Surrounding Brain Structures Research Articles

Late Removal of Brain-Penetrating Nails Adherent to Intracranial Arteries: A Case Report

BACKGROUND AND IMPORTANCE: Pneumatic nail guns are a rare cause of penetrating brain injury, and subsequent nail removal in the acute setting is well reported. However, reports of late removal or removal of nails adjacent to intracranial vessels are rare. In the delayed setting, scar formation around the nails and surrounding brain structures may complicate surgical removal. Here, we report a case of late removal of brain-penetrating nails adherent to the middle cerebral artery branches. CLINICAL PRESENTATION: A 70-year-old left-handed male presented with mild aphasia, vertigo, and facial nerve palsy. Imaging studies demonstrated two nails fired 2 months before in the right temporal lobe adjacent to the middle cerebral artery branches. The nails were surgically removed through a modified pterional approach after meticulous dissection of scar tissue adherent to the nails. Before removal, proximal vessel control was achieved. CONCLUSION: Brain-penetrating nail removal weeks after the original incident may be complicated by extensive scarring. This can be dealt with a generous craniotomy, proximal vessel control through microsurgical or endovascular means, and careful dissection of scar tissue around the nails.

An Improved Surgical Approach for Complete Interhemispheric Corpus Callosotomy Combined with Extended Frontoparietal Craniotomy in Mice.

Callosotomy is an invasive method that is used to study the role of interhemispheric functional connectivity in the brain. This surgical approach is technically demanding to perform in small laboratory animals, such as rodents, due to several methodological challenges. To date, there exist two main approaches for transecting the corpus callosum (CC) in rodents: trephine hole(s) or unilateral craniotomy, which cause damage to the cerebral cortex or the injury of large vessels, and may lead to intracranial hemorrhage and animal death. This study presents an improved surgical approach for complete corpus callosotomy in mice using an interhemispheric approach combined with bilateral and extended craniotomy across the midline. This study demonstrated that bilateral and extended craniotomy provided the visual space required for hemisphere and sinus retraction, thus keeping large blood vessels and surrounding brain structures intact under the surgical microscope using standardized surgical instruments. We also emphasized the importance of good post-operative care leading to an increase in overall animal survival following experimentation. This optimized surgical approach avoids extracallosal tissue and medium- to large-sized cerebral blood vessel damage in mice, which can provide higher study reproducibility/validity among animals when revealing the role of the CC in various neurological pathologies.

Predicting survival of glioblastoma from automatic whole-brain and tumor segmentation of MR images

Survival prediction models can potentially be used to guide treatment of glioblastoma patients. However, currently available MR imaging biomarkers holding prognostic information are often challenging to interpret, have difficulties generalizing across data acquisitions, or are only applicable to pre-operative MR data. In this paper we aim to address these issues by introducing novel imaging features that can be automatically computed from MR images and fed into machine learning models to predict patient survival. The features we propose have a direct anatomical–functional interpretation: They measure the deformation caused by the tumor on the surrounding brain structures, comparing the shape of various structures in the patient’s brain to their expected shape in healthy individuals. To obtain the required segmentations, we use an automatic method that is contrast-adaptive and robust to missing modalities, making the features generalizable across scanners and imaging protocols. Since the features we propose do not depend on characteristics of the tumor region itself, they are also applicable to post-operative images, which have been much less studied in the context of survival prediction. Using experiments involving both pre- and post-operative data, we show that the proposed features carry prognostic value in terms of overall- and progression-free survival, over and above that of conventional non-imaging features.

Estudo morfológico da glândula pineal de Alouatta belzebul

ABSTRACT The pineal is a neuroendocrine gland responsible for the synthesis and release of melatonin. It is present in the brain of vertebrates, but its morphology and location vary considerably among species. For the species Alouatta belzebul, although some anatomical aspects of the nervous system have been described, there is no information on the morphology and histological composition of this gland. Thus, the present study aimed to describe the morphological, morphometric, and histological aspects of the pineal of Alouatta belzebul. Seven adult specimens were dissected from which the location of the gland in relation to the surrounding brain structures was described, and its length and width were measured. Histological slides were then prepared and stained using hematoxylin-eosin and PAS techniques. It was observed that the pineal of Alouatta belzebul is located superior and cranial to the cerebellum, superior to the superior colliculi and below the splenium of the corpus callosum and was classified as sub-callosal. It had an average length of 2.6mm and an average width of 1.14mm. Histologically the gland is composed of irregular strands of pinealocytes and gliocytes. The pinealocytes showed pigments similar to melanin.

