Pyrazolo[3,4-d]pyrimidine Tyrosine Kinase Inhibitors Induce Oxidative Stress in Patient-Derived Glioblastoma Cells.

BACKGROUND: Glioblastoma (GBM) highly expresses Src tyrosine kinase involved in survival, proliferation, angiogenesis and invasiveness of tumor cells. Src activation also reduces reactive oxygen species (ROS) generation, whereas Src inhibitors are able to increase cellular ROS levels. METHODS: Pro-oxidative effects of two pyrazolo[3,4-d]pyrimidine derivatives-Src tyrosine kinase inhibitors, Si306 and its prodrug pro-Si306-were investigated in human GBM cells U87 and patient-derived GBM-6. ROS production and changes in mitochondrial membrane potential were assessed by flow cytometry. The expression levels of superoxide dismutase 1 (SOD1) and 2 (SOD2) were studied by Western blot. DNA damage, cell death induction and senescence were also examined in GBM-6 cells. RESULTS: Si306 and pro-Si306 more prominently triggered ROS production and expression of antioxidant enzymes in primary GBM cells. These effects were followed by mitochondrial membrane potential disruption, double-strand DNA breaks and senescence that eventually led to necrosis. CONCLUSION: Src kinase inhibitors, Si306 and pro-Si306, showed significant pro-oxidative potential in patient-derived GBM cells. This feature contributes to the already demonstrated anti-glioblastoma properties of these compounds in vitro and in vivo and encourages clinical investigations.

Pilomyxoid astrocytoma of the thoracic spinal cord: Extremely rare case report of over 70-year-old patient.

The Pilomyxoid is rare tumor in elderly population, in addition to the occurrence of an isolated lesion in spinal cord is extremely rare in non-pediatric population. Taking biopsy and subtotal resection is the starting point in essential approach for the treatment. After defining the histopathological nature of the tumor and specified that is Pilomyxoid, the next step is the combination of reoperation and adjuvant therapy.

GIANT CAVERNOUS MALFORMATION WITH UNUSUALLY AGGRESSIVE CLINICAL COURSE: A CASE REPORT.

Giant cavernomas (GC) are rare lesions, with less than 50 cases reported so far. Clinical presentation usually involves epileptic seizures and less typically focal neurological deficit, due to repeated hemorrhages and GC mass effect and consequentially increased intracranial pressure. Although individual cases have been reported, due to the rarity and variable imaging appearance, GCs are usually not considered in the differential diagnosis of large hemorrhagic lesions, especially when significant mass effect is present. A 17-year-old boy presented due to severe headache, right-sided weakness, and slurred speech. Symptoms started three days before with occasional headaches, which intensified gradually. Emergency computed tomography revealed a left frontal massive heterogeneous lesion. Soon after, right-sided hemiparesis and speech impairment progressed, and the patient became drowsy with the slightly dilated left pupil. Emergency surgery was performed, and the lobed grayish lesion was entirely removed. Based on the macroscopic appearance, the surgeon assumed it was a metastasis of melanoma. Histopathologic analysis result was cavernoma. GC should be considered as an option in hemorrhagic lesions, especially in the young age population. Emergency surgery for mass lesions is not uncommon in neurosurgery; however, bleeding cavernomas are usually planned for elective surgery due to the specific approach and complications.

Src Inhibitors Pyrazolo[3,4-d]pyrimidines, Si306 and Pro-Si306, Inhibit Focal Adhesion Kinase and Suppress Human Glioblastoma Invasion In Vitro and In Vivo.

