Successful shrinkage of a recurrent partially thrombosed symptomatic large basilar tip aneurysm using a Target 3D Coil.

Background: Standalone coil embolization is often less effective for partially thrombosed intracerebral aneurysms (PTIA) because of the risk of frequent recurrence if the coil migrates into the thrombus. This report describes a case of PTIA at the basilar tip in which simple coil embolization using a Target 3D Coil resulted in sustained remission without recurrence during long-term follow-up. Case Description: The patient was a 63-year-old male who presented with right oculomotor nerve palsy after having undergone direct surgery for a basilar artery aneurysm 15 years earlier. Recurrence with partial thrombosis of the basilar artery aneurysm was diagnosed. Target 3D Coil embolization with frame construction in the aneurysmal sac was performed, resulting in the complete disappearance of the aneurysm and improvement of the oculomotor nerve palsy. Magnetic resonance imaging at five years postoperatively confirmed that the thrombus had completely disappeared, and there was no recurrence of the aneurysm. The closed loops in the Target 3D Coil may have contributed to the cohesive mass of coils remaining in the sac of the PTIA, potentially leading to healing. Conclusion: The characteristics of the Target 3D Coil may have prevented migration of the coil into the thrombus, potentially contributing to the successful resolution of the aneurysm.

Sarcopenia assessed using a questionnaire can predict in-hospital mortality in older patients with pulmonary tuberculosis.

BACKGROUND & AIMS: Pulmonary tuberculosis is a severe disease with a high mortality rate. However, whether sarcopenia is a risk factor for in-hospital mortality remains unclear. The SARC-F (five items: strength, assistance in walking, rising from a chair, climbing stairs, and falls) is a questionnaire developed to screen for sarcopenia. This study aimed to determine whether the high risk of sarcopenia, assessed using the SARC-F questionnaire, affects in-hospital mortality in older patients with pulmonary tuberculosis. METHODS: This was a retrospective, observational study. We included patients with active pulmonary tuberculosis aged ≥65 years who required inpatient treatment between 30 April 2021 and 30 November 2022. We assessed sarcopenia using SARC-F, and SARC-F ≥ 4 points at admission was defined as a high risk of sarcopenia. The primary outcome was all-cause mortality during hospitalisation. We extracted information on age, sex, body mass index, comorbidities, blood and biochemical tests, modified Glasgow Prognostic Score, calf circumference, geriatric nutritional risk index, physiotherapy, and length of hospital stay from medical records. RESULTS: We included 147 patients (mean age: 83.0 ± 7.8 years; males: 61.9%). Ninety-three (63.3%) patients had a high risk of developing sarcopenia. Patients with a high risk of sarcopenia were significantly older (mean: 85.0 ± 7.1 years), had a lower body mass index (median: 18.1 kg/m2, range: 16.1-20.5 kg/m2), had a higher modified Glasgow Prognostic Score (median: 2, range: 2-2), and had a lower calf circumference (mean: 26.8 ± 3.6 cm), had a lower geriatric nutritional risk index (mean: 72.2 ± 12.9) than those without high-risk sarcopenia. More patients with a high risk of sarcopenia underwent physiotherapy (93.5%) than those without high-risk sarcopenia (P < 0.01, all). Kaplan-Meier survival curves showed that patients with a high risk of sarcopenia had significantly lower overall survival than those without high-risk sarcopenia (log-rank test, P = 0.001). Logistic regression analysis for in-hospital mortality showed that a high risk of sarcopenia significantly affected in-hospital mortality (odds ratio [OR]: 6.425, 95% confidence interval [CI]: 1.399-47.299). In addition, logistic regression analysis for each item of SARC-F showed that assistance in walking (OR: 3.931, 95% CI: 1.816-9.617) and rising from a chair (OR: 2.458, 95% CI: 1.235-5.330) significantly affected in-hospital mortality. CONCLUSION: A high risk of sarcopenia, as assessed using SARC-F at admission, was a risk factor for in-hospital mortality in older patients with pulmonary tuberculosis. Among the SARC-F items, assistance in walking and rising from a chair were the risk factors for in-hospital mortality.

Von Hippel-Lindau disease with intracranial hemorrhage due to arteriovenous anastomosis via multiple spinal hemangioblastomas: illustrative case.

