A Novel Intraoperative CT Navigation System for Spinal Fusion Surgery in Lumbar Degenerative Disease: Accuracy and Safety of Pedicle Screw Placement.

Background: In recent years, intraoperative computed tomography (CT) navigation has become widely used for the insertion of pedicle screws in spinal fusion surgery. However, conventional intraoperative CT navigation may be impaired by infrared interference between the infrared camera and surgical instruments, which can lead to the misplacement of pedicle screws. Recently, a novel intraoperative CT navigation system, NextAR, has been developed. It uses a small infrared camera mounted on surgical instruments within the surgical field. NextAR navigation can minimize the problem of infrared interference and be expected to improve the accuracy of pedicle screw placement. Methods: This study investigated the accuracy of pedicle screw insertion under NextAR navigation in spinal fusion surgery for lumbar degenerative diseases. The accuracy of pedicle screw placement was evaluated in 15 consecutive patients using a CT grading scale. Results: Screw perforation occurred in only 1 of the total 70 screws (1.4%). Specifically, there was one grade 1 perforation within 2 mm, but no perforations larger than 2 mm. There were no reoperations or neurological complications due to screw misplacement. Conclusions: NextAR navigation can provide high accuracy for pedicle screw insertion and help ensure safe spinal fusion surgery for lumbar degenerative diseases.

Primary Malignant Lymphoma of the Cauda Equina Diagnosed after Decompression for Lumbar Spinal Stenosis: A Case Report.

Primary malignant lymphoma confinement to the cauda equina is rare. Only 14 cases of primary malignant lymphoma in the cauda equina have been reported. In these cases, the clinical features were similar to those of lumbar spinal canal stenosis (LSCS). This report describes a case of diffuse large B-cell lymphoma of the cauda equina that was diagnosed after decompression surgery for LSCS. An 80-year-old man presented with gait disturbance due to progressive muscle weakness in the lower extremities over the previous two months. He was diagnosed with LSCS, and decompression surgery was performed. However, the muscle weakness worsened after surgery; therefore, he was referred to our department. Plain magnetic resonance imaging (MRI) revealed swelling of the cauda equina. It demonstrated marked homogenous enhancement by gadolinium-diethylenetriamine pentaacetic acid. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) revealed diffuse accumulation of 18F-FDG in the cauda equina. These imaging findings were consistent with those of cauda equina lymphomas. To confirm the diagnosis, we performed an open biopsy of the cauda equina. Histological examination indicated diffuse large B-cell lymphoma. Considering the patient's age and activities of daily living, further treatment was not performed. The patient died four months after the first surgery. Rapid progression of muscle weakness, which cannot be prevented by decompression surgery, and swollen cauda equina on MRI may be signs of this disorder. Gadolinium-enhanced MRI, 18F-FDG PET, and histological investigation of the cauda equina should be performed for diagnosing primary malignant lymphoma of the cauda equina.

Mid- to Long-Term Outcomes After Resection of Thoracic Dumbbell Tumors Managed by Laminectomy and Unilateral Total Facetectomy Without Instrumented Fusion.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVE: To evaluate mid- to long-term surgical outcomes of thoracic dumbbell tumors managed by laminectomy and unilateral total facetectomy without instrumented fusion. METHODS: A total of 15 patients with thoracic dumbbell tumors who underwent primary resection by laminectomy and unilateral total facetectomy without spinal instrumented fusion between 2000 and 2015 were reviewed. Patient characteristics, surgical outcomes (including spinal alignment and stability), disc degeneration, pain, disability, and health-related quality of life were evaluated. Additionally, to analyze the impact of the affected levels on these outcomes, we divided the patients into 2 groups: a middle thoracic group and a thoracolumbar group. RESULTS: The mean duration of follow-up was 100.5 months (range, 36-190 months). The affected level was T3-T4 or below in all patients. Although the local kyphosis angle (8.1° to 12.7°), thoracic kyphosis angle (25.6° to 33.9°), and coronal Cobb angle (6.6° to 9.5°) significantly increased from preoperative to the final visit (P ≤ .02), no patient demonstrated spinal instability. From magnetic resonance imaging, no patient had a worse grade of disc degeneration in the affected level than those in the adjacent levels. The percentage of patients who presented with an Oswestry disability index ≤ 22% was 80%. Moreover, the surgical region did not adversely affect the outcomes. No patient required additional surgery due to spinal instability or deformity. CONCLUSIONS: Unilateral total facetectomy without fusion to resect thoracic dumbbell tumors caused neither spinal deformity nor instability requiring additional surgery at the mid- to long-term follow-up.

Adolescent-onset Local Kyphosis with Anterior Column Hypoplasia and Subluxation of the Facet Joints of the Lumbar Spine: A Case Report.

