Incidental occlusion of anterior spinal artery due to Onyx reflux in embolization of spinal type II arteriovenous malformation.

PURPOSE: Onyx embolization is one of the standard treatments for brain arteriovenous malformations (AVMs) and is a promising method for spinal AVMs as well. Its advantages have been emphasized, and few complications have been reported with Onyx embolization in spinal AVMs. Here, we report an incidental anterior spinal artery (ASA) occlusion due to Onyx reflux during embolization of a spinal type II AVM. METHODS: A 15-year-old boy presented with weakness in both upper and lower extremities. Magnetic resonance imaging and spinal angiogram revealed a spinal type II AVM with two feeders including the right vertebral artery (VA) and the right deep cervical artery. RESULTS: Onyx embolization was performed gradually from the VA to the deep cervical artery and an unexpected Onyx reflux to the ASA was observed during the latter stage deep cervical artery embolization. Post-operative quadriplegia and low cranial nerves (CN) dysfunction were observed. Rehabilitation treatment was performed and the patient showed marked improvement of neurologic deterioration at 1-year follow-up. CONCLUSIONS: Onyx is an effective treatment choice for spinal AVMs. However, due to the small vasculature of the spine compared to the brain, the nidus is rapidly packed with a small amount of Onyx, which allows Onyx reflux to unexpected vessels. Extreme caution is required and dual-lumen balloon catheter could be considered for Onyx embolization in spinal AVMs treatment.

Myofibroblast in the ligamentum flavum hypertrophic activity.

PURPOSE: Majority of the previous studies compared lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH) patients for analyses of LFH. However, the separation of normal/hypertrophied LF has often been ambiguous and the severity of hypertrophic activity differed. Here, we present a novel analysis scheme for LFH in which myofibroblast is proposed as a major etiological factor for LFH study. METHODS: Seventy-one LF patient tissue samples were used for this study. Initially, mRNA levels of the samples were assessed by qRT-PCR: angiopoietin-like protein-2 (ANGPTL2), transforming growth factor-beta1 (TGF-ß1), vascular endothelial growth factor (VEGF), interleukin-6, collagen-1, 3, 4, 5, and 11, and elastin. Myofibroblasts were detected by immune stain using α-smooth muscle actin (αSMA) as a marker. To study the myofibroblast in TGF-ß pathway, LF tissues were analyzed for protein levels of αSMA/TGF-ß1 by Western blot. In addition, from LF cells cultured with exogenous TGF-ß1 conditioned medium, expression of αSMA/collagen-1 was assessed and the cell morphology was identified. RESULTS: The comparative analysis of mRNA expression levels (LSS vs LDH) failed to show significant differences in TGF-ß1 (p = 0.08); however, we found a significant positive correlation among ANGPTL2, VEGF, TGF-ß1, and collagen-1 and 3, which represent common trends in hypertrophic activity (p < 0.05). We detected myofibroblast in the patient samples by αSMA staining, and the protein levels of αSMA were positively correlated with TGF-ß1. In LF cell culture, exogenous TGF-ß1 upregulated αSMA/collagen-1 mRNA levels and facilitated trans-differentiation to myofibroblast. CONCLUSIONS: We conclude that the transition of fibroblast to myofibroblasts via TGF-ß pathway is a key linker between inflammation and fibrosis in LFH mechanism.

What are MRI findings of Spine Benign Metastasizing Leiomyoma? Case report with literature review.

INTRODUCTION: Benign Metastasizing Leiomyoma (BML) is a rare disease that results from metastasis of uterine leiomyoma to distant sites with benign pathologic features. Spine BML is very rare so the information of its features and pathophysiology is seldom known. MATERIALS AND METHODS: We experienced a case of 42-year-old woman who presented with right buttock and leg pain with paresthesia. She had a surgical history of uterine myomectomy. Magnetic resonance imaging (MRI) of the lumbar spine revealed a well-circumscribed mass lesion in the posterior compartment of the L4 vertebral body, with extension into the ventral epidural space and both foramina. The mass showed hypointensity on T1-, T2-weighted images and strong homogeneous enhancement on gadolinium enhanced T1-weighted images. Tumor removal was conducted, and permanent biopsy revealed the mass as leiomyoma. Nine previous spine BML reports, which are known for all, were reviewed along with our case. We collated the clinical information and MRI findings of spine BML to figure out its common denominators. RESULTS: Premenopausal women, previous history of uterine myoma, myomectomy/hysterectomy, and lung BML seemed to be predisposing clinical factors. For the imaging findings, posterior vertebral body invasion with bony destruction, neural foramen invasion, and canal encroachment were shown as common denominators. Especially in MRI findings, low T1 and T2 signal intensities with strong homogeneous enhancement were their common features. CONCLUSION: We gathered the fragmentary information of the spine BML for the first time, especially the MRI findings. Although spine BML is rare, it surely exists. Accordingly, spine surgeons should be suspicious of spine BML given its typical clinical history and MRI findings.

