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Yu-Feng Su,1– 3 Tai-Hsin Tsai,2– 4 Keng-Liang Kuo,2,4 Chieh-Hsin Wu,2,4 Cheng-Yu Tsai,1,2 Yen-Mou Lu,5 Shiuh-Lin Hwang,6 Pei-Chen Lin,7 Ann-Shung Lieu,2 Chih-Lung Lin,1,2,4 Chih-Hui Chang1,2,4 1Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 3Division of Neurosurgery, Department of Surgery, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; 4Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 6Department of Spinal Surgery, Chi-Hsien Spine Hospital, Kaohsiung, Taiwan; 7Department of Oral Hygiene, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Chih-Hui Chang, Email chchang20@gmail.comBackground: The aim of this study was to investigate the learning curve of robotic spine surgery quantitatively with the well-described power law of practice.Methods: Kaohsiung Medical University Hospital set up a robotic spine surgery team by the neurosurgery department in 2013 and the orthopedic department joined the well-established team in 2014. A total of consecutive 150 cases received robotic assisted spinal surgery. The 150 cases, with 841 transpedicular screws were enrolled into 3 groups: the first 50 cases performed by neurosurgeons, the first 50 cases by orthopedic surgeons, and 50 cases by neurosurgeons after the orthopedic surgeons joined the team. The time per screw and accuracy by each group and individual surgeon were analyzed.Results: The time per screw for each group was 9.56 ± 4.19, 7.29 ± 3.64, and 8.74 ± 5.77 minutes, respectively, with p-value 0.0017. The accuracy was 99.6% (253/254), 99.5% (361/363), and 99.1% (222/224), respectively, with p-value 0.77. Though the first group took time significantly more on per screw placement but without significance on the nonlinear parallelism F-test. Analysis of 5 surgeons and their first 10 cases of short segment surgery showed the time per screw by each surgeon was 12.28 ± 5.21, 6.38 ± 1.54, 8.68 ± 3.10, 6.33 ± 1.90, and 6.73 ± 1.81 minutes. The first surgeon who initiated the robotic spine surgery took significantly more time per screw, and the nonlinear parallelism test also revealed only the first surgeon had a steeper learning curve.Conclusion: This is the first study to demonstrate that differences of learning curves between individual surgeons and teams. The roles of teamwork and the unmet needs due to lack of active perception are discussed.Keywords: human computer communication, human–robot collaboration, learning curve, robotic spine surgery, teamwork

Background: The aim of this study was to investigate the learning curve of robotic spine surgery quantitatively with the well-described power law of practice.Methods: Kaohsiung Medical University Hospital set up a robotic spine surgery team by the neurosurgery department in 2013 and the orthopedic department joined the well-established team in 2014. A total of 150 cases and 841 transpedicular screws were enrolled into 3 groups: the first 50 cases performed by neurosurgeons, the first 50 cases by orthopedic surgeons, and 50 cases by neurosurgeons after the orthopedic surgeons joined the team. The time per screw and accuracy by each group and individual surgeon were analyzed.Results: The time per screw for each group was 9.56±4.19, 7.29±3.64, and 8.74±5.77 minutes respectively. The accuracy was 99.6% (253/254), 99.5% (361/363), and 99.1% (222/224), respectively. The first group took significantly more time per screw, but without significance on the nonlinear parallelism test. Analysis of 5 surgeons and their first 10 cases of short segment surgery showed the time per screw by each surgeon was 12.28±5.21, 6.38±1.54, 8.68±3.10, 6.33±1.90, and 6.73±1.81 minutes. The first surgeon who initiated the robotic spine surgery took significantly more time per screw and the nonlinear parallelism test also revealed only the first surgeon had a steeper learning curve. Conclusions: This is the first study to demonstrate that differences of learning curves between individual surgeons and teams. The roles of teamwork and the unmet needs due to lack of active perception are discussed.

We present the case of a 2-year-old boy with progressive left-sided weakness and a cranial magnetic resonance imaging (MRI) scan showing a lesion with a cystic component in the right thalamus and basal ganglia. The lesion was subtotally resected and diagnosed as a pilocytic astrocytoma by histopathology. Tumor seeding along the surgical tract was seen on MRI 16 days and 10 weeks after surgery. The patient received vincristine and carboplatin, and MRI performed 4 months after chemotherapy revealed no additional or residual lesions. This case illustrated that a World Health Organization grade I astrocytoma could disseminate along the surgical tract.

The target controlled infusion (TCI) of propofol with fentanyl facilitates easy titration of the depth of anesthesia, and thereby may improve the quality of anesthesia. The aim of this study is to investigate if propofol TCI-based anesthesia is practical for anterior cervical discectomy and fusion (ACDF), one of the most common surgical interventions in spine procedures, when compared with sevoflurane-based anesthesia with respect to the quality of anesthesia. Patients were classified into two groups according to the anesthesia regimen of maintenance of anesthesia with fentanyl and either propofol TCI (group FP) or inhalational sevoflurane (group FS), respectively. The primary endpoint was to evaluate quality of anesthesia and extubation time. Secondary endpoints were hemodynamic stability during the operation, operative fentanyl consumption, and postoperative complications. The study results revealed there were comparable results on time to extubation, changes in intraoperative hemodynamic parameters, and the occurrence of postoperative complications between the groups. No differences in average length of intensive care unit (ICU) stay and hospital stay were noticed. However, opioid consumption and blood loss during the operation for patients in group FP were significantly higher than those of patients in group FS (551.28 ± 193.98 vs. 446.86 ± 177.15 μg, p = 0.005; 52.06 ± 58.25 vs. 28.33 ± 40.74 mL, p = 0.019, respectively). In these adult patients undergoing ACDF, propofol TCI-based anesthesia appears to be as efficacious as sevoflurane-based anesthesia but consumed more fentanyl and experienced higher blood loss.

