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.

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.

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.

Reduction Capacity and Factors Affecting Slip Reduction Using Cortical Bone Trajectory Technique in Transforaminal Lumbar Interbody Fusion for Degenerative Spondylolisthesis.

Introduction: Vertebral slip reduction has been recommended in arthrodesis for lumbar degenerative spondylolisthesis (LDS) to achieve balanced spinal alignment and bone fusion. However, what determines the degree of slip reduction using cortical bone trajectory technique for lumbar pedicle screw insertion is yet to be determined. Thus, in this study, we aim to investigate the slip reduction capacity using cortical bone trajectory (CBT) technique and to identify factors affecting the slip reduction rate. Methods: This is a retrospective radiological evaluation of prospectively collected patients. In total, 49 consecutive patients who underwent single-level transforaminal lumbar interbody fusion for LDS using the CBT technique were included (mean follow-up: 28.9 months). Firstly, radiological parameters of fused segment including the percentage of anterior vertebral slip (%slip), lordotic angle, and disk height were measured. Then, patient and procedure-related parameters were examined to determine factors related to the slip reduction rate using multiple regression analysis. Results: The %slip was reduced from 15.0±4.8 to 1.6±2.3% immediately after surgery and 2.2±2.9% at the last follow-up (p<0.01), with a slip reduction rate of 87.5±15.7% and correction loss of 0.6±2.1%. As per multivariate regression analysis, it was found that preoperative %slip (standardized regression coefficient [ß]=-0.55, p=0.003) and the depth of screw insertion in the caudal vertebra (ß=0.38, p=0.03) were significant independent factors affecting slip reduction rate (adjusted R2=0.29, p=0.008). Conclusions: To the best of our knowledge, this study is the first to investigate the capacity for and factors affecting slip reduction using the CBT technique for LDS. The CBT technique may be a useful option for achieving slip reduction, and the depth of screw insertion in the caudal vertebra was identified as a significant technical factor to obtain a more significant reduction of slipped vertebra.

Normal pressure hydrocephalus due to an iatrogenic giant lumbar pseudomeningocele after posterior lumbar interbody fusion: illustrative case.

BACKGROUND: Iatrogenic pseudomeningocele incidence after lumbar surgery is 0.068%-2%, and most lumbar pseudomeningoceles are smaller than 5 cm; however, in rare cases, "giant" pseudomeningoceles greater than 8 cm in size may develop. Normal pressure hydrocephalus (NPH) is another rare condition in which the ventricles expand despite the presence of normal intracranial pressure. To date, pseudomeningocele associated with NPH has not been reported. OBSERVATIONS: An 80-year-old woman underwent L3-5 laminectomy and posterior lumbar interbody fusion, and her symptoms improved after surgery. However, dementia appeared 1 month after surgery. Repeated brain computed tomography showed ventricular enlargement, and lumbar magnetic resonance imaging showed a long pseudomeningocele in the subcutaneous tissues at the L4 level. Here, the authors report a rare case of an iatrogenic giant pseudomeningocele accompanied by NPH after lumbar surgery. The symptoms of NPH in the present case occurred after spinal surgery and recovered after dural repair surgery, indicating that the changes in cerebrospinal fluid circulation and/or pressure due to pseudomeningoceles may cause NPH. LESSONS: The prevention of dural tears through precise surgical technique and primary repair of dural tears are the best approaches to prevent pseudomeningocele incidence and subsequent events.

