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Intracranial gliomas are the most common primary central nervous system tumors in humans, and glioblastoma multiforme is the most malignant intracranial glioma. The nucleotide-binding domain leucine-rich repeat (NLR)-containing family are crucial regulators of inflammatory and innate immune responses. NLRP12 codes for the monarch-1 protein, which regulates immune responses in humans. Data from a next-generation sequencing database indicated that NLRP12 expression is increased in glioma cells. However, the relationship between NLRP12 levels and gliomas is unclear.To explore the role of NLRP12-related translation factors and proteins in glioma, we evaluated the clinical data and paraffin sections from glioma patients. The expression of NLRP12 was evaluated using immunohistochemical analysis, and clinical parameters were analyzed using chi-square and Kaplan-Meier survival tests.The degree of malignancy and prognosis highly correlated with NLRP12 levels. In addition, the siRNA-mediated downregulation of NLRP12 in glioma cell lines decreased proliferation, invasion, and migration. The levels of VEGF, N-cadherin, and cyclin D1 were downregulated after knockdown of NRLP12 in glioma cell lines, as observed using western blotting in vitro. Knockdown of NLRP12 attenuated the tumor progression in vivo.The expression of NLRP12 may be an independent prognostic factor and a potential target for the treatment of intracranial glioma.

Meningioma has the second highest incidence among primary intracranial tumors. There is no effective treatment or targeted therapy for meningioma except excision and radiotherapy. Sp1 (specificity protein 1) is a transcription factor that regulates tumor growth, but the literature describing the relationship between Sp1 and meningioma is scarce. The purpose of this study was to investigate the relationship between Sp1 expression and the clinicopathological parameters in meningioma by immunohistochemical staining.We collected samples from 74 patients from 2008-2012 in Kaohsiung Medical University Hospital, with staging and prognosis of the pathological section of the meningioma.Our results show that Sp1 expression was significantly associated with World Health Organization grade, malignancy, and recurrence in patients with meningioma.High expression of Sp1 in patients with meningioma was linked to poor prognosis of recurrence-free time. Therefore Sp1 may be a candidate biomarker of prognosis and therapy target in meningioma.

Background. Glioblastoma multiforme (GBM) is the most common malignant brain tumor in the world. Despite advances in surgical resection, radiotherapy, and chemotherapy, GBM continues to have a poor overall survival. CDDO (2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid), a synthetic triterpenoid, is an Nrf2 activator used to inhibit proliferation and induce differentiation and apoptosis in various cancer cells. One new trifluoroethylamide derivative of CDDO, RTA 404, has been found to have increased ability to cross the blood-brain barrier. However, it is not clear what effect it may have on tumorigenesis in GBM. Methods. This in vitro study evaluated the effects of RTA 404 on GBM cells. To do this, we treated GBM840 and U87 MG cell lines with RTA 404 and assessed apoptosis, cell cycle, cell locomotion, and senescence. DNA content and induction of apoptosis were analyzed by flow cytometry and protein expression by Western blot analysis. Results. RTA 404 significantly inhibited the proliferation of tumor cells at concentrations higher than 100 nM ( p < 0.05 ) and reduced their locomotion ability. In addition, treatment with RTA 404 led to an accumulation of RTA 404-treated G 2 / M phase cells and apoptosis. An analysis of the p21/AKT expression suggested that RTA 404 may not only help prevent brain cancer but it may also exert antitumor activities in established GBM cells. Conclusion. RTA404 can inhibit proliferation, cell locomotion, cell cycle progression, and induce apoptosis in GBM cells in vitro, possibly through its inhibition of N-cadherin and E-cadherin expression via its inhibition of the AKT pathway.

Yu-Feng Su,1,2 Tai-Hsin Tsai,1,3 Ann-Shung Lieu,1,3,4 Chih-Lung Lin,1– 3 Chih-Hui Chang,1,2 Cheng-Yu Tsai,4– 6 Hui-Yuan Su1,3 1Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University and National Health Research Institutes, Kaohsiung, Taiwan; 6Post Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Cheng-Yu Tsai; Hui-Yuan Su, Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100 Tzyou 1st Road, Kaohsiung, 80708, Taiwan, Tel +886-7-3215049, Fax +886-7-3215039, Email moutzyy691010@yahoo.com.tw; latimeria8@hotmail.comPurpose: Severe complications, including screw loosening events and low fusion rates, in spinal fusion surgery using the traditional open method are problematic. This retrospective study aimed to evaluate the rate of screw loosening and the clinical outcomes of bone-mounted miniature robot-assisted pedicle screw placement in patients treated for degenerative spinal disease.Patients and Methods: Data were collected from the medical records of 118 patients (mean age, 69 years). Differences in clinical outcomes, including the Oswestry disability index, visual analog scale score, screw loosening rate, cage fusion rate, and complications, were evaluated among different bone mineral densities.Results: The screw loosening and cage fusion rates for all patients, normal bone mineral density, osteopenia, and osteoporosis groups were 12%, 8.6%, 13.1%, and 14%, respectively, and 85.3%, 93%, 82.5%, and 81.4%, respectively. There was a higher screw loosening rate and a lower cage fusion rate in the osteopenia and osteoporosis groups than in the normal bone density group. The accuracy of the screw placement was 97.3%. There were no statistically significant differences in the Oswestry disability index and visual analog scale scores, and no major complications for dural tear or vascular or visceral injury.Conclusion: Our study demonstrated an acceptable screw loosening rate in patients with osteoporosis compared to that in patients with normal bone mineral density. The robotic system resulted in accurate screw placement in patients with osteoporosis.Keywords: robotic surgery, screw loosening rate, spinal fixation, spinal fusion, spinal fusion rate

Background and objectives: Managing people with trigeminal neuralgia (TN) and osteoporosis is challenging due to their debilitating conditions. Currently, the exact association between TN and osteoporosis in patients remains unknown, although there is potential overlapping of pathophysiological mechanisms. In response, we calculated TN risk in patients who have osteoporosis. Materials and Methods: 45,393 patients aged over 50 years diagnosed with osteoporosis were matched with 45,393 non-osteoporosis patients aged over 50 years (1:1 ratio) who were used as the control group, using data from 1996 to 2010 from Taiwan’s National Health Insurance Research Database. The cumulative incidences of subsequent TN and the hazard ratio were estimated using Cox proportional hazards modeling and the Kaplan–Meier method, respectively. Results: Among the total sample, 333 patients were diagnosed with TN during the follow-up period: 205 in the osteoporosis cohort and 128 in the control cohort. Through covariate adjustment, the overall TN incidence showed a 1.80-fold increase in the osteoporosis cohort in comparison with the control cohort (0.60 vs. 0.18 per 1000 person-years, respectively). The High Charlson Comorbidity Index, hypertension, and migraines were risk factors of TN. Conclusions: Osteoporosis patients had a higher TN risk than that of the control cohort. Therefore, early recognition of pain and symptoms in osteoporotic people may help to identify possible TN patients who need prompt therapy.

