Are T1-Weighted Three-Dimensional Magnetic Resonance Images Inferior to T2-Weighted Images for Diagnosing Lumbar Foraminal Stenosis in the Fifth Lumbar Nerve Root? A Prospective, Comparative Study in Identical Patients.

Introduction: Imaging analysis of foraminal stenosis in the fifth lumbar (L5) nerve root remains to be a challenge because of the anatomical complexity of the lumbosacral transition. T2-weighted three-dimensional (3D) magnetic resonance images (MRI) have been dominantly used for diagnosis of lumbar foraminal stenosis, while the reliability of T1-weighted images (WI) has also been proven. In this study, we aim to compare the reliability and reproducibility of T1- and T2-weighted 3D MRI in diagnosing lumbar foraminal stenosis (LFS) of the L5 nerve root. Methods: In this study, 39 patients with unilateral L5 radiculopathy (20 had L4-L5 intracanal stenosis; 19 had L5-S foraminal stenosis) were enrolled, prospectively. T1- and T2-weighted 3D lumbar MRI were obtained from each patient. T1WI and T2WI were blinded and then separately reviewed twice by four examiners randomly. The examiners were instructed to answer the side of LFS or absence of LFS. The correct answer rate, sensitivity, specificity, and area under the curve were analyzed and compared between T1WI and T2WI. Also, intra- and interobserver agreements were calculated using kappa (κ)-statistics and compared in the same manner. Results: The average correct answer rate, sensitivity, specificity, and area under the curve of the T1WI/T2WI were 84.6%/80.1%, 82.9%/80.3%, 86.3%/81.3%, and 0.846/0.801, respectively. The intraobserver κ-values of the four examiners ranged from 0.692 to 0.916 (average: 0.762) and from 0.669 to 0.801 (average: 0.720) for T1WI and T2WI, respectively. The interobserver κ-values calculated in a round-robin manner (24 combinations in total) ranged from 0.544 to 0.790 (average: 0.657) and from 0.524 to 0.828 (average: 0.652), respectively. Conclusions: As per our findings, T1- and T2-weighted 3D MRI were determined to have nearly equivalent reliability and reproducibility in terms of diagnosing LFS of the L5 nerve root.

Medial Condyle Fracture of the Distal Humerus in an Elderly Patient With Fishtail Deformity and Lateral Condyle Nonunion: A Case Report.

A medial condyle fracture of the humerus with preexisting fishtail deformity and lateral condyle nonunion is very rare, and there have been few reports describing favorable treatment options. We herein report the case of an 83-year-old woman who sustained a medial condyle fracture of her elbow with a comorbidity of long-lasting limited elbow motion with a history of elbow trauma in childhood. After conservative treatment with casting for four weeks, unstable medial condyle fracture in the presence of fishtail deformity and lateral condyle nonunion remained. Due to persistent pain, the patient underwent surgical treatment with semiconstrained total elbow arthroplasty (TEA) through the triceps-on approach. At the 12-month follow-up examination, the patient had no pain and achieved satisfactory functional outcomes. This case report demonstrated the efficacy of TEA for deteriorated stability due to bilateral condyle fracture/nonunion with fishtail deformity of the humerus.

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.

Spinal Cord Swelling After Surgery in Cervical Spondylotic Myelopathy: Relationship With Intramedullary Gd-DTPA Enhancement on MRI.

STUDY DESIGN: This is a prospective multicenter study. SUMMARY OF BACKGROUND DATA: Postoperative spinal cord swelling has been reported in patients with cervical spondylotic myelopathy. In the cases of the spinal cord swelling, the involvement in the intramedullary gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhancement on magnetic resonance imaging (MRI) was referred. OBJECTIVE: The prevalence and clinical relevance of postoperative spinal cord swelling and its relationship with intramedullary Gd-DTPA enhancement in patients with cervical spondylotic myelopathy were investigated. SUBJECTS AND METHODS: A total of 683 consecutive patients with cervical spondylotic myelopathy who underwent laminoplasty were examined. T1, T2, and Gd-DTPA-enhanced MRI were performed before surgery. Patients with intramedullary Gd-DTPA enhancement were allocated to the enhancement group. Fifty consecutive cases who did not exhibit intramedullary Gd-DTPA enhancement were allocated to the nonenhancement group. Both groups underwent MRI examinations at 1 month and 1 year after surgery. RESULTS: The prevalence of spinal cord swelling in the enhancement group (26%) was significantly higher than that in the nonenhancement group (4%) (P=0.0038). At 1 year after surgery, spinal cord swelling had resolved in all patients in the nonenhancement group, while it persisted in 3 of 13 patients (23%) in the enhancement group. On multiple regression analysis, intramedullary Gd-DTPA enhancement rather than the spinal cord swelling showed a significant influence in terms of recovery of the Japanese Orthopedic Association score. CONCLUSIONS: Surgical outcomes of patients with postoperative swelling should be evaluated separately according to the presence or absence of intramedullary Gd-DTPA enhancement on MRI. Spinal cord swelling associated with intramedullary Gd-DTPA enhancement was indicative of poor prognosis.