Deep automatic segmentation of brain tumours in interventional ultrasound data

Abstract Intraoperative imaging can assist neurosurgeons to define brain tumours and other surrounding brain structures. Interventional ultrasound (iUS) is a convenient modality with fast scan times. However, iUS data may suffer from noise and artefacts which limit their interpretation during brain surgery. In this work, we use two deep learning networks, namely UNet and TransUNet, to make automatic and accurate segmentation of the brain tumour in iUS data. Experiments were conducted on a dataset of 27 iUS volumes. The outcomes show that using a transformer with UNet is advantageous providing an efficient segmentation modelling long-range dependencies between each iUS image. In particular, the enhanced TransUNet was able to predict cavity segmentation in iUS data with an inference rate of more than 125 FPS. These promising results suggest that deep learning networks can be successfully deployed to assist neurosurgeons in the operating room.

High-Resolution Digital Panorama of Multiple Structures in Whole Brain of Alzheimer's Disease Mice.

Simultaneously visualizing Amyloid-β (Aβ) plaque with its surrounding brain structures at the subcellular level in the intact brain is essential for understanding the complex pathology of Alzheimer's disease, but is still rarely achieved due to the technical limitations. Combining the micro-optical sectioning tomography (MOST) system, whole-brain Nissl staining, and customized image processing workflow, we generated a whole-brain panorama of Alzheimer's disease mice without specific labeling. The workflow employed the steps that include virtual channel splitting, feature enhancement, iso-surface rendering, direct volume rendering, and feature fusion to extract and reconstruct the different signals with distinct gray values and morphologies. Taking advantage of this workflow, we found that the denser-distribution areas of Aβ plaques appeared with relatively more somata and smaller vessels, but show a dissimilar distributing pattern with nerve tracts. In addition, the entorhinal cortex and adjacent subiculum regions present the highest density and biggest diameter of plaques. The neuronal processes in the vicinity of these Aβ plaques showed significant structural alternation such as bending or abrupt branch ending. The capillaries inside or adjacent to the plaques were observed with abundant distorted micro-vessels and abrupt ending. Depicting Aβ plaques, somata, nerve processes and tracts, and blood vessels simultaneously, this panorama enables us for the first time, to analyze how the Aβ plaques interact with capillaries, somata, and processes at a submicron resolution of 3D whole-brain scale, which reveals potential pathological effects of Aβ plaques from a new cross-scale view. Our approach opens a door to routine systematic studies of complex interactions among brain components in mouse models of Alzheimer's disease.

Depiction of Cerebral Aneurysm Wall by Computational Fluid Dynamics (CFD) and Preoperative Illustration.

Introduction Preoperative illustration is a part of an important exercise to study the configuration, direction, and presence of any perforations, and is the weakest point in the wall of the cerebral aneurysm. The same illustration is used to study the surrounding brain structures to decide the best and safe surgical approach prior to any surgical procedure. With the evolution of the aneurysm wall study and study of flow dynamic within the involved artery and its aneurysm wall using computational fluid dynamics (CFD), a better surgical plan can be formulated to improve the flow dynamics. As one of the clinical applications of CFD, we propose a study using a composite image that combines preoperative illustration and CFD, which is traditionally widely used in neurosurgery. Methods and Materials We study the use of illustrations of the unruptured cerebral aneurysm of internal carotid-posterior communicating (ICPC) artery and anterior communicating artery (AcomA) treated at our hospital. The combinations of both preoperative illustrations and CFD images by using “ipad Pro” were used. Result and Conclusion Medical illustration in the preoperative study of unruptured cerebral aneurysm with combinations of CFD and surrounding brain structures is helpful to decide the surgical approaches and successful surgical treatments.