Influence of Intervertebral Level of Stenosis on Neurological Recovery and Reduction of Neck Pain After Posterior Decompression Surgery for Cervical Spondylotic Myelopathy: A Retrospective Multicenter Study with Propensity Scoring.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVE: To identify the impact of the intervertebral level of stenosis on surgical outcomes of posterior decompression for cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: As the upper affected cervical levels in elderly patients result from degenerative changes in the lower cervical levels with aging, it is usually difficult to determine the influence of the upper affected cervical levels on surgical outcomes after posterior decompression for CSM in older age. METHODS: This study involved 636 patients with CSM who underwent posterior decompression. According to the most stenotic intervertebral level, patients were divided into upper (n = 343, the most stenotic intervertebral level was C2/3, C3/4, or C4/5) and lower (n = 293, the most stenotic intervertebral level was C5/6, C6/7, or C7/T1) cervical stenosis groups. Propensity score matching of the baseline factors (characteristics, comorbidities, and neurological function) was performed to compare surgical outcomes, the Japanese Orthopaedic Association (JOA) scores, and visual analog scale (VAS) for neck pain between the upper (n = 135) and lower (n = 135) cervical stenosis groups. RESULTS: Before propensity score matching, age at surgery was older and pre- and postoperative JOA scores were lower in the upper cervical stenosis group (P < 0.001, P < 0.001, and P < 0.001, respectively). Following matching, baseline factors were comparable between the groups. Postoperative JOA scores, preoperative-to-postoperative changes in the JOA scores, and the JOA score recovery rate were not significantly different between the groups (P = 0.866, P = 0.825, and P = 0.753, respectively). No differences existed in postoperative VAS for neck pain and preoperative-to-postoperative changes in VAS for neck pain between the groups (P = 0.092 and P = 0.242, respectively). CONCLUSION: The intervertebral level of stenosis did not affect surgical outcomes after posterior decompression for CSM.Level of Evidence: 3.

Selective Anterior Fusion Surgery Does Not Influence Global Spinal Sagittal Alignment in Lenke Type 5 Adolescent Idiopathic Scoliosis Patients.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: The aim of this study was to evaluate the changes in global spinal sagittal alignment (GSSA) following selective anterior spinal fusion (ASF) in patients with Lenke type 5 adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Few studies have assessed the changes in postoperative GSSA, including cervical, thoracic, and lumbosacral sagittal alignment in AIS patients with major thoracolumbar/lumbar (TL/L) curve who underwent selective ASF. METHODS: Fifty-two patients with Lenke type 5 AIS (two males and 50 females, mean age at surgery of 16.4 ±â€Š3.1 years) were included in this study. The average final follow-up was 8.3 ±â€Š3.1 years after surgery. The variations of outcome variables were analyzed in various spinal sagittal profiles using radiographic outcomes (pre-operation, immediate post-operation, and final follow-up). The clinical outcomes at the final follow-up were assessed using Scoliosis Research Society (SRS)-22 and Oswestry Disability Index (ODI) questionnaires. RESULTS: The mean Cobb angle of the main TL/L and minor thoracic curve was significantly improved after selective ASF, which was maintained up to the final follow-up. However, in all cases, the various sagittal parameters examined (sagittal vertical axis [SVA], C2-7 SVA, C2-7 lordosis, T1 slope, thoracic kyphosis, T10-L2 kyphosis, lumbar lordosis, pelvic incidence, pelvic tilt, and sacral slope), did not significantly change in the immediate postoperative period, and all GSSA parameters were maintained up to the final follow-up. Furthermore, the magnitude of coronal curve correction and fused levels did not affect each GSSA parameter postoperatively. During the period up to the final follow-up, no significant clinical symptoms were observed. The final SRS-22 global score was 4.5 ±â€Š0.3, and ODI scored 0.8 ±â€Š2.4. CONCLUSION: Selective ASF did not influence various GSSA parameters postoperatively and could maintain excellent correction for coronal deformity with satisfactory final functional and clinical outcomes confirmed by long-term follow-up.Level of Evidence: 4.

Tuberculous spondylitis following intravesical Bacillus Calmette-Guérin therapy for bladder cancer surgically treated through the anterior approach.

