Surgical outcomes of anterior column reconstruction for spinal fractures caused by minor trauma-preoperative examination of the number of intervertebral bone bridges is key to obtaining good bone fusion.

BACKGROUND: To achieve good bone fusion in anterior column reconstruction for vertebral fractures, not only bone mineral density (BMD) and bone metabolism markers but also lever arms due to bone bridging between vertebral bodies should be evaluated. However, until now, no lever arm index has been devised. Therefore, we believe that the maximum number of vertebral bodies that are bony and cross-linked with the contiguous adjacent vertebrae (maxVB) can be used as a measure for lever arms. The purpose of this study is to investigate the surgical outcomes of anterior column reconstruction for spinal fractures and to determine the effect of bone bridging between vertebral bodies on the rate of bone fusion using the maxVB as an indicator of the length of the lever arm. METHODS: The clinical data of 81 patients who underwent anterior column reconstruction for spinal fracture between 2014 and 2022 were evaluated. The bone fusion rate, back pain score, between the maxVB = 0 and the maxVB ≥ 2 patients were adjusted for confounding factors (age, smoking history, diabetes mellitus history, BMD, osteoporosis drugs, surgical technique, number of fixed vertebrae, materials used for the anterior props, etc.) and analysed with multivariate or multiple regression analyses. The bone healing rate and incidence of postoperative back pain were compared among the three groups (maxVB = 0, 2≦maxVB≦8, maxVB ≧ 9) and divided by the maxVB after adjusting for confounding factors. RESULTS: Patients with a maxVB ≥ 2 had a significantly higher bone fusion rate (p < 0.01) and postoperative back pain score (p < 0.01) than those with a maxVB = 0. Among the three groups, the bone fusion rate and back pain score were significantly higher in the 2≦maxVB≦8 group (p = 0.01, p < 0.01). CONCLUSIONS: Examination of the maxVB as an indicator of the use of a lever arm is beneficial for anterior column reconstruction for vertebral fractures. Patients with no intervertebral bone bridging or a high number of bone bridges are in more need of measures to promote bone fusion than patients with a moderate number of bone bridges are.

Does the degree of preoperative gait disturbance remain after tumor resection in patients with intradural extramedullary spinal cord tumors?

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: This study aimed to determine whether the degree of preoperative gait disturbance remains following surgical resection in patients with intradural extramedullary spinal cord tumors (IDEMSCTs), and to investigate any factors that may influence poor improvement in postoperative gait disturbance. SETTING: The single institution in Japan. METHODS: In total, 78 IDEMSCTs patients who required surgical excision between 2010 and 2019 were included. According to the degree of preoperative gait disturbance using modified McCormick scale (MMCS) grade, they were divided into the Mild and Severe groups. The mean postoperative follow-up period was 50.7 ± 17.9 months. Data on demographic and surgical characteristics were compared between the two groups. RESULTS: There was no significant difference in terms of age at surgery, sex, tumor size, surgical time, estimated blood loss, tumor histopathology, and postoperative follow-up period between the Mild and Severe groups. At the final follow-up, 84.6% of IDEMSCTs patients were able to walk without support. Gait disturbance improved after surgery in most of the patients with preoperative MMCS grades II-IV, but remained in approximately half of patients with preoperative MMCS grade V. Age at surgery was correlated with poor improvement in postoperative gait disturbance in the Severe group. CONCLUSIONS: Regardless of the degree of preoperative gait disturbance, it improved after tumor resection in most of the IDEMSCTs patients. However, in the preoperative MMCS grade III-V cases, older age at surgery would be an important factor associated with poor improvement in postoperative gait disturbance.

Radiological comparison of penetrating endplate trajectory versus anterior bicortical trajectory for sacral pedicle screw insertion in posterior lumbosacral interbody fusion.

