The VEGF gene polymorphism in glioblastoma may be a new prognostic marker of overall survival.

PURPOSE: Glioblastoma (GBM) is the most aggressive primary brain tumor. Vascular endothelial growth factor (VEGF) gene polymorphisms and overexpression are involved in high-grade malignant gliomas. The aim of this study was to assess the distribution of +405C>G VEGF gene polymorphism in patients diagnosed by glioblastoma and to test its association with the overall survival (OS). METHODS: Patients diagnosed for glioblastoma were randomly selected, and follow-up was conducted for a minimum of 36 months. Tissue paraffin embedded GBM samples were subjected for the VEGF polymorphism detection. The associations of the observed genotypes and clinical data were evaluated. RESULTS: The most frequent single nucleotide polymorphism (SNP) variant was G (72.58%). The GG genotype was proved to have statistically significant longer OS and patient status (alive/dead) compared to CC and CG genotypes (p=0.022 and 0.005, respectively). CONCLUSION: Our results indicate that +405C>G VEGF gene polymorphism may be used as prognostic genetic marker of OS in GBM patients.

Benefit and outcome of using temozolomide-based chemoradiotherapy followed by temozolomide alone for glioblastoma in clinical practice.

PURPOSE: Temozolomide (TEM), an oral alkylating agent, has shown promising activity in the last 10 years in the treatment of glioblastoma multiforme (GBM). Our goal was to show the benefit of concomitant therapy involving 3D conformal radiotherapy and temozolomide in clinical practice. METHODS: This was a retrospective/prospective study and included a total of 113 patients with GBM diagnosis. Forty- seven patients received postoperative radiotherapy and 66 received concomitant temozolomide plus 3D conformal radiotherapy. RESULTS: The mean overall survival of patients who received postoperative radiotherapy alone was 9.93±6.475 months, compared to statistically longer overall survival in the group of patients who received radiotherapy plus temozolomide (13.89±8.049 months) (p=0.006). The latter group was divided into two subgroups, one consisting of patients who received 6 complete cycles of temozolomide, and a second with patients who received incomplete treatment. Statistically significant longer overall survival was registered in the first subgroup compared to the second (p=0.006). CONCLUSION: The concomitant usage of temozolomide and radiotherapy was beneficial, and statistically significant difference among groups and subgroups was observed regarding overall survival.

Multidisciplinary investigation links backward-speech trait and working memory through genetic mutation.

Case studies of unusual traits can provide unique snapshots of the effects of modified systems. In this study, we report on an individual from a Serbian family with the ability to rapidly, accurately and voluntarily speak backwards. We consider psychological, neural and genetic correlates of this trait to identify specific relevant neural mechanisms and new molecular pathways for working memory and speech-related tasks. EEG data suggest that the effect of word reversal precedes semantic integration of visually presented backward-words, and that event-related potentials above the frontal lobe are affected by both word reversal and the maintenance of backward-words in working memory. fMRI revealed that the left fusiform gyrus may facilitate the production of backward-speech. Exome sequencing identified three novel coding variants of potential significance in the RIC3, RIPK1 and ZBED5 genes. Taken together, our data suggest that, in this individual, the ability to speak backwards is afforded by an extraordinary working memory capacity. We hypothesise that this is served by cholinergic projections from the basal forebrain to the frontal cortex and supported by visual semantic loops within the left fusiform gyrus and that these neural processes may be mediated by a genetic mutation in RIC3; a chaperone for nicotinic acetylcholine receptors.

DYKE-DAVIDOFF-MASSON SYNDROME - TYPICAL IMAGING FEATURES.