Intravesical BCG therapy is commonly used to treat superficial bladder cancer. Although various complications associated with this therapy have been reported, tuberculous spondylitis is uncommon. Here, we report a rare case of tuberculous spondylitis that occurred after intravesical BCG therapy for bladder cancer. A man in his 80s received BCG immunotherapy for bladder cancer and developed low back pain after treatment. Remarkably, he presented with neurological symptoms. Spondylitis was suspected on imaging. CT-guided biopsy was performed to confirm the diagnosis. Consequently, Mycobacterium bovis was identified as the causative pathogen by multiplex PCR. Multidrug therapy, administered for several months, was ineffective. Therefore, surgery was performed through an anterior approach. The symptoms, including low back pain, improved and postoperative C reactive protein tests were within the normal range. Tuberculous spondylitis following BCG therapy should be considered in cases with a history of bladder cancer treatment.

Clinical Efficacies of the Minimal Retroperitoneal Approach for Infectious Spondylodiscitis: A Clinical Case Series.

INTRODUCTION: An anterior surgical approach for severe infectious spondylodiscitis in the lumbar region is optimal but not always atraumatic. The aim of this study was to evaluate the efficacy and safety of a minimal anterior-lateral retroperitoneal approach, also known as a surgical approach for oblique lumbar interbody fusion, for cases with severe infectious spondylodiscitis with osseous defects. METHODS: Twenty-four consecutive patients who underwent anterior debridement and spinal fusion with an autologous strut bone graft for infectious spondylodiscitis with osseous defects were reviewed retrospectively. Eleven patients underwent the minimal retroperitoneal approach (Group M), and 13 underwent the conventional open approach (Group C). Peri- and postoperative clinical outcomes, that is, estimated blood loss (EBL), operative time (OT), creatine kinase (CK) level, visual analog scale (VAS), and rates of bone union and additional posterior instrumentation, were evaluated, and the differences between both groups were assessed statistically. RESULTS: Mean EBL, serum CK on the 1st postoperative day, and VAS on the 14th postoperative day were 202.1 mL, 390.9 IU/L, and 9.5 mm in Group M and 648.3 mL, 925.5 IU/L, and 22.3 mm in Group C, respectively, with statistically significant differences between the groups. There were no statistically significant intergroup differences in OT and rates of bone union and additional posterior instrumentation. CONCLUSIONS: Anterior debridement and spinal fusion using the minimal retroperitoneal approach is a useful and safe surgical technique. Although a preponderance of the minimal approach regarding early bone union is not validated, this technique has the advantages of conventional open surgery, but reduces blood loss, muscle injury, and pain postoperatively.

Impact of Tobacco Smoking on Outcomes After Posterior Decompression Surgery in Patients With Cervical Spondylotic Myelopathy: A Retrospective Multicenter Study.

STUDY DESIGN: This was a case-control study. OBJECTIVE: The objective of this study was to clarify the surgical outcomes after cervical posterior decompression in patients who smoked. SUMMARY OF BACKGROUND DATA: Smoking is associated with poor outcomes in the field of spinal surgery. However, the impact of tobacco smoking on the outcomes after posterior decompression surgery has not been fully evaluated in patients with cervical spondylotic myelopathy. MATERIALS AND METHODS: In this retrospective multicenter study, 587 patients with cervical spondylotic myelopathy were enrolled at 17 institutions in Japan. Patients underwent cervical laminoplasty or laminectomy and were followed up for at least 1 year after surgery. Outcome measures were: preoperative smoking status, perioperative complications, the Japanese Orthopedic Association scale, and the Visual Analog Scale for neck pain. After adjusting for age and sex by exact matching, smoking and nonsmoking groups were compared using an unpaired t test for continuous variables or a χ test for categorical variables. RESULTS: There were 182 (31%) current smokers and 405 (69%) nonsmokers including previous smokers. After matching, 158 patients were extracted from each group. Demographic data and surgical information were almost the same between the groups. Regarding postoperative complications, there was no significant difference in the rate of surgical site infection, cerebrospinal fluid leakage, hematoma, segmental motor paralysis, or neurological deficit. However, smokers showed a significantly higher risk for delirium (3.8% vs. 0.0%, P=0.039). Smokers and nonsmokers showed comparable changes in functional recovery according to Japanese Orthopedic Association scores (3.2±2.1 vs. 3.0±2.1, P=0.425) and in neck pain reduction using the Visual Analog Scale (-1.7±3.1 vs. -1.4±2.8, P=0.417) at the final follow-up. CONCLUSIONS: Smokers exhibited functional restoration and neck pain reduction after cervical posterior decompression. Attention is required, however, for the postoperative complication of delirium, which could be caused by the acute cessation of tobacco smoking after admission. LEVEL OF EVIDENCE: Level III.

