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Background: Brain metastasis (BrM) is prevalent among patients with NSCLC, and surgical resection of BrM constitutes a promising treatment strategy for local management and histopathological diagnosis, although it is offered for a select group of patients. Limited information exists concerning the improvement in performance status (PS) following BrM resection or the outcomes stratified by subsequent systemic therapy., Methods: We conducted a retrospective single-center cohort study including NSCLC patients with surgically resected BrM and focused on the improvement in PS and subsequent therapy after BrM resection., Results: 71 patients were included, and the median overall survival was 18.3 months (95% confidence interval [95% CI]: 8.7, not reached). Patients with NSCLC who underwent surgical resection of BrM showed significant improvement in PS (18% and 39% showed ECOG PS of 0-1, before and after BrM resection, respectively [p = 0.006]), and patients with PS improvement were younger than those with PS unimprovement (median, 62 years versus 66 years; p = 0.041). Regarding subsequent systemic therapy after BrM resection, 21 patients (30%) received cytotoxic chemotherapy, 14 patients (20%) received tyrosine kinase inhibitors (TKIs), 3 patients (4%) received immune checkpoint inhibitors (ICIs), and 21 patients (30%) received no subsequent therapy. The survival outcomes of patients stratified by subsequent systemic treatments suggested the tendency that those who received TKI or ICI showed better survival outcomes, although a small number of patients hindered statistical comparisons., Conclusions: We describe the outcomes of patients with NSCLC who underwent surgical resection of BrM, revealing that younger patients were more likely to anticipate improvement in PS, and patients who received TKI or ICI after BrM resection tended to exhibit a more preferable prognosis., (© 2024. The Author(s).)

Purpose: The telomerase reverse transcriptase promoter (TERTp) mutation is an unfavorable prognostic factor in isocitrate dehydrogenase-wildtype (IDHwt) histologically lower-grade astrocytoma (LGA), which was incorporated as a key component in the WHO 2021 classification of IDHwt LGA, replacing histologic grades in the WHO 2016 classification. The purpose of this study was to identify the imaging characteristics predictive of TERTp mutations in IDHwt LGA., Methods: This retrospective study was approved by our institutional review board. This single-center study retrospectively included 59 patients with pathologically confirmed IDHwt LGA with known TERTp mutation status. In addition to clinical information and morphological characteristics, semi-quantitative imaging biomarkers such as the tumor-to-normal ratio (T/N ratio) on 18 F-FDG-PET, normalized apparent diffusion coefficient (nADC), and histogram parameters from normalized relative cerebral blood volume (nrCBV) maps were compared between (a) TERTp-wildtype and TERTp-mutant tumors or (b) grade II and grade III astrocytoma. A p value < 0.05 was considered significant., Results: There were no significant differences in the conventional imaging findings, T/N ratio on FDG-PET, nrCBV or ADC histogram metrics between IDHwt LGA with TERTp mutations and those without. Grade III IDHwt astrocytomas exhibited significantly higher nrCBV values, T/N ratio and lower ADC parameters than grade II IDHwt astrocytoma., Conclusions: In patients with IDHwt LGA, T/N ratio, nrCBV values and nADC may be surrogate markers for predicting histologic grade, but are not useful for predicting TERTp mutations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A 39-year-old man had an intracranial tumour without infiltration into the surrounding cerebral tissue. The tumour recurred seven times in 11 years but maintained a well-demarcated character. Histopathological examination of the 4th surgical specimens showed nests of tumour cells surrounding small blood vessels. The tumour cells harboured amphophilic cytoplasm and small round nuclei with fine chromatin, and perinuclear haloes and clear borders were frequently observed, which was unclassifiable histology. By the Deutsches Krebsforschungszentrum methylation classifier, the tumour was not classified into any of the methylation classes. mRNA sequencing identified a novel SREBF1::NACC1 gene fusion. This intracranial tumour could be a novel tumour entity with NACC1 rearrangement showing characteristic histological and diagnostic imaging findings., (© 2022 British Neuropathological Society.)

Glioblastoma is the most common adult brain tumour, representing a high degree of malignancy. Transcription factors such as RUNX1 are believed to be involved in the malignancy of glioblastoma. RUNX1 functions as an oncogene or tumour suppressor gene with diverse target genes. Details of the effects of RUNX1 on the acquisition of malignancy in glioblastoma remain unclear. Here, we show that RUNX1 downregulates p21 by enhancing expressions of BIRC5 and PIF1, conferring anti-apoptotic properties on glioblastoma. A gene switch-off therapy using alkylating agent-conjugated pyrrole-imidazole polyamides, designed to fit the RUNX1 DNA groove, decreased expression levels of BIRC5 and PIF1 and induced apoptosis and cell cycle arrest via p21. The RUNX1-BIRC5/PIF1-p21 pathway appears to reflect refractory characteristics of glioblastoma and thus holds promise as a therapeutic target. RUNX gene switch-off therapy may represent a novel treatment for glioblastoma., (© 2022. The Author(s).)

The number of awake craniotomies is increasing because of its beneficial features. However, not enough information is available regarding the current status of awake craniotomy in Japan. To evaluate the current status of awake craniotomy in institutes, a nationwide questionnaire survey was conducted. From June to August 2019, we conducted a questionnaire survey on awake craniotomy in the neurosurgery department of 45 institutes that perform awake craniotomies in Japan. Responses were obtained from 39 institutes (response rate, 86.7%). The main methods of awake craniotomy were almost the same in all institutes. Twenty-six institutes (66.7%) had fewer than 10 awake craniotomies (low-volume institutes) per year, and 13 high-volume institutes (33.3%) performed more than 10 awake craniotomies annually. Some institutes experienced a relatively high frequency of adverse events. In 11 institutes (28.2%), the frequency of intraoperative seizures was more than 10%. An intraoperative seizure frequency of 1%-9%, 10%-29%, and over 30% was identified in 12 (92%), 0 (0%), and 1 (8%) of the high-volume institutes, which was significantly less than in 16 (62%), 10 (38%), and 0 (0%) of the low-volume institutes (p = 0.0059). The routine usage of preoperative antiepileptic drugs was not different between them, but the old type was used more often in the low-volume institutes (p = 0.0022). Taken together, the annual number of awake craniotomies was less than 10 in over two-thirds of the institutes. Fewer intraoperative seizures were reported in the high-volume institutes, which tend not to preoperatively use the old type of antiepileptic drugs.