Study design: Experimental study. Objectives: To investigate a modified compression model of spinal cord injury (SCI) in adult rats by using a room-air- inflated Fogarty balloon catheter. Setting: Kaohsiung, Taiwan. Methods: The rats were divided into injury, sham-operated and control groups. A 2-French Fogarty catheter was passed from the lumbar spine (L3–L4) epidurally, with a mini-laminectomy under the microscope, to the level of thoracic spine (T6–T7). The actual site of the catheter tip was confirmed with X-ray. The balloon of Fogarty catheter then was inflated with room air, 0.2 ml, for 10 min. Mini-laminectomy was performed without inserting the catheter in the sham-operated group. Quantitative neurological outcomes were evaluated with the Basso, Beattie and Bresnahan (BBB) locomotor rating scale daily. The gene expression of nitric oxide synthases (NOSs) of the spinal cord was investigated at the end of the functional assessment. Results: The mean BBB locomotor scores were 10±1.85 and 10±1.85, respectively, on days 1 and 3 in the injury group, and 21 and 20.29±0.69, respectively, in the sham-operated group. There was a significantly increased gene expression of inducible NOS in the SCI group compared with the sham-operated group and control group. Endothelial NOS gene expression was not significantly different among the groups. Conclusion: The functional and molecular assessments show that this modified balloon-compression technique is a reproducible, simple and inexpensive model of SCI in rats.

Object The authors sought to analyze trends in hospital resource utilization and mortality rates in a population of patients who had received traumatic brain injury (TBI) surgery. Methods This nationwide population-based cohort study retrospectively analyzed 18,286 patients who had received surgical treatment for TBI between 1998 and 2010. The multiple linear regression model and Cox proportional hazards model were used for multivariate assessment of outcome predictors. Results The prevalence rate of surgical treatment for patients with TBI gradually but significantly (p < 0.001) increased by 47.6% from 5.0 per 100,000 persons in 1998 to 7.4 per 100,000 persons in 2010. Age, sex, Deyo-Charlson comorbidity index score, hospital volume, and surgeon volume were significantly associated with TBI surgery outcomes (p < 0.05). Over the 12-year period analyzed, the estimated mean hospital treatment cost increased 19.06%, whereas the in-hospital mortality rate decreased 10.9%. The estimated mean time of overall survival after TBI surgery (± SD) was 83.0 ± 4.2 months, and the overall in-hospital and 1-, 3-, and 5-year survival rates were 74.5%, 67.3%, 61.1%, and 57.8%, respectively. Conclusions These data reveal an increased prevalence of TBI, especially in older patients, and an increased hospital treatment cost but a decreased in-hospital mortality rate. Health care providers and patients should recognize that attributes of the patient and of the hospital may affect hospital resource utilization and the mortality rate. These results are relevant not only to other countries with similar population sizes but also to countries with larger populations.

Intraoperative intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were evaluated for use as prognostic indicators after surgery for severe traumatic brain injury (TBI), and threshold ICP and CPP values were determined to provide guidelines for patient management. This retrospective study reviewed data for 66 patients (20 females and 46 males) aged 13–83 years (average age, 48 years) who had received decompressive craniectomy and hematoma evacuation for severe TBI. The analysis of clinical characteristics included Glascow Coma Scale score, trauma mechanism, trauma severity, cerebral hemorrhage type, hematoma thickness observed on computed tomography scan, Glasgow Outcome Scale score, and mortality. Patients whose treatment included ICP monitoring had significantly better prognosis (p

Summary A unique case of pilocytic astrocytoma (PCA) with leptomeningeal dissemination occurring after surgery in a 2-year-old boy who presented with progressive left-sided weakness is reported. A cranial magnetic resonance imaging (MRI) disclosed a lesion with a cystic component in the right thalamus and basal ganglia. The lesion was subtotally resected and diagnosed by the pathology department to be a PCA. An MRI 16 days after surgery revealed a residual tumor with a tumor seeding along the surgical tract and in the meninges. The patient then underwent chemotherapy and a cranial MRI. Eleven months later the patient did not disclose any residual or additional lesions. The patient continues to do well at the time of this writing. This case illustrates a unique instance of leptomeningeal dissemination through the surgical tract of a resected cerebral PCA in a child.

SummaryPurposeTo assess clinical outcomes and kinematic changes in bridged and adjacent segments after hybrid stabilization by interbody fusion.BackgroundConventional management for multilevel lumbar degenerative disc disease is limited to either fusion or nonfusion surgery alone. The severity of degeneration and instability in multilevel lumbar degenerative disc disease vary widely. Therefore, surgical treatment for multilevel lumbar degenerative disc disease is usually performed in a single stage by either fusion, nonfusion, or a hybrid technique. To the best of our knowledge, no kinematic study of a Dynesys fusion–nonfusion technique has yet been reported.MethodsThis study analyzed 28 patients who had undergone posterior lumbar interbody fusion with posterior dynamic stabilization fixation for spondylolisthesis with adjacent level stenosis between May 2007 and June 2008. All patients were followed up for at least 2 years. Clinical characteristics were then retrospectively reviewed. The visual analog scale (VAS) was used to score both lower limb pain and back pain. Patient functioning was evaluated using the Oswestry Disability Index (ODI).ResultsBoth VAS and ODI significantly improved during the follow-up period (p

