (efficacy rate=100%) and numbness (78.3%) in certain patients, further investigation is needed to determine its optimal use.

Objective Diffuse idiopathic skeletal hyperostosis (DISH) causes spinal ankylosis, which can result in patients suffering specific spinal fractures that lead to a reduction in the activities of daily life in older patients. Currently, DISH is associated with diabetes mellitus and cardiovascular disease; however, the association between DISH and metabolic syndrome has not been established. The purpose of this study was to investigate a potential association between DISH and metabolic syndrome. Methods We retrospectively reviewed clinical data from consecutive subjects undergoing the musculoskeletal health medical checkups, and enrolled 327 subjects (174 men and 153 women; mean, 63.4 ± 13.7-years). Subjects who had spinal ankylosis at least 4 contiguous vertebral bodies were classified as the DISH group (n = 39) while the others were part of the non-DISH group (n = 288). The definition of the metabolic syndrome comes from diagnostic criteria used by the Japanese Society for Internal Medicine. Age, sex, body max index (BMI), hematological evaluation, blood pressure, presence of metabolic syndrome, the visceral fat area on abdominal computed tomography, and spinal epidural lipomatosis (SEL) on magnetic resonance imaging were evaluated. Results Compared to the non-DISH group, in the DISH group, mean age (DISH group, 74.3 years; non-DISH group, 1.9 years; p < 0.001), male prevalence were higher (DISH group, 82.1%; non-DISH group, 49.3%; p < 0.001), and BMI was greater (DISH group, 24.8; non-DISH group, 23.0; p = 0.006). the metabolic syndrome was more frequently observed in DISH group (28.9%) than in the non-DISH group (16.0%) (p = 0.045). The visceral fat area was significantly larger in the DISH group than in the non-DISH group (DISH group, 130.7 ± 58.2 cm2; Non-DISH group, 89.0 ± 48.1 cm2; p < 0.001). The prevalence of SEL was similar between the 2 groups (10.3% in the DISH group vs. 8.7% in the nonDISH group; p = 0.464). Poisson regression analysis revealed that the metabolic syndrome was significantly associated with DISH with odds ratio of 2.0 (95% confidence interval, 1.0–3.7; p = 0.004). Conclusion Metabolic syndrome was significantly associated with DISH. Our data showed metabolic syndrome is potentially related to DISH.

Study Design Single-center retrospective study. Purpose We aimed to explore the postoperative prognostic factors for spinal intramedullary ependymoma. Overview of Literature Ependymoma (World Health Organization grade II) is the most frequent intramedullary spinal tumor and is treated by total resection. However, postoperative deterioration of motor function occasionally occurs. Methods Eighty patients who underwent surgical resection at Keio University and Fujita Health University in Tokyo, Japan between 2003 and 2015 with more than 2 years of follow-up were enrolled. A good surgical result was defined as an improvement in the modified McCormick Scale score by one grade or more or having the same clinical grade as was observed preoperatively. Meanwhile, a poor result was defined as a reduction in the McCormick Scale score of one grade or more or remaining in grade IV or V at final follow-up. Univariate and multivariate logistic regression analyses of the following factors were performed in the two groups: sex, age, preoperative Visual Analog Scale (VAS), tumor location, the extent of tumor resection, hemosiderin caps, cavity length, and tumor length on magnetic resonance imaging. Results At final follow-up, 15 patients were included in the poor results group and 65 in the good results group. In the univariate analysis, the factors related to poor results were as follows: higher age, preoperative McCormick Scale score severity, higher preoperative VAS, thoracic location, hemosiderin capped, and non-gross total resection (GTR). A multiple logistic regression analysis was conducted and showed that age, worse preoperative McCormick Scale score, and non-GTR were significant factors for poor prognosis. Conclusions The independent risk factors for motor deterioration after ependymoma resection were age, worse preoperative McCormick Scale score, and non-GTR. Early surgery for patients with even mild neurological disorders could facilitate functional outcomes. These results may contribute to determining the optimal timing of surgery for spinal intramedullary ependymoma.

