Association of The IDH1 C.395G>A (R132H) Mutation with Histological Type in Malay Brain Tumors

PubMed Central

Yusoff, Abdul Aziz Mohamed; Zulfakhar, Fatin Najwa; Sul’ain, Mohd Dasuki; Idris, Zamzuri; Abdullah, Jafri Malin

2016-01-01

Background: Brain tumors, constituting one of the most deadly forms of cancer worldwide, result from the accumulation of multiple genetic and epigenetic alterations in genes and signaling pathways. Isocitrate dehydrogenase enzyme isoform 1 (IDH1) mutations are frequently identified in primary brain tumors and acute myeloid leukemia. Studies on IDH1 gene mutations have been extensively performed in various populations worldwide but not in Malaysia. This work was conducted to study the prevalence of IDH1 c.395G>A (R132H) hotspot mutations in a group of Malaysian patients with brain tumors in order to gain local data for the IDH1 mutation profile in our population. Methods: Mutation analysis of c.395G>A (R132H) of IDH1 was performed in 40 brain tumor specimens by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) and then verified by direct sequencing. Associations between the IDH1 c.395G>A (R132H) mutation and clinicopathologic characteristics were also analyzed. Results: The IDH1 c.395G>A (R132H) mutation was detected in 14/40 patients (35%). A significant association was found with histological tumor types, but not with age, gender and race. Conclusions: IDH1 is frequently mutated and associated with histological subtypes in Malay brain tumors. PMID:28125199

Changes in Cognition and Decision Making Capacity Following Brain Tumour Resection: Illustrated with Two Cases.

PubMed

Veretennikoff, Katie; Walker, David; Biggs, Vivien; Robinson, Gail

2017-09-24

Changes in cognition, behaviour and emotion frequently occur in patients with primary and secondary brain tumours. This impacts the ability to make considered decisions, especially following surgical resection, which is often overlooked in the management of patients. Moreover, the impact of cognitive deficits on decision making ability affects activities of daily living and functional independence. The assessment process to ascertain decision making capacity remains a matter of debate. One avenue for evaluating a patient's ability to make informed decisions in the context of brain tumour resection is neuropsychological assessment. This involves the assessment of a wide range of cognitive abilities on standard measurement tools, providing a robust approach to ascertaining capacity. Evidence has shown that a comprehensive and tailored neuropsychological assessment has greater sensitivity than brief cognitive screening tools to detect subtle and/or specific cognitive deficits in brain tumours. It is the precise nature and severity of any cognitive deficits that determines any implications for decision making capacity. This paper focuses on cognitive deficits and decision making capacity following surgical resection of both benign and malignant, and primary and secondary brain tumours in adult patients, and the implications for patients' ability to consent to future medical treatment and make decisions related to everyday activities.

Changes in Cognition and Decision Making Capacity Following Brain Tumour Resection: Illustrated with Two Cases

PubMed Central

Veretennikoff, Katie; Walker, David; Biggs, Vivien; Robinson, Gail

2017-01-01

Changes in cognition, behaviour and emotion frequently occur in patients with primary and secondary brain tumours. This impacts the ability to make considered decisions, especially following surgical resection, which is often overlooked in the management of patients. Moreover, the impact of cognitive deficits on decision making ability affects activities of daily living and functional independence. The assessment process to ascertain decision making capacity remains a matter of debate. One avenue for evaluating a patient’s ability to make informed decisions in the context of brain tumour resection is neuropsychological assessment. This involves the assessment of a wide range of cognitive abilities on standard measurement tools, providing a robust approach to ascertaining capacity. Evidence has shown that a comprehensive and tailored neuropsychological assessment has greater sensitivity than brief cognitive screening tools to detect subtle and/or specific cognitive deficits in brain tumours. It is the precise nature and severity of any cognitive deficits that determines any implications for decision making capacity. This paper focuses on cognitive deficits and decision making capacity following surgical resection of both benign and malignant, and primary and secondary brain tumours in adult patients, and the implications for patients’ ability to consent to future medical treatment and make decisions related to everyday activities. PMID:28946652

Blood-brain barrier dysfunction and amyloid precursor protein accumulation in microvascular compartment following ischemia-reperfusion brain injury with 1-year survival.

PubMed

Pluta, R

2003-01-01

This study examined the late microvascular consequences of brain ischemia due to cardiac arrest in rats. In reacted vibratome sections scattered foci of extravasated horseradish peroxidase were noted throughout the brain and did not appear to be restricted to any specific area of brain. Ultrastructural investigation of leaky sites frequently presented platelets adhering to the endothelium of venules and capillaries. Endothelial cells demonstrated pathological changes with evidence of perivascular astrocytic swelling. At the same time, we noted C-terminal of amyloid precursor protein/beta-amyloid peptide (CAPP/betaA) deposits in cerebral blood vessels, with a halo of CAPP/betaA immunoreactivity in the surrounding parenchyma suggested diffusion of CAPP/betaA out of the vascular compartment. Changes predominated in the hippocampus, cerebral and entorhinal cortex, corpus callosum, thalamus, basal ganglia and around the lateral ventricles. These data implicate delayed abnormal endothelial function of vessels following ischemia-reperfusion brain injury as a primary event in the pathogenesis of the recurrent cerebral infarction.

Combination of isocitrate dehydrogenase 1 (IDH1) mutation and podoplanin expression in brain tumors identifies patients at high or low risk of venous thromboembolism.

PubMed

Mir Seyed Nazari, P; Riedl, J; Preusser, M; Posch, F; Thaler, J; Marosi, C; Birner, P; Ricken, G; Hainfellner, J A; Pabinger, I; Ay, C

2018-06-01

Essentials Risk stratification for venous thromboembolism (VTE) in patients with brain tumors is challenging. Patients with IDH1 wildtype and high podoplanin expression have a 6-month VTE risk of 18.2%. Patients with IDH1 mutation and no podoplanin expression have a 6-month VTE risk of 0%. IDH1 mutation and podoplanin overexpression in primary brain tumors appear to be exclusive. Background Venous thromboembolism (VTE) is a frequent complication in primary brain tumor patients. Independent studies revealed that podoplanin expression in brain tumors is associated with increased VTE risk, whereas the isocitrate dehydrogenase 1 (IDH1) mutation is associated with very low VTE risk. Objectives To investigate the interrelation between intratumoral podoplanin expression and IDH1 mutation, and their mutual impact on VTE development. Patients/Methods In a prospective cohort study, intratumoral IDH1 R132H mutation and podoplanin were determined in brain tumor specimens (mainly glioma) by immunohistochemistry. The primary endpoint of the study was symptomatic VTE during a 2-year follow-up. Results All brain tumors that expressed podoplanin to a medium-high extent showed also an IDH1 wild-type status. A score based on IDH1 status and podoplanin expression levels allowed prediction of the risk of VTE. Patients with wild-type IDH1 brain tumors and high podoplanin expression had a significantly increased VTE risk compared with those with mutant IDH1 tumors and no podoplanin expression (6-month risk 18.2% vs. 0%). Conclusions IDH1 mutation and podoplanin overexpression seem to be exclusive. Although brain tumor patients with IDH1 mutation are at very low risk of VTE, the risk of VTE in patients with IDH1 wild-type tumors is strongly linked to podoplanin expression levels. © 2018 International Society on Thrombosis and Haemostasis.

High predictive value of brain MRI imaging in primary mitochondrial respiratory chain deficiency.

PubMed

de Beaurepaire, Isaure; Grévent, David; Rio, Marlène; Desguerre, Isabelle; de Lonlay, Pascale; Levy, Raphaël; Dangouloff-Ros, Volodia; Bonnefont, Jean-Paul; Barcia, Giulia; Funalot, Benoit; Besmond, Claude; Metodiev, Metodi D; Ruzzenente, Benedetta; Assouline, Zahra; Munnich, Arnold; Rötig, Agnès; Boddaert, Nathalie

2018-06-01

Because the mitochondrial respiratory chain (RC) is ubiquitous, its deficiency can theoretically give rise to any symptom in any organ or tissue at any age with any mode of inheritance, owing to the twofold genetic origin of respiratory enzyme machinery, that is, nuclear and mitochondrial. Not all respiratory enzyme deficiencies are primary and secondary or artefactual deficiency is frequently observed, leading to a number of misleading conclusions and inappropriate investigations in clinical practice. This study is aimed at investigating the potential role of brain MRI in distinguishing primary RC deficiency from phenocopies and other aetiologies. Starting from a large series of 189 patients (median age: 3.5 years (8 days-56 years), 58% males) showing signs of RC enzyme deficiency, for whom both brain MRIs and disease-causing mutations were available, we retrospectively studied the positive predictive value (PPV) and the positive likelihood ratio (LR+) of brain MRI imaging and its ability to discriminate between two groups: primary deficiency of the mitochondrial RC machinery and phenocopies. Detection of (1) brainstem hyperintensity with basal ganglia involvement (P≤0.001) and (2) lactate peak with either brainstem or basal ganglia hyperintensity was highly suggestive of primary RC deficiency (P≤0.01). Fourteen items had a PPV>95% and LR+ was greater than 9 for seven signs. Biallelic SLC19A3 mutations represented the main differential diagnosis. Non-significant differences between the two groups were found for cortical/subcortical atrophy, leucoencephalopathy and involvement of caudate nuclei, spinothalamic tract and corpus callosum. Based on these results and owing to invasiveness of skeletal muscle biopsies and cost of high-throughput DNA sequencing, we suggest giving consideration to brain MRI imaging as a diagnostic marker and an informative investigation to be performed in patients showing signs of RC enzyme deficiency. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Bevacizumab Plus Radiosurgery for Nonsquamous Non-Small Cell Lung Cancer Patients with Brain Metastases: Safe Combination?

PubMed

Guinde, Julien; Carron, Romain; Tomasini, Pascale; Greillier, Laurent; Régis, Jean; Barlesi, Fabrice

2017-11-01

In the context of bronchial cancers, the brain is one of the most frequent sites for metastases. Local treatments of these metastases have evolved and are often combined to obtain greater efficiency, while the main objective remains to reduce the symptoms. Radiosurgery is currently used as a primary option for patients harboring few numbers of small to middle-sized brain metastases. In nonsquamous non-small cell lung cancer (NSCLC), chemotherapy is often associated with bevacizumab. Our goal was to assess the safety of this early combination. Six patients with advanced nonsquamous NSCLC were treated with radiosurgery for the management of their brain metastases (n = 40), followed within <4 weeks by a treatment with bevacizumab. No systemic or cerebral adverse event of grade 3 (intratumoral or parenchymal hemorrhage) or unexpected toxicity secondary to bevacizumab has been indexed. Radiosurgery may be safely combined with bevacizumab quite early on for patients with nonsquamous NSCLC with brain metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

Use of primary cultures of Kenyon cells from bumblebee brains to assess pesticide side effects.

PubMed

Wilson, Daniel E; Velarde, Rodrigo A; Fahrbach, Susan E; Mommaerts, Veerle; Smagghe, Guy

2013-09-01

Bumblebees are important pollinators in natural and agricultural ecosystems. The latter results in the frequent exposure of bumblebees to pesticides. We report here on a new bioassay that uses primary cultures of neurons derived from adult bumblebee workers to evaluate possible side-effects of the neonicotinoid pesticide imidacloprid. Mushroom bodies (MBs) from the brains of bumblebee workers were dissected and dissociated to produce cultures of Kenyon cells (KCs). Cultured KCs typically extend branched, dendrite-like processes called neurites, with substantial growth evident 24-48 h after culture initiation. Exposure of cultured KCs obtained from newly eclosed adult workers to 2.5 parts per billion (ppb) imidacloprid, an environmentally relevant concentration of pesticide, did not have a detectable effect on neurite outgrowth. By contrast, in cultures prepared from newly eclosed adult bumblebees, inhibitory effects of imidacloprid were evident when the medium contained 25 ppb imidacloprid, and no growth was observed at 2,500 ppb. The KCs of older workers (13-day-old nurses and foragers) appeared to be more sensitive to imidacloprid than newly eclosed adults, as strong effects on KCs obtained from older nurses and foragers were also evident at 2.5 ppb imidacloprid. In conclusion, primary cultures using KCs of bumblebee worker brains offer a tool to assess sublethal effects of neurotoxic pesticides in vitro. Such studies also have the potential to contribute to the understanding of mechanisms of plasticity in the adult bumblebee brain. © 2013 Wiley Periodicals, Inc.

[Specificities of the logopenic variant of primary progressive aphasia].

PubMed

Magnin, E; Teichmann, M; Martinaud, O; Moreaud, O; Ryff, I; Belliard, S; Pariente, J; Moulin, T; Vandel, P; Démonet, J-F

2015-01-01

The logopenic variant of primary progressive aphasia is a syndrome with neuropsychological and linguistic specificities, including phonological loop impairment for which diagnosis is currently mainly based on the exclusion of the two other variants, semantic and nonfluent/agrammatic primary progressive aphasia. The syndrome may be underdiagnosed due (1) to mild language difficulties during the early stages of the disease or (2) to being mistaken for mild cognitive impairment or Alzheimer's disease when the evaluation of episodic memory is based on verbal material and (3) finally, it is not uncommon that the disorders are attributed to psychiatric co-morbidities such as, for example, anxiety. Moreover, compared to other variants of primary progressive aphasia, brain abnormalities are different. The left temporoparietal junction is initially affected. Neuropathology and biomarkers (cerebrospinal fluid, molecular amyloid nuclear imaging) frequently reveal Alzheimer's disease. Consequently this variant of primary progressive aphasia does not fall under the traditional concept of frontotemporal lobar degeneration. These distinctive features highlight the utility of correct diagnosis, classification, and use of biomarkers to show the neuropathological processes underlying logopenic primary progressive aphasia. The logopenic variant of primary progressive aphasia is a specific form of Alzheimer's disease frequently presenting a rapid decline; specific linguistic therapies are needed. Further investigation of this syndrome is needed to refine screening, improve diagnostic criteria and better understand the epidemiology and the biological mechanisms involved. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

α-synuclein transfer through tunneling nanotubes occurs in SH-SY5Y cells and primary brain pericytes from Parkinson’s disease patients

PubMed Central

Dieriks, Birger Victor; Park, Thomas I-H.; Fourie, Chantelle; Faull, Richard L. M.; Dragunow, Mike; Curtis, Maurice A.

2017-01-01

Parkinson’s disease (PD) is characterized by the presence of inclusions known as Lewy bodies, which mainly consist of α-synuclein (α-syn) aggregates. There is growing evidence that α-syn self-propagates in non-neuronal cells, thereby contributing to the progression and spread of PD pathology in the brain. Tunneling nanotubes (TNTs) are long, thin, F-actin-based membranous channels that connect cells and have been proposed to act as conduits for α-syn transfer between cells. SH-SY5Y cells and primary human brain pericytes, derived from postmortem PD brains, frequently form TNTs that allow α-syn transfer and long-distance electrical coupling between cells. Pericytes in situ contain α-syn precipitates like those seen in neurons. Exchange through TNTs was rapid, but dependent on the size of the protein. Proteins were able to spread throughout a network of cells connected by TNTs. Transfer through TNTs was not restricted to α-syn; fluorescent control proteins and labeled membrane were also exchanged through TNTs. Most importantly the formation of TNTs and transfer continued during mitosis. Together, our results provide a detailed description of TNTs in SH-SY5Y cells and human brain PD pericytes, demonstrating their role in α-syn transfer and further emphasize the importance that non-neuronal cells, such as pericytes play in disease progression. PMID:28230073

P15.04DEVELOPMENT OF A NEW QUESTIONNAIRE TO MEASURE INSTRUMENTAL ACTIVITIES OF DAILY LIVING (I-ADL) IN PATIENTS WITH PRIMARY BRAIN TUMOURS: RESULTS OF PHASE 1

PubMed Central

Dirven, L.; Meijer, W.; Sikkes, S.A.M.; Reijneveld, J.C.; Aaronson, N.K.; Uitdehaag, B.M.J.; Taphoorn, M. J. B.

2014-01-01

BACKGROUND: Next to health-related quality of life, information on daily life functioning in brain tumour patients is essential. Instrumental Activities of Daily Living (I-ADL) are complex daily activities, such as food preparation and shopping. I-ADL may be negatively influenced by a cognitive decline, characteristic of brain tumor patients. OBJECTIVE: In the first phase of this project, we generated a provisional list of items measuring I-ADL that are relevant for primary brain tumour patients. METHODS: Questions from the Amsterdam IADL Questionnaire®, a 70-item questionnaire developed and validated to measure I-ADL in patients with dementia, were evaluated for relevance to brain tumour patients. In addition, new activities were generated. In the first step, 6 professional experts in neuro-oncology and 10 primary brain tumour patient-proxy dyads were asked to evaluate items in the Amsterdam IADL Questionnaire®. Experts had to indicate if these activities (1) could be considered as I-ADL, (2) were affected in brain tumour patients and (3) were clearly formulated. Patients and their proxies only needed to answer the latter two questions. In the second step, the same 6 experts, and in addition 6 other patient-proxy dyads were asked to generate new activities. To do so, in-depth interviews were conducted. Decision rules were determined to aid in deciding which items to retain (step 1) or to add (step 2). Activities that were indicated as IADL, affected and clearly formulated were retained. Activities that were considered as IADL and affected, but not clearly formulated, were rephrased. New activities that were frequently generated were added to the existing list of items. RESULTS: In step 1, experts indicated that 37% of the activities described in the Amsterdam IADL questionnaire® fulfilled all three criteria: conform the definition of IADL, clearly formulated and affected in brain tumour patients. Twenty-three per cent of the activities were affected and conform the provided definition, but not clearly formulated. According to patients and their proxies, 19% and 17% of the activities were clearly formulated and affected in brain tumour patients, respectively. Moreover, 1-3% of the activities were indicated to be affected, but not clearly formulated. Several new activities (concerning social interaction and work) were generated in step 2. With the decision rules as guide, it was decided in consensus that a total of 30 questions of the Amsterdam IADL questionnaire® could also be used to measure I-ADL in primary brain tumour patients. In addition, 16 new questions covering other relevant activities for brain tumour patients were added. CONCLUSION: This first phase resulted in a provisional questionnaire of 46 items intending to measure I-ADL in primary brain tumour patients. The next step is to validate this provisional questionnaire in a larger sample of patients.