Objective: This study aimed to examine the association of preoperative intratumoral susceptibility signal (ITSS) grade with hemorrhage after stereotactic biopsy (STB)., Methods: The authors retrospectively reviewed 66 patients who underwent STB in their institution. Preoperative factors including age, sex, platelet count, prothrombin time-international normalized ratio, activated thromboplastin time, antiplatelet agent use, history of diabetes mellitus and hypertension, target location, anesthesia type, and ITSS data were recorded. ITSS was defined as a dot-like or fine linear low signal within a tumor on susceptibility-weighted imaging (SWI) and was graded using a 3-point scale: grade 1, no ITSS within the lesion; grade 2, 1-10 ITSSs; and grade 3, ≥ 11 ITSSs. Postoperative final tumor pathology was also reviewed. The association between preoperative variables and the size of postoperative hemorrhage was examined., Results: Thirty-four patients were men and 32 were women. The mean age was 66.6 years. The most common tumor location was the frontal lobe (27.3%, n = 18). The diagnostic yield of STB was 93.9%. The most common pathology was lymphoma (36.4%, n = 24). The ITSS was grade 1 in 37 patients (56.1%), grade 2 in 14 patients (21.2%), and grade 3 in 15 patients (22.7%). Interobserver agreement for ITSS was almost perfect (weighted kappa = 0.87; 95% CI 0.77-0.98). Age was significantly associated with ITSS (p = 0.0075). Postoperative hemorrhage occurred in 17 patients (25.8%). Maximum hemorrhage diameter (mean ± SD) was 1.78 ± 1.35 mm in grade 1 lesions, 2.98 ± 2.2 mm in grade 2 lesions, and 9.51 ± 2.11 mm in grade 3 lesions (p = 0.01). Hemorrhage > 10 mm in diameter occurred in 10 patients (15.2%), being symptomatic in 3 of them. Four of 6 patients with grade 3 ITSS glioblastomas (66.7%) had postoperative hemorrhages > 10 mm in diameter. After adjusting for age, ITSS grade was the only factor significantly associated with hemorrhage > 10 mm (p = 0.029). Compared with patients with grade 1 ITSS, the odds of postoperative hemorrhage > 10 mm in diameter were 2.57 times higher in patients with grade 2 ITSS (95% CI 0.31-21.1) and 9.73 times higher in patients with grade 3 ITSS (95% CI 1.57-60.5)., Conclusions: ITSS grade on SWI is associated with size of postoperative hemorrhage after STB.

Background: Intra-cranial schwannomas account for less than 8% of brain tumors, among which more than 80% arise from the vestibular nerve. Intra-cerebellar schwannomas are extremely rare. Several cases have been previously reported but without remarkable degenerative changes on histology., Case Presentation: A 61-year-old man presented with worsening disorientation, and an imaging study revealed a cystic lesion (6.5 cm in the largest diameter) in the left hemisphere of the cerebellum accompanied by a mural nodule (2.5 cm) located just inside the skull with enhancement and focal calcification, in addition to hydrocephalus. The lesion was more than 5 mm from the left acoustic nerve. The patient underwent gross total resection. Pathological examination revealed remarkable degenerative changes with various morphological features. Tumor cells were pleomorphic with rich cytoplasm containing numerous eosinophilic granules. Blood vessels and extracellular matrix showed remarkable hyalinization. Immunohistochemical staining revealed that the tumor cells were positive for S-100 protein and negative for Olig2. The tumor was diagnosed as a schwannoma with marked degenerative changes., Conclusions: The present case is discussed with reference to a systematic review of previous reports of intra-cerebellar schwannoma. Intra-cerebellar schwannoma should be included in the differential diagnosis of cystic lesions with heterogeneous histopathological morphology in the cerebellum., (© 2022. The Author(s).)

Background: Mutations in driver genes such as IDH and BRAF have been identified in gliomas. Meanwhile, dysregulations in the p53, RB1, and MAPK and/or PI3K pathways are involved in the molecular pathogenesis of glioblastoma. RAS family genes activate MAPK through activation of RAF and PI3K to promote cell proliferation. RAS mutations are a well-known driver of mutation in many types of cancers, but knowledge of their significance for glioma is insufficient. The purpose of this study was to reveal the frequency and the clinical phenotype of RAS mutant in gliomas., Methods: This study analysed RAS mutations and their clinical significance in 242 gliomas that were stored as unfixed or cryopreserved specimens removed at Kyoto University and Osaka National Hospital between May 2006 and October 2017. The hot spots mutation of IDH1/2, H3F3A, HIST1H3B, and TERT promoter and exon 2 and exon 3 of KRAS, HRAS, and NRAS were analysed with Sanger sequencing method, and 1p/19q codeletion was analysed with multiplex ligation-dependent probe amplification. DNA methylation array was performed in some RAS mutant tumours to improve accuracy of diagnosis., Results: RAS mutations were identified in four gliomas with three KRAS mutations and one NRAS mutation in one anaplastic oligodendroglioma, two anaplastic astrocytomas (IDH wild-type in each), and one ganglioglioma. RAS-mutant gliomas were identified with various types of glioma histology., Conclusion: RAS mutation appears infrequent, and it is not associated with any specific histological phenotype of glioma., (© 2021. The Author(s).)

Objective: High-grade gliomas are fast-growing and may exhibit more severe neurocognitive function (NCF) decline compared with low-grade gliomas. A comprehensive understanding of the NCF in patients with glioma may be critical for developing effective glioma treatments and rehabilitation interventions. This study evaluated NCF more comprehensively in patients with glioma using the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) and the Wechsler Memory Scale-Revised (WMS-R), and also determined the differences in NCF in relation with the WHO grades of gliomas., Methods: Thirty-five patients with newly diagnosed glioma were reviewed in the present study. The patients were divided into three groups, Grade II, III, and IV, based on the World Health Organization's classification of tumors of the central nervous system. NCF was assessed using the WAIS-III and WMS-R., Results: There were 14 (40.0%), 7 (20.0%), and 14 (40.0%) patients in the grade II, grade III, and grade IV groups, respectively. The results of the Kruskal-Wallis test showed significant differences in all the scores of the WAIS-III and WMS-R between grade II and grade IV. The scores of the WAIS-III and WMS-R in grade IV patients were borderline for NCF disorders, except in the attention/concentration domain. On the other hand, grade II and III groups had normal scores., Conclusion: Therefore, patients with a grade IV glioma presented NCF decline compared to grade II and III glioma. In contrast, the results of the WAIS-III and WMS-R indicated that the NCF of patients with grades II and III glioma was intact., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To propose a method for intraoperative mapping and monitoring of the medial frontal motor areas (MFMA)., Methods: We estimated the location of the MFMA using the corticocortical evoked potential (CCEP) provoked by electric stimuli to the primary motor area (M1) of the upper limb. We localized or defined the MFMA by recording the motor evoked potentials (MEPs) provoked by electric stimuli to the medial frontal cortex around the estimated area. We monitored the patients' motor function during awake craniotomy and sequentially recorded the MEPs of the upper and/or lower limbs. This method was applied to 8 patients., Results: Four patients who had part of the areas identified as the MFMA removed showed transient hemiparesis postoperatively (supplementary motor area [SMA] syndrome). The MEP from the M1 was preserved in the 4 patients. The resection of the identified MFMA might have caused their SMA syndrome. The CCEP showed a strong connection between the M1 and the SMA of the upper limb. Our method did not provoke any seizures., Conclusions: This is a safe and sensitive method for intraoperative mapping and monitoring of the MFMA by combining electrophysiologic monitoring and awake craniotomy. It is clinically useful for mapping the MFMA and can prevent permanent motor deficits., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introductions: [ N -methyl-C-11] α -Methylaminoisobutyric acid (MeAIB) is an artificial amino acid radiotracer used for PET study, which is metabolically stable in vivo. In addition, MeAIB is transported by system A neutral amino acid transport, which is observed ubiquitously in all types of mammalian cells. It has already been shown that MeAIB-PET is useful for malignant lymphoma, head and neck cancers, and lung tumors. However, there have been no reports evaluating the usefulness of MeAIB-PET in the diagnosis of brain tumors. The purpose of this study is to investigate the efficacy of system A amino acid transport PET imaging, MeAIB-PET, in clinical brain tumor diagnosis compared to [S-methyl-C-11]-L-methionine (MET)-PET., Methods: Thirty-one consecutive patients (male: 16, female: 15), who were suspected of having brain tumors, received both MeAIB-PET and MET-PET within a 2-week interval. All patients were classified into two groups: Group A as a benign group, which included patients who were diagnosed as low-grade astrocytoma, grade II or less, or other low-grade astrocytoma ( n =12) and Group B as a malignant group, which included patients who were diagnosed as anaplastic astrocytoma, glioblastoma multiforme (GBM), or recurrent GBM despite prior surgery or chemoradiotherapy ( n =19). PET imaging was performed 20 min after the IV injection of MeAIB and MET, respectively. Semiquantitative analyses of MeAIB and MET uptake using SUVmax and tumor-to-contralateral normal brain tissue ( T / N ) ratio were evaluated to compare these PET images. ROC analyses for the diagnostic accuracy of MeAIB-PET and MET-PET were also calculated., Results: In MeAIB-PET imaging, the SUVmax was 1.20 ± 1.29 for the benign group and 2.94 ± 1.22 for the malignant group ( p < 0.005), and the T / N ratio was 3.77 ± 2.39 for the benign group and 16.83 ± 2.39 for the malignant group ( p < 0.001). In MET-PET, the SUVmax was 3.01 ± 0.94 for the benign group and 4.72 ± 1.61 for the malignant group ( p < 0.005), and the T / N ratio was 2.64 ± 1.40 for the benign group and 3.21 ± 1.14 for the malignant group ( n.s. ). For the analysis using the T / N ratio, there was a significant difference between the benign and malignant groups with MeAIB-PET with p < 0.001. The result of ROC analysis using the T / N ratio indicated a better diagnosis accuracy for MeAIB-PET for brain tumors than MET-PET ( p < 0.01)., Conclusions: MeAIB, a system A amino acid transport-specific radiolabeled agents, could provide better assessments for detecting malignant type brain tumors. In a differential diagnosis between low-grade and high-grade astrocytoma, MeAIB-PET is a useful diagnostic imaging tool, especially in evaluations using the T / N ratio., Clinical Trial Registration: This trial was registered with UMIN000032498.

