Human Neural Stem Cells Encoding ChAT Gene Restore Cognitive Function via Acetylcholine Synthesis, Aß Elimination, and Neuroregeneration in APPswe/PS1dE9 Mice.

In Alzheimer disease (AD) patients, degeneration of the cholinergic system utilizing acetylcholine for memory acquisition is observed. Since AD therapy using acetylcholinesterase (AChE) inhibitors are only palliative for memory deficits without slowing or reversing disease progress, there is a need for effective therapies, and stem cell-based therapeutic approaches targeting AD should fulfill this requirement. We established a human neural stem cell (NSC) line encoding choline acetyltransferase (ChAT) gene, an acetylcholine-synthesizing enzyme. APPswe/PS1dE9 AD model mice transplanted with the F3.ChAT NSCs exhibited improved cognitive function and physical activity. Transplanted F3.ChAT NSCs in the AD mice differentiated into neurons and astrocytes, produced ChAT protein, increased the ACh level, and improved the learning and memory function. F3.ChAT cell transplantation reduced Aß deposits by recovering microglial function; i.e., the down-regulation of ß-secretase and inflammatory cytokines and up-regulation of Aß-degrading enzyme neprilysin. F3.ChAT cells restored growth factors (GFs) and neurotrophic factors (NFs), and they induced the proliferation of NSCs in the host brain. These findings indicate that NSCs overexpressing ChAT can ameliorate complex cognitive and physical deficits of AD animals by releasing ACh, reducing Aß deposit, and promoting neuroregeneration by the production of GFs/NFs. It is suggested that NSCs overexpressing ChAT could be a candidate for cell therapy in advanced AD therapy.

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.

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.

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.

Prognostic factors of clinical outcome after neuronavigation-assisted hematoma drainage in patients with spontaneous intracerebral hemorrhage.

OBJECTIVE: The prognostic factors that contribute to outcome after navigation-assisted drainage in patients with spontaneous intracerebral hemorrhage (ICH) have not been defined. We compared the characteristics and clinical outcomes of patients with spontaneous ICHs who underwent neuronavigation-assisted hematoma drainage. METHODS: Forty-seven patients were enrolled from January 2004 to August 2013. The patients were divided into two groups according to Glasgow Outcome Scale (GOS) scores: the good- (GOS 4-5) and poor-outcome (GOS 1-3) groups. A variety of factors, characteristics, and clinical outcomes were analyzed. RESULTS: Among the 47 patients, 16 and 31 showed good and poor outcomes, respectively. The mortality rate was 4.3%. Patients' ages, horizontal and vertical diameters and volume of the hematoma on the initial brain computed tomography scan, and the initial Glasgow Coma Scale (GCS) scores were significantly different between the two groups (P<0.05). Ages less than 60 years, smaller horizontal and vertical diameters of the hematoma, less initial hematoma volume, higher initial GCS scores, and the absence of intraventricular hemorrhages were significantly associated with good outcome (P<0.05). Among these factors, initial hematoma volume was a borderline prognostic factor (odds ratio [OR], 0.951; 95% confidence interval [CI], 0.904-1.001; P=0.054), whereas initial GCS score was a significant prognostic factor (OR, 2.737; 95% CI, 1.371-5.465; P=0.004), in the multivariate analysis. CONCLUSION: Initial GCS score and hematoma volume were important prognostic factors of clinical outcome in patients with spontaneous ICHs who underwent navigation-assisted drainage. Such factors should be carefully considered before patients are treated with navigation-assisted hematoma drainage.

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.

Comparison of cerebrospinal fluid biomarkers between idiopathic normal pressure hydrocephalus and subarachnoid hemorrhage-induced chronic hydrocephalus: a pilot study.