BACKGROUND: The bicortical or tricortical fixation technique with purchase into the anterior sacral wall or promontory has been recommended to achieve rigid sacral pedicle screw fixation, which carries the potential risk of neurovascular injuries. The penetrating endplate screw (PES) technique was proposed as an alternative screw trajectory to facilitate both strong fixation and safety. However, there has been no report on the practical significance of using the PES technique. The aim of the present study was to investigate radiological outcomes using the PES technique for lumbosacral fusion by comparing it with the anterior bicortical technique. METHODS: The subjects consisted of 44 patients with L5 isthmic spondylolisthesis who underwent single-level posterior lumbar interbody fusion at L5-S using the PES technique (20 patients) or the anterior bicortical technique (24 patients) and were followed up for > 2 years (mean follow-up: 36.6 months). Screw loosening and bone fusion were radiologically assessed and compared between the two groups. Factors contributing to bone fusion were investigated using the following factors: (1) age, (2) sex, (3) body mass index, (4) bone mineral density, (5) screw diameter, (6) screw length, (7) pelvic incidence, (8) crosslink connector, (9) cage material, and (10) sacral screw insertion technique. RESULTS: Respective screw loosening and bone fusion rates were 10.0 and 90.0% using the PES technique and 29.2 and 79.2% using the anterior bicortical technique, with no significant differences between the two techniques. Multivariate logistic regression analysis revealed that the age (odds ratio = 0.87, p = 0.02) and PES technique (odds ratio = 22.39, p = 0.02) were significant independent factors contributing to bone fusion. CONCLUSIONS: This is the first study to demonstrate the significance of using the PES technique to improve radiological outcomes. The PES technique could be a valid option for lumbosacral fixation for L5 isthmic spondylolisthesis in terms of improved bone fusion.

Concise Review: Laying the Groundwork for a First-In-Human Study of an Induced Pluripotent Stem Cell-Based Intervention for Spinal Cord Injury.

There have been numerous attempts to develop stem cell transplantation approaches to promote the regeneration of spinal cord injury (SCI). Our multicenter team is currently planning to launch a first-in-human clinical study of an induced pluripotent stem cell (iPSC)-based cell transplant intervention for subacute SCI. This trial was conducted as class I regenerative medicine protocol as provided for under Japan's Act on the Safety of Regenerative Medicine, using neural stem/progenitor cells derived from a clinical-grade, integration-free human "iPSC stock" generated by the Kyoto University Center for iPS Cell Research and Application. In the present article, we describe how we are preparing to initiate this clinical study, including addressing the issues of safety and tumorigenesis as well as practical problems that must be overcome to enable the development of therapeutic interventions for patients with chronic SCI. Stem Cells 2019;37:6-13.

Characteristic cerebral structural changes identified using voxel-based morphometry in patients with post-surgical chronic myelopathic pain.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: Patients who undergo intramedullary spinal surgery occasionally experience post-surgical chronic pain; however, the underlying mechanisms are not yet completely understood. Therefore, this study aimed to identify the cerebral structural changes in patients with post-surgical chronic myelopathic pain using voxel-based morphometry. SETTING: Single university hospital in Tokyo, Japan. METHODS: Forty-nine patients who had undergone intramedullary spinal surgery between January 2002 and April 2014 participated in this study. Participants were classified into two groups based on their post-surgical chronic pain intensity: control (numeric rating scale score of <3) and pain (numeric rating scale score of ≥3) groups. We compared pain questionnaire and brain MRI between two groups. Brain MRI data of each participants was analyzed using voxel-based morphometry. RESULTS: Voxel-based morphometry revealed that the gray matter volume in the left supplementary motor area, left primary motor area, and left posterior cingulate cortex was higher in the pain group than that in the control group. In addition, the numeric rating scale score was significantly correlated with increased gray matter volume in the left primary motor area, left posterior cingulate cortex, and right superior parietal lobule. CONCLUSION: Present study elucidates the characteristic cerebral structural changes after an intramedullary spinal surgery using voxel-based morphometry and indicates that the structural changes in specific cerebral areas are associated with post-surgical chronic myelopathic pain.

The characteristics of the patients with radiologically severe cervical ossification of the posterior longitudinal ligament of the spine: A CT-based multicenter cross-sectional study.