High-risk pituitary adenomas and strategies for predicting response to treatment.

High-risk pituitary adenomas are aggressive. They show clinical and imaging features similar to those of carcinomas, including infiltration of the surrounding brain structures, but lack cerebrospinal or systemic metastases. In addition, they display distinct behavior, including tendency for fast growth and frequent recurrences, which are difficult to control. The term "high-risk" adenoma was first introduced in the 4th edition of the World Health Organization Classification of Endocrine Tumors in 2017. Five defined adenoma types belong to this category, including sparsely granulated somatotroph, lactotroph in men, Crooke cell, silent corticotroph, and plurihormonal PIT-1 positive adenomas. The morphological and immunohistochemical characteristics of high-risk adenomas are herein described in detail. In addition, the clinical features and the treatment options are presented. This review focuses on predictive markers assessed by immunohistochemistry, which help clinicians to design the appropriate treatment strategies for high-risk adenomas. Somatostatin receptor status predicts effectiveness of postsurgical treatment with somatostatin analogs, and MGMT expression predicts response to treatment with temozolomide. This comprehensive review presents the clinical and pathological features of high-risk pituitary adenomas, underlines the contribution of immunohistochemistry, and emphasizes the leading role of pathology in the design of optimal clinical management.

Surgical Evacuation of Intracerebral Hemorrhage: The Potential Importance of Timing.

Surgical Evacuation of Intracerebral Hemorrhage: The Potential Importance of Timing.

The benefits of vestibular schwannoma treatment by the means of gamma knife radiosurgery. Literature review

Domantas Jakštas1, Gabija Pajedienė1, Monika Martusevičienė2 1Lithuanian University of Health Sciences, Medical Academy, Faculty of Medicine 2Lithuanian University of Health Sciences, Kaunas Hospital Abstract Vestibular schwannoma (VS), also known as acoustic neuroma, is a benign, slow-growing tumor that develops due to hyperproduction of Schwan‘s cells surrounding the balance and auditory nerves in the inner ear. Symptoms such as asymmetric hearing loss, tinnitus, dizziness, and imbalance occur as the tumor grows. Significant enlargement of the tumor may exhibit pressure on the surrounding brain structures, leading to various neurological deficits and life-threatening damage to the brain stem. Due to the complex localization of the tumor, surgical treatment is associated with a high risk of complications and more difficult recovery, leading to the increasing use of radiosurgical treatments. Gamma knife stereotaxic radiosurgery is a promising and effective treatment method that is increasingly used to treat VS. Aim: to collect publications on the treatment of vestibular schwannoma with stereotaxic radiosurgery using Gamma knife and to systematically evaluate the benefits provided by this method over traditional microsurgery. Methods. A comprehensive search of English-language literature in the PubMed database was performed. The search was performed using MeSH terms: Gamma knife, radiosurgery, stereotactic radiosurgery, vestibular schwannoma, acoustic neuroma. Article inclusion criteria: Article was published in English Article was not older than 15 years Article was describing the results of vestibular schwannoma treatment by the means of Gamma knife (LINAC radiosurgery and CyberKnife were excluded) Exclusion criteria: Articles, describing the use of other radiosurgery modalities, such as LINAC and CyberKnife Results: with the use of chosen keywords, 60 studies were found. After implementing inclusion and exclusion criteria, 31 articles were selected for further evaluation. After analyzing the information, presented in these articles, we have come to conclusion that Gamma Knife is an effective method of VS treatment, with an advantage as this method can avoid many of the complications associated with open surgical treatment, such as hearing loss, facial or trigeminal nerve dysfunction. Keywords: vestibular schwannoma, gamma knife, stereotactic radiosurgery. https://doi.org/10.53453/ms.2021.06.12