Glioblastoma (GBM), as the most aggressive brain tumor, displays a high expression of Src tyrosine kinase, which is involved in the survival, migration, and invasiveness of tumor cells. Thus, Src emerged as a potential target for GBM therapy. The effects of Src inhibitors pyrazolo[3,4-d]pyrimidines, Si306 and its prodrug pro-Si306 were investigated in human GBM cell lines (U87 and U87-TxR) and three primary GBM cell cultures. Primary GBM cells were more resistant to Si306 and pro-Si306 according to the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. However, the ability of all GBM cells to degrade the extracellular matrix was considerably compromised after Si306 and pro-Si306 applications. Besides reducing the phosphorylation of Src and its downstream signaling pathway components, both compounds decreased the phosphorylated form of focal adhesion kinase (FAK) and epidermal growth factor receptor (EGFR) expression, showing the potential to suppress the aggressiveness of GBM. In vivo, Si306 and pro-Si306 displayed an anti-invasive effect against U87 xenografts in the zebrafish embryo model. Considering that Si306 and pro-Si306 are able to cross the blood-brain barrier and suppress the spread of GBM cells, we anticipate their clinical testing in the near future. Moreover, the prodrug showed similar efficacy to the drug, implying the rationality of its use in clinical settings.

Intracerebral hemorrhage as a first sign of pheochromocytoma: case report and review of the literature.

Pheochromocytomas and sympathetic paragangliomas are rare catecholamine-secreting tumours that represent very rare causes of intracerebral haemorrhage in the young, with only a few cases reported. A 32-year-old man presented to our emergency department because of sudden onset of severe headache. He had a six-month history of paroxysmal headache, palpitations, and sweating. During examination he became somnolent and developed left-sided hemiplegia. A computed tomographic (CT) scan of the brain showed a right temporoparietal haematoma. He was admitted to the Clinic for Neurosurgery and the haematoma was evacuated. The patient was comatose, on assisted respiration, with frequent hypertensive crises. An examination for possible secondary causes of hypertension was undertaken. Plasma metanephrine value was elevated (414 pg/mL, reference values < 90 pg/mL). Abdominal CT scans revealed a large mass (6 cm) in the right adrenal gland. After adequate control of the hypertension was achieved with nonselectivealpha- and beta-adrenergic blockers the tumour was excised. The histopathologic findings confirmed the diagnosis of pheochromocytoma. The genetic analysis demonstrated a duplication in exon 1 of the VHL gene. We reported a rare, potentially fatal complication of pheochromocytoma - an intracerebral haemorrhage. This case and review of similar rare cases in the literature illustrate the importance of early recognition of the characteristic symptoms of catecholamine excess in young patients with hypertension.

SOX3 can promote the malignant behavior of glioblastoma cells.

PURPOSE: Glioblastoma is the most common and lethal adult brain tumor. Despite current therapeutic strategies, including surgery, radiation and chemotherapy, the median survival of glioblastoma patients is 15 months. The development of this tumor depends on a sub-population of glioblastoma stem cells governing tumor propagation and therapy resistance. SOX3 plays a role in both normal neural development and carcinogenesis. However, little is known about its role in glioblastoma. Thus, the aim of this work was to elucidate the role of SOX3 in glioblastoma. METHODS: SOX3 expression was assessed using real-time quantitative PCR (RT-qPCR), Western blotting and immunohistochemistry. MTT, immunocytochemistry and Transwell assays were used to evaluate the effects of exogenous SOX3 overexpression on the viability, proliferation, migration and invasion of glioblastoma cells, respectively. The expression of Hedgehog signaling pathway components and autophagy markers was assessed using RT-qPCR and Western blot analyses, respectively. RESULTS: Higher levels of SOX3 expression were detected in a subset of primary glioblastoma samples compared to those in non-tumoral brain tissues. Exogenous overexpression of this gene was found to increase the proliferation, viability, migration and invasion of glioblastoma cells. We also found that SOX3 up-regulation was accompanied by an enhanced activity of the Hedgehog signaling pathway and by suppression of autophagy in glioblastoma cells. Additionally, we found that SOX3 expression was elevated in patient-derived glioblastoma stem cells, as well as in oncospheres derived from glioblastoma cell lines, compared to their differentiated counterparts, implying that SOX3 expression is associated with the undifferentiated state of glioblastoma cells. CONCLUSION: From our data we conclude that SOX3 can promote the malignant behavior of glioblastoma cells.