Background Apoptosis is implicated in vasospasm and the long-term sequelae of subarachnoid hemorrhage (SAH). This study tested the hypothesis that attenuation of SAH-induced apoptosis after 17β-estradiol (E2) treatment is associated with an increase in phosphorylation of Akt via estrogen receptor-α (ER-α) in rats. Materials and methods We examined the expression of phospho-Akt, ERα and ERβ, and apoptosis in cerebral cortex, hippocampus, and dentate gyrus in a two-hemorrhage SAH model in rats. We subcutaneously implanted other rats with a silicone rubber tube containing E2; they received daily injections of nonselective estrogen receptor antagonist (ICI 182,780), selective ERα-selective antagonist (methyl-piperidino-pyrazole), or ERβ-selective antagonist (R,R-tetrahydrochrysene) after the first hemorrhage. Results At 7 d after the first SAH, protein levels of phospho-Akt and ERα were significantly decreased and caspase-3 was significantly increased in the dentate gyrus. The cell death assay revealed that DNA fragmentation was significantly increased in the dentate gyrus. Those actions were reversed by E2 and blocked by ICI 182,780 and methyl-piperidino-pyrazole, but not R,R-tetrahydrochrysene. However, there were no significant changes in the expression of the protein levels of phospho-Akt, ERα, ERβ, and caspase-3, and DNA fragmentation after SAH. Conclusions The present study shows that a beneficial effect of E2 in attenuating SAH-induced apoptosis is associated with activation of the expression of phospho-Akt and ERα, and alteration in caspase-3 protein expression via an ERα-dependent mechanism in the dentate gyrus. These data support further the investigation of E2 in the treatment of SAH in humans.

Object Most reports compare artificial neural network (ANN) models and logistic regression models in only a single data set, and the essential issue of internal validity (reproducibility) of the models has not been adequately addressed. This study proposes to validate the use of the ANN model for predicting in-hospital mortality after traumatic brain injury (TBI) surgery and to compare the predictive accuracy of ANN with that of the logistic regression model. Methods The authors of this study retrospectively analyzed 16,956 patients with TBI nationwide who were surgically treated in Taiwan between 1998 and 2009. For every 1000 pairs of ANN and logistic regression models, the area under the receiver operating characteristic curve (AUC), Hosmer-Lemeshow statistics, and accuracy rate were calculated and compared using paired t-tests. A global sensitivity analysis was also performed to assess the relative importance of input parameters in the ANN model and to rank the variables in order of importance. Results The ANN model outperformed the logistic regression model in terms of accuracy in 95.15% of cases, in terms of Hosmer-Lemeshow statistics in 43.68% of cases, and in terms of the AUC in 89.14% of cases. The global sensitivity analysis of in-hospital mortality also showed that the most influential (sensitive) parameters in the ANN model were surgeon volume followed by hospital volume, Charlson comorbidity index score, length of stay, sex, and age. Conclusions This work supports the continued use of ANNs for predictive modeling of neurosurgery outcomes. However, further studies are needed to confirm the clinical efficacy of the proposed model.

Object The purpose of this study was to evaluate temporal trends in traumatic brain injury (TBI); the impact of hospital volume and surgeon volume on length of stay (LOS), hospitalization cost, and in-hospital mortality rate; and to explore predictors of these outcomes in a nationwide population in Taiwan. Methods This population-based patient cohort study retrospectively analyzed 16,956 patients who had received surgical treatment for TBI between 1998 and 2009. Bootstrap estimation was used to derive 95% confidence intervals for differences in effect sizes. Hierarchical linear regression models were used to predict outcomes. Results Patients treated in very-high-volume hospitals were more responsive than those treated in low-volume hospitals in terms of LOS (−0.11; 95% CI −0.20 to −0.03) and hospitalization cost (−0.28; 95% CI −0.49 to −0.06). Patients treated by high-volume surgeons were also more responsive than those treated by low-volume surgeons in terms of LOS (−0.19; 95% CI −0.37 to −0.01) and hospitalization cost (−0.43; 95% CI −0.81 to −0.05). The mean LOS was 24.3 days and the average LOS for very-high-volume hospitals and surgeons was 61% and 64% shorter, respectively, than that for low-volume hospitals and surgeons. The mean hospitalization cost was US $7,292.10, and the average hospitalization cost for very-high-volume hospitals and surgeons was 19% and 22% lower, respectively, than that for low-volume hospitals and surgeons. Advanced age, male sex, high Charlson Comorbidity Index score, treatment in a low-volume hospital, and treatment by a low-volume surgeon were significantly associated with adverse outcomes (p < 0.001). Conclusions The data suggest that annual surgical volume is the key factor in surgical outcomes in patients with TBI. The results improve the understanding of medical resource allocation for this surgical procedure, and can help to formulate public health policies for optimizing hospital resource utilization for related diseases.