BACKGROUND: Some spinal hemangioblastomas (HBLs) resemble spinal vascular malformations. Intracranial subarachnoid hemorrhage (SAH) secondary to spinal HBL has rarely been reported. OBSERVATIONS: A 67-year-old man with a prolonged von Hippel-Lindau disease (VHL) history presented with sudden headache and vomiting. Cranial and cervical computed tomography (CT) revealed severe infratentorial, supratentorial, and cervical SAH. Cranial CT angiography and magnetic resonance imaging revealed a mismatch in hemorrhage and intracranial tumor localization, with no vascular lesions that could lead to intracranial SAH. Cervical CT angiography revealed abnormal blood vessels originating from 5 spinal tumors suspected to be HBLs. We considered that the SAH was caused by venous reflex from vascular malformation-like spinal HBLs. Transarterial embolization (TAE) of the feeding artery of HBLs was performed to improve symptoms and reduce rebleeding risk. Nine months after TAE, angiography showed no venous reflux into the intracranial space. Ten months later, the authors excised the T1-2 tumor because the patient complained of progressive paralysis of the right upper extremity. LESSONS: In HBL with prolonged VHL, intracranial hemorrhage due to venous regurgitation via a mimicked vascular malformation may occur. Reducing venous reflux with TAE may improve symptoms and prevent rebleeding.

Successful Thrombectomy for Endocarditis-Related Stroke in a Very Young Patient: Illustrative Case.

Objective: Unlike in older adults, ischemic stroke in young patients occurs secondary to preexisting conditions. Infective endocarditis (IE) is among the most important causes of stroke in young adults and has a severe prognosis. There are few reports of mechanical thrombectomy (MT) for IE-induced large-vessel occlusion (LVO). This paper reports a case of acute IE-induced LVO in a young patient who was successfully treated with MT. Case Presentation: An 18-year-old woman presented to our hospital with severe headache, high fever, and left fingertip pain. She was admitted to the Department of Neurology for conservative treatment of suspected meningitis. On day 2 of admission, she developed acute left hemiparesis, left hemispatial neglect, and dysarthria. MRA showed occlusion of the right M1 segment of the middle cerebral artery, and the patient immediately underwent MT. After a single pass, we achieved thrombolysis in cerebral infarction 2b. A white clot was diagnosed as a vegetation on pathological examination. As transesophageal echocardiography showed a vegetation on the mitral valve, the patient was diagnosed with IE and underwent cardiovascular surgery. The patient recovered well and underwent additional treatment and rehabilitation. Conclusion: Although rare, IE-induced septic emboli may occur in young patients with LVO, necessitating MT and pathological diagnosis of the clot.

Metabolic changes and anti-tumor effects of a ketogenic diet combined with anti-angiogenic therapy in a glioblastoma mouse model.

The ketogenic diet (KD) is a high fat and low carbohydrate diet that produces ketone bodies through imitation of starvation. The combination of KD and Bevacizumab (Bev), a VEGF inhibitor, is considered to further reduce the supply of glucose to the tumor. The metabolite changes in U87 glioblastoma mouse models treated with KD and/or Bev were examined using gas chromatography-mass spectrometry. The combination therapy of KD and Bev showed a decrease in the rate of tumor growth and an increase in the survival time of mice, although KD alone did not have survival benefit. In the metabolome analysis, the pattern of changes for most amino acids are similar between tumor and brain tissues, however, some amino acids such as aspartic acid and glutamic acid were different between tumors and brain tissues. The KD enhanced the anti-tumor efficacy of Bev in a glioblastoma intracranial implantation mouse model, based on lowest levels of microvascular density (CD31) and cellular proliferation markers (Ki-67 and CCND1) in KD + Bev tumors compared to the other groups. These results suggested that KD combined with Bev may be a useful treatment strategy for patients with GBM.

Successful multiple burr hole openings for limb-shaking transient ischemic attack due to moyamoya disease: illustrative case.