Chin on chest deformity caused by upper cervical kyphosis associated with ankylosing spondylitis is rare. A 66-year-old woman presented at our institute with chief complaints of difficulty in horizontal gaze and opening her mouth. Cervical radiographs showed a C0–2 angle of 1° on flexion and 7° on extension, and her chin-brow vertical angle was 49°. We planned fixation surgery at C0–5 posteriorly to prevent the progression of kyphosis, with slight correction of the kyphosis at C0–2. The correction was performed by pushing down the over lordotically contoured titanium rods connected to an occipital plate onto the C3–5 lateral mass screws, just like cantilever technique. No palpable cracking or loss of resistance was noticed during the correction. However, intraoperative radiographs revealed apparent anterior separation of the vertebral bodies between C3 and C4. Postoperative computed tomography images at the C3/4 level suggested hemorrhage from the fracture site. Tracheostomy was performed because of massive edema around the pharynx. To secure solid bone fusion, staged surgery to extend the fusion to T3 and to graft an additional iliac bone was performed. Fortunately, the C2–7 angle was corrected to 40°, and her chin-brow vertical angle was restored to 17° without any catastrophic complications. Although the patient finally obtained an ideal sagittal alignment, the surgeon should be aware that the technique had a higher perioperative risk for iatrogenic fracture, resulting in neurological and vascular injuries.

Abstract Transplantation of human‐induced pluripotent stem cell‐derived neural stem/progenitor cells (hiPSC‐NS/PCs) is a promising treatment for a variety of neuropathological conditions. Although previous reports have indicated the effectiveness of hiPSC‐NS/PCs transplantation into the injured spinal cord of rodents and nonhuman primates, long‐term observation of hiPSC‐NS/PCs post‐transplantation suggested some “unsafe” differentiation‐resistant properties, resulting in disordered overgrowth. These findings suggest that, even if “safe” NS/PCs are transplanted into the human central nervous system (CNS), the dynamics of cellular differentiation of stem cells should be noninvasively tracked to ensure safety. Positron emission tomography (PET) provides molecular‐functional information and helps to detect specific disease conditions. The current study was conducted to visualize Nestin (an NS/PC marker)‐positive undifferentiated neural cells in the CNS of immune‐deficient (nonobese diabetic‐severe combined immune‐deficient) mice after hiPSC‐NS/PCs transplantation with PET, using 18 kDa translocator protein (TSPO) ligands as labels. TSPO was recently found to be expressed in rodent NS/PCs, and its expression decreased with the progression of neuronal differentiation. We hypothesized that TSPO would also be present in hiPSC‐NS/PCs and expressed strongly in residual immature neural cells after transplantation. The results showed high levels of TSPO expression in immature hiPSC‐NS/PCs‐derived cells, and decreased TSPO expression as neural differentiation progressed in vitro. Furthermore, PET with [18F] FEDAC (a TSPO radioligand) was able to visualize the remnant undifferentiated hiPSC‐NS/PCs‐derived cells consisting of TSPO and Nestin+ cells in vivo. These findings suggest that PET with [18F] FEDAC could play a key role in the safe clinical application of CNS repair in regenerative medicine.

Introduction: As C7 slope increases, lordotic change of C2-C7 angle compensates for adjustments in cervical sagittal balance. However, ossification of the posterior longitudinal ligament (OPLL) may affect the compensatory mechanism of the cervical spine. This study aims to evaluate the impact of OPLL on cervical lordotic compensation after muscle-preserving selective laminectomy (SL). Methods: This study involved 235 patients with cervical spondylotic myelopathy (CSM) and OPLL who underwent 3 consecutive levels of SL. OPLL was classified into continuous, segmental, mixed, or localized type on the basis of the criteria previously reported. In this study, based on the motion preservation at the intervertebral level, patients were divided into CSM (n = 114), OPLL segmental type (OPLL-S; n = 44), and other types of OPLL (OPLL-O; i.e., continuous, mixed, and localized; n = 77). The cervical sagittal alignment, degree of spinal cord decompression, and surgical outcomes were compared among the three groups. Results: The OPLL-O group had a larger postoperative C7 slope (p = 0.020), larger pre- (p = 0.021) and postoperative (p = 0.001) C2-C7 sagittal vertical axis, and greater pre- (p = 0.034) and postoperative (p = 0.002) C7 slope minus C2-C7 angle. Narrower postoperative spinal cord clearance (PSCC) from OPLL (p < 0.001) and more residual spinal cord compression (p < 0.001) were observed in the OPLL-O group. Correlation between postoperative C7 slope minus C2-C7 angle and PSCC was detected (r = −0.238, p < 0.001). The recovery rate of the Japanese Orthopedic Association score was slightly lower in the OPLL-O group (p < 0.001), and it was correlated with postoperative residual spinal cord compression (r = −0.305, p < 0.001). Conclusions: OPLL-O limits cervical lordotic compensation, resulting in cervical sagittal balance mismatch. It affects the degree of spinal cord decompression, which might be related to surgical outcome.