Summary Pilocytic astrocytoma (PCA) is a common benign astrocytic tumor in children that usually arises in the cerebellum, brainstem, hypothalamic region, or optic pathways. It can also arise in the spinal cord as an intradural intramedullary PCA. In rare cases, it presents with leptomeningeal dissemination, which leads to a poor clinical outcome. We present a rare case of spinal cord pilocytic astrocytoma with leptomeningeal dissemination to the brain and spine with rapid progression. We present a 13-year-old girl with progressive weakness of her right arm. An intramedullary hypervascular neurogenic tumor at the C3–C6 level was identified by magnetic resonance imaging (MRI) and surgical excision was performed. PCA was proven by pathology. The tumor recurred 3 months later and an intramedullary polycystic astrocytoma at the C1–T1 level was confirmed by MRI. Total tumor resection was performed and pathological characteristics again confirmed PCA. However, diplopia with blurred vision was noted 1 month after the last surgery, which was accompanied by signs of increased intracranial pressure (IICP). MRI indicated leptomeningeal enhancement in the brain and tumor seeding along the spinal cord. Chemotherapy and radiotherapy were administered, but the clinical course rapidly deteriorated and the patient died of respiratory distress. Although the prognosis for low-grade astrocytomas is good in most reported studies, this case showed leptomeningeal dissemination with a rapid course that resulted in death. A fatal outcome might be anticipated when encountering difficult intramedullary spinal cord lesions, as in our case.

Transforming growth factor-beta 1 (TGF-β1) has been reported to be a possible marker for a number of tumors, including brain tumors. The aim of this study was to measure the plasma levels of TGF-β1 in patients with low- and high-grade astrocytomas before and after surgery. This prospective study included 14 patients with low-grade astrocytomas and 25 with high-grade astrocytomas who underwent tumor removal and 13 controls (patients who underwent cranioplasty for skull bone defects). Plasma levels of TGF-β1 were measured in all subjects using enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis showed that when the level of TGF-β1 before tumor removal was ≥ 2.52 ng/ml, astrocytoma was predicted with a sensitivity of 94.9% and specificity of 100%. The mean plasma level of TGF-β1 in both the low-grade and high-grade astrocytoma groups significantly decreased after tumor removal (p0.05); there was no significant change in TGF-β1 plasma level of the controls following surgery. Patients with high-grade astrocytomas had a significantly higher mortality rate than patients with low-grade astrocytomas (p=0.019) and significantly shorter survival (p=0.008). A positive correlation between TGF-β1 level after tumor removal and tumor volume was only found in the high-grade astrocytoma group (γ=0.597, p=0.002). The findings show that plasma TGF-β1 level was increased in patients with low-grade and high-grade astrocytoma, and that the levels significantly decreased after tumor removal in both groups. The results provide additional evidence that TGF-β1 might be useful as a tumor marker for astrocytomas.

Increased nuclear factor κB (NF-κB) bioexpression, as well as TNF-α, IL-1β and IL-6 levels, were observed after aneurysmal subarachnoid hemorrhage (SAH). It is of interest to investigate the effect of 6-mercaptopurine (6-mp) on cytokines/NF-κB in this SAH model. A rodent double-hemorrhage SAH model was employed. Serum and cerebrospinal fluid (CSF) samples were collected to examine IL-1, IL-6 and TNF-α levels. NF-κB subunit p65 and its inhibitor of nuclear factor κB (IκB) were examined (by Western blot). TNF-α was used to induce the phosphorylation of IκB in the presence or absence of 6-mp. Nuclear NF-κB subunit p65/IκB kinase in the basilar artery was over-expressed, and cytokines was notably increased in the SAH groups, compared with the controls (P

Transforming growth factor (TGF) β1 may be a candidate for a serologic tumor marker. In this study, the plasma levels of TGF-β1 in patients with brain tumors were measured using enzyme-linked immunosorbent assay before and after tumor removal. Patients were divided into four groups, the control group and the benign, malignant, and metastatic brain tumor groups. All brain tumor groups showed significant increases in the levels of TGF-β1 before tumor removal (6.36 ± 3.94, 17.0 ± 9.7, and 12.2 ± 10.3 ng/ml for the benign, malignant, and metastatic groups, respectively). When compared with the results obtained in the control group (1.12 ± 0.74 ng/ml), significant decreases in TGF-β1 concentrations after total tumor removal were found in both the benign and malignant brain tumor groups (2.55 ± 2.00 and 8.93 ± 5.73 ng/ml, respectively; p = 0.0001 and p = 0.003, respectively). On the other hand, plasma TGF-β1 levels in the metastatic brain tumor group showed a slight but significant increase (14.7 ± 9.3 ng/ml, p = 0.035) after tumor removal. In a case of low-grade astrocytoma, plasma levels of TGF-β1 were found to be 3.6 and 1.1 ng/ml before and after tumor removal, respectively. However, recurrent tumor was noted in this patient 7 months later, and the levels of TGF-β1 were 26.2 and 8.4 ng/ml before and after the second operation, respectively. The data show that plasma TGF-β1 was elevated in the circulation of patients with brain tumors and that significant decreases in TGF-β1 levels were observed after the removal of benign and malignant tumors. The results also suggest that TGF-β1 may be a useful serologic marker for brain tumors.

BACKGROUND AND IMPORTANCE Symptomatic lumbar disc herniation is common. Migration of a free disc fragment is usually found in rostral, caudal, or lateral directions. Posterior epidural migration is very rare. We report the first case with posterior epidural migration and sequestration into bilateral facet joints of a free disc fragment. CLINICAL PRESENTATION A 78-year-old female presented with low back pain and right leg pain. Plain radiographs showed lumbar spondylolisthesis. Magnetic resonance imaging revealed a posterior epidural mass and intrafacet mass, which was hypointense on T1-weighted images and hyperintense on T2-weighted images. The lesion in the left L3-4 facet joint had rim enhancement, whereas the right one was not contrasted after gadolinium injection. Preoperative differential diagnosis included abscess, tumor, hematoma, or synovial cyst. An interbody cage fusion at L3-4 and L4-5 for spondylolisthesis was performed, and a hybrid technique was applied with the Dynesys flexible rod system at L3-S1 for multisegment degenerative disc disease. The lesion proved to be an epidural disc fragment with sequestration into bilateral facet joints. CONCLUSION A free disc fragment should be considered in the differential diagnosis of posterior epidural lesions, and even in the facet joint.