INTRODUCTION: Dyke-Davidoff-Masson syndrome is an uncommon neurological disorder clinically presented with seizures, various degrees of mental retardation, motor weakness and sometimes body asymmetry. Typical neuroimaging features include cerebral hemiatrophy with ipsilateral hyper pneumatization of paranasal sinuses. The purpose of this report was to present a rare cause of seizures revealed by Magnetic resonance imaging. CASE REPORT: We report a case of a 17-year-old boy admitted to hospital due to a severe headache. He had been treated because of partial epileptic seizures for six years. Neuropsychological examination revealed mild mental retardation, mild speech and reading difficulties and discrete right-sided hemiparesis. Typical magnetic resonance imaging features confirmed clinical suspicion of Dyke-Davidoff-Masson syndrome. revealing left frontal lobe atrophy, with consecutive widening of the left lateral ventricle frontal horn, thickening of the nearby frontal squama and hypertrophy of left frontal sinus. CONCLUSION: Magnetic resonance imaging is the key imaging modality that confirms clinical suspicion of Dyke-Davidoff-Masson syndrome based on a proper physical and neurological examination.

Prediction of brain atrophy using three drug scores in neuroasymptomatic HIV-infected patients with controlled viremia

ABSTRACTBACKGROUND: Despite potent antiretroviral therapy, HIV still causes brain damage. Better penetration into the CNS and efficient elimination of monocyte/macrophages reservoirs are two main characteristics of an antiretroviral drug that could prevent brain damage. The aim of our study was to assess efficacy of three antiretroviral drug scores to predict brain atrophy in HIV-infected patients.METHODS:A cross sectional study consisting of 56 HIV-infected patients with controlled viremia, who had no clinically evident neurocognitive impairment. All patients had MRI of the head. A typical T2 transversal slice was analyzed and ventricles-brain ratio (VBr) as an overall brain atrophy index was calculated. Three antiretroviral drug scores were used and correlated with VBr: 2008 and 2010 CNS penetration effectiveness scores (SCPE2008 and SCPE2010) and the recently established monocyte efficacy (SME) score. A p-value <0.05 was considered significant.RESULTS:SCPE2010 was significantly associated with VBr in both univariate (r = -0.285, p = 0.033) and multivariate (ß = -0.299, p = 0.016) regression models, while SCPE2008 was not (r = -0.141, p = 0.300 and ß = -0.156,p = 0.214). SME was associated with VBr in multivariate model only (r = -0.297, p = 0.111 andß = -0.406, p = 0.029). Age and reported duration of HIV infection were also significant predictors of overall brain atrophy in multivariate regression models.CONCLUSIONS:Although based on similar type of research, SCPE2010 is a superior drug score compared to SCPE2008. SME is an efficient drug score in determining brain damage. Both SCPE2010 and SME scores should be taken into account in preventive strategies of brain atrophy and neurocognitive impairment in HIV-infected patients.

Prediction of brain atrophy using three drug scores in neuroasymptomatic HIV-infected patients with controlled viremia.

BACKGROUND: Despite potent antiretroviral therapy, HIV still causes brain damage. Better penetration into the CNS and efficient elimination of monocyte/macrophages reservoirs are two main characteristics of an antiretroviral drug that could prevent brain damage. The aim of our study was to assess efficacy of three antiretroviral drug scores to predict brain atrophy in HIV-infected patients. METHODS: A cross sectional study consisting of 56 HIV-infected patients with controlled viremia, who had no clinically evident neurocognitive impairment. All patients had MRI of the head. A typical T2 transversal slice was analyzed and ventricles-brain ratio (VBr) as an overall brain atrophy index was calculated. Three antiretroviral drug scores were used and correlated with VBr: 2008 and 2010 CNS penetration effectiveness scores (ΣCPE2008 and ΣCPE2010) and the recently established monocyte efficacy (ΣME) score. A p-value <0.05 was considered significant. RESULTS: ΣCPE2010 was significantly associated with VBr in both univariate (r=-0.285, p=0.033) and multivariate (ß=-0.299, p=0.016) regression models, while ΣCPE2008 was not (r=-0.141, p=0.300 and ß=-0.156, p=0.214). ΣME was associated with VBr in multivariate model only (r=-0.297, p=0.111 and ß=-0.406, p=0.029). Age and reported duration of HIV infection were also significant predictors of overall brain atrophy in multivariate regression models. CONCLUSIONS: Although based on similar type of research, ΣCPE2010 is a superior drug score compared to ΣCPE2008. ΣME is an efficient drug score in determining brain damage. Both ΣCPE2010 and ΣME scores should be taken into account in preventive strategies of brain atrophy and neurocognitive impairment in HIV-infected patients.

