Recently, a large number of surgical studies based on the objective evaluation of EOR have been published, suggesting that EOR has a significant effect not only on the rate of tumor progression and OS but also on the decrease Object. A growing number of published studies have recently demonstrated the role of resection in overall survival (OS) for patients with gliomas. In this retrospective study, the authors objectively investigated the role of the extent of resection (EOR) in OS in patients with low-grade gliomas (LGGs).Methods. Between 1998 and 2011, 190 patients underwent surgery for LGGs. All surgical procedures were conducted under corticosubcortical stimulation. The EOR was established by analyzing the pre-and postoperative volumes of the gliomas on T2-weighted MRI studies. The difference between the preoperative tumor volumes was also investigated by measuring the volumetric difference between the T2-and T1-weighted MRI images (DVT2T1) to evaluate how the diffusive tumor-growing pattern affected the EOR achieved.Results. The median preoperative tumor volume was 55 cm 3 , and in almost half of the patients the EOR was greater than 90%. In this study, patients with an EOR of 90% or greater had an estimated 5-year OS rate of 93%, those with EOR between 70% and 89% had a 5-year OS rate of 84%, and those with EOR less than 70% had a 5-year OS rate of 41% (p < 0.001). New postoperative deficits were noted in 43.7% of cases, while permanent deficits occurred in 3.16% of cases. There were 41 deaths (21.6%), and the median follow-up was 4.7 years.A further volumetric analysis was also conducted to compare 2 different intraoperative protocols (Series 1 [intraoperative electrical stimulation alone] vs Series 2 [intraoperative stimulation plus overlap of functional MRI/fiber tracking diffusion tensor imaging data on a neuronavigation system]). Patients in Series 1 had a median EOR of 77%, while those in Series 2 had a median EOR of 90% (p = 0.0001). Multivariate analysis showed that OS is influenced not only by EOR (p = 0.001) but also by age (p = 0.003), histological subtype (p = 0.005), and the DVT2T1 value (p < 0.0001). Progression-free survival is similarly influenced by histological subtype (fibrillary astrocytoma, p = 0.003), EOR (p < 0.0001), and DVT2T1 value (p < 0.0001), as is malignant progression-free survival (p = 0.003, p < 0.0001, and p < 0.0001, respectively). Finally, the study shows that the higher the DVT2T1 value, the less extensive the currently possible resection, highlighting an apparent correlation between the DVT2T1 value itself and EOR (p < 0.0001).Conclusions. The EOR and the DVT2T1 values are the strongest independent predictors in improving OS as well as in delaying tumor progression and malignant transformation. Furthermore, the DVT2T1 value may be useful as a predictive index for EOR. Finally, due to intraoperative corticosubcortical mapping and the overlap of functional data on the neuronavigation system, major resection is possible with an acceptable risk and a significant increase ...

A series of 11 patients with a basilar tip aneurysm were treated operatively. The aneurysm had ruptured in all cases and caused at least one haemorrhage prior to surgery. Four patients harboured large aneurysms, while in the rest of them the aneurysms were small in size. In all the 11 patients a modified pterional transcavernous-transsellar approach was used which considerably facilitated clipping and secured complete exclusion of all aneurysms, including the large ones. Eight patients made a complete recovery and resumed their original occupation. One is hemiparetic but capable of self care, one is hemiplegic, and one died after surgery. The purpose of this report is to present our modified surgical approach to basilar tip aneurysms, which provides good exposure of the entire region of the bifurcation of the basilar artery and adjacent blood vessels as far as the anterior inferior cerebellar arteries, and requires but minimal retraction of the brain.

A major contributing factor to glioma development and progression is its ability to evade the immune system. Nano-meter sized vesicles, exosomes, secreted by glioma-stem cells (GSC) can act as mediators of intercellular communication to promote tumor immune escape. Here, we investigated the immunomodulatory properties of GCS-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes. Phenotypic characterization, cell proliferation, Th1/Th2 cytokine secretion and intracellular cytokine production were analysed by distinguishing among effector T cells, regulatory T cells and monocytes. In unfractionated PBMCs, GSC-derived exosomes inhibited T cell activation (CD25 and CD69 expression), proliferation and Th1 cytokine production, and did not affect cell viability or regulatory T-cell suppression ability. Furthermore, exosomes were able to enhance proliferation of purified CD4+ T cells. In PBMCs culture, glioma-derived exosomes directly promoted IL-10 and arginase-1 production and downregulation of HLA-DR by unstimulated CD14+ monocytic cells, that displayed an immunophenotype resembling that of monocytic myeloid-derived suppressor cells (Mo-MDSCs). Importantly, the removal of CD14+ monocytic cell fraction from PBMCs restored T-cell proliferation. The same results were observed with exosomes purified from plasma of glioblastoma patients. Our results indicate that glioma-derived exosomes suppress T-cell immune response by acting on monocyte maturation rather than on direct interaction with T cells. Selective targeting of Mo-MDSC to treat glioma should be considered with regard to how immune cells allow the acquirement of effector functions and therefore counteracting tumor progression.

