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Positron emission tomography combined with computed tomography (PET/CT) is currently the standard imaging method in neuro-oncology for gliomas and metastatic lesions. There is much less experience with the use of PET/CT in meningioma, the most common primary tumor of the central nervous system, and there are some differences in how results are interpreted. The aim of the present work was to assess the potential for and features of the use of PET/CT to determine the degree of malignancy of meningioma, its prevalence, responses to radiotherapy, and diagnosis of relapse and/or post-radiation changes based on our own clinical experience and review of the literature. The study included 70 patients with 77 meningiomas who underwent 11C-methionine PET/CT. Mean age at investigation was 57.4 years (range 19–86 years). The main parameter evaluated, the tumor/normal ratio (T/N) of 11C-methionine (11C-MET) in tumors, averaged 3.13 (1.00–10.66). Meningiomas had high 11C-MET T/N, with values of >1.5 in 89.6% of cases. In histologically verified malignancy grade 1, 2, and 3 meningiomas (WHO scale), median T/N values were 4.06 [3.04; 4.57], 2.32 [2.12; 3.69], and 4.29 [2.60; 5.10] respectively, with no significant between-group differences. At the same time, non-growing or slowly growing histologically unverified meningiomas, i.e., incidentally discovered, had significantly lower 11C-MET T/N than grade 1 and 3 meningiomas. There was no significant difference in T/N between irradiated meningiomas with controls for tumor growth (3.81 [2.97, 3.98]) and relapse (3.62 [2.60, 4.30]). Comparison of irradiated and non-irradiated grade 1, 2, and 3 meningiomas, as well as the combined group of grade 1–3 tumors, revealed no significant differences in 11C-MET T/N. The use of PET/CT for meningiomas has a number of important characteristics. Meningiomas had high 11C-MET T/N. Our data indicate that 11C-MET PET/CT does not distinguish between meningiomas with different degrees of malignancy, i.e., WHO grades 1, 2, and 3. 11C-MET T/N in meningiomas remains stably high or shows a slight decrease in cases with effective radiotherapy and long-term local control. Comparison of growing and non-growing meningiomas revealed no significant differences in 11C-MET T/N between irradiated and non-irradiated tumors. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) leads to significant long-term cognitive deficits, so-called the post-SAH syndrome. Existing neurological scales used to assess outcomes of SAH are focused on sensory-motor functions. To better evaluate short-term and chronic consequences of SAH, we explored and validated a battery of neurobehavioral tests to gauge the functional outcomes in mice after the circle of Willis perforation-induced SAH. The 18-point Garcia scale, applied up to 4 days, detected impairment only at 24-h time point and showed no significant difference between the Sham and SAH group. A decrease in locomotion was detected at 4-days post-surgery in the open field test but recovered at 30 days in Sham and SAH groups. However, an anxiety-like behavior undetected at 4 days developed at 30 days in SAH mice. At 4-days post-surgery, Y-maze revealed an impairment in working spatial memory in SAH mice, and dyadic social interactions showed a decrease in the sociability in SAH mice, which spent less time interacting with the stimulus mouse. At 30 days after ictus, SAH mice displayed mild spatial learning and memory deficits in the Barnes maze as they committed significantly more errors and used more time to find the escape box but still were able to learn the task. We also observed cognitive dysfunction in the SAH mice in the novel object recognition test. Taken together, these data suggest dysfunction of the limbic system and hippocampus in particular. We suggest a battery of 5 basic behavioral tests allowing to detect neurocognitive deficits in a sub-acute and chronic phase following the SAH. [ABSTRACT FROM AUTHOR]