BACKGROUND: We examined the cerebrospinal fluid (CSF) markers of subarachnoid hemorrhage (SAH)-induced and idiopathic normal pressure hydrocephalus (INPH) to investigate the pathophysiology and mechanism of communicating hydrocephalus compared to obstructive hydrocephalus. MATERIAL/METHODS: We obtained CSF samples from 8 INPH, 10 SAH-induced hydrocephalus, and 6 unmatched patients with non-hemorrhagic obstructive hydrocephalus during their ventriculoperitoneal shunt operations. Transforming growth factor (TGF)-ß1, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), and total tau in the CSF were analyzed via enzyme-linked immunosorbent assay. RESULTS: The mean VEGF levels in the CSF of patients with SAH-induced hydrocephalus, INPH, and obstructive hydrocephalus were 239 ± 131, 239 ± 75, and 163 ± 122 pg/mL, respectively. The total tau concentrations in the CSF of the groups were 1139 ± 1900, 325 ± 325, and 1550 ± 2886 pg/mL, respectively. TNF-α values were 114 ± 34, 134 ± 38, and 55 ± 16 pg/mL, respectively. TGF-ß1 values were 953 ± 430, 869 ± 447, and 136 ± 63 pg/mL, respectively. A significant difference in TNF-α and TGF-ß1 levels was observed only between SAH-induced and chronic obstructive hydrocephalus, and between INPH and chronic obstructive hydrocephalus (p<0.01). CONCLUSIONS: No significant differences in the 4 CSF biomarker levels were observed between INPH and SAH-induced hydrocephalus, whereas CSF TNF-α and TGF-ß1 levels were increased compared to those in patients with chronic obstructive hydrocephalus. Post-SAH hydrocephalus and INPH are probably more destructive to neural tissues, and then stimulate the inflammatory reaction and healing process, compared with obstructive hydrocephalus.

Angiographic features and clinical outcomes of intra-arterial nimodipine injection in patients with subarachnoid hemorrhage-induced vasospasm.

OBJECTIVE: The aim of this study was to determine the role of intra-arterial (IA) nimodipine injections for cerebral vasospasm secondary to ruptured subarachnoid hemorrhage (SAH) and to investigate the factors that influence vasodilation and clinical outcomes. METHODS: We enrolled 29 patients who underwent aneurysm clipping for ruptured cerebral aneurysms between 2009 and 2011, and who received IA nimodipine after subsequently presenting with symptomatic vasospasm. The degree of vasodilation shown in angiography was measured, and the correlation between the degree of vasodilation and both the interval from SAH to cerebral vasospasm and the interval from clipping to cerebral vasospasm was determined. The change in blood flow rate after IA injection was assessed by transcranial Doppler ultrasound. Multiple clinical parameters were completed before and after IA nimodipine injection to evaluate any improvements in clinical symptoms. RESULTS: For eight patients, Glasgow Coma Scale (GCS) scores increased by two or more points. The regression analysis demonstrated a positive correlation between the change in GCS scores after IA nimodipine injection and the change in blood vessel diameter (p=0.025). A positive correlation was also observed between the interval from SAH to vasospasm and the change in diameter (p=0.040); and the interval from clipping to vasospasm and the change in diameter (p=0.022). CONCLUSION: IA nimodipine injection for SAH-induced vasospasm led to significant vasodilation in angiography and improvement in clinical symptoms without significant complications. Our findings suggest that IA nimodipine injection should be utilized when intractable vasospasm develops despite rigorous conservative management.

The Correlation between Insertion Depth of Prodisc-C Artificial Disc and Postoperative Kyphotic Deformity: Clinical Importance of Insertion Depth of Artificial Disc.

OBJECTIVE: This study was designed to investigate the correlation between insertion depth of artificial disc and postoperative kyphotic deformity after Prodisc-C total disc replacement surgery, and the range of artificial disc insertion depth which is effective in preventing postoperative whole cervical or segmental kyphotic deformity. METHODS: A retrospective radiological analysis was performed in 50 patients who had undergone single level total disc replacement surgery. Records were reviewed to obtain demographic data. Preoperative and postoperative radiographs were assessed to determine C2-7 Cobb's angle and segmental angle and to investigate postoperative kyphotic deformity. A formula was introduced to calculate insertion depth of Prodisc-C artificial disc. Statistical analysis was performed to search the correlation between insertion depth of Prodisc-C artificial disc and postoperative kyphotic deformity, and to estimate insertion depth of Prodisc-C artificial disc to prevent postoperative kyphotic deformity. RESULTS: In this study no significant statistical correlation was observed between insertion depth of Prodisc-C artificial disc and postoperative kyphotic deformity regarding C2-7 Cobb's angle. Statistical correlation between insertion depth of Prodisc-C artificial disc and postoperative kyphotic deformity was observed regarding segmental angle (p<0.05). It failed to estimate proper insertion depth of Prodisc-C artificial disc effective in preventing postoperative kyphotic deformity. CONCLUSION: Postoperative segmental kyphotic deformity is associated with insertion depth of Prodisc-C artificial disc. Anterior located artificial disc leads to lordotic segmental angle and posterior located artificial disc leads to kyphotic segmental angle postoperatively. But C2-7 Cobb's angle is not affected by artificial disc location after the surgery.