Quantitative analysis of intervertebral disc degeneration using Q-space imaging in a rat model.

The degree of intervertebral disc (IVD) degeneration is qualitatively evaluated on T2-weighted imaging (T2WI). However, it is difficult to assess subtle changes in IVD degeneration using T2WI. Q-space imaging (QSI) is a quantitative diffusion-weighted imaging modality used to detect subtle changes in microenvironments. This study aimed to evaluate whether QSI can detect the inhibitory effects of the antioxidant N-acetylcysteine (NAC) in IVD degeneration. We classified female Wistar rats into control, puncture, and NAC groups (n = 5 per group). In the puncture and NAC groups, IVDs were punctured using a needle. The antioxidant NAC, which suppresses the progression of IVD degeneration, was orally administered in the NAC group 1 week prior to puncture. The progression and inhibitory effect of NAC in IVD degeneration were assessed using magnetic resonance imaging (MRI): IVD height, T2 mapping, apparent diffusion coefficient (ADC), and QSI. MRI was performed using a 7-Tesla system with a conventional probe (20 IVDs in each group). QSI parameters that were assessed included Kurtosis, the probability at zero displacement (ZDP), and full width at half maximum (FWHM). IVD degeneration by puncture was confirmed by histology, IVD height, T2 mapping, ADC, and all QSI parameters (P < .001); however, the inhibitory effect of NAC was confirmed only by QSI parameters (Kurtosis and ZDP: both P < .001; FWHM: P < .01). Kurtosis had the largest effect size (Kurtosis: 1.13, ZDP: 1.06, and FWHM: 1.02) when puncture and NAC groups were compared. QSI has a higher sensitivity than conventional quantitative methods for detecting the progressive change and inhibitory effect of NAC in IVD degeneration.

Incidences and Risk Factors for Postoperative Non-Union after Posterior Lumbar Interbody Fusion with Closed-Box Titanium Spacers.

STUDY DESIGN: A retrospective, single-center clinical study with follow-up of more than 24 months. PURPOSE: To evaluate the union rates and relevant risk factors for non-union after posterior lumbar interbody fusion (PLIF) using porous-coated closed-box titanium spacers. OVERVIEW OF LITERATURE: Although the use of a closed-box interbody spacer for PLIF could avoid potential complications associated with the harvesting of autologous bone, few studies have reported detailed follow-up of fusion progression and risk factors for non-union in the early postoperative period. METHODS: PLIF using closed-box spacers without filling the autologous bone was performed in 78 (88 levels) consecutive patients. Surgical procedures included PLIF using traditional pedicle screw fixation (PLIF, n=37), PLIF using cortical bone trajectory screw fixation (CBT-PLIF, n=30), and transforaminal lumbar interbody fusion with traditional pedicle screw fixation (TLIF, n=11). Lateral dynamic radiography and computed tomography findings were investigated, and the relationship between the union status and variables that may be related to the risk of non-union was tested statistically. RESULTS: The overall bone union rates at 12 and 24 months were 68.0% and 88.5%, respectively. Incidences of bone cyst formation, subsidence, and retropulsion of spacers were 33.3%, 47.4%, and 14.1%, respectively. Union rates at 24 months were 94.6% in PLIF, 80.0% in CBT-PLIF, and 90.9% in TLIF. Multivariate logistic regression analyses showed that at 12 months postoperatively, the risk factor for non-union was age >75 years (p =0.02). In contrast, no significant risk factor was observed at 24 months. CONCLUSIONS: These findings demonstrated the efficacy of interbody closed-box spacers for PLIF without the need to fill the spacer with autologous bone. However, the risk of non-union should be considered in elderly patients, especially intra-operatively and during the early postoperative stage.