Clinical review: Neuromonitoring - an update

PubMed Central

2013-01-01

Critically ill patients are frequently at risk of neurological dysfunction as a result of primary neurological conditions or secondary insults. Determining which aspects of brain function are affected and how best to manage the neurological dysfunction can often be difficult and is complicated by the limited information that can be gained from clinical examination in such patients and the effects of therapies, notably sedation, on neurological function. Methods to measure and monitor brain function have evolved considerably in recent years and now play an important role in the evaluation and management of patients with brain injury. Importantly, no single technique is ideal for all patients and different variables will need to be monitored in different patients; in many patients, a combination of monitoring techniques will be needed. Although clinical studies support the physiologic feasibility and biologic plausibility of management based on information from various monitors, data supporting this concept from randomized trials are still required. PMID:23320763

RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis

PubMed Central

Hosonaga, Mari; Koya, Ikuko

2017-01-01

Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non–small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients. PMID:28210624

Brain tumor - primary - adults

MedlinePlus

... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

Primary lymphoma of the brain

MedlinePlus

Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

Memory Impairment in Multiple Sclerosis is Due to a Core Deficit in Initial Learning

PubMed Central

DeLuca, John; Leavitt, Victoria M.; Chiaravalloti, Nancy; Wylie, Glenn

2013-01-01

Persons with multiple sclerosis (MS) suffer memory impairment, but research on the nature of MS-related memory problems is mixed. Some have argued for a core deficit in retrieval, while others have identified deficient initial learning as the core deficit. We used a selective reminding paradigm to determine whether deficient initial learning or delayed retrieval represents the primary memory deficit in 44 persons with MS. Brain atrophy was measured from high-resolution MRIs. Regression analyses examined the impact of brain atrophy on (a) initial learning and delayed retrieval separately, and then (b) delayed retrieval controlling for initial learning. Brain atrophy was negatively associated with both initial learning and delayed retrieval (ps < .01), but brain atrophy was unrelated to retrieval when controlling for initial learning (p > .05). In addition, brain atrophy was associated with inefficient learning across initial acquisition trials, and brain atrophy was unrelated to delayed recall among MS subjects who successfully acquired the word list (although such learning frequently required many exposures). Taken together, memory deficits in MS are a result of deficits in initial learning; moreover, initial learning mediates the relationship between brain atrophy and subsequent retrieval, thereby supporting the core learning-deficit hypothesis of memory impairment in MS. PMID:23832311

What are the disruptive symptoms of behavioral disorders after traumatic brain injury? A systematic review leading to recommendations for good practices.

PubMed

Stéfan, Angélique; Mathé, Jean-François

2016-02-01

Behavioral disorders are major sequelae of severe traumatic brain injury. Before considering care management of these disorders, and in the absence of a precise definition for TBI-related behavioral disorder, it is essential to refine, according to the data from the literature, incidence, prevalence, predictive factors of commonly admitted disruptive symptoms. Systematic review of the literature targeting epidemiological data related to behavioral disorders after traumatic brain injury in order to elaborate good practice recommendations according to the methodology established by the French High Authority for Health. Two hundred and ninety-nine articles were identified. The responsibility of traumatic brain injury (TBI) in the onset of behavioral disorders is unequivocal. Globally, behavioral disorders are twice more frequent after TBI than orthopedic trauma without TBI (Masson et al., 1996). These disorders are classified into disruptive primary behaviors by excess (agitation 11-70%, aggression 25-39%, irritability 29-71%, alcohol abuse 7-26% drug abuse 2-20%), disruptive primary behaviors by default (apathy 20-71%), affective disorders - anxiety - psychosis (depression 12-76%, anxiety 0.8-24,5%, posttraumatic stress 11-18%, obsessive-compulsive disorders 1.2-30%, psychosis 0.7%), suicide attempts and suicide 1%. The improvement of care management for behavioral disorders goes through a first step of defining a common terminology. Four categories of posttraumatic behavioral clinical symptoms are defined: disruptive primary behaviors by excess, by default, affective disorders-psychosis-anxiety, suicide attempts and suicide. All these symptoms yield a higher prevalence than in the general population. They impact all of life's domains and are sustainable over time. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

QTc prolongation after brain surgery.

PubMed

Capparelli, Federico J; Abello, Mauricio; Patricio Maskin, L; Arista, Eugenia; Hlavnicka, Alejandro; Diaz, Maria Fernanda; Varela, Daniel; Wainsztein, Nestor A

2013-03-01

Abnormalities observed in the electrocardiogram (ECG) after acute central nervous system (CNS) events have been reported. Our objective was to assess the incidence of heart rate-corrected QT interval (QTc) prolongation in patients admitted to the intensive care unit (ICU) after brain surgery. Admission standard 12-lead ECGs were analyzed blinded to patient data. The QT interval was measured and Bazzett's formula was used to obtain QTc. Prolonged QTc was defined as ≧450 ms. We included 114 patients in the study. The mean age was 49±17 years. Brain neoplasm was the surgical indication in 90% of the patients. The mean QTc was 470±42 ms. Prolonged QTc was found in 71% patients. The heart rate-corrected QT interval was between 450 ms and 500 ms in 52% and >500 ms in 19% of the patients. The heart rate and concentration of serum glucose were higher in the prolonged QTc group. Only 7·5% of all patients had hypokalemia (≤3 mEq/l). In the prolonged QTc group 9·2% had hypokalemia compared to 3·2% in normal QTc patients (P = 0·406). There were no significant associations between categories of QTc and the serum levels of creatinine, magnesium, calcium, sodium, or pH. Phenytoin and metoclopramide were not frequently used in patients with prolonged QTc. This study supports our hypothesis that prolonged QTc is frequently observed after a brain surgery. Hypokalemia, hypocalcaemia, and drugs such as metoclopramide or phenytoin could not explain the high incidence of prolonged QTc. Brain injury during a surgical procedure may be one of the primary causes of QTc prolongation after neurosurgery.

Concomitant treatment of brain metastasis with whole brain radiotherapy [WBRT] and temozolomide [TMZ] is active and improves quality of life.

PubMed

Addeo, Raffaele; Caraglia, Michele; Faiola, Vincenzo; Capasso, Elena; Vincenzi, Bruno; Montella, Liliana; Guarrasi, Rosario; Caserta, Luigi; Del Prete, Salvatore

2007-01-25

Brain metastases (BM) represent one of the most frequent complications related to cancer, and their treatment continues to evolve. We have evaluated the activity, toxicity and the impact on Quality of Life (QoL) of a concomitant treatment with whole brain radiotherapy (WBRT) and Temozolomide (TMZ) in patients with brain metastases from solid tumors in a prospective Simon two stage study. Fifty-nine patients were enrolled and received 30 Gy WBRT with concomitant TMZ (75 mg/m2/day) for ten days, and subsequently TMZ (150 mg/m2/day) for up to six cycles. The primary end points were clinical symptoms and radiologic response. Five patients had a complete response, 21 patients had a partial response, while 18 patients had stable disease. The overall response rate (45%) exceeded the target activity per study design. The median time to progression was 9 months. Median overall survival was 13 months. The most frequent toxicities included grade 3 neutropenia (15%) and anemia (13%), and only one patient developed a grade 4 thrombocytopenia. Age, Karnofsky performance status, presence of extracranial metastases and the recursive partitioning analysis (RPA) were found to be predictive factors for response in patients. Overall survival (OS) and progression-free survival (PFS) were dependent on age and on the RPA class. We conclude that this treatment is well tolerated, with an encouraging objective response rate, and a significant improvement in quality of life (p < 0.0001) demonstrated by FACT-G analysis. All patients answered the questionnaires and described themselves as 'independent' and able to act on their own initiatives. Our study found a high level of satisfaction for QoL, this provides useful information to share with patients in discussions regarding chemotherapy treatment of these lesions.

Epidemiology and etiology of meningioma

PubMed Central

Wrensch, Margaret; Claus, Elizabeth B.

2010-01-01

Although most meningiomas are encapsulated and benign tumors with limited numbers of genetic aberrations, their intracranial location often leads to serious and potentially lethal consequences. They are the most frequently diagnosed primary brain tumor accounting for 33.8% of all primary brain and central nervous system tumors reported in the United States between 2002 and 2006. Inherited susceptibility to meningioma is suggested both by family history and candidate gene studies in DNA repair genes. People with certain mutations in the neurofibromatosis gene (NF2) have a very substantial increased risk for meningioma. High dose ionizing radiation exposure is an established risk factor for meningioma, and lower doses may also increase risk, but which types and doses are controversial or understudied. Because women are twice as likely as men to develop meningiomas and these tumors harbor hormone receptors, an etiologic role for hormones (both endogenous and exogenous) has been hypothesized. The extent to which immunologic factors influence meningioma etiology has been largely unexplored. Growing emphasis on brain tumor research coupled with the advent of new genetic and molecular epidemiologic tools in genetic and molecular epidemiology promise hope for advancing knowledge about the causes of intra-cranial meningioma. In this review, we highlight current knowledge about meningioma epidemiology and etiology and suggest future research directions. PMID:20821343

Grey matter brain injuries are common in Ugandan children with cerebral palsy suggesting a perinatal aetiology in full-term infants.

PubMed

Kakooza-Mwesige, Angelina; Byanyima, Rosemary K; Tumwine, James K; Eliasson, Ann-Christin; Forssberg, Hans; Flodmark, Olof

2016-06-01

There is limited literature on brain imaging studies of children with cerebral palsy (CP) in low and middle income countries. We investigated neuroimaging patterns of children with CP attending a tertiary referral centre in Uganda to determine how they differed from studies reported from high income countries and their relationship with prenatal and postnatal factors. Precontrast and postcontrast computed tomography (CT) scans of 78 CP children aged 2-12 years were conducted using a Philips MX 16-slice CT scanner. Two radiologists, blinded to the patient's clinical status, independently reviewed the scans. Abnormal CT scans were detected in 69% of the children sampled, with very few having primary white matter injuries (4%). Primary grey matter injuries (PGMI) (44%) and normal scans (31%) were most frequent. Children with a history of hospital admission following birth were three times more likely to have PGMI (odds ratio [OR] 2.8; 95% CI 1.1-7.1), suggesting a perinatal period with medical complications. Brain imaging patterns in this group of CP children differed markedly from imaging studies reported from high income countries, suggesting a perinatal aetiology in full-term infants and reduced survival in preterm infants. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Advances in the understanding of headache.

PubMed

Goadsby, Peter J

2005-01-01

Primary headache disorders account for a substantial part of the morbidity seen in medical practice and so advances in their understanding and management are of general importance. The classification of headache disorders has recently been revised, and the importance of frequent migraine, chronic (transformed) migraine and some important, albeit rarer, conditions that were previously not included has been recognized. Identification of the first genes for a migraine syndrome, namely familial hemiplegic migraine, and their classification as channelopathies opens up new understanding of these disorders and their possible pathophysiology. Functional brain imaging of migraine and cluster headache has placed the pathophysiology of these disorders firmly and clearly in the brain. As our understanding of migraine and related syndromes has increased, new therapies have been developed which reduce the significant disability associated with these important neurological disorders.

Current Management of Primary Central Nervous System Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultz, Christopher J.; Bovi, Joseph, E-mail: jbovi@mcw.ed

2010-03-01

Primary central nervous cell lymphoma (PCNSL) is an uncommon neoplasm of the brain, leptomeninges, and rarely the spinal cord. Initially thought to be characteristically associated with congenital, iatrogenic, or acquired immunosuppression, PCNSL is now recognized with increasing frequency in immunocompetent individuals. The role of surgery is limited to establishing diagnosis, as PCNSL is often multifocal with a propensity to involve the subarachnoid space. A whole-brain radiation volume has empirically been used to adequately address the multifocal tumor frequently encountered at the time of PCNSL diagnosis. Despite high rates of response after whole-brain radiotherapy (WBRT), rapid recurrence is common and long-termmore » survival is the exception. Chemotherapy alone or in combination with WBRT has more recently become the treatment of choice. Most effective regimens contain high-dose methotrexate and or other agents that are capable of penetrating the blood-brain barrier. High response rates and improved survival with the use of chemotherapy has led to treatment strategies that defer or eliminate WBRT in hopes of lessening the risk of neurotoxicity attributed to WBRT. Unfortunately, elimination of WBRT is also associated with a higher rate of relapse. Combined chemotherapy and WBRT regimens are now being explored that use lower total doses of radiation and altered fractionation schedules with the aim of maintaining high rates of tumor control while minimizing neurotoxicity. Pretreatment, multifactor prognostic indices have recently been described that may allow selection of treatment regimens that strike an appropriate balance of risk and benefit for the individual PCNSL patient.« less

Co-amplification of phosphoinositide 3-kinase enhancer A and cyclin-dependent kinase 4 triggers glioblastoma progression | Office of Cancer Genomics

Cancer.gov

Glioblastoma (GBM) is the most common primary brain tumor and has a dismal prognosis. Amplification of chromosome 12q13-q15 (Cyclin-dependent kinase 4 (CDK4) amplicon) is frequently observed in numerous human cancers including GBM. Phosphoinositide 3-kinase enhancer (PIKE) is a group of GTP-binding proteins that belong to the subgroup of centaurin GTPase family, encoded by CENTG1 located in CDK4 amplicon. However, the pathological significance of CDK4 amplicon in GBM formation remains incompletely understood.

What is dorso-lateral in the subthalamic Nucleus (STN)?--a topographic and anatomical consideration on the ambiguous description of today's primary target for deep brain stimulation (DBS) surgery.

PubMed

Coenen, Volker A; Prescher, Andreas; Schmidt, Thorsten; Picozzi, Piero; Gielen, Frans L H

2008-11-01

The most frequently used target for DBS in advanced Parkinson Disease (PD) is the sensorimotor subthalamic nucleus (STN), anatomically referred to as dorso-lateral STN [3]. Ambiguities arise, regarding the true meaning of this description in the STN. Does "dorsal" indicate posterior or superior? At its best, this definition assigns two directions in space to a three-dimensional structure. This paper evaluates the ambiguity and describes the sensorimotor part of the STN in stereotactic space.

Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis.

PubMed

Jurynczyk, Maciej; Geraldes, Ruth; Probert, Fay; Woodhall, Mark R; Waters, Patrick; Tackley, George; DeLuca, Gabriele; Chandratre, Saleel; Leite, Maria I; Vincent, Angela; Palace, Jacqueline

2017-03-01

Brain imaging characteristics of MOG antibody disease are largely unknown and it is unclear whether they differ from those of multiple sclerosis and AQP4 antibody disease. The aim of this study was to identify brain imaging discriminators between those three inflammatory central nervous system diseases in adults and children to support diagnostic decisions, drive antibody testing and generate disease mechanism hypotheses. Clinical brain scans of 83 patients with brain lesions (67 in the training and 16 in the validation cohort, 65 adults and 18 children) with MOG antibody (n = 26), AQP4 antibody disease (n = 26) and multiple sclerosis (n = 31) recruited from Oxford neuromyelitis optica and multiple sclerosis clinical services were retrospectively and anonymously scored on a set of 29 predefined magnetic resonance imaging features by two independent raters. Principal component analysis was used to perform an overview of patients without a priori knowledge of the diagnosis. Orthogonal partial least squares discriminant analysis was used to build models separating diagnostic groups and identify best classifiers, which were then tested on an independent cohort set. Adults and children with MOG antibody disease frequently had fluffy brainstem lesions, often located in pons and/or adjacent to fourth ventricle. Children across all conditions showed more frequent bilateral, large, brainstem and deep grey matter lesions. MOG antibody disease spontaneously separated from multiple sclerosis but overlapped with AQP4 antibody disease. Multiple sclerosis was discriminated from MOG antibody disease and from AQP4 antibody disease with high predictive values, while MOG antibody disease could not be accurately discriminated from AQP4 antibody disease. Best classifiers between MOG antibody disease and multiple sclerosis were similar in adults and children, and included ovoid lesions adjacent to the body of lateral ventricles, Dawson's fingers, T1 hypointense lesions (multiple sclerosis), fluffy lesions and three lesions or less (MOG antibody). In the validation cohort patients with antibody-mediated conditions were differentiated from multiple sclerosis with high accuracy. Both antibody-mediated conditions can be clearly separated from multiple sclerosis on conventional brain imaging, both in adults and children. The overlap between MOG antibody oligodendrocytopathy and AQP4 antibody astrocytopathy suggests that the primary immune target is not the main substrate for brain lesion characteristics. This is also supported by the clear distinction between multiple sclerosis and MOG antibody disease both considered primary demyelinating conditions. We identify discriminatory features, which may be useful in classifying atypical multiple sclerosis, seronegative neuromyelitis optica spectrum disorders and relapsing acute disseminated encephalomyelitis, and characterizing cohorts for antibody discovery. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Primary pulmonary hemangiopericytoma: 2 new cases].