Evaluation of factors for poor outcome in preterm newborns with posthemorrhagic hydrocephalus associated with late-onset neonatal sepsis.

PURPOSE: Preterm newborns, due to many factors, are at increased risk for poor neural development, intraventricular hemorrhages, infections, and higher rate of mortality. The aim of this study was to evaluate the risk factors associated with poor outcome in preterm neonates with late-onset neonatal sepsis (LONS) who had posthemorrhagic hydrocephalus and underwent neurosurgical procedures for treatment of the hydrocephalus. PATIENTS AND METHODS: Preterm neonates who had undergone insertion of ventriculoperitoneal shunt or Ommaya reservoir, during the 10-year period at University Children's Hospital, were retrospectively analyzed. According to the presence or absence of LONS, patients were divided into LONS group and non-LONS group. In both groups, we analyzed demographic and clinical data as well as nondependent factors. Additionally, we evaluated the patients who had lethal outcome in respect to all the analyzed factors. RESULTS: A total of 74 patients were included in the study, 35 in LONS group and 39 in control group. Patients in LONS group were born significantly earlier with lower birth weight, needed significantly higher O2 inspiratory concentration, and had longer duration of mechanical ventilation when compared to the nonseptic group. Five patients in LONS group had lethal outcome, and for these patients we identified a grade American Society of Anaesthesiologists score of 4 (P=0.000), ductus arteriosus persistens (P=0.000), bronchopulmonary dysplasia (P=0.003), and pneumothorax (P=0.003) as independent preoperative risk factors for lethal outcome. CONCLUSION: Neurosurgical procedures are relatively safe in neonates with posthemorrhagic hydrocephalus without LONS after birth. However, if LONS is present, various conditions such as preoperative high grade American Society of Anaesthesiologists score, ductus arteriosus persistens, bronchopulmonary dysplasia, and pneumothorax markedly increase the risk for a lethal outcome after the operation.

The Value of Multidetector Computed Tomography of Orbits in Globe Protrusion in Comparison to Hertel Exophthalmometry

The use of multidetector computed tomography (MDCT) is an integral part of contemporary diagnostics of Graves' orbitopathy. The aim of this study was to assess proptosis measurement by MDCT and to compare it to the current standard, Hertel exophthalmometry. A cross-sectional study was conducted at the Clinical Centre of Serbia and included 91 patients (19 male and 72 female) with verified Graves' orbitopathy. Globe protrusion measured by MDCT (globe protrusion, GPR) was correlated to Hertel measured protrusion (HR). There was no constant or any systematic bias between the two methods. GPR significantly correlated with the best-corrected visual acuity, while HR did not. Age, body mass index and duration of the disease did not influence proptosis measurement by either method. Proptosis was significantly larger in males. According to our results, GPR compared to HR provides better assessment of the protrusion in Graves' disease. GPR measurement is simple and should always be part of the radiological assessment of orbits in Graves' disease.

Determination of Predictive Anatomic Parameters for Bleeding of Brain Arteriovenous Malformations by Multidetector CT Angiography.

Patients with brain arteriovenous malformation (AVM) have a certain risk to bleed, and the goal of this study was to examine the effect of radiological and clinical predictive characteristics of AVM hemorrhage using multidetector computed tomographic (MDCT) angiography. The study included a series of 57 patients, mean age 35.46 years, who were diagnosed during their hospitalization at Clinical Department of Neurosurgery, Clinical Center of Serbia, in the period from January 2008 to March 2016. In all patients, the diagnosis was made using MDCT angiography. Two groups of patients were observed. The first group included patients who did not initially present with hemorrhage, while the second group initially presented with hemorrhage. Both groups were treated with medical therapy or a combination of medical therapy with embolization/surgery/radiotherapy. Deep venous drainage (p<0.05), combined arterial supply from different basins (p<0.05) with a length <60 mm, venous dilatation present in the drainage vein (p<0.01), and the angle of casting sup-ply arteries in the nidus (p<0.01) carry a risk of repeated bleeding. In the group of patients who had initial hemorrhage, the mean value of the casting angle size was 130°, while in the group that did not have initial bleeding the mean value of the measured angle size was 103.81° with standard deviation of 17.21° (p<0.01). In conclusion, AVMs with deep venous drainage from the carotid and vertebrobasilar basin, the length of the feeding arteries <60 mm, the angle of the casting feeding arteries in the nidus ≥130° and dilatation and/or venous aneurysm of drainage vessel are predictive for clinical presenting by hemorrhage.