BACKGROUND: Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by heterotopic bone formation in the posterior longitudinal ligament of the spine. We know that the size and distribution of the ossified lesions in patients with OPLL are different in each case. However, the characteristics of the patients with radiologically severe cervical OPLL remain unknown. METHODS: The participants of our study were symptomatic patients with cervical OPLL who were diagnosed by standard radiographs of the cervical spine. Whole-spine CT data and demographic data such as age and sex were obtained from 20 institutions belonging to the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament. According to the number of the levels involved by OPLL, we stratified the patients into two subgroups: severe group (S-group) and non-severe group (NS-group) to delineate the characteristics of radiologically severe patients with cervical OPLL. We also evaluated the most compressed level and the degree of occupying ratio of cervical spinal canal by OPLL at the most compressed level. RESULTS: A total of 234 patients with a mean age of 65 years were recruited. The S-group consisted of 48 patients (21%, 12 females and 36 males) and the NS-group consisted of 92 patients (79%, 22 females and 70 males). The mean age of males in the S-group (68 years old) was significantly higher than that of males in the NS-group (64 years old); however there was no significant difference in the mean age in females between the S-group (69 years old) and the NS-group (66 years old). No significant difference of body mass index, ossification of the nuchal ligament-positivity and presence of diabetes mellitus were found between the S- and the NS-group. CONCLUSIONS: It is likely that the manner of extension of cervical OPLL is different between male and female patients.

Analysis of skeletal-muscle condition after excessive loading of the lower legs by sequential magnetic resonance imaging.

OBJECTIVES: To determine the changes of muscle conditions of lower leg after stretch shortening cycle exercises by MRI. SUBJECTS AND METHODS: This study included 20 healthy male adult volunteers. After conducting control MRI, each subject performed 3 sets of exercise loading, each set consisting of 100 repetitions of rebound jumping on one foot. MRIs were performed immediately after exercise loading (0 h), 6, 30, and 168 h later. After constructing T1/T2/Fractional Anisotropy (FA)/Apparent Diffusion Coefficient (ADC) maps, the changes of three skeletal muscles of the leg (the tibialis anterior [TA], soleus [SOL], and gastrocnemius [GA]) were quantitatively evaluated in each map at each time point. RESULTS: The T1 and T2 values were prolonged after exercise loading, and there was a delay in the recovery of T1 at 6 and 30 h after exercise loading, as compared to those of T2 values over time. The ADC values were elevated in all three muscles immediately after exercise loading, then recovered more slowly than T1 and T2, and still had not returned to baseline 168 h after exercise loading. The FA value decreased in all three muscles after exercise loading, with the greatest decrease occurring immediately after exercise loading. As with the ADC values, the FA values were slow to recover from the decrease, and had not returned to baseline levels 168 h post-loading. CONCLUSION: The delay of T1 value recovery suggested that the T1 value may reflect the muscle condition like fatigue and damage. Changes in the ADC and FA values over time suggested that structural changes such as minute muscular injuries can be detected by diffusion-weighted MRI. Meanwhile, the changes observed in the T1 and T2 values suggested that the measured relaxation time data reflected not only the water volume in the muscle, but also the muscle condition after exercise loading.

Co-existence of ossification of the nuchal ligament is associated with severity of ossification in the whole spine in patients with cervical ossification of the posterior longitudinal ligament -A multi-center CT study.