Spinal canal morphology and clinical outcomes of microsurgical bilateral decompression via a unilateral approach for lumbar spinal canal stenosis.

PURPOSE: Microsurgical bilateral decompression via a unilateral approach for lumbar spinal stenosis is a less invasive technique compared to conventional laminectomy. Although many technical reports have demonstrated acceptable overall surgical outcomes for this approach, no studies have attempted to clarify the clinical outcomes thereof in regard to anatomical variance of the spinal canal. This study was conducted to analyze the clinical outcomes of microsurgical bilateral decompression via a unilateral approach according to spinal canal morphology in degenerative lumbar spinal stenosis. METHODS: Between January 2008 and December 2009, 144 patients with single-level spinal lumbar stenosis underwent microsurgical bilateral decompression via a unilateral approach by a single surgeon. Patients were categorized into three groups according to spinal canal shape: round (n = 42), oval (n = 36), and trefoil (n = 66), and clinical parameters were assessed both before and after surgery with 2-3 years of follow-up. RESULTS: Mean visual analog scale (VAS) and Oswestry disability index (ODI) decreased after surgery, respectively, from 8.1 and 59.8 % to 2.1 and 19.1 % in the round shaped spinal canal group, from 7.2 and 47.1 % to 2.2 and 15.1 % in the oval shaped spinal canal group, and from 6.8 and 53.6 % to 3.6 and 33.3 % in the trefoil shaped spinal canal group. In all groups, VAS and ODI scores significantly improved postoperatively (p < 0.01), although less improved VAS and ODI scores were observed in the trefoil shaped spinal canal group (p < 0.01). The overall patient satisfaction rate was 66.7 %; however, statistically significant lower satisfaction rates were reported in the trefoil shaped spinal canal group (p < 0.01). CONCLUSIONS: Microsurgical bilateral decompression via a unilateral approach may be a good modality for treating round or oval shape spinal canal stenosis, but is not recommended for trefoil-shaped-stenosis. The current authors recommend performing the bilateral decompression technique in cases of trefoil-shaped-spinal canal stenosis.

Evaluating the Efficacy and Safety of Hemofence (Thorombin Cross-linked Sodium Hyaluronate Gel Matrix) in Hemostasis for Intractable Exudative Bleeding in Spinal Surgery: A Multicenter, Randomized, Phase III Clinical Trial.

Objective: To demonstrate the non-inferiority of the novel hemostatic agent, Hemofence® (BMI Korea Co. Ltd., Jeju Korea, thrombin cross-linked sodium hyaluronate gel matrix) compared to the established agent, Floseal Hemostatic Matrix (Baxter, thrombin-gelatin matrix) in achieving hemostasis for spinal surgeries, with secondary objectives to assess additional efficacy and safety. Methods: This clinical trial was a multicenter, randomized, subject-blinded, active-controlled, parallel-group, phase 3 study. Investigational drugs were administered to the first and second bleeding sites of each participant (or only to the first site if a second site was absent), evaluating hemostasis success rate within 10 minutes and the time to achieve hemostasis. Subsequent visits were conducted for safety assessments. For non-inferiority test, a 97.5% one-sided confidence interval was used; the test group was deemed non-inferior if the lower limit exceeded -10%. Results: This trial showed a 97.10% success rate in the test group and 96.05% in the control group for primary efficacy. The 95% confidence interval (-4.90%, 7.44%) confirmed the test drug's non-inferiority. Time to hemostasis showed no significant difference between groups. All adverse events, adverse drug reactions, and serious adverse events were statistically similar between groups (p=1.0000, p=0.2427, and p=0.9663, respectively). Conclusion: A novel hemostatic agent, Hemofence®, demonstrated an efficacy and safety profile comparable to that of Floseal.

