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Pituitary carcinoma (metastatic neuroendocrine tumor of the pituitary gland) is the pituitary tumor with confirmed craniospinal and/or systemic metastases. These tumors are extremely rare accounting for only 0.1% to 0.5% of all pituitary tumours and are characterized by high mortality. In the presented case, pituitary carcinoma with intracranial metastasis was diagnosed in a young patient 25 years after manifestation of an aggressive recurrent prolactin-secreting pituitary tumor. Standard therapy (removal of metastasis, radiation therapy, cabergoline therapy) resulted in a long-term remission of the disease.

Despite slow growth of most pituitary tumors and high rates of total resection and/or effective therapy, pituitary neoplasms are characterized by aggressive behavior with high growth rate, frequent relapses and resistance to standard treatments in 10% of cases. In modern WHO classifications of tumors of the central nervous system, endocrine and neuroendocrine tumors, the authors propose the definition «pituitary neuroendocrine tumor» instead of previous «pituitary adenoma» and «metastasizing pituitary neuroendocrine tumor» instead of «pituitary carcinoma». Currently, there are no effective prognostic markers of aggressive tumors. This complicates early diagnosis. It is proposed to apply a five-stage prognostic classification based on proliferation rate (including mitotic count, Ki-67 index and p53 immunoexpression) and morphometric markers of invasiveness for all resected pituitary neoplasms. This approach would be valuable for earlier detection of aggressive tumors and pituitary carcinomas. Compression of visual pathways, third ventricle and brain stem due to rapid growth of aggressive tumors usually requires redo surgeries with subsequent radiotherapy. Hormonally active tumors require therapy with somatostatin analogues and dopamine agonists in maximum possible doses. Chemotherapy with temozolomide as first-line option is recommended if standard treatment is ineffective. Alternative treatment includes peptide receptor radionuclide therapy (PRRT), molecular targeted therapy (bevacizumab, tyrosine kinase inhibitors, everolimus and cyclin-dependent kinase inhibitors) and immunotherapy (checkpoint inhibitors). Considering the need for combined treatment, these cases should always be discussed by a multidisciplinary team (neurosurgeon, endocrinologist, radiotherapist, oncologist, pathologist) with necessary qualifications and experience in treating these patients. Treatment of aggressive tumors and pituitary carcinomas is becoming an active and rapidly developing direction in neurosurgery, endocrinology and oncology.

Objective: To study the relationship of NMDA receptors expression activity with proliferative activity and genetic properties of anaplastic astrocytomas, as well as the survival of patients with this disease., Material and Methods: To solve this problem, we compared the expression activity of the least studied NMDA receptors in the context under consideration, detected using immunofluorescent studies and polymerase chain reaction, with the results of histological and molecular studies, the proliferative activity of neoplasms, and the survival of patients., Results: The expression activity of NMDA receptors is higher in astrocytomas, grade 3, which do not carry mutations in IDH1 and IDH2 genes. In addition, the activity of NMDA receptors expression directly correlates with proliferative activity in the tumors. The activity of NMDA receptor expression has a significant impact on the prognosis of disease-free survival., Conclusion: We have shown for the first time the significant role of NMDA receptors in the progression of diffuse astrocytomas, which can become the basis for creating new therapeutic and diagnostic tools.

Anaplastic astrocytoma (AA) is a rare intracerebral tumor. Therefore, the number of studies devoted to risk factors of overall and disease-free survival is small. This single-center clinical study is devoted to various factors influencing prognosis of treatment in this group of patients., Material and Methods: A retrospective study included 389 patients diagnosed with grade 3 astrocytoma. We analyzed dependence of overall and disease-free survival from the following factors: gender, age of onset of disease, tumor extent, surgery, neurological disorders before and after surgery (NANO grading system), Ki67 index, postoperative radio- and chemotherapy (number courses, treatment regimens)., Results: Significant risk factors for overall and disease-free survival were spread and volume of tumor, postoperative neurological aggravation, Ki67 index, IDH mutation, radio- and chemotherapy. Age, frontal lobe tumor and disease manifestation variant were significant only for overall, but not for disease-free survival., Conclusion: This study was based on material of one of the largest clinical series of patients with AA operated on in one center in «molecular» era. Our results are consistent with previous data. Analysis of tumor biology and risk factors for IDH-negative AA without molecular signs of glioblastoma may be perspective.

Diffuse gliomas continue to be an important problem in neuro-oncology. To solve it, studies have considered the issues of molecular pathogenesis from the intratumoral heterogeneity point. Here, we carried out a comparative dynamic analysis of the different cell populations' content in diffuse gliomas of different molecular profiles and grades, considering the cell populations' functional properties and the relationship with patient survival, using flow cytometry, immunofluorescence, multiparametric fluorescent in situ hybridization, polymerase chain reaction, and cultural methods. It was shown that an increase in the IDH-mutant astrocytomas and oligodendrogliomas malignancy is accompanied by an increase in stem cells' proportion and mesenchymal cell populations' appearance arising from oligodendrocyte-progenitor-like cells with cell plasticity and cells' hypoxia response programs' activation. In glioblastomas, malignancy increase is accompanied by an increase in both stem and definitive cells with mesenchymal differentiation, while proneuronal glioma stem cells are the most likely the source of mesenchymal glioma stem cells, which, in hypoxic conditions, further give rise to mesenchymal-like cells. Clinical confirmation was a mesenchymal-like cell and mesenchymal glioma stem cell number, and the hypoxic and plastic molecular programs' activation degree had a significant effect on relapse-free and overall survival. In general, we built a multi-vector model of diffuse gliomas' pathogenetic tracing up to the practical plane.