Introduction: Hypoplasia of the anterior portion of the vertebral body is a relatively rare subtype of juvenile vertebral deformity. The common manifestations of this type of deformity are scoliosis and kyphoscoliosis, while kyphosis without scoliosis is rare. Here, we present a very rare case of adolescent-onset local kyphosis with anterior column hypoplasia and subluxation of the facet joints of the lumbar spine, as demonstrated by dynamic lateral radiograms, which was successfully treated by spine-shortening osteotomy. Case Report: A 16-year-old male adolescent presented with low back pain with progressive protrusion of the lumbar spinous process 3 years before the first visit. The protrusion was not found in his back until the age of 13 years. His chief complaint was lower back pain and a protruding spinous process in the upper lumbar spine. The anteroposterior radiogram of the whole spine revealed no obvious scoliosis. The lateral radiogram showed hypoplasia of the anterior portion of the L2 vertebral body with local kyphosis at L1-3 of 23°. The global alignment was posteriorly shifted, with hypokyphosis of the thoracic spine and hyperlordosis of the lower lumbar spine. In the dynamic lateral radiograms, the facet joints at the L2-3 spinal level were subluxated in the flexed position. Computed tomography showed symmetrical hypoplasia of the anterior portion of the vertebral body of L2. Spine-shortening osteotomy at L2 and L1-3 posterior fusion was performed for local stabilization and correction of sagittal malalignment. The lateral radiogram at the 2-year post-operative follow-up demonstrated that the global alignment was normal, with local kyphosis at L1-3 of -2°. The improvement of hypokyphosis of the thoracic spine and hyperlordosis of the lower lumbar spine was achieved. Conclusions: Adolescent-onset local lumbar kyphosis with anterior column hypoplasia and segmental subluxation of the facet joints is very rare. Local correction by spine-shortening osteotomy with short fusion can also improve the global alignment.

Chaperone-Mediated Autophagy in Neurodegenerative Diseases and Acute Neurological Insults in the Central Nervous System.

Autophagy is an important function that mediates the degradation of intracellular proteins and organelles. Chaperone-mediated autophagy (CMA) degrades selected proteins and has a crucial role in cellular proteostasis under various physiological and pathological conditions. CMA dysfunction leads to the accumulation of toxic protein aggregates in the central nervous system (CNS) and is involved in the pathogenic process of neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Previous studies have suggested that the activation of CMA to degrade aberrant proteins can provide a neuroprotective effect in the CNS. Recent studies have shown that CMA activity is upregulated in damaged neural tissue following acute neurological insults, such as cerebral infarction, traumatic brain injury, and spinal cord injury. It has been also suggested that various protein degradation mechanisms are important for removing toxic aberrant proteins associated with secondary damage after acute neurological insults in the CNS. Therefore, enhancing the CMA pathway may induce neuroprotective effects not only in neurogenerative diseases but also in acute neurological insults. We herein review current knowledge concerning the biological mechanisms involved in CMA and highlight the role of CMA in neurodegenerative diseases and acute neurological insults. We also discuss the possibility of developing CMA-targeted therapeutic strategies for effective treatments.

Retrospective comparison of the surgical results for patients with thoracic myelopathy caused by ossification of the posterior longitudinal ligament: Posterior decompression with instrumented spinal fusion versus modified anterior decompression through a posterior approach.

BACKGROUND: In Japan, approximately 75% of patients with thoracic myelopathy caused by ossification of the posterior longitudinal ligament (OPLL) are treated by posterior decompression with instrumented spinal fusion (PDF) because of its efficacy and safety. To achieve more effective decompression of the spinal cord using a posterior approach, anterior decompression through a posterior approach was developed. However, this technique has a high risk of postoperative paralysis. We have added a couple of ingenuities to this procedure (modified Ohtsuka procedure). This study was performed to report the surgical results of our modified Ohtsuka procedure and to compare them with the results of PDF. METHODS: This was a retrospective case series. From 2008 to 2018, we surgically treated 32 patients: 20 patients treated by PDF (PDF group) and 12 patients by our modified Ohtsuka procedure (modified Ohtsuka group) as the initial surgery. All patients were followed up for at least 12 months. The degree of surgical invasion and patients' neurological condition were assessed. RESULTS: The operative duration and intraoperative blood loss indicated no significant differences (PDF vs. Ohtuska: 507 ± 103 vs. 534 ± 99 min, 1022 ± 675 vs. 1160 ± 685 ml, respectively). The preoperative Japanese Orthopaedic Association (JOA) score was 4.5 ± 2.0 in the PDF group and 3.3 ± 1.4 in the modified Ohtsuka group (p < 0.05). However, the latest JOA score and recovery rate were significantly better in the modified Ohtsuka group than in the PDF group (8.9 ± 1.2 vs. 7.4 ± 2.5 and 70.8 ± 17.6% vs. 44.5 ± 40.2%, respectively). Postoperative paralysis did not occur in the modified Ohtsuka group while four patients had it in the PDF group. CONCLUSIONS: The present study clearly indicated the modified Ohtsuka group showed significantly better surgical outcomes than the PDF group with the recovery rate ≥70%.