True Continuous Segment of Ossification of Posterior Longitudinal Ligament is Protective Against Postoperative Early Kyphosis Progression After Laminoplasty.

BACKGROUND AND OBJECTIVES: Ossification of the posterior longitudinal ligament (OPLL) is a potentially catastrophic disease. Laminoplasty (LP) is a common surgical intervention, but postoperative kyphosis progression is a major complication, for which various risk factors have been identified and used in surgical decision-making. Our focus is on the ability of OPLL with specific morphological traits, designated as the true continuous segment (TCS), to stabilize alignment and prevent postoperative kyphosis after LP. METHODS: This retrospective case-control study included patients who underwent cervical LP for OPLL treatment with a minimum 1-year follow-up. Demographic, operative, and radiographic parameters were analyzed. TCS is defined as a continuous segment of OPLL that spans the disk space more than half of the adjacent vertebral body height without crack, or OPLL segment attached to both upper and lower adjacent vertebral bodies by bridging, or obvious interbody autofusion, and is identified from preoperative computed tomography. A subgroup analysis for preoperatively lordotic patients, divided into 2 groups based on cervical alignment at the final follow-up, was conducted to identify risk factors for kyphosis progression. Difference analysis, linear regression analysis for loss of lordosis (LoL), and logistic regression analysis for kyphosis progression were used. RESULTS: A total of 84 patients were identified. Among them, 78 patients with preoperatively lordotic alignment were divided into 2 groups: those who maintained lordotic alignment (n = 60) and those who progressed to kyphosis (n = 18). Regression analyses revealed a significant protective effect of TCS count against LoL and postoperative kyphosis, with a TCS count of 3 or more conclusively preventing kyphosis (sensitivity 1.000, specificity 0.283, area under the curve 0.629). CONCLUSION: For patients with OPLL, TCS was shown to protect against the LoL after LP. Therefore, TCS should be identified and considered when planning surgical treatment for OPLL.

Human induced neural stem cells support functional recovery in spinal cord injury models.

Spinal cord injury (SCI) is a clinical condition that leads to permanent and/or progressive disabilities of sensory, motor, and autonomic functions. Unfortunately, no medical standard of care for SCI exists to reverse the damage. Here, we assessed the effects of induced neural stem cells (iNSCs) directly converted from human urine cells (UCs) in SCI rat models. We successfully generated iNSCs from human UCs, commercial fibroblasts, and patient-derived fibroblasts. These iNSCs expressed various neural stem cell markers and differentiated into diverse neuronal and glial cell types. When transplanted into injured spinal cords, UC-derived iNSCs survived, engrafted, and expressed neuronal and glial markers. Large numbers of axons extended from grafts over long distances, leading to connections between host and graft neurons at 8 weeks post-transplantation with significant improvement of locomotor function. This study suggests that iNSCs have biomedical applications for disease modeling and constitute an alternative transplantation strategy as a personalized cell source for neural regeneration in several spinal cord diseases.

Radiological evaluation of atlantoaxial fusion using C2 translaminar screws and C2 pedicle screws: Does the screw halo sign imply fusion failure?

The purpose of this study was to identify the criteria for atlantoaxial (AA) fusion by comparing follow-up lateral radiographs and computed tomography (CT) images. We retrospectively analyzed data from 161 consecutive patients undergoing AA fusion. Patients with a minimum of 1 year of CT follow-up after AA fusion surgery using C2 pedicle screws or translaminar screws (C2TLS) were included. Patients were followed up radiographically at 3, 6, and 12 months after surgery, and dynamic lateral radiographs were also evaluated. A total of 49 patients were analyzed, with a mean CT image follow-up of 41.6 ±â€…37.6 months. Thirty eight patients had C2 pedicle screw placement, and 11 patients underwent planned C2TLS. AA fusion with bridging bone mass formation was achieved in 45/49 (91.8%) patients. Screw halos were observed in 14/49 (28.6%) patients. Among them, final fusion failure occurred in 2 (14.3%) patients. The last follow-up CT showed no difference in the fusion failure rate according to the presence or absence of a screw halo (no halo, 5.7%; halo, 14.3%; P = .33). The differences in C1-2 segmental angles (SA) in flexion-extension dynamic lateral radiographs were 1.99 ±â€…1.62° in the fusion group and 4.37 ±â€…2.13° in the non-fusion group (P = .01). The likelihood of fusion failure increased when the SA gap was greater than 2.62° (P = .05). C2TLS placement had a significantly higher incidence of screw halos. However, the halo sign was not significantly related to final bone fusion. Bone fusion could be predicted when the SA gap of C1-2 was less than 2.62° on the dynamic radiograph.