We present the first clinical application of non-invasive stereotaxic radioablation of ventricular tachycardia (VT) refractory to medical and surgical treatment. Based on the results of invasive navigational activation mapping, a pericicatrical zone in the interventricular septum associated with VT was verified. Radiosurgical irradiation of the target in the region of the interventricular septum and the posterior apical segment of the left ventricle was performed on a TrueBeam linear electron accelerator (Varian) in accordance with the segmental scheme of the left ventricle. Irradiation doses for 95% of the internal target volume (ITV, 17 cm3) and planned target volume (PTV, 46 cm3) (31.2 and 25 Gy, respectively) were delivered by two full coplanar arches in 1 session. Irradiation was performed during expiration using a respiratory control system. The loading dose to critical structures was within tolerance. The planned follow-up period is 6 months. According to remote monitoring, the intensity of VT paroxysms over 48 days after treatment was from daily to 2-3 per day. Then, the incidence of VT paroxysms decreased (1-3 per week), and from the 64th to the 185th day (the end of the observation period), no VT paroxysms were recorded, which suggests that the impact was highly precise, conformal, and involved the total wall thickness. No undesirable effects and damage to adjacent organs were observed. [ABSTRACT FROM AUTHOR]

We developed a new technique of noninvasive stereotactic radioablation for the treatment of life-threatening tachyrhythmias. The study is performed on pigs (Sus scrofa domesticus). The zones of planned exposure were atrioventricular node (heart loading dose 40 Gy) and the apex of the left ventricle with a part of the interventricular septum (35 Gy) in animal No. 1 and atrioventricular node (45 Gy) and free wall of the left ventricle (40 Gy) in animal No. 2. The study was conducted on the Varian TrueBeam linear accelerator. The planned follow-up duration was 6 months. Delivery of 40 Gy to the atrioventricular node did not lead to persistent electrophysiological effect due to the development of transient third-degree atrioventricular block. The dose of 45 Gy resulted in permanent third-degree atrioventricular block followed by development of ventricular standstill on day 21 of observation. Histological examination confirmed transmurality and high precision of performed intervention. [ABSTRACT FROM AUTHOR]

Medulloblastoma, a common pediatric malignant central nervous system tumour, represent a small proportion of brain tumours in adults. Previously it has been shown that in adults, Sonic Hedgehog (SHH)-activated tumours predominate, with Wingless-type (WNT) and Group 4 being less common, but molecular risk stratification remains a challenge. We performed an integrated analysis consisting of genome-wide methylation profiling, copy number profiling, somatic nucleotide variants and correlation of clinical variables across a cohort of 191 adult medulloblastoma cases identified through the Medulloblastoma Advanced Genomics International Consortium. We identified 30 WNT, 112 SHH, 6 Group 3, and 41 Group 4 tumours. Patients with SHH tumours were significantly older at diagnosis compared to other subgroups (p < 0.0001). Five-year progression-free survival (PFS) for WNT, SHH, Group 3, and Group 4 tumours was 64.4 (48.0–86.5), 61.9% (51.6–74.2), 80.0% (95% CI 51.6–100.0), and 44.9% (95% CI 28.6–70.7), respectively (p = 0.06). None of the clinical variables (age, sex, metastatic status, extent of resection, chemotherapy, radiotherapy) were associated with subgroup-specific PFS. Survival among patients with SHH tumours was significantly worse for cases with chromosome 3p loss (HR 2.9, 95% CI 1.1–7.6; p = 0.02), chromosome 10q loss (HR 4.6, 95% CI 2.3–9.4; p < 0.0001), chromosome 17p loss (HR 2.3, 95% CI 1.1–4.8; p = 0.02), and PTCH1 mutations (HR 2.6, 95% CI 1.1–6.2; p = 0.04). The prognostic significance of 3p loss and 10q loss persisted in multivariable regression models. For Group 4 tumours, chromosome 8 loss was strongly associated with improved survival, which was validated in a non-overlapping cohort (combined cohort HR 0.2, 95% CI 0.1–0.7; p = 0.007). Unlike in pediatric medulloblastoma, whole chromosome 11 loss in Group 4 and chromosome 14q loss in SHH was not associated with improved survival, where MYCN, GLI2 and MYC amplification were rare. In sum, we report unique subgroup-specific cytogenetic features of adult medulloblastoma, which are distinct from those in younger patients, and correlate with survival disparities. Our findings suggest that clinical trials that incorporate new strategies tailored to high-risk adult medulloblastoma patients are urgently needed. [ABSTRACT FROM AUTHOR]