One histopathological characteristic of intracranial germinoma is abundant tumor-infiltrating lymphocytes (TILs) showing a two-cell pattern with large undifferentiated tumor cells. The programmed cell death 1 (PD-1)/programmed cell death 1 ligand (PD-L) axis has recently been recognized as an anti-tumor immune system. To evaluate intratumor immune status in intracranial germinoma, we examined expressions of PD-1 and PD-L1 (clone 28-8) and subtypes of TILs. Expressions of PD-1 and PD-L1 were detected immunohistochemically in 25 formalin-fixed, paraffin-embedded tumor specimens from 24 patients with intracranial germinoma consisting of 22 primary and 3 recurrent tumors. To evaluate subtypes of TILs, quantification of lymphocytes with CD3, CD8, CD4, and Foxp3 was performed. Statistical analyses were performed among PD-1, PD-L1 and subtypes of TILs. In 25 tumor tissue, expressions of PD-1 in TILs and PD-L1 in tumor cells were identified in 96% (24/25) and 92% (23/25), respectively. Expression of PD-1 was associated with CD3+ TIL density. Expression of PD-1 correlated with Foxp3+ TIL density and CD8+ TIL density, but not with CD4+ TIL density. Furthermore, expression of PD-1 correlated strongly with Foxp3+/CD4+ ratio. Taken together, increase of PD-1+ expression is associated with accumulation of Foxp3+ and CD8+ TILs. These findings intimate that PD-1/PD-L1 axis might shape the immune infiltration suggesting a modulation of the immune response and subsequent tumor growth in intracranial germinoma. Anti-PD-1 and anti-PD-L1 are potential immune therapeutic strategies in intracranial germinoma.

Background: The recurrence rate of chronic subdural hematoma (CSDH) after trepanation is relatively high and involves various factors. We encountered an extremely rare case in which metastasis of an extracranial malignant tumor to the hematoma capsule was thought to be causing short-term repeated recurrences of CSDH., Case Description: The patient was a 74-year-old man who had undergone bur hole evacuation of left CSDH 7 months earlier and had been receiving chemotherapy for stage IV gastric cancer for the preceding 6 months. He presented with symptoms of right hemiparesis and was diagnosed with left CSDH. Bur hole evacuation was performed twice, but the hematoma enlarged again both times within a short period. A third bur hole evacuation was performed after middle meningeal artery embolization, but the hematoma again enlarged shortly thereafter. Hematoma enlargement was finally suppressed by extracting the hematoma capsule under craniotomy. In histopathologic examinations, hematoxylin-eosin staining showed poorly differentiated adenocarcinoma primarily along the luminal side of the hematoma capsule and immunohistochemical staining showed results identical to findings from the existing gastric cancer. Pathologic results confirmed metastasis of the gastric cancer to the hematoma capsule, and this was considered to be the cause of short-term repeated recurrence of CSDH., Conclusions: To the best of our knowledge, this is the first report of metastasis to a hematoma capsule originating from an extracranial malignant tumor. The clinical course in the present case suggests metastasis of extracranial malignant tumor to the CSDH capsule as an extremely rare cause of recurrence., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To explore the relationship among parameters of magnetic resonance spectroscopy (MRS) and amide proton transfer (APT) imaging, and to assess the diagnostic performance of MRS and APT imaging for grading brain tumors in comparison with contrast enhancement of conventional MRI for preoperative grading in patients with brain tumor., Materials and Methods: Institutional Review Board approval and written informed consent were obtained. Forty-one patients with suspected brain tumors were enrolled in the study. Single-voxel MRS and 2D APT imaging of the same slice level were conducted using a 3T MRI scanner. Positive or negative contrast enhancement on T 1 -weighted images was assessed by two neuroradiologists. Correlations among metabolite concentrations, metabolite ratios, and calculated histogram parameters, including mean APT (APT mean ) and the 90th percentile of APT (APT 90 ) were assessed using Spearman's correlation coefficient. Diagnostic performance was evaluated with receiver operating characteristic (ROC) curve analysis for contrast enhancement and MRS and APT imaging. Values of P < 0.05 were considered statistically significant., Results: Positive correlations with statistical significance were found between total concentration of choline (Cho) and APT 90 (r = 0.49), and between Cho/creatine (Cr) and APT mean (r = 0.65) as well as APT 90 (r = 0.49). A negative correlation with statistical significance was observed between NAA/Cr and APT mean (r = -0.52). According to ROC curves, Cho/Cr, APT mean , APT 90 , demonstrated higher area under the curve (AUC) values than that of contrast enhancement in grading gliomas., Conclusion: Significant correlations were observed between metabolite concentrations and ratios on MRS and APT values. MRS and APT imaging showed comparable diagnostic capability for grading brain tumors, suggesting that both MRS and APT imaging offer potential for quantitatively assessing similar biological characteristics in brain tumors on noncontrast MRI., Level of Evidence: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:732-739., (© 2017 International Society for Magnetic Resonance in Medicine.)