Eosinophilic granuloma (EG) refers to the most common and benign form of the disorder known as Langerhans’ cell histiocytosis. The disease is typically found in children and adolescents and rarely affects adults. We present a case of EG in the occipital bone in a 36-year-old man, who visited our hospital with the chief complaint of left occipital palpable tumor mass with local tenderness and pain for one month. An X-ray of the skull revealed a rounded osteolytic lesion. A computed tomography scan revealed a shadow of soft tissues in the left occipital site involving the entire thickness of the calvaria, which was indicative of marked destruction of the bone. The soft mass was successfully removed. The margins of the skull lesion were excised, and cranioplasty was performed simultaneously with bone cement. A definitive diagnosis of EG was made by histopathology and immunohistochemical detection of S-100 antigen in the tissue samples. With respect to management, we believe surgery is the best option for most accessible cranial lesions of EG. A cranioplasty with bone cement or autologous bone can be performed in the same session to repair the cranial defect.

Increased endothelin-1 (ET-1) production and diminished nitric oxide synthase (NOS) bioavailability has been observed in aneurysmal subarachnoid hemorrhage (SAH). The authors previously found that 6-mercaptopurine (6-mp) is effective in preventing and reversing arterial narrowing in a rodent SAH model. This present study is of interest to examine the effect of 6-mp on ET-1/endothelial nitric oxide synthase (eNOS) in this animal model.A rodent double hemorrhage SAH model was employed. Animals were randomly assigned to six groups (sham, SAH only, vehicle, 0.5, 1.0 and 2 mg kg(-1) day(-1) 6-mp treatment). Monoclonal CD45 immunostaining was utilized to evaluate monocytes and microglia. The level of pro-inflammatory cytokines, such as IL-1, IL-6 and TNF-α(RT-PCR), and ET-1 (ELISA) was measured. The basilar arteries (BAs) were harvested and sliced, and their cross-sectional areas were determined. Radiolabeled NOS assay kit was applied to detect eNOS.Morphologically, convolution of internal elastic lamina, endothelial cells distortion, and necrotic smooth muscle were prevalently present in the basilar artery of SAH groups, which was absent in the 1 and 2 mg kg(-1) day(-1) 6-mp plus SAH group or the healthy controls. Significant vasospasm was noted in the vehicle group (lumen patency, 54.6%, p ≤ 0.01 compared with the sham group), but it was less prominent in the 2 mg kg(-1) day(-1) 6-mp treatment group (lumen patency, 87.6%, p 0.05). In addition, administration with 2 mg kg(-1) day(-1) 6-mp reduced cytokine levels by 11%, 47%, and 34% for IL-1, IL-6, and TNF-α, respectively, and increased ET-1 levels were found in all the animals subject to SAH (SAH only, SAH plus vehicle, SAH plus 0.5 and 1.0 mg kg(-1) day(-1) 6-mp) except in the 2 mg kg(-1) day(-1) 6-mp SAH group, when compared with the healthy controls (no SAH). Meanwhile, treatment with 6-mp did not induce the levels of expressed eNOS in BAs in the 6-mp groups (0.5, 1.0, and 2 mg kg(-1) day(-1) 6-mp plus SAH) when compared with that in the SAH groups (p 0.1).In summary, treatment with 6-mp decreased the release of pro-inflammatory cytokines and diminished experimental vasospasm. This study offered first evidence that 6-mp dose-dependently reduces the level of ET-1 in a NO-independent mechanism, which corresponds to its antivasospastic effect in the condition of chronic vasospasm.

Induced endothelin-1 (ET-1) production and decreased nitric oxide synthase (NOS) bioavailability have been found in aneurysmal subarachnoid hemorrhage (SAH). Atorvastatin is recognized to have pleiotropic effects including increasing NOS bioavailability as well as reducing inflammation and oxidative damage other than reducing dyslipidemia. This study is of interest to examine the effect of atorvastatin on ET-1/endothelial nitric oxide synthase (eNOS) in experimental SAH.A rodent double-hemorrhage SAH model was employed. Animals were randomly assigned as sham-operated, SAH, vehicle plus SAH, 5 mg/day atorvastatin treatment plus SAH and 5 mg/day atorvastatin precondition plus SAH groups. Administration with atorvastatin (5 mg/day) was initiated 1 week before (precondition) and 24 hr later (treatment). Cerebrospinal fluid samples were collected at 72 hr after second SAH. ET-1 (ELISA) was measured. The basilar arteries (BAs) were harvested and sliced, and their cross-sectional areas were measured. Radiolabeled NOS assay kit was used to detect eNOS.Morphologically, convoluted internal elastic lamina, distorted endothelial cells and myonecrosis of the smooth muscle were predominantly observed in the BA of SAH and vehicle-treated SAH groups, which was not detected in the atorvastatin-preconditioned SAH group or the healthy controls. Significant vasospasm was noted in the vehicle group (lumen potency 64.5%, compared with the sham group, p/= 0.01) and less prominent in the atorvastatin treatment group (lumen potency, 76.6%, p0.05). In addition, increased ET-1 levels were found in all the animals subject to SAH (SAH only, SAH plus vehicle and SAH plus atorvastatin reversal) except in the atorvastatin precognition group when compared with the healthy controls (no SAH). Likewise, the levels of expressed NOS in BAs is induced in the atorvastatin groups (both atorvastatin treatment and precondition) when compared with that in the SAH group (p0.01).This study offers first evidence that atorvastatin in the preconditioning status reduces the level of ET-1, which corresponds to its antivasospastic effect in the condition of chronic vasospasm. Although there is increased expression of NOS in both atorvastatin precondition and reversal groups, BA's lumen potency is significantly increased in the atorvastatin precondition group when compared with the SAH group (p0.01).