Dynamic magnetic resonance imaging of endoscopic third ventriculostomy patency with differently acquired fast imaging with steady-state precession sequences.

The aim of the study was to determine the possibilities of two differently acquired two-dimensional fast imaging with steady-state precession (FISP 2D) magnetic resonance sequences in estimation of the third ventricle floor fenestration patency after endoscopic third ventriculostomy (ETV) in the subjects with aqueductal stenosis/obstruction.Fifty eight subjects (37 males, 21 females, mean age 27 years) with previously successfully performed ETV underwent brain MRI on 1.5T MR imager 3-6 months after the procedure. Two different FISP 2D sequences (one included in the standard vendor provided software package, and the other, experimentally developed by our team) were performed respectively at two fixed slice positions: midsagittal and perpendicular to the ETV fenestration, and displayed in a closed-loop cinematographic format in order to estimate the patency. The ventricular volume reduction has been observed as well.Cerebrospinal fluid (CSF) flow through the ETV fenestration was observed in midsagittal plane with both FISP 2D sequences in 93.11% subjects, while in 6.89% subjects the dynamic CSF flow MRI was inconclusive. In the perpendicular plane CSF flow through the ETV fenestration was visible only by use of experimentally developed FISP 2D (TR30/FA70) sequence. Postoperative volume reduction of lateral and third ventricle was detected in 67.24% subjects.Though both FISP 2D sequences acquired in midsagittal plane may be used to estimate the effects of performed ETV, due to achieved higher CSF pulsatile flow sensitivity, only the use of FISP 2D (TR30/FA70) sequence enables the estimation of the treatment effect in perpendicular plane in the absence of phase-contrast sequences. 

The functional neuroimaging evidence of cerebellar involvement in the simple cognitive task.

Cerebellar involvement in cognitive functions has been revealed in numerous anatomical, clinical and neuroimaging studies and several hypotheses about potential the role of the cerebellum in higher level brain function have been established. The aim of this study was to show involvement of the cerebellum in simple cognitive tasks. For this matter, we contrasted two tasks from the same semantic domain with specific cognitive content and level of practice: counting forward and counting backward. Twelve volunteers participated in this fMRI study and they were asked to perform both tasks within the same number range (1 to 30 and vice versa). Results showed greater activation in the right cerebellum for the task of counting forward than for counting backward, while for counting backward greater activation was found in prefrontal cortex, supplementary motor area, and anterior cingulate of both hemispheres. Our results correlate with already established hypotheses about cerebellar role in precise and smooth control, not only in well-trained motor but in well trained cognitive tasks as well.

Stent graft infixation after venous dislodgement in a patient with femoral posttraumatic arteriovenous fistula.

INTRODUCTION: An arteriovenous fistula (AVF) is an abnormal connection between an artery and a vein which may result from traumatic injury or may occur as congenital abnormality. Stent graft repair through arteriovenous fistula could lead to complications. CASE REPORT: Endovascular stent graft repair in a 23-year-old patient with posttraumatic superficial femoral arteriovenous fistula was performed to cover a fistula. During the procedure the device migrated through the fistula into the femoral vein. Due to eventual risk of migration to the heart, a prompt decision was made to fix the stent graft with three puncture needles in the common femoral vein region under fluoroscopy guidance. The vascular surgeon was called to perform open surgery. CONCLUSIONS: The presented way of treating this rare complication in an extreme and uncommon situation is very efficient, safe and inexpensive.