BACKGROUND: Previous studies have shown that patients with cervical ossification of the posterior longitudinal ligament (OPLL) often have co-existing ossification of the nuchal ligament (ONL). However, no studies have focused on ONL and its relevance to the severity of OPLL or ossification of other spinal ligaments, such as anterior longitudinal ligament (OALL), ligamentum flavum (OLF), and supraspinous/interspinous ligament (OSIL). METHODS: In this multicenter study, we investigated ossification of the spinal ligaments in the whole spine computed tomography (CT) images of 233 cervical OPLL patients. The severity of ossification was evaluated using ossification index for each spinal ligament, calculated as the sum of the level of ossification. We compared the severity of ossification in each spinal ligament between patients with ONL and those without ONL. Furthermore, we investigated how the number of segments, where ONL exists, affects the severity of ossification in each spinal ligament. RESULTS: One hundred thirty patients (55.8%) had co-existing ONL in the cervical OPLL patients included in this study. The ONL (+) group included more male and aged patients. The cervical ossification indexes of OPLL and OALL were higher in ONL (+) patients than in ONL (-) patients. The thoracolumbar ossification indexes of OALL and OSIL were also higher in ONL (+) patients. Logistic regression analysis revealed that age, gender and cervical OA-index were independent factors correlating to the existence of ONL. In the cervical spine, both the ossification indexes of OALL and OPLL increased as the levels of ONL increased. Similarly, in the thoracolumbar spine, both the ossification indexes of OALL and OSIL were increased as the levels of cervical ONL increased. In the multiple regression analysis, cervical OA-index and thoracolumbar OSI-index showed significant correlation with the number of ONL levels. CONCLUSIONS: Co-existence of ONL in cervical OPLL patients was associated with the severity of spinal hyperostosis especially in cervical OPLL, OALL, thoracolumbar OALL and OSIL.

Clinical outcomes of late decompression surgery following cervical spinal cord injury with pre-existing cord compression.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: The purpose of the current study was to examine the effectiveness of late decompression surgery for traumatic cervical spinal cord injury (CSCI) with pre-existing cord compression. SETTING: Murayama Medical Center, National Hospital Organization, Tokyo, Japan. METHODS: In total 78 patients with traumatic CSCI without bone injury hospitalized in 2012-2015 in our institute for rehabilitation after initial emergency care were divided into four groups according to the compression rate (CR) of the injured level and whether or not decompression surgery was performed. Neurological status was evaluated by American Spinal Injury Association impairment scale (AIS), Barthel index, and Spinal Cord Independence Measure (SCIM). RESULTS: In the severe compression group (CR ≥ 40%), >2 grade improvement in the AIS was observed in 30% of patients with surgical treatment, although it was not observed in any patient without surgery. The SCIM improvement rate at discharge was 60% in the surgical treatment group and 20% in the non-surgical treatment group. In the minor compression group (CR < 40%), >2 grade improvement in the AIS was observed in 18% of patients with surgical treatment and in 11% without surgery. The SCIM improvement rate at discharge was 52% in the surgical treatment group and 43% in the non-surgical treatment group. CONCLUSIONS: These results indicate that surgical treatment has an advantage for patients following traumatic CSCI with severe cord compression. In contrast, surgical efficacy is not proved for CSCI patients without severe cord compression.

Distribution of ossified spinal lesions in patients with severe ossification of the posterior longitudinal ligament and prediction of ossification at each segment based on the cervical OP index classification: a multicenter study (JOSL CT study).

BACKGROUND: In patients with ossification of the posterior longitudinal ligament (OPLL) in the cervical spine, it is well known that the thoracic ossified lesions often coexist with the cervical lesions and can cause severe myelopathy. However, the prevalence of OPLL at each level of the thoracic and lumbar spinal segments is unknown. The aims of this study were to investigate how often OPLL occurs at each level in the thoracolumbar spine in patients with a radiological diagnosis of cervical OPLL and to identify the spinal levels most likely to develop ossification. METHODS: Data were collected from 20 institutions in Japan. Three hundred and twenty-two patients with a diagnosis of cervical OPLL were included. The OPLL index (OP index), defined as the sum of the vertebral body and intervertebral disc levels where OPLL is present, was used to determine disease severity. An OP index ≥20 was defined as severe OPLL. The prevalence of OPLL at each level of the thoracic and lumbar spinal segments was calculated. RESULTS: Women were more likely to have ossified lesions in the thoracolumbar spine than men. Severe OPLL was significantly more common in women than in men (20% vs. 4.5%). For thoracic vertebral OPLL, the most frequently affected was the T1 segment in both men and women, followed by the T1/2 and T3/4 intervertebral levels in men and women, respectively. Ossified lesions were frequently seen at the intervertebral and vertebral levels around the cervicothoracic and thoracolumbar junctions in men with severe OPLL, whereas OPLL was more diffusely distributed in the thoracic spine in women with severe OPLL. CONCLUSION: Thoracolumbar OPLL occurred most often at T1 in men and at T3/4 in women. In severe OPLL cases, although ossified lesions were frequently seen at the intervertebral and vertebral levels around the cervicothoracic and thoracolumbar junctions in men, OPLL could be observed more diffusely in the thoracic spine in women.