The predisposition of human beings toward spiritual feeling, thinking, and behaviors is measured by a supposedly stable personality trait called self-transcendence. Although a few neuroimaging studies suggest that neural activation of a large fronto-parieto-temporal network may underpin a variety of spiritual experiences, information on the causative link between such a network and spirituality is lacking. Combining pre- and post-neurosurgery personality assessment with advanced brain-lesion mapping techniques, we found that selective damage to left and right inferior posterior parietal regions induced a specific increase of self-transcendence. Therefore, modifications of neural activity in temporoparietal areas may induce unusually fast modulations of a stable personality trait related to transcendental self-referential awareness. These results hint at the active, crucial role of left and right parietal systems in determining self-transcendence and cast new light on the neurobiological bases of altered spiritual and religious attitudes and behaviors in neurological and mental disorders.

The ability of exosomes to elicit specific cellular responses suggests that they may be increasingly used as therapeutics. Their vesicular nature makes them suitable as potential nanocarriers for drugs or nucleic acids delivery. Here we address the question whether the method of preparation of enriched exosomal fractions can affect their uptake by cells and their ability to trigger a response.We compared ultracentrifugation and polymer-based precipitation methods on supernatants of glioma-associated stem cells isolated from a high-grade glioma patient. We determined particle size distributions after purification and their correlation with uptake, proliferation and migration in glioblastoma cell cultures.Our findings indicate that polymer-based precipitation leads to smaller particle size distributions, faster uptake by target cells and increased cellular motility. The different effect that isolation method-dependent populations of particles have on cell motility suggests their size distribution could also profoundly affect exosomes therapeutic potential.

Background: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low-grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state-of-theart markers, hindering the decision-making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high-grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm. Methods and Findings: We isolated glioma-associated stem cells (GASC) from LGG (n540) and HGG (n573). GASC showed stem cell features, anchorage-independent growth, and supported the malignant properties of both A172 cells and human glioma-stem cells, mainly through the release of exosomes. Finally, starting from GASC obtained from HGG (n513) and LGG (n512) we defined a score, based on the expression of 9 GASC surface markers, whose prognostic value was assayed on 40 subsequent LGG-patients. At the multivariate Cox analysis, the GASCbased score was the only independent predictor of overall survival and malignant progression free-survival. Conclusions: The microenvironment of both LGG and HGG hosts non-tumorigenic multipotent stem cells that can increase in vitro the biological aggressiveness of gliomainitiating cells through the release of exosomes. The clinical importance of this finding is supported by the strong prognostic value associated with the characteristics of GASC. This patientbased approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor stroma.

A recently proposed theory on frontal lobe functions claims that the prefrontal cortex, particularly its dorso-lateral aspect, is crucial in defining a set of responses suitable for a particular task, and biasing these for selection. This activity is carried out for virtually any kind of non-routine tasks, without distinction of content. The aim of this study is to test the prediction of Frith's 'sculpting the response space' hypothesis by means of an 'insight' problem-solving task, namely the matchstick arithmetic task. Starting from Knoblich et al.'s interpretation for the failure of healthy controls to solve the matchstick problem, and Frith's theory on the role of dorsolateral frontal cortex, we derived the counterintuitive prediction that patients with focal damage to the lateral frontal cortex should perform better than a group of healthy participants on this rather difficult task. We administered the matchstick task to 35 patients (aged 26-65 years) with a single focal brain lesion as determined by a CT or an MRI scan, and to 23 healthy participants (aged 34-62 years). The findings seemed in line with theoretical predictions. While only 43% of healthy participants could solve the most difficult matchstick problems ('type C'), 82% of lateral frontal patients did so (Fisher's exact test, P < 0.05). In conclusion, the combination of Frith's and Knoblich et al.'s theories was corroborated.

Human brain astrocytomas range from the indolent low-grade to the highly infiltrating and aggressive high-grade form, also known as glioblastoma multiforme. The extensive heterogeneity of astrocytic tumors complicates their pathological classification. In this study, we compared the protein pattern of low-grade fibrillary astrocytomas to that of glioblastoma multiforme by 2D electrophoresis. The level of most proteins remains unchanged between the different grade tumors and only few differences are reproducibly observable. Fifteen differentially expressed proteins, as well as seventy conserved spots, were identified by mass spectrometry. Western and immnunohistochemical analysis confirmed the differential expression of the identified proteins. These data provide an initial reference map for brain gliomas. Among the proteins more highly expressed in glioblastoma multiforme, we found peroxiredoxin 1 and 6, the transcription factor BTF3, and alpha-B-crystallin, whereas protein disulfide isomerase A3, the catalytic subunit of the cAMP-dependent protein kinase, and the glial fibrillary acidic protein are increased in low-grade astrocytomas. Our findings contribute to deepening our knowledge of the factors that characterize this class of tumors and, at the same time, can be applied toward the development of novel molecular biomakers potentially useful for an accurate classification of the grade of astrocytomas.