Bilateral bloody nipple discharge in a male infant: sonographic findings and proposed diagnostic approach.

Bloody nipple discharge is an uncommon finding in the pediatric population, without clear diagnostic and therapeutic guidelines established. We noted a case of a 3-month-old male infant who presented with bilateral blood-stained nipple discharge, with unremarkable medical history. Sonographic findings revealed bilaterally dilated ducts and cysts with mixed iso- and hypoechoic intraductal content. Possible causes of this condition include hyperlaxity syndrome with decreased function of elastic fibers and fibrocystic changes in breasts, and unusual response to maternal hormones, transferred to the neonate either transplacentally or through breastfeeding. Given the most probable benign etiology and self-limiting nature of the described condition, a conservative approach is suggested. Unnecessary invasive procedures should be avoided.

[Ultrasonography and magnetic resonance imaging in prenatal diagnosis of tumour of the foetal head and neck].

INTRODUCTION: Foetal tumours are relatively rare; prenatal diagnosis enables additional diagnostics, and thus the decision on the continuation of pregnancy and planning of delivery. The paper presents prenatal ultrasound diagnostics of foetal head tumour with additionally analyzed magnetic resonance imaging (MRI). CASE OUTLINE: On ultrasound imaging, in a 27-year-old nullipara, a tumour of the foetal head was suspected at the 22nd gestational week. By consultative ultrasound, a 45 x 41 x 50 mm echogenic soft tissue tumour with hypoechogenic areas was confirmed, which originated from the left side of the skull spreading towards the neck on the left behind the ear. On colour Doppler no vascularisation was seen within the tumour but several vessels were seen along the border-line and on the surface. The scan showed no associated abnormalities. Karyotype was 46, XY. MRI scan using triplanar SSFSE and HASTE sequences was done at 26 weeks and confirmed a 84 x 45 x 71 mm tumour originating from the scalp, spreading along the endocranium over the entire surface of the fronto-temporal sqama and left parietal bone. The tumour did not disturb the integrity of the internal tabula, and did not spread intracranially. Based on these findings, the diagnosis of haemangioma was made. At 38 weeks gestation, a 3810 g male infant was delivered by Caesarean section. A bluish, well-defined, non-pulsatile tumour arising from the left frontoparietal region was seen, thus confirming the diagnosis of haemangioma. CONCLUSION: MRI improved delineation of the tumour facilitating better planning of postnatal management and mode of delivery, with the information on the postnatal course and prognosis. In the prenatal period, MRI following an ultrasound diagnosed foetal tumour, is an additional part of diagnostic examinations, and is not contraindicated during pregnancy.

Multivoxel MRS: right frontal parafalcine cortex - area of neurobiochemical gender differentiation?

OBJECTIVE: To determine the presence of gender neurometabolic differences in healthy men and women by multivoxel magnetic resonance spectroscopy (MRS). MATERIALS AND METHODS: We performed multivoxel magnetic resonance imaging and spectroscopy in 50 healthy volunteers (27 women and 23 men) using 1.5T scanner. Spectra from 12 different voxels were obtained, covering frontal, paracentral, and parietal white and gray matter. Three dominant signals were analyzed: NAA, tCr and Cho, and expressed as ratios of Cho/tCr, NAA/tCr, NAA/Cho. RESULTS: There was statistically significant gender difference between Cho/Cr and NAA/Cr metabolites ratio in only one location - the right frontal parafalcine cortex. There was no statistically significant difference in NAA/Cho ratio between men and women. CONCLUSION: Our study suggests that right frontal parafalcine cortex is a sexually dysmorphic area and supports the value of multivoxel MRS as a method able to define spatial biochemical heterogeneity of the cerebral tissue.

Color Doppler ultrasonography and multislice computer tomography angiography in carotid plaque detection and characterization.