Purpose: The aim of the study was to compare the parameters of blood flow in glioblastomas and primary central nervous system lymphomas (PCNSLs), measured by pseudo-continuous arterial spin labeling MRI (3D PCASL), and to determine the informativeness of this method in the differential diagnosis between these lesions., Methods: The study included MRI data of 139 patients with PCNSL (n = 21) and glioblastomas (n = 118), performed in the Burdenko Neurosurgical Center. No patients received chemotherapy, hormone therapy, or radiation therapy prior to MRI. On the 3D PCASL perfusion map, the absolute and normalized values of tumor blood flow were calculated in the glioblastoma and PCNSL groups (maxTBFmean and nTBF)., Results: MaxTBFmean and nTBF in the glioblastoma group were significantly higher than those in the PCNSL group: 168.9 ml/100 g/min versus 65.6 and 9.3 versus 3.7, respectively (p < 0.001). Arterial spin labeling perfusion had high sensitivity (86% for maxTBFmean, 95% for nTBF) and specificity (77% for maxTBFmean, 73% for nTBF) in the differential diagnosis between PCNSL and glioblastomas. Blood flow thresholds were 98.9 ml/100 g/min using absolute blood flow values and 6.1 using normalized values, AUC > 0.88., Conclusion: The inclusion of 3D PCASL in the standard MRI protocol can increase the specificity of the differential diagnosis between glioblastomas and PCNSL., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To study the effect of TERT mutation on overall and relapse-free survival in patients with IDH -negative diffuse astrocytomas grade III (anaplastic gliomas)., Material and Methods: The study included 45 patients aged 45.5 years. Forty-two patients underwent resection of tumor, other 3 ones - stereotactic biopsy. TERT mutation was identified in 21 patients. External beam radiation therapy was performed in 35 patients (60 Gy), chemotherapy - in 34 patients (mainly temozolomide). Follow-up data were available in 44 patients., Results: Median of overall survival in patients with TERT mutation was 15.3 months, in patients with TERT -negative tumors - 65.1 months. Median of relapse-free survival in patients with TERT-positive anaplastic astrocytoma (AA) was 13.3 months, in patients with TERT -negative glioma - 57.7 months. These differences were not significant. Relapse-free survival was higher in patients with AA and no TERT mutation at all intervals, but especially at early stages (12 and 24 months)., Conclusion: Inclusion of TERT mutation in mandatory examination panel for gliomas in general and, in particular, gliomas grade II/III without IDH mutation can lead to sub-classification of these tumors in the near future. Routine analysis of TERT mutation in these patients will be valuable for correct medical consultation regarding prognosis and adequate adjuvant treatment.

Anaplastic pleomorphic xanthoastrocytoma is a rare tumor. There are still no objective data on the incidence of its diagnosis., Objective: To study neuroimaging, morphological features of tumors, as well as factors affecting treatment and prognosis., Material and Methods: A retrospective study enrolled 42 patients operated on at the Burdenko Neurosurgery Center between 2003 and 2020. MR characteristics of anaplastic pleomorphic xanthoastrocytoma were analyzed. All patients underwent resection of tumor (total resection in 83.3% of cases). Redo surgeries were performed in 1/3 of patients. Mutational status of BRAF V600E was assessed in all patients. Adjuvant radio- and chemotherapy was performed in more than 80% of cases. Tyrosine kinase inhibitors were administered in 19% of cases. The follow-up period was 152 months (median 34 months)., Results: We found no pathognomonic MR signs of this disease. Indeed, anaplastic pleomorphic xanthoastrocytoma have the same signal characteristics as other malignant gliomas. The BRAF V600E mutation status was positive in 54.8% of cases. None patient had IDH-1 mutation. Mean Ki-67 index was 12.5%. The overall survival was 79 months (range 4-152). Seven (17%) patients are alive for more than 90 months. Only Ki-67 index and BRAF mutation significantly influenced the treatment prognosis and overall survival regardless the use of tyrosine kinase inhibitors., Conclusion: Such well-known factors for malignant glioma as patient age, total resection and adjuvant therapy did not significantly affect overall survival. Perhaps, searching for new molecular genetic features will reveal additional significant factors of prognosis in patients with anaplastic pleomorphic xanthoastrocytoma.

The authors present 2 patients. One of them had typical multifocal primary multiple synchronous wild-type IDH1/2 glioblastoma subtype RTK1, chromosome 7 duplication, homozygous CDKN2A deletion and chromosome 10 deletion. In another patient, the nature of tumors remains debatable. We can talk about either a rare atypical case of metachronous multicentric various glial tumors (oligodendroglioma, IDH1-mutant and 1p/19q-codeleted, WHO grade 2 and RTK2-glioblastoma) or secondary glioblastoma after previous oligodendroglioma arose a year after radiotherapy.