This study investigated the combined capability of thallium-201 (Tl)-SPECT and fluorine-18-fluoro-deoxy-glucose (FDG)-PET for differential diagnosis of posterior fossa brain tumors using multiple discriminant analysis.This retrospective study was conducted under approval of the institutional review board. In the hospital information system, 27 patients with posterior fossa intra-axial tumor between January 2009 and June 2015 were enrolled and grouped as the following 7 entities: low grade glioma (LGG) 6, anaplastic astrocytoma (AA) 2, glioblastoma (GBM) 3, medulloblastoma (MB) 3, hemangioblastoma (HB) 6, metastatic tumor (Mets) 3, and malignant lymphoma (ML) 4. Tl and FDG uptakes were measured at the tumors and control areas, and several indexes were derived. Using indexes selected by the stepwise method, discriminant analysis was conducted with leave-one-out cross-validation.The predicted accuracy for tumor classification was 70.4% at initial analysis and 55.6% at cross-validation to differentiate 7 tumor entities. HB, LGG, and ML were well-discriminated, but AA was located next to LGG. GBM, MB, and Mets largely overlapped and could not be well distinguished even applying multiple discriminant analysis. Correct classification in the original and cross-validation analyses was 44.4% and 33.3% for Tl-SPECT and 55.6% and 48.1% for FDG-PET.

Purpose: Gadolinium deposition in dentate nucleus (DN) has been reported after serial administration of gadolinium-based contrast agents (GBCAs). Gadolinium complexes have paramagnetic properties; therefore, we evaluated susceptibility changes of gadolinium deposition in DN using quantitative susceptibility mapping (QSM) for patients after serial administration of GBCAs., Materials and Methods: In all, 48 patients with brain tumors, who had had serial GBCA administrations (GBCA group), and 48 healthy volunteers without any history of GBCA administrations (non-GBCA group) were enrolled in this study. Susceptibility values in DN on QSM and DN-to-cerebellum signal intensity ratios on unenhanced T 1 -weighted images (T 1 ratios) on 3T were analyzed. The relationship between the number of times of GBCA administrations and susceptibility values or T 1 ratios were evaluated in the GBCA group., Results: Susceptibility values at DN in the GBCA group were 0.107 ± 0.029 ppm, and significantly higher than those of the non-GBCA group (0.079 ± 0.025 ppm) (P < 0.0001). T 1 ratios in DN of the GBCA group were 1.059 ± 0.070, and also significantly higher than that of the non-GBCA group (0.993 ± 0.016) (P < 0.0001). Spearman rank correlation coefficients between susceptibility values and the number of times of linear GBCA administration showed a modest significant correlation (ρ = 0.45, P = 0.0015). There was good correlation between T 1 ratios and the number of times of linear GBCA administration, as reported previously (ρ = 0.76, P < 0.0001)., Conclusion: Susceptibility values on QSM in DN of the GBCA group, after serial administration of GBCAs, were significantly higher than those of the non-GBCA group. Evidence Level: 3 J. MAGN. RESON. IMAGING 2017;45:1352-1358., (© 2016 International Society for Magnetic Resonance in Medicine.)

The objective of this phase I/II study was to examine the efficacy and toxicity profile of temozolomide (TMZ) plus nimustine (ACNU). Patients who had received a standard radiotherapy with one or two previous chemo-regimens were enrolled. In phase I, the maximum-tolerated dose (MTD) by TMZ (150 mg/m 2 /day) (Day 1-5) plus various doses of ACNU (30, 35, 40, 45 mg/m 2 /day) (Day 15) per 4 weeks was defined on a standard 3 + 3 design. In phase II, these therapeutic activity and safety of this regimen were evaluated. Forty-nine eligible patients were enrolled. The median age was 50 years-old. Eighty percent had a KPS of 70-100. Histologies were glioblastoma (73%), anaplastic astrocytoma (22%), anaplastic oligodendroglioma (4%). In phase I, 15 patients were treated at four cohorts by TMZ plus ACNU. MTD was TMZ (150 mg/m 2 ) plus ACNU (40 mg/m 2 ). In phase II, 40 patients were treated at the dose of cohort 3 (MTD). Thirty-five percent of patients experienced grade 3 or 4 toxicities, mainly hematologic. The overall response rate was 11% (4/37). Sixty-eight percent (25/37) had stable disease. Twenty-two percent (8/37) showed progression. Progression-free survival (PFS) rates at 6 and 12 months were 24% (95% CI, 12-35%) and 8% (95% CI, 4-15%). Median PFS was 13 months (95% CI, 9.2-17.2 months). Overall survival (OS) at 6 and 12 were 78% (95% CI, 67-89%) and 49% (95% CI, 33-57%). Median OS was 11.8 months (95% CI, 8.2-14.5 months). This phase I/II study showed a moderate toxicity in hematology and may has a promising efficacy in OS, without inferiority in PFS., Competing Interests: The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices in the article. All authors who are members of The Japan Neurosurgical Society (JNS) have registered online Self-reported COI Disclosure Statement Forms through the website for JNS members. This manuscript has no COI that should be disclosed.

Background: Although hypofractionated radiotherapy (HFRT) is preferred to conventionally fractionated radiotherapy when treating elderly patients with glioblastoma, the benefits and tolerability of HFRT with concurrent temozolomide (TMZ) remain unknown for such patients. We assessed the feasibility and outcomes of elderly patients with glioblastoma treated with HFRT and concurrent TMZ., Methods: We retrospectively reviewed the medical records of 11 patients aged ≥70 years who were treated with HFRT and concurrent TMZ. All patients had newly diagnosed and histologically confirmed glioblastoma and were treated at our institution between October 2011 and April 2015. The median age was 74 years (range, 70-85 years). Total resection/subtotal resection/biopsy were performed in 2/5/4 patients, respectively. The planning target volume included the T1-enhancing tumor and the resection cavity plus 2-cm margins, and all surrounding edema. The median prescription dose was 35 Gy (range, 35-42.5 Gy), delivered in 10 fractions. Seven patients received TMZ at 150 mg/m 2 for 5 days and 4 received TMZ at 75 mg/m 2 during HFRT. Overall survival (OS) was defined as the time from surgery to death or the last follow-up., Results: The median follow-up period was 13.2 months. The median OS and progression-free survival (PFS) times were 13.2 and 7.0 months, respectively. One patient experienced grade 4 neutropenia, lymphocytopenia, and thrombocytopenia. No grade 3 or higher nonhematological adverse event was noted., Conclusion: Our analysis demonstrated the feasibility of HFRT with concurrent TMZ used to treat elderly patients with glioblastoma. Further prospective clinical trials are needed to define therapies that balance efficacy with tolerability.