BACKGROUND: Limb-shaking transient ischemic attacks (LS-TIAs) are a rare form of TIAs that present as involuntary movements of the limbs and indicate severe cerebral hypoperfusion. LS-TIAs are often reported in patients with carotid artery stenosis but can also affect patients with intracranial artery stenosis and moyamoya disease (MMD). OBSERVATIONS: A 72-year-old woman presented with repeated episodes of involuntary shaking movements of the right upper limb. Cerebral angiography revealed complete occlusion of the M1 segment of the left middle cerebral artery (MCA), and the left hemisphere was supplied by moyamoya vessels. She was treated with left direct revascularization without complications, and her involuntary movements subsided. However, she demonstrated involuntary shaking movements of the right lower limb 2 months postoperatively. Cerebral angiography revealed complete occlusion of the A1 segment of the left anterior cerebral artery (ACA). The multiple burr hole opening (MBHO) procedure was performed to improve perfusion in the left ACA territory and after 3 months, the patient's symptoms resolved. LESSONS: This case demonstrated that LS-TIAs can also develop as ischemic symptoms due to MMD. Moreover, instances of LS-TIA of the upper and lower limbs developed separately in the same patient. The patient's symptoms improved with direct revascularization and MBHO.

Multi-marker algorithms based on CXCL13, IL-10, sIL-2 receptor, and ß2-microglobulin in cerebrospinal fluid to diagnose CNS lymphoma.

Tumor biopsy is essential for the definitive diagnosis of central nervous system (CNS) lymphoma. However, the biopsy procedure carries the risk of complications such as bleeding, convulsions, and infection. Cerebrospinal fluid (CSF) ß2-microglobulin (ß2-MG), soluble IL-2 receptor (sIL-2R), and interleukin-10 (IL-10) are known to be useful diagnostic biomarkers for CNS lymphoma. The C-X-C motif chemokine ligand 13 (CXCL13) was recently reported to be another useful biomarker for CNS lymphoma. The purpose of this study is to establish a diagnostic algorithm that can avoid biopsy by combining these diagnostic biomarkers. In the first, we conducted a case-control study (n = 248) demonstrating that the CSF CXCL13 concentration was significantly increased in CNS lymphoma patients compared with various other brain diseases (AUC = 0.981). We established a multi-marker diagnostic model using CSF CXCL13, IL-10, ß2-MG, and sIL-2R from the results of the case-control study and then applied the model to a prospective study (n = 104) to evaluate its utility. The multi-marker diagnostic algorithms had excellent diagnostic performance: the sensitivity, specificity, positive predictive value, and negative predictive value were 97%, 97%, 94%, and 99%, respectively. In addition, CSF CXCL13 was a prognostic biomarker for CNS lymphoma patients. Our study suggests that multi-marker algorithms are important diagnostic tools for patients with CNS lymphoma.

Tumor-associated macrophage related interleukin-6 in cerebrospinal fluid as a prognostic marker for glioblastoma.

Interleukin-6 (IL-6) is one of the pleiotropic cytokines and has received attention as a critical factor implicated in the invasion and the angiogenesis of various cancers. In glioma, IL-6 is known to be associated with the prognosis; however, the roles of IL-6 in cerebrospinal fluid (CSF) has not been studied sufficiently. We examined the concentration of CSF IL-6 using 75 CSF samples of glioma (54 glioblastomas (GBMs) and 21 other grades of gliomas) and analyzed the association CSF IL-6 with infiltration levels of tumor-associated macrophages (TAMs) and prognosis. The concentration of CSF IL-6 in GBM patients was significantly higher than that in other grades of gliomas. CSF IL-6 levels were associated with the infiltration rate of TAMs in GBMs, and IL-6 levels were increased in the GBM cells co-cultured with TAM-like macrophages. The CSF of GBM patients, which contained high concentration of IL-6, promoted the migration ability of GBM cells, and neutralization antibodies of IL-6 inhibited its migration ability. Finally, in both univariate and multivariate analysis, higher CSF IL-6 levels were associated with poorer prognosis in GBM patients. These results indicated that the concentration of CSF IL-6 is associated with TAMs' infiltration level and may be a useful prognostic biomarker for the GBM patients.

MicroRNA regulating stanniocalcin-1 is a metastasis and dissemination promoting factor in glioblastoma.