Giant Prolactinomas: Case Series and Review of the Literature

Giant prolactinomas are rare and constitute only 2-3% of prolactinomas. They are defined as prolactinomas greater than 4 cm in size with a prolactin level of > 1,000 µg/L. Unlike prolactinomas, giant prolactinomas have a male preponderance and present a decade earlier in men as compared to women. Giant prolactinomas may present with galactorrhea, irregular periods or decreased libido. Due to their large size, they can involve surrounding brain structures and may present with hydrocephalus, dizziness, seizures, deafness, and cognitive dysfunction. Laboratory assessment may reveal a falsely low prolactin level secondary to “hook effect” which is due to saturation of the capture and detection antibodies used in the assay. Dilution of the sample would show a paradoxical increase in prolactin levels confirming the hook effect. Magnetic resonance imaging (MRI) is warranted to assess the extent of the tumor. Dopamine agonists are the treatment of choice in giant prolactinomas and lead to rapid resolution of symptoms, normalization of prolactin levels, and reduction in the size of the tumors. Refractory giant prolactinomas may be treated with surgery, temozolomide or radiotherapy. Giant prolactinomas can pose unique diagnostic and management challenges because of atypical presentations and confounding laboratory assessments. We present four cases of giant prolactinomas each presenting in a unique manner and discuss the diagnostic and management dilemmas associated with them. J Endocrinol Metab. 2020;10(6):182-189 doi: https://doi.org/10.14740/jem652

Giant Prolactinomas: Case Series and Review of the Literature

Giant prolactinomas are rare and constitute only 2-3% of prolactinomas. They are defined as prolactinomas greater than 4 cm in size with a prolactin level of > 1,000 µg/L. Unlike prolactinomas, giant prolactinomas have a male preponderance and present a decade earlier in men as compared to women. Giant prolactinomas may present with galactorrhea, irregular periods or decreased libido. Due to their large size, they can involve surrounding brain structures and may present with hydrocephalus, dizziness, seizures, deafness, and cognitive dysfunction. Laboratory assessment may reveal a falsely low prolactin level secondary to “hook effect” which is due to saturation of the capture and detection antibodies used in the assay. Dilution of the sample would show a paradoxical increase in prolactin levels confirming the hook effect. Magnetic resonance imaging (MRI) is warranted to assess the extent of the tumor. Dopamine agonists are the treatment of choice in giant prolactinomas and lead to rapid resolution of symptoms, normalization of prolactin levels, and reduction in the size of the tumors. Refractory giant prolactinomas may be treated with surgery, temozolomide or radiotherapy. Giant prolactinomas can pose unique diagnostic and management challenges because of atypical presentations and confounding laboratory assessments. We present four cases of giant prolactinomas each presenting in a unique manner and discuss the diagnostic and management dilemmas associated with them. J Endocrinol Metab. 2020;10(6):182-189 doi: https://doi.org/10.14740/jem652

Evaluation of galectin 3 and phosphohistone H3 immunoexpression as prognostic markers for meningioma

Background Meningiomas are not uncommon tumors of central nervous system. Their incidence is ∼25.6% of intracranial tumors in Egypt. Usually, meningiomas do not invade the surrounding brain structures. However, some variants acquire invasive and infiltrative nature. Galectin 3 is found in many cell types. It is expressed in various cellular processes such as cell growth, apoptosis, adhesion, chemotaxis, and differentiation. It is also expressed in different malignancies. Usually it is correlated with tumor progression. Histone H3 phosphorylation is specific to mitosis in premitosis stage and late G2 phase. Phosphohistone H3 (PHH3) immunohistochemistry is significant for mitosis detection in malignancy, and its expression is usually linked to worse prognosis. Aim To study immunohistochemical expression of galectin 3 and PHH3 with other clinicopathological parameters of different grades of meningioma. Results Galectin 3 expressions were related significantly with large tumor size, advancing grade, and brain invasion. PHH3 high proliferative score was also significantly associated with large tumor size, advancing grade, presence of postoperative recurrence, and brain invasion. Conclusion PHH3 is involved in tumor recurrence. Both PHH3 and galectin 3 are involved in brain invasion. These molecules can be used as important potential therapeutic targets and predictors for meningioma prognosis.