Diagnosis of benign notochordal cell tumor of the spine: is a biopsy necessary?

Benign notochordal cell tumor is a benign intraosseous lesion, demonstrates characteristic imaging features. The lesion demonstrates low-signal intensity in T1-weighted images, high-signal intensity in T2-weighted images, and no enhancement with contrast medium in MRI and slight osteosclerosis in CT. If typical imaging findings are identified, biopsy is not necessary.

Successful Management of Gorham-Stout Disease in the Cervical Spine by Combined Conservative and Surgical Treatments: A Case Report.

Gorham-Stout disease (GSD) is a rare condition characterized by intraosseous proliferation of endothelial-lined vessels and progressive osteolysis. The precise etiology and pathophysiology of the disease remain poorly understood. Current therapeutic options for GSD include chemotherapy, radiotherapy, and surgical resection, but the surgical treatment of GSD is difficult, especially in the spinal lesion. The indication of wide-margined resection was limited because of anatomical features. Herein, we report a case of GSD of the cervical spine in which the lesions were successfully stabilized with combined conservative and surgical treatments. A 15-year-old male patient was admitted because of severe neck pain. The patient presented no neurological deficiency. However, the radiological findings revealed osteolytic lesions on the laminae and vertebrae between C1 to C5. An open biopsy confirmed an irregular, thin-walled vessel formation in the bone trabeculae, which was diagnosed as GSD. Conservative treatment was initiated with chemotherapy and radiotherapy. After one and a half year, the osteolytic condition had regressed. Spinal fusion surgery was then performed from C2 to C5 to prevent for progression of the cervical kyphotic changes, and spinal fusion was confirmed 7 months after the surgery. The patient showed no recurrence of GSD in the 5-year follow-up period after surgery. We were able to provide successful treatment by giving priority to the combined conservative treatments. If a patient has no severe deformity or progressive neurologic deficits, it might be better to prioritize conservative treatments and to perform the surgery after the osteolytic changes have stopped.

Rapamycin suppresses microglial activation and reduces the development of neuropathic pain after spinal cord injury.

Rapamycin is an inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway, plays an important role in multiple cellular functions. Our previous study showed rapamycin treatment in acute phase reduced the neural tissue damage and locomotor impairment after spinal cord injury (SCI). However, there has been no study to investigate the therapeutic effect of rapamycin on neuropathic pain after SCI. In this study, we examined whether rapamycin reduces neuropathic pain following SCI in mice. We used a mouse model of thoracic spinal cord contusion injury, and divided the mice into the rapamycin-treated and the vehicle-treated groups. The rapamycin-treated mice were intraperitoneally injected with rapamycin (1 mg/kg) 4 h after SCI. The rapamycin treatment suppressed phosphorylated-p70S6K in the injured spinal cord that indicated inhibition of mTOR. The rapamycin treatment significantly improved not only locomotor function, but also mechanical and thermal hypersensitivity in the hindpaws after SCI. In an immunohistochemical analysis, Iba-1-stained microglia in the lumbar spinal cord was significantly decreased in the rapamycin-treated mice. In addition, the activity of p38 MAPK in the lumbar spinal cord was significantly attenuated by rapamycin treatment. Furthermore, phosphorylated-p38 MAPK-positive microglia was relatively decreased in the rapamycin-treated mice. These results indicated rapamycin administration in acute phase to reduce secondary neural tissue damage can contribute to the suppression of the microglial activation in the lumbar spinal cord and attenuate the development of neuropathic pain after SCI. The present study first demonstrated that rapamycin has significant therapeutic potential to reduce the development of neuropathic pain following SCI. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:93-103, 2017.

Low-energy extracorporeal shock wave therapy for promotion of vascular endothelial growth factor expression and angiogenesis and improvement of locomotor and sensory functions after spinal cord injury.