Objective: The analyze the neuro-ophthalmic outcomes in patients with pineal and suprasellar germinoma after complex treatment., Material and Methods: There were 125 patients (88 males, 37 females) with primary CNS germinoma for the period 2008-2017. All patients were divided into 3 groups depending on the tumor localization: pineal area - 62 patients, suprasellar neoplasm - 38 patients, bifocal germinoma - 25 patients. Treatment was performed in accordance with the «Germinoma-2008» protocol. Tumors were histologically patients (partial - 32 cases, subtotal - 16 cases). Surgery was followed by postoperative chemotherapy and stereotactic radiotherapy. The results were evaluated by neuro-ophthalmological examination at all stages of complex treatment., Results: Pineal germinoma resulted oculomotor and pupillary disorders (58 patients - 94%) and papilledema. The last one completely regressed under the treatment. Partial reduction of oculomotor and pupillary abnormalities occurred throughout chemotherapy (6 patients - 10%). More than half of patients ( n =24, 63%) with suprasellar germinoma had visual impairment. Improvement of visual functions including severe visual disturbance was observed in 14 patients (58%). Predominantly, functional recovery occurred under chemotherapy (12 patients - 86%). Bifocal germinoma was followed by various combinations of oculomotor, pupillary and/or visual impairments. We observed regression of only mild visual disorders. Stereotactic radiotherapy did not ensure any changes in neuro-ophthalmic symptoms in all groups.

Background: Despite the combined treatment in accordance with modern standards, recurrent glioblastoma usually occurs within several months after resection and causes low relapse-free and overall survival. One of the most effective methods for malignant glioma progression is repeated radiotherapy. Indications for this approach have expanded after introduction of stereotactic irradiation into routine clinical practice., Objective: To evaluate the results of radiosurgery in patients with recurrent glioblastoma and to identify the factors determining its effectiveness., Material and Methods: Radiosurgery has been carried out in 168 patients with relapses of glioblastoma between 2005 and 2021. This study enrolled 88 patients with 180 foci of local and distant progression. Mean age of patients was 42.8±2.1 years (range 4-73). Mean period between diagnosis and repeated irradiation was 12.7 months. Mean volume of focus was 2.4 cm 3 , mean dose - 20 Gy. Median follow-up period after radiosurgery was 11.2 months., Results: Repeated irradiation with correction of systemic therapy improved progression-free survival and overall survival with insignificant radiation-induced toxicity. Annual overall survival was 62.2%, median of overall survival after radiosurgery - 15.1 months. Significant factors of local control were marginal dose of at least 18 Gy and distant relapse. Median of progression-free survival in the group of distant progression of glioblastoma was only 3.6 months vs. 9.1 months in patients with local recurrence., Conclusion: Repeated irradiation in radiosurgery mode with a dose of 18 Gy and higher is an effective option for local treatment increasing progression-free and overall survival in patients with progression of glioblastoma.

The authors report a patient with recurrent bifocal germinoma of the optical nerves and chiasm after previous combined treatment. The tumor resulted progressive visual acuity loss despite subsequent therapy (glucocorticoid therapy, chemo- and radiotherapy). Differential diagnosis between tumor progression and consequences of radiotherapy was complicated by MRI negative pattern. Subsequent development of the process, signs of anterior visual pathway damage and tumor spread throughout the ventricular system and subarachnoid spaces according to neuroimaging data indicated recurrence of disease.

Awake craniotomy (AC) has gained fantastic popularity over the past years. This approach is no longer the destiny of only highly specialized neurosurgical centers. Technical features of AC are completely developed. However, certain aspects of patients' sensations and their satisfaction are still unclear. The review is devoted to these issues. It was shown that AC is positively evaluated by the vast majority of patients. Many patients would choose this technique for redo surgery. However, there are certain important details that can adversely affect satisfaction of patients. Thus, these features should be considered in AC.

Dendritic cell-based vaccines are an intensively studied active immunotherapy technology. Aim of this article is to review the results of the key clinical studies of such vaccines in the treatment of neuro-oncological diseases. Their effectiveness was studied most widely in the treatment of malignant glial tumors, the study went from experimental work to phase III clinical studies, preliminary results of which indicate some positive results of this immunotherapy method in adults. Currently, emphasis is also being placed on the identification of clinical and immunological correlates of the patient's response to therapy and on the search for new antigens for sensitization of dendritic cells Studies of dendritic cell vaccines also include a number of other neuro-oncological diseases. A separate part of this article is devoted to the treatment of intracerebral tumors in children, for example, medulloblastomas and gliomas of the pons. In addition, the potential use of dendritic cell vaccines for intracerebral metastases is considered.

Aim: To clarify the concept of 'aggressive pituitary adenoma' using analysis of the current concepts, as well as to determine the optimal treatment algorithm for this disease and the place of chemotherapy in this treatment. Pituitary adenomas comprise from 10 to 15% of intracranial neoplasms. Despite the fact that pituitary adenomas are benign neoplasms, in 25-55% of cases they demonstrate invasive growth, growing into the surrounding structures (sphenoid sinus, cavernous sinus, etc.). Due to the lack of a standard definition of aggressive pituitary adenomas (due to the lack of clear criteria for this disease), there are no studies in the literature reporting optimal treatment for this group of patients, except for several publications describing the use of Temozolomide as palliative therapy.

Sinonasal malignant tumors are characterized by high histological variability and complexity of the differential diagnosis. Currently, there are classifications of these tumors, which are based on their localization and involvement of various anatomical structures. However, generally accepted algorithms for treatment of this pathology have not yet been developed. This review describes the most important algorithms for treatment of the most common histological variants of sinonasal malignant tumors: squamous cell carcinoma, adenocarcinoma, sinonasal undifferentiated carcinoma, esthesioneuroblastoma, adenoid cystic cancer, and sinonasal adenocarcinoma. The main problems in choosing the approach for treating these tumors are the lack of generally accepted resectability criteria and contradictions between oncological and neurosurgical indications for surgical treatment. Further research is needed to study the role of radiosensitizers and radioprotectors in comprehensive treatment of sinonasal malignant tumors.