Unusual fatal infections after anterior cervical spine surgeries.

We report two cases of cervical spinal epidural abscess (SEA), which are related to anterior cervical surgeries. The first case reveals a late postoperative infection without any predisposing factor. The second case reveals combined complication of infection and instrument failure (artificial disc). Both two cases manifested ascending infections that are unusual courses of anterior cervical infections. The abscess extended upwards and, finally, caused life threatening bacterial meningitis. We suggest aggressive surgical interventions with anti-bacterial therapies in such cases.

Usefulness of thallium-201 SPECT for prediction of early progression in low-grade astrocytomas diagnosed by stereotactic biopsy.

OBJECTIVE: To establish the value of thallium-201 single-photon emission computed tomography ((201)Tl-SPECT) as a predictor of early progression in low-grade astrocytomas (LGAs). METHODS: We studied 57 consecutive patients who underwent 201 Tl-SPECT before stereotactic biopsy (n=33) or surgical resection (n=24). The value of radiologic and histopathological variables ((201)Tl index and MIB-1 index) in predicting progression free survival (PFS) was examined in each group of patients. RESULTS: During a median follow up of 55 months (range, 11-101), progression of the primary lesion was identified in 46 patients (80.7%). Based on Cox's proportional hazards model, the increased thallium uptake was associated with a short PFS in both biopsy and resection groups, whereas the MIB-1 index was significant only in the resection group. Considering the cut-off value, (201)Tl index>1.7 was statistically significant for reduced PFS in the biopsy group; however, MIB-1 index was not directly related to the PFS at any level. For the surgical resection group, both a (201)Tl index>1.9 and a MIB-1 index>6% were associated with short PFS. CONCLUSION: (201)Tl SPECT may play a role in prediction of early tumor progression not only in resected LGAs, but also in biopsy-proven LGAs. Therefore, we suggest that patients with LGAs established from biopsy should be considered as high-risk groups for early progression if the tumor shows a high (201)Tl uptake, even if the tumor demonstrates low proliferative activity on histopathologic examination.

Transplantation of umbilical cord blood stem cells for treating spinal cord injury.

Spinal cord injury (SCI) develops primary and secondary damage to neural tissue and this often results in permanent disability of the motor and sensory functions. However, there is currently no effective treatment except methylprednisolone, and the use of methylprednisolone has also been questioned due to its moderate efficacy and the drug's downside. Regenerative medicine has remarkably developed since the discovery of stem cells, and many studies have suggested the potential of cell-based therapies for neural injury. Especially, the therapeutic potential of human umbilical cord blood cells (hUCB cells) for intractable neurological disorders has been demonstrated using in vitro and vivo models. The hUCB cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Their ability to produce several neurotropic factors and to modulate immune and inflammatory reactions has also been noted. Recent evidence has emerged suggesting alternative pathways of graft-mediated neural repair that involve neurotrophic effects. These effects are caused by the release of various growth factors that promote cell survival, angiogenesis and anti-inflammation, and this is all aside from a cell replacement mechanism. In this review, we present the recent findings on the stemness properties and the therapeutic potential of hUCB as a safe, feasible and effective cellular source for transplantation in SCI. These multifaceted protective and restorative effects from hUCB grafts may be interdependent and they act in harmony to promote therapeutic benefits for SCI. Nevertheless, clinical studies with hUCB are still rare because of the concerns about safety and efficiency. Among these concerns, the major histocompatibility in allogeneic transplantation is an important issue to be addressed in future clinical trials for treating SCI.

Traumatic cervical cord transection without facet dislocations--a proposal of combined hyperflexion-hyperextension mechanism: a case report.

A patient is presented with a cervical spinal cord transection which occurred after a motor vehicle accident in which the air bag deployed and the seat belt was not in use. The patient had complete quadriplegia below the C5 level and his imaging study showed cervical cord transection at the level of the C5/6 disc space with C5, C6 vertebral bodies and laminar fractures. He underwent a C5 laminectomy and a C4-7 posterior fusion with lateral mass screw fixation. Previous reports have described central cord syndromes occurring in hyperextension injuries, but in adults, acute spinal cord transections have only developed after fracture-dislocations of the spine. A case involving a post-traumatic spinal cord transection without any evidence of radiologic facet dislocations is reported. Also, we propose a combined hyperflexion-hyperextension mechanism to explain this type of injury.

Influence of interleukin-6 on the development of peritumoral brain edema in meningiomas.