Adult Brainstem Gliomas: Retrospective Analysis of 51 Patients.

AIM: Brainstem gliomas (BSG) constitute less than 2% of brain tumors in adults. Therapeutic options are limited and BSG are associated with a high morbidity and mortality. MATERIAL AND METHODS: We reviewed the records of 51 patients with BSG treated at the Institute of Neurosurgery, Clinical Center of Serbia in Belgrade between 1998 and 2012. We recorded demographic and clinical variables as well as radiological findings and survival. RESULTS: Of the 51 patients, 62.7% were male and 37.3% were female. The mean age was 30.6±19.3 years. High grade glioma (Astrocytoma grade III and IV) was most common at the age of 38.2±17.9 years (t=.481, p=0.017) while low grade glioma (Astrocytoma grade I and II) was common in younger age as 25.4±17.4 years (X2=4.013; p=0.045), with localization in the pons (X2=5.299; p=0.021) and exophytic presentation (X2=3.862; p=0.049). Ataxia, as initial symptom, was a predictor of poor outcome (HR:5.546, p=0.012). CONCLUSION: Due to its specific localization, BSG present a major challenge for neurosurgery, because of the necessity of safe approach for radical resection. Histological verification of BSG determines the need for additional therapeutic procedures such as radiotherapy and chemotherapy. Benefit from correct diagnosis is reflected in the avoidance of potentially adverse effects of treatment.

GLIOBLASTOMA MULTIFORME BRAIN TUMORS LOCATED IN THE MOTOR CORTEX--SPECIFIC FINDINGS IN COMPARISON WITH LOW GRADE GLIOMAS OF THE SAME LOCALIZATION: ANALYSIS OF A SIXTY PATIENT SERIES.

The verified presence of a glioblastoma multiforme (GBM) tumor in the motor area of the brain, in a patient lacking preoperative neurological deficit, offers no certainty that the tumor can be radically removed without the possibility of causing postoperative motor deficit. We present a series of 60 patients hospitalized at the Clinical Department of Neurosurgery, Clinical Center of Serbia in Belgrade between October 2011 and February 2015, harboring tumors located within and in the vicinity of the motor zone of the brain. By using Karnofsky's index (KI), the pre- and postoperative conditions of the patients were evaluated. Regarding electrical stimulation of the motor cortex, significantly lower values of the electrical current intensity, frequency, and pulse wave duration (p < 0.01) were needed for triggering motor response in case of GBM tumor compared to a slowly growing tumor (low-grade). Patients with low-grade gliomas (LGG) had statistically significantly higher KI values pre- and postoperatively than patients with GBM (p < 0.01). Using electrical stimulation of the cortex, a higher grade of resection of LGG could be achieved as compared with the group presenting with GBM (χ² = 5.281; df = 1; p < 0.05). Our findings and review of the results reported by other authors underline the necessity of routine application of electrical stimulation of the cerebral cortex in order to identify the primary motor field (M1).

Surgical treatment problems of hydrocephalus caused by spontaneus intraventricular hemorrhage in prematurely born children.