Introduction: Germinogenic central nervous system (CNS) tumors represent a heterogeneous group of tumors, constituting approximately 0.4% of all primary brain tumors. Removal of the tumor has no prognostic value. In "pure" primary germinomas of the CNS, the alpha-fetoprotein and human chorionic gonadotropin levels are within normal limits, and no specific biochemical tumor markers currently exist for this tumor type, making histological verification crucial for the choice of treatment tactics. When the tumor is located in the chiasmosellar region, one of the possible verification methods is endoscopic endonasal transsphenoidal biopsy., Objective: The main objective of the study is to demonstrate the feasibility and safety of endoscopic transsphenoidal approach for histological verification of primary germinomas of the CNS with chiasmosellar localization., Materials and Methods: The current study includes 13 patients with "pure" germinomas of the chiasmosellar region who underwent endoscopic endonasal surgical interventions with subsequent treatment according to the "Germinoma 2008" protocol., Results: The extent of surgical intervention ranged from biopsy (4) to partial (5) and total (4) removal of the tumor. In all cases, histological verification of the diagnosis was achieved and none of the patients presented with cerebrospinal fluid leaks and/or meningitis in the postoperative period, allowing to evaluate endoscopic intervention in our patient series as safe and effective. Two out of 13 patients were lost to follow-up., Conclusion: The endoscopic endonasal approach for histological verification and removal of chiasmosellar region germinomas is safe, and in some cases, less traumatic for the patient than transcranial and transventricular approaches., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Asian Journal of Neurosurgery.)

Brain tumors rank third in the incidence rate among cancer nosologies. However, improvement of neurosurgical treatment methods and the use of modern regimens of chemotherapy and radiotherapy have increased survival of patients with benign and malignant brain tumors. A significant proportion of patients with brain tumors are young people in the reproductive age who are interested in maintaining their fertility. Surgical removal of tumors, mainly in the hypothalamo-pituitary area as well as the use of chemotherapy and radiotherapy for malignant brain tumors of any localization may be complicated by hypogonadism and infertility. At present, a simple and reliable method of preserving male fertility is sperm cryopreservation. Neurosurgeons as well as oncologists and radiologists should inform patients with brain tumors about a potential risk of hypogonadism and infertility after treatment and about opportunities of sperm cryopreservation, which increases the chances of having future genetic progeny.

Li-Fraumeni syndrome (LFS) is a clinically and genetically heterogeneous hereditary syndrome with predominantly oncological manifestations, which is associated with mutations in the TP53, MDM2, and CHEK2 genes. The most common variant is a TP53 mutation., Objective: To analyze the literature and present a clinical case of a patient with Li-Fraumeni syndrome and multiple anaplastic oligodendrogliomas of the brain., Clinical Case: A 42-year-old male patient presented with complaints of headaches, word finding difficulty, memory loss, right hemianopsia, and generalized convulsive attacks. For 10 years, he underwent multiple interventions and chemotherapy courses for colon adenocarcinoma and recurrent B-cell lymphoma. MRI revealed multiple space-occupying lesions of the cerebraln hemispheres, which were located in the left temporo-occipital and right frontal regions., Results: The patient underwent resection of multiple space-occupying lesions of the left temporo-occipital and right frontal regions. The postoperative period proceeded without complications. The histological diagnosis was WHO grade III anaplastic oligodendroglioma. The patient and one of his sons were detected with a R248W missense mutation in the TP53 gene. The patient underwent six courses of temozolomide chemotherapy. At a follow-up examination 20 months after surgery and chemotherapy, the patient's condition was satisfactory; he returned to work. Control MRI of the brain revealed no signs of continued tumor growth., Conclusion: An analysis of the literature and the clinical case indicate the success of multiple surgical interventions and chemotherapy courses performed for a long time in the patient with Li-Fraumeni syndrome manifested by colon adenocarcinoma, recurrent B-cell lymphoma, and multiple anaplastic oligodendroglioma of the brain. The patient had a good quality of life and returned to professional activity.

