FFAR1/GPR40 Contributes to the Regulation of Striatal Monoamine Releases and Facilitation of Cocaine-Induced Locomotor Activity in Mice.

The free fatty acid receptor 1 (FFAR1) is suggested to function as a G protein-coupled receptor (GPR40) for medium-to-long-chain free fatty acids. Previous studies on the expression of FFAR1 revealed that the nigrostriatal region is one of the areas which express abundant FFAR1 mRNA/protein in the central nervous system (CNS). However, the role of FFAR1 in the CNS has been still largely unclarified. Here, we examined a possible functional role of FFAR1 in the control of extracellular concentrations of striatal monoamines and cocaine-induced locomotor activity. Microdialysis analysis revealed that the basal level of extracellular dopamine (DA) was significantly elevated, while the basal serotonin (5-HT) level tended to be reduced in the striatum of FFAR1 knockout (-/-) mice. Interestingly, local application of a FFAR1 agonist, GW9508, markedly augmented the striatal 5-HT release in FFAR1 wild-type (+/+) mice, whereas topical application of a FFAR1 antagonist, GW1100, significantly reduced the 5-HT release. However, the enhanced 5-HT release was completely lost in -/- mice. Although acute administration of cocaine enhanced the locomotor activity in both +/+ and -/- mice, the magnitude of the enhancement was significantly reduced in -/- mice. In addition, intraperitoneal injection of GW1100 significantly decreased the cocaine-induced locomotor enhancement. These results suggest that FFAR1 has a facilitatory role in striatal 5-HT release, and the evoked 5-HT release might contribute to enhance cocaine-induced locomotor activity.

Deep Sylvian Meningioma without Dural Attachment - A Case Report.

Deep Sylvian meningiomas are rare, accounting for 0.3-0.4% of all meningiomas, and mostly present in young adults and children. We report on a 32-year-old man who presented with headache but had no neurological deficits. Computed tomography of brain revealed a 24 × 19 × 21 mm3 mass lesion in the right Sylvian fissure with calcification. Magnetic resonance imaging showed that the lesion was isointense on T1- and T2-weighted images (WI), with homogenous enhancement on post-gadolinium T1WI. The lesion was surgically removed via right fronto-temporal craniotomy. The tumor was located in deep Sylvian fissure and had no dural attachment. Histopathological examination of the lesion revealed both meningothelial and fibroblastic features, thereby suggesting the diagnosis of transitional meningioma (WHO grade I), with Ki-67 labeling index of 6.9%. Thus, meningioma should be considered as a differential diagnosis of enhancing mass lesions in the Sylvian fissure even in the absence of dural tail sign, especially in young adults and children.

Efficacy of bevacizumab therapy for unresectable malignant glioma: A retrospective analysis.

Bevacizumab (BEV), an inhibitor of vascular endothelial growth factor A, has been used for primary and recurrent malignant gliomas in Japan since June, 2013. Previous randomized controlled studies demonstrated that BEV prolonged the progression-free survival, but not the overall survival (OS) of patients with newly diagnosed glioblastoma. The aim of the present study was to elucidate the effect of BEV on the OS of patients with unresectable malignant gliomas. Of the 440 cases of malignant glioma initially treated in our institute between 2000 and 2015, 88 were not suitable for maximal resection due to patient age, physical condition, tumor location and extent, or the patient's wishes. Based on the biopsy results, the pathological diagnosis was glioblastoma, anaplastic astrocytoma and anaplastic oligodendroglioma in 60, 19 and 9 patients, respectively. Kaplan-Meier and log-rank analyses were performed to investigate the effect of BEV on OS. OS was longer in the BEV group (n=24) compared with that in the non-BEV group [n=64; median survival time (MST), 566 vs. 243 days, respectively; hazard ratio (HR)=0.413; 95% confidence interval (CI): 0.216-0.787; P=0.003]. In the 41 patients who received temozolomide (TMZ) and radiotherapy and the 31 patients with glioblastoma who received TMZ and radiotherapy, OS was longer in the BEV group compared with that in the non-BEV group (MST, 568 vs. 334 days, HR=0.404, 95% CI: 0.175-0.933, P=0.016; and MST, 566 vs. 160 days, HR=0.253, 95% CI: 0.099-0.646, P=0.001, respectively). In the Cox hazard model analysis of 41 patients who underwent TMZ-based chemoradiotherapy after biopsy, the use of BEV was the strongest independent beneficial factor associated with prolonged OS (HR=0.101; P=0.0002). Our retrospective survey suggested that BEV prolongs the OS of patients with unresectable malignant gliomas. However, these results must be verified by a well-designed prospective randomized controlled trial.

