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OBJECTIVE An autologous formalin-fixed tumor vaccine (AFTV) derived from resected glioblastoma (GBM) tissue can be used against unidentified tumor antigens. Thus, the authors conducted a multicenter double-blind phase IIb trial to investigate the efficacy of an AFTV. METHODS Eligible patients were adults with supratentorial GBMs, 16–75 years of age, with Karnofsky Performance Scale (KPS) scores ≥ 60%, and no long-term steroid administration. An AFTV comprising fixed paraffin-embedded tumor tissue with immune adjuvants or an identical placebo without fixed tumor tissue was injected intradermally over three courses before and after chemoradiotherapy. The primary and secondary end points were overall survival (OS), progression-free survival (PFS), and 3-year survival rate. RESULTS Sixty-three patients were enrolled. The average patient age was 61 years. The median KPS score was 80%, and the median resection rate was 95%. The full analysis set of 57 patients indicated no significant difference in OS (p = 0.64) for the AFTV group (median OS 25.6 months, 3-year OS rate 38%) compared with the placebo group (31.5 months and 41%, respectively) and no difference in PFS (median PFS 13.3 months in both groups, p = 0.98). For patients with imaging-based total tumor removal, the 3-year PFS rate was 81% in the AFTV group versus 46% in the placebo group (p = 0.067), whereas the 3-year OS rate was 80% versus 54% (p = 0.16), respectively. Similar results were obtained in the p53-negative subgroups. Severe adverse effects were not observed. CONCLUSIONS The AFTV may have potential effects in certain patient subgroups. A phase III study for patients with total tumor removal remains warranted to confirm these findings. Clinical trial registration no.: UMIN000010602 (UMIN Clinical Trials Registry)

Patients with distant metastases of borderline phyllodes tumors (PT) are rare, and their prognosis is very poor. Here, we report the case of a 59-year-old Japanese woman with metastatic brain, lung, stomach, and colon lesions originating from a borderline PT in her left breast. After surgical treatment of the left frontal lobe tumor and the right upper lung tumor, and first-line chemotherapy with doxorubicin monotherapy, magnetic resonance imaging (MRI) revealed new metastatic lesions in the left cerebrum and bilateral frontal lobe. A next-generation sequencing clinical assay revealed that her tumor had platelet-derived growth factor receptor beta (PDGFRB) point mutation (p.N666K). On the basis of genetic analysis, a multitargeted tyrosine kinase inhibitor, pazopanib, was administered as the second-line chemotherapy. Most of her metastatic lesions, including brain metastases, showed a deep shrinkage, which persisted for 12 months. This is the first report that PDGFRB, which is a druggable pathogenic alteration, exists in PT. Genotype-matched therapy can be effectively used to treat rare malignant tumors.

Backgrounds Mutations in the isocitrate dehydrogenase (IDH)1 gene are favourable prognostic factors in newly diagnosed diffuse gliomas, whereas it remains controversial in the recurrent glioblastoma setting. Methods A total of 171 patients with newly diagnosed glioblastoma, either ‘primary’ glioblastoma or ‘secondary’ glioblastoma, treated at Kyorin University Hospital or Japanese Red Cross Medical Center from 2000 to 2015 were included. Patients with confirmed IDH1 status and O6-methylguanine-DNA methyltransferase promoter methylation status were retrospectively analysed for overall survival from the initial diagnosis (n = 147) and after the first progression (n = 122). Results IDH1 mutation but not IDH2 was noted in 19 of 147 patients with glioblastoma (12.9%). In patients with ‘primary’ glioblastoma (n = 136), median overall survival after the first progression was 13.5 and 10.5 months for mutant IDH1 and wild-type IDH1 glioblastoma, respectively (P = 0.747). Multivariate analysis revealed O6-methylguanine-DNA methyltransferase promoter methylation, and Karnofsky Performance status 60 or higher, were independent prognostic factors for better overall survival after the first progression. When ‘primary’ glioblastoma and ‘secondary’ glioblastoma were combined, median overall survival from the first progression was not significantly different between the mutant IDH1 group (10.1 months) and wild-type IDH1 group (10.5 months) (P = 0.559), whereas median overall survival from the initial diagnosis was significantly different (47.5 months vs.18.3 months, respectively; P = 0.035). Conclusions These results suggest that IDH1 mutation may not be a prognostic factor for survival at the first progression of patients with ‘primary’ glioblastoma and pretreated ‘secondary’ glioblastoma, and further warrant investigation in prospective studies., Overall survival after first progression of patients with primary glioblastoma was not significantly different between those with mutant IDH1 and wild-type IDH1. O6-methylguanine-DNA methyltransferase status and Karnofsky Performance status were independent better prognosticators.