Surgery of intracerebral tumors involving long association fibers is a challenge. In this study, we analyze the results of intraoperative mapping of the superior longitudinal, arcuate, and frontal aslant tracts in surgery of brain gliomas., Purpose: The study purpose was to compare the results of intraoperative mapping and the postoperative speech function in patients with gliomas of the premotor area of the speech-dominant frontal lobe, which involved the superior longitudinal, arcuate, and frontal aslant tracts, who were operated on using awake craniotomy., Material and Methods: Twelve patients with left frontal lobe gliomas were operated on: 11 patients were right-handed, and one patient was a left-hander retrained at an early age. Histological types of tumors were represented by Grade II diffuse astrocytomas (6 patients), Grade III anaplastic astrocytomas (1 patient), Grade IV glioblastoma (1 patient), Grade II oligodendroglioma (1 patient), and Grade III anaplastic oligodendrogliomas (3 patients). The mean age of patients was 45 (29-67) years; there were 6 males and 6 females. All patients underwent preoperative and postoperative MRI with reconstruction of the long association fibers and determination of the topographic anatomical relationships between the fibers and the tumor. Surgery was performed using the asleep-awake-asleep protocol with intraoperative awakening of patients. All patients underwent cortical and subcortical electrophysiological stimulation to control the localization of eloquent structures and to clarify the safe limits of resection. For intraoperative speech monitoring, a computerized naming test was used with naming of nouns or verbs, and automatic speech was evaluated (counting from 1 to 10, enumeration of months and days of the week), which was complemented by a talk with the patient. Speech disorders before, during, and after surgery were evaluated by a neuropsychologist. The mean current strength during direct electrical stimulation was 3 (1.9-6.5) mA., Results: The association fibers were intraoperatively identified in all patients (SLF/AF in 11 patients; FAT in one patient). In 4 patients, the cortical motor speech area was intraoperatively mapped; in three cases, tumor resection was accompanied by speech disturbances outside the stimulation. During direct electrical stimulation, speech disturbances developed in 7 of 12 cases. All patients underwent control MRI within the first 48-72 h: total resection (more than 90% of the tumor) was performed in 7 cases; subtotal resection was achieved in two patients; partial resection was performed in two cases. According to postoperative MR tractography, the resected tumor bed was adjacent to the SLF/AF complex in 7 cases, located near the SLF/AF complex in three cases, and adjacent to the FAT in two cases. Postoperatively, 11 out of 12 patients had worsening of neurological symptoms in the form of various speech disturbances. In one patient, speech disturbances developed 2 days after surgery, which was associated with an increase in edema. On examination 3 months after surgery, severe speech disturbances remained in 1 patient., Conclusion: Resection of frontal lobe tumors in the speech-dominant hemisphere using early postoperative awakening is associated with a high rate of complex speech disorders due to injury to the SLF/AF complex and FAT. In these cases, intraoperative speech mapping with allowance for the course of long association fibers is an essential procedure. Preoperative tractography in combination with intraoperative speech mapping enables identification of association fibers of the SLF/AF complex and FAT, which may help to avoid severe conduction aphasia with poor speech recovery after tumor resection.

This article is devoted to the latest edition of the 2016 WHO classification of primary CNS tumors. The authors, who are clinicians and not morphologists, have tried to analyze and briefly present the main changes to the new edition of the WHO classification of primary CNS tumors, the main difference of which from the previous 2007 classification is inclusion of the molecular genetic features of primary CNS tumors in the classification criteria. The article focuses mainly on the classification issues of diffuse gliomas and glioblastoma, with assessment of the role of IDH-1,2, ATRX, TERT, and MGMT mutations as well as a 1p/19q co-deletion. The article briefly describes some new nosological forms (e.g., Grade III anaplastic pleomorphic xanthoastrocytoma) and presents a new approach to the classification of embryonic (medulloblastoma) and glial childhood tumors as well as tables of the main differences between 2016 and 2007 WHO classifications of primary CNS tumors. Based on their own clinical experience, the authors dispute with the described classification and suggest their own ideas for improving the classification of primary CNS tumors in the future.

Purpose: We describe our experience of using intra-arterial administration of Verapamil to resolve vasospasm in two patients who underwent surgery for insular glial tumors., Material and Methods: Severe vasospasm (an increased systolic LBFV in the M1 MCA, more than 250 cm/s, and a Lindegaard index of 4.1) was observed in 2 (3.2%) of 62 patients in the early postoperative period after removal of intracerebral insular tumors. In both cases, vasospasm was confirmed by angiography, was clinically significant, and manifested by the development of pyramidal hemisyndrome., Results: Intra-arterial administration of Verapamil led to relief of angiospasm, which was confirmed by angiographic data, and complete regression of neurological symptoms., Conclusion: Vasospasm symptoms in patients after removal of insular tumors largely resemble those after aneurysm hemorrhage. An increase in the LBFV in the MCA and related neurological symptoms develop lately and persists for up to 2 weeks after surgery. LBFV values are similar to those in patients after SAH and reach 250-300 cm/s. Among the causes of focal symptoms developed after removal of insular tumors, injury to the inner capsule structures, injury to arteries of the MCA territory (especially perforators), and angiospasm should be differentiated.

Rationale: There are no studies on application of functional MRI (fMRI) for long-term monitoring of the condition of patients after resection of frontal and temporal lobe tumors., Purpose: The study purpose was to correlate, using fMRI, reorganization of the speech system and dynamics of speech disorders in patients with left hemisphere gliomas before surgery and in the early and late postoperative periods., Material and Methods: A total of 20 patients with left hemisphere gliomas were dynamically monitored using fMRI and comprehensive neuropsychological testing. The tumor was located in the frontal lobe in 12 patients and in the temporal lobe in 8 patients. Fifteen patients underwent primary surgery; 5 patients had repeated surgery. Sixteen patients had WHO Grade II and Grade III gliomas; the others had WHO Grade IV gliomas. Nineteen patients were examined preoperatively; 20 patients were examined at different times after surgery. Speech functions were assessed by a Luria's test; the dominant hand was determined using the Annette questionnaire; a family history of left-handedness was investigated. Functional MRI was performed on an HDtx 3.0 T scanner using BrainWavePA 2.0, Z software for fMRI data processing program for all calculations >7, p<0.001., Results: In patients with extensive tumors and recurrent tumors, activation of right-sided homologues of the speech areas cold be detected even before surgery; but in most patients, the activation was detected 3 months or more after surgery. Therefore, reorganization of the speech system took time. Activation of right-sided homologues of the speech areas remained in all patients for up to a year. Simultaneous activation of right-sided homologues of both speech areas, the Broca's and Wernicke's areas, was detected more often in patients with frontal lobe tumors than in those with temporal lobe tumors. No additional activation foci in the left hemisphere were found at the thresholds used to process fMRI data. Recovery of the speech function, to a certain degree, occurred in all patients, but no clear correlation with fMRI data was found., Conclusion: Complex fMRI and neuropsychological studies in 20 patients after resection of frontal and temporal lobe tumors revealed individual features of speech system reorganization within one year follow-up. Probably, activation of right-sided homologues of the speech areas in the presence of left hemisphere tumors depends not only on the severity of speech disorder but also reflects individual involvement of the right hemisphere in enabling speech function. This is confirmed by right-sided activation, according to the fMRI data, in right-sided patients without aphasia and, conversely, the lack of activation of right-sided homologues of the speech areas in several patients with severe postoperative speech disorders during the entire follow-up period.