Long-term complications such as radiation-induced second malignancies occur in a subset of patients following radiation-therapy, particularly relevant in pediatric patients due to the long follow-up period in case of survival. Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies such as acute lymphoblastic leukemia (ALL) and medulloblastoma (MB). We perform comprehensive (epi-) genetic and expression profiling of RIGs arising after cranial irradiation for MB (n =23) and ALL (n =9). Our study reveals a unifying molecular signature for the majority of RIGs, with recurrent PDGFRA amplification and loss of CDKN2A/B and an absence of somatic hotspot mutations in genes encoding histone 3 variants or IDH1/2, uncovering diagnostic markers and potentially actionable targets. [ABSTRACT FROM AUTHOR]

Recently, there has been a significant amount of interest in additive manufacturing of aerospace parts from heat-resistant alloys due to the ability of producing more complex shapes parts in comparison with conventional technologies. This paper describes the research results of selective laser melting (SLM) of nickel-based IN-738 superalloy powder. The main research results of studies are microstructure investigation after SLM, hot isostatic pressing (HIP), and heat treatment on the cylindrical samples. The article presents results of short-term strength tests of cylindrical specimens at room temperature and 900 °C, and long-term strength. The research studies the influence of HIP on stress-strain behavior of specimens, which are built at different angles: 0, 45, 90°. The tensile strength of vertical samples is increasing by 60 MPa, at 45° is decreasing by 75 MPa, and at 0° is increasing by 139 MPa compared with the initial state. The developing IN-738 selective laser melting technology is approving by fabrication of GTE nozzle guide vane. [ABSTRACT FROM AUTHOR]

Desmoplastic/nodular medulloblastomas (DNMB) and medulloblastomas with extensive nodularity (MBEN) were outlined in the current WHO classification of tumors of the nervous system as two distinct histological MB variants. However, they are often considered as cognate SHH MB entities, and it is a reason why some clinical MB trials do not separate the patients with DNMB or MBEN histology. In the current study, we performed an integrated DNA/RNA-based molecular analysis of 83 DNMB and 36 MBEN to assess the etiopathogenetic relationship between these SHH MB variants. Methylation profiling revealed "infant" and "children" SHH MB clusters but neither DNMB nor MBEN composed separate epigenetic cohorts, and their profiles were intermixed within the "infant" cluster. In contrast, RNA-based transcriptional profiling disclosed that expression signatures of all MBEN were clustered separately from most of DNMB and a set of differentially expressed genes was identified. MBEN transcriptomes were enriched with genes associated with synaptic transmission, neuronal differentiation and metabolism, whereas DNMB profiling signatures included sets of genes involved in phototransduction and NOTCH signaling pathways. Thus, DNMB and MBEN are distinct tumor entities within the SHH MB family whose biology is determined by different transcriptional programs. Therefore, we recommend a transcriptome analysis as an optimal molecular tool to discriminate between DNMB and MBEN, which may be of benefit for patients' risk stratification in clinical trials. Molecular events identified in DNMB by RNA sequencing could be considered in the future as potent molecular targets for novel therapeutic interventions in treatment-resistant cases. [ABSTRACT FROM AUTHOR]

Medulloblastoma with extensive nodularity (MBEN) is a rare histological variant of medulloblastoma (MB). These tumors are usually occurring in the first 3 years of life and are associated with good prognosis. Molecular analyses of MBEN, mostly limited to single cases or small series, have shown that they always classify as sonic hedgehog (SHH)-driven MB. Here, we have analyzed 25 MBEN through genome-wide DNA methylation, copy-number profiling and targeted next-generation sequencing. Results of these analyses were compared with molecular profiles of other SHH MB histological variants. As expected, the vast majority of MBEN (23/25) disclosed SHH-associated epigenetic signatures and mutational landscapes but, surprisingly, two MBEN were classified as Group 3/4 MB. Most MBEN classified as SHH MB displayed SHH-related and mutually exclusive mutations in either SUFU, or PTCH1, or SMO at similar frequencies. However, only SUFU mutations were also identified in the germ-line. Most of SUFU-associated MBEN eventually recurred but patients were treated successfully with second-line high-dose chemotherapy. Altogether, our data show that risk stratification even for well-recognizable histologies such as MBEN cannot rely on histology alone but should include additional molecular analyses such as methylation profiling and DNA sequencing. For all patients with “MBEN” histology, we recommend sequencing SUFU and PTCH1 in the tumor as well as in the germ-line for further clinical stratification and choice of the optimal treatment strategy upfront. [ABSTRACT FROM AUTHOR]