Background During the coronavirus disease 2019 (COVID-19) pandemic, a rapid screening method for COVID-19 detection is needed to decide the appropriate strategy to treat stroke patients. In acute ischemic stroke treatment, the efficacy and safety of emergent carotid artery stenting (eCAS) for hyperacute ischemic stroke (hAIS) due to internal carotid artery stenosis (ICS) have not been sufficiently established. Case Description A 71-year-old man with hAIS caused by severe ICS was treated via intravenous alteplase infusion. The patient underwent screening for COVID-19 by the loop-mediated isothermal amplification (LAMP) assay shortly after arrival at our institution. The LAMP result was obtained within 90 minutes, during intravenous alteplase infusion, and turned out to be negative. The symptom of hemiplegia worsened during alteplase infusion, and he, therefore, underwent eCAS after administration of aspirin (200 mg). Recanalization was achieved successfully by eCAS, and dual antiplatelet therapy and argatroban were administrated following eCAS. Hemorrhagic complications or restenosis/occlusion of the carotid artery were not observed. He was discharged without neurologic deficits 15 days following eCAS. Because of the rapid negative diagnosis for COVID-19 using the LAMP method, eCAS could be performed following standard procedures, along with infectious defense, without delay. Conclusions This case report suggests that eCAS for hAIS due to ICS following intravenous alteplase can be an effective treatment, along with appropriate antiplatelet medication and management in select patients. During the COVID-19 pandemic, the LAMP assay for COVID-19 detection might be a suitable diagnostic strategy preceding stroke treatment because of the rapid turnaround time.

// Ryota Tamura 1 , Toshihide Tanaka 2 , Keisuke Miyake 3 , Yusuke Tabei 4 , Kentaro Ohara 5 , Oltea Sampetrean 6 , Maya Kono 1 , Katsuhiro Mizutani 1 , Yohei Yamamoto 2 , Yuichi Murayama 7 , Takashi Tamiya 3 , Kazunari Yoshida 1 and Hikaru Sasaki 1 1 Department of Neurosurgery, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan 2 Department of Neurosurgery, Jikei University Kashiwa Hospital, Kashiwashita, Kashiwa-shi, Chiba, Japan 3 Department of Neurosurgery, Kagawa University Hospital, Ikedo, Mituki-cho, Kita-gun, Kagawa, Japan 4 Department of Neurosurgery, Japan Red Cross Medical Center, Hiroo, Shibuya-ku, Tokyo, Japan 5 Division of Diagnostic Pathology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan 6 Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan 7 Department of Neurosurgery, Jikei University Hospital, Nishishinbashi, Minato-ku, Tokyo, Japan Correspondence to: Hikaru Sasaki, email: // Keywords : bevacizumab; neoadjuvant; vascular normalization; hypoxia; glioma stem cell Received : February 08, 2016 Accepted : May 09, 2016 Published : May 17, 2016 Abstract To date, no clinical observations have been reported for histopathological changes in human gliomas under antiangiogenic treatment. We collected six glioblastomas resected under bevacizumab treatment. Histopathological investigation was performed by hematoxilyn-eosin staining and immunohistochemistry for CD34, VEGF, VEGFR1/2, HIF-1α, CA9, and nestin as compared to eleven control glioblastomas to assess the differences in histological features, microvessel density, expression of VEGF and its receptors, tumor oxygenation, and status of glioma stem-like cells. In the six tumors resected under bevacizumab, microvascular proliferation was absent, and microvessel density had significantly decreased compared with that of the controls. The expressions of VEGF and its receptors were downregulated in two cases of partial response. HIF-1α or CA9 expression was decreased in five of the six tumors, whereas the decreased expression of these markers was noted in only one of the 11 control glioblastomas. The expression of nestin significantly decreased in the six tumors compared with that of the controls, with the remaining nestin-positive cells being relatively concentrated around vessels. We provide the first clinicopathological evidence that antiangiogenic therapy induces the apparent normalization of vascular structure, decrease of microvessel density, and improvement of tumor oxygenation in glioblastomas. These in situ observations will help to optimize therapy.

The aim of the present study was to evaluate the safety and feasibility of hypofractionated stereotactic radiotherapy (SRT) with CyberKnife for growth hormone-secreting pituitary adenoma (GH-PA). Fifty-two patients with GH-PA were treated with hypofractionated SRT between September 2001 and October 2012. Eight patients had clinically silent GH-PA and 44 were symptomatic. Only 1 patient was inoperable. The other patients had recurrent or postoperative residual tumors on MRI. All patients had received pharmacotherapy prior to SRT with a somatostatin analog, dopamine agonist, and/or GH receptor antagonist. The marginal doses were 17.4-26.8 Gy for the 3-fraction schedule and 20.0-32.0 Gy for the 5-fraction schedule. Endocrinological remission was assessed by the Cortina consensus criteria 2010 (random GH

Background Brain radiation necrosis (BRN) can be a complication of radiotherapy for primary and secondary brain tumors, as well as head and neck tumors. Since vascular endothelial growth factor (VEGF) is also a vascular permeability factor in the brain, bevacizumab, a humanized antibody that inhibits VEGF, would be expected to reduce perilesional edema that often accompanies BRN. Methods Patients with surgically untreatable, symptomatic BRN refractory to conventional medical treatments (eg, corticosteroid, anticoagulants, or hyperbaric oxygen therapy) were enrolled. We judged that a major cause of perilesional edema with a lesion-to-normal brain ratio ≤1.8 on 11C-methionine or ≤2.5 on 18F-boronophenylalanine PET was BRN, not tumor recurrence, and 6 cycles of biweekly bevacizumab (5 mg/kg) were administered. The primary endpoint was a ≥30% reduction from the patients' registration for perilesional edema continuing for ≥1 month. Results Of the 41 patients enrolled, 38 were fully eligible for the response assessment. The primary endpoint was achieved in 30 of the 38 (78.9%) patients at 3.0 months (median) after enrollment. Sixteen patients (42.1%) experienced improvement of their Karnofsy Performance Score. Corticosteroid use could be reduced in 29 patients (76.3%). Adverse events at grade ≥3 occurred in 10 patients (24.4%). Conclusions Bevacizumab treatment offers certain clinical benefits for patients with surgically untreatable, symptomatic BRN. The determination of BRN using amino-acid PET, not biopsy, is adequate and less invasive for determining eligibility to receive bevacizumab.

