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Study Design.: A prospective multicenter study. Objective.: The objective of this study is to compare the surgical outcomes of anterior and posterior fusion surgeries in patients with K-line (−) cervical ossification of the posterior longitudinal ligament (OPLL). Summary of Background Data.: Although laminoplasty is effective for patients with K-line (+) OPLL, fusion surgery is recommended for those with K-line (−) OPLL. However, whether the anterior or posterior approach is preferable for this pathology has not been effectively determined. Materials and Methods.: A total of 478 patients with myelopathy due to cervical OPLL from 28 institutions were prospectively registered from 2014 to 2017 and followed up for two years. Of the 478 patients, 45 and 46 with K-line (−) underwent anterior and posterior fusion surgeries, respectively. After adjusting for confounders in baseline characteristics using a propensity score-matched analysis, 54 patients in both the anterior and posterior groups (27 patients each) were evaluated. Clinical outcomes were assessed using the cervical Japanese Orthopaedic Association and the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire. Results.: Both approaches showed comparable neurological and functional recovery. The cervical range of motion was significantly restricted in the posterior group because of the large number of fused vertebrae compared with the anterior group. The incidence of surgical complications was comparable between the cohorts, but the posterior group demonstrated a higher frequency of segmental motor paralysis, whereas the anterior group more frequently reported postoperative dysphagia. Conclusions.: Clinical improvement was comparable between anterior and posterior fusion surgeries for patients with K-line (−) OPLL. The ideal surgical approach should be informed based on the balance between the surgeon's technical preference and the risk of complications. [ABSTRACT FROM AUTHOR]

The features of non-neoplastic lesions are often similar to those of intramedullary tumors, and a differential diagnosis is challenging to obtain in some cases. A surgical biopsy, which is performed on highly invasive tumors, should be avoided in cases of non-neoplastic lesions. Therefore, an accurate diagnosis is important prior to treatment. We evaluated 43 patients suspected of having spinal cord tumors and, finally, were diagnosed with non-neoplastic intramedullary lesions via magnetic resonance imaging. The patients commonly presented with myelitis. The patients with non-neoplastic neurological diseases had a significantly shorter symptom duration than those with intramedullary astrocytomas. The proportion of patients with non-neoplastic neurological diseases who presented with lesions at the cervical spinal level and focal lesions on axial imaging but without a spinal cord enlargement was significantly higher than that of patients with intramedullary astrocytomas. The current study aimed to distinguish spinal cord tumors from non-neoplastic intramedullary lesions based on their distinct features. [ABSTRACT FROM AUTHOR]

Expectations for neural stem/progenitor cell (NS/PC) transplantation as a treatment for spinal cord injury (SCI) are increasing. However, whether and how grafted cells are incorporated into the host neural circuit and contribute to motor function recovery remain unknown. The aim of this project was to establish a novel non-invasive in vivo imaging system to visualize the activity of neural grafts by which we can simultaneously demonstrate the circuit-level integration between the graft and host and the contribution of graft neuronal activity to host behaviour. We introduced Akaluc, a newly engineered luciferase, under the control of enhanced synaptic activity-responsive element (E-SARE), a potent neuronal activity-dependent synthetic promoter, into NS/PCs and engrafted the cells into SCI model mice. Through the use of this system, we found that the activity of grafted cells was integrated with host behaviour and driven by host neural circuit inputs. This non-invasive system is expected to help elucidate the therapeutic mechanism of cell transplantation treatment for SCI. Visualisation of the activity of neural grafts using engineered luciferase provides insights into the integration between the graft and host. [ABSTRACT FROM AUTHOR]

Study Design: A prospective multicenter study.Objective: This study aims to evaluate patient-reported outcomes using the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) and clarify clinical factors that affect the therapeutic effects for patients with cervical ossification of the posterior longitudinal ligament (OPLL).Summary Of Background Data: Although previous studies identified factors that affected the surgical outcomes, their assessment was mainly based on the Japanese Orthopedic Association score, which only includes neurological function. Investigating this pathology through multiple functions and quality of life (QOL) is pivotal to understanding the comprehensive clinical pictures of the cervical OPLL and its therapeutic outcomes.Materials and Methods: This study was performed by the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament. A total of 478 patients with myelopathy caused by cervical OPLL from 28 institutions were prospectively registered from 2014 to 2017 and followed up for 2 years. Of the patients, 168 received laminoplasties and fully completed questionnaires. Demographic information, imaging findings, and clinical outcomes were collected. Patients were grouped according to effective or ineffective surgical outcomes as defined by the JOACMEQ using logistic regression analyses.Results: Laminoplasty resulted in functional improvement in the cervical spine and upper extremity around 40% of the patients, while QOL showed only 21.4% ( P <0.01). Multivariable analyses revealed that younger age and a postoperative decrease in arm or hand pain were correlated with significantly improved function of the upper extremities. A reduction in lower limb pain favorably affected the postoperative lower extremity function. A postoperative reduction in upper extremity pain enhanced the QOL recovery.Conclusions: Surgeons should recognize the diversity of surgical outcomes after laminoplasty and understand the necessity of pain management even after the surgery to enhance bodily functions and QOL in patients with cervical OPLL. [ABSTRACT FROM AUTHOR]

Background: The K-line in the neck-flexed position (FK-line) on radiography reflects dynamic factors and cervical alignment. Although the FK-line has been reported to affect the neurological recovery after muscle-preserving selective laminectomy for cervical spondylotic myelopathy (CSM), its influence on surgical outcomes after expansive open-door laminoplasty (ELAP) has not been investigated.Methods: We reviewed the surgical outcomes in 81 patients with multilevel CSM who underwent C4-C6 ELAP combined with C3 and C7 partial laminectomy using a laminoplasty plate and were followed up for at least 2 years. We defined the K-line (-) as some portion of a bony spur or the vertebral body crossing the FK-line, whereas the FK-line (+) was defined as that never crossing the FK-line. Patients were divided into the FK-line (+) (n = 61) and FK-line (-) groups (n = 20), and the surgical outcomes were compared between the groups. A multivariate analysis was performed to identify the factors that influenced the neurological outcomes.Results: The FK-line (-) group had a smaller C2-C7 angle, smaller C7 slope, greater postoperative increase in the C2-C7 sagittal vertical axis, greater kyphosis in cervical flexion and less lordosis in cervical extension, and higher incidence of postoperative residual spinal cord compression. The preoperative-to-postoperative changes in the Japanese Orthopedic Association (JOA) score and JOA score recovery rate (RR) were lower in the FK-line (-) group. The multiple linear regression analysis revealed that the K-line (-) (β = -0.327, P = 0.011) and high signal intensity (SI) changes on T2-weighted imaging (WI) combined with the low SI changes on T1-WI in the spinal cord (β = -0.320, P = 0.013) negatively affected the JOA score RR.Conclusions: The FK-line can be used for patients with CSM as a simple indicator of neurological outcomes after ELAP. [ABSTRACT FROM AUTHOR]