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.

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.

Prevalence and Distribution of Diffuse Idiopathic Skeletal Hyperostosis on Whole-spine Computed Tomography in Patients With Cervical Ossification of the Posterior Longitudinal Ligament: A Multicenter Study.

STUDY DESIGN: This was a retrospective multicenter study. OBJECTIVE: To clarify the progression of diffuse idiopathic skeletal hyperostosis (DISH) using whole-spine computed tomography in patients with cervical ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: DISH and cervical OPLL frequently coexist, and can cause ankylosing spinal fractures due to biomechanical changes and fragility of the affected vertebrae. The epidemiology and pathophysiology of DISH occurring with cervical OPLL are unclear. MATERIALS AND METHODS: We used whole-spine computed tomography to determine the prevalence of DISH in 234 patients with a diagnosis of cervical OPLL based on plain cervical radiographs. We established a novel system for grading the progression of DISH based on a cluster analysis of the DISH distribution along the spine. We calculated the correlation coefficient between this grading system and patient age. RESULTS: The prevalence of DISH in patients with cervical OPLL was 48.7%. Patients with DISH were significantly older than those who did not have DISH (67.3 vs. 63.4 y; P=0.005). Cluster analysis classified the DISH distribution into 6 regions, based on the levels affected: C2-C5, C3-T1, C6-T5, T3-10, T8-L2, and T12-S1. DISH was observed most frequently at T3-T10. We defined a system for grading DISH progression based on the number of regions involved, from grade 0 to 6. DISH was distributed at T3-T10 in >60% of the grade 1 patients, whereas most patients with DISH at the cervical or lumbar spine were grade 4 or 5. There was a weak but significant correlation between the DISH grade and patient age. CONCLUSIONS: DISH was present in nearly half of the patients with cervical OPLL. DISH was more common in older patients. DISH developed at the thoracic level and progressed into the cervical and/or lumbar spine with age. LEVEL OF EVIDENCE: Level III.

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.

Walking balance and compensatory gait mechanisms in surgically treated patients with adult spinal deformity.

BACKGROUND CONTEXT: Gait patterns and their relationship to demographic and radiographic data in patients with adult spinal deformity (ASD) have not been fully documented. PURPOSE: This study aimed to assess gait pattern in patients with ASD and the effect of corrective spinal surgery on gait. DESIGN/SETTING: This is a prospective case series. PATIENT SAMPLE: The gait patterns of 33 consecutive women with ASD (age 67.1 years; body mass index [BMI] 22.5±2.5 kg/m2, Cobb angle 46.8±18.2°, coronal vertical axis [CVA] 1.5±3.7 cm, C7 sagittal vertical axis [SVA] 9.1±6.4 cm, pelvic incidence minus lumbar lordosis [PI-LL] 38.2±22.1°, and lean volume of the lower leg, 5.5±0.6 kg) before and after corrective surgery were compared with those of 33 age- and gender-matched healthy volunteers. OUTCOME MEASURES: Scoliosis Research Society Patient Questionnaire (SRS22r), Oswestry Disability Index (ODI), and forceplate analysis. METHODS: All subjects underwent gait analysis on a custom-built forceplate using optical markers placed on all joints and spinal processes. Dual X-ray absorptiometry scores were used to calculate the lean composition of the lower legs. Subjects with ASD were followed for at least 2 years post operation. RESULTS: Preop mean values showed that patients with ASD had a significantly worse gait velocity (54±10 m/min vs. 70.7±12.9 m/min, p<.01) and stride (97.8±13.4 cm vs. 115.3±15.1 cm, p<.01), but no difference was observed in the stance-to-swing ratio. The right and left ground reaction force vectors were also discordant in the ASD group (vertical direction; r=0.84 vs. r=.97, p=.01). The hip range of motion (ROM) was also significantly decreased in ASD. Correlation coefficient showed moderate correlations between the preoperative gait velocity and the gravity line (GL), PI, ROM of the lower extremity joints, and lean volume, and between the stride and the lean volume, GL, and PI-LL. Gait pattern, stride, and velocity all improved significantly in the patients with ASD after surgery, but were still not as good as in healthy volunteers. The SRS22r satisfaction domain correlated moderately with postoperative gait velocity (r=0.34). CONCLUSIONS: The patients with ASD had an asymmetric gait pattern and impaired gait ability compared with healthy volunteers. Gait ability correlated significantly with the GL, spinopelvic alignment, lower extremity joint ROM, and lean volume. The surgical correction of spinopelvic alignment and exercises to build muscle strength may improve the gait pattern and ability in patients with ASD.