Application of q-Space Diffusion MRI for the Visualization of White Matter.

White matter abnormalities in the CNS have been reported recently in various neurological and psychiatric disorders. Quantitation of non-Gaussianity for water diffusion by q-space diffusional MRI (QSI) renders biological diffusion barriers such as myelin sheaths; however, the time-consuming nature of this method hinders its clinical application. In the current study, we aimed to refine QSI protocols to enable their clinical application and to visualize myelin signals in a clinical setting. For this purpose, animal studies were first performed to optimize the acquisition protocol of a non-Gaussian QSI metric. The heat map of standardized kurtosis values derived from optimal QSI (myelin map) was then created. Histological validation of the myelin map was performed in myelin-deficient mice and in a nonhuman primate by monitoring its variation during demyelination and remyelination after chemical spinal cord injury. The results demonstrated that it was sensitive enough to depict dysmyelination, demyelination, and remyelination in animal models. Finally, its utility in clinical practice was assessed by a pilot clinical study in a selected group of patients with multiple sclerosis (MS). The human myelin map could be obtained within 10 min with a 3 T MR scanner. Use of the myelin map was practical for visualizing white matter and it sensitively detected reappearance of myelin signals after demyelination, possibly reflecting remyelination in MS patients. Our results together suggest that the myelin map, a kurtosis-related heat map obtainable with time-saving QSI, may be a novel and clinically useful means of visualizing myelin in the human CNS. SIGNIFICANCE STATEMENT: Myelin abnormalities in the CNS have been gaining increasing attention in various neurological and psychiatric diseases. However, appropriate methods with which to monitor CNS myelin in daily clinical practice have been lacking. In the current study, we introduced a novel MRI modality that produces the "myelin map." The myelin map accurately depicted myelin status in mice and nonhuman primates and in a pilot clinical study of multiple sclerosis patients, suggesting that it is useful in detecting possibly remyelinated lesions. A myelin map of the human brain could be obtained in <10 min using a 3 T scanner and it therefore promises to be a powerful tool for researchers and clinicians examining myelin-related diseases.

Astrocyte-mediated infantile-onset leukoencephalopathy mouse model.

Astrocytes have recently been shown to provide physiological support for various brain functions, although little is known about their involvement in white matter integrity. Several inherited infantile-onset leukoencephalopathies, such as Alexander disease and megalencephalic leukoencephalopathy with subcortical cysts (MLC), implicate astrocytic involvement in the formation of white matter. Several mouse models of MLC had been generated by knocking out the Mlc1 gene; however, none of those models was reported to show myelin abnormalities prior to formation of the myelin sheath. Here we generated a new Mlc1 knockout mouse and a Mlc1 overexpressing mouse, and demonstrate that astrocyte-specific Mlc1 overexpression causes infantile-onset abnormalities of the white matter in which astrocytic swelling followed by myelin membrane splitting are present, whereas knocking out Mlc1 does not, and only shows myelin abnormalities after 12 months of age. Biochemical analyses demonstrated that MLC1 interacts with the Na+ /K+ ATPase and that overexpression of Mlc1 results in decreased activity of the astrocytic Na+ /K+ pump. In contrast, no changes in Na+ /K+ pump activity were observed in Mlc1 KO mice, suggesting that the reduction in Na+ /K+ pump activity resulting from Mlc1 overexpression causes astrocytic swelling. Our infantile-onset leukoencephalopathy model based on Mlc1 overexpression may provide an opportunity to further explore the roles of astrocytes in white matter development and structural integrity. We established a novel mouse model for infantile-onset leukoencephalopathy by the overexpression of Mlc1. Mlc1 overexpression reduced activity of the astrocytic sodium pump, which may underlie white matter edema followed by myelin membrane splitting. GLIA 2016 GLIA 2017;65:150-168.