AIM: The aim of this study was to identify the most appropriate method of surgical treatment of hydrocephalus in preterm infants that is caused by spontaneous intraventricular hemorrhage (IVH) and to identify predictive factors of poor perioperative outcomes. MATERIAL AND METHODS: We present a series of 60 patients with IVH and hydrocephalus, to whom a VP shunt or subcutaneous (Omaya) reservoir was placed, during the period from March 2006 to March 2011. RESULTS: Predictors of poor outcome with VP shunt placement were: gestational age (t=2.323, p=0.024), head circumference at birth (t=2.072, p=0.043), birth weight (t=2.832, p=0.006), Apgar score at birth (t=5.026, p < 0.01), number of days on assisted ventilation (Z=6.203, p < 0.001), peripartal asphyxia (χ < sup > 2 < /sup > =17.376, p < 0.01), respiratory distress (χ < sup > 2 < /sup > =9.176 p=0.002). Predictors of poor outcome in getting Omaya reservoir are: low birth weight (t=2.560, p=0.016), low Apgar scores (t=3.059, p=0.005), an extended number of days on assisted ventilation (Z=4.404, p < 0.001), presence of peripartal asphyxia (χ2=9.977, p=0.002) and cardio-respiratory arrest (χ2=12.804, p < 0.001). CONCLUSION: The outcome of hydrocephalus caused by IVH in premature born children is the worst in perinatology. Our results suggest that the main predictive factor is preoperative condition of the child and that the VP shunt and Omaya reservoir are complementary methods of surgical treatment.

Comparative analysis of the animal model and results of the clinical research of the aneurysm inclination angle as the predisposing factor for the occurrence of rupture.

INTRODUCTION: Natural course of aneurysms that occur on blood vessels of the brain singles out the need for understanding the mechanism of the occurrence of aneurysm wall rupture and identification of anatomic characteristics as predictive factors for hemorrhage to occur. OBJECTIVE: In this study we comparatively present results of our researches and experimental models on animals. METHODS: We made a comparative analysis of anatomical characteristics of blood vessels of the brain and aneurysms obtained on the basis of digital subtraction angiography and intraoperative finding. In this article we review recent research in the anatomic characteristics of intracranial aneurysms and parent blood vessels. We present a series of 185 aneurysms (ruptured and unruptured) dissected at the Neurosurgical Clinic of Clinical Center of Serbia in Belgrade. RESULTS: Inclination angle may be considered as the vital predesposing factor for intracranial aneurysm rupture. In aneurysms that ruptured it was 139.748+/-27.242 degrees, while in unruptured aneurysms it was considerably smaller and amounted to 100.882+/-22.001 degrees (p<0.01). CONCLUSION: Inclination angle may be regarded as the vital predisposing factor since it differs considerably in unruptured and ruptured aneurysms. Aneurysms with blood stream angle smaller than 115 degrees have very small probability of rupture, while blood stream angle bigger than 150 degrees presents a high risk of rupture.

Application of the Ommaya reservoir in the treatment of hydrocephalus in prematurely born children: correlation with animal results.

INTRODUCTION: Intraventricular hemorrhage occurs in almost one fifth of prematurely born children. Due to present complications, such as hydrocephalus and neurological deficit, it endangers the child's life, therefore there is the need for understanding and prevent risk factors as well as the need for finding most optimal methods of treatment. OBJECTIVE: The aim of the study was to point out the current therapeutic modalities of the treatment of posthemorrhagic hydrocephalus in prematurely born children. METHODS: The study included 60 patients divided into two groups of 30 patients treated at the University Children's Hospital of Belgrade in the period 2003-2008. RESULTS: Treatment outcome of the control group of patients treated by standard methods was influenced by gestational age (p=0.024), head circumference on birth (p = 0.043), body mass on birth (p = 0.006), Apgar score on birth (p < 0.001), peripartum asphyxia (p < 0.001), cardiorespiratory arrest (p < 0.001), respiratory distress (p = 0.002) and intraventricular hemorrhagic grade (p < 0.001). As statistically significant predictors of the poor treatment outcome of the experimental group of patients treated by using Ommaya reservoir were identified: low body mass on birth (p < 0.05), low Apgar score (p < 0.05), prolonged number of days on assisted ventilation (p < 0.05), presence of peripartum asphyxia (p < 0.05) and cardiorespiratory arrest (p < 0.05). CONCLUSION: No statistically significant difference was detected in the outcome between the patients treated by the standard method and those with installed Ommaya reservoir. However, the difference of 10% in mortality between the two groups may be clinically significant so that further studies of larger samples are necessary.