Human-induced pluripotent stem cell-derived neural stem/progenitor cell (hiPSC-NS/PC) transplantation during the acute phase of spinal cord injury (SCI) is not effective due to the inflammatory response occurring immediately after SCI, which negatively impacts transplanted cell survival. Therefore, we chose to study the powerful chemoattractant complement C5a as a method to generate a more favorable transplantation environment. We hypothesized that suppression of the inflammatory response immediately after SCI by C5a receptor antagonist (C5aRA) would improve the efficacy of hiPSC-NS/PCs transplantation for acute phase SCI. Here, we evaluated the influence of C5aRA on the inflammatory reaction during the acute phase after SCI, and observed significant reductions in several inflammatory cytokines, macrophages, neutrophils, and apoptotic markers. Next, we divided the SCI mice into four groups: 1) phosphate-buffered saline (PBS) only; 2) C5aRA only; 3) PBS + transplantation (PBS+TP); and 4) C5aRA + transplantation (C5aRA+TP). Immediately after SCI, C5aRA or PBS was injected once a day for 4 consecutive days, followed by hiPSC-NS/PC transplantation or PBS into the lesion epicenter on Day 4. The C5aRA+TP group had better functional improvement compared with the PBS only group. The C5aRA+TP group also had a significantly higher cell survival rate compared with the PBS+TP group. This study demonstrates that administration of C5aRA can suppress the inflammatory response during the acute phase of SCI, while improving the survival rate of transplanted hiPSC-NS/PCs, as well as enhancing motor functional restoration. Human-induced pluripotent stem cell-derived neural stem/progenitor cell transplantation with C5aRA is a promising treatment during the acute injury phase for SCI patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Study Design: A prospective multicenter study.Objective: To evaluate and compare the surgical outcomes after open-door (OD) and double-door (DD) laminoplasties in subjects with cervical ossification of the posterior longitudinal ligament (OPLL).Summary Of Background Data: Although previous studies compared clinical results after OD and DD laminoplasties, they were performed at a single institution with a relatively small sample size targeting mixed pathologies, including cervical spondylotic myelopathy.Methods: This study was performed by the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament. A total of 478 patients with myelopathy caused by cervical OPLL from 28 institutions were prospectively registered from 2014 to 2017 and followed up for 2 years. Of these, 41 and 164 patients received OD and DD laminoplasties, respectively. Demographic information, medical history, and imaging findings were collected. Clinical outcomes were assessed using the cervical Japanese Orthopaedic Association, Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire, and visual analog scale scores.Results: Age, sex, symptom duration, and comorbidities were not significantly different between the groups. Segmental ossification was the most frequent in both the groups. No significant differences in K-line type, canal occupying ratio, C2 to C7 angles, and range of motion were found. Both the procedures reduced the cervical range of motion postoperatively. A comparable frequency of perioperative complications was observed between the groups. The cervical Japanese Orthopaedic Association scores showed a similar improvement at 2 years postopera- tively. The reduction in visual analog scale score for neck pain was favorable in the OD group (P = 0.02), while other pain assessments did not show any significant differences between the groups. The functional outcomes assessed using the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire presented equivalent effective rates.Conclusion: The results demonstrated almost comparable surgical outcomes between OD and DD laminoplasties. Lamino- plasty is a valuable technique as a therapeutic option for cervical OPLL.Level of Evidence: 2. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is an abrupt traumatic injury that leads to permanent functional loss, and no practical treatment is available. We have developed pharmaceutical recombinant human hepatocyte growth factor (KP-100), and its efficacy for SCI has been verified using animal models. The purpose of this study was to evaluate the safety and efficacy of intrathecal KP-100 administration for SCI patients in the acute phase. This investigation was a multi-center, randomized, double-blind study. Subjects with modified Frankel grade A/B1/B2 at 72 h after SCI were included. KP-100 was administered intrathecally. Subjects were followed up for 168 days after the first administration. Outcomes were evaluated using American Spinal Injury Association (ASIA) scores and subjected to analysis of covariance. Our results demonstrated that the subjects did not show any serious adverse events caused by KP-100. Forty-three subjects underwent neurological function testing (26 in KP-100 group; 17 in placebo group), which revealed that KP-100 contributed to motor improvement at Days 140 (p = 0.050) and 168 (p = 0.079). In the subset of subjects with Frankel grade A, the proportions of subjects who gained at least 1 point on their lower-extremity motor scores were 33.3% (5/15) and 6.3% (1/16) in the KP-100 and placebo groups, respectively (p = 0.083). Therefore, KP-100 has the potential to be useful and beneficial for SCI patients during the acute phase. However, this was a phase I/II trial and did not definitely address the question of efficacy; a larger phase III trial would be required to assess the efficacy. [ABSTRACT FROM AUTHOR]

There is no choice other than rehabilitation as a practical medical treatment to restore impairments or improve activities after acute treatment in people with spinal cord injury (SCI); however, the effect is unremarkable. Therefore, researchers have been seeking effective pharmacological treatments. These will, hopefully, exert a greater effect when combined with rehabilitation. However, no review has specifically summarized the combinatorial effects of rehabilitation with various medical agents. In the current review, which included 43 articles, we summarized the combinatorial effects according to the properties of the medical agents, namely neuromodulation, neurotrophic factors, counteraction to inhibitory factors, and others. The recovery processes promoted by rehabilitation include the regeneration of tracts, neuroprotection, scar tissue reorganization, plasticity of spinal circuits, microenvironmental change in the spinal cord, and enforcement of the musculoskeletal system, which are additive, complementary, or even synergistic with medication in many cases. However, there are some cases that lack interaction or even demonstrate competition between medication and rehabilitation. A large fraction of the combinatorial mechanisms remains to be elucidated, and very few studies have investigated complex combinations of these agents or targeted chronically injured spinal cords. [ABSTRACT FROM AUTHOR]

Study Design: A retrospective study.Objective: To identify the radiographic differences between Chinese and Japanese patients with cervical ossification of the posterior longitudinal ligament (OPLL) using computed tomography (CT) and magnetic resonance imaging (MRI), and to compare the characteristics of OPLL between the two nationalities.Summary Of Background Data: OPLL has a high prevalence in East Asia. However, the differences between Chinese and Japanese OPLL patients are poorly known.Methods: This was a retrospective study of Chinese (n = 300) and Japanese (n = 102) consecutive patients who received a diagnosis of cervical OPLL between January 2010 and December 2014. All patients underwent CT and MRI. The type and distribution of OPLL were determined. Spinal compression was assessed by MRI. OPLL type, distribution, comorbidity, and compression of the spinal cord were examined. The ossification index (OP-index) was used to evaluate the OPLL. Factors contributing to the OP-index were examined by multivariate analysis.Results: The Chinese patients were younger than the Japanese patients (P < 0.0001), and there were more women among the Chinese patients (P = 0.0002). The OP-index was higher among the Japanese patients (median, 5 vs. 4, P = 0.003). Among men, OPLL lesions were more frequent in the under 55-year-old Japanese at C7 (P = 0.04), in the 55 to 64-year-old Japanese at C4, C5, and C6 (all P < 0.05), and in the over 64-year-old Japanese at C3/4 (P = 0.01), compared with their Chinese counterparts. Among women, OPLL lesions were more frequent in the 55 to 64-year-old Japanese at C6 (P = 0.04). The multivariate analysis showed that only age was independently associated with the OP-index (odds ratio [OR] = 1.023, 95% confidence interval [CI]: 1.002-1.045, P = 0.034).Conclusion: Japanese patients had a higher frequency of OPLL lesions at C5, C6, and C7. Age was independently associated with OPLL.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

A number of studies have demonstrated that transplantation of neural precursor cells (NPCs) promotes functional recovery after spinal cord injury (SCI). However, the NPCs had been mostly harvested from embryonic stem cells or fetal tissue, raising the ethical concern. Yamanaka and his colleagues established induced pluripotent stem cells (iPSCs) which could be generated from somatic cells, and this innovative development has made rapid progression in the field of SCI regeneration. We and other groups succeeded in producing NPCs from iPSCs, and demonstrated beneficial effects after transplantation for animal models of SCI. In particular, efficacy of human iPSC–NPCs in non-human primate SCI models fostered momentum of clinical application for SCI patients. At the same time, however, artificial induction methods in iPSC technology created alternative issues including genetic and epigenetic abnormalities, and tumorigenicity after transplantation. To overcome these problems, it is critically important to select origins of somatic cells, use integration-free system during transfection of reprogramming factors, and thoroughly investigate the characteristics of iPSC–NPCs with respect to quality management. Moreover, since most of the previous studies have focused on subacute phase of SCI, establishment of effective NPC transplantation should be evaluated for chronic phase hereafter. Our group is currently preparing clinical-grade human iPSC–NPCs, and will move forward toward clinical study for subacute SCI patients soon in the near future. [ABSTRACT FROM AUTHOR]

To date, 2 cases of adjacent level spondylodiscitis occurring a few months after initial spinal fusion were reported. However, the development of delayed adjacent level spondylodiscitis is very rare. The authors report 3 cases of spondylodiscitis that occurred at the proximal adjacent level of the fused spine more than 1 year after the initial surgery. Antibiotic treatment was initially chosen in all three cases. In two of the cases, progressive neurological deficit occurred at the level of the infection due to compression of neural elements and spinal instability. For these patients, additional spinal fusion was performed. In each of the three cases, the selected treatment resulted in successful bony fusion at the level of the spondylodiscitis. According to the National Nosocomial Infections Surveillance System, deep wound infection is defined as occurring within 1 year after surgery with instrumentation. The spondylodiscitis in the present cases occurred more than 1 year after the initial surgery, suggesting that these cases may be considered as adjacent segment disease rather than surgical site infection. [ABSTRACT FROM AUTHOR]