Background and Objectives: Minimally invasive spine surgery reduces destruction of the paraspinal musculature and improves spinal stability. Nevertheless, screw loosening remains a challenging issue in osteoporosis patients receiving spinal fixation and fusion surgery. Moreover, adjacent vertebral compression fracture is a major complication, particularly in patients with osteoporosis. We assessed long-term imaging results to investigate the outcomes of osteoporosis patients with two-level degenerative spine disease receiving minimally invasive surgery with the assistance of a robotic system. Materials and Methods: We retrospectively analyzed consecutive osteoporosis patients who underwent minimally invasive surgery with the assistance of a robotic system at our institution during 2013–2016. All patients were diagnosed with osteoporosis according to the World Health Organization criteria. All patients were diagnosed with two levels of spinal degenerative disease, including L34, L45, or L5S1. The study endpoints included screw-loosening condition, cage fusion, and vertebral body heights of the adjacent, first fixation segment, and second fixation segments before and after surgery, including the anterior, middle, and posterior third parts of the vertebral body. Differences in vertebral body heights before and after surgery were evaluated using the F-test. Results: Nineteen consecutive osteoporosis patients were analyzed. A lower rate of screw loosening was observed in osteoporosis patients in our study. There were no significant differences between the preoperative and postoperative vertebral body heights, including adjacent and fixation segments. Conclusions: According to our retrospective study, we report that minimally invasive surgery with the assistance of a robotic system provided better screw fixation, a lower rate of screw loosening, and a lesser extent of vertebral compression fracture after spinal fixation and fusion surgery in osteoporosis patients.

We previously reported that Aurora-A and the hNinein binding protein AIBp facilitate centrosomal structure maintenance and contribute to spindle formation. Here, we report that AIBp also interacts with Plk1, raising the possibility of functional similarity to Bora, which subsequently promotes Aurora-A–mediated Plk1 activation at Thr210 as well as Aurora-A activation at Thr288. In kinase assays, AIBp acts not only as a substrate but also as a positive regulator of both Aurora-A and Plk1. However, AIBp functions as a negative regulator to block phosphorylation of hNinein mediated by Aurora-A and Plk1. These findings suggest a novel AIBp-dependent regulatory machinery that controls mitotic entry. Additionally, knockdown of hNinein caused failure of AIBp to target the centrosome, whereas depletion of AIBp did not affect the localization of hNinein and microtubule nucleation. Notably, knockdown of AIBp in HeLa cells impaired both Aurora-A and Plk1 kinase, resulting in phenotypes with multiple spindle pole formation and chromosome misalignment. Our data show that depletion of AIBp results in the mis-localization of TACC3 and ch-TOG, but not CEP192 and CEP215, suggesting that loss of AIBp dominantly affects the Aurora-A substrate to cause mitotic aberrations. Collectively, our data demonstrate that AIBp contributes to mitotic entry and bipolar spindle assembly and may partially control localization, phosphorylation, and activation of both Aurora-A and Plk1 via hNinein during mitotic progression.

Background Primary melanocytic neoplasms (PMNs) are rare neoplasms, especially within the central nervous system. Meningeal melanocytomas, a subtype of PMN, are even rarer. Nevus of Ota results from the incomplete migration of melanocytes from the neural crest. Synchronous nevus of Ota and meningeal melanocytoma are infrequently encountered in clinical practice. Objective To evaluate and elucidate 12 cases of synchronous meningeal melanocytoma and nevus of Ota, thereby improving the understanding of the relationship between these 2 diseases. Methods We reviewed cases and searched the English-language literature from the PubMed database and collected clinical parameters of 12 cases of synchronously occurring nevus of Ota and meningeal melanocytoma. Results Among the 12 cases, 90.90% and 91.66% of the lesions were located ipsilaterally and supratentorially, respectively. Conclusions Our findings indicated a trend for both types of lesion to be located ipsilaterally and supratentorially. When a patient with nevus of Ota is found to harbor an intracranial neoplasm, the most likely diagnosis is PMN.

Bcl2L12 as a new member of the Bcl2 family, which contains a BH2 domain and shares a lower amino acid similarity with other Bcl2 family proteins. Bcl2L12 is reported to be involved in apoptosis regulation, but this role remains controversial in different cancer type. Temozolomide (TMZ) is currently used to intervene glioma multiforme (GBM), but an acquired chemotherapeutic resistance maybe occurred due to undesired autophagy. Previous studies uncovered that Bcl2L12 may interact with Bcl-xL and may harbor a BH3-like domain. Therefore, we investigated whether this BH3-like domain is responsible for the Bcl2L12 anti-apoptotic property. Moreover, we tested whether ABT-737, a BH3 mimetic agent, can be combined with TMZ to treat GBM. We aligned Bcl2L12 with Bcl2 family members, compared interacting pattern of BH3 domain and their protein 3D structure. We identified that Bcl2L12 interacts with Bcl-xL and Bcl2 in yeast two-hybrid system. Bcl2L12192-220 was a minimal region for Bcl2L12-Bcl-xL interaction. Five-point mutations with respect to hydrophobic and charge residues were generated to test whether they are the key residue of BH3-like domain. Our data showed that both h1 (L213) and h2 residue (L217) are essential for Bcl2L12 interacting with Bcl2 family proteins. Ectopically expressed h1 or h2 mutant in U87MG cell line resulted in reactivation of cleaved-PARP, caspase-3 and cytochrome c releasing compared to Bcl2L12 wt group. Implementing ABT-737 combined with TMZ provided a superior effect on apoptosis induction in Bcl2L12 wt group, which effectively reactivated apoptotic markers. Altogether, our findings indicated that Bcl2L12 retains a BH3-like domain, which is important for the Bcl2L12 anti-apoptotic property and TMZ-induced autophagy. Our results basically support the idea of using ABT-737 to counteract the anti-apoptotic role of Bcl2L12 and sensitize drug response of the GBM cells to TMZ.