Assessing the quality of angiographic display of brain blood vessels aneurysms compared to intraoperative state.

BACKGROUND/AIM: Aneurysms in brain blood vessels are expanding bags composed of a neck, body and fundus. Clear visibility of the neck, the position of the aneurysm and surrounding structures are necessary for a proper choice of methods for excluding the aneurysm from the circulation. The aim of this study was to evaluate the reliability of spatial reconstruction of blood vessels of the brain based on the original software for 3D reconstruction of the equipment manufacturer and a personal computer model developed earlier in the Clinic for Neurosurgery, Clinical Center of Serbia, Belgrade, compared to intraoperative identification of these aneurysms. METHODS: This study included 137 patients of both sexes. The presence of an aneurysm was verified by angiographic methods [computed tomographic angiography (CTA), multislice computed tomography angiography (MSCTA), magnetic resonance imaging angiography (MRA), or digital subtraction angiography (DSA)]. RESULTS: The quality score (0 to 5) for CTA was 3.180 +/- 0.961, MSCTA 4.062 +/- 0.928, and for DSA 4.588 +/- 0.758 (p < 0.01). The results of this study favorite conventional angiography as the gold standard for diagnostic of intracranial aneurysms. CONCLUSION: The results of this study are consistent with current publications review and clearly recognize the advantages and disadvantages of diagnostic neuroradiological procedures, with DSA of brain blood vessels as a binding preoperative diagnostic procedure in cases in who it is not possible to clearly visualize the supporting blood vessel and neck of the aneurysm by using the findings of CTA, MRA and MSCTA.

The results of treatment of primary brain tumors in children.

During the period of 2009-2011 in UCH in Belgrade, we treated 22 patients with brain tumors. Treatment included the diagnosis and therapy that included surgery and postoperative neuroradiological follow-up of all patients regardless of whether radiotherapy was conducted with or without chemotherapy. The most frequent were low grade astrocytomas and medulloblastomas. Patients with supratentorial localization of tumor had significantly smaller neurological sequelae compared with patients with infratentorial as well as patients diagnosed with low grade astrocytomas of any localization. From 10 patients with supratentorial localization, 7 of them had no neurological deficit, while from 11 patients with infratentorial localization, 3 of them were Without deficit. Patients with histological diagnosis of low grade astrocytoma of any localization had less neurological deficits compared with other tumors. From 7 low grade astrocytoma in 5 of them there was no neurological deficit, while only in one patient residual tumor was verified. In 7 patients the rest of the tumor was diagnosed, while in 14 patients no residual tumors was diagnosed during follow-up based on the MRI diagnosis. Surgery, postoperative radiotherapy and chemotherapy in some cases represent an effective therapeutic approach in the treatment of brain tumors in children.

Predictable morphometric parameters for rupture of intracranial aneurysms - a series of 142 operated aneurysms.

AIM: Intracranial aneurysm rupture is followed by high mortality and morbidity. In order to understand the aneurysm's natural course, it is necessary to recognize the predisposing factors for the rupture. MATERIAL AND METHODS: Analysis included 142 operated aneurysms (94 hemorrhaging and 48 unruptured) in the period from 2008 to 2010. RESULTS: The ratio between the width of the aneurysm neck and diameter of the carrying blood vessel - artery in ruptured aneurysms (OR) was 1.58 ± 0.61, and in unruptured aneurysms 1.14 ± 0.52 (p < 0.01). Aspect ratio of ruptured aneurysm was 1.89 ± 0.59, and in unruptured 1:33 ± 0.17. The angle of inclination of ruptured aneurysms was 139.22 ± 21.53, while in unruptured aneurysms it was 101.73 ± 21.26. CONCLUSION: Based on the results of our research, a predictive model of morphometric characteristics of the vessel bearing the aneurysm to rupture can be identified: an irregular shape of the aneurysm, AR > 1.6, OR > 1.5 and inclination angle > 135 deg.