Ligamentum flavum hypertrophy significantly contributes to the severity of neurogenic intermittent claudication in patients with lumbar spinal canal stenosis.

Ligamentum flavum hypertrophy (LFH) is a known contributor to lumbar spinal canal stenosis (LSCS). However, the clinical significance and quantitative role of LFH compared to other components, such as disc bulging and facet hypertrophy, have not yet been examined. We investigated the correlation between the quantitative radiological factors, clinical symptoms, and outcomes in patients with LSCS. In total, 163 patients diagnosed with single-level (L4-L5) stenosis were included. The patients were divided into 2 groups according to claudication severity: >100 m for mild (n = 92) and < 100 m for severe (n = 71). The visual analog scale (VAS) was used to quantify back and leg pain, and the Oswestry Disability Index (ODI) and Short form-36 (SF-36) physical component summary (PCS) scores, and Macnab criteria were evaluated as clinical factors 6 months after treatment. We measured the baseline canal cross-sectional area, ligamentum flavum (LF) area, disc herniation area, dural sac area, fat area, and LF thickness using MRI. A comparative analysis was performed to evaluate the association between radiologic and clinical factors. Additionally, further comparative analyses between the types of surgeries were performed. Among various radiologic factors, the baseline LF thickness (odds ratio [OR] 1.73; 95% confidence interval [CI] 1.25-2.41) was the only major contributing factor to the severity of claudication in the multivariate logistic regression analysis. The types of surgery (decompression alone vs fusion) did not significantly differ in terms of their clinical outcomes, including back and leg VAS, ODI, SF-36 PCS, and satisfaction with the MacNab classification. LF thickness is a major factor contributing to claudication severity.

Clinicopathological considerations in patients with lumbosacral extraforaminal stenosis.

Lumbosacral extraforaminal stenosis is not uncommon among patients being treated for radicular symptoms. Patients who had lumbosacral extraforaminal stenosis were reviewed, and cadaver dissection was used to determine the anatomy of extraforaminal lesions. A total of 167 patients with lumbosacral spinal stenosis who underwent surgery from March 2004 to February 2006 were reviewed retrospectively. Among these, extraforaminal stenosis was observed in 26 patients (mean age 61.4 y; range 46-79). Leg pain and neurogenic claudication were common in patients with extraforaminal stenosis. One level was involved for 15 patients and 2 levels were involved for 11 patients. Complete decompression of the dorsal root ganglion or a root compressed by the fibrocartilagenous ligamentum flavum or a hypertrophied superior facet was performed. The mean follow-up was 8.3 months (range 6-26 months). The causes of extraforaminal stenosis were superior facet hypertrophy, especially hypertrophy of the superior lateral portion, or thickening of the ligamentum flavum, intertransverse ligament, or transforaminal ligament. T1-weighted, coronal MRI showed root impingement in the far-lateral zone. Postoperative outcomes were assessed using the Prolo scale; 13 patients demonstrated excellent outcomes, while 11 patients had good outcomes. No major complications or recurrences were observed during follow-up. Therefore, lumbosacral extraforaminal stenosis should be included in the differential diagnosis of lumbar radicular pain. A precise diagnosis using MRI is important, and complete decompression with an understanding of the extraforaminal anatomy is required.

CCN5 Reduces Ligamentum Flavum Hypertrophy by Modulating the TGF-ß Pathway.