BACKGROUND/AIM: Cerebrovascular diseases are the third leading cause of mortality in the world, following malignant and cardiovascular diseases. Therefore, their timely and precise diagnostics is of great importance. The aim of this study was to compare duplex scan Color Doppler ultrasonography (CDU) with multislice computed tomography angiography (MSCTA) in detection of morphological and functional disorders at extracranial level of carotid arteries. METHODS: The study included 75 patients with 150 carotid arteries examined in the period from January 2008 to April 2009. The patients were firstly examined by CDU, then MSCTA, followed by the surgery of extracranial segment of carotid arteries. In 10 patients, the obtained material was referred for histopathological (HP) examination. We used both CDU and MSCT in the analysis of: plaque surface, plaque structure, degree of stenosis, and the presence of in-traplaque hemorrhage. RESULTS: The results obtained by CDU and MSCTA were first compared between themselves, and then to intraoperative findings. Retrospective analysis showed that MSCTA is more sensitive than CDU in assessment of plaque surface (for smooth plaques CDU 89%: MSCTA 97%; for plaques with irregular surface CDU 75% : MSCTA 87%; for ulcerations CDU 54%: MSCTA 87%). Regarding determination of plaque structure (mixed plaque CDU 66% : MSCTA 70%; correlation with HP findings CDU 94% : MSCTA 96%) and localization (CDU 63%: MSCTA 65%), and in terms of sensitivity and specificity, both methods showed almost the same results. Also, there is no statistical difference between these two methods for the degree of stenosis (CDU 96%: MSCTA 98%). CONCLUSION: Atherosclerotic disease of extracranial part of carotid arteries primarily affects population of middle-aged and elderly, showing more associated risk factors. Sensitivity and specificity of CDU and MSCTA regarding plaque composition, the degree of stenosis and plaque localization are almost the same. These results and the fact that there are no adverse effects (high radiation dose) compared to MSCTA indicate that CDU should be the initial method in diagnostic algorythm for carotid arteries.

Partial rhombencephalosynapsis: prenatal MR imaging diagnosis and postnatal follow up.

We present a case of partial rhombencephalosynapsis, diagnosed by magnetic resonance imaging (MRI), in fetus aged 27 gestational weeks, in a dizygotic twin pregnancy. The distinctive MRI features of this cerebellar malformation (segmental hypogenesis of the cerebellar vermis, partial fusion of the cerebellar hemispheres and dentate nuclei) without associated cerebral abnormalities were confirmed by 32-weeks prenatal and 3-months postnatal MRI studies. At the age of 12 months the affected twin had a slight delay in psychomotor development, mild hypotonia with normal cognitive development. To the authors' best knowledge, this is the first report of a fetal case with isolated partial rhombencephalosynapsis. Its MRI features enlarges the narrow spectrum of uncommon variants of rhombencephalosynapsis, and allow an accurate differentiation from other vermian and cerebellar anomalies with less favorable postnatal outcome.

[Magnetic resonance imaging and bone scintigraphy in bone metastasis detection: a comparative study].

BACKGROUND/AIM: Bone scintigraphy is well-known method for the detection of neoplastic lesions with a high sensitivity and, at the same time, a lower specificity. On the other hand magnetic resonance imaging (MRI) is previously established noninvasive imaging method regar ding its diagnostic specificity. The aim of this study was to determine the possibilities and to correlate two different diagnostic methods--bone scintigraphy and MRI in the detection of bone metastasis in the spine and pelvic bones. METHODS: A total of 123 patients who underwent both bone scintigraphy and spine and pelvic MRI on 1.5 T MR imager were enrolled in this study. Scans were subsequently analyzed in total and divided in regions of interest (cervical, upper, middle and lower thoracic, upper and lower lumbar and pelvic region, which includes sacral spinal segment); afterwards the total number of 585 mat ching regions were compared and statistically analyzed. RESULTS: The statistical analysis demonstrated significant correlation between the findings of both methods in total. Divided by regions of interest, significant degrees of correlation were demonstrated in all of them, except in the cervical spine region where the r-value was in the range of low correlation. CONCLUSION: Having a high mutual correlation, bone scintigraphy and MRI are to be considered as the complementary diagnostic methods in the detection of bone metastases. Still, increased diagnostic potential of MRI may highlights negative bone scintigraphy findings in the patients with solitary metastatic lesions or diffuse vertebral infiltration. Advances in the bone scintigraphy (single photon emission tomography--SPECT, SPECT-computed tomography--SPECT-CT) and MRI (whole body MRI, diffusion MRI), make it possible the diagnostic potential of both methods will result in a further improvement in bone metastasis detection.