PubMed

Essola, B; Remmelink, M; Kessler, R; Scillia, P; Rocmans, P

2003-10-01

We describe two new resected cases of primary pulmonary hemangiopericytoma and the review of cases published in the period 1954-2002. The first patient has a large pulmonary mass of the right apex revealed by scapular pain. The right upper lobectomy with free margins reveals hemangiopericytoma. Pelvic and pulmonary metastases appear two years after surgery, treated by two series of chemotherapy without clinical response. After acute nephrotoxicity controlled by hemodialysis, the patient dies with distant metastases three years and an half after thoracotomy. The second patient develops dry cough and thoracic pain with discovery of a cavitary mass in the right pulmonary field. Fine needle aspiration cytology suggests a mesenchymatous lesion. Three months after extended pneumonectomy, the intrathoracic tumour relapses and regresses partially under chemotherapy. Femoral and brain metastases are irradiated. The patient dies 22 months after thoracotomy. Histology and immunohistochemistry of both tumours closely related to solitary fibrous tumour confirm malignant hemangiopericytoma. Primary pulmonary hemangiopericytoma is rare and may be benign or malignant. Radical resection is the best treatment. Chemotherapy and radiotherapy may improve the prognosis. Compared with lung cancer, the tumour is a slow growing mass, often voluminous, with delayed symptoms, very few lymph node dissemination, rare brain metastasis, more frequent cutaneous or retroperitoneal dissemination, often after long-term and requiring indeed a 10 to 20 years follow-up.

Huntingtin interacting protein 1 is a novel brain tumor marker that associates with epidermal growth factor receptor.

PubMed

Bradley, Sarah V; Holland, Eric C; Liu, Grace Y; Thomas, Dafydd; Hyun, Teresa S; Ross, Theodora S

2007-04-15

Huntingtin interacting protein 1 (HIP1) is a multidomain oncoprotein whose expression correlates with increased epidermal growth factor receptor (EGFR) levels in certain tumors. For example, HIP1-transformed fibroblasts and HIP1-positive breast cancers have elevated EGFR protein levels. The combined association of HIP1 with huntingtin, the protein that is mutated in Huntington's disease, and the known overexpression of EGFR in glial brain tumors prompted us to explore HIP1 expression in a group of patients with different types of brain cancer. We report here that HIP1 is overexpressed with high frequency in brain cancers and that this overexpression correlates with EGFR and platelet-derived growth factor beta receptor expression. Furthermore, serum samples from patients with brain cancer contained anti-HIP1 antibodies more frequently than age-matched brain cancer-free controls. Finally, we report that HIP1 physically associates with EGFR and that this association is independent of the lipid, clathrin, and actin interacting domains of HIP1. These findings suggest that HIP1 may up-regulate or maintain EGFR overexpression in primary brain tumors by directly interacting with the receptor. This novel HIP1-EGFR interaction may work with or independent of HIP1 modulation of EGFR degradation via clathrin-mediated membrane trafficking pathways. Further investigation of HIP1 function in brain cancer biology and validation of its use as a prognostic or predictive brain tumor marker are now warranted.

Frequent occurrence of therapeutically reversible CMV-associated encephalopathy during radiotherapy of the brain.

PubMed

Goerig, Nicole L; Frey, Benjamin; Korn, Klaus; Fleckenstein, Bernhard; Überla, Klaus; Schmidt, Manuel A; Dörfler, Arnd; Engelhorn, Tobias; Eyüpoglu, Ilker; Rühle, Paul F; Putz, Florian; Semrau, Sabine; Gaipl, Udo S; Fietkau, Rainer

2016-12-01

Neurological decline during radio(chemo)therapy of the brain is often attributed to disease progression or side effects of radiotherapy. Diagnosis of opportunistic neurotropic infections such as cytomegalovirus (CMV) infections is uncommon, even though high-grade gliomas and some brain metastases are known to contain CMV particles. We prospectively examined the frequency of CMV encephalopathy during radiotherapy of the brain. Fifty patients requiring whole-brain radiotherapy for brain metastases (n = 27) or local radio(chemo)therapy of the brain for high-grade gliomas (n = 23) were observed in the prospective observational GLIO-CMV-01 study. MRIs and blood samples were obtained before, halfway through, and at the end of radiotherapy. MRIs were screened for disease progression or increased intracranial pressure. Blood was tested for anti-CMV immunoglobulin (Ig)M, anti-CMV IgG, and CMV DNA. Thirty-two of 50 (64%) patients were positive for anti-CMV IgG before radio(chemo)therapy. Fifteen of those 32 (48%) developed viremia during or up to 28 days after treatment. Thirteen of those 15 (87%) required treatment for CMV-associated encephalopathy. MRIs were negative for disease progression, edema, or bleeding. None of the patients negative for anti-CMV IgG developed viremia, suggesting a reactivation rather than a primary infection.In the group at risk consisting of anti-CMV IgG+ patients, age >65 (P = .004) and the amount of dexamethasone taken during radio(chemo)therapy (P = .004) were associated with an increased risk for CMV-associated encephalopathy. One hundred and fifty days after the start of radio(chemo)therapy, survival was 74% (14/19) (no encephalopathy) versus 54% (7/13) (encephalopathy) (odds ratio, 0.42; 95% CI, 0.03-1.86; P = .25). CMV reactivation frequently causes encephalopathy during radio(chemo)therapy of the brain. The unexpected high incidence of this infection makes it highly clinically relevant for every treating physician. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Optimal Treatment Decision for Brain Metastases of Unknown Primary Origin: The Role and Timing of Radiosurgery

PubMed Central

Han, Hyun Jin; Chang, Won Seok; Jung, Hyun Ho; Park, Yong Gou

2016-01-01

Background Up to 15% of all patients with brain metastases have no clearly detected primary site despite intensive evaluation, and this incidence has decreased with the use of improved imaging technology. Radiosurgery has been evaluated as one of the treatment modality for patients with limited brain metastases. In this study, we evaluated the effectiveness of radiosurgery for brain metastases from unknown primary tumors. Methods We retrospectively evaluated 540 patients who underwent gamma knife radiosurgery (GKRS) for brain metastases radiologically diagnosed between August 1992 and September 2007 in our institution. First, the brain metastases were grouped into metachronous, synchronous, and precocious presentations according to the timing of diagnosis of the brain metastases. Then, synchronous and precocious brain metastases were further grouped into 1) unknown primary; 2) delayed known primary; and 3) synchronous metastases according to the timing of diagnosis of the primary origin. We analyzed the survival time and time to new brain metastasis in each group. Results Of the 540 patients, 29 (5.4%) presented precocious or synchronous metastases (34 GKRS procedures for 174 lesions). The primary tumor was not found even after intensive and repeated systemic evaluation in 10 patients (unknown primary, 34.5%); found after 8 months in 3 patients (delayed known primary, 1.2%); and diagnosed at the same time as the brain metastases in 16 patients (synchronous metastasis, 55.2%). No statistically significant differences in survival time and time to new brain metastasis were found among the three groups. Conclusion Identification of a primary tumor before GKRS did not affect the patient outcomes. If other possible differential diagnoses were completely excluded, early GKRS can be an effective treatment option for brain metastases from unknown primary tumor. PMID:27867920

Neuropathology of Cervical Dystonia

PubMed Central

Prudente, C.N.; Pardo, C.A.; Xiao, J.; Hanfelt, J.; Hess, E.J.; LeDoux, M.S.; Jinnah, H.A.

2012-01-01

The aim of this study was to search for neuropathological changes in postmortem brain tissue of individuals with cervical dystonia (CD). Multiple regions of formalin-preserved brains were collected from patients with CD and controls and examined with an extensive battery of histopathological stains in a two-stage study design. In stage one, 4 CD brains underwent a broad screening neuropathological examination. In stage two, these 4 CD brains were combined with 2 additional CD brains, and the subjective findings were quantified and compared to 16 age-matched controls. The initial subjective neuropathological assessment revealed only two regions with relatively consistent changes. The substantia nigra had frequent ubiquitin-positive intranuclear inclusions known as Marinesco bodies. Additionally, the cerebellum showed patchy loss of Purkinje cells, areas of focal gliosis and torpedo bodies. Other brain regions showed minor or inconsistent changes. In the second stage of the analysis, quantitative studies failed to reveal significant differences in the numbers of Marinesco bodies in CD versus controls, but confirmed a significantly lower Purkinje cell density in CD. Molecular investigations revealed 4 of the CD cases and 2 controls to harbor sequence variants in non-coding regions of THAP1, and these cases had lower Purkinje cell densities regardless of whether they had CD. The findings suggest that subtle neuropathological changes such as lower Purkinje cell density may be found in primary CD when relevant brain regions are investigated with appropriate methods. PMID:23195594

Brain tumor - children

MedlinePlus

... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors.

PubMed

Capper, David; Weissert, Susanne; Balss, Jörg; Habel, Antje; Meyer, Jochen; Jäger, Diana; Ackermann, Ulrike; Tessmer, Claudia; Korshunov, Andrey; Zentgraf, Hanswalter; Hartmann, Christian; von Deimling, Andreas

2010-01-01

Heterozygous point mutations of isocitrate dehydrogenase (IDH)1 codon 132 are frequent in grade II and III gliomas. Recently, we reported an antibody specific for the IDH1R132H mutation. Here we investigate the capability of this antibody to differentiate wild type and mutated IDH1 protein in central nervous system (CNS) tumors by Western blot and immunohistochemistry. Results of protein analysis are correlated to sequencing data. In Western blot, anti-IDH1R132H mouse monoclonal antibody mIDH1R132H detected a specific band only in mutated tumors. Immunohistochemistry of 345 primary brain tumors demonstrated a strong cytoplasmic and weaker nuclear staining in 122 cases. Correlation with direct sequencing of 186 cases resulted in consensus of 177 cases. Genetic retesting of cases with conflicting findings resulted in a match of 186/186 cases, with all discrepancies resolving in favor of immunohistochemistry. Intriguing is the ability of mIDH1R132H to detect single infiltrating tumor cells. The very high frequency and the distribution of this mutation among specific brain tumor entities allow the highly sensitive and specific discrimination of various tumors by immunohistochemistry, such as anaplastic astrocytoma from primary glioblastoma or diffuse astrocytoma World Health Organization (WHO) grade II from pilocytic astrocytoma or ependymoma. Noteworthy is the discrimination of the infiltrating edge of tumors with IDH1 mutation from reactive gliosis.

Cleft Lip and Cleft Palate Surgery: Malpractice Litigation Outcomes.

PubMed

Justin, Grant A; Brietzke, Scott E

2017-01-01

  This study examined malpractice claims related to cleft lip and cleft palate surgery to identify common allegations and injuries and reviewed financial outcomes.   The WestlawNext legal database was analyzed for all malpractice lawsuits and settlements related to the surgical repair of cleft lip and palate.   Inclusion criteria included patients undergoing surgical repair of a primary cleft lip or palate or revision for complications of previous surgery. Data evaluated included patient demographics, type of operation performed, plaintiff allegation, nature of injury, and litigation outcomes.   A total of 36 cases were identified, with 12 unique cases from 1981 to 2006 meeting the inclusion criteria. Six cases (50%) were decided by a jury and six by settlement. Five cases involved complications related to the specific surgery, and the other seven were associated with any surgery and perioperative care of children and adults. Cleft palate repair (50%) was the most frequently litigated surgery. Postoperative negligent supervision was the most common allegation (42%) and resulted in a payout in each case (mean = $3,126,032). Death (42%) and brain injury (25%) were the most frequent injuries reported. Financial awards were made in nine cases (after adjusting for inflation, mean = $2,470,552, range = $0 to $7,704,585). The awards were significantly larger for brain injury than other outcomes ($4,675,395 versus $1,368,131 after adjusting for inflation, P = .0101).   Malpractice litigation regarding cleft lip and palate surgery is uncommon. However, significant financial awards involving perioperative brain injury have been reported.

Primary Angiitis of the Central Nervous System: Magnetic Resonance Imaging Spectrum of Parenchymal, Meningeal, and Vascular Lesions at Baseline.

PubMed

Boulouis, Grégoire; de Boysson, Hubert; Zuber, Mathieu; Guillevin, Loïc; Meary, Eric; Costalat, Vincent; Pagnoux, Christian; Naggara, Olivier

2017-05-01

Primary angiitis of the central nervous system remains challenging. To report an overview and pictorial review of brain magnetic resonance imaging findings in adult primary angiitis of the central nervous system and to determine the distribution of parenchymal, meningeal, and vascular lesions in a large multicentric cohort. Adult patients from the French COVAC cohort (Cohort of Patients With Primary Vasculitis of the Central Nervous System), with biopsy or angiographically proven primary angiitis of the central nervous system and brain magnetic resonance imaging available at the time of diagnosis were included. A systematic imaging review was performed blinded to clinical data. Sixty patients met inclusion criteria. Mean age was 45 years (±12.9). Patients initially presented focal deficit(s) (83%), headaches (53%), cognitive disorder (40%), and seizures (38.3%). The most common magnetic resonance imaging finding observed in 42% of patients was multiterritorial, bilateral, distal acute stroke lesions after small to medium artery distribution, with a predominant carotid circulation distribution. Hemorrhagic infarctions and parenchymal hemorrhages were also frequently found in the cohort (55%). Acute convexity subarachnoid hemorrhage was found in 26% of patients and 42% demonstrated pre-eminent leptomeningeal enhancement, which is found to be significantly more prevalent in biopsy-proven patients (60% versus 28%; P =0.04). Seven patients had tumor-like presentations. Seventy-seven percent of magnetic resonance angiographic studies were abnormal, revealing proximal/distal stenoses in 57% and 61% of patients, respectively. Adult primary angiitis of the central nervous system is a heterogenous disease, with multiterritorial, distal, and bilateral acute stroke being the most common pattern of parenchymal lesions found on magnetic resonance imaging. Our findings suggest a higher than previously thought prevalence of hemorrhagic transformation and other hemorrhagic manifestations. © 2017 American Heart Association, Inc.

Intracranial pressure monitoring after primary decompressive craniectomy in traumatic brain injury: a clinical study.

PubMed

Picetti, Edoardo; Caspani, Maria Luisa; Iaccarino, Corrado; Pastorello, Giulia; Salsi, Pierpaolo; Viaroli, Edoardo; Servadei, Franco

2017-04-01

Intracranial pressure (ICP) monitoring represents an important tool in the management of traumatic brain injury (TBI). Although current information exists regarding ICP monitoring in secondary decompressive craniectomy (DC), little is known after primary DC following emergency hematoma evacuation. Retrospective analysis of prospectively collected data. Inclusion criteria were age ≥18 years and admission to the intensive care unit (ICU) for TBI and ICP monitoring after primary DC. Exclusion criteria were ICU length of stay (LOS) <1 day and pregnancy. Major objectives were: (1) to analyze changes in ICP/cerebral perfusion pressure (CPP) after primary DC, (2) to evaluate the relationship between ICP/CPP and neurological outcome and (3) to characterize and evaluate ICP-driven therapies after DC. A total of 34 patients were enrolled. Over 308 days of ICP/CPP monitoring, 130 days with at least one episode of intracranial hypertension (26 patients, 76.5%) and 57 days with at least one episode of CPP <60 mmHg (22 patients, 64.7%) were recorded. A statistically significant relationship was discovered between the Glasgow Outcome Scale (GOS) scores and mean post-decompression ICP (p < 0.04) and between GOS and CPP minimum (CPPmin) (p < 0.04). After DC, persisting intracranial hypertension was treated with: barbiturate coma (n = 7, 20.6%), external ventricular drain (EVD) (n = 4, 11.8%), DC diameter widening (n = 1, 2.9%) and removal of newly formed hematomas (n = 3, 8.8%). Intracranial hypertension and/or low CPP occurs frequently after primary DC; their occurence is associated with an unfavorable neurological outcome. ICP monitoring appears useful in guiding therapy after primary DC.

Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross-sectional Study and Questionnaire Survey in China

PubMed Central

Luo, Xu-Ying; Hu, Ying-Hong; Cao, Xiang-Yuan; Kang, Yan; Liu, Li-Ping; Wang, Shou-Hong; Yu, Rong-Guo; Yu, Xiang-You; Zhang, Xia; Li, Bao-Shan; Ma, Zeng-Xiang; Weng, Yi-Bing; Zhang, Heng; Chen, De-Chang; Chen, Wei; Chen, Wen-Jin; Chen, Xiu-Mei; Du, Bin; Duan, Mei-Li; Hu, Jin; Huang, Yun-Feng; Jia, Gui-Jun; Li, Li-Hong; Liang, Yu-Min; Qin, Bing-Yu; Wang, Xian-Dong; Xiong, Jian; Yan, Li-Mei; Yang, Zheng-Ping; Dong, Chen-Ming; Wang, Dong-Xin; Zhan, Qing-Yuan; Fu, Shuang-Lin; Zhao, Lin; Huang, Qi-Bing; Xie, Ying-Guang; Huang, Xiao-Bo; Zhang, Guo-Bin; Xu, Wang-Bin; Xu, Yuan; Liu, Ya-Ling; Zhao, He-Ling; Sun, Rong-Qing; Sun, Ming; Cheng, Qing-Hong; Qu, Xin; Yang, Xiao-Feng; Xu, Ming; Shi, Zhong-Hua; Chen, Han; He, Xuan; Yang, Yan-Lin; Chen, Guang-Qiang; Sun, Xiu-Mei; Zhou, Jian-Xin

2016-01-01

Background: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. Methods: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. Results: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0–8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5–6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. Conclusions: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. Trial Registration: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073. PMID:27411450

Pancreatic solitary and synchronous metastasis from breast cancer: a case report and systematic review of controversies in diagnosis and treatment.