Ligamentum flavum hypertrophy (LFH) is the most important component of lumbar spinal canal stenosis. Although the pathophysiology of LFH has been extensively studied, no method has been proposed to prevent or treat it. Since the transforming growth factor-ß (TGF-ß) pathway is known to be critical in LFH pathology, we investigated whether LFH could be prevented by blocking or modulating the TGF-ß mechanism. Human LF cells were used for the experiments. First, we created TGF-ß receptor 1 (TGFBR1) knock out (KO) cells with CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 biotechnology and treated them with TGF-ß1 to determine the effects of blocking the TGF-ß pathway. Subsequently, we studied the effect of CCN5, which has recently been proposed to modulate the TGF-ß pathway. To assess the predisposition toward fibrosis, α-smooth muscle actin (αSMA), fibronectin, collagen-1, collagen-3, and CCN2 were evaluated with quantitative real-time polymerase chain reaction, western blotting, and immunocytochemistry. The TGFBR1 KO LF cells were successfully constructed with high KO efficiency. In wild-type (WT) cells, treatment with TGF-ß1 resulted in the overexpression of the messenger RNA (mRNA) of fibrosis-related factors. However, in KO cells, the responses to TGF-ß1 stimulation were significantly lower. In addition, CCN5 and TGF-ß1 co-treatment caused a notable reduction in mRNA expression levels compared with TGF-ß1 stimulation only. The αSMA protein expression increased with TGF-ß1 but decreased with CCN5 treatment. TGF-ß1 induced LF cell transdifferentiation from fibroblasts to myofibroblasts. However, this cell transition dramatically decreased in the presence of CCN5. In conclusion, CCN5 could prevent LFH by modulating the TGF-ß pathway. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2634-2644, 2019.

Brain cancer stem-like cell genesis from p53-deficient mouse astrocytes by oncogenic Ras.

Here, we show that H-ras(V12) causes the p53-knockout mouse astrocytes (p53-/- astrocytes) to be transformed into brain cancer stem-like cells. H-ras(V12) triggers the p53-/- astrocytes to express a Nestin and a Cd133, which are expressed in normal and cancer neural stem cells. H-ras(V12) also induces the formation of a single cell-derived neurosphere under neural stem cell culture conditions. Furthermore, H-ras(V12)-overexpressing p53-/- astrocytes (p53-/-ast-H-ras(V12)) possess an in vitro self-renewal capacity, and are aberrantly differentiated into Tuj1-positve neurons both in vitro and in vivo. Amongst a variety of Ras-mediated canonical signaling pathways, we demonstrated that the MEK/ERK signaling pathway is responsible for neurosphere formation in p53-deficient astrocytes, whereas the PI3K/AKT signaling pathway is involved in oncogenic transformation in these cells. These findings suggest that the activation of Ras signaling pathways promotes the generation of brain cancer stem-like cells from p53-deficient mouse astrocytes by changing cell fate and transforming cell properties.

Angiographic features, surgical management and outcomes of proximal middle cerebral artery aneurysms.

OBJECTIVE: Understanding the microanatomy of the proximal middle cerebral artery (M1) and its early branches is very important for aneurysm surgery in this region. However, few articles provide detailed descriptions of such aneurysms. We report the angiographic characteristics of a series of M1 aneurysms and our experience with M1 aneurysm surgery. MATERIALS AND METHODS: Twenty-three patients with 25 (combined) M1 aneurysms presented to our institution from January 2001 to December 2006. We examined the general characteristics and angiographic features of the M1 aneurysms, such as site, size, direction, and their association with early branches. RESULTS: Of the 23 patients with M1 aneurysms, 13 were women and 10 were men. Nineteen of the aneurysms had ruptured prior to presentation. Multiple aneurysms were observed in 10 of the patients. Angiography showed that 14 of the aneurysms were less than 5mm in size, and most of the aneurysmal projections were superior. Eighteen of the aneurysms involved early frontal branches and three involved the lenticulostriate arteries. Postoperative infarction was seen in eight patients. Five of the eight patients showed either no or slight neurological deficits at the follow-up visit. One patient, however, suffered from hemiparesis and aphasia that corresponded to the vascular territory of the early frontal branches and lenticulostriate arteries. Two patients had a total MCA infarction and a posterior fossa infarction, respectively. CONCLUSIONS: This study highlights the need for the critical management of M1 aneurysms, taking into consideration the size and number of aneurysms. By performing careful angiographic investigation of the aneurysm and related early arterial branches of M1, postoperative complications may be minimized.

Thrombosed giant aneurysm of the pericallosal artery with inconclusive findings of multiple neuroimaging studies.

A 65-year-old woman presented with a thrombosed giant pericallosal artery aneurysm manifesting as headache and memory loss that developed over a 2-year period. Computed tomography (CT), magnetic resonance (MR) imaging, and conventional and CT angiography could not establish the differential diagnosis. Open craniotomy revealed the mass as thrombosed giant aneurysm from the pericallosal artery. Direct clipping with thrombectomy was performed successfully with an uneventful postoperative course. Thrombosed giant aneurysm of the distal anterior cerebral artery should be considered in the differential diagnosis of an unusual mass in the mid-frontal area, particularly in the presence of inconclusive angiographic and MR imaging findings.