INTRODUCTION In recent years, hypofractionated radiotherapy (HRT) 40Gy in 15 fractions with concomitant temozolomide(TMZ) has come to be used as standard treatment for elderly glioblastoma. However, the treatment duration of 3–4 weeks for radiation is not enough short, and there is also a problem of radiation sickness. We performed hypofractionated stereotactic radiotherapy with CyberKnife (CK) for less than 2weeks. We retrospectively analyzed eight newly diagnosed elderly patients with glioblastoma treated by CK. METHODS Surgical cavity, contrast enhanced lesion, FLAIR high signal intensity area were set as gross tumor volume (GTV). To planned target volume (PTV) as GTV + 2 mm, Marginal dose (D95) 35 Gy in 5 fractions (Fr) was prescribed. The dose prescription and number of fractions were adjusted taking into consideration dose distribution, dose-limiting for important organs such as optic chiasm and brainstem. RESULTS The eight patients consisted of 3 men and 5 women. The median age was 78 (range 68–84) years old. All patients were pathologically diagnosed as glioblastoma. Two of 8 cases had undergone gross total removal of contrast area. Median postoperative KPS was 70 (40–80). Thirty three (28–33.5) Gy was administered in 5 (3–10) Fr to PTV 117 (44–243) ml. TMZ was used in 7 patients. Bevacizumab (BEV) was used together from 4 weeks after surgery in 5 patients. Progression-free survival was 6.5 (2.9–10.6) months and overall survival was 17.5 (7.1–28.5) months. 7 patients had experienced controllable hypertension with antihypertensive agents, Two patients had suffered from deep vein thrombosis, and anticoagulation therapy was used. One patient had nausea and malaise due to TMZ and had continue BEV alone. Asymptomatic cerebral infarction in the radiation field was observed in a patient. CONCLUSION CK treated in less than half duration of conventional HRT is expected as less invasive treatment.

BACKGROUND The prognosis for patients with recurrent glioblastoma after Bevacizumab (Bev) treatment is extremely poor. No effective treatment has been established. PURPOSE We retrospectively investigated the efficacy and safety of hypofractionated stereotactic radiotherapy with Cyberknife (CK-HSRT) for recurrent glioblastoma after Bev treatment in our institution. METHODS GTV (Gross tumor volume) was set in the FLAIR abnormal high signal area that resulted in the contrast lesion and invasive recurrence, and PTV (Planning target volume) = GTV + 2 mm. As aimed CK dose,30 Gray(Gy) in 5 fraction was performed on PTV. Bev(10mg/kg biweekly) was continued after CK. The case background, treatment effect, survival and adverse events were investigated for 21 cases from January 2013 to the end of May 2018. RESULTS The median age was 69 (range;31–85) years, and The D95% marginal dose was 27.5 (23–35) Gy in 5 (3–8) divisions. Median PTV was 112 (2–305) ml. The median time to progression after CK was 3.9 months, and the median overall survival after CK was 10.9 months. Early treatment-related adverse events included hair loss in the irradiated area, seizures, headache, nausea and vomiting. As late treatment-related adverse events, symptomatic cerebral radiation necrosis was not observed, but 2 cases of symptomatic cerebral infarction and a case of cerebral hemorrhage were observed. All cases were treated conservatively. CONCLUSION CK-HSRT may be well tolerated and effective as a salvage treatment for the patients with recurrent glioblastoma after Bev.

This study investigated the relationship between organizational stressors in sport and athlete burnout and involved a cross-cultural comparison of English and Japanese soccer players. Ninety-eight male players completed the Athlete Burnout Questionnaire (Raedeke & Smith, 2001) to determine levels of perceived burnout. Based on data reported in previous research, and the thresholds developed by Hodge, Lonsdale, and Ng (2008), 22 of the players were identified as exhibiting higher levels of perceived burnout. Nine members of this subsample (4 English and 5 Japanese players) were subsequently interviewed to explore the relationship between their experiences of burnout and the organizational stressors they encountered. Results revealed multiple demands linked to the dimensions of athlete burnout and identified specific organizational-related issues that players associated with the incidence of burnout. Cultural differences between English and Japanese players in terms of the prevalence and organizational stressors associated with burnout were also identified, with the main differences being the relationship with senior teammates and the coaching style.

This study compares the male and female soccer players’ technical characteristics of ball impact and swing motion before the impact in instep kicks and inside kicks. High-speed video cameras and 3D motion capture were used to examine the characteristics and mechanics of the kicks. During both types of kick, the female players exhibited lower ball velocity, foot velocity immediately before the impact, striking mass, and average ball-to-foot velocity ratio than the male players. The ball-to-foot velocity ratio decreased as the distance of the impact point from the foot's centre of gravity increased. The results of this study suggested that when training female players it is important to instruct them how to impact the ball near the foot's centre of gravity under a variety of conditions. Moreover, the female players exhibited lower inclination of hip and thigh immediately before the impact compared to the male players.