Prevalence and distribution of ossification of the supra/interspinous ligaments in symptomatic patients with cervical ossification of the posterior longitudinal ligament of the spine: a CT-based multicenter cross-sectional study.

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

Grafted human-induced pluripotent stem-cell-derived neurospheres promote motor functional recovery after spinal cord injury in mice.

Once their safety is confirmed, human-induced pluripotent stem cells (hiPSCs), which do not entail ethical concerns, may become a preferred cell source for regenerative medicine. Here, we investigated the therapeutic potential of transplanting hiPSC-derived neurospheres (hiPSC-NSs) into nonobese diabetic (NOD)-severe combined immunodeficient (SCID) mice to treat spinal cord injury (SCI). For this, we used a hiPSC clone (201B7), established by transducing four reprogramming factors (Oct3/4, Sox2, Klf4, and c-Myc) into adult human fibroblasts. Grafted hiPSC-NSs survived, migrated, and differentiated into the three major neural lineages (neurons, astrocytes, and oligodendrocytes) within the injured spinal cord. They showed both cell-autonomous and noncell-autonomous (trophic) effects, including synapse formation between hiPSC-NS-derived neurons and host mouse neurons, expression of neurotrophic factors, angiogenesis, axonal regrowth, and increased amounts of myelin in the injured area. These positive effects resulted in significantly better functional recovery compared with vehicle-treated control animals, and the recovery persisted through the end of the observation period, 112 d post-SCI. No tumor formation was observed in the hiPSC-NS-grafted mice. These findings suggest that hiPSCs give rise to neural stem/progenitor cells that support improved function post-SCI and are a promising cell source for its treatment.

Surgical Outcomes of Adults with Spinal Caries from 1992 to 2019: A Single-Center Study-Risk Factors for the Progression of Kyphosis after Anterior Spinal Fixation Reveal Cases Needing Additional Posterior Instrumentation.

Background: This study aims to investigate the postoperative improvement of paralysis, fusion rate and risk factors for kyphosis progression in adults affected with spinal caries. Methods: Overall, 134 patients with spinal caries from the thoracic to lumbar spine from 1992 to 2021 were included in this study. Data concerning the affected level (thoracic, thoracolumbar, lumbar, and lumbosacral), bone fusion rate, and progression of the postoperative local kyphosis angle were collected. The risk factors for the progression of local kyphosis angle after anterior spinal fixation (ASF) were determined using linear regression analysis. Results: Preoperatively, the degree of spinal cord paralysis was D and E on Frankel classification. Improvement of paralysis was good with surgery, especially from C, D. The overall bone fusion rate was 83.2%. The only factor influencing the progression of local kyphosis angle after ASF was the level of the affected vertebra. Progression of kyphosis angle after ASF was very advanced in the thoracolumbar transition area. Conclusions: Surgical improvement in paraplegia and the fusion rate of ASF with only grafted bone was good. However, in patients affected in the thoracolumbar spine region, posterior instrumentation is desirable because of local kyphosis progression risk after surgery.

Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury.