Prevalence of pre-existing factors causing spinal cord compression: Is there a difference between patients suffering from cervical spinal cord injury with and without bone injury?

BACKGROUND: Recently, the prevalence of elderly patients suffering from cervical spinal cord injury (CSCI) without bone injury has been increasing in various countries. Pre-existing factors causing spinal cord compression, such as ossification of the posterior longitudinal ligament (OPLL), can increase the risk of CSCI without bone injury. However, no study has compared the prevalence of pre-existing factors between CSCI with and without bone injury. This study aimed to compare the prevalence of pre-existing factors between CSCI with and without bone injury. METHODS: In 168 consecutive patients with CSCI, pre-existing factors including OPLL, posterior spur of the vertebral body, developmental stenosis, disc bulge and calcification of yellow ligament (CYL) were evaluated on imaging studies. The prevalence of each type of pre-existing factors was compared between patients with and without bone injury. RESULTS: The prevalence of pre-existing factors in patients without bone injury (86%) was significantly higher than in those with bone injury (20%) (P < 0.001; odds ratio, 23.9). The most common pre-existing factor was OPLL followed by developmental stenosis, posterior spur, disc bulge and CYL in both groups. OPLL, development stenosis and posterior spur were significantly more common in patients without bone injury compared to those with bone injury (P < 0.01). CONCLUSIONS: Prevalence of pre-existing factors, such as OPLL, development stenosis and posterior spur was significantly higher in patients without bone injury than in those with bone injury. Thus, these pre-existing factors might be a potential risk of CSCI without bone injury.

Changes in Expression of Receptor-Interacting Protein Kinase 1 in Secondary Neural Tissue Damage Following Spinal Cord Injury.

INTRODUCTION: Necroptosis is a form of programmed cell death that is different from apoptotic cell death. Receptor-interacting protein kinase 1 (RIPK1) plays a particularly important function in necroptosis execution. This study investigated changes in expression of RIPK1 in secondary neural tissue damage following spinal cord injury in mice. The time course of the RIPK1 expression was also compared with that of apoptotic cell death in the lesion site. METHODS AND MATERIALS: Immunostaining for RIPK1 was performed at different time points after spinal cord injury. The protein expressions of RIPK1 were determined by western blot. The RIPK1 expressions in various neural cells were investigated using immunohistochemistry. To investigate the time course of apoptotic cell death, TUNEL-positive cells were counted at the different time points. To compare the incidence of necroptosis and apoptosis, the RIPK1-labeled sections were co-stained with TUNEL. RESULTS: The RIPK1 expression was significantly upregulated in the injured spinal cord. The upregulation of RIPK1 expression was observed in neurons, astrocytes, and oligodendrocytes. The increase in RIPK1 expression started at 4 hours and peaked at 3 days after injury. Time course of the RIPK1 expression was similar to that of apoptosis detected by TUNEL. Interestingly, the increased expression of RIPK1 was rarely observed in the TUNEL-positive cells. Furthermore, the number of RIPK1-positive cells was significantly higher than that of TUNEL-positive cells. CONCLUSIONS: This study demonstrated that the expression of RIPK1 increased in various neural cells and peaked at 3 days following spinal cord injury. The temporal change of the RIPK1 expression was analogous to that of apoptosis at the lesion site. However, the increase in RIPK1 expression was barely seen in the apoptotic cells. These findings suggested that the RIPK1 might contribute to the pathological mechanism of the secondary neural tissue damage after spinal cord injury.

Chaperone-Mediated Autophagy after Spinal Cord Injury.

Autophagy is the degradation process of dysfunctional intracellular components and has a crucial function in various human diseases. There are three different types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). CMA is a major route for the elimination of cellular aberrant proteins and can provide a cytoprotective effect. The present study investigated the expression of lysosome-associated membrane protein type 2A (LAMP2A), which is the hallmark of CMA activity, in damaged neural tissue after spinal cord injury (SCI) in mice. The number of LAMP2A-expressing cells was significantly increased at the lesion following SCI. The increased number of LAMP2A-positive cells was observed from 24 h and peaked at 3 days after injury. A western blot analysis confirmed that the level of LAMP2A protein was significantly increased in the injured spinal cord compared with the uninjured cord. On double staining for LAMP2A and different neural cell type markers, the increased expression of LAMP2A was observed in neurons, astrocytes, oligodendrocytes, and microglia/macrophages following injury. An electron microscopic analysis showed that secondary lysosomes were increased in damaged neurons at the lesion site. Immunoelectron microscopy revealed that the gold particles with anti-LAMP2A antibody were frequently localized at the secondary lysosomes in the injured site. These findings indicated that CMA was clearly activated in damaged neural tissue after SCI. The activation of CMA may contribute to the elimination of intracellular aberrant proteins and exert a neuroprotective effect following SCI.

