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.

mRNA-Driven Generation of Transgene-Free Neural Stem Cells from Human Urine-Derived Cells.

Human neural stem cells (NSCs) hold enormous promise for neurological disorders, typically requiring their expandable and differentiable properties for regeneration of damaged neural tissues. Despite the therapeutic potential of induced NSCs (iNSCs), a major challenge for clinical feasibility is the presence of integrated transgenes in the host genome, contributing to the risk for undesired genotoxicity and tumorigenesis. Here, we describe the advanced transgene-free generation of iNSCs from human urine-derived cells (HUCs) by combining a cocktail of defined small molecules with self-replicable mRNA delivery. The established iNSCs were completely transgene-free in their cytosol and genome and further resembled human embryonic stem cell-derived NSCs in the morphology, biological characteristics, global gene expression, and potential to differentiate into functional neurons, astrocytes, and oligodendrocytes. Moreover, iNSC colonies were observed within eight days under optimized conditions, and no teratomas formed in vivo, implying the absence of pluripotent cells. This study proposes an approach to generate transplantable iNSCs that can be broadly applied for neurological disorders in a safe, efficient, and patient-specific manner.

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.

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.

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.

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.

A combination of small molecules directly reprograms mouse fibroblasts into neural stem cells.

The generation of induced neural stem cells (iNSCs) from somatic cells using defined factors provides new avenues for basic research and cell therapies for various neurological diseases, such as Parkinson's disease, Huntington's disease, and spinal cord injuries. However, the transcription factors used for direct reprogramming have the potential to cause unexpected genetic modifications, which limits their potential application in cell therapies. Here, we show that a combination of four chemical compounds resulted in cells directly acquiring a NSC identity; we termed these cells chemically-induced NSCs (ciNSCs). ciNSCs expressed NSC markers (Pax6, PLZF, Nestin, Sox2, and Sox1) and resembled NSCs in terms of their morphology, self-renewal, gene expression profile, and electrophysiological function when differentiated into the neuronal lineage. Moreover, ciNSCs could differentiate into several types of mature neurons (dopaminergic, GABAergic, and cholinergic) as well as astrocytes and oligodendrocytes in vitro. Taken together, our results suggest that stably expandable and functional ciNSCs can be directly reprogrammed from mouse fibroblasts using a combination of small molecules without any genetic manipulation, and will provide a new source of cells for cellular replacement therapy of neurodegenerative diseases.

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.

A Rare Case of Malignant Lymphoma Occurred at Spinal Epidural Space: A Case Report.

The sacral spinal epidural space is an uncommon site for primary malignant lymphomas, presenting with symptoms associated with cauda equina compression. Especially, lumbo-sacral epidural lymphoma has been reported to be very rare. We present a rare case of 29-year-old male with sacral spinal epidural malignant lymphoma. The patient complained of tingling sensation in his buttocks that was radiating to his calf. The neurological examination was normal. Magnetic resonance imaging (MRI) with contrast showed a well-defined extradural mass lesion at the mid L5 to mid S2 level. The lesion was iso- to hypointense on T1 and T2 weighted images and showed homogenous enhancement and a focal enhancement in the L5 vertebral body on post-contrast images. The patient underwent a L5-S2 laminectomy and subtotal excision of the lesion. Intra-operatively, the lesion was extradural and not densely adherent to the dura; the lesion was friable, not firm, fleshy, brownish and hypervascular. The histologic diagnosis was grade 2 non-Hodgkin's follicular lymphoma. Even though the primary spinal epidural non-Hodgkin's lymphoma is a very rare disease, clinicians should take it into consideration in the differential diagnosis of patients with spinal epidural tumor.

Cervical Stand-Alone Polyetheretherketone Cage versus Zero-Profile Anchored Spacer in Single-Level Anterior Cervical Discectomy and Fusion : Minimum 2-Year Assessment of Radiographic and Clinical Outcome.

OBJECTIVE: We compared the clinical and radiographic outcomes of stand-alone polyetheretherketone (PEEK) cage and Zero-Profile anchored spacer (Zero-P) for single level anterior cervical discectomy and fusion (ACDF). METHODS: We retrospectively reviewed 121 patients who underwent single level ACDF within 2 years (Jan 2011-Jan 2013) in a single institute. Total 50 patients were included for the analysis who were evaluated more than 2-year follow-up. Twenty-nine patients were allocated to the cage group (m : f=19 : 10) and 21 for Zero-P group (m : f=12 : 9). Clinical (neck disability index, visual analogue scale arm and neck) and radiographic (Cobb angle-segmental and global cervical, disc height, vertebral height) assessments were followed at pre-operative, immediate post-operative, post-3, 6, 12, and 24 month periods. RESULTS: Demographic features and the clinical outcome showed no difference between two groups. The change between final follow-up (24 months) and immediate post-op of Cobb-segmental angle (p=0.027), disc height (p=0.002), vertebral body height (p=0.033) showed statistically better outcome for the Zero-P group than the cage group, respectively. CONCLUSION: The Zero-Profile anchored spacer has some advantage after cage for maintaining segmental lordosis and lowering subsidence rate after single level anterior cervical discectomy and fusion.

Preliminary Experiences of the Combined Midline-Splitting French Door Laminoplasty with Polyether Ether Ketone (PEEK) Plate for Cervical Spondylosis and OPLL.