While rapid advancements in regenerative medicine strategies for spinal cord injury (SCI) have been made, most research in this field has focused on the early stages of incomplete injury. However, the majority of patients experience chronic severe injury; therefore, treatments for these situations are fundamentally important. Here, we hypothesized that environmental modulation via a clinically relevant hepatocyte growth factor (HGF)-releasing scaffold and human iPS cell-derived neural stem/progenitor cells (hNS/PCs) transplantation contributes to functional recovery after chronic complete transection SCI. Effective release of HGF from a collagen scaffold induced progressive axonal elongation and increased grafted cell viability by activating microglia/macrophages and meningeal cells, inhibiting inflammation, reducing scar formation, and enhancing vascularization. Furthermore, hNS/PCs transplantation enhanced endogenous neuronal regrowth, the extension of graft axons, and the formation of circuits around the lesion and lumbar enlargement between host and graft neurons, resulting in the restoration of locomotor and urinary function. This study presents an effective therapeutic strategy for severe chronic SCI and provides evidence for the feasibility of regenerative medicine strategies using clinically relevant materials. [ABSTRACT FROM AUTHOR]

Numerous basic research studies have suggested the potential efficacy of neural precursor cell ( NPC) transplantation in spinal cord injury ( SCI). However, in most such studies, the origin of the cells used was mainly fetal tissue or embryonic stem cells, both of which carry potential ethical concerns with respect to clinical use. The development of induced pluripotent stem cells ( iPSCs) opened a new path toward regenerative medicine for SCI. iPSCs can be generated from somatic cells by induction of transcription factors, and induced to differentiate into NPCs with characteristics of cells of the central nervous system. The beneficial effect of iPSC-derived NPC transplantation has been reported from our group and others working in rodent and non-human primate models. These promising results facilitate the application of iPSCs for clinical applications in SCI patients. However, iPSCs also have issues, such as genetic/epigenetic abnormalities and tumorigenesis because of the artificial induction method, that must be addressed prior to clinical use. The selection of somatic cells, generation of integration-free iPSCs, and characterization of differentiated NPCs with thorough quality management are all needed to address these potential risks. To enhance the efficacy of the transplanted iPSC- NPCs, especially at chronic phase of SCI, administration of a chondroitinase or semaphorin3A inhibitor represents a potentially important means of promoting axonal regeneration through the lesion site. The combined use of rehabilitation with such cell therapy approaches is also important, as repetitive training enhances neurite outgrowth of transplanted cells and strengthens neural circuits at central pattern generators. Our group has already evaluated clinical grade iPSC-derived NPCs, and we look forward to initiating clinical testing as the next step toward determining whether this approach is safe and effective for clinical use.. [ABSTRACT FROM AUTHOR]

Study Design: This is a systematic review.Purpose: The study aimed to evaluate whether spinal cord concussion (SCC) patients can safely return to play sports and if there are factors that can predict SCC recurrence or the development of a spinal cord injury (SCI).Background Context: Although SCC is a reversible neurologic disturbance of spinal cord function, its management and the implications for return to play are controversial.Methods: We conducted a systematic search of the literature using the keywords Cervical Spine AND Sports AND Injuries in six databases. We examined return to play in patients (1) without stenosis, (2) with stenosis, and (3) who underwent single-level anterior cervical discectomy and fusion (ACDF). We also investigated predictors for the risk of SCC recurrence or SCI.Results: We identified 3,655 unique citations, 16 of which met our inclusion criteria. The included studies were case-control studies or case series and reports. Two studies reported on patients without stenosis: pediatric cases returned without recurrence, whereas an adult case experienced recurrent SCC after returning to play. Seven studies described patients with stenosis. These studies included cases with and without recurrence after return to play, as well as patients who suffered SCI with permanent neurologic deficits. Three studies reported on patients who underwent an ACDF. Although some patients played after surgery without problems, several patients experienced recurrent SCC due to herniation at levels adjacent to the surgical sites. With respect to important predictors, a greater frequency of patients who experienced recurrence of symptoms or SCI following return to play had a "long" duration of symptoms (>24 hours; 36.36%) compared with those who were problem-free (11.11%; p=.0311).Conclusions: There is limited evidence on current practice standards for return to play following SCC and important risk factors for SCC recurrence or SCI. Because of small sample sizes, future prospective multicenter studies are needed to determine important predictive factors of poor outcomes following return to play after SCC. [ABSTRACT FROM AUTHOR]

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

Every year, 0.93 million people worldwide suffer from spinal cord injury (SCI) with irretrievable sequelae. Rehabilitation, currently the only available treatment, does not restore damaged tissues; therefore, the functional recovery of patients remains limited. The pathophysiology of spinal cord injuries is heterogeneous, implying that potential therapeutic targets differ depending on the time of injury onset, the degree of injury, or the spinal level of injury. In recent years, despite a significant number of clinical trials based on various types of stem cells, these aspects of injury have not been effectively considered, resulting in difficult outcomes of trials. In a specialty such as cancerology, precision medicine based on a patient's characteristics has brought indisputable therapeutic advances. The objective of the present review is to promote the development of precision medicine in the field of SCI. Here, we first describe the multifaceted pathophysiology of SCI, with the temporal changes after injury, the characteristics of the chronic phase, and the subtypes of complete injury. We then detail the appropriate targets and related mechanisms of the different types of stem cell therapy for each pathological condition. Finally, we highlight the great potential of stem cell therapy in cervical SCI. [ABSTRACT FROM AUTHOR]

The development of tissue clearing technologies allows 3D imaging of whole tissues and organs, especially in studies of the central nervous system innervated throughout the body. Although the three-dimensional imaging of solvent-cleared organs (3DISCO) method provides a powerful clearing capacity and high transparency, the rapid quenching of endogenous fluorescence and peroxide removal process decreases its practicability. This study provides a modified method named tDISCO to solve these limitations. The tDISCO protocol can preserve AAV-transduced endogenous EGFP fluorescence for months and achieve high transparency in a fast and simple clearing process. In addition to the brain, tDISCO was applied to other organs and even hard bone tissue. tDISCO also enabled us to visualize the long projection neurons and axons with high resolution. This method provides a fast and simple clearing protocol for 3D visualization of the AAV- transduced long projection neurons throughout the brain and spinal cord. [ABSTRACT FROM AUTHOR]

The supraspinal inputs play a major role in tuning the hindlimb locomotion function. While most research on spinal cord injury (SCI) with rodents is based on thoracic segments, the difference in connectivity of the supraspinal centers to the thoracic and lumbar cord is still unknown. Here, we combined retrograde tracing and 3D imaging to map the connectivity of supraspinal neurons projecting to thoracic (T9‐vertebral) and lumbar (T13‐vertebral) spinal levels in adult female mice. We dissected the difference in connections of corticospinal neurons (CSNs), rubrospinal neurons, and reticulospinal neurons projecting to thoracic and lumbar cords. The ratio of double‐labeled neurons is higher in T13‐vertebral projection CSNs and parvocellular part of the red nucleus (RPC) than in T9‐vertebral projection. Using the Cre‐DIO system, we precisely targeted CSNs projecting to T9‐vertebral or T13‐vertebral. We found that abundant axon branches communicated with the red nucleus and reticular formation and distributed from cervical gray matter to the lumbar cord. Their collateral branches showed a distinct innervation pattern in thoracic and lumbar gray matters and a similar distribution pattern in the cervical spinal cord. These results revealed the difference in connectivity between the thoracic and lumbar projection supraspinal centers and clarified the collateralization of thoracic/lumbar projection CSNs throughout the brain and spinal cord. This study highlights brain‐spinal cord neural networks and the complexity of the axon terminals of spinal projection CSNs, which could contribute to the development of targeted therapeutic strategies connecting CST fibers and hindlimb function recovery. Cover Image for this issue: https://doi.org/10.1111/jnc.15414 [ABSTRACT FROM AUTHOR]