Epilepsy in patients with pineal gland cyst

ObjectiveThe aim of the study is to describe types of epileptic seizures in patients with pineal gland cyst (PGC) and their outcome during follow up period (6–10 years). We wanted to determine whether patients with epilepsy differ in PGC volume and compression of the PGC on surrounding brain structures compared to patients with PGC, without epilepsy. Patients and methodsWe analyzed prospectivelly 92 patients with PGC detected on magnetic resonance (MR) of the brain due to various neurological symptoms during the period 2006–2010. Data on described compression of the PGC on surrounding brain structures and size of the PGC were collected. Results29 patients (16 women, 13 men), mean age 21.17 years had epilepsy and PGC (epilepsy group). 63 patients (44 women, 19 men), mean age 26.97 years had PGC without epilepsy (control group). Complex partial seizures were present in 8 patients, complex partial seizures with secondary generalization in 8 patients, generalized tonic clonic seizures (GTCS) in 10 and absance seizures in 3 patients. Mean PGC volume in epilepsy group was 855.93 mm3, in control group 651.59 mm3. There was no statistically significant difference between epilepsy and control group in PGC volume. Compression of PGC on surrounding brain structures was found in 3/29 patients (10.34%) in epilepsy group and in 11/63 patients (17.46%) in control group with no statistically significant difference between epilepsy and control group. All patients with epilepsy were put on antiepileptic therapy (AET). During the follow up period, 23 patients (79.31%) were seizure free, 3 patients (13.04%) had reduction in seizure frequency, whereas 3 patients had no improvement in seizure frequency. Two patients from epilepsy group and 3 patients from control group were operated with histologically confirmed diagnosis of PGC in 4, and pinealocytoma in 1 patient. ConclusionsIn patients with PGC, epileptic seizures were classified as: complex partial seizures (with or without secondary generalization), GTCS and absance seizures. All patients were put on AET. During follow up period 79.31% patients were seizure free. There was no difference in PGC volume, nor in described compression of the PGC on surrounding brain structures between epilepsy and control group. Based on our findings, pathomechanism of epileptic seizures in patients with PGC cannot be attributable solely to PGC volume or described compression on surrounding brain structures based on MRI findings.

Predisposing Factors Responsible for the Occurrence of Bacterial Purulent Meningoencephalitis

Bacterial purulent meningoencephalitis (BPME) is a life-threatening infectious disease caused by various pyogenic bacteria. The disease is defined as the inflammatory process of leptomeninges (visceral layer, pia mater and arachnoid membrane) and brain parenchyma with exudates in the subarachnoid space and surrounding brain structures. The aim of the study was to define the predisposing factors responsible for the occurrence of BPME, as well as the possible correlation between the presence of predisposing factors and patient demographic characteristics, etiology and outcome of the disease. This retrospective-prospective study included 90 patients with BPME confirmed by clinical, neuroradiological and laboratory findings. Multivariate logistic regression models were fitted to analyze the impact of the predisposing factors on the disease outcomes. Predisposing factors that were related to BPME were found in 61% of patients. Cranial trauma as the leading factor was recorded in 23.3% of patients, followed by previous neurological disease in 14.4% of patients, while 13 patients were exposed to previous chemotherapy or long-term corticosteroid therapy. Cardiovascular diseases were reported in 12.2% and diabetes in 7.8% of patients. The existence of cardiovascular diseases significantly influenced unfavorable outcome of the disease, i.e. ”deceased” in comparison to ”cured” (OR=8.418; 95% CI=1.007-76.270), independently of age and gender. None of the examined predisposing factors was significantly related to the ”recovered with sequels” outcome as compared with ”cured” outcome. Older age and presence of cardiovascular disease as a predisposing factor significantly increased the odds of the BPME unfavorable outcome ”deceased” as compared to ”cured” outcome.