OBJECTIVE Extracorporeal shock wave therapy (ESWT) is widely used to treat various human diseases. Low-energy ESWT increases expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. The VEGF stimulates not only endothelial cells to promote angiogenesis but also neural cells to induce neuroprotective effects. A previous study by these authors demonstrated that low-energy ESWT promoted expression of VEGF in damaged neural tissue and improved locomotor function after spinal cord injury (SCI). However, the neuroprotective mechanisms in the injured spinal cord produced by low-energy ESWT are still unknown. In the present study, the authors investigated the cell specificity of VEGF expression in injured spinal cords and angiogenesis induced by low-energy ESWT. They also examined the neuroprotective effects of low-energy ESWT on cell death, axonal damage, and white matter sparing as well as the therapeutic effect for improvement of sensory function following SCI. METHODS Adult female Sprague-Dawley rats were divided into the SCI group (SCI only) and SCI-SW group (low-energy ESWT applied after SCI). Thoracic SCI was produced using a New York University Impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks after SCI. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan open-field locomotor score for 42 days after SCI. Mechanical and thermal allodynia in the hindpaw were evaluated for 42 days. Double staining for VEGF and various cell-type markers (NeuN, GFAP, and Olig2) was performed at Day 7; TUNEL staining was also performed at Day 7. Immunohistochemical staining for CD31, α-SMA, and 5-HT was performed on spinal cord sections taken 42 days after SCI. Luxol fast blue staining was performed at Day 42. RESULTS Low-energy ESWT significantly improved not only locomotion but also mechanical and thermal allodynia following SCI. In the double staining, expression of VEGF was observed in NeuN-, GFAP-, and Olig2-labeled cells. Low-energy ESWT significantly promoted CD31 and α-SMA expressions in the injured spinal cords. In addition, low-energy ESWT significantly reduced the TUNEL-positive cells in the injured spinal cords. Furthermore, the immunodensity of 5-HT-positive axons was significantly higher in the animals treated by low-energy ESWT. The areas of spared white matter were obviously larger in the SCI-SW group than in the SCI group, as indicated by Luxol fast blue staining. CONCLUSIONS The results of this study suggested that low-energy ESWT promotes VEGF expression in various neural cells and enhances angiogenesis in damaged neural tissue after SCI. Furthermore, the neuroprotective effect of VEGF induced by low-energy ESWT can suppress cell death and axonal damage and consequently improve locomotor and sensory functions after SCI. Thus, low-energy ESWT can be a novel therapeutic strategy for treatment of SCI.

Closed Reduction of "Irreducible" Posterolateral Knee Dislocation - A Case Report.

INTRODUCTION: Posterolateral rotary knee dislocation is a rare orthopedic injury that is considered to be irreducible by closed reduction because of soft tissue incarceration. Here, we present a case of posterolateral rotary knee dislocation, which was reduced by closed manipulation. CASE REPORT: The patientwas a 33-year-old man who sustained a twisting injury to his right knee that was diagnosed as posterolateral rotary knee dislocation by plain radiographs and the characteristic physical finding known as a dimple sign. Under general anesthesia, the knee dislocation was reduced by closed manipulation with internal rotation of the lower leg at knee flexion and reproduced by valgus and external rotation stress. There were was complete tear of posterior cruciate ligament, and partial tear of the anterior cruciate ligament which were not reconstructed. The medial collateral ligament that was detached from the femoral footprint was repaired. One year postoperatively, the range of motion was 0-145°. There was no knee symptom and no ligament instability. CONCLUSION: This is the first report of a successful closed reduction for posterolateral knee dislocation. The mechanism of dislocation was considered valgus and external rotation stress during knee flexion.

Upregulation of the receptor-interacting protein 3 expression and involvement in neural tissue damage after spinal cord injury in mice.

BACKGROUND: Necroptosis is a newly identified type of programmed cell death that differs from apoptosis. Recent studies have demonstrated that necroptosis is involved in multiple pathologies of various human diseases. Receptor-interacting protein 3 (RIP3) is known to be a critical regulator of necroptosis. This study investigated alterations in the RIP3 expression and the involvement in neural tissue damage after spinal cord injury (SCI) in mice. RESULTS: Immunohistochemical analysis demonstrated that the RIP3 expression was significantly increased in the lesion site after spinal cord hemisection. The increased expression of RIP3 started at 24 h, peaked at 3 days and lasted for at least 21 days after hemisection. The RIP3 expression was observed in neurons, astrocytes and oligodendrocytes. Western blot analysis also demonstrated the RIP3 protein expression significantly upregulated in the injured spinal cord. RIP3 staining using propidium iodide (PI)-labeled sections showed most of the PI-labeled cells were observed as RIP3-positive. Double staining of TUNEL and RIP3 demonstrated that TUNEL-positive cells exhibiting shrunken or fragmented nuclei, as generally observed in apoptotic cells, rarely expressed RIP3. CONCLUSIONS: The present study first demonstrated that the expression of RIP3 is dramatically upregulated in various neural cells in the injured spinal cord and peaked at 3 days after injury. Additionally, most of the PI-labeled cells expressed RIP3 in response to neural tissue damage after SCI. The present study suggested that the upregulation of the RIP3 expression may play a role as a novel molecular mechanism in secondary neural tissue damage following SCI. However, further study is needed to clarify the specific molecular mechanism underlying the relationship between the RIP3 expression and cell death in the injured spinal cord.