Introduction: The purpose of this study was to elucidate the duration for which the dural tube continues to expand after muscle-preserving cervical laminectomy and the extent to which the expansion affects surgical outcomes. Methods: We analyzed 83 patients with cervical myelopathy who underwent muscle-preserving selective laminectomy of three consecutive laminae between C4 and C6. On the lateral radiographs, parameters considered were C2-7 Cobb angles, range of flexion-extension neck motions, and C2-7 sagittal vertical axis. Neck alignment was classified into four types with lateral radiographs. Anteroposterior (AP) diameter of the dural tube was measured at mid-level of the C5 vertebral body on T2 sagittal image. Expansion ratio (ER) was defined as the extent of expansion at a particular time divided by the final extent of expansion of the dural tube diameter. Operative outcomes were examined using the Japanese Orthopaedic Association scores. Results: The mean age was 62.3 years, and the mean follow-up period was 2 years and 9 months. AP diameter of the dural tube had been expanding until 1-year after surgery. ER in cases with kyphosis was lower at 6 months than that in cases without kyphosis, indicating that the speed of dural expansion was slower in cases with kyphosis. There was no correlation between the extent of expansion of the dural tube and neurological recovery. Conclusions: The dural tube continued to expand for approximately 1-year after surgery. The dural tube of patients with kyphosis slowly expanded possibly because of the hardness of the dura mater. A small extent of dural expansion does not necessarily indicate bad surgical outcomes.

Summary: Treatment of chronic spinal cord injury (SCI) is challenging due to cell loss, cyst formation, and the glial scar. Previously, we reported on the therapeutic potential of a neural progenitor cell (NPC) and chondroitinase ABC (ChABC) combinatorial therapy for chronic SCI. However, the source of NPCs and delivery system required for ChABC remained barriers to clinical application. Here, we investigated directly reprogrammed human NPCs biased toward an oligodendrogenic fate (oNPCs) in combination with sustained delivery of ChABC using an innovative affinity release strategy in a crosslinked methylcellulose biomaterial for the treatment of chronic SCI in an immunodeficient rat model. This combinatorial therapy increased long-term survival of oNPCs around the lesion epicenter, facilitated greater oligodendrocyte differentiation, remyelination of the spared axons by engrafted oNPCs, enhanced synaptic connectivity with anterior horn cells and neurobehavioral recovery. This combinatorial therapy is a promising strategy to regenerate the chronically injured spinal cord. : Fehlings and colleagues investigated the use of directly reprogrammed human neural progenitor cells biased toward an oligodendrogenic fate (oNPCs) combined with sustained delivery of chondroitinase ABC to treat chronic spinal cord injury in an immunodeficient rat model. This combinatorial therapy increased long-term survival of oNPCs, facilitated greater oligodendrocyte differentiation, remyelination of the spared axons by engrafted oNPCs, and neurobehavioral recovery. Keywords: neural progenitor cells, oligodendrocyte, chronic spinal cord injury, glial scar, ChABC, cell transplantation, combinatorial therapy, remyelination, crosslinked methylcellulose hydrogel, regenerative medicine

Proximal junctional failure (PJF) is one of the most devastating complications that develop after adult spinal deformity (ASD) surgery. Here, we report 2 rare cases of PJF accompanied by delayed infection after ASD surgery with a review of the relevant literatures. Late-onset infection is an infrequent complication despite acute postoperative infection is common after posterior spinal instrumentation and fusion. Among them, delayed onset pyogenic spondylitis of the adjacent vertebra to the instrumented vertebrae is an extremely rare phenomenon. We do not have a clear explanation for this pathology. Since the delayed infections developed not in the fused segments but in the adjacent vertebra, the cause of the first case can be speculated as stimulation of low-virulent organisms to fester and hematogenous seeding and that of the second case as metal fretting and a sterile inflammatory response causing hematogenous microbial seeding, respectively. Additional studies on this phenomenon are warranted to elucidate the pathogenesis of this complication.

Introduction: The characteristics of cervical spondylolisthesis are not currently fully understood, because of the shortage of reports covering the large population of patients with cervical spondylolisthesis. The purpose of this study was to elucidate the characteristics of cervical spondylolisthesis by examining a relatively large number of cases. Methods: We analyzed 101 cases with more than 2 mm of vertebral listhesis as determined from X-ray or computed tomography (CT) images among 731 patients who underwent surgery at a single institute. We considered the C2-7 angle, range of motion, and C2-7 sagittal vertical axis on lateral X-ray images. From sagittal CT images, classifications into five grades based on the slipped disc and adjacent caudal levels were made. We examined the orientation of facet joints at the slipped level using axial CT images. Results: Spondylolisthesis was recognized in 101 cases at 124 levels. Anterior and posterior spondylolisthesis were detected in 68 and 40 cases, respectively. Anterior spondylolisthesis developed predominantly at C3 or C4, usually at the level adjacent to the narrowed disc, or at C7, adjacent to the stiffened thoracic spine. The disc height was relatively preserved at the anterior slipped level. Posterior spondylolisthesis developed predominantly at the level of the significantly narrowed disc associated with advanced intervertebral osteoarthritis. At the segment with listhesis in the lower cervical spine, the direction of the facet joint in the axial plane tended to be posteromedial. Conclusions: Cervical degenerative spondylolisthesis was classified into two types. The first and more common listhesis occurred adjacent to stiffened levels, and anterior slippage was common in this type. The second and less common listhesis occurred within progressively degenerated segments, and posterior slippage was prominent. We have uniquely described the morphological changes in orientation of the cervical facet joints at the slipped level in the transverse plane.