We aimed to investigate the risk factors of spontaneous osseous fusion (SOF) of the atlantoaxial joint after closed reduction under general anesthesia followed by halo fixation (remodeling therapy) for chronic atlantoaxial rotatory fixation, and to elucidate the recovery mechanism of the rotatory range of motion (ROM) after halo removal. Twelve patients who underwent remodeling therapy were retrospectively reviewed. Five patients with SOF were categorized as the fusion group and seven patients without SOF as the non-fusion group. Three dimensional CT was used to detect direct osseous contact (DOC) of facet joints before and during halo fixation, while dynamic CT at neutral and maximally rotated head positions was performed to measure rotatory ROM after halo removal. The duration from onset to initial visit was significantly longer (3.2 vs. 5.7 months, p = 0.04), incidence of DOC during halo fixation was higher (0/7 [0%] vs. 4/5 [80%], p = 0.004), and segmental rotatory ROM of Occiput/C1 (Oc/C1) at final follow-up was larger (9.8 vs. 20.1 degrees, p = 0.003) in the fusion group. Long duration from the onset to the initial visit might induce irreversible damage to the articular surface of the affected facet, which was confirmed as DOC during halo fixation and resulted in SOF. Long duration from the onset to the initial visit and DOC during halo fixation could be used to suggest the risk for SOF. Nonetheless, rotatory ROM of Oc/C1 increased to compensate for SOF. [ABSTRACT FROM AUTHOR]

Background/Objectives: An important aspect of the pathophysiology of frailty seems to be the dysregulation of inflammatory pathways and the coagulation system. However, an objective assessment of the impact of frailty on the recovery from surgery is not fully studied. This study sought to assess how frailty affects the recovery of adult spinal deformity (ASD) surgery using blood biomarkers. Methods: 153 consecutive ASD patients (age 64 ± 10 yr, 93% female) who had corrective spine surgery in a single institution and reached 2y f/u were included. The subjects were stratified by frailty using the modified frailty index-11 (robust [R] group or prefrail and frail [F] group). Results of commonly employed laboratory tests at baseline, 1, 3, 7, and 14 post-operative days (POD) were compared. Further comparison was performed in propensity-score matched-39 paired patients between the groups by age, curve type, and baseline alignment. A correlation between HRQOLs, major complications, and biomarkers was performed. Results: Among the propensity-score matched groups, CRP was significantly elevated in the F group at POD1,3(POD1; 5.3 ± 3.1 vs. 7.9 ± 4.7 p = 0.02, POD3; 6.6 ± 4.6 vs. 8.9 ± 5.2 p = 0.02). Transaminase was also elevated in the F group at POD3(ASD: 36 ± 15 vs. 51 ± 58 U/L, p = 0.03, ALT: 32 ± 16 vs. 47 ± 55 U/L, p = 0.04). Interestingly, moderate correlation was observed between transaminase at POD1 and 2 y SRS22 (AST; function r = −0.37, mental health r = −0.39, satisfaction −0.28, total r = −0.40, ALT; function r = −0.37, satisfaction −0.34, total r = −0.39). Conclusions: Frailty affected the serum CRP and transaminase differently following ASD surgery. Transaminase at early POD was correlated with 2 y HRQOLs. These findings support the hypothesis that there is a specific physiological basis to the frailty that is characterized in part by increased inflammation and that these physiological differences persist. [ABSTRACT FROM AUTHOR]

Hepatocyte growth factor (HGF) was first identified as a potent mitogen for mature hepatocytes, and has also gained attention as a strong neurotrophic factor in the central nervous system. We found that during the acute phase of spinal cord injury (SCI) in rats, c-Met, the specific receptor for HGF, increases sharply, while the endogenous HGF up-regulation is relatively weak. Introducing exogenous HGF into the spinal cord by injecting an HGF-expressing viral vector significantly increased the neuron and oligodendrocyte survival, angiogenesis, and axonal regeneration, to reduce the area of damage and to promote functional recovery in rats after SCI. Other recent studies in rodents have shown that exogenously administered HGF during the acute phase of SCI reduces astrocyte activation to decrease glial scar formation, and exerts anti-inflammatory effects to reduce leukocyte infiltration. We also reported that the intrathecal infusion of recombinant human HGF (intrathecal rhHGF) improves neurological hand function after cervical contusive SCI in the common marmoset, a non-human primate. Based on these collective results, we conducted a phase I/II clinical trial of intrathecal rhHGF for patients with acute cervical SCI who showed a modified Frankel grade of A/B1/B2 72 h after injury onset, from June 2014 to May 2018. [ABSTRACT FROM AUTHOR]

Purpose: Postoperative complication prediction helps surgeons to inform and manage patient expectations. Deep learning, a model that finds patterns in large samples of data, outperform traditional statistical methods in making predictions. This study aimed to create a deep learning-based model (DLM) to predict postoperative complications in patients with cervical ossification of the posterior longitudinal ligament (OPLL). Methods: This prospective multicenter study was conducted by the 28 institutions, and 478 patients were included in the analysis. Deep learning was used to create two predictive models of the overall postoperative complications and neurological complications, one of the major complications. These models were constructed by learning the patient's preoperative background, clinical symptoms, surgical procedures, and imaging findings. These logistic regression models were also created, and these accuracies were compared with those of the DLM. Results: Overall complications were observed in 127 cases (26.6%). The accuracy of the DLM was 74.6 ± 3.7% for predicting the overall occurrence of complications, which was comparable to that of the logistic regression (74.1%). Neurological complications were observed in 48 cases (10.0%), and the accuracy of the DLM was 91.7 ± 3.5%, which was higher than that of the logistic regression (90.1%). Conclusion: A new algorithm using deep learning was able to predict complications after cervical OPLL surgery. This model was well calibrated, with prediction accuracy comparable to that of regression models. The accuracy remained high even for predicting only neurological complications, for which the case number is limited compared to conventional statistical methods. [ABSTRACT FROM AUTHOR]

The coexistence of vascular malformations in the conus medullaris and cauda equina has been rarely reported, and the complex angioarchitecture in multiple arteriovenous lesions remains poorly understood. A 17-year-old woman presented with a sudden-onset, stepwise worsening of weakness and pain in the bilateral legs. Angiography revealed conus medullaris arteriovenous malformation and cauda equina arteriovenous fistulas. One of the drainers was shared between the coexisting lesions and harboured a varix. Targeted embolisation of a fistulous point in the conus lesion was performed with precaution to prevent occluding the common drainage route, which led to symptom improvement with angiographical diminishment of the varix. Recognising that communications between drainers can be observed in multiple spinal arteriovenous lesions is important in facilitating a safe embolisation. Cautious assessment of angiogram with fusion images of cone-beam computed tomography and volumetric T2 magnetic resonance imaging can help in establishing the diagnosis and treatment strategy. [ABSTRACT FROM AUTHOR]

Since osteopenia has been reported to potentially associated with the progression of scoliosis, bone mineral density (BMD) might have some influences on adolescent idiopathic scoliosis (AIS). However, little is known about longitudinal BMD changes in AIS patients. This study aimed to investigate whether osteopenia in preoperative AIS patients persist at bone maturity, and to evaluate the association between BMD and AIS severity. We reviewed 61 AIS patients who underwent surgery when they were Risser grade 4 or below and less than 20 years old (16.6 ± 1.9 years), were followed until they were at least 18 years old and had a Risser grade of 5, and followed at least 2 years after the surgery (mean follow-up 4.9 ± 1.7 years). We evaluated radiographical parameters and proximal femur BMD before surgery and at the final follow-up. A BMD of less than the mean minus 1SD was considered as low BMD. Based on preoperative BMD, 37 patients were assigned to normal BMD (N) group (1.02 ± 0.08 g/cm2) and 24 patients to low BMD (L) group (0.82 ± 0.06 g/cm2). All patients in the N-group had normal BMD at the final follow-up. In the L group, 15 patients (62.5%) had low BMD at the final follow-up (L–L group; preoperative 0.79 ± 0.05 g/cm2 and final follow-up 0.78 ± 0.05 g/cm2). The mean preoperative Cobb angle was significantly larger in the L–L group (67.8 ± 11.2°) than in those with normal BMD at the final follow-up (L–N group, 55.6 ± 11.8°) or the N–N group (50.8 ± 7.6°). Preoperative BMD was significantly negative correlated with the preoperative Cobb angle. The age at surgery and mean preoperative BMI were similar in the L–N and L–L groups. Of AIS patients with low preoperative BMD, 62.5% still had low BMD after reaching bone maturity, and low BMD was associated with the severity of scoliosis. [ABSTRACT FROM AUTHOR]