Low-energy extracorporeal shock wave therapy promotes vascular endothelial growth factor expression and improves locomotor recovery after spinal cord injury.

OBJECT: Extracorporeal shock wave therapy (ESWT) is widely used for the clinical treatment of various human diseases. Recent studies have demonstrated that low-energy ESWT upregulates the expression of vascular endothelial growth factor (VEGF) and promotes angiogenesis and functional recovery in myocardial infarction and peripheral artery disease. Many previous reports suggested that VEGF produces a neuroprotective effect to reduce secondary neural tissue damage after spinal cord injury (SCI). The purpose of the present study was to investigate whether low-energy ESWT promotes VEGF expression and neuroprotection and improves locomotor recovery after SCI. METHODS: Sixty adult female Sprague-Dawley rats were randomly divided into 4 groups: sham group (laminectomy only), sham-SW group (low-energy ESWT applied after laminectomy), SCI group (SCI only), and SCI-SW group (low-energy ESWT applied after SCI). Thoracic spinal cord contusion injury was inflicted using an impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan (BBB) Scale (open field locomotor score) at different time points over 42 days after SCI. Hematoxylin and eosin staining was performed to assess neural tissue damage in the spinal cord. Neuronal loss was investigated by immunostaining for NeuN. The mRNA expressions of VEGF and its receptor, Flt-1, in the spinal cord were assessed using real-time polymerase chain reaction. Immunostaining for VEGF was performed to evaluate VEGF protein expression in the spinal cord. RESULTS: In both the sham and sham-SW groups, no animals showed locomotor impairment on BBB scoring. Histological analysis of H & E and NeuN stainings in the sham-SW group confirmed that no neural tissue damage was induced by the low-energy ESWT. Importantly, animals in the SCI-SW group demonstrated significantly better locomotor improvement than those in the SCI group at 7, 35, and 42 days after injury (p < 0.05). The number of NeuN-positive cells in the SCI-SW group was significantly higher than that in the SCI group at 42 days after injury (p < 0.05). In addition, mRNA expressions of VEGF and Flt-1 were significantly increased in the SCI-SW group compared with the SCI group at 7 days after injury (p < 0.05). The expression of VEGF protein in the SCI-SW group was significantly higher than that in the SCI group at 7 days (p < 0.01). CONCLUSIONS: The present study showed that low-energy ESWT significantly increased expressions of VEGF and Flt-1 in the spinal cord without any detrimental effect. Furthermore, it significantly reduced neuronal loss in damaged neural tissue and improved locomotor function after SCI. These results suggested that low-energy ESWT enhances the neuroprotective effect of VEGF in reducing secondary injury and leads to better locomotor recovery following SCI. This study provides the first evidence that low-energy ESWT can be a safe and promising therapeutic strategy for SCI.

The role of mTOR signaling pathway in spinal cord injury.

The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in multiple cellular functions, such as cell metabolism, proliferation and survival. Many previous studies have shown that mTOR regulates both neuroprotective and neuroregenerative functions in trauma and various diseases in the central nervous system (CNS). Recently, we reported that inhibition of mTOR using rapamycin reduces neural tissue damage and locomotor impairment after spinal cord injury (SCI) in mice. Our results demonstrated that the administration of rapamycin at four hours after injury significantly increases the activity of autophagy and reduces neuronal loss and cell death in the injured spinal cord. Furthermore, rapamycin-treated mice show significantly better locomotor function in the hindlimbs following SCI than vehicle-treated mice. These findings indicate that the inhibition of mTOR signaling using rapamycin during the acute phase of SCI produces neuroprotective effects and reduces secondary damage at lesion sites. However, the role of mTOR signaling in injured spinal cords has not yet been fully elucidated. Various functions are regulated by mTOR signaling in the CNS, and multiple pathophysiological processes occur following SCI. Here, we discuss several unresolved issues and review the evidence from related articles regarding the role and mechanisms of the mTOR signaling pathway in neuroprotection and neuroregeneration after SCI.