Pediatric glioblastoma (pedGBM) is an extremely aggressive pediatric brain tumor, accounting for ~6% of all central nervous system neoplasms in children. Approximately half of pedGBM harbor recurrent somatic mutations in histone 3 variants or, infrequently, IDH1/2. The remaining subset of pedGBM is highly heterogeneous, and displays a variety of genomic and epigenetic features. In the current study, we aimed to further stratify an H3-/IDH-wild type (wt) pedGBM cohort assessed through genome-wide molecular profiling. As a result, we identified three molecular subtypes of these tumors, differing in their genomic and epigenetic signatures as well as in their clinical behavior. We designated these subtypes 'pedGBM_MYCN' (enriched for MYCN amplification), 'pedGBM_RTK1' (enriched for PDGFRA amplification) and 'pedGBM_RTK2' (enriched for EGFR amplification). These molecular subtypes were associated with significantly different outcomes, i.e. pedGBM_RTK2 tumors show a significantly longer survival time (median OS 44 months), pedGBM_MYCN display extremely poor outcomes (median OS 14 months), and pedGBM_RTK1 tumors harbor an intermediate prognosis. In addition, the various molecular subtypes of H3-/IDH-wt pedGBM were clearly distinguishable from their adult counterparts, underlining their biological distinctiveness. In conclusion, our study demonstrates significant molecular heterogeneity of H3-/IDH-wt pedGBM in terms of DNA methylation and cytogenetic alterations. The recognition of three molecular subtypes of H3-/IDH-wt pedGBM further revealed close correlations with biological parameters and clinical outcomes and may therefore, be predictive of response to standard treatment protocols, but could also be useful for stratification for novel, molecularly based therapies. [ABSTRACT FROM AUTHOR]

In December of 2016, a Consensus Conference on unruptured AVM treatment, involving 24 members of the three European societies dealing with the treatment of cerebral AVMs (EANS, ESMINT, and EGKS) was held in Milan, Italy. The panel made the following statements and general recommendations: (1) Brain arteriovenous malformation (AVM) is a complex disease associated with potentially severe natural history; (2) The results of a randomized trial (ARUBA) cannot be applied equally for all unruptured brain arteriovenous malformation (uBAVM) and for all treatment modalities; (3) Considering the multiple treatment modalities available, patients with uBAVMs should be evaluated by an interdisciplinary neurovascular team consisting of neurosurgeons, neurointerventionalists, radiosurgeons, and neurologists experienced in the diagnosis and treatment of brain AVM; (4) Balancing the risk of hemorrhage and the associated restrictions of everyday activities related to untreated unruptured AVMs against the risk of treatment, there are sufficient indications to treat unruptured AVMs grade 1 and 2 (Spetzler-Martin); (5) There may be indications for treating patients with higher grades, based on a case-to-case consensus decision of the experienced team; (6) If treatment is indicated, the primary strategy should be defined by the multidisciplinary team prior to the beginning of the treatment and should aim at complete eradication of the uBAVM; (7) After having considered the pros and cons of a randomized trial vs. a registry, the panel proposed a prospective European Multidisciplinary Registry. [ABSTRACT FROM AUTHOR]