GSK3β interacting protein (GSKIP) is a naturally occurring negative regulator of GSK3β and retains both the Protein Kinase A Regulatory subunit binding (PKA-RII) domain and GSK3β interacting domain. Of these two domains, we found that PKA-RII is required for forming a working complex comprising PKA/GSKIP/GSK3β/Drp1 to influence phosphorylation of Drp1 Ser637. In this study, bioinformatics and experimental explorations re-analyzing GSKIP's biofunctions suggest that the evolutionarily conserved Domain of Unknown Function (DUF727) is an ancestral prototype of GSKIP in prokaryotes, and acquired the C-terminal GSK3β binding site (tail) in invertebrates except for Saccharomyces spp., after which the N-terminal PKA-RII binding region (head) evolved in vertebrates. These two regions mutually influence each other and modulate GSKIP binding to GSK3β in yeast two-hybrid assays and co-immunoprecipitation. Molecular modeling showed that mammalian GSKIP could form a dimer through the L130 residue (GSK3β binding site) rather than V41/L45 residues. In contrast, V41/L45P mutant facilitated a gain-of-function effect on GSKIP dimerization, further influencing binding behavior to GSK3β compared to GSKIP wild-type (wt). The V41/L45 residues are not only responsible for PKA RII binding that controls GSK3β activity, but also affect dimerization of GSKIP monomer, with net results of gain-of-function in GSKIP-GSK3β interaction. In addition to its reported role in modulating Drp1, Ser637 phosphorylation caused mitochondrial elongation; we postulated that GSKIP might be involved in the Wnt signaling pathway as a scavenger to recruit GSK3β away from the β-catenin destruction complex and as a competitor to compete for GSK3β binding, resulting in accumulation of S675 phosphorylated β-catenin.

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

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.

The prognosis of patients with brain tumor diagnoses is often uncertain. Therefore, the primary caregivers of these patients must not only adjust their lives to patient care but also often deal with patient anxiety and depression, which may significantly increase patient-care needs.The present study explores the care needs of primary caregivers of patients awaiting brain tumor surgery and the factors that are associated with these needs.A correlational research design was used. Convenience sampling was used to recruit 80 pre-brain-tumor operation patient/caregiver pairs. Data were collected using a questionnaire survey, which included Supportive Care Needs Survey-PartnersCaregivers 45 (SCNS-PC45) and the Hospital Anxiety and Depression Scales (HADS). Descriptive and inferential statistics were used for data analysis.The information-needs and healthcare-service-needs subscales earned the highest subscale scores on the SCNS-PC45. Higher anxiety perception (r = .37, p.01) and higher depression status (r = .27, p.05) were significantly correlated with increased care needs. In addition, decreased patient functional status was significantly associated with increased depression in the primary caregiver. Anxiety perception was the only significant predictor of care needs that was identified (R(2) = 12.8%).Healthcare providers should provide patient education on the disease and disease-related care information soon after a diagnosis of brain tumor in order to decrease the anxiety and depression perceptions of caregivers and to reduce the care needs of caregivers.腦瘤手術前病人的主要照顧者之照護需求及相關因素之探討.腦瘤主要照顧者在面對病人疾病的不確定性與必須調整自己的生活以照顧病人，可能出現焦慮及憂鬱，進而產生更高的照護需求。.探討腦瘤病人在接受手術前之主要照顧者照護需求及其相關因素。.採相關性研究設計，以方便取樣招募80位腦瘤病人及其主要照顧者進行問卷填答，於病人在被診斷為腦瘤並等待手術前，以支持性照護需求量表—照顧者45及醫院焦慮憂鬱量表進行資料收集。以描述性統計及推論性統計法進行資料分析。.本研究發現在主要照顧者照護需求方面，以訊息需求與健康照護服務需求二層面之需求最高。較高的焦慮感受（r = .37, p.01）及憂鬱狀態（r = .27, p.05）與較高的照護需求有關，此外，病人的身體功能狀態愈差時，主要照顧者較容易有憂鬱狀態，而「焦慮感受」為照護需求的最重要之預測因子（R臨床醫護人員於病人被診斷出腦瘤在等待手術前，即應開始進行與疾病及照護有關之衛教，有助於主要照顧者減輕其焦慮及憂鬱，進而降低其照護需求。.

Dysregulated centrosomal expression has been observed in high grade gliomas. Thus, this study aimed to examine the expression of Aurora family kinase and various centrosomal proteins, including centrin, γ-tubulin, and hNinein isoforms, in human brain tumors, including 29 meningiomas, 34 astrocytomas, 6 pituitary adenomas, and 6 metastatic tumors. mRNA expression was evaluated using reverse transcription polymerase chain reaction. The role of hNinein isoform 6 expression in cell differentiation was assessed in BrdU-treated IMR-32 cells. Differential expression of centrosomal proteins of brain tumors and cell lines was observed. Specifically, centrin 2 and centrin 3 expression levels were classified as moderate or abundant in >97% of samples in the meningioma group, 63% of astrocytomas, >83% of metastatic and pituitary tumors. Alternatively, hNinein isoform 6 expression was only detected in normal brain and astrocytoma tumors (17/34); however, it was not expressed in meningioma (0/29), metastatic tumors (0/6) (P < 0.001). Of the six neuroblastoma cell lines analyzed only IMR-32 cells expressed hNinein isoform 6. Furthermore, downregulated expression of hNinein isoform 6 and upregulation of γ-tubulin was correlated to astrocytoma tumor grade (P < 0.001). Increased hNinein isoform 6 mRNA expression was observed in response to BrdU treatment, and its expression was greater in teratomas as compared to embryonic stem cells. Further studies are necessary to determine if hNinein isoform 6 functions as a tumor-suppressor gene in brain tumors. Differential centrosomal protein expression may result in altered centrosome function that is observed the in progression of various brain tumors. © 2012 International Union of Biochemistry and Molecular Biology, Inc.

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.

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.

Rationale Radiotherapy (RT) is widely used for both malignant and benign tumors in order to reduce the risk of recurrence, to promote tumor control, and to improve survival. However, there have been studies reported that RT is also a risk factor of secondary cancer. Very few cases of secondary malignancy after RT to high grade brain cancer have been reported due to short survival of this disease, and most RT-induced malignancies presented with sarcomatous histology. Here we present a patient with basal cell carcinoma (BCC) 14 years after RT to his brain. Patient concerns A 28-year-old man without any underlying disease had suffered from left side weakness and clonic-tonic seizures for 12 days. Diagnoses His brain images showed a tumor in the right frontal lobe. The pathologic report confirmed anaplastic astrocytoma (WHO Grade III). Interventions After craniotomy and tumor biopsy, RT was delivered. Fourteen years later, a gray-colored skin papule was noted in the previously irradiated area. The scalp biopsy revealed BCC. The scalp BCC was adequately resected. He then suffered from brain tumor recurrence and received further craniotomy for three times combined with chemotherapy with temozolomide. Outcomes After treatment, follow-up brain images showed that the disease was under control. There was no neurological sequela. For scalp BCC, no skin tumor recurrence has been noted to date after the resection 14 years after initial RT. He has survived for more than 26 years since his initial diagnosis of anaplastic astrocytoma, and more than 12 years from the diagnosis of scalp BCC. Lessons Notwithstanding the risk of radiation-induced skin cancer, RT contributed to this patient's survival. The possible late adverse events should be informed to the patients.