PubMed

Molino, Carlo; Mocerino, Carmela; Braucci, Antonio; Riccardi, Ferdinando; Trunfio, Martino; Carrillo, Giovanna; Vitale, Maria Giuseppa; Cartenì, Giacomo; De Sena, Guido

2014-01-05

Metastases from breast cancer cause the frequent involvement of lung, bone, liver, and brain, while the occurrence of metastases to the gastrointestinal tract is rare, and more frequently discovered after a primary diagnosis of breast cancer. Solitary pancreatic metastases from breast cancer, without widespread disease, are actually unusual, and only 19 cases have been previously described; truly exceptional is a solitary pancreatic metastasis becoming evident together with the primary breast cancer. A 68-year-old woman reported general fatigue, lethargy, and jaundice. Abdominal ultrasound (US) and magnetic resonance imaging (MRI) showed an ampulloma of Vater's papilla; moreover, a neoplastic nodule in the left breast was diagnosed. She underwent surgery for both breast cancer and ampulloma of Vater's papilla. Pathological examination of pancreatic specimen, however, did not confirm primary carcinoma of the duodenal papilla, but showed a metastatic involvement of pancreas from lobular breast cancer. Immunohistochemistry has been essential to confirm the origin of the malignancy: hormone receptors and mammaglobin were expressed in both the primary breast tumor and the pancreatic metastasis. This is one of the few reported cases in literature of an isolated and synchronous pancreatic metastasis from breast cancer, where the definitive diagnosis was obtained only after surgery. We discuss the controversies in this diagnosis and the choice of correct treatment. The surgical resection of solitary metastases can be performed in the absence of disseminated disease.

Neuroprotective effect of ethanol in acute carbon monoxide intoxication: A retrospective study.

PubMed

Kim, Hyuk-Hoon; Choi, Sang Chun; Chae, Minjung Kathy; Min, Young-Gi

2018-01-01

In acute carbon monoxide (CO) intoxication, treatment of neurologic injury and prevention of neurological sequelae are primary concerns. Ethanol is the one of the frequent substances which is co-ingested in intentional CO poisoning. Neuroprotective effect of ethanol was highlighted and demonstrated in isolated brain injury recently. We assessed the neuroprotective effect of ethanol in acute CO intoxication using magnetic resonance imaging (MRI).We retrospectively reviewed medical records for patients who visited an emergency medical center of a university-affiliated hospital during a period of 73 months, from March 2009 to April 2015. Enrolled patients were divided into 2 groups, patients with or without abnormal brain lesion in brain MRI. Multivariate logistic regression analysis was performed to assess the factors associated with brain injury in MRI.A total of 109 patients with acute CO intoxication were evaluated of which 66 (60.55%) tested positive in brain MRI. MRI lesion-positive patients were more likely to have electrocardiogram change, elevation of serum troponin I and s100 protein level and lower serum ethanol level. Serum ethanol positivity was an independent factor for prevalence of brain injury in MRI in acute CO poisoning.This study revealed that ethanol which is co-ingested in acute CO intoxication may work the neuroprotective effect and could consequence more favorable neurological outcome in acute CO intoxication. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Diagnosis of organic brain syndrome: an emergency department dilemma.

PubMed

Dubin, W R; Weiss, K J

1984-01-01

Delirium and dementia frequently pose a diagnostic dilemma for clinicians in the emergency department. The overlap of symptoms between organic brain syndrome and functional psychiatric illness, coupled with a dramatic presentation, often leads to a premature psychiatric diagnosis. In this paper, the authors discuss those symptoms of organic brain syndrome that most frequently generate diagnostic confusion in the emergency department and result in a misdiagnosis of functional illness.

Endothelial Cell Implantation and Survival within Experimental Gliomas

NASA Astrophysics Data System (ADS)

Lal, Bachchu; Indurti, Ravi R.; Couraud, Pierre-Olivier; Goldstein, Gary W.; Laterra, John

1994-10-01

The delivery of therapeutic genes to primary brain neoplasms opens new opportunities for treating these frequently fatal tumors. Efficient gene delivery to tissues remains an important obstacle to therapy, and this problem has unique characteristics in brain tumors due to the blood-brain and blood-tumor barriers. The presence of endothelial mitogens and vessel proliferation within solid tumors suggests that genetically modified endothelial cells might efficiently transplant to brain tumors. Rat brain endothelial cells immortalized with the adenovirus E1A gene and further modified to express the β-galactosidase reporter were examined for their ability to survive implantation to experimental rat gliomas. Rats received 9L, F98, or C6 glioma cells in combination with endothelial cells intracranially to caudate/putamen or subcutaneously to flank. Implanted endothelial cells were identified by β-galactosidase histochemistry or by polymerase chain reaction in all tumors up to 35 days postimplantation, the latest time examined. Implanted endothelial cells appeared to cooperate in tumor vessel formation and expressed the brain-specific endothelial glucose transporter type 1 as identified by immunohistochemistry. The proliferation of implanted endothelial cells was supported by their increased number within tumors between postimplantation days 14 and 21 (P = 0.015) and by their expression of the proliferation antigen Ki67. These findings establish that genetically modified endothelial cells can be stably engrafted to growing gliomas and suggest that endothelial cell implantation may provide a means of delivering therapeutic genes to brain neoplasms and other solid tumors. In addition, endothelial implantation to brain may be useful for defining mechanisms of brain-specific endothelial differentiation.

A multicenter study of primary brain tumor incidence in Australia (2000–2008)

PubMed Central

Dobes, Martin; Shadbolt, Bruce; Khurana, Vini G.; Jain, Sanjiv; Smith, Sarah F.; Smee, Robert; Dexter, Mark; Cook, Raymond

2011-01-01

There are conflicting reports from Europe and North America regarding trends in the incidence of primary brain tumor, whereas the incidence of primary brain tumors in Australia is currently unknown. We aimed to determine the incidence in Australia with age-, sex-, and benign-versus-malignant histology-specific analyses. A multicenter study was performed in the state of New South Wales (NSW) and the Australian Capital Territory (ACT), which has a combined population of >7 million with >97% rate of population retention for medical care. We retrospectively mined pathology databases servicing neurosurgical centers in NSW and ACT for histologically confirmed primary brain tumors diagnosed from January 2000 through December 2008. Data were weighted for patient outflow and data completeness. Incidence rates were age standardized and trends analyzed using joinpoint analysis. A weighted total of 7651 primary brain tumors were analyzed. The overall US-standardized incidence of primary brain tumors was 11.3 cases 100 000 person-years (±0.13; 95% confidence interval, 9.8–12.3) during the study period with no significant linear increase. A significant increase in primary malignant brain tumors from 2000 to 2008 was observed; this appears to be largely due to an increase in malignant tumor incidence in the ≥65-year age group. This collection represents the most contemporary data on primary brain tumor incidence in Australia. Whether the observed increase in malignant primary brain tumors, particularly in persons aged ≥65 years, is due to improved detection, diagnosis, and care delivery or a true change in incidence remains undetermined. We recommend a direct, uniform, and centralized approach to monitoring primary brain tumor incidence that can be independent of multiple interstate cancer registries. PMID:21727214

Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets

PubMed Central

Santagata, Sandro; Cahill, Daniel P.; Taylor-Weiner, Amaro; Jones, Robert T.; Van Allen, Eliezer M.; Lawrence, Michael S.; Horowitz, Peleg M.; Cibulskis, Kristian; Ligon, Keith L.; Tabernero, Josep; Seoane, Joan; Martinez-Saez, Elena; Curry, William T.; Dunn, Ian F.; Paek, Sun Ha; Park, Sung-Hye; McKenna, Aaron; Chevalier, Aaron; Rosenberg, Mara; Barker, Frederick G.; Gill, Corey M.; Van Hummelen, Paul; Thorner, Aaron R.; Johnson, Bruce E.; Hoang, Mai P.; Choueiri, Toni K.; Signoretti, Sabina; Sougnez, Carrie; Rabin, Michael S.; Lin, Nancy U.; Winer, Eric P.; Stemmer-Rachamimov, Anat; Meyerson, Matthew; Garraway, Levi; Gabriel, Stacey; Lander, Eric S.; Beroukhim, Rameen; Batchelor, Tracy T.; Baselga, Jose; Louis, David N.

2016-01-01

Brain metastases are associated with a dismal prognosis. Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown. We performed whole-exome sequencing of 86 matched brain metastases, primary tumors and normal tissue. In all clonally related cancer samples, we observed branched evolution, where all metastatic and primary sites shared a common ancestor yet continued to evolve independently. In 53% of cases, we found potentially clinically informative alterations in the brain metastases not detected in the matched primary-tumor sample. In contrast, spatially and temporally separated brain metastasis sites were genetically homogenous. Distal extracranial and regional lymph node metastases were highly divergent from brain metastases. We detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases. PMID:26410082

Profiles of Brain Metastases: Prioritization of Therapeutic Targets.

PubMed

Ferguson, Sherise D; Zheng, Siyuan; Xiu, Joanne; Zhou, Shouhao; Khasraw, Mustafa; Brastianos, Priscilla K; Kesari, Santosh; Hu, Jethro; Rudnick, Jeremy; Salacz, Michael E; Piccioni, David; Huang, Suyun; Davies, Michael A; Glitza, Isabella C; Heymach, John V; Zhang, Jianjun; Ibrahim, Nuhad K; DeGroot, John F; McCarty, Joseph; O'Brien, Barbara J; Sawaya, Raymond; Verhaak, Roeland G W; Reddy, Sandeep K; Priebe, Waldemar; Gatalica, Zoran; Spetzler, David; Heimberger, Amy B

2018-06-19

We sought to compare the tumor profiles of brain metastases from common cancers with those of primary tumors and extracranial metastases in order to identify potential targets and prioritize rational treatment strategies. Tumor samples were collected from both the primary and metastatic sites of non-small cell lung cancer, breast cancer, and melanoma from patients in locations worldwide, and these were submitted to Caris Life Sciences for tumor multiplatform analysis, including gene sequencing (Sanger and next-generation sequencing with a targeted 47-gene panel), protein expression (assayed by immunohistochemistry), and gene amplification (assayed by in situ hybridization). The data analysis considered differential protein expression, gene amplification, and mutations among brain metastases, extracranial metastases, and primary tumors. The analyzed population included: 16,999 unmatched primary tumor and/or metastasis samples: 8178 non-small cell lung cancers (5098 primaries; 2787 systemic metastases; 293 brain metastases), 7064 breast cancers (3496 primaries; 3469 systemic metastases; 99 brain metastases), and 1757 melanomas (660 primaries; 996 systemic metastases; 101 brain metastases). TOP2A expression was increased in brain metastases from all 3 cancers, and brain metastases overexpressed multiple proteins clustering around functions critical to DNA synthesis and repair and implicated in chemotherapy resistance, including RRM1, TS, ERCC1, and TOPO1. cMET was overexpressed in melanoma brain metastases relative to primary skin specimens. Brain metastasis patients may particularly benefit from therapeutic targeting of enzymes associated with DNA synthesis, replication, and/or repair. This article is protected by copyright. All rights reserved. © 2018 UICC.

Adeno-Associated Virus Serotypes 1, 8, and 9 Share Conserved Mechanisms for Anterograde and Retrograde Axonal Transport

PubMed Central

Castle, Michael J.; Gershenson, Zachary T.; Giles, April R.; Holzbaur, Erika L.F.

2014-01-01

Abstract Adeno-associated virus (AAV) vectors often undergo long-distance axonal transport after brain injection. This leads to transduction of brain regions distal to the injection site, although the extent of axonal transport and distal transduction varies widely among AAV serotypes. The mechanisms driving this variability are poorly understood. This is a critical problem for applications that require focal gene expression within a specific brain region, and also impedes the utilization of vector transport for applications requiring widespread delivery of transgene to the brain. Here, we compared AAV serotypes 1 and 9, which frequently demonstrate distal transduction, with serotype 8, which rarely spreads beyond the injection site. To examine directional AAV transport in vitro, we used a microfluidic chamber to apply dye-labeled AAV to the axon termini or to the cell bodies of primary rat embryonic cortical neurons. All three serotypes were actively transported along axons, with transport characterized by high velocities and prolonged runs in both the anterograde and retrograde directions. Coinfection with pairs of serotypes indicated that AAV1, 8, and 9 share the same intracellular compartments for axonal transport. In vivo, both AAV8 and 9 demonstrated anterograde and retrograde transport within a nonreciprocal circuit after injection into adult mouse brain, with highly similar distributions of distal transduction. However, in mass-cultured neurons, we found that AAV1 was more frequently transported than AAV8 or 9, and that the frequency of AAV9 transport could be enhanced by increasing receptor availability. Thus, while these serotypes share conserved mechanisms for axonal transport both in vitro and in vivo, the frequency of transport can vary among serotypes, and axonal transport can be markedly increased by enhancing vector uptake. This suggests that variability in distal transduction in vivo likely results from differential uptake at the plasma membrane, rather than fundamental differences in transport mechanisms among AAV serotypes. PMID:24694006

Primary headache pathophysiology in children: the contribution of clinical neurophysiology.

PubMed

Pro, S; Tarantino, S; Capuano, A; Vigevano, F; Valeriani, M

2014-01-01

Although primary headaches are very prevalent also in pediatric age, most neurophysiologic studies in these diseases concerned only the adulthood. The neurophysiologic investigation of the pathophysiological mechanisms subtending migraine and tension-type headache in children and adolescents could be particularly interesting, since during the developmental age the migrainous phenotype is scarcely influenced by many environmental factors that can typically act on adult headache patients. The neurophysiologic abnormality most frequently found in adult migraineurs, that is the reduced habituation of evoked potentials, was confirmed also in migraine children, although it was shown to involve also children with tension-type headache. Some studies showed abnormalities in the maturation of brain functions in migraine children and adolescents. While the visual system maturation seems slowed in young migraineurs, the psychophysiological mechanisms subtending somatosensory spatial attention in migraine children are more similar to those of healthy adults than to those of age-matched controls. There are some still unexplored fields that will have to be subjects of future studies. The nociceptive modality, which has been investigated in adult patients with primary headaches, should be studied also in pediatric migraine. Moreover, the technique of transcranial magnetic stimulation, not yet used in young migraineurs, will possibly provide further elements about brain excitability in migraine children. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Intracarotid Delivery of Drugs: The Potential and the Pitfalls

PubMed Central

Joshi, Shailendra; Meyers, Phillip M.; Ornstein, Eugene

2014-01-01

The major efforts to selectively deliver drugs to the brain in the last decade have relied on smart molecular techniques to penetrate the blood brain barrier while intraarterial drug delivery has drawn relatively little attention. In the last decade there have been rapid advances in endovascular techniques. Modern endovascular procedures can permit highly targeted drug delivery by intracarotid route. Intracarotid drug delivery can be the primary route of drug delivery or it could be used to facilitate the delivery of smart-neuropharmaceuticals. There have been few attempts to systematically understand the kinetics of intracarotid drugs. Anecdotal data suggests that intracarotid drug delivery is effective in the treatment of cerebral vasospasm, thromboembolic strokes, and neoplasms. Neuroanesthesiologists are frequently involved in the care of such high-risk patients. Therefore, it is necessary to understand the applications of intracarotid drug delivery and the unusual kinetics of intracarotid drugs. PMID:18719453

[Immunotherapy in brain tumors].

PubMed

De Carli, Emilie; Delion, Matthieu; Rousseau, Audrey

2017-02-01

Diffuse gliomas represent the most common primary central nervous system (CNS) tumors in adults and children alike. Glioblastoma is the most frequent and malignant form of diffuse glioma with a median overall survival of 15 months despite aggressive treatments. New therapeutic approaches are needed to prolong survival in this always fatal disease. The CNS has been considered for a long time as an immune privileged organ, in part because of the existence of the blood-brain barrier. Nonetheless, immunotherapy is a novel approach in the therapeutic management of glioma patients, which has shown promising results in several clinical trials, especially in the adult population. Vaccination, with or without dendritic cells, blockade of the immune checkpoints, and adoptive T cell transfer are the most studied modalities of diffuse glioma immunotherapy. The future most likely resides in combinatorial approaches, with administration of conventional treatments (surgery, radiochemotherapy) and immunotherapy following yet to determine schedules. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Market mechanisms protect the vulnerable brain.