Various types of induced pluripotent stem (iPS) cells have been established by different methods, and each type exhibits different biological properties. Before iPS cell-based clinical applications can be initiated, detailed evaluations of the cells, including their differentiation potentials and tumorigenic activities in different contexts, should be investigated to establish their safety and effectiveness for cell transplantation therapies. Here we show the directed neural differentiation of murine iPS cells and examine their therapeutic potential in a mouse spinal cord injury (SCI) model. "Safe" iPS-derived neurospheres, which had been pre-evaluated as nontumorigenic by their transplantation into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse brain, produced electrophysiologically functional neurons, astrocytes, and oligodendrocytes in vitro. Furthermore, when the safe iPS-derived neurospheres were transplanted into the spinal cord 9 d after contusive injury, they differentiated into all three neural lineages without forming teratomas or other tumors. They also participated in remyelination and induced the axonal regrowth of host 5HT(+) serotonergic fibers, promoting locomotor function recovery. However, the transplantation of iPS-derived neurospheres pre-evaluated as "unsafe" showed robust teratoma formation and sudden locomotor functional loss after functional recovery in the SCI model. These findings suggest that pre-evaluated safe iPS clone-derived neural stem/progenitor cells may be a promising cell source for transplantation therapy for SCI.

Incidence and predictive factors of shoulder imbalance after selective anterior spinal fusion surgery in Lenke type 5C adolescent idiopathic scoliosis.

Background: No study has assessed the incidence or predictors of postoperative shoulder imbalance (PSI) in patients with Lenke type 5C adolescent idiopathic scoliosis (AIS) who underwent selective anterior spinal fusion (ASF). This study evaluated the incidence and predictors of shoulder imbalance after selective ASF for Lenke type 5C AIS. Methods: In total, 62 patients with Lenke type 5C AIS (4 men and 58 women, mean age at surgery of 15.5 ± 1.5 years) were included and divided into the following two groups according to the radiographic shoulder height (RSH) at the final follow-up: PSI and non-PSI groups. All patients in this study underwent a whole-spine radiological evaluation. Various spinal coronal and sagittal profiles on radiographs were compared between the 2 groups. The clinical outcomes were assessed using the Scoliosis Research Society (SRS)-22 questionnaires. Results: The mean final follow-up duration was 8.6 ± 2.7 years. PSI was observed in 10 patients (16.1%) immediately after surgery; however, in the long-term follow-up period, PSI improved in 3 patients spontaneously, whereas the remaining 7 patients had residual PSI. The preoperative RSH and correction rates of the major curve immediately after surgery or at the final follow-up were significantly larger in the PSI group than in the non-PSI group (p=.001, p=.023, and p=.019, respectively). Receiver operating characteristic curve analysis indicated that the cutoff values for preoperative RSH and the correction rates immediately after surgery and at the final follow-up were 11.79 mm (p=.002; area under the curve [AUC], 0.948), 71.0% (p=.026; AUC, 0.822), and 65.4% (p=.021; AUC, 0.835), respectively. No statistically significant difference was observed in the preoperative and final follow-up SRS-22 scores in any domain between the PSI and non-PSI groups. Conclusions: Paying attention to the preoperative RSH and avoiding excessive correction of the major curve can prevent the occurrence of shoulder imbalance after selective ASF for Lenke type 5C AIS.

Effects of Bone Cross-Link Bridging on Fracture Mechanism and Surgical Outcomes in Elderly Patients with Spine Fractures.

STUDY DESIGN: This study adopted a cross-sectional study design. PURPOSE: This study was designed to investigate the effects of bone cross-link bridging on fracture mechanism and surgical outcomes in vertebral fractures using the maximum number of vertebral bodies with bony bridges between adjacent vertebrae without interruption (maxVB). OVERVIEW OF LITERATURE: The complex interplay of bone density and bone bridging in the elderly can complicate vertebral fractures, necessitating a better understanding of fracture mechanics. METHODS: We examined 242 patients (age >60 years) who underwent surgery for thoracic to lumbar spine fractures from 2010 to 2020. Subsequently, the maxVB was classified into three groups: maxVB (0), maxVB (2-8), and maxVB (9-18), and parameters, including fracture morphology (new Association of Osteosynthesis classification), fracture level, and neurological deficits were compared. In a sub-analysis, 146 patients with thoracolumbar spine fractures were classified into the three aforementioned groups based on the maxVB and compared to determine the optimal operative technique and evaluate surgical outcomes. RESULTS: Regarding the fracture morphology, the maxVB (0) group had more A3 and A4 fractures, whereas the maxVB (2-8) group had less A4 and more B1 and B2 fractures. The maxVB (9-18) group exhibited an increased frequency of B3 and C fractures. Regarding the fracture level, the maxVB (0) group tended to have more fractures in the thoracolumbar transition region. Furthermore, the maxVB (2-8) group had a higher fracture frequency in the lumbar spine area, whereas the maxVB (9-18) group had a higher fracture frequency in the thoracic spine area than the maxVB (0) group. The maxVB (9-18) group had fewer preoperative neurological deficits but a higher reoperation rate and postoperative mortality than the other groups. CONCLUSIONS: The maxVB was identified as a factor influencing fracture level, fracture type, and preoperative neurological deficits. Thus, understanding the maxVB could help elucidate fracture mechanics and assist in perioperative patient management.