Rationale: Primary spinal primitive neuroectodermal tumor (PNET) is relatively rare in all age groups, and the prognosis in most cases of spinal PNETs appears to be poor, with a median patient survival of 1 to 2 years. We present a case with recurrent spinal PNET with brain and bone metastases that was successfully treated by multimodality treatment. Patient concerns: A 14-year-old teenage girl had suffered from progressive left upper back pain with bilateral lower legs weakness and numbness for 1 year. After treatment, left neck mass was noted 3 years later. Diagnoses: Initially, magnetic resonance imaging (MRI) showed neurogenic tumor involving intradural extramedullary space of T5-T10. Pathology report showed PNET (World Health Organization grade IV) featuring lobules of neoplastic cells with round regular nuclei, high nucleus-to-cytoplasm ratio, and fibrillary cytoplasm. At the time of tumor recurrence, chest MRI then showed recurrent tumor at T2-T3 level of the epidural space with right neural foramina invasion. Brain MRI showed extensive bilateral calvarial metastases and leptomeningeal metastases in the right frontoparietal regions. Bone scan showed multiple bone metastases. Interventions: T-spine tumor removal and adjuvant radiotherapy (RT) to T-spine tumor bed were performed in the initial treatment. After clinical tumor recurrence, tumor removal was done again. She then received chemotherapy followed by whole brain irradiation with hippocampal sparing with 35 gray in 20 fractions. Outcomes: After treatment, follow-up images showed that the disease was under control. There was no neurological sequela. She has survived more than 7 years from diagnosis and more than 4 years from recurrence to date. Lessons: Multimodality treatments including operation, RT, and chemotherapy should be considered in the initial treatment planning, and salvage chemotherapy was useful in this case.

BACKGROUND Brain tumors are uncommon etiologies of parkinsonism. The clinical manifestations of tumoral parkinsonism may sometimes resemble those of idiopathic origin. Increased awareness of this rare entity is important for an earlier prompt diagnosis and treatment. REVIEW SUMMARY A previously healthy, 60-year-old man developed slowly progressive right-sided resting tremor and bradykinesia over 8 months. Although idiopathic Parkinson disease was the initial diagnosis, the parkinsonian symptoms were not responsive to medical treatment with levodopa and a dopamine agonist. Brain computed tomography failed to reveal an intracranial lesion. Brain magnetic resonance imaging demonstrated an infiltrative, slightly enhancing mass in the left mesial temporal lobe extending to the left basal ganglion and insula. Histopathologic findings confirmed the diagnosis of high-grade astrocytoma. The parkinsonian symptoms subsided after tumor removal; however, ipsilateral hemiparesis developed postoperatively. CONCLUSIONS Neuroimaging is recommended for investigation of atypical parkinsonism. We suggest that brain magnetic resonance imaging is preferred for patients with drug-resistant parkinsonism or concurrent signs apart from extrapyramidal symptoms, because some mass lesions are not observed by computed tomography scan.

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.

Patients who have liver cirrhosis are at increased risk of bacterial infections, such as bacteremia, meningitis, pneumonia, urinary tract infections, and spontaneous bacterial peritonitis, due to immunodeficiency associated with the severity of the cirrhosis. Although bacterial infections are frequent in cirrhotic patients, only isolated cases of brain abscess have been reported. In these cirrhotic patients, the initial presentation of brain abscess may not be fever or leukocytosis, but focal neurologic deficits. In addition, for consideration of blood-brain barrier penetration, the anti-biotic choice postoperatively is also quite different from other infections outside the central nervous system. We will discuss two cases of brain abscess in cirrhotic patients with special emphasis on the clinical presentation, magnetic resonance spectroscopic findings, organism encountered, therapeutic strategy, and prognosis.

Developmental venous anomaly (DVA) is now considered common and benign disease within the field of cerebral vascular malformation. Though symptomatic DVA is uncommon, further management is necessary to alleviate the symptoms and signs induced by symptomatic DVA, such as parenchymal hemorrhage, venous infarction, brain edema, obstructive hydrocephalus, and nerve root compression. From the viewpoint of obstructive hydrocephalus, mostly resulted from obstruction of aqueduct of Sylvius. Herein, we reported a case with presentation of obstructive hydrocephalus caused by DVA induced fourth ventricle outlet obstruction.

Object Promotion of the repair and regeneration of damaged adult neurons is a major goal of neurological science. In this study, the effects of G protein–coupled receptor kinase interacting protein 1 (GIT1) overexpression in human neuron cells were tested in human neuronal cells by using an adenoviral vector. Methods A recombinant GIT1 and enhanced green fluorescent protein (EGFP) adenoviral vector (AdGIT1) was created by using a standard viral construction procedure. Human neuronal (NT2N) cells, which had been derived from an NT2 human teratocarcinoma cell line, were used in this experiment. Immunocytochemical methods were applied to identify NT2N cells with neural features and to probe the relationship among signaling proteins. Several biological activities were assessed, including neural spine formation, cell migration, and the levels of expression of growth-associated protein–43 (GAP-43) and active Cdc42. The number of cells with spine formation and the number of migrated cells were significantly higher in the AdGIT1-treated group of NT2N cells than in untreated (control) NT2N cells or in AdEGFP-treated NT2N cells. The levels of GAP-43 and active Cdc42 expression were significantly higher in the AdGIT1-treated group than that in the other two cell groups. Conclusions The results of this study demonstrate that GIT1 overexpression has the potential to promote neural spine formation and cell migration in human neuronal cells. At the same time, the increased level of GAP-43 in GIT1-overexpressed cells indicates that GIT1 may have the potential to improve growth and regeneration of damaged axons. The GIT1–β-PIX–Cdc42–PAK pathway may play an important role in neuronal outgrowth.

The osteogenic potential of AAV5hBMP6 was compared with that of ADhBMP6 in immunodeficient and immunocompetent rats. AAV5hBMP6 (2.3 x 10(12) particles) and ADhBMP6 (5 x 10(7) PFU) elicited viral antibody production in immunocompetent rats. Among rats that received AAV5hBMP6, the earliest time points at which the bone was visible under CT scanner were 30 days in 2-month-old Sprague-Dawley (SD) rats and 60 days in 18-month-old SD rats. The mean volumes of ectopic bone 90 days after viral injection were 0.31 +/- 0.14 cm(3) in athymic nude rats, 0.64 +/- 0.12 cm(3) in 2-month-old SD rats, and 0.21 +/- 0.10 cm(3) in 18-month-old SD rats. In contrast, among rats that received ADhBMP6, the earliest time points to observe the bone formation by CT scan were 15 days in 2-month-old rats and no bone formation in 18-month-old SD rats. The mean volumes of ectopic bone were 4.17 +/- 0.05 cm(3) in athymic nude rats and 0.06 +/- 0.03 cm(3) in 2-month-old SD rats. Although both types of viruses induced an immune response in immunocompetent animals, this response played different roles in the process of bone formation induced by the BMP6 vectors.