Purpose: This study aims to investigate difference between magnetization-prepared rapid gradient-echo imaging (MPRAGE) and spin-echo (SE) imaging for evaluating glioma on pre-contrast-enhanced (CE) and post-CE T1-weighted images at 3 T., Materials and Methods: We retrospectively assessed pre-CE and post-CE T1-weighted images for tumor contrast in 64 consecutive glioma patients., Results: In the nonenhancing tumors, the contrast was significantly clearer in MPRAGE than SE. In the enhancing tumors, post-CE contrast ratio was significantly higher in SE than MPRAGE, but when subtraction images are evaluated, the difference got smaller., Conclusion: MPRAGE can be a good substitute of SE for T1-weighted imaging of glioma., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Preoperative glioma grading is important for therapeutic strategies and influences prognosis. Intratumoral heterogeneity can cause an underestimation of grading because of the sampling error in biopsies. We developed a voxel-based unsupervised clustering method with multiple magnetic resonance imaging (MRI)-derived features using a self-organizing map followed by K-means. This method produced novel magnetic resonance-based clustered images (MRcIs) that enabled the visualization of glioma grades in 36 patients. The 12-class MRcIs revealed the highest classification performance for the prediction of glioma grading (area under the receiver operating characteristic curve = 0.928; 95% confidential interval = 0.920-0.936). Furthermore, we also created 12-class MRcIs in four new patients using the previous data from the 36 patients as training data and obtained tissue sections of the classes 11 and 12, which were significantly higher in high-grade gliomas (HGGs), and those of classes 4, 5 and 9, which were not significantly different between HGGs and low-grade gliomas (LGGs), according to a MRcI-based navigational system. The tissues of classes 11 and 12 showed features of malignant glioma, whereas those of classes 4, 5 and 9 showed LGGs without anaplastic features. These results suggest that the proposed voxel-based clustering method provides new insights into preoperative regional glioma grading.

Background: Cavernomas frequently are associated with intractable epilepsy. When cavernomas located in the temporal lobe are associated with intractable epilepsy, the hippocampus also may have an epileptic focus. The objective in the present study was to clarify the importance of evaluation of the posterior hippocampal epileptogenicity during epilepsy surgery for posteromedial temporal lobe cavernoma., Case Descriptions: In this study, we describe 2 rare cases of medically intractable epilepsy in patients with posteromedial temporal lobe cavernomas who underwent surgery via the occipital approach. Using longitudinal insertion of depth electrodes into the hippocampus, we evaluated epileptogenicity in both patients from the cavernoma cavity and its surrounding hemosiderin, as well as from the posterior hippocampus near the cavernoma. We show that the transoccipital approach to the posteromedial temporal lobe is compatible with depth electrode insertion and subdural electrode placement on the temporal lobe, enabling an accurate evaluation of potential epileptogenic zones in the posterior part of the hippocampus. Both patients did not experience any seizures and had no postoperative neurologic deficits, and their cognitive functions were intact., Conclusions: The transoccipital approach enables the optimization of the extent of posterior hippocampectomy while avoiding unnecessary resection for seizure control. We suggest resecting the posterior part of the hippocampus in addition to the cavernoma and surrounding areas in patients with medically refractory epilepsy due to a posteromedial temporal cavernoma. Tailored systematic resection guided by intraoperative electrocorticography and electroencephalography with a depth electrode was important and necessary in the present cases., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The aim of this study was to explore the difference in high mobility group A1 (HMGA1) expression and isocitrate dehydrogenase (IDH) 1 R132H point mutation in initial and recurrent glioblastoma multiforme (GBM), and to further identify whether the expression of HMGA1 has a role in the malignant progression of GBM. Paired initial and recurrent GBM specimens from the same patient were evaluated using immunohistochemical analysis. The association between HMGA1 expression and progression-free survival time (PFST) was analyzed. Three patients were confirmed with IDH-1 R132H mutations in both initial and recurrent groups (3/25, 12%). There was a significant difference in HMGA1 expression between initial and recurrent GBM (P=0.002), and patients with tumors expressing HMGA1 at higher level had a significantly shorter PFST (7.3 months versus 11.1months; P=0.044). Our study indicates that recurrent GBM express HMGA1 at a higher level and that HMGA1 overexpressoin is associated with shorter PFST in patients with GBM. These findings suggest that HMGA1 potentially plays an important role in the treatment of GBM., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Physiological high frequency activities (HFA) are related to various brain functions. Factors, however, regulating its frequency have not been well elucidated in humans. To validate the hypothesis that different propagation modes (thalamo-cortical vs. cortico-coritcal projections), or different terminal layers (layer IV vs. layer II/III) affect its frequency, we, in the primary somatosensory cortex (SI), compared HFAs induced by median nerve stimulation with those induced by electrical stimulation of the cortex connecting to SI. We employed 6 patients who underwent chronic subdural electrode implantation for presurgical evaluation. We evaluated the HFA power values in reference to the baseline overriding N20 (earliest cortical response) and N80 (late response) of somatosensory evoked potentials (HFA(SEP(N20)) and HFA(SEP(N80))) and compared those overriding N1 and N2 (first and second responses) of cortico-cortical evoked potentials (HFA(CCEP(N1)) and HFA(CCEP(N2))). HFA(SEP(N20)) showed the power peak in the frequency above 200 Hz, while HFA(CCEP(N1)) had its power peak in the frequency below 200 Hz. Different propagation modes and/or different terminal layers seemed to determine HFA frequency. Since HFA(CCEP(N1)) and HFA induced during various brain functions share a similar broadband profile of the power spectrum, cortico-coritcal horizontal propagation seems to represent common mode of neural transmission for processing these functions.

Glioblastoma multiforme (GBM) is associated with high mortality due to infiltrative growth and recurrence. Median survival of the patients is less than 15 months, increasing requirements for new therapies. We found that both arsenic trioxide and 10058F4, an inhibitor of Myc, induced differentiation of cancer stem-like cells (CSC) of GBM and that arsenic trioxide drastically enhanced the anti-proliferative effect of 10058F4 but not apoptotic effects. EGFR-driven genetically engineered GBM mouse model showed that this cooperative effect is higher in EGFRvIII-expressing INK4a/Arf-/- neural stem cells (NSCs) than in control wild type NSCs. In addition, treatment of GBM CSC xenografts with arsenic trioxide and 10058F4 resulted in significant decrease in tumor growth and increased differentiation with concomitant decrease of proneural and mesenchymal GBM CSCs in vivo. Our study was the first to evaluate arsenic trioxide and 10058F4 interaction in GBM CSC differentiation and to assess new opportunities for arsenic trioxide and 10058F4 combination as a promising approach for future differentiation therapy of GBM.

Objective: The objective was to evaluate diagnostic performance of dynamic susceptibility-contrast perfusion-weighted imaging, diffusion-weighted imaging, and (18)F-fluorodeoxyglucose positron emission tomography in differentiating primary central nervous system lymphoma (PCNSL) and glioblastoma., Materials and Methods: Twenty-three glioblastomas and 11 PCNSLs were analyzed with uncorrected cerebral blood volume (CBV) ratio, fifth percentile value of cumulative apparent diffusion coefficient histogram (ADC5%), and maximum standardized uptake value (SUVmax) using regions of interest created semiautomatically on enhancing areas., Results: Uncorrected CBV ratio was highly capable of differentiating PCNSL from glioblastoma, as well as SUVmax and ADC5%., Conclusions: Uncorrected CBV ratio demonstrates high diagnostic performance comparable to SUVmax., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Amide proton transfer (APT) magnetic resonance imaging is gaining attention for its capability for grading glial tumors. Usually, a representative slice is analyzed. Different definitions of tumor areas have been employed in previous studies. We hypothesized that the accuracy of APT imaging for brain tumor grading may depend upon the analytical methodology used, such as selection of regions of interest (ROIs), single or multiple tumor slices, and whether or not there is normalization to the contralateral white matter. This study was approved by the institutional review board, and written informed consent was waived. Twenty-six patients with histologically proven glial tumors underwent preoperative APT imaging with a three-dimensional gradient-echo sequence. Two neuroradiologists independently analyzed APT asymmetry (APTasym) images by placing ROIs on both a single representative slice (RS) and all slices including tumor (i.e. whole tumor: WT). ROIs indicating tumor extent were separately defined on both FLAIR and, if applicable, contrast-enhanced T1-weighted images (CE-T1WI), yielding four mean APTasym values (RS-FLAIR, WT-FLAIR, RS-CE-T1WI, and WT-CE-T1WI). The maximum values were also measured using small ROIs, and their differences among grades were evaluated. Receiver operating characteristic (ROC) curve analysis was also conducted on mean and maximum values. Intra-class correlation coefficients for inter-observer agreement were excellent. Significant differences were observed between high- and low-grade gliomas for all five methods (P < 0.01). ROC curve analysis found no statistically significant difference among them. This study clarifies that single-slice APT analysis is robust despite tumor heterogeneity, and can grade glial tumors with or without the use of contrast material.