Aim: To study the peri-insular association tract anatomy and define the permissible anatomical boundaries for resection of glial insular tumors with allowance for the surgical anatomy of the peri-insular association tracts., Material and Methods: In an anatomic study of the superior longitudinal fascicle system (SLF I, SLF II, SLF III, arcuate fascicle), we used 12 anatomical specimens (6 left and 6 right hemispheres) prepared according to the Klingler's fiber dissection technique. To confirm the dissection data, we used MR tractography (HARDI-CSD-tractography) of the conduction tracts, which was performed in two healthy volunteers., Results: Except the SLF I (identified in 7 hemispheres by fiber dissection), all fascicles of the SLF system were found in all investigated hemispheres by both fiber dissection and MR tractography. The transcortical approach to the insula through the frontal and (or) parietal operculum is associated with a significant risk of transverse transection of the SLF III fibers passing in the frontal and parietal opercula. The most optimal area for the transcortical approach to the insula is the anterior third of the superior temporal gyrus that lacks important association tracts and, consequently, a risk of their injury. The superior peri-insular sulcus is an intraoperative landmark for the transsylvian approach, which enables identification of the SLF II and arcuate fascicle in the surgical wound., Conclusion: Detailed knowledge of the peri-insular association tract anatomy is the prerequisite for neurosurgery in the insular region. Our findings facilitate correct identification of both the site for cerebral operculum dissection upon the transcortical approach and the intraoperative landmarks for locating the association tracts in the surgical wound upon the transsylvian approach to the insula.

Unlabelled: Glioblastoma is the most common primary malignant glial tumor of the brain in adult patients., Aim: to define the prognostic value of isocitrate dehydrogenase-1 (IDH-1) mutation and methylguanine-DNA methyltransferase (MGMT) methylation status in patients with glioblastoma (GB) and to analyze the impact of clinical data (gender, age, and tumor site), histological variants of the tumor structure, and time to development of recurrences on the course of the disease., Subjects and Methods: The investigation enrolled 63 GB patients aged 18 to 71 years who had received combined treatment (surgery, chemo- and radiotherapy) at the N.I. Burdenko Research Institute of Neurosurgery, Ministry of Health of the Russian Federation, in the period 2008 to 2011. The investigators performed a morphological examination of all tumor tissue samples and an immunohistochemical examination using anti-IDH-1 R-132 antibody clone («Dianova», Germany) and defined MGMT methylation status by a polymerase chain reaction using the CpGenome DNA Modification Kit («Chemicon International», USA). The data were statistically processed using a package of Statistica 6.0 programs., Results: Patient age, time to development of recurrent glioblastoma, mutations in the IDH-1 gene and MGMT were found to be prognostic factors for overall survival among adult patients in this category., Conclusion: Analysis of clinical findings and identification of molecular genetic aberrations in the tumor cells will be able to elaborate an individual approach to treating patients with glioblastoma in order to increase their survival rates and to improve quality of life.

A review of literature presents up-to-date information on the prevalence, incidence, clinical manifestations, diagnosis, and classification of malignant primary skull base tumors (MPSBTs). In the structure of total cancer incidence, malignant head and neck tumors account for 5% of all annual cancer deaths in the USA and are among the 5 most common groups of tumors in males worldwide. These tumors develop most often in the sixth decade of life, occurring 2 times more often in males than in females. In Russia, the MPSBT incidence (as of 2012) was 0.62% out of all newly diagnosed malignant tumors. The incidence rate amounts to 0.66 per 100 000 population and is significantly higher than the global rate (0.44 per 100 000). About half of all malignant skull base tumors have the epithelial nature and affect the anterior parts of the skull base. The most frequent histological types of malignant skull base tumors are squamous cell carcinoma, adenocarcinoma, and non-Hodgkin's B cell lymphoma. Treatment of skull base tumors is an interdisciplinary problem and the area of interest of otolaryngologists, dentists, ophthalmologists, neurosurgeons, plastic surgeons, radiologists, and chemotherapists. Physical and endoscopic examinations, endoscopic transnasal biopsy, CT, MRI, PET/CT, and ultrasound are typically used for verification of the diagnosis, tumor staging, and selection of the treatment approach. The review describes the criteria for TNM staging of malignant tumors of the nasal cavity and paranasal sinuses in accordance with the 7th version of the TNM recommendations of the American Joint Committee on Cancer (AJCC). The TNM-based staging depends on the location (maxillary sinus, nasal cavity, or ethmoid labyrinth) and histological structure of the tumor, which, in turn, determines the tactics of comprehensive treatment and a prognosis group.