RNA interference (RNAi) has recently emerged as an efficient method to silence gene expression in mammalian cells by transfection of small interfering RNAs (siRNAs). The Janus kinase 3 (JAK3) is also pertinent to the development of a new immuno-suppressant. This study aimed to inhibit JAK3 expression using RNAi to determine allograft tolerance. To silence JAK3 expression, one dsRNA was tested to incorporate the JAK3 mRNA sequence. The expression vector containing the pre-mRNA expression cassette was transfected into rat basophilic leukemia cell line, RBL-2H3, for RNAi analysis (in vitro). The alloskin and composite tissue allograft were then transplanted to recipients using RNAi protocol to determine the allograft tolerance (in vivo). The results showed effective in vitro and in vivo downregulation of JAK3 expression by RNAi. Moreover, the histology of alloskin graft and composite tissue allograft (in vivo) under the siRNA showed more prominently diminished inflammatory infiltration than the control group. This is the first time in the literature that the suppressive effect of JAK3 silenced by siRNA has been tested both in vitro and in vivo, and shows that siRNA is capable of specific and functional silencing in allograft rejection.

Dendritic cells (DCs) are now recognised as the most potent professional antigen presenting cells (APCs) involved in initiating primary immune responses. The medicinal mushroom Antrodia camphorata (AC) is one of the most popular chemopreventive mushrooms in Taiwan. Polysaccharides of mushroom products are among emerging new agents that activate maturation and functions of DCs. The aim of this study is to investigate the immunomodulating activity of A. camphorata extract (ACW) on functional maturation of DCs. Compared with lipopolysaccharides (LPS), ACW effectively promoted the functional maturation of DCs in the expression of phenotypic characteristics and IL-12 production and chemotaxic activity. Moreover, ACW increased the phosphorylation of Akt, p38, and JNK/MAPKs in DCs. Specific inhibitors, SB203580 and LY94002, significantly blocked the ACW-induced up-regulation of costimulatory factor expression, IL-12 production. These findings suggest that ACW is a potent adjuvant for cancer immunotherapy and promotes Th1 immune responses.

The endemic species of Antrodia camphorate (AC) is a promising chemotherapeutic drug for cancer. We found that the ethanol extract from wild fruiting bodies of Antrodia camphorata (EEAC) could induce HL 60 cells apoptosis via histone hypoacetylation, up-regulation of histone deacetyltransferase 1 (HDAC 1), and down-regulation of histone acetyltransferase activities including GCN 5, CBP and PCAF in dose-dependent manner. In combination with histone deacetylase inhibitor, trichostatin A (TSA), did not block EEAC-induced apoptosis. Interestingly, combined treatment (100 nM of TSA and 100 microg/ml EEAC) caused synergistic inhibition of cell growth and increase of apoptotic induction. EEAC could effectively increase the cytotoxic sensitivity of TSA through the up-regulation of DR5 and NFkappaB activation. In this present study, bioassay-guided fractionation of EEAC led to a major active compound, zhankuic acid A, as the bioactive marker. Moreover, our findings may represent an experimental basis for developing EEAC as a potential chemotherapeutic adjuvant.

A 53-year-old man presented with a history of slight weakness in the right lower limb. Giant invasive cauda equina schwannoma was diagnosed according to the criteria of Sridhar et al. Schwannomas are usually benign and common tumors arising from nerve sheath cells, particularly from sensory nerves. Giant invasive schwannomas, however, are rare, and most of patients with them present with severe neurologic deficits independent of daily activity, although in the case presented here, in spite of the large size of the tumor causing pedicle erosion, expansive destruction of the vertebral body and widening of the neural foramina, there were only minimal neurologic deficits. We have therefore decided to report this case, with a review of the relevant English literature emphasizing clinical presentations, plain film images and magnetic resonance image findings of giant invasive cauda equina schwannoma for early diagnosis and differential diagnosis.

Background Coldness, numbness, or causalgia usually affects the lower limbs in patients after back surgeries. The treatment of causalgia is still the source of continuing debate. We treated patients presenting with causalgia secondary to LD with CT-guided CLS and determined the therapeutic outcome at long-term follow-up. Methods From January 2002 to December 2002, a total of 15 patients (16 limbs) with causalgia after LD underwent the percutaneous CT-guided CLS. There were 7 male patients and 8 female patients, with an average age of 49.1 years. A total of 14 patients underwent unilateral procedures, and 1 patient underwent staged bilateral procedures. We followed up our patients for at least 24 months (24-36 months). Results There were 13 patients (14 limbs) diagnosed as Drucker stage I and 2 patients as stage II. There were 88% (14 limbs) that had an early satisfactory outcome after CLS and 75% (12 limbs) that had a late satisfactory outcome (more than 24 months after CLS). Stage I patients had more satisfying early and late outcome than stage II patients ( P = .014 and P = .039, respectively). Female patients were more likely to have satisfactory late outcome than male patients ( P = .034). There was no operative mortality. A patient had a complication of genitofemoral neuralgia, which had recovered in a month. Conclusions We concluded that the percutaneous CT-guided CLS is an easy, safe, and reproducible technique, and it carries long-term benefit to patients with pain after LD presenting with causalgia, especially for patients with Drucker stage I and female patients.