"Formes frustes" of encephalopathy associated with anti-NMDAR antibody have been recently described in cases of chronic epilepsy. We report a young woman with a parietal lesion and anti-NMDAR antibody who acquired bilateral, secondary epileptogenesis in the temporal lobes within a period as short as six years. Removal of the primary epileptogenic lesion of oligoastrocytoma in the right parietal lobe resulted in seizure freedom, disappearance of secondary foci, and substantial decrease of the antibody titre. Chronic exposure to anti-NMDAR antibody, albeit at a low titre, may have resulted in a smoldering chronic course and relatively early acquisition of "reversible" secondary foci without development of a high degree of epileptogenicity and structural changes.

Objective: Hemangioblastomas remain a surgical challenge because of their arteriovenous malformation-like character. Recently, indocyanine green (ICG) videoangiography has been applied to neurosurgical vascular surgery. The aim of this study was to evaluate the usefulness of tumor blood flow imaging by intraoperative ICG videoangiography in surgery for hemangioblastomas., Methods: Twenty intraoperative ICG videoangiography procedures were performed in 12 patients with hemangioblastomas. Seven lesions were located in the cerebellum, two lesions were in the medulla oblongata, and three lesions were in the spinal cord., Results: Ten procedures were performed before or during dissection, and 10 procedures were performed after tumor resection. ICG videoangiography could provide dynamic images of blood flow in the tumor and its related vessels under surgical view. Interpretation of these dynamic images of tumor blood flow was useful for discrimination of transit feeders (feeders en passage) and also for estimation of unexposed feeders covered with brain parenchyma. Postresection ICG videoangiography could confirm complete tumor resection and normalized blood flow in surrounding vessels., Conclusions: In surgery for hemangioblastomas, careful interpretation of dynamic ICG images can provide useful information on transit feeders and unexposed hidden vessels that cannot be directly visualized by ICG., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Gliomas are the most common intra-axial primary brain tumour; therefore, predicting glioma grade would influence therapeutic strategies. Although several methods based on single or multiple parameters from diagnostic images exist, a definitive method for pre-operatively determining glioma grade remains unknown. We aimed to develop an unsupervised method using multiple parameters from pre-operative diffusion tensor images for obtaining a clustered image that could enable visual grading of gliomas. Fourteen patients with low-grade gliomas and 19 with high-grade gliomas underwent diffusion tensor imaging and three-dimensional T1-weighted magnetic resonance imaging before tumour resection. Seven features including diffusion-weighted imaging, fractional anisotropy, first eigenvalue, second eigenvalue, third eigenvalue, mean diffusivity and raw T2 signal with no diffusion weighting, were extracted as multiple parameters from diffusion tensor imaging. We developed a two-level clustering approach for a self-organizing map followed by the K-means algorithm to enable unsupervised clustering of a large number of input vectors with the seven features for the whole brain. The vectors were grouped by the self-organizing map as protoclusters, which were classified into the smaller number of clusters by K-means to make a voxel-based diffusion tensor-based clustered image. Furthermore, we also determined if the diffusion tensor-based clustered image was really helpful for predicting pre-operative glioma grade in a supervised manner. The ratio of each class in the diffusion tensor-based clustered images was calculated from the regions of interest manually traced on the diffusion tensor imaging space, and the common logarithmic ratio scales were calculated. We then applied support vector machine as a classifier for distinguishing between low- and high-grade gliomas. Consequently, the sensitivity, specificity, accuracy and area under the curve of receiver operating characteristic curves from the 16-class diffusion tensor-based clustered images that showed the best performance for differentiating high- and low-grade gliomas were 0.848, 0.745, 0.804 and 0.912, respectively. Furthermore, the log-ratio value of each class of the 16-class diffusion tensor-based clustered images was compared between low- and high-grade gliomas, and the log-ratio values of classes 14, 15 and 16 in the high-grade gliomas were significantly higher than those in the low-grade gliomas (p < 0.005, p < 0.001 and p < 0.001, respectively). These classes comprised different patterns of the seven diffusion tensor imaging-based parameters. The results suggest that the multiple diffusion tensor imaging-based parameters from the voxel-based diffusion tensor-based clustered images can help differentiate between low- and high-grade gliomas.

Dysembryoplastic neuroepithelial tumor (DNT) rarely has aggressive behavior with recurrence. The authors describe a case of DNT with rapid re-growth and features of pilocytic astrocytoma. A 19-year-old girl presented with a 3-year history of complex partial seizure, which was presumably because of DNT located in the left parietal lobe. The tumor was resected, although a tiny residual lesion with cystic space enlarged with ring enhancement identified on MRI 14 days after surgery resulted in re-excision. The recurrent tumor was eventually proved to be predominantly composed of pilocytic astrocytoma. DNT is known to recur only rarely as a tumor with morphologically different components, and no cases of recurrent DNT with rapidly-growing pilocytic astrocytoma have hitherto been reported in the literature. This phenomenon may be histological "replacement" at recurrence.

Objective: We qualitatively evaluated the differences among susceptibility-weighted (SWI), magnitude (MAG), and high pass filtered phase (PHA) images in depicting interlobar differences in the appearance of the signal of the corticomedullary junction (CMJ). We conducted quantitative evaluation to validate the qualitative results., Materials and Methods: We obtained SWI images from 25 preoperative brain tumor patients (12 men, 13 women, aged 19 to 82 years, mean, 52 years). Two trained neuroradiologists evaluated MAG, PHA, and SWI images. Qualitative evaluation of the CMJ signal and quantitative calculation of the relative signal ratio (RSR) percentages between the CMJ and deep white matter (WM) were conducted at 3 different slice levels of the brain independently for 4 different lobes (frontal, parietal, temporal, and occipital) and compared among MAG, PHA, and SWI. The extent of the area of the CMJ signal was graded on a 4-point scale (Grade 3, >75%; Grade 2, 50 to 75%; Grade 1, 25 to 50%; Grade 0, <25%). Data were statistically analyzed using a nonparametric Friedman test., Results: The Kappa coefficients between the qualitative and quantitative grades were 0.002 for MAG, 0.0047 for PHA, and 0.050 for SWI. Qualitatively, on the PHA images and SWI, grades of the occipital lobes were significantly higher than those of the other lobes (P < 0.005). Quantitatively, PHA images showed statistically significant interlobar differences in RSR percentage values of the CMJ (P = 0.025)., Conclusion: Qualitatively, the appearance of the CMJ differed significantly among the different lobes of the brain on SWI and underlying PHA images but not on MAG images. Quantitatively, only PHA images showed significant interlobar differences in the RSR. PHA images are most sensitive to the CMJ signal contrast due to local paramagnetic iron content.