In contrast to the relative morphological uniformity of histone H3 K27-mutant high-grade gliomas, H3 G34-mutant tumors present as a histopathologically heterogeneous group of neoplasms, with microscopic characteristics typical of either glioblastoma (GBM) or central nervous system primitive neuroectodermal tumors (CNS-PNET). In the current study, we performed an integrative clinical, histopathological and molecular analysis of 81 G34-mutant CNS tumors. Routinely prepared tumor tissues were investigated for genomic and epigenomic alterations. Despite their divergent histopathological appearance, CNS tumors with H3.3 G34 mutations displayed uniform epigenetic signatures, suggesting a single biological origin. Comparative cytogenetic analysis with other GBM subtypes disclosed a high frequency and high specificity of 3q and 4q loss across G34-mutant tumors. PDGFRA amplification was more common in cases with GBM than with PNET morphology (36 vs. 5 %, respectively), while CCND2 amplifications showed the opposite trend (5 vs. 27 %). Survival analysis revealed the presence of amplified oncogene(s) and MGMT methylation as independent prognostic markers for poor and favorable outcomes, respectively. No difference in outcome was found between morphological variants (GBM vs. PNET). Thus, different histological variants of G34-mutant CNS tumors likely comprise a single biological entity (high-grade glioma with H3 G34 mutation, HGG_G34), which should be outlined in future diagnostic and therapeutic classifications. Screening for H3.3 G34 mutation should therefore be recommended as a routine diagnostic marker for supratentorial CNS tumors across a broad histological spectrum. [ABSTRACT FROM AUTHOR]

We studied the effect of γ-irradiation on HUVEC endothelial cells co-cultured with allogeneic astrocytes. This 2D in vitro model of the blood-brain barrier has the same parameters as cerebral microvascular endothelial cells forming the blood-brain barrier and allows reproducing its functions in vivo. Dose-dependent changes in cell morphology and violation of monolayer integrity were observed. Real-time PCR and immunocytochemical analysis revealed changes in the expression of tight (ZO-1, claudin-5) and adherens junction protein (vascular endothelial cadherin, β-catenin) mRNA. Expression of tight and adherens junction proteins mRNA decreased in 2, 24, and 48 h after irradiation in doses of 2, 4, and 6 Gy. Significant dosedependent changes were found only for β-catenin mRNA expression in 2 h after exposition. This model of blood-brain barrier in vitro can be used for studying the molecular mechanisms regulating permeability of cerebral endothelium under normal conditions and after pathological exposures, e.g. γ-irradiation. [ABSTRACT FROM AUTHOR]

The expression of VEGF, GFAP, and BDNF genes in the nervous tissue changed on weeks 4, 8, and 12 after fractionated irradiation of the brain according to different protocols in a fi xed total dose of 36 Gy. The expression of VEGF gene decreased in the prefrontal cortex and hippocampus after 4 and 8 weeks. After week 12, the expression of VEGF normalized in the prefrontal cortex and remained low in the hippocampus. The expression of GFAP gene was maximum in the prefrontal cortex after week 4 and returned to normal in week 12. In the hippocampus, the expression of GFAP was low only after week 12. The expression of BDNF gene was reduced only during the week 8 and this decrease was directly proportional to the single dose. Hence, fractionated γ-irradiation with fi xed total dose differently modifi ed gene expression in the nervous tissue. [ABSTRACT FROM AUTHOR]

Antitumor efficiencies of monoclonal antibodies to connexin-43 second extracellular loop (MAbE2Cx43), temozolomide, and fractionated γ-irradiation in the monotherapy mode and in several optimized combinations were studied in Wistar rats with induced C6 glioma. The survival of animals with glioma and the dynamics of intracerebral tumor development were evaluated by MRT. Temozolomide monotherapy (200 mg/m) and isolated radiotherapy in a total dose of 36 Gy shifted the survival median from 28 days (no therapy) to 34 and 38 days, respectively; 100% animals died under conditions of temozolomide monotherapy and radiotherapy. Monotherapy with MAbE2Cx43 in a dose of 5 mg/kg led to significant regression of the tumor (according to MRT data), cure of 19.23% animals with glioma, and prolongation of the survival median to 39.5 days after tumor implantation. Combined therapy with MAbE2Cx43 and temozolomide completely abolished the antitumor effect (survival median 29 days). Treatment with MAbE2Cx43 in combination with radiotherapy was associated with mutual boosting of the therapeutic efficiencies, leading to a significant inhibition of tumor development and prolongation of the survival median to 60 days. The mechanism of tumorsuppressive activity of the antibodies could be due to connexon blockade in Cx43-positive glioma cells in the peritumor invasion zone. Higher efficiency of combined therapy was presumably due to the increase in blood-brain barrier permeability for antibodies after irradiation of the brain and to additional inhibitory effect of antibodies towards radioresistant migrating glioma cells. The results suggested that MAbE2Cx43 could be effective as the first-line drug in combined therapy for poorly differentiated gliomas. [ABSTRACT FROM AUTHOR]