A shift of brain network hub after spinal cord injury.

Background: Spinal cord injury (SCI) causes severe sequelae and significant social loss, depending on the extent of the damage. Most previous studies have focused on the pathology of the spinal cord to develop treatments for SCI. However, it is now known that the brain, which is not directly damaged, also undergoes morphological changes after spinal cord injury, which could affect natural recovery and treatment. In recent years, magnetic resonance imaging (MRI) has been developed to analyze functional changes in the brain. Resting-state functional MRI (rsfMRI), which captures brain activity at rest, can calculate functional connections between brain areas and identify central hubs by network analysis. Purpose: We aim to investigate functional connectivity in the brain using rsfMRI after SCI and to determine how brain-network main hubs change over time. Methods: We evaluated rsfMRI in 10 mice of the contusional SCI model and calculated connectivity using graph theory. We evaluated "centrality," a representative parameter of network analysis. The subtype of centrality was degree centrality, which indicates the hub function of a single area. The five times of rsfMRI were performed in each individual mouse: before injury and at 1, 3, 7, and 14 weeks post-injury. Results: Before the injury, the degree centralities of the primary and secondary motor cortex were high, suggesting that these motor cortices served as main hubs for motor function. After SCI, the hub function of the motor cortices decreased by 14 weeks. In contrast, hub function in the external capsule and the putamen comparatively increased with time after injury, suggesting that the extrapyramidal/subcortical system, which runs the ventral side of the spinal cord and remains after injury in this model, becomes dominant. Conclusion: We demonstrated the shift of the brain network hub after SCI. The results of this study provide basic information for understanding brain network changes after SCI and would be useful for treatment selection and evaluation of its efficacy in SCI patients.

Conditions for quantitative evaluation of injured spinal cord by in vivo diffusion tensor imaging and tractography: preclinical longitudinal study in common marmosets.

Conventional magnetic resonance imaging (MRI) can detect hemorrhage, edema, syrinx, and spinal cord atrophy, but not axonal disruption after spinal cord injury (SCI). We previously demonstrated that diffusion tensor tractography (DTT) could depict axonal disruption after hemisection SCI in common marmosets. In the present study, to determine the relationship between DTT results and functional recovery after contusive SCI, we performed longitudinal DTT, behavioral, and histological analyses before and after contusive SCI in common marmosets. By comparing the tract fiber estimate depicted by DTT with neuronal fibers labeled with RT97 and SMI-31, anti-neurofilament antibodies, we determined the optimal fractional anisotropy (FA) threshold for fiber tracking to be 0.40. The ratio of the number of tract fiber estimates at the lesion site to the number before SCI, determined by DTT, was significantly correlated with the functional recovery after SCI. Moreover, comparison of the longitudinal pre- and post-SCI FA and axial diffusivity (λ(‖)) values revealed that they decreased after injury at the sites caudal to the lesion epicenter in the corticospinal tract and rostral to the lesion epicenter in the dorsal column. The FA values, then, showed partial recovery in the dorsal column. FA-value-oriented color DTT was used to represent axonal sparing or regeneration of the different tracts. These findings indicated that DTT analysis might be a versatile non-invasive tool for evaluating the axonal disruption after SCI.