Radiologic and histologic features of the T2 hyperintensity rim of meningiomas on magnetic resonance images.

A hyperintensity rim is often seen at the brain-tumor interface of meningiomas upon T2-weighted (T2WI) magnetic resonance imaging (MRI), and it is referred to as the cerebrospinal fluid (CSF) space; however, the true nature of the rim remains unclear. We surveyed the MRI findings and the histopathologic characteristics of such rims. Our study population consisted of 53 consecutive patients who underwent meningioma removal at our hospital. The intensity of the rim on MRI scans obtained with different imaging sequences was assessed in all patients. We used 22 tumors for histopathologic investigation: tissue samples were acquired from both the tumor surface and from a deep intratumoral site. Of the 53 meningiomas, 37 (69.8%) manifested a hyperintensity rim on T2WI (T2-rim). The other 16 showed neither a hyperintense nor a hypointense rim on their T2WI. An enhancement effect corresponding to the rim was observed in 28 of the 37 (75.7%) T2-rim positive tumors. While 9 among the 37 tumors with a T2-rim (24.3%) did not show rim enhancement, they showed low intensity on fluid-attenuated inversion recovery (FLAIR) images. The microvascular density in the tumor capsule was significantly greater in the 12 T2-rim and rim enhancement positive tumors than in 10 tumors that were T2-rim negative or T2-rim positive, but rim enhancement-negative ( p < 0.001, Mann-Whitney U test). We found that 75.7% of T2 hyperintense rims that were detected at the brain-meningioma interface reflected a microvascular-rich capsule layer, rather than the CSF space.

A Novel Bilateral Approach for Suprasellar Arachnoid Cysts: A Case Report.

The endoscopic method is used to treat suprasellar arachnoid cysts (SACs) but it is sometimes difficult to make sufficiently sized fenestrations. Creating a larger fenestration on the cyst wall is preferable to prevent closure of the stoma. In this paper, we report a novel endoscopic approach for SAC treatment in which we use bilateral burr holes to achieve a more extensive cyst fenestration. A 7-year-old girl was referred to our hospital because of incidentally detected hydrocephalus by computed tomography scans. Physical examination did not show any signs of intracranial hypertension, but a digital impression of her skull on X-ray implied chronic intracranial hypertension. Magnetic resonance imaging (MRI) revealed enlargement of both lateral ventricles and a cystic mass occupying the third ventricle. We performed cyst wall fenestration using a bilateral approach in which we created two burr holes to introduce a flexible endoscope and a rigid endoscope. The cyst wall was held by forceps with the flexible endoscope, and resection of the cyst wall was achieved by using a pair of scissors with the rigid endoscope. There were no postoperative complications, and MRI performed 1 year after treatment showed disappearance of the superior part of the cyst wall.

[Extranodal marginal zone lymphoma of the dura: a case report].

The authors present the case of a 65-year-old woman who initially was diagnosed as having intracranial dural B-cell malignant lymphoma. She survived more than 9 years after surgery and radiation. We re-examined the specimens pathologically. Histological findings confirmed an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) that showed numerous IgG4-positive plasma cells. MALT lymphomas are already recognized as a distinct clinico-pathological entity. A primary dural MALT lymphoma is very rare and has a favorable clinical outcome, and patients are expected to have an excellent long-term survival with local therapy alone.

Intracranial germinoma presenting with hemiatrophy--follow-up results and literature review--two case reports.

Two boys aged 8 and 12 years presented with intracranial germinoma manifesting as cerebral hemispheric atrophy, hemiparesis, and decline in academic performance. First magnetic resonance (MR) imaging showed no enhanced lesions, but follow-up MR imaging obtained 12 or 23 months after the first visit showed new mass lesions in the temporal lobe or pituitary gland. Biopsy of these lesions resulted in a histological diagnosis of germinoma. Chemoradiation therapy produced complete remission but both patients continued to manifest mild hemiparesis and impaired cognitive function. Review of 18 previous and our 2 patients presenting with hemispheric atrophy revealed strong male predominance (18:2), mean age of 12.8 ± 5.2 (standard deviation) years, hemiparesis in all patients, and cognitive decline in 9 patients. Initial MR imaging detected mass lesions in only 9 patients, but follow-up MR imaging performed 10-38 months later detected new mass lesions in 5 patients. Radiation with/without chemotherapy provided good tumor control in all patients, but none of the 9 patients with cognitive dysfunction recovered their intellectual ability. We recommend early diagnosis based on biopsy of the atrophic site and timely treatment to improve the quality of life in these patients.