PubMed

Ramchandran, Kanchna; Nayakankuppam, Dhananjay; Berg, Joyce; Tranel, Daniel; Denburg, Natalie L

2011-07-01

Markets are mechanisms of social exchange, intended to facilitate trading. However, the question remains as to whether markets would help or hurt individuals with decision-makings deficits, as is frequently encountered in the case of cognitive aging. Essential for predicting future gains and losses in monetary and social domains, the striatal nuclei in the brain undergo structural, neurochemical, and functional decline with age. We correlated the efficacy of market mechanisms with dorsal striatal decline in an aging population, by using market based trading in the context of the 2008 U.S. Presidential Elections (primary cycle). Impaired decision-makers displayed higher prediction error (difference between their prediction and actual outcome). Lower in vivo caudate volume was also associated with higher prediction error. Importantly, market-based trading protected older adults with lower caudate volume to a greater extent from their own poorly calibrated predictions. Counterintuitive to the traditional public perception of the market as a fickle, risky proposition where vulnerable traders are most surely to be burned, we suggest that market-based mechanisms protect individuals with brain-based decision-making vulnerabilities. Copyright © 2011 Elsevier Ltd. All rights reserved.

Market mechanisms protect the vulnerable brain

PubMed Central

Ramchandran, Kanchna; Nayakankuppam, Dhananjay; Berg, Joyce; Tranel, Daniel

2011-01-01

Markets are mechanisms of social exchange, intended to facilitate trading. However, the question remains as to whether markets would help or hurt individuals with decision-makings deficits, as is frequently encountered in the case of cognitive aging. Essential for predicting future gains and losses in monetary and social domains, the striatal nuclei in the brain undergo structural, neurochemical, and functional decline with age. We correlated the efficacy of market mechanisms with dorsal striatal decline in an aging population, by using market based trading in the context of the 2008 U.S Presidential Elections (primary cycle). Impaired decision-makers displayed higher prediction error (difference between their prediction and actual outcome). Lower in vivo caudate volume was also associated with higher prediction error. Importantly, market-based trading protected older adults with lower caudate volume to a greater extent from their own poorly calibrated predictions. Counterintuitive to the traditional public perception of the market as a fickle, risky proposition where vulnerable traders are most surely to be burned, we suggest that market-based mechanisms protect individuals with brain-based decision-making vulnerabilities. PMID:21600226

An overview of attention deficits after paediatric traumatic brain injury.

PubMed

Ginstfeldt, Tim; Emanuelson, Ingrid

2010-01-01

Attention could be categorized into sustained, selective, shifting, divided and attention span. The primary objective was to evaluate the type of attention deficits that occurs after paediatric traumatic brain injury. Keywords were used such as 'attention', 'child', 'traumatic', 'brain' and 'injury' on MEDLINE articles published in 1991-2009. Articles found through MEDLINE were manually cross-referenced. Out of the examined categorizes, divided and sustained attention seem to be the most vulnerably, frequently displaying deficits in the children with TBI. Attention span seemed to be the most resistant and the shifting and selective categories falling somewhere in between. Most of the recovery is expected within the first year post-injury, even if some individuals continue to improve for years, and deficits often persist into adulthood. The attention domains are not affected to the same extent by TBI and this should be taken into consideration when evaluating a child. The commonly used tests also seem to differ in how sensitive they are in detecting deficits. The definition of attention domains and TBI would benefit to be stricter and agreed upon, to further facilitate research and rehabilitation programmes.

Portable Functional Neuroimaging as an Environmental Epidemiology Tool: A How-To Guide for the Use of fNIRS in Field Studies.

PubMed

Baker, Joseph M; Rojas-Valverde, Daniel; Gutiérrez, Randall; Winkler, Mirko; Fuhrimann, Samuel; Eskenazi, Brenda; Reiss, Allan L; Mora, Ana M

2017-09-21

The widespread application of functional neuroimaging within the field of environmental epidemiology has the potential to greatly enhance our understanding of how environmental toxicants affect brain function. Because many epidemiological studies take place in remote and frequently changing environments, it is necessary that the primary neuroimaging approach adopted by the epidemiology community be robust to many environments, easy to use, and, preferably, mobile. Here, we outline our use of functional near-infrared spectroscopy (fNIRS) to collect functional brain imaging data from Costa Rican farm workers enrolled in an epidemiological study on the health effects of chronic pesticide exposure. While couched in this perspective, we focus on the methodological considerations that are necessary to conduct a mobile fNIRS study in a diverse range of environments. Thus, this guide is intended to be generalizable to all research scenarios and projects in which fNIRS may be used to collect functional brain imaging data in epidemiological field surveys. https://doi.org/10.1289/EHP2049.

Portable Functional Neuroimaging as an Environmental Epidemiology Tool: A How-To Guide for the Use of fNIRS in Field Studies

PubMed Central

Rojas-Valverde, Daniel; Gutiérrez, Randall; Winkler, Mirko; Fuhrimann, Samuel; Eskenazi, Brenda; Reiss, Allan L.; Mora, Ana M.

2017-01-01

Summary: The widespread application of functional neuroimaging within the field of environmental epidemiology has the potential to greatly enhance our understanding of how environmental toxicants affect brain function. Because many epidemiological studies take place in remote and frequently changing environments, it is necessary that the primary neuroimaging approach adopted by the epidemiology community be robust to many environments, easy to use, and, preferably, mobile. Here, we outline our use of functional near-infrared spectroscopy (fNIRS) to collect functional brain imaging data from Costa Rican farm workers enrolled in an epidemiological study on the health effects of chronic pesticide exposure. While couched in this perspective, we focus on the methodological considerations that are necessary to conduct a mobile fNIRS study in a diverse range of environments. Thus, this guide is intended to be generalizable to all research scenarios and projects in which fNIRS may be used to collect functional brain imaging data in epidemiological field surveys. https://doi.org/10.1289/EHP2049 PMID:28937962

Paediatric brain tumours: A review of radiotherapy, state of the art and challenges for the future regarding protontherapy and carbontherapy.

PubMed

Laprie, A; Hu, Y; Alapetite, C; Carrie, C; Habrand, J-L; Bolle, S; Bondiau, P-Y; Ducassou, A; Huchet, A; Bertozzi, A-I; Perel, Y; Moyal, É; Balosso, J

2015-12-01

Brain tumours are the most frequent solid tumours in children and the most frequent radiotherapy indications in paediatrics, with frequent late effects: cognitive, osseous, visual, auditory and hormonal. A better protection of healthy tissues by improved beam ballistics, with particle therapy, is expected to decrease significantly late effects without decreasing local control and survival. This article reviews the scientific literature to advocate indications of protontherapy and carbon ion therapy for childhood central nervous system cancer, and estimate the expected therapeutic benefits. A systematic review was performed on paediatric brain tumour treatments using Medline (from 1966 to March of 2014). To be included, clinical trials had to meet the following criteria: age of patients 18 years or younger, treated with radiation, and report of survival. Studies were also selected according to the evidence level. A secondary search of cited references found other studies about cognitive functions, quality of life, the comparison of photon and proton dosimetry showing potential dose escalation and/or sparing of organs at risk with protontherapy; and studies on dosimetric and technical issues related to protontherapy. A total of 7051 primary references published were retrieved, among which 40 clinical studies and 60 papers about quality of life, dose distribution and dosimetry were analysed, as well as the ongoing clinical trials. These papers have been summarized and reported in a specific document made available to the participants of a final 1-day workshop. Tumours of the meningeal envelop and bony cranial structures were excluded from the analysis. Protontherapy allows outstanding ballistics to target the tumour area, while substantially decreasing radiation dose to the normal tissues. There are many indications of protontherapy for paediatric brain tumours in curative intent, either for localized treatment of ependymomas, germ-cell tumours, craniopharyngiomas, low-grade gliomas; or panventricular irradiation of pure non-secreting germinoma; or craniospinal irradiation of medulloblastomas and metastatic pure germinomas. Carbon ion therapy is just emerging and may be studied for highly aggressive and radioresistant tumours, as an initial treatment for diffuse brainstem gliomas, and for relapse of high-grade gliomas. Both protontherapy and carbon ion therapy are promising for paediatric brain tumours. The benefit of decreasing late effects without altering survival has been described for most paediatric brain tumours with protontherapy and is currently assessed in ongoing clinical trials with up-to-date proton devices. Unfortunately, in 2015, only a minority of paediatric patients in France can receive protontherapy due to the lack of equipment. Copyright © 2015. Published by Elsevier SAS.

Pathophysiogenesis of Mesial Temporal Lobe Epilepsy: Is Prevention of Damage Antiepileptogenic?

PubMed Central

Curia, G.; Lucchi, C.; Vinet, J.; Gualtieri, F.; Marinelli, C.; Torsello, A.; Costantino, L.; Biagini*,, G.

2014-01-01

Temporal lobe epilepsy (TLE) is frequently associated with hippocampal sclerosis, possibly caused by a primary brain injury that occurred a long time before the appearance of neurological symptoms. This type of epilepsy is characterized by refractoriness to drug treatment, so to require surgical resection of mesial temporal regions involved in seizure onset. Even this last therapeutic approach may fail in giving relief to patients. Although prevention of hippocampal damage and epileptogenesis after a primary event could be a key innovative approach to TLE, the lack of clear data on the pathophysiological mechanisms leading to TLE does not allow any rational therapy. Here we address the current knowledge on mechanisms supposed to be involved in epileptogenesis, as well as on the possible innovative treatments that may lead to a preventive approach. Besides loss of principal neurons and of specific interneurons, network rearrangement caused by axonal sprouting and neurogenesis are well known phenomena that are integrated by changes in receptor and channel functioning and modifications in other cellular components. In particular, a growing body of evidence from the study of animal models suggests that disruption of vascular and astrocytic components of the blood-brain barrier takes place in injured brain regions such as the hippocampus and piriform cortex. These events may be counteracted by drugs able to prevent damage to the vascular component, as in the case of the growth hormone secretagogue ghrelin and its analogues. A thoroughly investigation on these new pharmacological tools may lead to design effective preventive therapies. PMID:24251566

Long-term effects of frequent cannabis use on working memory and attention: an fMRI study.

PubMed

Jager, Gerry; Kahn, Rene S; Van Den Brink, Wim; Van Ree, Jan M; Ramsey, Nick F

2006-04-01

Excessive use of cannabis may have long-term effects on cognitive abilities. Mild impairments have been found in several cognitive domains, particularly in memory and attention. It is not clear, however, whether these effects also occur with moderate, recreational use of cannabis. Furthermore, little is known about underlying brain correlates. The aim of this study is to assess brain function in frequent but relatively moderate cannabis users in the domains of working memory and selective attention. Functional magnetic resonance imaging was used to examine verbal working memory and visuo-auditory selective attention in ten frequent cannabis users (after 1 week of abstinence) and ten non-using healthy controls. Groups were similar in age, gender and estimated IQ. Cannabis users and controls performed equally well during the working memory task and the selective attention task. Furthermore, cannabis users did not differ from controls in terms of overall patterns of brain activity in the regions involved in these cognitive functions. However, for working memory, a more specific region-of-interest analysis showed that, in comparison to the controls, cannabis users displayed a significant alteration in brain activity in the left superior parietal cortex. No evidence was found for long-term deficits in working memory and selective attention in frequent cannabis users after 1 week of abstinence. Nonetheless, frequent cannabis use may affect brain function, as indicated by altered neurophysiological dynamics in the left superior parietal cortex during working memory processing.

Spectrum of metastatic neoplasms of the brain: A clinicopathological study in a tertiary care cancer centre.

PubMed

Singh, Smrita; Amirtham, Usha; Premalata, Chennagiri S; Lakshmaiah, Kuntegowdanahalli C; Viswanath, Lokesh; Kumar, Rekha V

2018-01-01

While brain metastases (BM) are the most common causes of neurologic disorders in patients with known systemic malignancies, they can often be the initial manifestations of an undetected primary elsewhere. BM are major causes of morbidity and mortality in cancer patients. We describe a mixed population (data from both retrospective and prospective collection) having a BM from a solid tumor. We report the percentage distribution of the most frequent types of BM, confirming the data published in the literature. This paper may play a role in presenting the Southeast Asian reality compared with the Western countries. A tertiary-care cancer centre. Data for 4 years were retrieved from the records of the Department of Pathology of our institute. Hematolymphoid and meningeal tumors were excluded. Hematoxylin and eosin (H and E) stained slides were reviewed, and in cases with an unknown primary, immunohistochemistry (IHC) was advised. The panel of markers was chosen based on the histomorphology on H and E sections. IHC was done in cases with an unknown primary where paraffin blocks were available. Lung cancer was found to be the most common primary malignancy (n = 30; 48.4%) followed by breast cancer (n = 13; 21%), colorectal cancer (n = 6; 9.6%), and skin cancer (melanoma) [n = 3; 4.8%]. The incidence of BM from lung and breast cancer was similar to that seen in the Western studies. However, BM from colorectal cancer and melanoma show a higher and lower incidence, respectively, in comparison with the Western literature.

Fuel not fun: Reinterpreting attenuated brain responses to reward in obesity.

PubMed

Kroemer, Nils B; Small, Dana M

2016-08-01

There is a well-established literature linking obesity to altered dopamine signaling and brain response to food-related stimuli. Neuroimaging studies frequently report enhanced responses in dopaminergic regions during food anticipation and decreased responses during reward receipt. This has been interpreted as reflecting anticipatory "reward surfeit", and consummatory "reward deficiency". In particular, attenuated response in the dorsal striatum to primary food rewards is proposed to reflect anhedonia, which leads to overeating in an attempt to compensate for the reward deficit. In this paper, we propose an alternative view. We consider brain response to food-related stimuli in a reinforcement-learning framework, which can be employed to separate the contributions of reward sensitivity and reward-related learning that are typically entangled in the brain response to reward. Consequently, we posit that decreased striatal responses to milkshake receipt reflect reduced reward-related learning rather than reward deficiency or anhedonia because reduced reward sensitivity would translate uniformly into reduced anticipatory and consummatory responses to reward. By re-conceptualizing reward deficiency as a shift in learning about subjective value of rewards, we attempt to reconcile neuroimaging findings with the putative role of dopamine in effort, energy expenditure and exploration and suggest that attenuated brain responses to energy dense foods reflect the "fuel", not the fun entailed by the reward. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization of subtle brain abnormalities in a mouse model of Hedgehog pathway antagonist-induced cleft lip and palate.

PubMed

Lipinski, Robert J; Holloway, Hunter T; O'Leary-Moore, Shonagh K; Ament, Jacob J; Pecevich, Stephen J; Cofer, Gary P; Budin, Francois; Everson, Joshua L; Johnson, G Allan; Sulik, Kathleen K

2014-01-01

Subtle behavioral and cognitive deficits have been documented in patient cohorts with orofacial clefts (OFCs). Recent neuroimaging studies argue that these traits are associated with structural brain abnormalities but have been limited to adolescent and adult populations where brain plasticity during infancy and childhood may be a confounding factor. Here, we employed high resolution magnetic resonance microscopy to examine primary brain morphology in a mouse model of OFCs. Transient in utero exposure to the Hedgehog (Hh) signaling pathway antagonist cyclopamine resulted in a spectrum of facial dysmorphology, including unilateral and bilateral cleft lip and palate, cleft of the secondary palate only, and a non-cleft phenotype marked by midfacial hypoplasia. Relative to controls, cyclopamine-exposed fetuses exhibited volumetric differences in several brain regions, including hypoplasia of the pituitary gland and olfactory bulbs, hyperplasia of the forebrain septal region, and expansion of the third ventricle. However, in affected fetuses the corpus callosum was intact and normal division of the forebrain was observed. This argues that temporally-specific Hh signaling perturbation can result in typical appearing OFCs in the absence of holoprosencephaly--a condition classically associated with Hh pathway inhibition and frequently co-occurring with OFCs. Supporting the premise that some forms of OFCs co-occur with subtle brain malformations, these results provide a possible ontological basis for traits identified in clinical populations. They also argue in favor of future investigations into genetic and/or environmental modulation of the Hh pathway in the etiopathogenesis of orofacial clefting.

Central diabetes insipidus, central hypothyroidism, renal tubular acidosis and dandy-walker syndrome: new associations.

PubMed

Alafif, M M; Aljaid, S S; Al-Agha, A E

2015-01-01

Dandy-Walker syndrome (DWS) is a rare brain malformation involving the cerebellum, and the fluid filled spaces around it, usually detected during the antenatal period or the early infancy. Clinically, it is characterized by mental retardation, developmental delay as well as cerebellar ataxia. It has been frequently associated with other conditions such as congenital heart diseases, primary hypothyroidism, and other disorders of the central nervous, gastrointestinal, genitourinary, and orthopedic systems. In this report, we describe a 3-month-old Saudi boy with the rare association of DWS with central diabetes insipidus, congenital central hypothyroidism, and type-2 renal tubular acidosis.

Central Diabetes Insipidus, Central Hypothyroidism, Renal Tubular Acidosis and Dandy-Walker Syndrome: New Associations

PubMed Central

Alafif, MM; Aljaid, SS; Al-Agha, AE

2015-01-01

Dandy-Walker syndrome (DWS) is a rare brain malformation involving the cerebellum, and the fluid filled spaces around it, usually detected during the antenatal period or the early infancy. Clinically, it is characterized by mental retardation, developmental delay as well as cerebellar ataxia. It has been frequently associated with other conditions such as congenital heart diseases, primary hypothyroidism, and other disorders of the central nervous, gastrointestinal, genitourinary, and orthopedic systems. In this report, we describe a 3-month-old Saudi boy with the rare association of DWS with central diabetes insipidus, congenital central hypothyroidism, and type-2 renal tubular acidosis. PMID:25861538

[Guidelines for the radiotherapy of gliomas].