BACKGROUND: MicroRNAs (miRs) regulate many biological processes, such as invasion, angiogenesis, and metastasis. Glioblastoma (GBM) patients with metastasis/metastatic dissemination have a very poor prognosis; therefore, inhibiting metastasis/metastatic dissemination has become an important therapeutic strategy for GBM treatment. METHODS: Using 76 GBM tissues, we examined the expression levels of 23 GBM-related miRs and compared the miRs' expression levels between GBMs with metastasis/metastatic dissemination and GBMs without metastasis/metastatic dissemination. Using the bioinformatics web site, we searched the target genes of miRs. To analyze the function of target gene, several biological assays and survival analysis by the Kaplan-Meier method were performed. RESULTS: We found that eight miRs were significantly decreased in GBM with metastasis/metastatic dissemination. By the bioinformatics analysis, we identified stanniocalcin-1 (STC1) as the most probable target gene against the combination of these miRs. Four miRs (miR-29B, miR-34a, miR-101, and miR-137) have predictive binding sites in STC1 mRNA, and mRNA expression of STC1 was downregulated by mimics of these miRs. Also, mimics of these miRs and knockdown of STC1 by siRNA suppressed invasion in GBM cells. GBM with metastasis/metastatic dissemination had significantly higher levels of STC1 than GBM without metastasis/metastatic dissemination. Finally, Kaplan-Meier analysis demonstrated that GBMs with high STC1 level had significantly shorter survival than GBMs with low STC1 level. CONCLUSIONS: STC1 may be a novel metastasis/metastatic dissemination promoting factor regulated by several miRs in GBM. Because STC1 is a secreted glycoprotein and functions via the autocrine/paracrine signals, inhibiting STC1 signal may become a novel therapeutic strategy for GBM.

Strategy for patients with co-existence of meningioma and intracerebral aneurysm, especially unruptured aneurysm (-seven cases and review of the literature-).

BACKGROUND: Intracerebral aneurysms co-existing with meningiomas are rare. Treatment strategies for intracerebral aneurysms co-existing with meningiomas have not yet been established. METHODS: We studied 62 patients with intracerebral aneurysms co-existing with meningiomas in the literature including our seven cases, evaluated the various managements and outcomes, and discussed the strategy for intracerebral aneurysms, especially unruptured cases, co-existing with meningiomas. The aim of this study was to develop a guide for the management of non-subarachnoid hemorrhage (SAH) intracerebral aneurysms co-existing with meningiomas. RESULTS: Most intracerebral aneurysms co-existing with meningiomas are unruptured. Of course, aneurysms presenting with SAH should be treated first followed by the resection of meningiomas. In addition, intracerebral aneurysms inside or adjacent to meningiomas have a high risk of intraoperative rupture during the surgery for meningiomas, and it may be necessary to treat them first followed by the resection of meningiomas with one or two-step surgery. In nine out of 62 patients, ten intracerebral unruptured aneurysms were not treated; however, no intracerebral aneurysms ruptured during the follow-up period, and outcomes of these patients were good in eight and poor in only one. CONCLUSIONS: Intracerebral unruptured aneurysms remote from meningiomas may be treated according to the guidelines for unruptured aneurysms. In advance of microsurgery and endovascular techniques, both lesions should be treated, if possible.

Supratentorial extraventricular WHO grade III (anaplastic) ependymoma 17 years after total removal of WHO grade II ependymoma of the fourth ventricle.

We report a WHO grade III ependymoma of the supratentorial interhemispheric fissure and grew to form a large mass with anaplastic transformation without local recurrence 17 years after the total removal of a fourth ventricular WHO grade II ependymoma. We emphasize the necessity of long-term follow-up, even in benign ependymomas.

Tumor-Associated Macrophages Associate with Cerebrospinal Fluid Interleukin-10 and Survival in Primary Central Nervous System Lymphoma (PCNSL).

Increased tumor-associated macrophages (TAMs) have been reported to be associated with poor prognosis in various tumors; however, the importance of TAMs in primary central nervous system lymphoma (PCNSL) has not been clarified. In 47 patients with PCNSL who were treated with high-dose methotrexate (MTX) and radiotherapy, the relationships between the infiltration levels of TAMs and the clinicopathological parameters were analyzed. Univariate analysis of the Cox proportional hazards model using continuous scales revealed that increased CD68 positive (+) TAMs was significantly associated with inferior progression-free survival (PFS) (P = 0.04), and trends were observed for the increased CD163(+) TAMs and having shorter PFS (P = 0.05). However, increased TAMs were not associated with overall survival. Because TAMs are known to produce various cytokines, we examined the relationships between cerebrospinal fluid (CSF) cytokines and TAMs. CSF interleukin-6 (IL-6) and soluble IL-2 receptor were not correlated with the infiltration rate of TAMs; however, CSF IL-10 level was correlated with infiltration levels of CD68 and CD163(+) TAMs. We also confirmed the expression of IL-10 in CD68(+) and CD163(+) TAMs by double immunostaining analysis. Our results indicate that a high level of IL-10 in CSF may be positively associated with the infiltration level of TAMs in PCNSLs.