Selective cell death of oncogenic Akt-transduced brain cancer cells by etoposide through reactive oxygen species mediated damage.

We have established several glioma-relevant oncogene-engineered cancer cells to reevaluate the oncogene-selective cytotoxicity of previously well-characterized anticancer drugs, such as etoposide, doxorubicin, staurosporine, and carmustine. Among several glioma-relevant oncogenes (activated epidermal growth factor receptor, Ras, and Akt, as well as Bcl-2 and p53DD used in the present study), the activated epidermal growth factor receptor, Ras, and Akt exerted oncogenic transformation of Ink4a/Arf(-/-) murine astrocyte cells. We identified that etoposide, a topoisomerase II inhibitor, caused selective killing of myristylated Akt (Akt-myr)-transduced Ink4a/Arf(-/-) astrocytes and U87MG cells in a dose- and time-dependent manner. Etoposide-selective cytotoxicity in the Akt-myr-transduced cells was shown to be caused by nonapoptotic cell death and occurred in a p53-independent manner. Etoposide caused severe reactive oxygen species (ROS) accumulation preferentially in the Akt-myr-transduced cells, and elevated ROS rendered these cells highly sensitive to cell death. The etoposide-selective cell death of Akt-myr-transduced cells was attenuated by pepstatin A, a lysosomal protease inhibitor. In the present study, we show that etoposide might possess a novel therapeutic activity for oncogenic Akt-transduced cancer cells to kill preferentially through ROS-mediated damage.

Radiological findings following postsurgical intratumoral bleomycin injection for cystic craniopharyngioma.

OBJECTIVES: The purpose of this study was to compare the radiological findings before and after intratumoral bleomycin injection in patients with cystic craniopharyngioma so as to define the role of adjuvant intracavitary bleomycin chemotherapy for cystic craniopharyngiomas. PATIENTS AND METHODS: Eleven patients whose craniopharyngioma was confirmed cytologically and/or histologically were retrospectively reviewed. The follow-up duration ranged from 9 to 79 months (mean, 31.6 months). Only the solid portion of the cystic craniopharyngiomas was excised before repeated injections of bleomycin (15-180 mg in total) into the cystic portion through an Ommaya reservoir were given. The patients were evaluated neuroradiologically before and after bleomycin administration. RESULTS: After the completion of all treatment cycles, the disappearance or shrinkage of the tumor was initially noted in all cases on follow-up CT and/or MR imaging studies. However, tumor recurrence was seen in four cases with a mixed tumor type. CONCLUSION: Postoperative bleomycin injection in cystic craniopharyngioma does not appear to totally eradicate the tumor and does not stop tumor recurrence unless the cyst is the only portion of the craniopharyngioma that is left. Nevertheless, postoperative bleomycin injection decreases and stabilizes tumor size, and thus may be considered as an option of treatment modalities in patients with predominantly cystic craniopharyngiomas.

Spinal cord infarction after decompressive laminectomy for spontaneous spinal epidural hematoma--case report.

A 68-year-old woman presented to the emergency department for evaluation of bilateral leg weakness. On admission, she had paraparesis with incomplete sensory deficit. Magnetic resonance (MR) imaging of the thoracolumbar spine revealed spontaneous spinal epidural hematoma (SSEH) compressing the spinal cord. The patient was taken to the operating room for urgent surgical decompression and evacuation of the SSEH. After the surgery, she woke up with complete paraplegia. Postoperative MR imaging showed the spinal cord was edematous, with minimal remnant hematoma. MR imaging after 1 month clearly showed anterior spinal artery thrombosis. No significant neurological improvement occurred during the 3-month follow up. Surgeons should consider the possibility of this devastating complication before aggressive and early surgical intervention in a patient with SSEH causing cord compression and neurological deficit.

Interferon regulatory factor 3 activates p53-dependent cell growth inhibition.