PubMed

Feuvret, L; Antoni, D; Biau, J; Truc, G; Noël, G; Mazeron, J-J

2016-09-01

Gliomas are the most frequent primary brain tumours. Treating these tumours is difficult because of the proximity of organs at risk, infiltrating nature, and radioresistance. Clinical prognostic factors such as age, Karnofsky performance status, tumour location, and treatments such as surgery, radiation therapy, and chemotherapy have long been recognized in the management of patients with gliomas. Molecular biomarkers are increasingly evolving as additional factors that facilitate diagnosis and therapeutic decision-making. These practice guidelines aim at helping in choosing the best treatment, in particular radiation therapy. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Crystals in brain and meninges in primary hyperoxaluria and oxalosis.

PubMed Central

Haqqani, M T

1977-01-01

A case of primary hyperoxaluria and oxalosis with chronic renal failure, crystalline myocarditis, and disseminated calcium oxalate crystal deposition in various tissues including the brain and meninges is described. Deposition of crystals in brain and meninges is exceptionally rare in primary oxalosis. Images PMID:838867

Coagulopathy and transfusion requirements in war related penetrating traumatic brain injury. A single centre study in a French role 3 medical treatment facility in Afghanistan.

PubMed

Bordes, J; Joubert, C; Esnault, P; Montcriol, A; Nguyen, C; Meaudre, E; Dulou, R; Dagain, A

2017-05-01

Traumatic brain injury associated coagulopathy is frequent, either in isolated traumatic brain injury in civilian practice and in combat traumatic brain injury. In war zone, it is a matter of concern because head and neck are the second most frequent site of wartime casualty burden. Data focusing on transfusion requirements in patients with war related TBI coagulopathy are limited. A descriptive analysis was conducted of 77 penetrating traumatic brain injuries referred to a French role 3 medical treatment facility in Kabul, Afghanistan, deployed on the Kabul International Airport (KaIA), over a 30 months period. On 77 patients, 23 died during the prehospital phase and were not included in the study. Severe traumatic brain injury represented 50% of patients. Explosions were the most common injury mechanism. Extracranial injuries were present in 72% of patients. Traumatic brain injury coagulopathy was diagnosed in 67% of patients at role 3 admission. Red blood cell units (RBCu) were transfused in 39 (72%) patients, French lyophilized plasma (FLYP) in 41 (76%), and fresh whole blood (FWB) in 17 (31%). The results of this study support previous observations of coagulopathy as a frequent complication of traumatic brain injury. The majority of patients with war related penetrating traumatic brain injury presented with extracranial lesions. Most of them required a high level of transfusion capacity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acupuncture-induced changes in functional connectivity of the primary somatosensory cortex varied with pathological stages of Bell's palsy.

PubMed

He, Xiaoxuan; Zhu, Yifang; Li, Chuanfu; Park, Kyungmo; Mohamed, Abdalla Z; Wu, Hongli; Xu, Chunsheng; Zhang, Wei; Wang, Linying; Yang, Jun; Qiu, Bensheng

2014-10-01

Bell's palsy is the most common cause of acute facial nerve paralysis. In China, Bell's palsy is frequently treated with acupuncture. However, its efficacy and underlying mechanism are still controversial. In this study, we used functional MRI to investigate the effect of acupuncture on the functional connectivity of the brain in Bell's palsy patients and healthy individuals. The patients were further grouped according to disease duration and facial motor performance. The results of resting-state functional MRI connectivity show that acupuncture induces significant connectivity changes in the primary somatosensory region of both early and late recovery groups, but no significant changes in either the healthy control group or the recovered group. In the recovery group, the changes also varied with regions and disease duration. Therefore, we propose that the effect of acupuncture stimulation may depend on the functional connectivity status of patients with Bell's palsy.

Changes in Signal Intensity of the Dentate Nucleus and Globus Pallidus in Pediatric Patients: Impact of Brain Irradiation and Presence of Primary Brain Tumors Independent of Linear Gadolinium-based Contrast Agent Administration.

PubMed

Tamrazi, Benita; Nguyen, Binh; Liu, Chia-Shang J; Azen, Colleen G; Nelson, Mary B; Dhall, Girish; Nelson, Marvin D

2018-05-01

Purpose To determine whether whole-brain irradiation, chemotherapy, and primary brain pathologic conditions affect magnetic resonance (MR) imaging signal changes in pediatric patients independent of the administration of gadolinium-based contrast agents (GBCAs). Materials and Methods This institutional review board-approved, HIPAA-compliant study included 144 pediatric patients who underwent intravenous GBCA-enhanced MR imaging examinations (55 patients with primary brain tumors and whole-brain irradiation, 19 with primary brain tumors and chemotherapy only, 52 with primary brain tumors without any treatment, and 18 with neuroblastoma without brain metastatic disease). The signal intensities (SIs) in the globus pallidus (GP), thalamus (T), dentate nucleus (DN), and pons (P) were measured on unenhanced T1-weighted images. GP:T and DN:P SI ratios were compared between groups by using the analysis of variance and were analyzed relative to group, total cumulative number of doses of GBCA, age, and sex by using multivariable linear models. Results DN:P ratio for the radiation therapy group was greater than that for the other groups except for the group of brain tumors treated with chemotherapy (P < .05). The number of GBCA doses was correlated with the DN:P ratio for the nontreated brain tumor group (P < .0001). The radiation therapy-treated brain tumor group demonstrated higher DN:P ratios than the nontreated brain tumor group for number of doses less than or equal to 10 (P < .0001), whereas ratios in the nontreated brain tumor group were higher than those in the radiation therapy-treated brain tumor group for doses greater than 20 (P = .05). The GP:T ratios for the brain tumor groups were greater than that for the neuroblastoma group (P = .01). Conclusion Changes in SI of the DN and GP that are independent of the administration of GBCA occur in patients with brain tumors undergoing brain irradiation, as well as in patients with untreated primary brain tumors. © RSNA, 2017.

The significance of BRAF V600E mutation status discordance between primary cutaneous melanoma and brain metastases: The implications for BRAF inhibitor therapy.

PubMed

Hannan, Enda J; O'Leary, Donal P; MacNally, Stephen P; Kay, Elaine W; Farrell, Michael A; Morris, Patrick G; Power, Colm P; Hill, Arnold D K

2017-12-01

To compare BRAF V600E status of primary melanoma and brain metastases to assess for discordance by cross-sectional study, and to evaluate clinical implications on BRAF inhibitor therapy.Brain metastases are common in patients with advanced melanoma. Between 40% and 60% of melanomas demonstrate BRAF mutations, BRAF V600E being most common. Selective BRAF inhibitor therapy has shown improvement in outcome in patients with melanoma. It has been demonstrated that not all metastatic lesions carry the same BRAF mutation status as the primary, but the frequency in which discordance occurs remains unclear. Establishing this may have implications in the use of BRAF inhibitors in patients with melanoma brain metastases.Patients who underwent metastectomy for melanoma brain metastases were identified using our local histopathology database. A review of histology of the primary lesion and the metastasis was performed for each patient, assessing for BRAF mutation status discordance.Fourty-two patients who underwent a brain metastectomy following excision of a melanoma primary were identified over a 7-year period. Median survival was 9 months. The median Breslow thickness for the primary lesion was 3.4 mm. Six patients (14%) had discrepancy between the BRAF status of a melanoma primary and metastatic lesion. Of these 6 patients, 3 had a BRAF mutation positive primary with a BRAF mutation negative metastatic lesion, while the other 3 had a BRAF mutation negative primary with BRAF mutation positive metastasis.There is an important discordance rate in the BRAF mutation status of melanoma primaries versus brain metastases.

Quality of Life in Patients With Primary and Metastatic Brain Tumors in the Literature as Assessed by the FACT-Br.

PubMed

Chiu, Nicholas; Chiu, Leonard; Zeng, Liang; Zhang, Liying; Cella, David; Popovic, Marko; Chow, Ronald; Lam, Henry; Poon, Michael; Chow, Edward

2012-12-01

The Functional Assessment of Cancer Therapy-Brain (FACT-Br) is a quality of life (QOL) assessment tool that was originally developed for use in patients with primary brain tumors. However, the tool has also been used to assess QOL in patients with metastatic brain tumors. The purpose of this study is to compare the differences in QOL responses as assessed by the FACT-Br in patients with primary and metastatic brain neoplasms. A systematic literature search was conducted using the OvidSP platform in MEDLINE (1946 to July Week 2 2012) and EMBASE (1980 to 2012 Week 28). Articles in which the FACT-Br was used as a QOL assessment for patients with malignant brain tumors (both primary and metastatic) were included in the study. The weighted means of FACT-Br subscale and overall scores were calculated for the studies. To compare these scores, weighted analysis of variance was conducted and PROC GLM was performed for the data. A P-value of < 0.05 was considered statistically significant. A total of 23 studies (four in brain metastases, 18 in primary brain tumors and 1 in a mixed sample) using the FACT-Br for assessment of QOL were identified. Social and functional well-being were significantly better in patients with primary brain tumors (weighted mean score of 22.2 vs. 10.7, P = 0.0026, 16.9 vs. 6.2, P = 0.0025, respectively). No other scale of the FACT-Br was significantly different between the two groups and the performance status of patients included in both groups was similar. Patients with primary brain cancer seemed to have better social and functional well-being scores than those with metastatic brain tumors. Other QOL domains were similar between these two groups. However, the heterogeneity in the included studies and the low sample size of included samples in patients with metastatic brain tumors could have confounded our findings.

Pathogenesis of amyotrophic lateral sclerosis.

PubMed

Morgan, Sarah; Orrell, Richard W

2016-09-01

Amyotrophic lateral sclerosis (ALS) or motor neuron disease is a rapidly progressive neurodegenerative disorder. The primary involvement is of motor neurons in the brain, spinal cord and peripherally. There is secondary weakness of muscles and primary involvement of other brain regions, especially involving cognition. Peer-reviewed journal articles and reviews. PubMed.gov The pathogenesis of ALS remains largely unknown. There are a wide range of potential mechanisms related to neurodegeneration. An increasing number of genetic factors are recognized. There remains controversy, or lack of knowledge, in explaining how cellular events manifest as the complex human disease. There is controversy as to how well cellular and animal models of disease relate to the human disease. Large-scale international collaborative genetic epidemiological studies are replacing local studies. Therapies related to pathogenesis remain elusive, with the greatest advances to date relating to provision of care (including multidisciplinary management) and supportive care (nutrition and respiratory support). The identification of C9orf72 hexanucleotide repeats as the most frequent genetic background to ALS, and the association with frontotemporal dementia, gives the potential of a genetic background against which to study other risk factors, triggers and pathogenic mechanisms, and to develop potential therapies. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Consequence of secondary complications during the rehabilitation of patients with severe brain injury].

PubMed

Dénes, Zoltán

2009-01-25

Recovery from brain injury is not only determined by the primary injury, but a very important element is the development of secondary complications which have a major role in determining the possibility of the achievement of available maximal functional abilities and the quality of life of the patients and their family after rehabilitation. This is why during medical treatment the prevention of secondary complications is at least as important as the prevention of primary injury. Determination of the most important secondary complications after severe brain injury, and observation of these effects on the rehabilitation process. Retrospective study in the Brain Injury Rehabilitation unit of the National Institute for Medical Rehabilitation in Hungary. 166 patients were treated with brain injury; the mean age of the patients was 33 (8-83) years in 2004. The majority of patients suffered traumatic brain injury in traffic accidents (125/166), while the rest of them through falls or acts of violence. Sixty-four patients were admitted directly from an intensive care unit, 18 from a second hospital ward (traumatology, neurosurgery or neurology) and the rest of the patients were treated in several different units before they were admitted for rehabilitation. The time that has elapsed between injury and rehabilitation admission was 50 days (21-177). At the time of admission 27 patients were in a vegetative state, 38 patients in a minimal conscious state, and 101 patients had already regained consciousness. 83 patients were hemiparetic, 54 presented tetraparesis, and 1 paraparesis, but 28 patients were not paretic. The most frequent complications in patients with severe brain injury at admission in our rehabilitation unit were: contractures (47%), pressure sores (35%), respiratory (14%) and urinary (11%) tract infections, malnutrition (20%). The functional outcome was worse in the cases arriving with secondary complications during the same rehabilitation period. The length of stay in the rehabilitation unit was much longer in these cases. We strongly suggest that actions to prevent secondary complications must be started at the acute care unit. After acute care, rehabilitation of patients with severe brain injury should be performed in specialised centers with multidisciplinary team for different functional deficits (physical, cognitive, communicative, psycho-social impairments). Early and direct admission from the neurologic intensive care unit to the rehabilitation centrum seems to be optimal for best patient outcome, because this lowers the chance for the development of secondary complications.

Trends in incidence of primary brain cancer in New Zealand, 1995 to 2010.

PubMed

Kim, Stella J-H; Ioannides, Sally J; Elwood, J Mark

2015-04-01

Case-control studies have linked mobile phone use to an increased risk of glioma in the most exposed brain areas, the temporal and parietal lobes, although inconsistently. We examined time trends in the incidence rates of brain malignancies in New Zealand from 1995 to 2010. Data from the New Zealand Cancer Registry was used to calculate incidence rates of primary brain cancer, by age, gender, morphology and anatomical site. Log-linear regression analysis was used to assess trends in the annual incidence of primary brain cancer; annual percentage changes and their 95% confidence intervals were estimated. No consistent increases in all primary brain cancer, glioma, or temporal or parietal lobe glioma were seen. At ages 10-69, the incidence of all brain cancers declined significantly. Incidence of glioma increased at ages over 70. In New Zealand, there has been no consistent increase in incidence rates of primary brain cancers. An increase in glioma at ages over 70 is likely to be due to improvements in diagnosis. As with any such studies, a small effect, or one with a latent period of more than 10 to 15 years, cannot be excluded. © 2015 Public Health Association of Australia.

Brain injury as a risk factor for fever upon admission to the intensive care unit and association with in-hospital case fatality: a matched cohort study.

PubMed

Rincon, Fred; Patel, Utkal; Schorr, Christa; Lee, Elizabeth; Ross, Steven; Dellinger, R Phillip; Zanotti-Cavazzoni, Sergio

2015-02-01

To test the hypothesis that fever was more frequent in critically ill patients with brain injury when compared to nonneurological patients and to study its effect on in-hospital case fatality. Retrospective matched cohort study utilizing a single-center prospectively compiled registry. Critically ill neurological patients ≥18 years and consecutively admitted to the intensive care unit (ICU) with acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and traumatic brain injury (TBI) were selected. Patients were matched by sex, age, and Acute Physiology and Chronic Health Evaluation II (APACHE-II) to a cohort of nonneurological patients. Fever was defined as any temperature ≥37.5°C within the first 24 hours upon admission to the ICU. The primary outcome measure was in-hospital case fatality. Mean age among neurological patients was 65.6 ± 15 years, 46% were men, and median APACHE-II was 15 (interquartile range 11-20). There were 18% AIS, 27% ICH, and 6% TBI. More neurological patients experienced fever than nonneurological patients (59% vs 47%, P = .007). The mean hospital length of stay was higher for nonneurological patients (18 ± 20 vs 14 ± 15 days, P = .007), and more neurological patients were dead at hospital discharge (29% vs 20%, P < .0001). After risk factor adjustment, diagnosis (neurological vs nonneurological), and the probability of being exposed to fever (propensity score), the following variables were associated with higher in-hospital case fatality: APACHE-II, neurological diagnosis, mean arterial pressure, cardiovascular and respiratory dysfunction in ICU, and fever (odds ratio 1.9, 95% confidence interval 1.04-3.6, P = .04). These data suggest that fever is a frequent occurrence after brain injury, and that it is independently associated with in-hospital case fatality. © The Author(s) 2013.

Sleep disordered breathing in cardiac surgery patients: The NU-SLEEP trial.

PubMed

Sezai, Akira; Akahoshi, Toshiki; Osaka, Shunji; Yaoita, Hiroko; Arimoto, Munehito; Hata, Hiroaki; Tanaka, Masashi; Sekino, Hisakuni; Akashiba, Tsuneto

2017-01-15

Sleep disordered breathing (SDB) is associated with lifestyle-related diseases and its treatment influence the prognosis of cardiac disease, but little investigation of SDB has been conducted in cardiac surgery patients. A prospective study was performed in 1005 patients undergoing cardiac surgery. The primary endpoint was the severity of SDB determined from the apnea/hypopnea index. The secondary endpoints were patient background factors, cardiovascular risk factors, ejection fraction, atrial and brain natriuretic peptides, oxidative stress and inflammatory markers, and postoperative atrial fibrillation. While 227 patients (22.6%) did not have SDB, there were 361 patients (35.9%) with mild SDB, 260 patients (25.9%) with moderate SDB, and 157 patients (15.6%) with severe SDB. Patients with severe SDB had a lower ejection fraction and higher levels of atrial and brain natriuretic peptides than the other groups. Postoperative atrial fibrillation occurred in 28 patients without SDB (13.6%), 43 patients with mild SDB (13.5%), 74 patients with moderate SDB (31.9%), and 73 patients with severe SDB (52.5%), being significantly more frequent in the severe group than the other groups. SDB was frequent in cardiac surgery patients. Activation of the renin-angiotensin-aldosterone system, postoperative atrial fibrillation atrial, and cardiac dysfunction were associated with severe SDB. Markers of inflammation and oxidative stress also increased as SDB became more severe. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Brain pathologies in extreme old age.