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.

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.

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.

Seizures and epilepsy in adults are important and increasingly common clinical problems. Despite this, the investigation of seizures in adults with astrocytic tumors remains a grey area. The incidence and influencing factors of preoperative and postoperative seizures were evaluated in 101 patients of 45 years or older with supratentorial astrocytic tumors. Preoperative seizures occurred in 14 (14%) patients. Seizures at presentation were significantly correlated with pathological grades of astrocytic tumors (p = 0.0318). The risk of seizures at presentation was greatest in patients with well-differentiated astrocytomas as compared with anaplastic astrocytomas (Odds ratio = 4.364, p = 0.056) or glioblastomas multiforme (Odds ratio = 5.673, p = 0.007). There was no association of preoperative seizures with age, sex, location or site of the tumors. Postoperative seizures occurred in 18 (18%) patients, including 8 (8/14, 57%) recurrent seizures and 10 (10/87, 12%) late-onset seizures. Postoperative seizures were significantly correlated with the presence of preoperative seizures (p = 0.0003). The presence of preoperative seizures was potentially predictive of postoperative seizures when evaluated by logistic regression model (Odds ratio = 6.650). Thirteen (72%) of 18 patients with postoperative seizures were associated with tumor recurrence in 7 cases, hemorrhage in 3 cases and malignant progression in 3 cases. There was no association of postoperative seizures with age, sex, location or site of the tumors, grades of tumors, type of preoperative seizures, duration of preoperative seizures, serum level of anticonvulsant drug, extent of surgery, postoperative radiation or chemotherapy. The patients with preoperative seizures had a higher risk of postoperative seizures and should be carefully monitored. Imaging examination of brain to exclude the possibilities of tumor recurrence or hemorrhage is warrantable in supratentorial astrocytoma patients with postoperative seizures.

The human dynamin-like protein, HdynIV, has recently been cloned and shown to be involved in the formation and trafficking of coated vesicles. In particular, one of the HdynIV variant overexpressions has been suggested to contribute to the pathogenesis of brain tumors. In this paper, we report on the genomic organization of the human HdynIV gene. The gene was found to correspond to 20 exons of genomic sequence on human chromosome 12, distributed over 64 kb of genomic DNA. The two exons, numbers 15 and 16, are subjected to differential splicing, generating four different transcripts of a perfect match to our recent report on the four different spliced HdynIV variants [DNA Cell Biol. 19 (2000) 189]. We have also characterized the 5′ regulatory region of the HdynIV gene in order to understand the molecular mechanisms regulating its expression. The transcriptional initiation site was identified by 5′-RACE. The 5′-flanking sequence of the HdynIV gene contains three GC boxes that concatenate Ap2- and Sp1-binding motifs, but that does not contain either the TATA or CAAT consensus sequence. A region between −140 and +92 contributed to high promoter activity. Deletion analysis demonstrated that the minimal promoter activity required the region of −110 to −100. Electrophoretic mobility shift assay demonstrated that a putative transcriptional factor bound to the region of −119 to −90. Site-directed mutagenesis analysis of this region revealed that nucleotides at −108 to −100 were essential for transactivation mediated by this transcriptional factor. In conclusion, we have characterized the minimal HdynIV promoter and shown that CTCCCAGCA (−108 to −100) sequence may act as a novel transcriptional element for regulating HdynIV gene expression.

Aims. Rac1 is a member of the Ras superfamily of small GTPase and plays a fundamental role in cytoskeleton reorganization, regulation of gene expression and cell proliferation, and cellular transformation. Though recent studies point to an involvement of rac1 in tumorigenesis, little is known about the alteration of rac1 gene in human brain tumours. Methods. Reverse transcription-polymerase chain reaction (RT-PCR), TA cloning, and DNA sequencing were performed to detect rac1 gene mutations in the surgical specimens of 45 human brain tumours. Results. Twelve of 45 cases had base changes in the rac1 gene. The frequency of rac1 alterations was seven of 18 meningiomas, three of 14 astrocytomas, one of seven pituitary adenomas, and one of four metastatic brain tumours. No mutation was detected in acoustic neurilemomas. The subtypes of seven meningiomas include three meningotheliomatous, two atypical, one transitional and one angioblastic meningioma. Three astrocytomas had rac1 gene mutation, including one grade II, one grade III, and one grade IV astrocytoma. All of single base changes were transitions, five of them being T to C transitions. Sites of rac1 mutation were found in codons 34, 41 (two cases), 42 (two cases), 43, 44, 46 and 58. These mutations are mainly localized in the putative effector-domain of rac1 gene and may enhance the activity of rac1, which increases the survival of brain tumours. Conclusion. Our results suggest that rac1 gene may play a role in some brain tumours of divergent histogenesis and that the alterations of rac1 gene may contribute to tumorigenesis and/or metastasis.

The purpose of this study was to demonstrate the existence of a newly recognized midline posterior column pathway that mediates the perception of visceral pain resulting from hepatobiliary or pancreatic cancer. A punctate midline myelotomy (PMM) of T(3) level was performed in 6 patients who experienced severe visceral pain caused by hepatobiliary or pancreatic cancer. Preoperatively, the pain was refractory to strong opioids. Clinical efficacy of PMM was evaluated by comparing patient pain rating on a visual analogue scale. Follow-up periods ranged from 2-18 weeks after operation. All 6 patients had immediate pain relief after operation. Although the pain recurred from 2-12 weeks later in 3 patients, the severity of recurrent cancer pain markedly decreased. No adverse neurological sequelae were observed. Our results of high thoracic PMM offer clinical support for the concept that neurosurgical interruption of midline visceral pain pathway can effectively control severe visceral pain without causing adverse neurological sequelae in patients with hepatobiliary or pancreatic cancer.

Breast carcinoma has a high predisposition to metastasize to the brain parenchyma. An association between carcinoma of the breast and intracranial meningioma has been reported. The available published articles regarding patients with intracranial meningioma and breast carcinoma have been reviewed. To the best of our knowledge, 86 cases including our 4 cases have so far been reported. All cases were female, and the mean age was 62.4 years when intracranial meningioma was diagnosed. The mean interval of the 2 tumours was 4.5 years. Twenty-five cases of breast tumour were infiltrating duct carcinomas. The location of intracranial meningioma and pathologic subtype showed no specific predominance. Hormone receptor study was performed in 28 cases. In meningioma, the positive rate of progesterone receptor (32.1%) is higher than oestrogen receptor (7.1%); while the positive rate of oestrogen receptor (53.6%) is higher than the progesterone receptor (42.9%) in breast cancer. A review of this study is presented with emphasis on the existence of intracranial meningioma and breast cancer in one patient at different periods. Lesions of the central nervous system in patients with breast cancer should not be immediately labeled as metastases. Intracranial meningioma should be excluded. Likewise, patients with meningioma should have periodic physical examinations and mammographies whereby disease may be diagnosed and treated at an early stage

Four novel small nucleolar RNAs (snoRNAs), h5sn1, h5sn2, h5sn3, and h5sn4, were successfully amplified from human total RNAs using RT-PCR. They exhibited the structural hallmarks of box H/ACA snoRNAs and formed sequence complementarity to 5S rRNA. The nucleotide sequences of the snoRNAs from different donors were highly conserved as evidenced by single-stranded conformational polymorphism and direct nucleotide sequence analysis. Although their host genes had no protein-coding potential, the expression of the snoRNAs was differentially displayed in different tissues. Noticeably, h5sn2 was highly expressed in normal brain, but its expression drastically decreased in meningioma. This opens the fascinating possibility of the relationship between the processing of snoRNAs and carcinogenesis.