In this study, we assessed the efficacy of salvage stereotactic radiotherapy (SRT) for recurrent glioma. From August 2008 to December 2012, 30 patients with recurrent glioma underwent salvage SRT. The initial histological diagnoses were World Health Organization (WHO) grades II, III, and IV in 6, 9, and 15 patients, respectively. Morphologically, the type of recurrence was classified as diffuse or other. Two methods of clinical target delineation were used: A, a contrast-enhancing tumor; or B, a contrast-enhancing tumor with a 3-10-mm margin and/or surrounding fluid attenuation inversion recovery (FLAIR) high-intensity areas. The prescribed dose was 22.5-35 Gy delivered in five fractions at an isocenter using a dynamic conformal arc technique. The overall survival (OS) and local control probability (LCP) after SRT were calculated using the Kaplan-Meier method. A univariate analysis was used to test the effect of clinical variables on OS/LCP. The median follow-up period was 272 days after SRT. The OS and LCP were 83% and 56% at 6 months after SRT, respectively. Morphologically, the tumor type correlated significantly with both OS and LCP (P = 0.006 and <0.001, respectively). The method of target delineation also had a significant influence on LCP (P = 0.016). Grade 3 radiation necrosis was observed in two patients according to Common Terminology Criteria for Adverse Events, version 3. Salvage SRT was safe and effective for recurrent glioma, especially non-diffuse recurrences. Improved local control might be obtained by adding a margin to contrast-enhancing tumors or including increased FLAIR high-intensity areas., (© 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: To analyze initial recurrence patterns in patients with newly diagnosed glioblastoma after radiotherapy plus concurrent and adjuvant temozolomide, and to investigate cumulative recurrence patterns after salvage treatment, including surgery, stereotactic radiotherapy, and chemotherapy., Methods: Twenty-one patients with glioblastoma that recurred after concurrent temozolomide and localized radiotherapy were retrospectively analyzed (11 male, 10 female; median age, 57 years; range, 27-74). Disease progression was assessed by new response criteria proposed by the Response Assessment in Neuro-Oncology Working Group of the American Society of Clinical Oncology. The pattern of recurrence was determined by relationships between locations of recurrent tumors and irradiated doses. Central, in-field, marginal, and out-field recurrences were defined relative to the prescribed isodose line. Distant recurrence was operationally defined as subependymal or disseminated disease. Initial and cumulative patterns of recurrence were evaluated in each patient., Results: The median follow-up of the recurrent patients was 501 (range, 217-1815) days after initial surgery. Initial recurrences were central in 14 patients (66.7%), in-field in four patients (19.0%), marginal in no patient (0%), out-field in two patients (9.5%), and distant in four patients (19.0%). One patient had both central and in-field recurrences simultaneously, and two had both central and distant recurrences. In the analysis of cumulative recurrence patterns, five patients, who had no scans after initial recurrences, were excluded and the remaining 16 were included. Cumulative recurrences were central in 11 patients (68.8%), in-field in five patients (31.3%), marginal in three patients (18.8%), out-field in five patients (31.3%), and distant in 14 patients (87.5%). Regarding salvage treatments, 11 (52.4%), 11 (52.4%) and 17 (81.0%) patients underwent surgery, stereotactic radiotherapy and chemotherapy, respectively. Eighteen (85.7%) patients had died at the time of analysis, and 16 of them (88.9%) had suffered distant recurrences, which could have been the immediate causes of death., Conclusions: Recurrence patterns of glioblastoma after radiotherapy plus concomitant and adjuvant temozolomide were mainly central at first, and distant recurrences were often detected during the clinical course. Much better local control and prevention of distant recurrence, including effective salvage treatment, seem to be important.

High grade glioma is a highly invasive brain tumor and recurrence is almost inevitable, even after radical resection of the tumor mass. Cytotoxic immune responses and immunological memory induced by immunotherapy might prevent tumor recurrence. Dendritic cells (DCs) are professional antigen-presenting cells of the innate immune system with the potential to generate robust antigen-specific T cell immune responses. DC-based immunotherapeutic strategies have been intensively studied in both preclinical and clinical settings. Although advances have been made in the experimental use of DCs, there are still considerable challenges that need to be addressed for clinical translation. In this review, we describe the variability of regimens currently available for DC-based immunotherapy and then review strategies to optimize DC therapeutic efficacy against glioma.

Bevacizumab has been reported to be effective for recurrent glioblastoma. In our hospital, ifosfamide, carboplatin, etoposide (ICE) is the second-line chemotherapy for first recurrence of glioblastoma after temozolomide failure. In the present analysis, we retrospectively investigated the feasibility and effectiveness of bevacizumab combined with ICE in patients with glioblastoma at second relapse during ICE treatment. Between 2010 and 2012, tumor progressions were diagnosed in consecutive 8 patients who were treated with ICE for the first recurrence of glioblastoma. These patients were administered 3 cycles of 10 mg/kg bevacizumab every two weeks in combination with ICE treatment. The objective response rate of bevacizumab combination was 75% in Neuro-Oncology Working Group (RANO criteria), including complete response and partial response. Median progression free survival (PFS) and median overall survival (OS) after second relapse were 3.7 months (95% confidence interval [CI], 2.5-18.5 months) and 6.0 months (95% CI, 3.2-19.7 months), respectively. The 6-month PFS rates were 25% (95% CI, 0-55.0%). The median OS after initial diagnosis was 23.3 months (95% CI, 16.2-55.8 months). The grade 2 or 3 hematologic adverse events were identified in 7 of 8 patients, most of which might be due to ICE chemotherapy. The results of our retrospective analysis suggest that combination treatment with bevacizumab and ICE may be safe and beneficial in patients with recurrent glioblastoma.

The present study aimed to analyze outcomes of hypofractionated stereotactic radiotherapy (HFSRT) delivered in five fractions to metastatic brain tumors. Between June 2008 and June 2011, 39 consecutive patients with 46 brain metastases underwent HFSRT at Kyoto University Hospital. Selection criteria included high risk factors such as eloquent location, history of whole-brain radiotherapy (WBRT), or large tumor size. Given these factors, fractionated schedules were preferable in terms of radiobiology. The prescribed dose at the isocenter was basically 35 Gy in five fractions. Brainstem lesions with a history of WBRT were treated with 20-25 Gy in five fractions. Planning target volume was covered by the 80 % isodose line of the prescribed dose to the isocenter. Local-control probability and overall survival were estimated using the Kaplan-Meier method. For the analysis of local control, the response criteria were defined as follows: complete response (CR) was defined as no visible gross tumor or absence of contrast enhancement, partial response (PR) as more than a 30 % decrease in size, progressive disease as more than a 20 % increase in size, and stable disease (SD) as all other responses. Local control was defined as a status of CR, PR, or SD. Only patients with at least 3 months or longer follow-up (21 patients, 27 tumors) were included in the analysis. Median age and Karnofsky performance status were 59 years (range, 39-84 years) and 90 (range, 40-100), respectively. Tumor volumes and maximum diameters ranged from 0.08 to 15.38 cm(3) (median, 3.67 cm(3)) and from 3 to 34 mm (median, 18 mm), respectively. The median follow-up period was 329 days (range, 120-1,321 days). Local-control probabilities at 6 and 12 months were 92.1 and 86.7 %, respectively. Overall survival after HFSRT at 6 and 12 months was 85.4 and 64.5 %, respectively. Grade 3 radiation necrosis was observed in one patient according to the Common Terminology Criteria for Adverse Events version 3.0. The patient was successfully managed conservatively. HFSRT for metastatic brain tumors yields high local-control probabilities without increasing severe adverse events despite high risk factors.