There has been no clinical observation about histopathological changes in human gliomas under control of the anti-angiogenic treatment, and the tissue-based observation is likely crucial to understand mechanism of action of these treatment. We collected 4 glioblastomas resected under control of neoadjuvant bevacizumab (Bev). Histopathological investigation was performed by hematoxilyn- eosin staining and immunohistochemistry for CD34, VEGF, VEGFR1/2, HIF-1α, and Nestin as compared to 6 control glioblastomas to assess changes in histological features, microvessel density, expression of VEGF and its receptors, tumor hypoxic condition, and cancer stem cells. Tumor resection under control of Bev was uneventful in all of the 4 cases. Intraoperatively, the tumors were clearly less vasculized than usual. Histopathologically, vascular morphology was quite different from usual glioblastomas with universal disappearance of microvascular proliferation. Microvessel density was significantly decreased in the 4 tumors as compared to control tumors. The expression of VEGF and its receptors was decreased in 2 cases of partial response, suggesting possible correlation with radiologic response. The expression of HIF-1α was similar or somewhat decreased in the 4 tumors. The expression of Nestin was significantly decreased in the 4 tumors as compared to control tumors, but there still remained numerous Nestin-positive cells especially around vessels. We provide the first clinicopathological evidence that the anti-angiogenic therapy induces vascular normalization and decrease of microvessel density in glioblastomas. These in situ observation will help to elucidate the mechanism of resistance to Bev and to optimize therapy.

Objective: Some patients with temporal lobe brain tumours show aggressive or escape behaviour during awake surgery. As the amygdala plays a critical role in coping with stress, we evaluated whether the left or right amygdala was involved in aggressive or escape behaviour in six patients undergoing awake surgery for temporal lobe brain tumours.Methods: Brain tumours were located in the left temporal lobe in cases 1–3 and in the right temporal lobe in cases 4–6. In cases 1, 2, 4 and 5, the tumours invaded the amygdala.Results: In case 1, the patient showed aggressive behaviour before partial removal of the left amygdala during awake surgery; just after partial removal of left amygdala, the patient was calm and cooperative. In case 2, the patient showed aggressive behaviour when the tumour near the left amygdala was removed. In case 3, the patient showed aggressive behaviour when awakening during awake surgery. In case 4, the patient showed escape behaviour when removal of the tumour near the right amygdala was initiated. In cases 5 and 6, patients showed escape behaviour upon awakening and upon initiation of tumour removal from the temporal lobe.Conclusion: In conclusion, these results suggest that left or right temporal lesions might induce aggressive or escape behaviour during awake surgery, respectively, and that the amygdala on the respective side may play a role in these behaviours.

Patients undergoing awake surgery for resection of brain tumours in the primary motor cortex (M1) are at high risk of developing new motor deficits. Thus, use of this procedure requires consideration of several important points, including the optimal modality to localise M1 on the affected side and the overall advantages and disadvantages of the procedure. In our experience with awake surgery for 21 brain tumours located in the M1 from January 2004 through October 2008, we found that functional magnetic resonance imaging was the most reliable modality in terms of localising the M1 and that the anatomic relationship between motor tracts and brain tumours is a critical determinant of postoperative motor function. Other considerations, including potential complications of this procedure and relative efficacy and safety versus surgery under general anaesthesia for patients with brain tumours in the M1, are discussed.

The functional characteristics of the left inferior longitudinal fasciculus (ILF) remain unclear. The present study describes a case of a right-handed 74-year-old woman with a brain tumor who showed marked deterioration in object naming ability after invasion of the tumor into the medial region of the left posterior (middle and inferior) temporal lobe just beside the atrium of the lateral ventricle. Diffusion tensor imaging showed possible interruption of the left ILF after invasion of tumor at this site. By contrast, the left superior longitudinal fasciculus (SLF) remained intact after invasion of tumor, and the inferior fronto-occipital fasciculus (IFOF) was already disrupted prior to tumor invasion. These observations indicate that intact ILF function may be required for object naming ability.

Direct evidence of the anatomical localization of brain function is provided by functional neurological changes during awake surgery combined with data from preoperative functional magnetic resonance imaging and diffusion tensor imaging studies. The goal of the present study was to analyze the etiology and mechanism of motor hemineglect using these techniques. Of 29 patients with brain tumors within and near the primary motor area (M1) in whom awake surgery was employed from April 2004 through March 2007, 2 patients evinced motor hemineglect of the left hand during awake surgery. The brain tumors in these 2 cases alone were located just beside the hand area of M1 and the primary sensory area (S1) in the right hemisphere. In case 1, the U fibers that connected the areas activated by hand clenching in M1 with S1 were compressed by the brain tumor. These results suggest that the combination of damage to the right hemispheric hand area in M1 and S1 plays a critical role in the development of motor hemineglect.

Mirror therapy is effective in the rehabilitation of patients with hemiparesis, but its mechanism is not clear. In this study, a patient with brain tumor (patient 1) who underwent mirror therapy after surgery and showed drastic recovery of hand paresis, a patient with visual memory disturbance (patient 2), and five normal volunteers performed tasks related to mirror therapy in fMRI study. In patient 1 and all normal volunteers, right and left hand clenching with looking at a mirror (eye open) activated outside of cerebellum, while right and left hands clenching with eye closed activated inside of cerebellum. In patient 2, mirror therapy did not activate outside of cerebellum. In patient 1, and 3 out of 5 normal volunteers, the area of right (affected) M1 activated by right and left hands clenching with eye open was more than that by right and left hands clenching with eye closed, and that right M1 was activated by right hand clenching with eye open. In conclusion, mirror therapy facilitate the paresis of patients by activating ipsilateral M1 and outside of cerebellum, which is possibly related to visual memory function.