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.

Reoperation rate and risk factors of elective spinal surgery for degenerative spondylolisthesis: minimum 5-year follow-up.

BACKGROUND CONTEXT: The favorable outcome of surgical treatment for degenerative lumbar spondylolisthesis (DS) is widely recognized, but some patients require reoperation because of complications, such as pseudoarthrosis, persistent pain, infection, and progressive degenerative changes. Among these changes, adjacent segmental disease (ASD) and same segmental disease (SSD) are common reasons for reoperation. However, the relative risks of the various factors and their interactions are unclear. PURPOSE: The purpose of this study was to determine the longitudinal reoperation rate after surgery for DS and to assess the incidence and independent risk factors for ASD and SSD. STUDY DESIGN: This study is a retrospective consecutive case series of patients with DS who were surgically treated. PATIENT SAMPLE: We assessed 163 consecutive patients who were surgically treated for DS between 2003 and 2008. Individual patients were followed for at least 5 years after the initial surgery. OUTCOME MEASURES: The primary end point was any type of second lumbar surgery. Radiographic measurements and demographic data were reviewed. We compared patients who underwent reoperation with those who did not. Logistic regression analysis was used to determine the relative risk of ASD and SSD in patients surgically treated for DS. METHODS: Radiographic measurements and demographic data were reviewed. We identified the incidence and risk factors for reoperation, and we performed univariate and multivariate analyses to determine the independent risk factors for revision surgery for SSD and for ASD as the two distinct reasons for the reoperation. Age, gender, etiology, body mass index (BMI), and other radiographic data were analyzed to determine the risk factors for developing SSD and ASD. RESULTS: The average patient age was 65.8 (50-81 years; 73 women and 90 men; mean follow-up, 5.9±1.6 years). Eighty-nine patients had posterior lumbar interbody fusion and 74 had laminotomies. Twenty-two patients had L3-L4 involvement and 141 had L4-L5 involvement. The cumulative reoperation rate was 6.1% at 1 year, 8.5% at 2 years, 15.2% at 3 years, 17.7% at 5 years, and 23.3% (38/163 patients) at the final follow-up. A significantly higher reoperation rate was observed for patients undergoing laminotomy than for patients undergoing posterior lumbar interbody fusion (33.8% vs. 14.4%, p=.01). Eighteen patients (11.0%) had SSD, and 13 patients (8.9%) developed ASD. Higher BMI (obesity) and greater disc height (greater than 10 mm) predicted the occurrence of SSD in the multivariate model (BMI=odds ratio 4.11 [95% confidence interval 1.29-13.11], p=.016; disc height=3.18 [1.03-9.82], p=.044), and gender (male) and facet degeneration (Fujiwara grade greater than 3) predicted the development of ASD in the multivariate model (gender=4.74 [1.09-20.45], p=.037; facet degeneration=6.31 [1.09-36.52], p=.039). CONCLUSIONS: The incidence of reoperation in patients surgically treated for DS was 23.2% at a mean time of 5.9 years. A significantly higher incidence of reoperation was observed in patients treated with decompression alone compared with those treated with decompression and fusion. Body mass index and disc height were identified as independent risk factors for SSD, whereas male gender and facet degeneration were identified as independent risk factors for ASD. The results of this comprehensive review will guide spine surgeons in their preoperative planning and in the surgical management of patients with DS, thereby reducing the reoperation rate.