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of cervical midline-splitting French-door laminoplasty with a polyether ether ketone (PEEK) plate. The authors retrospectively analyzed the results of patients with cervical laminoplasty miniplate (MAXPACER®) without bone grafts in multilevel cervical stenosis. METHODS: Fifteen patients (13 males and 2 females, mean age 50.0 years (range 35-72)) with multilevel cervical stenosis (ossification of the posterior longitudinal ligament and cervical spondylotic myelopathy) underwent a combined surgery of midline-splitting French-door laminoplasty with or without mini plate. All 15 patients were followed for at least 12 months (mean follow-up 13.3 months) after surgery, and a retrospective review of the clinical, radiological and surgical data was conducted. RESULTS: The radiographic results showed a significant increase over the postoperative period in anterior-posterior diameter (9.4±2.2 cm to 16.2±1.1 cm), open angles in cervical lamina (46.5±16.0° to 77.2±13.1°), and sectional volume of cervical central canal (100.5±0.7 cm(2) to 146.5±4.9 cm(2)) (p<0.001). The sagittal alignment of the cervical spine was well preserved (31.7±10.0° to 31.2±7.6°, p=0.877) during the follow-up period. The clinical results were successful, and there were no significant intraoperative complications except for screw displacement in two cases. The mini plate constructs did not fail during the 12 month follow-up period, and the decompression was maintained. CONCLUSION: Despite the small cohort and short follow-up duration, the present study demonstrated that combined cervical expansive laminoplasty using the mini plate is an effective treatment for multilevel cervical stenosis.

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.

Three cases of hemiplegia after cervical paraspinal muscle needling.

BACKGROUND CONTEXT: Muscle needling therapy is common for chronic pain management, but the development of unusual complications such as hemiplegia is not well understood. PURPOSE: We report on three cases with hemiplegia after cervical paraspinal muscle needling and propose possible explanations for these unusual complications. STUDY DESIGN: Case report. METHODS: The authors retrospectively reviewed the medical charts from a decade (2002-2013) at Korea University Hospital. The records were systematically searched, and the cases with hemiplegia (grade<3) after needing therapy were collected. No conflict of interest reported. No funding received. RESULTS: A 54-year-old woman, a 38-year-old woman, and a 60-year-old man with hemiplegia by cervical subdural or epidural hematoma after cervical posterior paraspinal muscle needling without direct invasion (intramuscular stimulation, acupuncture, or intramuscular lidocaine) were observed. All patients were taken for emergent decompressive laminectomy, and their postoperative motor function improved substantially. CONCLUSION: Spinal hematoma after muscle needling is unusual but was thought to result after a rupture of the epidural or subarachnoid veins by a sharp increase in blood pressure delivered in the intraabdominal or intrathoracic areas after needling therapy.

Induced neural stem cells have protective effects on cortical neuronal cells in vitro.

Reprogramming of fibroblasts into induced neural stem cells (NSCs) is a potentially unlimited source of neurons. In this study, we cocultured cortical neuronal cells with iNSCs in a transwell system. We then investigated the effects of coculture on apoptosis and the secretion of cytokines and growth factors. Compared with the cultured cortical neuronal culture alone, cortical neuronal cells cocultured with iNSCs exhibited increased proliferation. TUNEL assay was used to assess the rate of apoptosis at selected time intervals (24, 48 and 72 h). Cells cocultured with iNSCs had fewer apoptotic cells than those cultured without iNSCs. When TUNEL assay was performed in parallel with staining for the neuronal marker Tuj1, the number of neuronal apoptotic cells was found to be lower in cells cocultured with iNSCs than in those cultured without iNSCs for 72 h. Secretion of cytokines and growth factors by iNSCs was evaluated by ELISA. Compared to cells cultured without iNSCs, coculture decreased levels of the inflammatory cytokines and increased levels of HGF and VEGF. These findings indicated that iNSCs could be used as a new treatment strategy for neurodegenerative conditions by promoting proliferation and decreasing apoptosis of cortical neuronal cells.

iNSC suppress macrophage-induced inflammation by repressing COX-2.

Brain inflammation causes cell damage and death in diseases such as Alzheimer's and Parkinson's. In this study, we investigated whether early induced neural stem cells (iNSCs) could protect against cell death after treatment with THP1-derived macrophages. We developed an inflammatory model system with THP1-derived macrophages and cortical neuronal cells and investigated the therapeutic efficacy of iNSC against macrophage-induced inflammation in this model. Apoptosis was confirmed by double immunocytochemistry with NeuN and 4',6-diamidino-2-phenylindole using terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling. Cortical neuronal cells cultured with iNSCs exhibited fewer apoptotic cells than did cultures without iNSCs. The levels of inflammatory cytokines and vascular endothelial growth factor (VEGF) were analyzed by enzyme-linked immunosorbent assay. Cells cultured with iNSCs had lower levels of inflammatory cytokines and higher VEGF levels than those cultured without iNSCs. Western blot analysis for cyclooxygenase-2 (COX-2) showed a significantly lower level of COX-2 in cells cultured with iNSCs than in those cultured without iNSCs. Thus, early iNSCs administration reduced inflammation associated with neurological recovery, and this effect is mediated by COX-2 regulation. Our results suggest that iNSCs have potential therapeutic relevance, because they display strong anti-inflammatory functions that promote neuroprotection thorough the inflammatory response.