Background: Practical application of methods for intravital examination of the brain pathways, such as preoperative diffusion tensor imaging (DTI) tractography and intraoperative neurophysiological monitoring, facilitates safer resection of intracranial tumors located near the pyramidal tracts (PTs)., Purpose: The study purpose was to investigate the relationships between intracerebral tumors of different histological nature and the pyramidal tract based on preoperative DTI tractography and various methods of intraoperative neurophysiological monitoring for intraoperative identification of the pyramidal tract, depending on different variants of the topographo-anatomic relationships between the pyramidal fascicle and the tumor., Material and Methods: The study included 29 patients with supratentorial tumors of a different histological structure. Of these, 2 patients had grade I tumors, 8 patients had grade II tumors, 4 patients had grade III tumors, 11 patients grade IV tumors, and 4 patients had brain metastases. The patients underwent preoperative DTI tractography with PT reconstruction and evaluation of the topographo-anatomic relationships between the pyramidal tract and the tumor (tract: intact, infiltrated, displaced). Neurophysiological monitoring (direct electrical stimulation in 24 patients and transcranial motor evoked potentials in 26 patients) was used during surgery. The strength of stimulating current for direct stimulation was varied from 10 to 30 mA. Postoperatively, the motor function was evaluated by using a 5-score scale, and the data were compared to the preoperative data., Results: According to preoperative DTI tractography in patients with grade I-II gliomas, the corticospinal tracts were infiltrated in 2 cases, displaced in 3 cases, and intact in 5 cases. In patients with grade III-IV gliomas and metastases, the tracts were infiltrated in 8 cases, displaced in 4 cases, and intact in 7 cases. Motor responses evoked by direct electrical stimulation were obtained in 5 out of 6 patients with the pyramidal tract displaced by the tumor and in 7 out of 8 patients with the tract infiltrated by the tumor. In the case of the intact tract, the PT to tumor distance and the stimulus strength play an important role: responses were obtained in 4 out of 10 patients. In the case of transcranial motor evoked potentials (TCMEPs), no dynamics of the potential amplitude was detected in 17 out of 26 patients during surgery; a reduced TCMEP amplitude was detected in 9 patients., Conclusion: 1. Patients with an infiltrated or displaced pyramidal tract had significantly more often hemiparesis before surgery and aggravation of hemiparesis after the surgery compared to patients with an intact tract. 2. In the case of direct electrical stimulation of the PT, motor responses (according to preoperative DTI tractography) were significantly more often observed for the pyramidal tract infiltrated and displaced by the tumor. 3. A reduction in the motor neurologic deficit in the postoperative period was significantly more often observed for application of a larger current strength during direct electrical stimulation. 4. Persistence of the TCMEP amplitude during surgery is a reliable predictor for no aggravation of the motor neurological deficit after surgery. Postoperative aggravation of hemiparesis was significantly more often observed when TC MEPs decreased during surgery.

Objective: To describe a procedure and outcomes of comprehensive first-line treatment in glioblastoma patients., Material and Methods: We analyzed 107 glioblastoma patients operated on in 2010-2011. Seventy five patients underwent combined chemoradiotherapy (CRT) with simultaneous administration of 75 mg/m2 temozolomide (TMZ), followed by chemotherapy with 200 mg/m2 TMZ for 5 days, every 28 days. Separately, we examined 32 patients with large tumors who received alternative treatments., Results: The median time to progression was 11.7 months in the study group and 7.2 and 8.1 months in groups of alternative therapy. The one-year progression-free survival rate was 37%. Overall survival was 29.2 months., Conclusion: The chemoradiotherapy regimen involving TMZ followed by one-year TMZ monotherapy is the appropriate treatment for patients with resected glioblastoma. With this approach, no tumor progression occurs in one third of patients during the first year. A careful study of the clinical and radiological findings in the course of treatment makes it possible to achieve the maximum efficacy, avoid unreasonably early switch to second-line therapy, and timely detect tumor recurrence signs. The Response Assessment in Neuro-Oncology (RANO) criteria should be used for assessment of MRI detected changes in the tumor size. The rates of overall and recurrence-free survival were significantly lower in patients with inoperable or partially resected tumors. The applied approaches provide only a slight advantage in control of tumor growth, which necessitates searching for more efficient treatment options for these patients. One of the approaches may be addition of bevacizumab to the first-line therapy regimen.

Unlabelled: Basal ganglia germinomas are a specific group of intracranial germinomas. Their early diagnosis is complicated due to their atypical localization and diversity of neuroimaging and clinical signs., Material and Methods: We describe 4 cases of basal ganglia germinoma in boys of 13, 14, 15, and 16 years of age. The medical history data, clinical features, neuroimaging and histological characteristics of basal ganglia germonomas, and preliminary results of the treatment are presented., Conclusion: Basal ganglia germinomas are usually verified at the late stage of the disease when patients are detected with extended lesions of the basal ganglia and severe neurological and neuroendocrine deficits. This situation is due to clinical and imaging signs that are untypical of common germinomas.