Central neurocytomas are rare central nervous system neoplasms. Since the first description, approximately 500 cases of these tumors have been published to date. Nevertheless, only a limited number of genetic studies on these tumors have been reported. Here we investigated 20 “typical” central neurocytomas using array-based comparative genomic hybridization (array-CGH) with the GenoSensor Array 300. The functional significance of detected chromosomal aberrations harboring potent candidate genes was also examined at the mRNA expression level. Each tumor examined displayed DNA copy-number aberrations (CNAs), and mean number of CNAs per tumor was 38.1 ± 7.1 (range 19–53). Frequent gains were mapped at 2p24.1–22.1, 10q23.3–26.3, 11q23–25, and 18q21.3–qter. Frequent losses were identified at 1pter–36.3, 1p34.3, 6q13–21, 12q23–qter, 17p13.3, 17q11–23, and 20pter–12.3. There were 10 gained and 23 lost single DNA clones affecting ≥40% of samples tested. mRNA expression levels of 24 selected candidate genes harbored in these imbalanced clones were analyzed. MYCN, PTEN, and OR5BF1 were strongly overexpessed, whereas BIN1, SNRPN, and HRAS were found to be strongly underrepresented at the transcriptional level. Thus these data support that MYCN oncogene gain/overexpression accompanied by reduced expression of BIN1 tumor suppressor may contribute to central neurocytoma tumorigenesis. [ABSTRACT FROM AUTHOR]

To optimize treatment strategies for patients with glioblastoma, a more precise understanding of the molecular basis of this disease clearly is necessary. Therefore, numerous studies have focused on the molecular biology of glioblastoma and its linkage to clinical behavior. Here we investigated 70 glioblastomas using the array-based comparative genomic hybridization (array-CGH) with GenoSensor Array 300 to identify recurrent DNA copy number imbalances associated with patient outcomes. Univariate log-rank analysis of array-CGH data revealed 46 copy number aberrations (CNAs) associated with outcome. Among them, 26 CNAs were associated with shortened survival whereas the remaining 20 CNAs correlated with good prognosis. A hierarchical cluster analysis disclosed two genetically distinct groups of glioblastomas (1 and 2; 56 and 14 tumors, respectively). Univariate log-rank test discerned significant difference in survival between both genetic subsets while the 5-year survival rate consisted of 0 for group 1 and 63% for group 2. Multivariate analysis revealed that unfavorable genetic signature is an independent prognostic factor increasing a risk of patient death (hazard ratio, 4.38; P=0.00001). In conclusion, our current study suggests that glioblastomas can be subdivided into clinically relevant genetic subsets. Therefore, array-CGH screening of glioblastomas could provide clinically useful information and, perhaps, potentially improve the quality of treatment. [ABSTRACT FROM AUTHOR]

Studies the role of rostral-ventromedial pole in cerebral blood flow (CBF) regulation and the influence of the region on modifying the brain tissue consequences of cerebral ischemia. Fastigial nucleus (FN) and systemic circulation; FN and cerebral circulation; Neurogenic neuroprotection.