Combined IDH1 mutation and MGMT methylation status on long-term survival of patients with cerebral low-grade glioma.

OBJECTIVE: The management of low-grade glioma (LGG) still remains controversial because the effectiveness of early and extensive resection is unclear, and the use of radiation therapy or chemotherapy is not well-defined. In particular, the importance of prognostic factors for survival remains a matter of discussion. The purpose of this study was to validate prognostic factors for survival in patients with LGG. MATERIALS AND METHODS: A consecutive series of 55 patients with WHO grade II LGG treated in our institute between 1983 and 2013 were retrospectively reviewed to determine the prognostic factors for survival. All data were retrospectively analyzed from the aspect of baseline characteristics, pathological findings, genetic change, surgical treatments, adjuvant therapies, and survival time. Cox multivariate analysis was performed to determine the prognostic factors for survival. RESULTS: There were 28 patients with diffuse astrocytoma (DA), 21 patients with oligodendroglioma (OG), and 6 patients with oligoastrocytoma (OA) diagnosed on initial surgery. The median overall survival was 193 months and fifteen patients (27.3%) died. A mutation in isocitrate dehydrogenase-1 (IDH1) was found in 72.9% of LGG, and this mutation was positively correlated with methylation of O6-methylguanine-DNA methyltransferase (MGMT) (p=0.02). A better prognosis was significantly associated with combined IDH1 mutation and MGMT methylation status (both positive vs both negative, HR 0.079 [95% CI 0.008-0.579], p=0.012), as well as histology (OG vs DA and OA, HR 0.158 [95% CI 0.022-0.674], p=0.011) and tumor size (<6 cm vs ≥6 cm, HR 0.120 [95% CI 0.017-0.595], p=0.008). CONCLUSIONS: Tumor histology, size and IDH-mutation status are important predictors for prolonged overall survival in patients with LGG and may provide a reliable tool for standardizing future treatment strategies.

STAT3 activation is associated with cerebrospinal fluid interleukin-10 (IL-10) in primary central nervous system diffuse large B cell lymphoma.

Signal transducers and activators of transcription 3 (STAT3) are activated by various cytokines and oncogenes; however, the activity and pathogenesis of STAT3 in diffuse large B cell lymphoma of the central nervous system have not been thoroughly elucidated. We investigated the phosphorylation levels of STAT3 in 40 specimens of primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) and analyzed the association between phsopho-STAT3 (pSTAT3) expression and cerebrospinal fluid (CSF) concentration of interleukin-10 (IL-10) or IL-6. Immunohistochemistry and Western blot analysis revealed that most of the specimens in PCNS DLBCL expressed pSTST3 protein, and a strong phosphorylation levels of STAT3 was statistically associated with high CSF IL-10 levels, but not with CSF IL-6 levels. Next, we demonstrated that recombinant IL-10 and CSF containing IL-10 induced the phosphorylation of STAT3 in PCNS DLBCL cells. Furthermore, molecular subtype classified by Hans' algorithm was correlated with pSTAT3 expression levels and CSF IL-10 levels. These results suggest that the STAT3 activity is correlated with CSF IL-10 level, which is a useful marker for STAT3 activity in PCNS DLBCLs.

Diagnostic yield and morbidity by neuronavigation-guided frameless stereotactic biopsy using magnetic resonance imaging and by frame-based computed tomography-guided stereotactic biopsy.

BACKGROUND: We compared the diagnostic yield and morbidity by frame-based computed tomography-guided stereotactic biopsy (CTSTB) with Brown-Roberts-Wells (BRW) unit and by neuronavigation-guided frameless stereotactic biopsy (NSTB) using magnetic resonance imaging (MRI). METHODS: The subjects' age range was 15-83 years. CTSTB with BRW unit was performed for 59 tumors (58 cases, 1988-2007). NSTB was performed for 38 tumors (35 cases, 2007-2013) with the needle sheath attached to the head holder. By NSTB, target locations of sampling points and trajectories were confirmed by using MRI. Diffusion tensor imaging-based fiber tractography was used to achieve safe trajectories. STB by using BRW did not visualize the trajectory virtually; however, the planning images for NSTB were able to show the trajectory virtually before the procedure. RESULTS: Histological diagnoses were established for 93 tumors at the first biopsy. The diagnostic yield was 94.9% by CTSTB and 97.4% by NSTB (P = 0.944). The morbidity rate was 5.1% by CTSTB and 0% by NSTB (P = 0.417). The absolute risk reduction was 23.1% by NSTB when the targets were basal ganglia (putamen, globus pallidus) or thalamus. In the cases of glioma for which the targets were basal ganglia (putamen, globus pallidus) or thalamus, the absolute risk reduction by NSTB was 30%. CONCLUSIONS: There was no significant difference between CTSTB and NSTB concerning the diagnostic yield and morbidity. However, when the target is the basal ganglia (putamen, globus pallidus) or thalamus and glioma is suspected, NSTB by using MRI with virtual trajectory is preferable to CTSTB concerning morbidity.