Current treatments for gliomas, including surgery, chemotherapy, and radiation therapy, frequently result in unsuccessful outcomes. Studies on glioma resection were reviewed to assess better treatment outcomes applying the newest neurosurgical multimodalities. We reviewed reports of surgical removal of gliomas utilizing functional brain mapping, monitoring, and other functional neurosurgery techniques such as neuronavigation and awake surgery. Attempts to maximize the extent of glioma resection improved survival. A close proximity of the resection to the eloquent areas increased the risk of perioperative neurological deficits. However, those deficits often improved during the postoperative rehabilitation and recovery period when the essential or the compensative eloquent areas remained intact. Pre- and intraoperative application of the latest brain function analysis methods promoted safe elimination of gliomas. These methods are expected to help explore the long-term prognosis of glioma treatment and the mechanism for recovery from functional disabilities.

To clarify the generator mechanism of sensory and motor facial responses ipsilateral to electrical stimulation of the inferior fronto-temporal cortex in epilepsy patients. Out of 30 patients who have been evaluated with chronically implanted subdural electrodes for medically intractable partial seizure or brain tumor involving the basal frontal or temporal cortex, 4 patients (age ranging 24-57 years) showed sensory and motor responses in the ipsilateral face to high frequency electrical cortical stimulation of the inferior fronto-temporal cortex. We investigated motor evoked potentials (MEPs) in the facial muscle by single pulse stimulation in 2 out of 4 patients. Three patients showed both sensory symptoms and muscle contraction in the ipsilateral lower face when the orbitofrontal or basal temporal cortex was stimulated with 50 Hz electric current. One patient had only sensory symptoms in the lower face when ipsilateral basal temporal area was stimulated. MEPs at the left orbicularis oris muscle were constantly elicited with the onset latency of 7 ms throughout the stimulus rate of 2-30 Hz in 1 patient out of 2 patients was tested. In another patient, MEP onset latency was 3.0 ms with 11 Hz stimulation. With electrical stimulation of the basal fronto-temporal cortex, the ipsilateral facial twitch might occur through either the direct activation of the facial nerve by the current spread in the middle cranial fossa or through the mechanism similar to blink reflex.

To delineate a surgical strategy for long-term intractable epilepsy associated with nonmalignant brain tumor, we developed a protocol for 25 patients whereby removal of tumor alone and additional irritative peritumoral tissue between sulci (gyrectomy), as well as further resectioning, was performed based on intraoperative electrocorticogram results. In five patients, no irritative zones were observed that required resectioning following complete removal of tumors. Additional gyrectomy was indicated in 18 patients who demonstrated gliosis or cortical dysplasia in the peritumoral residual irritative zone. Remote irritative zone observed in two patients was correlated with long-term and frequent seizures. During a follow-up period of at least 5 years, seizure outcome was Engel category I in 92%, and all patients have remained tumor-free. Peritumoral gyrectomy as a means of removing likely epileptic tissue following tumor resection appears to be a useful method for treating long-term intractable tumoral epilepsy. Further resectioning of remote tissue should be considered in patients with severely intractable seizures.

Objective: To minimize therapeutic morbidity such as cognitive function disturbance and vascular injury to perforating arteries, preoperative functional mapping of the basal temporal lobe functions was performed and the medial temporal lesions were resected via a combined subtemporal and transventricular/transchoroidal fissure approach., Methods: Twenty-one patients with medial temporal lesions including tumors, arteriovenous malformations, and medial temporal lobe epilepsy underwent operation. The neurovascular structures in the ambient cistern were first dissected free from the medial temporal lobe with a conventional subtemporal approach. Then, the temporal horn was opened through the basal surface of the temporal lobe. Finally, the ambient cistern was accessed from the temporal horn through the choroidal fissure. In five patients whose lesions were revealed to be located on the dominant side by preoperative intracarotid amytal administration test (Wada test), functional mapping of the basal temporal lobe language cortex was monitored for 1 week by use of a subdural electrocorticogram grid before the extirpation surgery. The entrance point from the temporal base to the temporal horn was determined by the result of the functional mapping., Results: The lesions were resected safely and completely in all cases. Language and cognitive functions were preserved even in patients with the basal language area on the dominant side., Conclusion: Surgeons can confirm the important neurovascular structures from the subtemporal route and from the transtemporal horn route by a combined subtemporal and transventricular/transchoroidal fissure approach. This approach is especially effective for avoiding ischemic complications by allowing direct confirmation of the anterior choroidal and thalamoperforating arteries.

Objective: To clarify the cortical areas involved in motor preparation and execution by investigating Bereitschaftspotentials (BPs) and electrocorticogram-electromyogram (ECoG-EMG) coherence from subdural electrodes placed around the rolandic area., Methods: BPs and ECoG-EMG coherence were investigated for presurgical evaluation in a patient with cavernoma in the left frontal lobe. BPs were recorded in association with the tongue, right hand and right foot movements. ECoG-EMG coherence was calculated in association with weak muscle contraction of the right hand., Results: Two cortical areas related to voluntary motor control were identified; one in the primary hand motor area, which generated surface-negative BPs with hand movements and showed significant coherence of ECoG with EMG of the contralateral hand muscle, and the other in the ventral rolandic area posterior to the central sulcus, which generated surface-positive BPs with voluntary movements of multiple sites (hand, tongue and foot) but did not show any ECoG-EMG coherence., Conclusions: It is postulated that the former area represents the primary motor area involved in both motor preparation and execution, and the latter area represents the non-primary motor area involved in motor preparation., Significance: BP recording combined with ECoG-EMG coherence analysis could reveal the functional roles of motor cortices and the reorganization induced by structural brain lesion.

Object: In their pursuit of a better substitute for dura mater in neurosurgical procedures, the authors review their experience with GM972., Methods: A newly developed synthetic dural substitute composed of bioabsorbable polymers (GM972) was placed in 53 patients during neurosurgical procedures. The handling properties of the material, surgical wound features. and findings of hematological, computerized tomography, and/or magnetic resonance imaging examinations were evaluated. The average follow-up period was 35.5 months. The handling properties and biocompatibility of this new dural substitute were highly satisfactory, and no significant complication was observed. In patients who underwent a second surgery performed more than 18 months after the initial operation, this new dural substitute was found to have been replaced by autologous collagenous tissue. Because of its bioabsorbability, chronic foreign body reactions to this synthetic dural substitute were negligible., Conclusions: In this report the authors support the effectiveness and safety of this bioabsorbable artificial dural substitute that provides a reduced risk of transmission of latent infection.