The authors sought to analyze trends in hospital resource utilization and mortality rates in a population of patients who had received traumatic brain injury (TBI) surgery.This nationwide population-based cohort study retrospectively analyzed 18,286 patients who had received surgical treatment for TBI between 1998 and 2010. The multiple linear regression model and Cox proportional hazards model were used for multivariate assessment of outcome predictors.The prevalence rate of surgical treatment for patients with TBI gradually but significantly (p0.001) increased by 47.6% from 5.0 per 100,000 persons in 1998 to 7.4 per 100,000 persons in 2010. Age, sex, Deyo-Charlson comorbidity index score, hospital volume, and surgeon volume were significantly associated with TBI surgery outcomes (p0.05). Over the 12-year period analyzed, the estimated mean hospital treatment cost increased 19.06%, whereas the in-hospital mortality rate decreased 10.9%. The estimated mean time of overall survival after TBI surgery (± SD) was 83.0 ± 4.2 months, and the overall in-hospital and 1-, 3-, and 5-year survival rates were 74.5%, 67.3%, 61.1%, and 57.8%, respectively.These data reveal an increased prevalence of TBI, especially in older patients, and an increased hospital treatment cost but a decreased in-hospital mortality rate. Health care providers and patients should recognize that attributes of the patient and of the hospital may affect hospital resource utilization and the mortality rate. These results are relevant not only to other countries with similar population sizes but also to countries with larger populations.

Anterior discectomy and fusion to treat cervical degenerative disc disease is the preferred procedure for many spine surgeons. The ideal device for structural reconstruction of the anterior cervical spine remains controversial. The purpose of this prospective study was to investigate the effectiveness of a non-threaded titanium cage in performing anterior spinal fusion for cervical degenerative disc disease. The clinical and radiologic data of 78 consecutive patients were reviewed. Neurologic outcome was assessed using Odom's criteria. Neck pain was graded using a 10-point visual analog scale. The cervical spinal curvature, the height of foramina, and fusion status were evaluated on preoperative and postoperative radiographs. Mean follow-up was 24.9 (range 18-35) months. An excellent or good result was found in 92% of the patients with radiculopathy, 69% of those with myelopathy, and 73% of those with myeloradiculopathy. Statistical analyses also showed improvement of cervical pain after surgery (P < 0.001) and a significant increase in foraminal height (P = 0.035). Cervical kyphosis was present in 27 (34%) patients before surgery; it was corrected to lordosis in 9. The fusion rate at 12 months and 24 months was 91% and 95%, respectively. No surgery or cage-related complication occurred in these patients. Non-threaded interbody cage fusion in this study achieved a high fusion rate and had a good neurologic outcome. These results suggest that non-threaded cage fusion is a safe and effective method for anterior cervical discectomy.

Selective transforaminal periradicular infiltration with local corticosteroids and anesthetics has been performed for preoperative evaluation of lumbosacral pain and for patients with sciatia. From July 2001 to November 2003, 143 patients with unilateral sciatica were treated with computed tomography (CT)-guided transforaminal periradicular infiltration. Needle puncture was possible without difficulty in all patients. Of all 143 infiltrations, 140 were followed up with the recovery of leg and back pain and improvement of the straight leg-raising test (SLRT). Minor complications were seen, but major complications and mortality did not occur in our series. In summary, CT guidance allows safe and precise needle positioning, and it can readily demonstrate the spread of the medications in the exact periradicular space.

Background: Recent studies have demonstrated that Rac is a regulator of cell morphology and growth. Rac1 gene appears to have involvement in tumorigenesis and metastatic potential. In our previous study of rac1 gene in 45 human brain tumors, rac1 pseudogene was found. The rac1 pseudogene is an intronless pseudogene and has a similarity of 86% with rac1 nucleotide sequence. The rac1 pseudogene contains 579 nucleotides and only 46 amino acids can be translated. Little is known about the expression of rac1 pseudogene in human tissues or tumors. Materials and Methods: The expression of rac1 gene and rac1 pseudogene in different human tissues and brain tumors was investigated by the use of reverse transcriptase-polymerase chain reaction and Northern blotting. Results: The rac1 gene is apparently expressed in these 8 human tissues. The rac1 pseudogene is also apparently expressed in human tissues except for brain tissue. The overexpression of rac1 gene in brain tumors was 8% (2/25) and the overexpression of rac1 pseudogene was 76.9% (20/26). Only two astrocytomas had overexpression of rac1 gene, compared with normal brain tissues. The overexpression of rac1 pseudogene was 6 of 9 in meningiomas, 7 of 9 in astrocytomas, and 7 of 8 in pituitary adenomas. Conclusions: High frequency of overexpression of rac1 pseudogene was detected in the human brain tumors when compared with that expressed in the normal brain tissues. Our study suggested that the rac1 pseudogene may play an important role of the tumorigenesis of brain.