Progressive histomorphometric analysis of the lateral ventricle and cerebral cortex of Wistar rats following kaolin-induced hydrocephalus

Context: Hydrocephalus results in ventriculomegaly following excess production and/or impaired drainage of cerebrospinal fluid. The lateral ventricle (LV) is surrounded by critical structures such as hippocampus and thalamus; its enlargement will adversely impact surrounding brain structures including the cerebral cortex. Aims: This study aims to evaluate the morphometry of cerebral cortex and LV in hydrocephalus over 4 weeks. Settings and Design: Fifty-one 3-week-old rats were divided into Groups A (experimental = 6; control = 5), B (experimental = 8; control = 6), C (experimental = 8; control = 6) and D (experimental = 6; control = 6), sacrificed at the end of 1, 2, 3 and 4 weeks, respectively. Materials and Methods: Experimental rats were induced by injection of 0.04 ml of 200 mg/ml kaolin suspension into the cisterna magnum under ketamine (90 mg/kbw) and diazepam (12.5 mg/kbw) anaesthesia. Rats were sacrificed by cervical dislocation and brain fixed in 10% formal saline. Brain slices at the level of the optic chiasma were processed and stained with haematoxylin and eosin. Statistical Analysis Used: One-way ANOVA and Student–Newman–Keuls test. Results: In experimental rats, lethargy, poor feeding, globular head and exophthalmos were noted. The LV width and the LV/cortical thickness (CT) ratio were significantly increased from the 1st to the 4th post-induction week (P Conclusions: White matter/cortical thinning and ventriculomegaly are acute-phase features, although cortical thinning lags behind others. Detachment of the choroid plexus and reversal of SWM thinning are features of chronicity.

Visualization of Anatomic Variation of the Anterior Septal Vein on Susceptibility-Weighted Imaging.

Background and PurposeUnderstanding the anatomy of the anterior septal vein (ASV) is critical for minimally invasive procedures to the third ventricle and for assessing lesion size and venous drainage in the anterior cranial fossa. Accordingly, this study evaluated topographic anatomy and anatomic variation of the ASV using susceptibility-weighted imaging (SWI).MethodsSixty volunteers were examined using a 3.0T MR system. The diameter of the ASV and distance between bilateral septal points were measured. ASVs were divided into types 1 (only drains frontal lobe) and 2 (drains both frontal lobe and head of the caudate nucleus). We evaluated the ASV-internal cerebral vein (ICV) junction based on its positional relationship with the appearance of a venous angle or a false venous angle and the foramen of Monro. Fused SW and T1-weighted images were used to observe positional relationships between the course of the ASV and the surrounding brain structures.ResultsThe ASV and its small tributaries were clearly visualized in 120 hemispheres (100%). The average diameter of ASVs was 1.05±0.17 mm (range 0.9–1.6 mm). The average distance between bilateral septal points was 2.23±1.03 mm (range 1.3–6.6 mm). The ASV types 1 and 2 were in 77 (64.2%) and 43 (35.8%) hemispheres, respectively. In 83 (69.2%) hemispheres, the ASV-ICV junction was situated at the venous angle and the posterior margin of the foramen of Monro. In 37 (30.8%) hemispheres, the ASV-ICV junction was situated beyond the posterior margin of the foramen of Monro. The average distance between the posteriorly located ASV-ICV junction and the posterior margin of the foramen of Monro was 6.41±3.95 mm (range 2.4–15.9 mm).ConclusionUsing SWI, the topographic anatomy and anatomic variation of the ASV were clearly demonstrated. Preoperative assessment of anatomic variation of the ASV may be advantageous for minimally invasive neurosurgical procedures.

Hypnosis for Awake Surgery of Low-grade Gliomas: Description of the Method and Psychological Assessment.