Function of the inferior longitudinal fasciculus (ILF), which connects the anterior temporal and occipital lobes, has not been clearly demonstrated in the human brain. A 47-year-old woman with visual memory disturbance as demonstrated by the Wechsler Memory Scale-Revised presented with possible brain tumor in the right temporal lobe. Diffusion tensor imaging showed partial disconnection of the right ILF, indicating that function of the ILF is highly involved in visual memory.

Radiation therapy with concomitant and adjuvant temozolomide (TMZ) is the standard therapy for nonelderly patients with glioblastoma. However, TMZ-based chemoradiotherapy for elderly patients with glioblastoma is controversial. The aim of this study was to investigate the benefits and adverse effects of this combined therapy in elderly patients with glioblastoma. Of the 76 newly diagnosed glioblastoma patients who were treated with standard radiotherapy (60 Gy/30 fractions) and TMZ, treatment toxicity and therapeutic outcome were evaluated in 27 elderly patients (age 65 years or older) and compared with those of 49 nonelderly counterparts (age younger than 65 years). The incidence of common toxicity criteria Grade 4 adverse events during the concomitant course was higher in the elderly group than that in the nonelderly group (26% versus 8%; p = 0.046). Cognitive dysfunction was observed only in the elderly group (p = 0.042). The median overall survival (OS) and median progression-free survival in the elderly group were 15.2 months (95% confidence interval [CI]; 12.9–18.5) and 8.4 months (95% CI; 5.1–11.7), respectively. OS was significantly shorter in the elderly group than in the nonelderly group (p = 0.021). The recursive partitioning analysis score was a prognostic factor for OS. TMZ-based chemoradiotherapy was associated with an increased risk of Grade 4 adverse events in the elderly patients during concomitant use. Thus, elderly patients who undergo a concomitant course of TMZ must be closely monitored for adverse events. Treatment of glioblastoma in elderly patients must be optimized to reduce toxicity to acceptable levels and to maintain efficacy.

The incidence of brain metastases has increased over time as a consequence of an increase in the overall survival of patients with various types of cancer and the improved detection by magnetic resonance imaging (MRI). In this study, the guidelines and evidence for the radiotherapeutic, surgical, and chemotherapeutic management of patients newly diagnosed with brain metastases have been reviewed. For patients with good prognosis (expected survival, ≥ 3 months) and single brain metastases (3-4 cm) in whom safe complete resection is possible, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiation boost to the resection cavity (level 3). For single brain metastases (3-4 cm) that are not resectable, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For selected patients with a limited number of multiple brain metastases (all3-4 cm) and good prognosis (expected survival, ≥ 3 months), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered (level 1). However, data from recent clinical trials have shown that adjuvant WBRT after radiosurgery or surgery for a limited number of brain metastases reduces intracranial relapses and neurologic deaths but fails to improve the duration of functional independence and overall survival. Many clinical studies have reported the effectiveness of molecular targeted therapies for brain metastases. Gefitinib or erlotinib should be considered for the treatment of asymptomatic patients harboring activating epidermal growth factor receptor (EGFR) mutations. Lapatinib should also be considered for the treatment of patients with brain metastases from human epidermal growth factor receptor (HER)-2-overexpressing metastatic breast cancer. In Japan, the intravenous administration of bevacizumab is currently being used for the treatment of symptomatic radiation necrosis of the brain.

Recent investigation suggests that the dorsal anterior cingulate cortex (ACC) is involved in the interplay between cognition and emotion. The present study described three patients who underwent removal of brain tumors just above the right dorsal ACC. These patients had residual tumor following surgery and showed anxiety disorder (AD) both before and after surgery. Visual memory or attention was abnormal before surgery in these patients, but these deficits improved following surgery, possibly due to a decrease in compression of the right dorsal ACC. These results suggest that damage to the right dorsal ACC is involved in AD and well as in deficits in visual memory or attention. Therefore, the right dorsal ACC might play a role in vision-related cognition and emotion, such as anxiety.

The anatomic localization of brain functions can be characterized via diffusion tensor imaging in patients with brain tumors and neurological symptoms. The goal of the present study was to evaluate the function of the ventral, arcuate fasciculus (AF) and the superior longitudinal fasciculus (SLF)-related language pathways using these techniques by analyzing 9 patients treated in our hospital between 2007 and 2011. In cases 1-3, the left ventral pathways, namely, the inferior longitudinal fasciculus, uncinate fasciculus or inferior fronto-occipital fasciculus, were mainly damaged, and the common dysfunction experienced by these patients was a deficit in object naming. In cases 4-6, the left SLF was mainly damaged, and the common deficit was dysgraphia. In cases 7-9, the left AF was mainly damaged, and almost all language functions related to phonology were abnormal. These results suggest that the left ventral, AF and SLF-related pathways are closely related to visual, auditory and hand-related language function, respectively.

Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are found frequently in malignant gliomas and are likely involved in early gliomagenesis. To understand the prevalence of these mutations and their relationship to other genetic alterations and impact on prognosis for Japanese glioma patients, we analyzed 250 glioma cases. Mutations of IDH1 and IDH2 were found in 73 (29%) and 2 (1%) cases, respectively. All detected mutations were heterozygous, and most mutations were an Arg132His (G395A) substitution. IDH mutations were frequent in oligodendroglial tumors (37/52, 71%) and diffuse astrocytomas (17/29, 59%), and were less frequent in anaplastic astrocytomas (8/29, 28%) and glioblastomas (13/125, 10%). The pilocytic astrocytomas and gangliogliomas did not have either mutation. Notably, 28 of 30 oligodendroglial tumors harboring the 1p/19q co‐deletion also had an IDH mutation, and these alterations were significantly correlated (P

Objectives: Comparison of preoperative and postoperative neurological functions in patients undergoing resection of brain tumors, in combination with data from diffusion tensor imaging (DTI) studies, can provide direct evidence of anatomical localization of brain function. The goal of the present study was to use these techniques to characterize memory function of the right temporal lobe in five patients with right temporal lobe brain tumors. Methods: Memory function was tested using the Wechsler Memory Scale-Revised (WMS-R) before and after surgery in five patients with right temporal lobe brain tumors. Preoperative DTI was performed in four of five cases. Results: In all cases, general and verbal memory, including verbal paired association, significantly improved after surgery (P

Brain imaging studies suggest that panic disorder (PD) is mediated by several brain regions, including the anterior cingulate cortex (ACC). In the present report we describe a patient who experienced a panic attack during awake surgery (case 1) and another patient who developed PD after surgery and radiotherapy (case 2). In case 1, the patient experienced repeated panic attacks when the tumor at the upper border of right dorsal ACC was removed during awake surgery. In case 2, the patient developed PD at six months after surgery and Cyberknife radiotherapy. MRI examination revealed that the dorsal ACC size was reduced at six months after surgery and that the dorsal ACC was absent at two years after surgery, possibly due to radiotherapy-induced damage by radiotherapy. Profile of mood states (POMS) testing characterized the presence of tension-anxiety as the common abnormal symptom in cases 1 and 2. In conclusion, these results suggest that damage to the right dorsal ACC can induce PD and that this structure likely plays a pathophysiologic role in PD.

Analysis of lesions and symptoms in patients with brain tumors combined with information from diffusion tensor imaging provides direct evidence of the anatomical localization of brain function. Using these methods, we evaluated 8 patients who underwent surgery for metastatic brain tumors located in the left occipital lobes between 2007 and 2009. Preoperatively, 4 patients (cases 1–4) had alexia with agraphia while the other 4 patients (cases 5–8) did not. Tractography for the superior longitudinal fasciculus (SLF) was performed before surgery in case 1. The common brain tumors in cases 1–4 were located in the upper portion of area 19, and peritumor edema in that area resulted in compromise of the deep white matter of the inferior parietal lobe (IPL). The SLF was compressed and disrupted in the white matter of the IPL near the upper portion of area 19 in case 1. In cases 5–8, the brain tumors were not located in the upper portion of area 19. These results suggest that damage to the upper portion of area 19 and to the white matter in the left IPL, including the SLF, resulted in alexia with agraphia.

The present study describes a case of a right-handed 74-year-old woman with a brain tumor who showed conversion of speech to Sutra, a Buddhist prayer, which was stored in the right hemisphere according to the Wada test. After surgery, relative improvement in the speech disorder was observed, and frequency of speech production of simple normal words with normal phonology increased. These observations indicate that damage to left temporal lobe resulted in conversion of speech to Sutra, and that Sutra was stored in this patient's right hemisphere.

Awake surgery provides accurate localization of brain function based on rapid reversible neurological changes during surgical manipulation. In this study, hand clenching rapidly deteriorated due to surgical manipulation during awake surgery and instantly recovered not by hand clenching alone but by combined movement of hand clenching and elbow flexion. Postoperative fMRI (functional MRI) showed a smaller area activated by combined movement of hand clenching and elbow flexion than the sum of areas activated by hand clenching alone and elbow flexion alone. Conversely, the activated area by combined movement of hand clenching and elbow flexion was almost the same as the sum of areas by hand clenching alone and elbow flexion alone in fMRI of normal volunteers. These findings indicate reorganization of the motor area by combined movement including the motor function of previous transient weakness, and might suggest the effectiveness of combined movement to improve motor paresis in rehabilitation.

Diffusion tensor tractography provides useful information regarding the surgical strategy for brain tumors. The goal of the present study was to analyze relationships between visual field deficits and the locations of brain tumors compared with optic tracts as visualized by tractography, and compared with the calcarine fissure.Subjects comprised 11 patients with brain tumor in the occipital lobe or atrium of the lateral ventricle who underwent surgery between October 2006 and February 2009. Tumors were categorized as Type A, with almost all the optic tract in the occipital lobe or atrium of the lateral ventricle running close to and stretched by the brain tumor; and Type B, with the optic tract running at least partially distant to the brain tumor and remaining unstretched.Those type A optic tracts that were laterally compressed by brain tumors (Cases 1-3) displayed hemianopsia after surgery. When the brain tumor was located rostro-medial to the calcarine fissure and optic tracts were compressed caudally by the tumor, lower quadrant hemianopsia remained after surgery (Cases 4, 5). In other cases, the visual field remained or improved to normal after surgery.The relationship between optic tracts or the calcarine fissure, and brain tumors in the occipital lobe or atrium of the lateral ventricle is related to visual field deficits after surgery. In particular, those Type A optic tracts that are compressed laterally show hemianopsia of the visual field after surgery.