Although clinical and histological criteria for ependymoma prognosis are recognized, studies have reported contradictory results. Prognostic significance based on immunohistochemistry of ependymomas has been described in a few studies and a strong prognostic value of p53 aberrant expression has been established. Recently, p53 regulation has found to be dependent on the function of the p14ARF gene product, which has been shown to be critically involved in human carcinogenesis. In this study we have examined patients with intracranial ependymomas (n=103) for immunoexpression of the novel antibody FL-132 to human p14ARF protein. We found that: (1) the polyclonal FL-132 antibody seems to be suitable for studying p14ARF protein status in routinely processed and paraffin-embedded specimens; (2) decreasing p14ARF protein expression is associated with patterns of ependymoma biological aggressiveness, i.e., increasing tumor grade, elevated growth fraction and p53 protein accumulation; however, there was no any association between p14 and MDM2 immunoexpression in ependymomas; (3) although the biological events underlying p14ARF inactivation in ependymal neoplasms are still unclear, FL-132 immunohistochemistry appears to be useful for assessing an individual prognosis in these tumors; when the p14 score was considered as "high" versus "low" (cut-off p14 labeling index at 10%), it represented an independent prognostic factor in both univariate and multivariate analyses (hazard ratio –3.56; P=0.0003); and (4) most beneficial information for evaluation of malignant ependymoma outcome should be elicited from simultaneous immunohistochemical investigation of p14 ARF and p53 in tumor specimen. [ABSTRACT FROM AUTHOR]

Pleomorphic xanthoastrocytomas (PXAs) are characterized as a well-delineated tumor entity with clear peculiarities in clinico-radiological picture, pathological appearance and biological behavior. Usually the PXAs are associated with relatively good prognosis. Nevertheless, up to 35% of patients die following one and more recurrence with or without tumor malignant transformation. Till now, there is no agreement on what histopathological features constitute to objective and reliable signs of PXAs malignancy and clinical outcome. Thirty-four PXAs were subdivided on three subsets: typical (Grade I) – tumors without mitoses per 20 high power fields, proliferating (Grade II) – tumors with mitoses but without necroses, and malignant (Grade III) – tumors with elevated mitotic index and necrotic foci. Also, immunohistochemical investigation with various tumor-associated antigens was performed. All PXAs subtypes showed differences in clinical outcomes. There were no recurrences and death among the tumors Grade I. Five out of 14 (36%) Grade II PXAs have recurred and one of them died. All 5 patients with PXAs Grade III have rapidly recurred and four of them died. Immunohistochemical variables, such as Ki-S1, p27/Kip1, vascular endothelial growth factor expression, p53 immunoreactivity and apoptotic index also exhibited significant differences among the three PXAs grades. The progression-free survival was significantly reduced for PXAs grade and presence of mitoses, whereas overall survival was reduced for mitotic index ≥ 3 and presence of necroses. No one from immunohistochemical variables reached significant value. In summary, the three-tiered PXAs subdivision proposed by us is carrying some element of rationality but, undoubtedly, requires further prospective studies. [ABSTRACT FROM AUTHOR]

Oligodendrogliomas continue to generate considerable difficulties in identifying prognostic factors, including single histopathological patterns. Among the latter, vascular productive changes have been intensively examined but the obtained results appear to be controversial. Numerous studies have revealed an indisputable importance of vascular endothelial growth factor (VEGF) immunoreactivity for malignant progression of astrocytomas but the data regarding oligodendrogliomas are heterogeneous. Ninety-one patients with oligodendroglioma were examined retrospectively for VECF immunoexpression. The results demonstrated significant preponderance of intracellular VEGF expression for WHO grade III tumors. Nevertheless, VEGF staining patterns correlated with both progression-free and overall survival only in univariate, but not in multivarite analysis. Only WHO tumor grade was found to be an independent prognostic factor for oligodendroglioma outcome. Therefore, it seems unlikely that VEGF immunohistochemistry will be of value in assessing individual oligodendroglioma prognosis, especially for determining of both progression-free and overall survival from histologically low-grade tumors. [ABSTRACT FROM AUTHOR]