Awake craniotomy with intraoperative electric stimulation is a reliable method for extensive removal of low-grade gliomas while preserving the functional integrity of eloquent surrounding brain structures. Although fully awake procedures have been proposed, asleep-awake-asleep remains the standard technique. Anesthetic contraindications are the only limitation of this method, which is therefore not reliable for older patients with high-grade gliomas. To describe and assess a novel method for awake craniotomy based on hypnosis. We proposed a novel hypnosedation procedure to patients undergoing awake surgery for low-grade gliomas in our institution between May 2011 and April 2015. Surgical data were retrospectively recorded. The subjective experience of hypnosis was assessed by 3 standardized questionnaires: the Cohen Perceived Stress Scale, the Posttraumatic Stress Disorder Checklist Scale, the Peritraumatic Dissociative Experience Questionnaire, and a fourth questionnaire designed specifically for this study. Twenty-eight questionnaires were retrieved from 43 procedures performed on 37 patients. The Peritraumatic Dissociative Experience Questionnaire revealed a dissociation state in 17 cases. The Perceived Stress Scale was pathological in 8 patients. Two patients in this group stated that they would not accept a second hypnosedation procedure. The Posttraumatic Stress Disorder Checklist Scale revealed 1 case of posttraumatic stress disorder. Burr hole and bone flap procedures were the most frequently reported unpleasant events during opening (15 of 52 events). The main findings of our study are the effectiveness of the technique, which in all cases allowed resection of the tumor up to functional boundaries, and the positive psychological impact of the technique in most of the patients.

Abstract 585: WIF1 re-expression in glioblastoma impairs migration through downregulation of the lncRNA MALAT1

Abstract Glioblastoma is the most aggressive form of human glioma. Despite progress in brain tumor therapy the prognosis remains dismal with a median survival of 15 months. We have recently shown that WIF1, an inhibitor of the WNT pathway, is downregulated in glioblastoma where it functions as strong tumor suppressor gene. Indeed, WIF1 re-expression impairs cell growth, cell migration, induces a senescence-like phenotype, and inhibits tumorigenicity in several orthotopic xenograft models. To analyse the molecular mechanisms underlying the tumor suppressive functions of WIF1 we developed a TET-on inducible system. Gene expression profiling following WIF1 induction revealed several interesting candidate genes validated in additional cell lines. The gene with strongest downregulation in WIF1-induced cells was MALAT1. MALAT1 is a long non-coding RNA that has been associated with tumor aggressiveness and invasion. Hence, MALAT1 is a plausible candidate, and its downregulation may contribute to the attenuation of malignancy seen in WIF1 expressing cells. Preliminary results show that the expression of a MALAT1 specific short-hairpin drastically reduces the infiltrative capability of glioblastoma cells. Analysis of gene xpression profiles revealed that MALAT1 is overexpressed in glioblastoma as compared to non-tumoral brain. These observations suggest that MALAT1 may contribute to the aggressive phenotype of glioblastoma. Experiments to test the effect of downregulation of MALAT1 in vivo are now ongoing. The poor prognosis is partially due to the extremely high capability of glioblastoma cells to migrate and to invade the surrounding brain structures, impairing complete surgical resection, hence leading inevitably to recurrence. This provides the rational to further investigate implications of MALAT1 in migration. Understanding the mechanisms of high invasive properties may indeed lead to the identification of new targets for therapy. Citation Format: Irene Vassallo, Marie-France Hamou, Monika E. Hegi. WIF1 re-expression in glioblastoma impairs migration through downregulation of the lncRNA MALAT1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 585. doi:10.1158/1538-7445.AM2014-585

Secondary hemorrhagic progression of contusion foci in patients with traumatic brain injury

Introduction. Secondary posttraumatic changes of the brain often are determining in the clinical flow of traumatic brain injury (TBI). Prevention, detection and determination of treatment strategy at secondary hemorrhagic progression of contusion (SHPC) are very actual for neurotraumatology. Materials and methods. The results of 110 injured persons with TBI were analyzed. Results. It was found that SHPC occurs in 50% patients with TBI, as in areas of primary brain damage as in remote areas on the other side of the brain during 12 h ad also after 3–4 days. SHPC often is revealed in patients with subdural hematoma. The bigger contusion foci, the higher the probability of their progression and the need of surgical decompression. Conclusions. SHPC is one of most important TBI complications associated with considerable risk of clinical deterioration and serious cause of morbidity and lethality. Treatment tactics depends on severity of volumetric effect on surrounding brain structures and manifestations of compression-dislocation syndrome.