Chitosan has various tissue regeneration effects. This study was designed to investigate the nerve regeneration effect of Schwann cell (SC)-encapsulated chitosan-collagen hydrogel nerve conduit (CCN) transplanted into a rat model of sciatic nerve defect. We prepared a CCN consisting of an outer layer of chitosan hydrogel and an inner layer of collagen hydrogel to encapsulate the intended cells. Rats with a 10-mm sciatic nerve defect were treated with SCs encapsulated in CCN (CCN+), CCN without SCs (CCN−), SC-encapsulated silicone tube (silicone+), and autologous nerve transplanting (auto). Behavioral and histological analyses indicated that motor functional recovery, axonal regrowth, and myelination of the CCN+ group were superior to those of the CCN− and silicone+ groups. Meanwhile, the CCN− and silicone+ groups showed no significant differences in the recovery of motor function and nerve histological restoration. In conclusion, SC-encapsulated CCN has a synergistic effect on peripheral nerve regeneration, especially axonal regrowth and remyelination of host SCs. In the early phase after transplantation, SC-encapsulated CCNs have a positive effect on recovery. Therefore, using SC-encapsulated CCNs may be a promising approach for massive peripheral nerve defects. [ABSTRACT FROM AUTHOR]

Study Design.: A prospective longitudinal magnetic resonance imaging (MRI) study. Objective.: The objective of this study was to describe the progression of intervertebral disk (IVD) degeneration in patients who underwent posterior decompression surgery for lumbar spinal canal stenosis (LSS). Summary of Background Data.: IVD degeneration contributes to the pathogenesis of LSS; however, the long-term consequences of degenerative changes after decompression surgery remain unknown. Materials and Methods.: Of 258 consecutive patients who underwent posterior lumbar decompression surgery for LSS, 62 who underwent MRI at their 10-year follow-up were included; 17 age-matched asymptomatic volunteers were analyzed as controls. Three MRI findings representing IVD degeneration were graded on their severity: decrease in signal intensity, posterior disk protrusion (PDP), and disk space narrowing (DSN). Clinical outcome was assessed using the low back pain (LBP) score from the Japanese Orthopaedic Association scoring system. We examined the association between the progression of degenerative changes on MRI and LBP/associated factors using logistic regression adjusting for age at baseline and sex. Results.: The severity of IVD degeneration tended to be higher in patients with LSS than asymptomatic volunteers at both baseline and follow-up. IVD degeneration progressed in all patients during the 10-year follow-up period. Progression of decrease in signal intensity and PDP was observed at L1/2 in 73% and at L2/3 in 34%, respectively (the highest frequencies in the lumbar spine). Progression of DSN was highest at L4/5 in 42%. The rates of PDP and DSN progression during the 10-year follow-up period tended to be greater in patients with LSS than in asymptomatic volunteers. No significant difference in the proportion of LBP deterioration was evident for individuals with and without MRI findings of progression. Conclusions.: Our study reveals a natural history of the long-term postoperative course of IVD degeneration after posterior decompression surgery for LSS. Compared with healthy controls, patients with LSS seemed to be predisposed to IVD degeneration. Lumbar decompression surgery may promote the progression of DSN; however, progression of IVD degeneration after lumbar decompression surgery was not associated with worsening LBP scores. [ABSTRACT FROM AUTHOR]

Extreme lateral interbody fusion (XLIF) is often used with posterior spinal fixation (PSF) to treat adult spinal deformity (ASD). However, the amount of intraoperative blood loss (IBL) reported for XLIF may underestimate the total blood loss (TBL). The objective of this study was to determine the total perioperative blood loss in XLIF for ASD. We assessed 30 consecutive ASD patients with Schwab-SRS type L (mean age: 68.7 ± 8.2 years; mean follow-up 2.0 ± 1.3 years) who were treated by multilevel XLIF (mean, 2.5 ± 0.6 levels) followed by PSF after 3–5 days. We calculated the TBL after XLIF by the Gross equation, by hemoglobin (Hb) balance, and by the Orthopedic Surgery Transfusion Hemoglobin European Overview (OSTHEO) formula. We defined hidden blood loss (HBL) as the difference between the TBL and IBL. Pearson correlation, Spearman correlation, and multiple logistic regression analysis were performed to investigate the risk factors related to HBL. Post-XLIF blood tests showed a significant decrease in the Hb (from 11.8 ± 1.1 mg/dl to 10.6 ± 1.1 mg/dl) and hematocrit (from 36.0 ± 3.2% to 32.5 ± 3.2%). Although the mean IBL was relatively small (33 ± 52 mL), we calculated the TBL as 291 ± 171 mL (Gross equation) and the HBL as 258 ± 168 mL by Gross equation, which was 8 times greater than the IBL on average. There was no difference in the results obtained using the three methods. Multiple logistic regression analysis indicated preoperative lumber lordosis was the risk factor of high HBL (Odds ratio = 1.085, 95%CI: 1.006–1.170, p = 0.035). The HBL in XLIF was 8 times greater than the IBL. During the perioperative course of correction and fusion surgery for ASD with XLIF, surgeons need to pay attention not to underestimate the TBL. [ABSTRACT FROM AUTHOR]

Study Design.: Multicenter retrospective study. Objective.: This study reports long-term clinical and radiographic outcomes in surgically treated patients with adult symptomatic lumbar deformity (ASLD). Summary of Background Data.: The short-term results of corrective spinal surgery for ASLD are often favorable despite a relatively high complication profile. However, long-term outcomes have not been completely characterized. Methods.: A total of 169 surgically treated consecutive ASLD patients (≥50 yr) who achieved minimum 5 year follow-up were included (average 7.5 yr observation window, average age 67±8 yr, 96% female). The subjects were stratified by current age (50s, 60s, and 70s) and compared. Kaplan-Meier analysis was used to estimate the cumulative incidence of unplanned reoperation stratified by age group. Initial and overall direct costs of surgery were also analyzed. Results.: The SRS-22 at final follow-up was similar among the three groups (50s, 60s, and 70s; 4.0±0.5 vs. 3.8±0.7 vs. 3.8±0.7, respectively). The overall major complication rate was 56%, and 12% experienced late complications. The cumulative reoperation rate was 23%, and 4% required late reoperation. Patients in their 70s had a significantly higher reoperation rate (33%) and overall complication rate (65%). However, the late complication rate was not significantly different between the three groups (9% vs. 12% vs. 13%). Sagittal alignment was improved at two years and maintained to the final follow-up, whereas reciprocal thoracic kyphosis developed in all age groups. The direct cost of initial surgery was $45K±9K and increased by 13% ($53K±13K) at final follow-up. Conclusions.: Long-term surgical outcomes for ASLDs were favorable, with a relatively low rate of late-stage complications and reoperations, as well as reasonable direct costs. Despite the higher reoperation and complication rate, ASLD patients of more advanced age achieved similar improvement to those in the younger age groups. [ABSTRACT FROM AUTHOR]