Spontaneous intraspinal intramedullary hemorrhage is a rare isease that usually presents as myelopathy. There are limited umbers of reports in the literature, and most of them were caused y vascular lesions, tumors or anticoagulant treatment. A few cases ave occurred with unknown etiology [1–5]. We present two cases f idiopathic spontaneous intramedullary hemorrhage and review he reported literature.

Simultaneous occurrence of multiple intracerebral haemorrhages (ICHs) in different arterial territories is a rare clinical event which has been reported to be associated with cerebral amyloid angiopathy, venous sinus thrombosis, coagulopathy, vasculitis, haemorrhagic transformation of cerebral infarcts and multiple intracranial pathologies such as vascular anomalies or tumours. Although hypertension is the most common etiological factor for the development of spontaneous single intracerebral bleeding, its role in simultaneous multiple ICHs is not clear.The authors have reviewed all patients with non-traumatic ICH admitted to Kaohsiung Medical University Hospital from 1993 to 2002. Ten hypertensive patients with simultaneous multiple ICHs were found. For the purpose of comparison, another 600 cases with solitary hypertensive ICH were also reviewed as a control group. Computerized tomographic scans and medical records concerning patients' histories, clinical presentations, locations of haematomas, associated risk factors, and outcome were analyzed.The mean age and sex distribution were similar in both patient groups. Bilateral putaminal or thalamic haemorrhages were the most common combinations of simultaneous bleedings. As for the individual location of haematoma, there was a strong preponderance for the supratentorial space with the thalamus being the most preferable site. The duration of hypertension was longer and the percentage of previous stroke was higher in patients with multiple ICHs. Other associated risk factors were similar in both groups except for higher incidence of hypercholesterolemia in multiple ICHs group. Patients with simultaneous multiple ICHs had a much worse outcome compared to those with solitary ICH.As with solitary ICH, hypertension is still the most important etiological factor for simultaneous multiple ICHs. The widespread and prolonged degeneration of intracerebral arterioles predispose patients to the development of multiple ICHs, which could be justified by the longer history of hypertension and higher incidence of former strokes. Only hypercholesterolemia was identified to be significantly associated with this unusual brain event in our study. The mechanism underlying the development of simultaneous multiple ICHs is not clear although structural and haemodynamic changes of first haemorrhage may be responsible for the second one. Poorer outcome in patients with multiple ICHs can be explained by the concomitant destruction of crossing and non-crossing fiber tracts and bilateral diaschisis phenomenon.

Magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) were evaluated for differentiating metastatic brain tumors, radiation necroses, and brain abscesses. Twelve histologically verified lesions in 12 patients were studied using preoperative MRI and proton MRS. The signal intensities of four major metabolites, N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine and phosphocreatine (Cr), and lactate (Lac), were observed over the region of interest. Metastatic brain tumors showed a decrease in NAA/Cr and an increase in Cho/Cr ratios. Radiation necroses showed a decrease in NAA/Cr and no change in Cho/Cr ratios. Brain abscesses showed an increase in Lac/Cr ratio. Correlation with histopathologic findings showed that a high Cho signal was suggestive of a metastatic brain tumor. Lac signals were observed in brain abscesses, presumably reflecting the anerobic glycolysis of living cells. Although more cases and studies are necessary, metabolic information provided by proton MRS combined with MRI is useful for differentiating among metastatic brain tumors, radiation necroses, and brain abscesses.

Object. Cage-assisted anterior cervical discectomy and fusion (ACDF) has proven to be a safe and effective procedure for the treatment of one- and two-level degenerative disc disease (DDD). To the authors' knowledge, clinical results after three- and four-level interbody cage—augmented ACDF have not been reported in the literature. The authors investigated the safety and effectiveness of titanium cages used in such procedures and evaluated the results in cases with or without plate fixation. Methods. Fifty-six patients suffering from cervical DDD were divided into two groups. Group 1 included 32 patients who underwent titanium cage—assisted ACDF; Group 2 included 24 patients who underwent the same procedure, supplemented with plate fixation. The cervical DDD was confirmed by radiography and magnetic resonance imaging. The patients underwent radiographic evaluation to assess cervical lordosis, segmental height of cervical spine, the height of the foramina, and spinal stability. Neurological outcomes were assessed using the Japanese Orthopaedic Association (JOA) scores. Neck pain was graded using a 10-point visual analog scale (VAS). The follow-up period ranged from 13 to 28 months (mean 17.2 months). In both Groups 1 and 2 significant increase (p < 0.001) was demonstrated in the JOA scores (preoperatively 10.7 ± 2.4 and 11.1 ± 2, postoperatively 13.9 ± 2.2 and 14.1 ± 2.3, respectively) and VAS pain scores (preoperatively 8.8 ± 0.9 and 8.5 ± 1, postoperatively 3.1 ± 2.1 and 2.8 ± 1.8, respectively); however, there was no significant intergroup difference. A significant increase in the cervical lordosis, foraminal height, and segmental height was observed in both groups. Good stability of cage fusion was obtained in both groups 12 months postoperatively (90.6% in Group 1 and 91.7% in Group 2); however, there were no statistically significant intergroup differences. The complication rate in Group 2 was higher than that in Group 1. The hospital length of stay in Group 1 was significantly lower than in Group 2 (p < 0.001). Conclusions. Analysis of these findings demonstrated that titanium cage—assisted ACDF provided long-term stabilization, increased lordosis, increased segmental height, and increased foraminal height. In both groups good neurological outcomes were achieved and donor site morbidity was avoided. The lower complication rate and shorter hospital stay, however, make the cage-assisted fusion without plate fixation better than with plate fixation.