GC/MS-based metabolomic analysis of cerebrospinal fluid (CSF) from glioma patients.

Metabolomics has recently undergone rapid development; however, metabolomic analysis in cerebrospinal fluid (CSF) is not a common practice. We analyzed the metabolite profiles of preoperative CSF samples from 32 patients with histologically confirmed glioma using gas chromatography/mass spectrometry (GC/MS). We assessed how alterations in the metabolite levels were related to the World Health Organization (WHO) tumor grades, tumor location, gadolinium enhancement on magnetic resonance imaging (MRI), and the isocitrate dehydrogenase (IDH) mutation status. Sixty-one metabolites were identified in the CSF from glioma patients using targeted, quantitative and non-targeted, semi-quantitative analysis. The citric and isocitric acid levels were significantly higher in the glioblastoma (GBM) samples than in the grades I-II and grade III glioma samples. In addition, the lactic and 2-aminopimelic acid levels were relatively higher in the GBM samples than in the grades I-II glioma samples. The CSF levels of the citric, isocitric, and lactic acids were significantly higher in grade I-III gliomas with mutant IDH than in those with wild-type IDH. The tumor location and enhancement obtained using MRI did not significantly affect the metabolite profiles. Higher CSF levels of lactic acid were statistically associated with a poorer prognosis in grades III-IV malignant gliomas. Our study suggests that the metabolomic analysis of CSF from glioma patients may be useful for predicting the glioma grade, metabolic state, and prognosis of gliomas.

MicroRNA-183 upregulates HIF-1α by targeting isocitrate dehydrogenase 2 (IDH2) in glioma cells.

MicroRNAs (miRs) are small, non-coding RNAs that regulate gene expression and contribute to cell proliferation, differentiation and metabolism. Our previous study revealed the extensive modulation of a set of miRs in malignant glioma. In that study, miR microarray analysis demonstrated the upregulation of microRNA-183 (miR-183) in glioblastomas. Therefore, we examined the expression levels of miR-183 in various types of gliomas and the association of miR-183 with isocitrate dehydrogenase 2 (IDH2), which has complementary sequences to miR-183 in its 3'-untranslated region (3'UTR). In present study, we used real-time PCR analysis to demonstrate that miR-183 is upregulated in the majority of high-grade gliomas and glioma cell lines compared with peripheral, non-tumorous brain tissue. The mRNA and protein expression levels of IDH2 are downregulated via the overexpression of miR-183 mimic RNA in glioma cells. Additionally, IDH2 mRNA expression is upregulated in glioma cells expressing anti-miR-183. We verified that miR-183 directly affects IDH2 mRNA levels in glioma cells using luciferase assays. In malignant glioma specimens, the expression levels of IDH2 were lower in tumors than in the peripheral, non-tumorous brain tissues. HIF-1α levels were upregulated in glioma cells following transfection with miR-183 mimic RNA or IDH2 siRNA. Moreover, vascular endothelial growth factor and glucose transporter 1, which are downstream molecules of HIF-1α, were upregulated in cells transfected with miR-183 mimic RNA. These results suggest that miR-183 upregulation in malignant gliomas induces HIF-1α expression by targeting IDH2 and may play a role in glioma biology.

Supratentorial pure cortical ependymoma.