To evaluate the radiological differences between diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS) using whole spine computed tomography (CT), including the spine and sacroiliac joint (SIJ). The ossification and bridging of spinal ligament and fusion of the facet joint and SIJ were evaluated in 111 patients who were diagnosed with DISH and 27 patients with AS on the whole spine CT. The number of anterior bridging and shape of bridging (candle-wax-type/ smooth-type) were also evaluated. We further evaluated patients with DISH and AS by matching their age and sex. Complete SIJ fusion was more common in AS, whereas anterior and posterior bony bridging around SIJ was more common in DISH. However, 63% of patients with DISH had a partial or complete fusion. In spinal anterior bony bridging, the majority of patients with AS had the smooth-type, whereas those with DISH had the candle-wax-type. However, some of the patients with DISH (11%) had smooth-type. Intervertebral facet joint fusion is more common in AS. The number of anterior spinal bony bridging was greater in AS than in DISH, especially in the lumbar spine. These results are useful in differentiating DISH from AS and should therefore be considered when making a diagnosis. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective case series.Objective: The purpose of this study was to investigate the outcome of multilevel posterior decompression surgery for degenerative lumbar spinal stenosis compared with single-level surgery.Summary Of Background Data: The clinical outcomes of multilevel decompression surgery are still controversial because previous studies have not been designed to randomize or adjust the patient background.Materials and Methods: A retrospective review of prospectively collected data from 659 surgically treated lumbar spinal stenosis patients with a minimum 2-year follow-up was performed. Among them, we compared baseline and 2-year postoperative patient-reported outcomes (PROs) including the Visual Analog Scale and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire scores of 122 patients who underwent three or more levels of surgery (M group) and 304 patients who underwent single-level surgery (S group). Further analyses were performed of 116 paired patients from both groups who were propensity score matched by age and baseline PROs.Results: The number of perioperative complications including extradural hematoma, surgical site infection, and spinal fluid leakage [M vs. S: 10 (8%) vs. 19 (6%), P =0.47], and frequency of revision surgery [5 (4%) vs. 23 (8%), P =0.10] were similar between the two groups. In the analysis of propensity score-matched patients, there were comparable improvements in the Visual Analog Scale score for lower back pain (2.6 vs. 2.4, P =0.55), buttock-leg pain (3.1 vs. 3.4, P =0.48), and buttock-leg numbness (2.9 vs. 2.9, P =0.77) in both groups. There were also similar improvements in the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire scores including lower back pain, lumbar function, walking ability, and mental health domains, except for the social life function domain (20.7±26.5 vs. 28.0±27.5, P =0.04).Conclusions: Despite the longer surgical time and a larger volume of estimated blood loss, multilevel decompression surgery showed similar improvement to that of single-level surgery in terms of recovery of PROs and frequency of revision surgery. Multilevel decompression surgery provides good clinical outcomes with acceptable complication and revision rates when selecting appropriate patient and spinal levels. [ABSTRACT FROM AUTHOR]

The ideal surgical strategy for cervical ossification of the posterior longitudinal ligament (OPLL) remains controversial due to the lack of high-quality evidence. Herein, we prospectively investigated the surgical outcomes of anterior cervical decompression with fusion (ADF) and laminoplasty (LAMP) with cervical OPLL. Three hundred patients were included in this study (ADF: n = 89; LAMP: n = 211 patients), and propensity score matching yielded 67 pairs of patients with ADF and LAMP, in which clinical outcomes were compared. Crude analysis revealed that the ADF group showed greater neurological recovery in cervical Japanese Orthopedic Association scores at two years, compared with that in the LAMP group (53.1% vs. 44.3%, p = 0.037). The ratio of minimum clinically important difference (MCID) success was significantly greater in the ADF group (59.6% vs. 43.6%, p = 0.016). Multivariate analysis showed that the factors affecting MCID success were age, body mass index, duration of symptoms, and choice of ADF. In the 1:1 matched analysis, neurological improvement was more favorable in the ADF group (57.2%) compared to the LAMP group (46.8%) at two years (p = 0.049). However, perioperative complications, such as dysphagia and graft-related complications, were more common in the ADF group. [ABSTRACT FROM AUTHOR]

Background: Open-door laminoplasty (ODL) and French-door laminoplasty (FDL) are the main laminoplasty techniques used to treat cervical ossification of the posterior longitudinal ligament (C-OPLL). However, few studies have compared the outcomes of ODL and modified FDL (mFDL) for C-OPLL. We explored the differences in outcomes between ODL and mFDL for C-OPLL and analyzed the technical efficacy of each procedure in patients with K-line (+) or (−) C-OPLL. Methods: From January 2010 to December 2015, 202 patients with K-line (+) or (−) C-OPLL were retrospectively recruited from 4 institutions. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) score, JOA score recovery rate, operative time, blood loss, and complications. Univariate analysis and binary logistic regression models were adjusted for confounding factors. Results: Two hundred patients (mFDL, n = 69; ODL, n = 131) with a median follow-up of 42 months (range 36–54 months) were included. The postoperative JOA score significantly improved in both groups (P < 0.05). After adjusting for confounding factors, there was a statistically significant difference in blood loss (≥ 300 mL) between the two groups (P = 0.005), but there was no significant difference in the postoperative JOA score (≥ 14) (P = 0.062), JOA score recovery rate (≥ 0.82) (P = 0.187), or operative time (≥ 90 min) (P = 0.925). C5 palsy tended to occur more often in the mFDL group, although the difference was not significant (P > 0.05). The stratified analysis of the K-line status showed more blood loss in K-line (+) patients who underwent mFDL, but there was no significant difference in the postoperative JOA score, JOA score recovery rate, or operative time between the ODL and mFDL groups. Additionally, there was no significant difference in blood loss, postoperative JOA score, JOA score recovery rate, or operative time among all patients with K-line (+) or (−) C-OPLL in both groups. Conclusions: Both ODL and mFDL are effective for patients with C-OPLL. However, more blood loss tends to occur during mFDL. This study showed no significant difference in the operative time or incidence of complications between the two techniques. The efficacy of ODL and mFDL was not affected by the K-line status (+ or −) in patients with C-OPLL. [ABSTRACT FROM AUTHOR]

Background Context: Although the results of decompression surgery for lumbar spinal canal stenosis (LSS) are favorable, it is still difficult to predict the postoperative health-related quality of life of patients before surgery.Purpose: The purpose of this study was to develop and validate a machine learning model to predict the postoperative outcome of decompression surgery for patients with LSS.Study Design/setting: A multicentered retrospective study.Patient Sample: A total of 848 patients who underwent decompression surgery for LSS at an academic hospital, tertiary center, and private hospital were included (age 71±9 years, 68% male, 91% LSS, level treated 1.8±0.8, operation time 69±37 minutes, blood loss 48±113 mL, and length of hospital stay 12±5 days).Outcome Measures: Baseline and 2 years postoperative health-related quality of life.Methods: The subjects were randomly assigned in a 7:3 ratio to a model building cohort and a testing cohort to test the models' accuracy. Twelve predictive algorithms using 68 preoperative factors were used to predict each domain of the Japanese Orthopedic Association Back Pain Evaluation Questionnaire and visual analog scale scores at 2 years postoperatively. The final predictive values were generated using an ensemble of the top five algorithms in prediction accuracy.Results: The correlation coefficients of the top algorithms for each domain established using the preoperative factors were excellent (correlation coefficient: 0.95-0.97 [relative error: 0.06-0.14]). The performance evaluation of each Japanese Orthopedic Association Back Pain Evaluation Questionnaire domain and visual analog scale score by the ensemble of the top five algorithms in the testing cohort was favorable (mean absolute error [MAE] 8.9-17.4, median difference [MD] 8.1-15.6/100 points), with the highest accuracy for mental status (MAE 8.9, MD 8.1) and the lowest for buttock and leg numbness (MAE 1.7, MD 1.6/10 points). A strong linear correlation was observed between the predicted and measured values (linear correlation 0.82-0.89), while 4% to 6% of the subjects had predicted values of greater than±3 standard deviations of the MAE.Conclusions: We successfully developed a machine learning model to predict the postoperative outcomes of decompression surgery for patients with LSS using patient data from three different institutions in three different settings. Thorough analyses for the subjects with deviations from the actual measured values may further improve the predictive probability of this model. [ABSTRACT FROM AUTHOR]