Asymptomatic perforation of large bowel and urinary bladder as a complication of ventriculoperitoneal shunt: report of two cases.

INTRODUCTION: Insertion of a ventriculoperitoneal (VP) shunt, the method of choice in the treatment of hydrocephalus, is often followed by various mechanical and/or infective complications. We present two children with asymptomatic perforation of the large bowel and urinary bladder, relatively rare and potentially severe complications of this surgical procedure. OUTLINE OF CASES: In both patients a VP shunt was implanted in the first month after birth; in a boy due to congenital hydrocephalus and in a girl due to the consequences of intracranial haemorrhage. Immediately after surgery, as well as during the further course, in both children growth and development were optimal and without any signs of infection or VP shunt malfunction. In the boy at age 6 months and in the girl at age 4 years, without any signs of complications, mothers noted the prominence of the VP shunt tip from the anus in the first case and from the urethral orifice in the second one. The VP shunts were immediately changed, so that both complications were resolved without any consequences. CONCLUSION: Insertion of a VP shunt represents the most frequent method of choice of the surgical treatment of hydrocephalus, but also potentially a highly risky procedure followed by various complications about which parents should be informed when patients are children. Owing to adequate approach in the follow-up of children with implanted VP shunt, large bowel and urinary bladder perforation, examples of severe and potentially fatal complications of this surgical intervention, could be disclosed on time and adequately resolved.

Surgical treatment of glioblastoma multiforme localized in the motor area of the brain using the technique of cortical electrostimulation.

AIM: Glioblastoma multiforme in the motor area is the surgical challenge because of the need for more radical resection in order to extend the life of the patient, and the risk that radicalism could lead to additional neurological deficit. MATERIAL AND METHODS: We present series of 26 patients with glioblastoma multiforme localized in and around the motor area, who were hospitalized from October 2004 to February 2009. During all operations, we conducted electrostimulation display area of the brain, to the anatomical location of M1 segment of the motor cortex. RESULTS: Distance of the central sulcus in relation to the coronary suture, measured by magnetic resonance imaging (MRI) was 18.38 mm ± 9.564 mm. The volume of electricity required for a motor response was mean 8.79 ± 1.484 mA, with increasing distance from the coronary suture the amperage required to explicit motor responses decreased. The difference (mm) between the distance from the coronary suture measured using MRI and distances measured electrostimulation smaller and power consumption was less (F = 13.285, p < 0.01). CONCLUSION: The method of cortical cerebral cortex electrostimulation is simple and safe method and a binding protocol to the patient safe operation glioblastoma multiforme localized in the motor area of the brain.

Natural course of the arteriovenous malformations of the brain initially presented by hemorrhage: analysis of a clinical series of 39 patients.

AIM: AVM because of outstanding tendency toward bleeding, even though 20 times more rare then aneurysm on the blood vessels of the brain and her own specific anatomical structure even today represents big neurosurgical challenge. MATERIAL AND METHODS: Series which is shown here consists of 39 patients which were hospitalized in the institute for neurosurgery of the Clinical Center of Serbia in the period between 1995 and 2004. This group was exposed to symptomatic therapy or it was estimated that surgery, embolization and radio surgery. RESULTS: Combined type of venous drainage brings a high risk (p < 0.001) from repeated bleeding. Combined artery bringing from different flows (p < 0.05) contributes to genesis of 'steal phenomenon', in combination with deep venous drainage it presents predisposing anatomical characteristics for repeated bleeding (p < 0.001) according to our results should present AVM with dimensions 2.5 to 5 cm localized in eloquent zone of big brain with combined type of venous drainage and cobined artery bringing from vertebro-basilar flow and carotid flow. CONCLUSION: Perception of natural course of AVM point to certainly more benign pathology in regard to other vascular malformations. Specific anatomical structure requires planning of treatment from case to case, most often combination of embolization, radio surgery and surgical treatment.