Medulloblastomas (MB) are the most common central nervous system malignancies in children. Numerous publications describe efforts to identify the predictive value of various patterns of MB pathology and immunohistochemistry, but received data appear to be controversial. Seventy-three patients with cerebellar MB were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to various tumor-associated antigens. Also, apoptosis detection by the in situ end-labeling method was performed. Survival analysis was made using univariate and multivariate models. Tenascin immunoreactivity and apoptotic index (AI)>or=1.5% were found to be closely associated with poor prognosis according to an univariate analysis ( P=0.008 and 0.003, respectively). The multivariate Cox proportional hazard model exhibited independent prognostic value for the apoptotic rate only ( P=0.023). Tumors with tenascin expression and AI>or=1.5% significantly prevailed among MB with metastatic dissemination, whereas expression of c-erbB2 oncoprotein and epidermal growth factor receptor was found to be more typical for cases with local tumor recurrence. We came to the conclusion that tenascin immunoreactivity and AI were useful for individual MB prognosis. [ABSTRACT FROM AUTHOR]

Intracranial ependymomas are the third most common primary brain tumor in children. A variety of chemotherapy protocols have been introduced for the treatment of ependymoma although overall these have not contributed to patients outcome. To our knowledge, data on the prognostic value of immunoexpression of the chemoresistance-related proteins (ChRPs) in ependymomas are absent. Seventy-six patients with intracranial ependymomas who received combined treatment were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to metallothioneins (MT), glutathione S-transferase pi (GST pi) and P-glycoprotein (P-GP). The results demonstrated significant preponderance of expression of all the above-mentioned ChRPs for the low-grade tumors. The progression-free survival time was found to be significantly shorter for immunonegative tumors in both tumor grades. Multivariate analysis using a Cox hazard model revealed that recurrence-free survival time is significantly associated with tumor grade, and MT and P-GP expression. Risk of recurrence increased for the high-grade ependymomas (hazard ratio 2.85; P=0.004), and decreased for the MT-positive tumors (hazard ratio −2.72; P=0.005) and for the P-GP-positive tumors (hazard ratio −2.02; P=0.02). The obtained results allow one to conclude that ChRPs expression is closely associated with low-grade ependymomas and immunohistochemical findings may be estimated as a predictor for local tumor progression. [ABSTRACT FROM AUTHOR]

States that the excitatory amino acid, L-glutamate, acting through its N-methyl-D-aspartate (NMDA) receptor, may contribute to neuronal death following cerebral vascular occlusion. Demonstration that the inhibition of the synthesis of NMDA-R1 by treatment with antisense oligodeoxynucleotides selectively reduces the expression of NMDA receptors; Reduction of the volume of focal ischemic infarction produced by occlusion of the middle cerebral artery in the rat.

A computer-assisted technique was developed for CT-guided stereotactic microsurgical resection of small intracerebral lesions. An original stereotactic retractor was developed to work with the Riechert-Mundinger's equipment for precise localisation, safe exposure and microsurgical removal of these tumours. A software-program was developed to work on an ordinary IBM-compatible PC/AT. It assisted the procedure from treatment planning till the end, including tumour excision, and provided computerized support for the removal of pathological tissues within the CT-defined boundaries of the lesion. 6 patients, harbouring supratentorial intracerebral lesions underwent surgery using this technique. 2 of them suffered from brain metastases, in 1 patient a cavernous angioma was removed, 2 patients had glial tumours, and in the last patient only radiation necrotic tissue was found to be the cause of ring-enhanced lesion, which had been suspected to be a recurrent glioma. Their largest dimensions varied between 18 and 30 mm and the age of the patients ranged from 15 to 52 years. In 2 cases the lesions were localised deeply in the region of basal ganglia and thalamus. In the remaining patients the tumours were rather superficial, infiltrating subcortical white-matter close to the central sulci. There was no mortality nor significant morbidity following the procedure, the Karnofsky Performance Status (KPS) cumulative scores being either unchanged (in 3), or improved (in 3 patients). Current state and modern concepts in image-guided open stereotactic methodology is discussed. [ABSTRACT FROM AUTHOR]

The article offers information on the ultra-slow oscillations in brain signals across hemispheres in humans. A study conducted by medical researchers revealed that the spontaneous ultra-slow activity in brain signals is correlated between functionally related areas in human body. The activity in brain signals is a signature of intercortical communication.