Low-energy extracorporeal shock wave therapy promotes BDNF expression and improves functional recovery after spinal cord injury in rats.

Low-energy extracorporeal shock wave therapy (ESWT) has been used to treat various human diseases. Previous studies have shown that low-energy ESWT promotes the release of various cell growth factors and trophic factors from the cells surrounding the target lesion. The aim of the current study was to determine whether the application of low-energy ESWT upregulates the expression of brain-derived neurotrophic factor (BDNF) and reduces neural tissue damage and functional impairment using a rat model of thoracic spinal cord contusion injury. We found that low-energy ESWT promoted BDNF expression in the damaged neural tissue. The expression of BDNF was increased in various neural cells at the lesion. Additionally, low-energy ESWT increased the area of spared white matter and the number of oligodendrocytes in the injured spinal cord compared with untreated control animals. There were more axonal fibers around the injured site after the application of low-energy ESWT than control. Importantly, low-energy ESWT improved the locomotor functions evaluated by both the BBB scale and ladder rung walking test in addition to the sensory function measured using a von Frey test. Moreover, the electrophysiological assessment confirmed that the conductivity of the central motor pathway in the injured spinal cord was restored by low-energy ESWT. These findings indicate that low-energy ESWT promotes BDNF expression at the lesion site and reduces the neural tissue damage and functional impairment following spinal cord injury. Our results support the potential application of low-energy ESWT as a novel therapeutic strategy for treating spinal cord injury.

B-RAFV600E Inhibitor Dabrafenib Attenuates RIPK3-Mediated Necroptosis and Promotes Functional Recovery after Spinal Cord Injury.

The receptor-interacting protein kinase 3 (RIPK3) is a key regulator of necroptosis and is involved in various pathologies of human diseases. We previously reported that RIPK3 expression is upregulated in various neural cells at the lesions and necroptosis contributed to secondary neural tissue damage after spinal cord injury (SCI). Interestingly, recent studies have shown that the B-RAFV600E inhibitor dabrafenib has a function to selectively inhibit RIPK3 and prevents necroptosis in various disease models. In the present study, using a mouse model of thoracic spinal cord contusion injury, we demonstrate that dabrafenib administration in the acute phase significantly inhibites RIPK3-mediated necroptosis in the injured spinal cord. The administration of dabrafenib attenuated secondary neural tissue damage, such as demyelination, neuronal loss, and axonal damage, following SCI. Importantly, the neuroprotective effect of dabrafenib dramatically improved the recovery of locomotor and sensory functions after SCI. Furthermore, the electrophysiological assessment of the injured spinal cord objectively confirmed that the functional recovery was enhanced by dabrafenib. These findings suggest that the B-RAFV600E inhibitor dabrafenib attenuates RIPK3-mediated necroptosis to provide a neuroprotective effect and promotes functional recovery after SCI. The administration of dabrafenib may be a novel therapeutic strategy for treating patients with SCI in the future.

Surgical Management of Giant Sacral Schwannoma: A Case Series and Literature Review.

OBJECTIVE: Giant sacral schwannomas are rare and difficult to treat. Unexpected neurologic deficits after surgery and tumor recurrence should be considered when surgery is performed. We attempt to remove the tumors via piecemeal total or subtotal excision, leaving parts of the capsule adjacent to nerves to preserve the nerves. This study aimed to present the cases of giant sacral schwannoma at our institutions as well as review the relevant literature and to discuss surgical management. METHODS: This study included 11 patients (5 male and 6 female, mean age 53 years) with giant sacral schwannoma who were treated surgically. The clinical features, surgical details, and outcomes were investigated retrospectively. RESULTS: The tumors were intraosseous type in 4 cases, dumb-bell type in 3 cases, and retroperitoneal type in 4 cases. The surgeries were performed by a combined anterior and posterior approach in 4 cases, a posterior approach in 4 cases, and an anterior approach in 3 cases. The tumors were removed via piecemeal total or subtotal excision in 7 cases, partial excision in 3 cases, and enucleation in 1 case. After surgery, symptoms improved in all cases. The tumor recurred in 2 patients after partial excision. No patients receiving piecemeal total or subtotal excision showed recurrence. One patient developed motor weakness after piecemeal subtotal excision, but the symptoms resolved. CONCLUSIONS: Adopting an appropriate surgical approach based on the location of the tumor is important. Piecemeal total or subtotal excision, with parts of the capsule adjacent to nerves left behind may help achieve a good outcome, avoiding a postoperative neurologic deficit.