Changes in motor function in response to lesions in the premotor area (PM) and the primary motor area (M1) are difficult to predict. The goal of the present study was to use awake surgery to characterize the functional property of the PM or the M1 in patients with brain tumors. Neurological change before, during and after awake surgery was compared among 8 cases of patients with brain tumors located in the PM or M1. Degree of recovery after awake surgery was better for those with brain tumors in the PM (average motor strength, 2.3) when compared with those with brain tumors in the M1 (average motor strength, 1.0). Mean duration until recovery of motor strength after awake surgery was significantly shorter for those with brain tumors in the PM (4.3 days) when compared with those with brain tumors in the M1 (7.8 days) (p0.05). Since the degree of removal of brain tumors was greater in those with tumors in the PM when compared with those with tumors in the M1, and because the size of brain tumors in both areas were comparable, the marked and rapid recovery of motor strength after awake surgery for those with brain tumors in PM was likely related to the specific neurological properties of PM such as the redundant network of the secondary motor area. Recovery of motor strength after awake surgery for those with brain tumors located in PM was relatively marked and rapid when compared with those with brain tumors in the M1.

Purpose:Cortical mapping during awake surgery assesses intraoperative neurological change in response to electrical stimulation to provide direct information regarding the anatomical localization of the primary motor area (M1). The goal of the present study was to analyze the reliability of the identification of the precentral knob in the axial image of magnetic resonance imaging or functional MRI (fMRI) for the detection of M1.Materials and Methods:Among patients with brain tumors within or near M1 in whom awake surgery was employed from April 2004 through March 2007, 14 cases were analyzed in which either the M1 or premotor area (PMA) was successfully detected by mapping during awake surgery.Results:The precentral knob was localized to the PMA in 4 cases and to M1 in 10 cases. By contrast, the gyrus activated by hand clenching in fMRI on the affected side at least partially corresponded to M1 in all cases, while those on the unaffected side corresponded to M1 in 12 of 12 cases.Conclusion:These results indicate that the precentral knob corresponds to PMA as well as to M1, whereas the gyrus activated in fMRI corresponds to M1 on the affected and unaffected side.

Awake surgery has been reported to play a role in the safe removal of brain tumors and detection of the functional localization of the cortex or neuronal tracts. In our hospital, from November 2004 to May 2007, we performed awake surgery with continuous tasks in 33 cases of brain tumors within or near the primary motor area (M1). The relationship between the extent of resection and postoperative motor function in awake surgery cases was compared with that in cases of surgery under general anesthesia, which were performed prior to November 2004. In 32 of 33 cases of awake surgery, the final postoperative motor function was either preserved or improved relative to the preoperative levels; however, in 9 of 14 patients who underwent surgery under general anesthesia, deterioration in motor function was noted after surgery. Gross total removal (GTR) was achieved in 20 of 33 cases of awake surgery and in 8 of 14 cases of surgery under general anesthesia, indicating that the extent of resection was similar between awake surgery and surgery under general anesthesia. In most cases of awake surgery, neurological deterioration occurred during internal decompression of the tumors or compression of the normal brain, while surgical manipulation of the tumor margin did not induce neurological deterioration in most cases of surgery under general anesthesia. Moreover, various new findings regarding the function of the cortex or neuronal tract have been reported in awake surgery. We discussed the advantages and future directions of awake surgery. In conclusion, awake surgery plays an important role in neurosurgery and neuroscience.

Anatomical localization of brain function can be achieved by functional changes during awake surgery combined with tractography constructed by diffusion tensor imaging studies. We aimed to use these techniques to characterize the sensory tract in the corona radiata in patients with closely associated brain tumors. Of nine patients who had brain tumors in the primary sensory area (S1) and who underwent awake surgery between October 2004 and July 2007, two patients showed deterioration in deep sensation during and after awake surgery. Both of these patients also developed involuntary movements (for patient 1 this was myoclonus of the left hand, while patient 2 experienced unintentional lifting of the arm). In these two patients, tumors were located just beside the sensory tract in the corona radiata of the right hemisphere. In patient 2, Wallerian degeneration of the sensory tract and concomitant deterioration of superficial and deep sensation were observed at 6 months after awake surgery. These results suggest that damage to a closely associated sensory tract in the corona radiata is critical to the development of sensory deficits and involuntary movements. For patients who undergo surgical resection of S1 brain tumors, pre-operative tractography to detect the sensory tract in the corona radiata may allow protection of the sensory tract during awake surgery, thereby preventing post-operative sensory deficits.