Awake craniotomy is a neurosurgical intervention aimed at identifying and preserving the eloquent functional brain areas during resection of tumors located near the cortical and subcortical language centers. This article provides a review of the modern literature devoted to the issue. The anatomical rationale and data of preoperative functional neuroimaging, intraoperative electrophysiological monitoring, and neuropsychological tests as well as the strategy of active surgical intervention are presented. Awake craniotomy is a rapidly developing technique aimed at both preserving speech and motor functions and improving our knowledge in the field of speech psychophysiology.

Awake craniotomy is a "gold standard"for intraoperative brain language mapping. One of the main anesthetic challenge of awake craniotomy is providing of optimal sedation for initial stages of intervention. The goal of this study was comparison of different technics of anesthesia for awake craniotomy. Materials and methods: 162 operations were divided in 4 groups: 76 cases with propofol sedation (2-4mg/kg/h) without airway protection; 11 cases with propofol sedation (4-5 mg/kg/h) with MV via LMA; 36 cases of xenon anesthesia; and 39 cases with dexmedetomidine sedation without airway protection. Results and discussion: brain language mapping was successful in 90% of cases. There was no difference between groups in successfulness of brain mapping. However in the first group respiratory complications were more frequent. Three other technics were more safer Xenon anesthesia was associated with ultrafast awakening for mapping (5±1 min). Dexmedetomidine sedation provided high hemodynamic and respiratory stability during the procedure.

In this paper, we present a review of current literature on the application of intraoperative fluorescence diagnosis and fluorescence spectroscopy using 5-aminolevulinic acid in surgery for various types of brain tumors, both alone and in combination with other neuroimaging methods. Authors' extensive experience with these methods allowed them to develop a set of clinical guidelines for the use of intraoperative fluorescence diagnosis and fluorescence spectroscopy in surgery of brain tumors.

Unlabelled: Awake craniotomy is recognized as method that can decrease the frequency of neurological complications after surgery for gliomas located near eloquent brain regions. Unfortunately good neurological outcome can't be ensured even by using of this technique. This paper discusses reasons and possible ways of prevention of such complications., Material and Methods: 162 awake craniotomies were performed in our clinic., Results: 152 of patients were discharged from the clinic with good outcome. In 10 (6%) cases sustained severe neurological deficit was noted. These complications were associated with anatomic or ischemic injury of subcortical pathways and internal capsule., Conclusion: Awake craniotomy is effective instrument of brain language mapping and prevention of neurological deterioration. Severe neurological complications of awake craniotomy are associated with underestimate neurosurgical risks, especially in terms of blood vessel injury and depth of resection. The main way of prevention of such complications is meticulous planning of operation and adequate using of mapping facilities.

The expression profiles of 10 mature microRNA (7, 10a, 17, 20a, 21, 23a, 26a, 137, 222) in biopsy specimens of gliomas of different malignancy were studied by the real time PCR with SYBR Green I fluorescent stain. The expression of microRNA-21 increased significantly, while that of microRNA-137 decreased, depending on the tumor malignancy. The expression of microRNA-9, -17, -20a, -23a, -26a was significantly higher, while that of microRNA-7 lower in the tumor vs. control tissue samples. New data on the molecular pathological mechanisms of gliomas related to their malignancy were obtained. Quantitative analysis of microRNA was suggested as a potential diagnostic marker of brain tumors.

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(2)) 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.

Background: MicroRNAs (miRNAs) are a class of small non-coding RNA molecules involved in the regulation of key biological processes. Different miRNAs with pro-oncogenic and anti-oncogenic properties have been identified in glioblastomas. We decided to analyze expression profiles of 10 mature miRNAs (miR-7-1, miR-10а, miR-17, miR-20а, miR-21, miR-23а, miR-26а, miR-137, and miR-222) in post-surgery glioma specimens of different grades in order to find whether the expression level correlates with tumor grades. We also measured expression of six key genes such as PTEN, p21/CDKN1A, MDR1, ABCG2, BAX, and BCL-2 involved in the regulation of critical glioma signaling pathways to establish the effect of miRNAs on these signaling mechanisms., Methods: Using RT-PCR, we performed expression analysis of 25 tumor fresh samples (grades II-IV)., Results: We found gradual increase in miR-21 and miR-23a levels in all tumor grades whereas miR-7 and miR-137 were significantly down-regulated depending on the glioma grade. MDR, ABCG2, and p21/CDKN1A levels were significantly up-regulated while expression of PTEN was down-regulated in tumor samples compared to the normal brain tissue., Conclusions: These observations provide new insights into molecular pathogenic mechanisms of glioma progression and suggest about a potential value of miRNAs as a putative diagnostic marker of brain tumors., (Copyright © 2014 Elsevier B.V. All rights reserved.)

This work was aimed at studying the optimal diagnosis methods and features of clinical signs of malignant B-cell lymphoma of the anterior visual pathways and choosing the most reasonable treatment method. Six immunocompetent patients with lymphomas in the chiasm-sellar region were examined. The outcomes of high-dose methothrexate chemotherapy and radiotherapy in these patients are analyzed.

This review presents basic information about white matter tracts of the human brain, with a special emphasis being placed on long associative fibers (superior and inferior longitudinal fascicles, inferior frontooccipital fascicles, fasciculus arcuatus and fasciclus uncinatus): their structure, history, functions, methods of preoperative and intraoperative identification during neurosurgical operations. Neurological symptoms caused by a damage to each of the above-described long associative fiber are described. There is a detailed analysis of methods of neuropsychological testing and neurophysiological identification in white matter fiber tract mapping in focal brain lesions.