PubMed

Neltner, Janna H; Abner, Erin L; Jicha, Gregory A; Schmitt, Frederick A; Patel, Ela; Poon, Leonard W; Marla, Gearing; Green, Robert C; Davey, Adam; Johnson, Mary Ann; Jazwinski, S Michal; Kim, Sangkyu; Davis, Daron; Woodard, John L; Kryscio, Richard J; Van Eldik, Linda J; Nelson, Peter T

2016-01-01

With an emphasis on evolving concepts in the field, we evaluated neuropathologic data from very old research volunteers whose brain autopsies were performed at the University of Kentucky Alzheimer's Disease Center, incorporating data from the Georgia Centenarian Study (n = 49 cases included), Nun Study (n = 17), and University of Kentucky Alzheimer's Disease Center (n = 11) cohorts. Average age of death was 102.0 (range: 98-107) years overall. Alzheimer's disease pathology was not universal (62% with "moderate" or "frequent" neuritic amyloid plaque densities), whereas frontotemporal lobar degeneration was absent. By contrast, some hippocampal neurofibrillary tangles (including primary age-related tauopathy) were observed in every case. Lewy body pathology was seen in 16.9% of subjects and hippocampal sclerosis of aging in 20.8%. We describe anatomic distributions of pigment-laden macrophages, expanded Virchow-Robin spaces, and arteriolosclerosis among Georgia Centenarians. Moderate or severe arteriolosclerosis pathology, throughout the brain, was associated with both hippocampal sclerosis of aging pathology and an ABCC9 gene variant. These results provide fresh insights into the complex cerebral multimorbidity, and a novel genetic risk factor, at the far end of the human aging spectrum. Copyright © 2016 Elsevier Inc. All rights reserved.

Antiretroviral Therapy and Central Nervous System HIV-1 Infection

PubMed Central

Price, Richard W.; Spudich, Serena

2008-01-01

Central nervous system (CNS) HIV-1 infection begins during primary viremia and continues throughout the course of untreated systemic infection. While frequently accompanied by local inflammatory reactions detectable in cerebrospinal fluid (CSF), CNS HIV-1 infection is not usually clinically apparent. In a minority of patients, CNS HIV-1 infection evolves late in the course of systemic infection into encephalitis, which compromises brain function and presents clinically as AIDS dementia complex (ADC). Combination highly active antiretroviral therapy (HAART) has had a major impact on all aspects of HIV-1 CNS infection and disease. In those with asymptomatic infection, HAART usually effectively suppresses CSF HIV-1 and markedly reduces the incidence of symptomatic ADC. In those presenting with ADC, HAART characteristically prevents neurological progression and leads to variable, and at times substantial, recovery. Treatment has similarly reduced CNS opportunistic infections. With better control of these severe disorders, attention has turned to the possible consequences of chronic silent infection, and the issue of whether indolent, low-grade brain injury might require earlier treatment intervention. PMID:18447615

Tic disorders.

PubMed

Martino, Davide; Mink, Jonathan W

2013-10-01

Primary tic disorders are complex, multifactorial disorders in which tics are accompanied by other sensory features and an array of comorbid behavioral disorders. Secondary tics are proportionally much less frequent, but their etiology is diverse. This review aims to guide clinicians in the recognition of the phenomenology, pathophysiology, and treatment of these disorders. Advances include greater phenomenologic insights, particularly of nonmotor (sensory) features; increased knowledge of disease mechanisms, particularly coming from neuropsychological, functional imaging, pathologic, and animal model studies; growing evidence on the efficacy of alpha-2 agonists and the newer generation of dopamine-modulating agents; and recent strides in the evaluation of cognitive-behavioral therapy and deep brain stimulation surgery. The correct diagnostic approach to tic disorders requires accurate historical gathering, a thorough neurologic examination, and detailed definition of the patient's psychopathologic profile. Treatment should always begin with individualized psychoeducational strategies. Although pharmacologic treatments remain beneficial for most patients, cognitive-behavioral treatments have thus far shown promising efficacy. Deep brain stimulation surgery should still be limited to adult patients refractory to pharmacotherapy and cognitive-behavioral therapy.

Primary postural instability: a cause of recurrent sudden falls in the elderly.

PubMed

Djaldetti, R; Lorberboym, M; Melamed, E

2006-12-01

Elderly patients with recurrent falls are frequently diagnosed with an extrapyramidal syndrome. This study aims to characterise a distinct group of patients with recurrent falls and postural instability as a hallmark of the clinical examination. The study took place in the Movement Disorders Unit, Rabin Medical Center, Petah Tiqva, Israel among 26 patients with recurrent falls who had no clinical evidence of a neurodegenerative disease. Medical records, neurological examination and brain imaging studies were assessed. Falls in these patients were sudden, unprovoked, with no vertigo or loss of consciousness. All had postural instability with minimal or no abnormality on the neurological examination. Brain imaging showed diffuse ischaemic changes in 65%. [(123)I]-FPCIT SPECT with the dopamine transporter ligand, performed in five patients, was normal in all. Recurrent falls might be caused by a neurological syndrome that primarily affects balance control. The importance of identifying this disorder is its distinction from other parkinsonian syndromes causing falls.

Use of a multi-level mixed methods approach to study the effectiveness of a primary care progressive return to activity protocol after acute mild traumatic brain injury/concussion in the military.

PubMed

Gregory, Emma; West, Therese A; Cole, Wesley R; Bailie, Jason M; McCulloch, Karen L; Ettenhofer, Mark L; Cecchini, Amy; Qashu, Felicia M

2017-01-01

The large number of U.S. service members diagnosed with concussion/mild traumatic brain injury each year underscores the necessity for clear and effective clinical guidance for managing concussion. Relevant research continues to emerge supporting a gradual return to pre-injury activity levels without aggravating symptoms; however, available guidance does not provide detailed standards for this return to activity process. To fill this gap, the Defense and Veterans Brain Injury Center released a recommendation for primary care providers detailing a step-wise return to unrestricted activity during the acute phase of concussion. This guidance was developed in collaboration with an interdisciplinary group of clinical, military, and academic subject matter experts using an evidence-based approach. Systematic evaluation of the guidance is critical to ensure positive patient outcomes, to discover barriers to implementation by providers, and to identify ways to improve the recommendation. Here we describe a multi-level, mixed-methods approach to evaluate the recommendation incorporating outcomes from both patients and providers. Procedures were developed to implement the study within complex but ecologically-valid settings at multiple military treatment facilities and operational medical units. Special consideration was given to anticipated challenges such as the frequent movement of military personnel, selection of appropriate design and measures, study implementation at multiple sites, and involvement of multiple service branches (Army, Navy, and Marine Corps). We conclude by emphasizing the need to consider contemporary approaches for evaluating the effectiveness of clinical guidance. Copyright © 2016 Elsevier Inc. All rights reserved.

[Immunohistochemical hormonal mismatch and human epidermal growth factor type 2 [HER2] phenotype of brain metastases in breast cancer carcinoma compared to primary tumors].

PubMed

Joubert, C; Boissonneau, S; Fina, F; Figarella-Branger, D; Ouafik, L; Fuentes, S; Dufour, H; Gonçalves, A; Charaffe-Jauffret, E; Metellus, P

2016-06-01

Phenotype changes between primary tumor and the corresponding brain metastases are recent reported data. Breast cancer, with biological markers predicting prognosis and guiding therapeutic strategy remains an interesting model to observe and evaluate theses changes. The objective of our study was to compare molecular features (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor type 2, [HER2]) between brain metastases and its primary tumor in patients presenting with pathologically confirmed breast cancer. This retrospective study was based on the immunohistochemical analysis of the brain metastases paraffin embedded samples stored in our institutional tumor bank, after surgical resection. The level of expression of hormonal receptors and HER2 on brain metastases were centrally reviewed and compared to the expression status in primary breast cancer from medical records. Forty-four samples of brain metastases were available for analysis. Hormonal receptor modification status was observed in 11/44 brain metastases (25%) for ER and 6/44 (13.6%) for PR. A modification of HER2 overexpression was observed in brain metastases in 6/44 (13.6%). Molecular subtype modification was shown in 17 cases (38.6%). A significant difference was demonstrated between time to develop brain metastases in cases without status modification (HER2, ER and PR) (med=49.5months [7.8-236.4]) and in cases in which brain metastases status differs from primary tumor (med=27.5months [0-197.3]), (P=0.0244, IC95=3.09-51.62, Mann and Whitney test). the main interest of this study was to focus on the molecular feature changes between primary tumor and their brain metastases. Time to develop brain metastases was correlated to phenotypic changes in brain metastases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases - results and lessons learnt.

PubMed

Gupta, Avinash; Roberts, Corran; Tysoe, Finn; Goff, Matthew; Nobes, Jenny; Lester, James; Marshall, Ernie; Corner, Carie; Wolstenholme, Virginia; Kelly, Charles; Wise, Adelyn; Collins, Linda; Love, Sharon; Woodward, Martha; Salisbury, Amanda; Middleton, Mark R

2016-11-08

Brain metastases occur in up to 75% of patients with advanced melanoma. Most are treated with whole-brain radiotherapy (WBRT), with limited effectiveness. Vandetanib, an inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and rearranged during transfection tyrosine kinases, is a potent radiosensitiser in xenograft models. We compared WBRT with WBRT plus vandetanib in the treatment of patients with melanoma brain metastases. In this double-blind, multi-centre, phase 2 trial patients with melanoma brain metastases were randomised to receive WBRT (30 Gy in 10 fractions) plus 3 weeks of concurrent vandetanib 100 mg once daily or placebo. The primary endpoint was progression-free survival in brain (PFS brain). The main study was preceded by a safety run-in phase to confirm tolerability of the combination. A post-hoc analysis and literature review considered barriers to recruiting patients with melanoma brain metastases to clinical trials. Twenty-four patients were recruited, six to the safety phase and 18 to the randomised phase. The study closed early due to poor recruitment. Median PFS brain was 3.3 months (90% confidence interval (CI): 1.6-5.6) in the vandetanib group and 2.5 months (90% CI: 0.2-4.8) in the placebo group (P=0.34). Median overall survival (OS) was 4.6 months (90% CI: 1.6-6.3) and 2.5 months (90% CI: 0.2-7.2), respectively (P=0.54). The most frequent adverse events were fatigue, alopecia, confusion and nausea. The most common barrier to study recruitment was availability of alternative treatments. The combination of WBRT plus vandetanib was well tolerated. Compared with WBRT alone, there was no significant improvement in PFS brain or OS, although we are unable to provide a definitive result due to poor accrual. A review of barriers to trial accrual identified several factors that affect study recruitment in this difficult disease area.

Some Problems for Representations of Brain Organization Based on Activation in Functional Imaging

ERIC Educational Resources Information Center

Sidtis, John J.

2007-01-01

Functional brain imaging has overshadowed traditional lesion studies in becoming the dominant approach to the study of brain-behavior relationships. The proponents of functional imaging studies frequently argue that this approach provides an advantage over lesion studies by observing normal brain activity in vivo without the disruptive effects of…

Altered Proteins in the Aging Brain

PubMed Central

Elobeid, Adila; Libard, Sylwia; Leino, Marina; Popova, Svetlana N.

2016-01-01

We assessed the prevalence of common altered brain proteins in 296 cognitively unimpaired subjects ranging from age 50 to 102 years. The incidence and the stage of hyperphosphorylated-τ (HPτ), β-amyloid, α-synuclein (αS), and transactive response DNA (TDP) binding protein 43 (TDP43)-immunoreactivity (-IR) increased with age. HPτ-IR was observed in 98% of the subjects; the locus coeruleus was solely affected in 46%, and 79% of the subjects were in Braak stages a to II. β-Amyloid was seen in 47% of subjects and the Thal phase correlated with the HPτ Braak stage and age. Intermediate Alzheimer disease-related pathology (ADRP) was seen in 12%; 52% of the subjects with HPτ-IR fulfilled criteria for definite primary age-related tauopathy (PART). The incidence of concomitant pathology (αS, TDP43) did not differ between those with PART and those with ADRP but the former were younger. TDP43-IR was observed in 36%; the most frequently affected region was the medulla; αS-IR was observed in 19% of subjects. In 41% of the subjects from 80 to 89 years at death, 3 altered proteins were seen in the brain. Thus, altered proteins are common in the brains of cognitively unimpaired aged subjects; this should be considered while developing diagnostic biomarkers, particularly for identifying subjects at early stages of neurodegenerative diseases. PMID:26979082

Evidence for Acute Electrophysiological and Cognitive Changes Following Routine Soccer Heading.

PubMed

Di Virgilio, Thomas G; Hunter, Angus; Wilson, Lindsay; Stewart, William; Goodall, Stuart; Howatson, Glyn; Donaldson, David I; Ietswaart, Magdalena

2016-11-01

There is growing concern around the effects of concussion and sub-concussive impacts in sport. Routine game-play in soccer involves intentional and repeated head impacts through ball heading. Although heading is frequently cited as a risk to brain health, little data exist regarding the consequences of this activity. This study aims to assess the immediate outcomes of routine football heading using direct and sensitive measures of brain function. Nineteen amateur football players (5 females; age 22±3y) headed machine-projected soccer balls at standardized speeds, modelling routine soccer practice. The primary outcome measure of corticomotor inhibition measured using transcranial magnetic stimulation, was assessed prior to heading and repeated immediately, 24h, 48h and 2weeks post-heading. Secondary outcome measures were cortical excitability, postural control, and cognitive function. Immediately following heading an increase in corticomotor inhibition was detected; further to these electrophysiological alterations, measurable reduction memory function were also found. These acute changes appear transient, with values normalizing 24h post-heading. Sub-concussive head impacts routine in soccer heading are associated with immediate, measurable electrophysiological and cognitive impairments. Although these changes in brain function were transient, these effects may signal direct consequences of routine soccer heading on (long-term) brain health which requires further study. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Cerebral motor function in very premature-at-birth adolescents: a brain stimulation exploration of kangaroo mother care effects.

PubMed

Schneider, Cyril; Charpak, Nathalie; Ruiz-Peláez, Juan G; Tessier, Réjean

2012-10-01

  Given that prematurity has deleterious effects on brain networking development beyond childhood, the study explored whether an early intervention such as Kangaroo Mother Care (KMC) in very preterm preemies could have influenced brain motor function up to adolescence.   Transcranial magnetic stimulation (TMS) was applied over the primary motor cortex (M1) of 39 adolescents born very prematurely (<33 weeks' gestational age, 21 having received KMC after birth, 18 Controls with no KMC) and nine adolescents born at term (>37 weeks' gestational age, >2500 g) to assess the functional integrity of motor circuits in each hemisphere (motor planning) and between hemispheres (callosal function).   All TMS outcomes were similar between KMC and term adolescents, with typical values as in healthy adults, and better than in Controls. KMC adolescents presented faster conduction times revealing more efficient M1 cell synchronization (p < 0.05) and interhemispheric transfer time (p < 0.0001), more frequent inhibitory processes with a better control between hemispheres (p < 0.0001).   The enhanced synchronization, conduction times and connectivity of cerebral motor pathways in the KMC group suggests that the Kangaroo Mother Care positively influenced the premature brain networks and synaptic efficacy up to adolescence. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

Magnetoencephalographic study of hand and foot sensorimotor organization in 325 consecutive patients evaluated for tumor or epilepsy surgery

PubMed Central

Willemse, Ronald B.; Hillebrand, Arjan; Ronner, Hanneke E.; Peter Vandertop, W.; Stam, Cornelis J.

2015-01-01

Objectives The presence of intracranial lesions or epilepsy may lead to functional reorganization and hemispheric lateralization. We applied a clinical magnetoencephalography (MEG) protocol for the localization of the contralateral and ipsilateral S1 and M1 of the foot and hand in patients with non-lesional epilepsy, stroke, developmental brain injury, traumatic brain injury and brain tumors. We investigated whether differences in activation patterns could be related to underlying pathology. Methods Using dipole fitting, we localized the sources underlying sensory and motor evoked magnetic fields (SEFs and MEFs) of both hands and feet following unilateral stimulation of the median nerve (MN) and posterior tibial nerve (PTN) in 325 consecutive patients. The primary motor cortex was localized using beamforming following a self-paced repetitive motor task for each hand and foot. Results The success rate for motor and sensory localization for the feet was significantly lower than for the hands (motor_hand 94.6% versus motor_feet 81.8%, p < 0.001; sensory_hand 95.3% versus sensory_feet 76.0%, p < 0.001). MN and PTN stimulation activated 86.6% in the contralateral S1, with ipsilateral activation < 0.5%. Motor cortex activation localized contralaterally in 76.1% (5.2% ipsilateral, 7.6% bilateral and 11.1% failures) of all motor MEG recordings. The ipsilateral motor responses were found in 43 (14%) out of 308 patients with motor recordings (range: 8.3–50%, depending on the underlying pathology), and had a higher occurrence in the foot than in the hand (motor_foot 44.8% versus motor_hand 29.6%, p = 0.031). Ipsilateral motor responses tended to be more frequent in patients with a history of stroke, traumatic brain injury (TBI) or developmental brain lesions (p = 0.063). Conclusions MEG localization of sensorimotor cortex activation was more successful for the hand compared to the foot. In patients with neural lesions, there were signs of brain reorganization as measured by more frequent ipsilateral motor cortical activation of the foot in addition to the traditional sensory and motor activation patterns in the contralateral hemisphere. The presence of ipsilateral neural reorganization, especially around the foot motor area, suggests that careful mapping of the hand and foot in both contralateral and ipsilateral hemispheres prior to surgery might minimize postoperative deficits. PMID:26693401

Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis

PubMed Central

Salhia, Bodour; Kiefer, Jeff; Ross, Julianna T. D.; Metapally, Raghu; Martinez, Rae Anne; Johnson, Kyle N.; DiPerna, Danielle M.; Paquette, Kimberly M.; Jung, Sungwon; Nasser, Sara; Wallstrom, Garrick; Tembe, Waibhav; Baker, Angela; Carpten, John; Resau, Jim; Ryken, Timothy; Sibenaller, Zita; Petricoin, Emanuel F.; Liotta, Lance A.; Ramanathan, Ramesh K.; Berens, Michael E.; Tran, Nhan L.