Interferon regulatory factor 3 (IRF3) is a transcriptional factor that plays a crucial role in activation of innate immunity and inflammation in response to viral infection. We investigated the biological function of IRF3 overexpressed in somatic cells such as fibroblasts and astrocytes. Similar to overexpression of oncogenic H-ras in the normal human fibroblast, overexpression of IRF3 in human fibroblast BJ cells was shown to decrease cell growth and increase senescence-associated beta-galactosidase activity by activating a p53 tumor suppressor. BCNU, a DNA damage agent, further accelerated p53 function and cell death in the IRF3-overexpressed BJ cells compared to control BJ cells, without increased expression of IRF3 target genes. IRF3 failed to activate p53 function and cell growth inhibition in BJ cells downregulating p53 by RNAi-mediated p53 knockdown. Furthermore, enforced expression of IRF3 did not show any effect of cell growth inhibition in astrocytes or embryonic fibroblasts derived from the p53(-/-) mouse. When compared to control BJ cells, BJ cells which downregulated IRF3 by RNAi-mediated IRF3 knockdown showed extended in vitro life span. Taken together, the present study indicates that IRF3 should be a novel inducer of cell growth inhibition and cellular senescence through activation of p53 tumor suppressor.

Surgery versus Nerve Blocks for Lumbar Disc Herniation : Quantitative Analysis of Radiological Factors as a Predictor for Successful Outcomes.

OBJECTIVE: To assess the clinical and radiological factors as predictors for successful outcomes in lumbar disc herniation (LDH) treatment. METHODS: Two groups of patients with single level LDH (L4-5) requiring treatment were retrospectively studied. The surgery group (SG) included 34 patients, and 30 patients who initially refused the surgery were included in the nerve blocks group (NG). A visual analogue scale (VAS) for leg and back pain and motor deficit were initially evaluated before procedures, and repeated at 1, 6, and 12 months. Radiological factors including the disc herniation length, disc herniation area, canal length-occupying ratio, and canal area-occupying ratio were measured and compared. Predicting factors of successful outcomes were determined with multivariate logistic regression analysis after the optimal cut off values were established with a receiver operating characteristic curve. RESULTS: There was no significant demographic difference between two groups. A multivariate logistic regression analysis with radiological and clinical (12 months follow-up) data revealed that the high disc herniation length with cutoff value 6.31 mm [odds ratio (OR) 2.35; confidence interval (CI) 1.21-3.98] was a predictor of successful outcomes of leg pain relief in the SG. The low disc herniation length with cutoff value 6.23 mm (OR 0.05; CI 0.003-0.89) and high baseline VAS leg (OR 12.63; CI 1.64-97.45) were identified as predictors of successful outcomes of leg pain relief in the NG. CONCLUSION: The patients with the disc herniation length larger than 6.31 mm showed successful outcomes with surgery whereas the patients with the disc herniation length less than 6.23 mm showed successful outcomes with nerve block. These results could be considered as a radiological criteria in choosing optimal treatment options for LDH.

Intrathecal transplantation of autologous adipose-derived mesenchymal stem cells for treating spinal cord injury: A human trial.

CONTEXT: Spinal cord injury (SCI) can cause irreversible damage to neural tissues. However, there is currently no effective treatment for SCI. The therapeutic potential of adipose-derived mesenchymal stem cells (ADMSCs) has been emerged. OBJECTIVE: We evaluated the effects and safety of the intrathecal transplantation of autologous ADMSCs in patients with SCI. Participants/Interventions: Fourteen patients with SCI were enrolled (12 for ASIA A, 1 for B, and 1 for D; duration of impairments 3-28 months). Six patients were injured at cervical, 1 at cervico-thoracic, 6 at thoracic, and 1 at lumbar level. Autologous ADMSCs were isolated from lipoaspirates of patients' subcutaneous fat tissue and 9 × 107 ADMSCs per patient were administered intrathecally through lumbar tapping. MRI, hematological parameters, electrophysiology studies, and ASIA motor/sensory scores were assessed before and after transplantation. RESULTS: ASIA motor scores were improved in 5 patients at 8 months follow-up (1-2 grades at some myotomes). Voluntary anal contraction improvement was seen in 2 patients. ASIA sensory score recovery was seen in 10, although degeneration was seen in 1. In somatosensory evoked potential test, one patient showed median nerve improvement. There was no interval change of MRI between baseline and 8 months post-transplantation. Four adverse events were observed in three patients: urinary tract infection, headache, nausea, and vomiting. CONCLUSIONS: Over the 8 months of follow-up, intrathecal transplantation of autologous ADMSCs for SCI was free of serious adverse events, and several patients showed mild improvements in neurological function. Patient selection, dosage, and delivery method of ADMSCs should be investigated further.