Gender differences in brain areas involved in silent counting by means of fMRI.

BACKGROUND: Pattern of brain asymmetries varies with handedness, gender, age, and with variety of genetic and social factors. Large-scale neuroimaging analyses can optimize the detection of asymmetric features and confirm the factors that might modulate pattern of brain asymmetries. We attempted to evaluate eventual differences between genders in hemodynamic responses to a simple language task. METHODS: 12 healthy right-handed volunteers (age 24-46), 6 men and 6 women underwent fMRI scanning while performing the simple cognitive - language processing task - silent number counting in Serbian. RESULTS: Group analysis of hemodynamic responses shows activation in expected brain language areas of inferior frontal gyrus (IFG) and superior temporal gyrus (STG) in both hemispheres. In the male group, aside from dedicated language areas in IFG and STG, activation was noted in right frontal region and interhemispheric supplementary motor area. On the other hand, in the female group, besides activation in dedicated language areas, activation was noted, in right hippocampus, limbic brain and cerebellum bilaterally. CONCLUSIONS: Our results on differences in silent counting by means of fMRI suggest that those differences may be based on different brain pattern activation in men and women. The relation between performance, strategies and regional brain activation should be the topic of further studies when considering not only gender differences in language processing but also differences that may be attributed to the variations in the task details, stimuli, and the stimulus presentation methods.

[Dynamic magnetic resonance imaging of the cerebrospinal fluid flow within the cerebral aqueduct by different FISP 2D sequences].

BACKGROUND/AIM: A vast majority of current radiogical techniques, such as computerized tomography (CT) and magnetic resonance imaging (MRI) have great potencial of vizualization and delineation of cerebrospinal fuid spaces morphology within cerebral aqueduct. The aim of this study was to determine the possibilities of two differently acquired FISP (Fast Imaging with Steady State Precession) 2D MR sequences in the estimation of the pulsatile cerebrospinal fluid (CSF) flow intensity through the normal cerebral aqueduct. METHODS: Sixty eight volunteers underwent brain MRI on 1.5T MR imager with additionally performed ECG retrospectively gated FISP 2D sequences (first one, as the part of the standard software package, with following technical parameters: TR 40, TE 12, FA 17, Matrix: 192 x 256, Acq 1, and the second one, experimentally developed by our investigation team: TR 30, TE 12, FA 70, Matrix: 192 x 256, Acq 1) respectively at two fixed slice positions--midsagittal and perpendicular to cerebral aqueduct, displayed and evaluated by multiplegated images in a closed-loop cinematographic (CINE) format. RESULTS: Normal brain morphology with preserved patency of the cerebral aqueduct in all of 68 healthy volunteers was demonstrated on MRI examination. Cerebrospinal fluid flow within the cerebral aqueduct was distinguishable on both CINE MRI studies in midsagittal plane, but the estimation of intraaqueductal CSF flow in perpendicular plane was possible on CINE MRI studies acquired with experimentally improved FISP 2D (TR 30, FA 70) sequence only. CONCLUSION: Due to the changes of technical parameters CINE MRI study acquired with FISP 2D (TR 30, FA 70) in perpendicular plane demonstrated significantly higher capability in the estimation of the CSF pulsation intensity within the cerebral aqueduct.