A 14-year-old boy with no history of trauma complained of left-side weakness and ataxia during the previous 24 h. The symptoms first appeared while playing the trumpet in the school orchestra. Neurologic examination on admission showed left hemiparesis (grade 3/5) with brisk reflexes. The remainder of the neurological and general examinations was normal. Lateral skull radiograph showed air in the frontal lobe (Fig.1a). Computed tomography (CT) scan revealed an ethmoid sinus osseous lesion and large right frontal pneumatocele (Fig. 1b–d).The patient underwent a right frontal craniotomy, which revealed an ethmoid roof bony mass that had eroded the upper sinus wall and breached the dura (Fig. 2). The tumor had also encroached into the frontal lobe. After complete removal of the ossifying tumoral tissue, the dura was repaired and covered with a fascia graft. Osteoma was confirmed by pathological examination. The postoperative course was uneventful, and the symptoms progressively improved. He was discharged 1 week after surgery and the 2year follow-up revealed no neurologic sequelae. Discussion

The purpose was to evaluate the association of Aurora A and gamma-tubulin expression with disease characteristics and survival in patients with astrocytoma.This is a retrospective study of patients who had surgical specimens that were pathologically diagnosed as astrocytoma. The expression level of Aurora A and gamma-tubulin in tumor tissue was evaluated by immunohistochemistry. Clinical information, Karnofsky performance status scale, and survival status of patients were collected.We found that high protein levels of gamma-tubulin or Aurora A were associated with patients 45 years of age, high tumor grade, more advanced non-fully resectable tumors, and poorer survival status. The survival time for patients whose tumors had high gamma-tubulin and Aurora A expression was about 12 months compared with approximately 41 months for patients with low levels of expression of these proteins. Poor patient performance status following resection was also associated with high levels of gamma-tubulin and Aurora A expression.The expression levels of gamma-tubulin or Aurora A kinase were associated with patients' age, astrocytoma grade, respectability, as well as patient survival and performance. These findings support the idea that these factors may potentially be important prognostic indicators for patients with astrocytomas.

Background. Central neurocytoma and oligodendroglioma are rare tumors of the central nervous system. However, diagnosis between these two types of tumors is challenging due to their many cytological and histological similarities. Death-associated protein kinase (DAPK) is a calcium/calmodulin-regulated serine/threonine protein kinase involved in many apoptosis pathways, and repressed expression of DAPK by promoter hypermethylation has been found in a variety of human cancers. The purpose of this study was to assess DAPK protein expression and promoter hypermethylation in central neurocytoma and oligodendroglioma.Method. Central neurocytoma and oligodendroglioma samples were obtained from age- and sex-matched patients. DAPK protein expression was performed using immunohistochemical assays in formalin-fixed, paraffin-embedded sections. DAPK promoter hypermethylation was carried out using bisulfite-modified genomic DNA in methylation-specific PCR followed by separation in agarose gels.Findings. A statistically significant difference (P=0.021) in DAPK promoter hypermethylation between central neurocytoma (76.9%) and oligodendroglioma (20%) was observed. High levels of DAPK protein expression were generally found in oligodendroglioma (90%), compared with 38.5% in central neurocytoma (P=0.054; not statistically significant). There was an inverse correlation between DAPK protein expression and DAPK promoter hypermethylation in the cohort of 23 patients (P=0.002).Conclusions. The results show that DAPK promoter hypermethylation and repressed expression of DAPK protein were more common in central neurocytoma than in oligodendroglioma. Thus, DAPK promoter hypermethylation could be useful for differential diagnosis between these two types of tumors, whereas DAPK protein expression might be less predictive. The role of DAPK promoter hypermethylation in the pathogenesis of central neurocytoma warrants further study.

To evaluate the incidence and influencing factors related to preoperative and postoperative seizures, a retrospective analysis was performed in 190 patients with astrocytic tumours. Preoperative seizures occurred in 50 (26%) patients and 27 (54%) of the m had recurrent seizures. Late-onset seizures developed after craniotomy in 11 (8%) of 140 patients. Seizures at presentation were significantly correlated with age at diagnosis (P=0.0204) and pathological grade of tumour (P=0.0040). The patients aged less than 40 years had a high risk of seizures at presentation (odds ratio=3.076, P=0.0134). Postoperative seizures were significantly associated with the presence of preoperative seizures (P

In a retrospective study of a consecutive series of 222 surgically treated meningiomas, it was found that 26.6% of the patients presented epilepsy as their initial symptom. In this group, surgical excision of the intracranial meningiomas stopped the epilepsy in about 62.7% of the patients. But approximately one-fifth of the patients with intracranial meningiomas and no history of preoperative epilepsy developed new onset postoperative seizures. Of the patients with early onset of postoperative epilepsy, epilepsy appeared in 66.7% within first 48 h after surgery. Of the patients with postoperative epilepsy, 71.2% were seizure-free following 1 year of anticonvulsant therapy. Regarding preoperative existing factors, intracranial meningiomas located at supratentorium, convexity, and with evidence of or severe peritumoral edema significantly contributed to preoperative epilepsy. And in patients with preoperative epilepsy, those tumors with evidence of or severe perifocal edema and cerebral edema at the operative site were significantly more likely to suffer from postoperative epilepsy.

Centrosomes are organelles involved in the organization of the mitotic spindle and may also be the targets of autoantibodies in autoimmune diseases. Human Ninein (hNinein) is a centrosomal autoantigen that is identified by autoimmune patient sera. However, none of the hNinein-specific fragments recognized by the autoantibodies in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) sera have been thoroughly characterized. We thus attempted to identify the fine specificity within the hNinein protein. In this study, four recombinant proteins in two isoforms of hNinein were used as autoantigens along with immunoassays as a molecular tool to investigate the prevalence of hNinein autoreactivity and its specificity in 22 RA and 32 SLE autoimmune disease sera. The data indicated a 50% higher prevalence of isoform 4 hNinein N-terminal autoantibodies in RA sera, whereas 22% of SLE patients were autoreactive to the N-terminal of isoform 4 hNinein compared to only a small percentage of autoreactive normal sera (5%). These results showed that autoepitopes on autoantigen hNinein are restricted to the N-terminal region and that a more significant proportion of RA patients exhibited centrosome reactivity.