The spatial complexity of neuronal circuits in the central nervous system is a hurdle in understanding and treating brain and spinal cord injury (SCI). Although several methods have recently been developed to render the spinal cord transparent and label specific neural circuits, three-dimensional visualization of long segments of spinal cord with high resolution remains challenging for SCI researchers. We present a method that combines tissue staining of neuronal tracts traced with biotinylated dextran amine (BDA) and a modified passive clarity clearing protocol to describe individual fibers in long segments of mouse spinal cord. Corticospinal tract was traced with BDA with a mouse model of thoracic spinal cord injury. The spinal cord was stained and cleared in two weeks with four solutions: staining solution, hydrogel solution, clearing solution, and observation solution. The samples were observed with a light-sheet microscope, and three-dimensional reconstruction was performed with ImageJ software. High resolution-images comparable with tissue sections were obtained continuously and circumferentially. By tiling, it was possible to obtain high-resolution images of long segments of the spinal cord. The tissue could be easily re-stained in case of fading. The present method does not require special equipment such as vacuum devices, can label specific circuits without genetic technology, and re-staining rounds can be easily implemented. By using simple neural staining and clearing methods, it was possible to acquire a wide range of high-resolution three-dimensional images of the spinal cord. • No special devices or genetic tracers are required for a modified clearing method. • Neuronal fibers are individually depicted in long segments of mouse spinal cord. • Re-staining of neuronal fiber is possible. • Stereotaxic observation is achieved by 3-D reconstruction with open-source software. [ABSTRACT FROM AUTHOR]

Case: A 45-year-old woman had a grade II chondrosarcoma (T2N0M0G2) located at the spinous processes and laminas of T3-6 with the tumor extension into the spinal canal at T3-4. To perform en bloc tumor resection, we released or disarticulated bilateral costovertebral ligaments from T3-6 and cut the bilateral pedicles at T3-5 all from posteriorly. Then, we completed en bloc resection without violating the tumor capsule. Conclusion: Our novel procedure, bilateral osteotomy of pedicles for en bloc resection successfully allowed for en bloc tumor resection involving the posterior elements with wide surgical margins. [ABSTRACT FROM AUTHOR]

Background: Degenerative cervical myelopathy (DCM) is an all-encompassing term that includes cervical spondylotic myelopathy (CSM), ossification of the posterior longitudinal ligament (OPLL), and other spinal abnormalities that cause cervical cord compression. It is unclear whether surgery is equally effective and safe for patients with OPLL as it is for those with other forms of DCM. The purpose of this study was to compare surgical outcomes of patients with OPLL and those with other forms of DCM.Methods: Four hundred and seventy-nine patients with symptomatic DCM were prospectively enrolled in the CSM-International study at sixteen sites. Patients' functional status was evaluated using the modified Japanese Orthopaedic Association scale (mJOA) and the Nurick score. Quality of life was assessed using patient-reported outcome measures, including the Neck Disability Index (NDI) and the Short Form (SF)-36. Postoperative functional and quality-of-life outcomes were assessed at two years of follow-up, and scores were compared between patients with and without OPLL.Results: Of 479 patients, 135 (28.2%) had radiographic evidence of OPLL, and 344 (71.8%) had other forms of DCM. The two groups did not differ significantly in demographics, surgical approach, or baseline myelopathy severity. Patients with OPLL achieved similar functional outcomes by two years following surgery compared with patients with other forms of DCM. With respect to quality of life, the NDI and most of the subscales of the SF-36 were not different between the two diagnostic groups. There was a higher risk of perioperative complications in the OPLL group (p = 0.054), although this relationship did not reach statistical significance. Rates of neurological complications did not differ significantly between diagnostic groups.Conclusions: Surgical decompression for the treatment of OPLL resulted in improvements in functional status and quality of life comparable to those seen in patients with other forms of DCM. Patients with OPLL were at a higher risk of perioperative complications than patients with other forms of DCM. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to clarify the clinical features of ossification of the posterior longitudinal ligament (OPLL) and extreme ossification at multiple sites. Methods: This prospective study involved patients with a diagnosis of cervical OPLL at 16 institutions in Japan. Patient-reported outcome measures, including responses on the Japanese Orthopaedic Association (JOA) Cervical Myelopathy Evaluation Questionnaire (JOA-CMEQ), JOA Back Pain Evaluation Questionnaire (JOA-BPEQ), and visual analog scale pain score, were collected to investigate clinical status. In each patient, the sum of the levels at which OPLL was located (OP index) was evaluated on whole-spine computed tomography, along with ossification of other spinal ligaments including the anterior longitudinal ligament (OALL), ligament flavum (OLF), supra- and intraspinous ligaments (SSL), and diffuse idiopathic skeletal hyperostosis (DISH). The distribution of OP index values in the study population was investigated, and the clinical and radiologic characteristics of patients in the top 10% were assessed. Results: In total, 236 patients (163 male, 73 female; mean age 63.5 years) were enrolled. Twenty-five patients with OP index ≥ 17 were categorized into a high OP index group and the remainder into a moderate/low OP index group. There were significantly more women in the high OP index group. Patients in the high OP index group also had significantly poorer scores for lower extremity function and quality of life on the JOA-CMEQ and in each domain but not for body pain on the JOA-BPEQ compared with those in the moderate/low OP index group. Patients in the high OP index group had more OALL in the cervical spine and more OLF and SSL in the thoracic spine. The prevalence of DISH was also significantly higher in the high OP index group. In the high OP index group, interestingly, OPLL was likely to be present adjacent to DISH in the cervicothoracic and thoracolumbar spine, especially in men, and often coexisted with DISH in the thoracic spine in women. Conclusion: This prospective cohort registry study is the first to demonstrate the clinical and radiologic features of patients with OPLL and a high OP index. In this study, patients with a high OP index had poorer physical function in the lumbar spine and lower extremities and were also predisposed to extreme ossification of spinal ligaments other than the OPLL. [ABSTRACT FROM AUTHOR]

Background Context: The risk factors for radiographical adjacent segment disease (ASD) in patients with degenerative spondylolisthesis have been previously reported. However, there are only few reports on patients with spondylolytic spondylolisthesis who underwent single-level posterior lumbar interbody fusion (PLIF).Purpose: The study aimed to investigate the risk factors for radiographical ASD in patients with L5-S1 spondylolytic spondylolisthesis who underwent single-level PLIF.Study Design/setting: A retrospective study PATIENT SAMPLE: This study retrospectively reviewed 135 consecutive patients (91 men and 44 women) with symptomatic L5-S1 spondylolytic spondylolisthesis who underwent single-level PLIF.Outcome Measures: The pre- and postoperative (at the final follow-up) spinopelvic parameters, % slip, sacral slope, lumbar lordosis (LL), pelvic tilt, pelvic incidence (PI), PI minus LL (PI - LL), lumbosacral angle, C7 sagittal vertical axis, and thoracic kyphosis were measured using standing radiographs.Methods: Radiographical ASD was defined as disc height loss (>3 mm), increase of posterior angulation (>5°), or progression of spondylolisthesis (>3 mm) between the pre- and postoperative radiographs. Pfirrmann's classification was used to evaluate disc degeneration. The radiographical parameters and changes between the pre- and postoperative values were evaluated and compared for the non-ASD and ASD groups. Binary logistic regression analysis was performed to evaluate the adjusted associations between each potential explanatory variable and ASD development.Results: The radiographical ASD incidence was 11%. Additionally, 60% of the patients with ASD had radiographical ASD at 1 year and all cases of radiographical ASD in this follow-up period occurred within 3 years after the initial surgery. The mean period of ASD occurrence after initial surgery was 21.7 ± 12.6 months. No patients required reoperation for radiographical ASD. Multivariate analysis revealed that a preoperative (odds ratio [OR], 5.9; 95% confidence interval [CI], 1.2-28.9; p=.03) and a postoperative (OR, 6.5; 95% CI, 1.2-34.5; p=.03) PI - LL of ≥15° were risk factors for radiographical ASD.Conclusions: Pre- and postoperative PI - LL value mismatch was identified as significant independent risk factors for radiographical ASD in patients with L5-S1 spondylolytic spondylolisthesis. Obtaining larger lordosis at L5-S1 may be the key to preventing radiographical ASD. [ABSTRACT FROM AUTHOR]