OBJECT: Peritumoral brain edema (PTBE) is associated with perioperative neurological deficits in patients with meningiomas. However, the pathogenesis of meningioma-associated edema remains unclear. In the present study, the authors investigated the expression of interleukin-6 (IL-6) and its relationship with PTBE in resected meningiomas. METHODS: Thirty-six benign meningiomas obtained in 36 patients were studied retrospectively. Edema volume was assessed on MR images, and an edema index (EI) was calculated. Interleukin-6 mRNA and protein expression were examined by real-time reverse transcriptase polymerase chain reaction and immunohistochemical staining. RESULTS: Peritumoral brain edema was found in 16 patients (44%). Neither age, sex, histological subtype, nor tumor location were related to PTBE. The level of IL-6 mRNA was 7.72 times greater in the edema group (EI > 0.2) than in the nonedema group (EI < 0.2; p = 0.011). On immunohistochemical analysis, IL-6 protein was found localized in the cytoplasm of the tumor cells, and was detected in 12 (75%) of 16 cases of edematous meningiomas, but in only 6 (30%) of 20 nonedematous cases. There was a significant correlation between the severity of PTBE and IL-6 expression (p = 0.004). CONCLUSIONS: The authors' results in this study indicate that IL-6 expression may contribute to the development of brain edema associated with meningiomas.

Rapid spontaneous remission of a spontaneous spinal chronic subdural hematoma in a child.

A 13-year-old boy presented with a rare spontaneous spinal chronic subdural hematoma (SCSDH) with no associated trauma or medical problems manifesting as back and bilateral lower extremity pain persisting for 10 days. Neurological examination revealed mild weakness and paresthesia in both lower extremities. Magnetic resonance (MR) imaging performed 1 week after the appearance of symptoms revealed a chronic subdural hematoma at the thoracolumbosacral region. Follow-up MR imaging performed 1 week later showed significant resolution of the hematoma without the need for surgery. The patient was discharged with only conservative management. This case of spontaneous SCSDH with rapid spontaneous remission in a child not associated with coagulopathy indicates that aggressive surgical treatment should be delayed as long as possible in pediatric patients because the spinal structure is still developing.

Effect of lower two-level anterior cervical fusion on the superior adjacent level.

OBJECT: Symptomatic multisegment disease is most common at the C5-6 and C6-7 levels, and two-level anterior cervical discectomy and fusion (ACDF) is performed most often at these levels. Therefore, it may be clinically important to know whether a C5-7 fusion affects the superior C4-5 segment. A biomechanical study was carried out using cadaveric cervical spine specimens to determine the effect of lower two-level anterior cervical fusion on intradiscal pressure and segmental motion at the superior adjacent vertebral level. METHODS: Five cadaveric cervical spine specimens were used in this study. The specimens were stabilized at T-1 and loaded at C-3 to 15 degrees flexion, 10 degrees extension, and 10 degrees lateral bending before and after simulated two-level ACDF with plate placement at C5-7. Intradiscal pressure was recorded at the C4-5 level, and segmental motion was recorded from C-4 through C-7. Differences in mean intradiscal pressures were calculated and analyzed using a paired Student t-test. When the maximum calibrated intradiscal pressures were exceeded ("overshot") during measurements, data from the specimens involved were analyzed using the motion data with a Student t-test. Values for pressure and motion obtained before and after simulated ACDF were compared. RESULTS: During flexion, the mean intradiscal pressure changes (+/- standard deviations) in the pre- and post-ACDF measurements were 1275 (+/- 225) mm Hg and 2475 (+/- 75) mm Hg, respectively (p < 0.05). When the results of pre-ACDF testing were compared with post-ACDF results, no significant difference was found in the mean changes in the intradiscal pressure during extension and lateral bending. The maximum calibrated intradiscal pressures were exceeded during the post-ACDF testing in four specimens in extension, three in flexion, and two in lateral bending. Comparison of pre- and post-ACDF data for all five specimens revealed significant differences in motion and intradiscal pressure (p < 0.05) during flexion, significant differences in motion (p < 0.05) but not in intradiscal pressure during extension, and significant differences in intradiscal pressure changes (p < 0.05) but not in motion during lateral bending. CONCLUSIONS: Simulated C5-7 ACDF caused a significant increase in intradiscal pressure and segmental motion in the superior adjacent C4-5 level during physiological motion. The increased pressure and hypermobility might accelerate normal degenerative changes in the vertebral levels adjacent to the anterior cervical fusion.