Extraventricular neurocytoma (EVN) in the spinal cord is extremely rare and only 15 cases have been reported in the English literature. Fourteen cases presented as an intramedullary lesion with spinal cord enlargement in cervico-thoracic segment and one case presented as an extramedullary lesion originating from cauda equina. Herein, we report an unusual spinal neurocytoma with exophytic growth from the thoracic spinal cord with cord compression mimicking meningioma. To our knowledge, this is the first case of exophytic spinal neurocytoma recorded in the English literature.

We describe a rare case of desmoplastic infantile ganglioglioma that appears to have transformed into a glioblastoma multiforme tumor in a 5-year-old girl. The patient was initially treated with total removal of the tumor, without subsequent radiation therapy or chemotherapy. She was in good health for 3 years, but manifested a sudden onset of seizures, followed by severe headache, vomiting, and left-sided weakness. Cranial magnetic resonance imaging revealed a large mass with rim enhancement at the previously operated site. The mass was completely removed, and the pathology report revealed glioblastoma multiforme. Postoperative chemotherapy and radiation treatment were administered. She has been followed for 11 years, and is alive without recurrence.

The hedgehog (Hh) transcription factor Gli induces transformation of epithelial cells via induction of Snail, a repressor of E-cadherin. Epithelial-mesenchymal transition is also a determinant of the progression of tumorigenesis, following down-regulation of E-cadherin. However, the role of Hh signaling components and Snail/E-cadherin in brain tumors is not yet fully understood. We analyzed the expression of Hh signaling components and Snail/E-cadherin in 69 brain tumors by reverse transcription-polymerase chain reaction (RT-PCR). The data showed that overexpression of Smo (35/69), Ptch (50/69), Gli1 (56/69), Gli2 (29/69) and N-myc (39/69) might contribute to brain tumorigenesis. Our results also indicated that Snail and E-cadherin showed opposing expression in malignant tumors (high grade astrocytoma and metastasis). Snail and E-cadherin showed less correlation in benign brain tumors. We further investigated mutations of Gli2 and Snail by RT-PCR and direct sequencing. No mutation was observed on Gli2 but several sporadic mutations on Snail were found, including S96G, S111L, S111L/ S119Y and one nonsense mutation at codon 158 (Y158*) . An in vitro E-cadherin promoter assay showed that S96G, S111L, S111L/S119Y Snail mutants were decreased by 15, 25 and 50%, respectively, whereas Y158 * was increased by 40% compared to wild-type. Furthermore, our data showed that wild-type Snail and S96G, S 111L, S111L/S119Y translocated to the nucleus, while the Y158 * mutant failed to translocate to the nucleus. Taken together, our results demonstrate that Hh signaling components, the expression and mutations of Snail and the expression of E-cadherin may play an important role in human brain tumorigenesis.

Aurora-A is involved in chromosome alignment, centrosome maturation, mitotic spindle assembly and regards to an oncogene. Aurora-A is also known to bind to several other proteins affecting its up-regulation or down-regulation and localization. However, how these different binding signals work together to regulate Aurora-A is not properly known. To explore more Aurora-A interacting proteins, the low-copy yeast two-hybrid screening using Aurora-A as bait protein was performed. One novel gene, AIBp, was demonstrated to associate with Aurora-A by the yeast two-hybrid method and in vitro GST pull-down assay. Molecular characterization showed that AIBp possessed a binding site at the C-terminal with Aurora-A (kinase domain). Interestingly, AIBp also interacts with hNinein at the N-terminal, which overlaps with a previously reported hNinein and GSK3beta binding site. Using a kinase assay, AIBp interacts with the Aurora-A kinase domain functions as a positive regulator, whereas AIBp binding to hNinein appears to block the phosphorylation of hNinein by both Aurora-A and GSK3beta. siRNA-mediated elimination of AIBp from HeLa cells, results in a doughnut-like shape, asymmetrical spindle pole and multiple spindle pole formation. We also demonstrated that both AIBp and Aurora-A are co-overexpressed in various brain tumors. These studies demonstrate that AIBp may not only be required for the dynamic movement of Aurora-A at the centrosomes and spindle apparatus during the cell cycle, but may also be important during brain tumorigenesis.

Although instrumented posterior lumbar interbody fusion (PLIF) has been becoming a popular and effective method for treating degenerative lumbar scoliosis, the clinical outcome is rarely reported. We retrospectively evaluated the clinical and radiographic outcomes in patients with degenerative lumbar scoliosis after instrumented PLIF.A total of 58 patient's clinical characteristics had been reviewed retrospectively including clinical presentations, preoperative medical comorbidities, intraoperative status, and postoperative status. Oswestry disability index (ODI), visual analog scale (VAS), and patient satisfaction were evaluated before surgery and last follow-up period. The relationship between the difference of radiographic parameter and functional outcome was evaluated.Functional outcomes including ODI scores and VAS were significantly improved at the last visit. The ODI was 28.1 ± 8.0 before surgery and 12.2 ± 8.8 at the last visit. VAS was 7.4 ± 2.0 before surgery and 2.4 ± 2.0 at the last visit. Patient satisfaction was 72% at the last visit. ODI was significantly related to postoperative radiographic parameters including Cobb's angle (p 0.001), L4 inclination (p = 0.011), coronal balance (p = 0.007), lateral vertebral translation (p 0.001), Nash-Moe grade (p = 0.033), Nash-Moe degree (p = 0.025), and sagittal balance (p = 0.041) Using multiple regression analysis, ODI was significantly related to female gender, number of levels fixed, coronal balance, lateral vertebral translation, and Nash-Moe degree. The was no significant correlation between postoperative radiographic parameters and pain (VAS). Only lateral vertebral translation demonstrated a significant correlation in multiple regression analysis.Based on the VAS and ODI instrument, our studies demonstrated that instrumented PLIF for adult degenerative lumbar scoliosis can achieve a high rate of patient satisfaction and improvement in radiographic and clinical outcomes at a minimum of 2 years of follow-up.

Background Kocuria, established by Stackebrandt et al., previously was classified into Micrococcus. Only two species, K. rosea and K. kristinae are reported to be associated as pathogenic and found with catheter-related bacteremia and acute cholecystitis. Case presentation We herein report the first case of brain abscess caused by Kocuria varians, a gram-positive microorganism, in a 52-year-old man. Hematogenous spread is the probable pathogenesis. Conclusions This report presents a case of Kocuria varians brain abscess successfully treated with surgical excision combined with antimicrobial therapy. In addition, Vitek 2 system has been used to identify and differentiate between coagulase-negative staphylococcus.