The oral alkylating agent, temozolomide (Temodal: TMZ), is the only anticancer drug that has been shown in a phase III study to improve survival in glioblastoma (GBM) when administered with concomitant radiotherapy. Pharmacokinetic studies have documented relatively high concentrations of TMZ in brain tumors and cerebrospinal fluid (20-40% of the area under the plasma concentration curve), and other studies have demonstrated that TMZ is effective for treatment of various brain tumors, including recurrent and newly diagnosed glioma, primary CNS lymphoma, metastatic melanoma, and neuroblastoma. Molecular markers that predict a favorable response to TMZ plus concomitant radiotherapy include methylguanine methyltransferase (MGMT) promoter methylation patients with GBM and chromosome 1p/19q deletion in patients with anaplastic oligodendroglioma or low-grade glioma. Myelosuppression, nausea and constipation are relatively frequent in patients undergoing treatment with TMZ, and prophylaxis against Pneumocystis carinii pneumonia should be instituted. This article will summarize and discuss these issues as well as review ongoing and anticipated studies of TMZ in combination with other anti-cancer therapies.

Resection of brain tumors in the primary motor area (M1) is difficult to achieve without adversely affecting motor function. Between November 2003 and November 2006, 16 patients with 18 brain tumors involving the M1 (11 metastatic, 6 gliomas, 1 cavernous angioma) underwent craniotomy and awake surgery with continuous motor testing at our hospital. Patients were classified as either type A (9 patients), indicating that motor tracts ran in close proximity to the brain tumors, or type B (7 patients), indicating that motor tracts ran distant to the tumor. The relationship between the extent of resection and post-operative motor function was subsequently evaluated. In 17 out of 18 cases, final post-operative motor function was either preserved or improved relative to pre-operative levels, although transient deterioration of motor function and partial removal of the tumor were observed in 7 and 8 cases, respectively. The remaining patients experienced slight deterioration in motor function of the upper extremities. All type A patients experienced suboptimal outcomes, involving transient or permanent deterioration of motor function after surgery or only partial removal of the tumor. By contrast, most type B patients experienced good outcomes (no deterioration of motor function and gross total removal of the tumor). In conclusion, awake surgery with continuous motor testing allowed for resection of brain tumors in the M1 and preservation of motor function, although the patients in whom motor tracts ran in close proximity to the tumors experienced suboptimal outcomes.

Use of intrathecal (IT) chemotherapy combined with radiotherapy can extend survival of patients with untreated leptomeningeal dissemination of malignant tumors from one month to two to six months. The goal of the present study was to determine the effect of continuous IT (CIT) via a subcutaneous port that was placed using a neuronavigation system. Twenty patients with leptomeningeal dissemination (primary disease: 10 cancers, 6 gliomas and 4 lymphomas) were given 2-7 cycles of continuous IT (CIT) with methotrexate (MTX; 10 mg) administered into the lateral ventricle for 5 consecutive days biweekly. The concentration of MTX in the lateral ventricle was 7 to 10 x 10(-6 )M from Day 1 to 4. Response to this therapy included 6 patients with complete remission, 7 with progressive disease, and 7 with stable disease. Kaplan-Meier analysis revealed a median overall survival of 8 months while the overall survival rate for leptomeningeal specific death or for metastasis from cancer was 13 or 5 months, respectively. Complications of CIT with MTX were relatively low (

A 54-year-old human immunodeficiency virus type 1 (HIV-1)-infected homosexual Japanese male was found to have collapsed in his bathroom and was brought to our facility with diminished level of consciousness. Computed tomography showed subarachnoid hemorrhage (SAH). He was severely dehydrated with unstable general status that deterred us from performing emergent surgery. Cerebral angiography performed on the 18th hospital day revealed bilateral distal anterior cerebral artery aneurysms. Clipping of these aneurysms was performed on the 30th hospital day and no postoperative complications were experienced. The scalp wound showed no delayed healing, whereas the tracheostomy wound showed repeated wound dehiscence and delayed healing. Postoperative highly active antiretroviral therapy with antibiotic treatment gradually improved his general and immunological conditions. The patient was finally discharged as independent with mild muscle weakness in the bilateral lower extremities. HIV-1 infection should not be the guiding factor in the decision to aggressively treat concomitant aneurysmal disease. Clipping of cerebral aneurysms with full craniotomy or endovascular obliteration should be considered even in HIV-1-infected patients with SAH.

BACKGROUND: NovoTTF-100A System is an FDA-approved treatment for recurrent glioblastoma (GBM) and is defined as a device of high unmet medical need in Japan. Subsequently, the device has been made available on a restricted case basis for compassionate use in Japan. Here we report initial experience with 10 patients treated at Tokyo Women's Medical University, Kashiwaba Neurosurgical Hospital and Japanese Red Cross Medical Center. METHODS: Using retrospective chart review, we analyzed patient demographics, tumor size, location, and treatment compliance with NovoTTF-100A System from the device log files. Duration of therapy was estimated using the Kaplan-Meier estimate. Adverse event frequency and severity was also evaluated. RESULTS: Ten (10) patients with supra-tentorial recurrent GBM were treated between July 8, 2013 and June 3, 2014 at 3 Japanese hospitals. 80% were male and 20% female. The median age was 41 years (range 32-66). The average baseline tumor burden was 13.3 cm2. 40% of patients had bi-hemispheric tumors and 30% left hemispheric tumors. The K-M median duration of therapy was 7.8 months. Average daily device compliance was 17.4 hours. This is consistent with prior global studies which have demonstrated average daily device compliance of 70-80%. The device was well-tolerated with no reported serious adverse events. The only device-related adverse events were mild skin irritation. CONCLUSIONS: NovoTTF-100A System was safe and well-tolerated in an initial cohort of Japanese patients with GBM. Device usage and compliance was consistent with that observed in non-Japanese patients.