Ependymoma usually occurs in the lateral or the fourth ventricle. Supratentorial extraventricular ependymoma is relatively rare. However, extraventricular ependymoma located at the cerebral cortex is extremely rare. We treated a 20-year-old woman who presented with generalized seizures. Cranial CT scan revealed a calcified mass in the left precentral gyrus. MRI confirmed an extraventricular, 12-mm-diameter intracortical mass. After gadolinium injection, tumor enhancement was mild and heterogeneous. The tumor was totally resected without neurological deterioration. Histological features were consistent with ependymoma, forming perivascular pseudorosettes without anaplastic figures. Immunohistochemistry showed positive staining for glial fibrillary acidic protein, S-100, and epithelial membrane antigen. A diagnosis of ependymoma of World Health Organization grade II was made. The patient has not had a seizure since the operation. There has been no clinical or radiologic evidence of recurrence during a 16-month postoperative follow-up.

Patterns of failure after multimodal treatments for high-grade glioma: effectiveness of MIB-1 labeling index.

BACKGROUND: The purpose of the present study was to analyze the recurrence pattern of high-grade glioma treated with a multimodal treatment approach and to evaluate whether the MIB-1 labeling index (LI) could be a useful marker for predicting the pattern of failure in glioblastoma (GB). METHODS AND MATERIALS: We evaluated histologically confirmed 131 patients with either anaplastic astrocytoma (AA) or GB. A median dose was 60 Gy. Concomitant and adjuvant chemotherapy were administered to 111 patients. MIB-1 LI was assessed by immunohistochemistry. Recurrence patterns were categorized according to the areas of recurrence as follows: central failure (recurrence in the 95% of 60 Gy); in-field (recurrence in the high-dose volume of 50 Gy; marginal (recurrence outside the high-dose volume) and distant (recurrence outside the RT field). RESULTS: The median follow-up durations were 13 months for all patients and 19 months for those remaining alive. Among AA patients, the 2-year progression-free and overall survival rates were 23.1% and 39.2%, respectively, while in GB patients, the rates were 13.3% and 27.6%, respectively. The median survival time was 20 months for AA patients and 15 months for GB patients. Among AA patients, recurrences were central in 68.7% of patients; in-field, 18.8%; and distant, 12.5%, while among GB patients, 69.0% of recurrences were central, 15.5% were in-field, 12.1% were marginal, and 3.4% were distant. The MIB-1 LI medians were 18.2% in AA and 29.8% in GB. Interestingly, in patients with GB, the MIB-1 LI had a strong effect on the pattern of failure (P = 0.014), while the extent of surgical removal (P = 0.47) and regimens of chemotherapy (P = 0.57) did not. CONCLUSIONS: MIB-1 LI predominantly affected the pattern of failure in GB patients treated with a multimodal approach, and it might be a useful tool for the management of the disease.

Cerebrospinal fluid interleukin-10 is a potentially useful biomarker in immunocompetent primary central nervous system lymphoma (PCNSL).

The diagnosis of primary central nervous system lymphoma (PCNSL) by radiographical examination is often difficult because of its similarity to other brain tumors. To test whether interleukin-10 (IL-10) and IL-6 can be used to distinguish PCNSL from other brain tumors that are radiographically similar, cerebrospinal fluid (CSF) levels of IL-10 and IL-6 were measured in 66 patients with intracranial tumors (PCNSLs: 26 cases; other brain tumors: 40 cases). In the patients with PCNSLs, the median CSF levels of IL-10 and IL-6 were 27 pg/mL and 5.4 pg/mL, respectively. The CSF IL-10 and IL-6 levels were significantly higher in PCNSLs than in the other brain tumors. To validate the diagnostic value of CSF IL-10 in PCNSL, we prospectively examined 24 patients with brain lesions that were suspected to be PCNSL. We observed that the CSF IL-10 levels were significantly higher in PCNSLs than in other brain tumors. At an IL-10 cutoff level of 9.5 pg/mL, the sensitivity and specificity were 71.0% and 100%, respectively. After therapy, the CSF IL-10 levels were decreased in all patients and were increased at relapse in most of these patients. Immunohistochemically, all PCNSLs, except for 1 unclassified PCNSL, expressed both IL-10 and IL-10 receptor-A. In the patients with high CSF IL-10, IL-10 expression levels in tumor were relatively higher, compared with low CSF IL-10; however, there was no significant difference between these groups. In addition, elevated CSF level of IL-10 was significantly associated with having a shorter progression-free survival (hazard ratio, 3.37; 95% confidence interval, 0.985-11.528; log-rank, P= .038). These results indicate that the CSF level of IL-10 may be a useful diagnostic and prognostic biomarker in patients with PCNSLs.