Background: : Chronic subdural hematoma (CSDH) is a relatively frequent problem in neurologic or neurosurgical practice. Although CSDH is a well-known disease, data on bilateral CSDH are scarce compared with data on unilateral CSDH. The purpose of this study was to compare the clinical presentations, precipitating factors, computed tomography (CT) scan findings, postoperative complications, and outcomes between patients with bilateral and unilateral CSDH. Methods: : A retrospective study was performed on 129 surgical patients with CSDH from January 2002 to January 2005. These patients were divided into two groups: bilateral CSDH (45 cases) and unilateral CSDH (84 cases). Clinical presentations, precipitating factors, CT scan findings, postoperative complications, and outcomes of patients were analyzed. Results: : The mean age was 75 years for patients with bilateral CSDH and was 68 years for patients with unilateral CSDH (p = 0.696). Males predominated in each group (p = 0.696). The frequency of presenting symptoms of nausea and vomiting, headache, or unsteady gait was significantly greater in bilateral CSDH than in unilateral CSDH (p < 0.05). The incidence of usage of anticoagulant and antiplatelet therapy was significantly higher in bilateral CSDH group than in unilateral CSDH group (p < 0.05). The frequency of marked midline shift on CT scans was significantly greater in unilateral CSDH than in bilateral CSDH (p < 0.05). Coexisting systemic diseases, postoperative complications, and outcomes had no significant differences between both groups. Conclusions: : Bilateral CSDH tended to occur more in patients with anticoagulant or antiplatelet therapy. Compared with patients with unilateral CSDH, patients with bilateral CSDH had more symptoms of increased intracranial pressure and lower incidences of midline shift on CT scans. Most patients with either bilateral or unilateral CSDH had a good postoperative outcome.

Background High-grade gliomas have poor prognosis, requiring aggressive treatment. The aim of this study is to explore mitotic and centrosomal dysregulation in gliomas, which may provide novel targets for treatment. Methods A case-control study was performed using 34 resected gliomas, which were separated into low- and high-grade groups. Normal human brain tissue was used as a control. Using immunohistochemical analysis, immunofluorescent microscopy, and RT-PCR, detection of centrins 1 and 2, γ-tubulin, hNinein, Aurora A, and Aurora B, expression was performed. Analysis of the GBM8401 glioma cell line was also undertaken to complement the in vivo studies. Results In high-grade gliomas, the cells had greater than two very brightly staining centrioles within large, atypical nuclei, and moderate-to-strong Aurora A staining. Comparing with normal human brain tissue, most of the mRNAs expression in gliomas for centrosomal structural proteins, including centrin 3, γ-tubulin, and hNinein isoforms 1, 2, 5 and 6, Aurora A and Aurora B were elevated. The significant different expression was observed between high- and low-grade glioma in both γ-tubulin and Aurora A mRNA s. In the high-grade glioma group, 78.6% of the samples had higher than normal expression of γ-tubulin mRNA, which was significantly higher than in the low-grade glioma group (18.2%, p < 0.05). Conclusions Markers for mitotic dysregulation, such as supernumerary centrosomes and altered expression of centrosome-related mRNA and proteins were more frequently detected in higher grade gliomas. Therefore, these results are clinically useful for glioma staging as well as the development of novel treatments strategies.

The specificity and regulation of GSK3beta are thought to involve in the docking interactions at core kinase domain because of the particular amino acid residues. Recent X-ray diffraction studies illuminated the relative binding residues on AxinGID and FRATtide for GSK3beta docking and appeared that GSK3beta Val267Gly (V267G) and Tyr288Phe (Y288F) could distinguish the direct interaction between AxinGID and FRATtide. In order to explore the mode that involved the binding of GSKIP to GSK3beta and compare it with that of AxinGID and FRATtide, we pinpointed the binding sites of GSKIP to GSK3beta through the single-point mutation of four corresponding sites within GSK3beta (residues 260-300) as scaffold-binding region I (designated SBR-I(260-300)). Our data showed that these three binding proteins shared similar binding sites on GSK3beta. We also found that the binding of GSK3beta V267G mutant to GSKIP and AxinGID, but not that of Y288F mutant (effect on FRATtide), was affected. Further, based on the simulation data, the electron-density map of GSKIPtide bore closer similarity to the map AxinGID than to that of FRATtide. Interestingly, many C-terminal helix region point-mutants of GSK3beta L359P, F362A, E366K, and L367P were able to eliminate the binding with FRATtide, but not AxinGID or GSKIP. In addition, CABYR exhibited a unique mode in binding to C-terminal helix region of GSK3beta. Taken together, our data revealed that in addition to the core kinase domain, SBR-I(260-300), another novel C-terminus helix region, designated SBR-II(339-383), also appeared to participate in the recognition and specificity of GSK3beta in binding to other specific proteins.

Objective Meningiomas are the second most common primary tumors of the central nervous system. Meningiomas at the cranial base pose technical challenges and result in increased morbidity. To investigate the molecular mechanisms of meningioma formation, the expression profiles of 12 000 genes from meningiomas and dural specimens were compared. Methods Ribonucleic acid from 6 meningiomas (World Health Organization Grade I) and 4 dural specimens was profiled using U95A GeneChips (Affymetrix, Inc., Santa Clara, CA). Expression profiles of the 2 groups were compared using dChip and Data Mining Tool software packages (Affymetrix, Inc.) to identify differentially expressed genes. Down-regulation of a differentially expressed tumor suppressor gene, deleted in liver cancer 1 (DLC1), was verified by quantitative real-time reverse transcription-polymerase chain reaction and immunohistochemical staining. Function and methylation of DLC1 were assessed by ectopic expression in 5 primary cultures, demethylation assay using 5-aza-2'-deoxycytidine, and methylation-specific polymerase chain reaction in 4 meningioma samples. Results Gene expression profiling revealed up-regulation of 5 genes (fibroblast growth factor 9, gibbon leukemia virus receptor 2, cyclin D1, eukaryotic translation initiation factor 5A, and 28S ribosomal ribonucleic acid) and down-regulation of 35 genes, including DLC1, in meningiomas. The down-regulation of DLC1 in meningiomas was confirmed by quantitative real-time reverse transcription-polymerase chain reaction and immunohistochemical staining. Transfection of DLC1 complementary deoxyribonucleic acid into primary cultures of 5 meningiomas resulted in decreased replication. Although demethylation decreased meningioma cell growth rates in vitro, methylation-specific polymerase chain reaction did not detect DLC1 promoter methylation. Conclusion The results suggest that DLC1 may function as a tumor suppressor gene in meningiomas. Furthermore, DLC1 promoter methylation does not appear to be responsible for the decreased DLC1 expression in these tumors.