The number of elderly patients with spinal cord injury (SCI) is increasing worldwide, representing a serious burden for both the affected patients and the community. Previous studies have demonstrated that neural stem cell (NSC) transplantation is an effective treatment for SCI in young animals. Here we show that NSC transplantation is as effective in aged mice as it is in young mice, even though aged mice exhibit more severe neurological deficits after SCI. NSCs grafted into aged mice exhibited better survival than those grafted into young mice. Furthermore, we show that the neurotrophic factor HGF plays a key role in the enhanced functional recovery after NSC transplantation observed in aged mice with SCI. The unexpected results of the present study suggest that NSC transplantation is a potential therapeutic modality for SCI, even in elderly patients.

Previously, we described the safety and therapeutic potential of neurospheres (NSs) derived from a human induced pluripotent stem cell (iPSC) clone, 201B7, in a spinal cord injury (SCI) mouse model. However, several safety issues concerning iPSC-based cell therapy remain unresolved. Here, we investigated another iPSC clone, 253G1, that we established by transducing OCT4, SOX2, and KLF4 into adult human dermal fibroblasts collected from the same donor who provided the 201B7 clone. The grafted 253G1-NSs survived, differentiated into three neural lineages, and promoted functional recovery accompanied by stimulated synapse formation 47 days after transplantation. However, long-term observation (for up to 103 days) revealed deteriorated motor function accompanied by tumor formation. The tumors consisted of Nestin+ undifferentiated neural cells and exhibited activation of the OCT4 transgene. Transcriptome analysis revealed that a heightened mesenchymal transition may have contributed to the progression of tumors derived from grafted cells.

Transplantation of glial-rich neural progenitors has been demonstrated to attenuate motor neuron degeneration and disease progression in rodent models of mutant superoxide dismutase 1 (SOD1)-mediated amyotrophic lateral sclerosis (ALS). However, translation of these results into a clinical setting requires a renewable human cell source. Here, we derived glial-rich neural progenitors from human iPSCs and transplanted them into the lumbar spinal cord of ALS mouse models. The transplanted cells differentiated into astrocytes, and the treated mouse group showed prolonged lifespan. Our data suggest a potential therapeutic mechanism via activation of AKT signal. The results demonstrated the efficacy of cell therapy for ALS by the use of human iPSCs as cell source.

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 ff Luc-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.

Murine and human iPSC-NS/PCs (induced pluripotent stem cell-derived neural stem/progenitor cells) promote functional recovery following transplantation into the injured spinal cord in rodents. However, for clinical applicability, it is critical to obtain proof of the concept regarding the efficacy of grafted human iPSC-NS/PCs (hiPSC-NS/PCs) for the repair of spinal cord injury (SCI) in a non-human primate model. This study used a pre-evaluated "safe" hiPSC-NS/PC clone and an adult common marmoset (Callithrix jacchus) model of contusive SCI. SCI was induced at the fifth cervical level (C5), followed by transplantation of hiPSC-NS/PCs at 9 days after injury. Behavioral analyses were performed from the time of the initial injury until 12 weeks after SCI. Grafted hiPSC-NS/PCs survived and differentiated into all three neural lineages. Furthermore, transplantation of hiPSC-NS/PCs enhanced axonal sparing/regrowth and angiogenesis, and prevented the demyelination after SCI compared with that in vehicle control animals. Notably, no tumor formation occurred for at least 12 weeks after transplantation. Quantitative RT-PCR showed that mRNA expression levels of human neurotrophic factors were significantly higher in cultured hiPSC-NS/PCs than in human dermal fibroblasts (hDFs). Finally, behavioral tests showed that hiPSC-NS/PCs promoted functional recovery after SCI in the common marmoset. Taken together, these results indicate that pre-evaluated safe hiPSC-NS/PCs are a potential source of cells for the treatment of SCI in the clinic.