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. Although the patients with OPLL are more common in the 60s and 70s, we know that there are markedly young patients (e.g., early 40s). However, to the best of our knowledge, there is few reports characterize young patients with cervical OPLL in terms of the imaging features, subjective symptoms, and ADL problems.Methods: This is the multicenter cross-sectional study. Two hundred and thirty-seven Japanese symptomatic patients with cervical OPLL confirmed by standard X-rays collected from 16 institutions belonging to the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament formed by the Japanese Ministry of Health, Labor and Welfare were recruited. Whole spine CT data as well as demographic data such as age, gender, patients-based evaluations, and the 36-item Short Form Health Survey (SF-36) were evaluated.Results: Young group (≦ 45 years old) consisted of 23 patients (8 females and 15 males), accounting for 9.7% of the total. Their characteristics were high body mass index (BMI), significant involvement of trauma in the onset and deterioration of symptoms, and the predominance of thoracic OPLL. The patient-based evaluations did not show a significant difference between the young and non-young groups, or between the genders in the young group except for bodily pain (BP) of SF-36. Female patients in young group had significantly lower BP score of SF-36 than that of male in young group.Conclusions: Characteristics of young patients with cervical OPLL were high BMI, significant involvement of trauma in the onset and deterioration of symptoms, lower BP score of SF-36 in female, and the predominance of thoracic OPLL. [ABSTRACT FROM AUTHOR]

Positive association between ossification of the posterior longitudinal ligament of the spine (OPLL) and obesity is widely recognized; however, few studies focused on the effects of obesity on treatment of cervical OPLL. The effects of obesity on surgical treatment of cervical OPLL were investigated by a Japanese nationwide, prospective study. Overall, 478 patients with cervical myelopathy due to OPLL were prospectively enrolled. To clarify the effects of obesity on the surgical treatment for cervical OPLL, patients were stratified into two groups, non-obese (< BMI 30.0 kg/m2) and obese (≥ BMI 30.0 kg/m2) groups. The mean age of the obese group was significantly younger than that of non-obese group. There were no significant differences between the two groups in other demographic information, medical history, and clinical and radiographical findings. Alternatively, the obese group had a significantly higher rate of surgical site infection (SSI) than that of non-obese group. Approach-specific analyses revealed that the SSI was significantly higher in the obese group than in the non-obese group. A logistic regression analysis revealed that age, BMI, and duration of symptoms were significant factors affecting the postoperative minimum clinically important difference success. The result of this study provides useful information for future cervical OPLL treatment. [ABSTRACT FROM AUTHOR]

Study Design: This is an international multicenter retrospective review of 219 surgically treated consecutive adult spinal deformity (ASD) patients who had a minimum of five fused segments, completed a 2-year follow-up.Objective: The purpose of this study was to add the indices of preventive procedures to improve and to validate the predictive probability of the PRISM (patient demographics, radiographic index, and surgical invasiveness for mechanical failure) for mechanical failure (MF) following ASD surgery.Summary Of Background Data: The PRISM was developed from the data of 321 ASD patients, which stratified the risk of MF from six types of risk.Methods: Data from 136 Japanese ASD patients (age 49 ± 21 yr, 88% female) were used to develop PRISM2, and data from 83 US ASD patients (age 58 ± 12 yr, 86% female) were used for the external validation. We analyzed the associations between three preventive procedures (UIV+1 tethering [TH], teriparatide [TP], and multirod [MR]) and MF by multivariate logistic regression analysis (MRA). The values for the nearest integer of the β of the procedures were added to the six indices of the original PRISM to establish the PRISM2. The discriminative ability of the PRISM/ PRISM2 for MF was evaluated using the area under the receiver operating characteristic curve (AUC) and the precision-recall (PR) curve. The Cochran-Armitage test was used to analyze the trend between PRISM/PRISM2 scores and MF.Results: MF developed in 25% (34 cases). The β values for the preventive procedures calculated by MRA were TH: -2.5, TP: -3.0, and MR: -2.1. The Cochran-Armitage test showed an excellent trend between MF and PRISM/2. The diagnostic ability was superior for the PRISM2 compared with the PRISM (PRISM2; AUC = 0.94 [0.90-0.98], PRISM; AUC = 0.87 [0.81-0.93], difference = -0.07 [-0.11 to -0.03], P  < 0.01). The AUC of the PRISM2 was 0.70 [0.59-0.81, P < 0.01] in the US patient cohort.Conclusion: We refined the PRISM by adding preventive procedures to the risk indices. Further validation and adjustment in a large different patient cohorts may improve the predictive probability of PRISM2.Level of Evidence: 3. [ABSTRACT FROM AUTHOR]

Study Design: Multicenter retrospective case series of patients treated surgically for lumbar spinal stenosis (LSS).Objective: We investigated how laminectomy improves lower back pain (LBP) and the factors associated with poor improvement.Summary Of Background Data: Lumbar laminectomy is effective for alleviating neurological symptoms caused by LSS, whereas its effect on LBP is still controversial.Methods: A retrospective review of prospectively collected data from 436 patients (age 72 yrs, 69% males) who underwent laminectomy for LSS with 2 years of follow-up. We analyzed the following risk factors for residual LBP by uni- and multivariate analyses: age, sex, smoking, occupation, comorbidities, frailty, joint replacement, vertebral fracture, DISH, HRQOL, complications, and the presence of spinal instability. The LBP of male and female patients was analyzed after propensity score matching of known confounders. Patient-reported outcomes (JOABPEQ and VAS scores) were obtained at baseline and the 2-year postoperative follow-up.Results: LBP was significantly improved at 2 years post operation (VAS change 2.3 [95% CI 2.0-2.6], P < 0.01). Fifty-five percent of the patients achieved an MCID, with 67% having no or mild LBP. In the multivariate analysis, sex and baseline LBP were independent risk factors (female: OR 1.9 [1.2-3.0], baseline LBP [VAS≥7.5]: OR 1.9 [1.2-3.1]). Furthermore, the independent risk factors for severe baseline LBP were sex and mental status (female: OR 1.7 [1.1-2.7], P = 0.03, mental status: OR 3.8 [2.4-6.0], P < 0.01). However, an analysis of 102 pairs of propensity-score-matched male and female patients showed no difference in the improvement of LBP (male vs. female: VAS 3.8 ± 2.8 vs. 4.0 ± 2.9, P = 0.61, VAS change 3.1 ± 2.9 vs. 2.7 ± 3.0, P = 0.38).Conclusion: Decompression surgery for LSS significantly improved LBP. Sex and baseline LBP were risk factors for residual LBP. However, when males and females were matched by confounders, no difference was found in the LBP after surgery. Patients with severe baseline LBP may need further evaluation for their mental status because these patients are likely to have mental problems that potentially contribute to persistent LBP.Level of Evidence: 4. [ABSTRACT FROM AUTHOR]

Study Design: A retrospective study of consecutive collected data.Objective: To investigate risk factors for postoperative distal adding-on (DA) in Lenke Type 1B and 1C curves using intraoperative radiographs.Summary Of Background Data: In adolescent idiopathic scoliosis (AIS), DA radiographic complication can negatively affect postoperative clinical results. However, few studies have focused on assessing risk factors for DA using intraoperative radiographs.Methods: We retrospectively evaluated 69 AIS patients with Lenke Type 1B or 1C curves who underwent posterior selective thoracic fusion. We divided patients into DA and non-DA groups based on radiograph data at 2-year follow-up using Wang et al (Spine 2011) definition of DA. We compared coronal radiographic parameters, including relative positions of end vertebra (EV), stable vertebra (SV), neutral vertebra (NV), and last touching vertebra (LTV) to lowest instrumented vertebra (LIV), and intraoperative radiographic parameters, between the two groups.Results: DA was present in 13 patients (18.8%) at 2-year follow-up. The mean LIV-EV, LIV-NV, LIV-SV, and LIV-LTV relative positions were significantly smaller in the DA group than in the non-DA group. Multivariate analysis showed that LIV-LTV was significantly associated with DA (DA: -0.2 ± 0.7, non-DA: 0.6 ± 0.7). Intraoperative radiographs showed that the mean angulation of the first disc below the LIV after final adjustment was significantly larger in the DA group (2.3° ± 1.1°) than in the non-DA group (0.9° ± 0.7°). Patients whose angulation of the first disc below the LIV was more than 3° were significantly associated with DA.Conclusion: The LIV selected at more cranial to the LTV may be a risk factor for postoperative DA in Lenke Type 1B and 1C curves. Moreover, it was suggested that LIV extension might be considered when the first disc's angulation below the LIV is >3° in intraoperative radiographs.Level of Evidence: 3. [ABSTRACT FROM AUTHOR]