2014-01-01

The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies. PMID:24489661

Biomarkers of brain injury in the premature infant.

PubMed

Douglas-Escobar, Martha; Weiss, Michael D

2012-01-01

The term "encephalopathy of prematurity" encompasses not only the acute brain injury [such as intraventricular hemorrhage (IVH)] but also complex disturbance on the infant's subsequent brain development. In premature infants, the most frequent recognized source of brain injury is IVH and periventricular leukomalacia (PVL). Furthermore 20-25% infants with birth weigh less than 1,500 g will have IVH and that proportion increases to 45% if the birth weight is less than 500-750 g. In addition, nearly 60% of very low birth weight newborns will have hypoxic-ischemic injury. Therefore permanent lifetime neurodevelopmental disabilities are frequent in premature infants. Innovative approach to prevent or decrease brain injury in preterm infants requires discovery of biomarkers able to discriminate infants at risk for injury, monitor the progression of the injury, and assess efficacy of neuroprotective clinical trials. In this article, we will review biomarkers studied in premature infants with IVH, Post-hemorrhagic ventricular dilation (PHVD), and PVL including: S100b, Activin A, erythropoietin, chemokine CCL 18, GFAP, and NFL will also be examined. Some of the most promising biomarkers for IVH are S100β and Activin. The concentrations of TGF-β1, MMP-9, and PAI-1 in cerebrospinal fluid could be used to discriminate patients that will require shunt after PHVD. Neonatal brain injury is frequent in premature infants admitted to the neonatal intensive care and we hope to contribute to the awareness and interest in clinical validation of established as well as novel neonatal brain injury biomarkers.

Microsurgery Versus Stereotactic Radiosurgery for Brain Arteriovenous Malformations: A Matched Cohort Study.

PubMed

Chen, Ching-Jen; Ding, Dale; Wang, Tony R; Buell, Thomas J; Ilyas, Adeel; Ironside, Natasha; Lee, Cheng-Chia; Kalani, M Yashar; Park, Min S; Liu, Kenneth C; Sheehan, Jason P

2018-05-12

Microsurgery (MS) and stereotactic radiosurgery (SRS) remain the preferred interventions for the curative treatment of brain arteriovenous malformations (AVM), but their relative efficacy remains incompletely defined. To compare the outcomes of MS to SRS for AVMs through a retrospective, matched cohort study. We evaluated institutional databases of AVM patients who underwent MS and SRS. MS-treated patients were matched, in a 1:1 ratio based on patient and AVM characteristics, to SRS-treated patients. Statistical analyses were performed to compare outcomes data between the 2 cohorts. The primary outcome was defined as AVM obliteration without a new permanent neurological deficit. The matched MS and SRS cohorts were each comprised of 59 patients. Both radiological (85 vs 11 mo; P < .001) and clinical (92 vs 12 mo; P < .001) follow-up were significantly longer for the SRS cohort. The primary outcome was achieved in 69% of each cohort. The MS cohort had a significantly higher obliteration rate (98% vs 72%; P = .001), but also had a significantly higher rate of new permanent deficit (31% vs 10%; P = .011). The posttreatment hemorrhage rate was significantly higher for the SRS cohort (10% for SRS vs 0% for MS; P = .027). In subgroup analyses of ruptured and unruptured AVMs, no significant differences between the primary outcomes were observed. For patients with comparable AVMs, MS and SRS afford similar rates of deficit-free obliteration. Nidal obliteration is more frequently achieved with MS, but this intervention also incurs a greater risk of new permanent neurological deficit.

Breast cancer brain metastases show increased levels of genomic aberration based homologous recombination deficiency scores relative to their corresponding primary tumors.

PubMed

Diossy, M; Reiniger, L; Sztupinszki, Z; Krzystanek, M; Timms, K M; Neff, C; Solimeno, C; Pruss, D; Eklund, A C; Tóth, E; Kiss, O; Rusz, O; Cserni, G; Zombori, T; Székely, B; Tímár, J; Csabai, I; Szallasi, Z

2018-06-18

Based on its mechanism of action, PARP inhibitor therapy is expected to benefit mainly tumor cases with homologous recombination deficiency (HRD). Therefore, identification of tumor types with increased HRD is important for the optimal use of this class of therapeutic agents. HRD levels can be estimated using various mutational signatures from next generation sequencing data and we used this approach to determine whether breast cancer brain metastases show altered levels of HRD scores relative to their corresponding primary tumor. We used a previously published next generation sequencing dataset of twenty-one matched primary breast cancer/brain metastasis pairs to derive the various mutational signatures/HRD scores strongly associated with HRD. We also performed the myChoice HRD analysis on an independent cohort of seventeen breast cancer patients with matched primary/brain metastasis pairs. All of the mutational signatures indicative of HRD showed a significant increase in the brain metastases relative to their matched primary tumor in the previously published whole exome sequencing dataset. In the independent validation cohort the myChoice HRD assay showed an increased level in 87.5% of the brain metastases relative to the primary tumor, with 56% of brain metastases being HRD positive according to the myChoice criteria. The consistent observation that brain metastases of breast cancer tend to have higher HRD measures may raise the possibility that brain metastases may be more sensitive to PARP inhibitor treatment. This observation warrants further investigation to assess whether this increase is common to other metastatic sites as well, and whether clinical trials should adjust their strategy in the application of HRD measures for the prioritization of patients for PARP inhibitor therapy.

Expression of Antigen Processing and Presenting Molecules in Brain Metastasis of Breast Cancer

PubMed Central

Liu, Yan; Komohara, Yoshihiro; Domenick, Natalie; Ohno, Masasuke; Ikeura, Maki; Hamilton, Ronald L.; Horbinski, Craig; Wang, Xinhui; Ferrone, Soldano; Okada, Hideho

2012-01-01

Defects in human leukocyte antigen (HLA) class I antigen processing machinery (APM) component expression can have a negative impact on the clinical course of tumors and the response to T-cell-based immunotherapy. Since brain metastases of breast cancer are of increasing clinical significance, the APM component expression levels and CD8+ T-cell infiltration patterns were analyzed in primary breast and metastatic brain lesions of breast cancer by immunohistochemistry. Comparison of unpaired 50 primary and 33 brain metastases showed lower expression of β2-microgloblin, transporter associated with antigen processing (TAP) 1, TAP2 and calnexin in the brain lesions. Although no significant differences were found in APM component scores between primary breast and brain lesions in 15 paired cases, primary breast lesions of which patients eventually developed brain metastases showed lower levels of β2-microgloblin, TAP1 and calnexin compared with breast lesions without known brain metastases. The extent of CD8+ T cell infiltration was significantly higher in the lesions without metastasis compared with the ones with brain metastases, and was positively associated with the expression of TAP1 and calnexin. Furthermore, mouse tumor cells stably transfected with silencing hairpin (sh)RNA for TAP1 demonstrated a decreased susceptibility to cytotoxic T lymphocytes (CTL) in vitro and enhanced spontaneous brain metastasis in vivo. These data support the functional significance of TAP1 expression in tumor cells. Taken together, our data suggest that patients with low or defective TAP1 or calnexin in primary breast cancers may be at higher risks for developing brain metastasis due to the defects in T cell-based immunosurveillance. PMID:22065046

Judo as a possible cause of anoxic brain damage. A case report.

PubMed

Owens, R G; Ghadiali, E J

1991-12-01

The rules of judo provide for strangulation techniques in which the blood supply to the brain is blocked by pressure on the carotid arteries; such techniques produce anoxia and possible unconsciousness if the victim fails to submit. A case is presented of a patient with signs of anoxic brain damage, with psychometric investigation showing memory disturbance consistent with a left temporal lobe lesion. This patient had been frequently strangled during his career as a judo player; it is suggested that such frequent strangulation was the cause of the damage. Such an observation indicates the need for caution in the use of such techniques.

Clinical presentation, diagnosis, and pharmacotherapy of patients with primary brain tumors.

PubMed

Newton, H B; Turowski, R C; Stroup, T J; McCoy, L K

1999-01-01

To briefly review the clinical presentation and diagnosis of patients with primary brain tumors, followed by an in-depth survey of the pertinent pharmacotherapy. A detailed search of the neurologic, neurosurgical, and oncologic literature for basic science research, clinical studies, and review articles related to chemotherapy and pharmacotherapy of primary brain tumors. Relevant studies on tissue culture systems, animals, and humans examining the mechanisms of action, pharmacokinetics, clinical pharmacology, and treatment results of chemotherapeutic agents for primary brain tumors. In addition, studies of pharmacologic agents administered for supportive care and symptom control are reviewed. Primary brain tumors derive from cells within the intracranial cavity and generally present with headache, seizure activity, cognitive changes, and weakness. They are diagnosed most efficiently with magnetic resonance imaging. After diagnosis, the most common supportive medications include corticosteroids, gastric acid inhibitors, and anticonvulsants. Chemotherapy is adjunctive treatment for patients with malignant tumors and selected recurrent or progressive benign neoplasms. In general, the most effective chemotherapeutic drugs are alkylating agents such as the nitrosoureas, procarbazine, cisplatin, and carboplatin. Other agents used include cyclophosphamide, methotrexate, vincristine, and etoposide. Angiogenesis inhibitors and gene therapy comprise some of the novel therapeutic strategies under investigation. The efficacy of chemotherapy for primary brain tumors remains modest. Novel agents must be discovered that are more specific and attack tumor cells at the molecular level of tumorigenesis. Furthermore, strategies must be developed to counteract the pervasive problem of brain tumor chemoresistance.

Intraspinal Rewiring of the Corticospinal Tract Requires Target-Derived Brain-Derived Neurotrophic Factor and Compensates Lost Function after Brain Injury

ERIC Educational Resources Information Center

Ueno, Masaki; Hayano, Yasufumi; Nakagawa, Hiroshi; Yamashita, Toshihide

2012-01-01

Brain injury that results in an initial behavioural deficit is frequently followed by spontaneous recovery. The intrinsic mechanism of this functional recovery has never been fully understood. Here, we show that reorganization of the corticospinal tract induced by target-derived brain-derived neurotrophic factor is crucial for spontaneous recovery…

Nanocarriers for the treatment of glioblastoma multiforme: Current state-of-the-art.

PubMed

Karim, Reatul; Palazzo, Claudio; Evrard, Brigitte; Piel, Geraldine

2016-04-10

Glioblastoma multiforme, a grade IV glioma, is the most frequently occurring and invasive primary tumor of the central nervous system, which causes about 4% of cancer-associated-deaths, making it one of the most fatal cancers. With present treatments, using state-of-the-art technologies, the median survival is about 14 months and 2 year survival rate is merely 3-5%. Hence, novel therapeutic approaches are urgently necessary. However, most drug molecules are not able to cross the blood-brain barrier, which is one of the major difficulties in glioblastoma treatment. This review describes the features of blood-brain barrier, and its anatomical changes with different stages of tumor growth. Moreover, various strategies to improve brain drug delivery i.e. tight junction opening, chemical modification of the drug, efflux transporter inhibition, convection-enhanced delivery, craniotomy-based drug delivery and drug delivery nanosystems are discussed. Nanocarriers are one of the highly potential drug transport systems that have gained huge research focus over the last few decades for site specific drug delivery, including drug delivery to the brain. Properly designed nanocolloids are capable to cross the blood-brain barrier and specifically deliver the drug in the brain tumor tissue. They can carry both hydrophilic and hydrophobic drugs, protect them from degradation, release the drug for sustained period, significantly improve the plasma circulation half-life and reduce toxic effects. Among various nanocarriers, liposomes, polymeric nanoparticles and lipid nanocapsules are the most widely studied, and are discussed in this review. For each type of nanocarrier, a general discussion describing their composition, characteristics, types and various uses is followed by their specific application to glioblastoma treatment. Moreover, some of the main challenges regarding toxicity and standardized evaluation techniques are narrated in brief. Copyright © 2016 Elsevier B.V. All rights reserved.

Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy.

PubMed

Kovacs, Gabor G; Ferrer, Isidro; Grinberg, Lea T; Alafuzoff, Irina; Attems, Johannes; Budka, Herbert; Cairns, Nigel J; Crary, John F; Duyckaerts, Charles; Ghetti, Bernardino; Halliday, Glenda M; Ironside, James W; Love, Seth; Mackenzie, Ian R; Munoz, David G; Murray, Melissa E; Nelson, Peter T; Takahashi, Hitoshi; Trojanowski, John Q; Ansorge, Olaf; Arzberger, Thomas; Baborie, Atik; Beach, Thomas G; Bieniek, Kevin F; Bigio, Eileen H; Bodi, Istvan; Dugger, Brittany N; Feany, Mel; Gelpi, Ellen; Gentleman, Stephen M; Giaccone, Giorgio; Hatanpaa, Kimmo J; Heale, Richard; Hof, Patrick R; Hofer, Monika; Hortobágyi, Tibor; Jellinger, Kurt; Jicha, Gregory A; Ince, Paul; Kofler, Julia; Kövari, Enikö; Kril, Jillian J; Mann, David M; Matej, Radoslav; McKee, Ann C; McLean, Catriona; Milenkovic, Ivan; Montine, Thomas J; Murayama, Shigeo; Lee, Edward B; Rahimi, Jasmin; Rodriguez, Roberta D; Rozemüller, Annemieke; Schneider, Julie A; Schultz, Christian; Seeley, William; Seilhean, Danielle; Smith, Colin; Tagliavini, Fabrizio; Takao, Masaki; Thal, Dietmar Rudolf; Toledo, Jon B; Tolnay, Markus; Troncoso, Juan C; Vinters, Harry V; Weis, Serge; Wharton, Stephen B; White, Charles L; Wisniewski, Thomas; Woulfe, John M; Yamada, Masahito; Dickson, Dennis W

2016-01-01

Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators.

Image understanding systems based on the unifying representation of perceptual and conceptual information and the solution of mid-level and high-level vision problems

NASA Astrophysics Data System (ADS)

Kuvychko, Igor

2001-10-01

Vision is a part of a larger information system that converts visual information into knowledge structures. These structures drive vision process, resolving ambiguity and uncertainty via feedback, and provide image understanding, that is an interpretation of visual information in terms of such knowledge models. A computer vision system based on such principles requires unifying representation of perceptual and conceptual information. Computer simulation models are built on the basis of graphs/networks. The ability of human brain to emulate similar graph/networks models is found. That means a very important shift of paradigm in our knowledge about brain from neural networks to the cortical software. Starting from the primary visual areas, brain analyzes an image as a graph-type spatial structure. Primary areas provide active fusion of image features on a spatial grid-like structure, where nodes are cortical columns. The spatial combination of different neighbor features cannot be described as a statistical/integral characteristic of the analyzed region, but uniquely characterizes such region itself. Spatial logic and topology naturally present in such structures. Mid-level vision processes like clustering, perceptual grouping, multilevel hierarchical compression, separation of figure from ground, etc. are special kinds of graph/network transformations. They convert low-level image structure into the set of more abstract ones, which represent objects and visual scene, making them easy for analysis by higher-level knowledge structures. Higher-level vision phenomena like shape from shading, occlusion, etc. are results of such analysis. Such approach gives opportunity not only to explain frequently unexplainable results of the cognitive science, but also to create intelligent computer vision systems that simulate perceptional processes in both what and where visual pathways. Such systems can open new horizons for robotic and computer vision industries.

Primary pleuropulmonary synovial sarcoma with brain metastases in a paediatric patient: an unusual presentation.

PubMed

Chirmade, Pushpak Chandrakant; Parikh, Sonia; Anand, Asha; Panchal, Harsha; Patel, Apurva; Shah, Sandip

2017-01-01

Primary lung neoplasms are rare in children. The most common primary lung malignancies in children are pleuropulmonary blastoma and carcinoid tumour. Synovial sarcoma (SS) accounts for approximately 1% of all childhood malignancies. In absolute terms, the SS of the lungs and pleura are extremely rare and pose a diagnostic difficulty. Soft tissue sarcomas usually have a high potential for metastases, however, metastasis to the brain is rare, even in widely disseminated disease, and it has been described only in 3 case reports previously. Primary pleuropulmonary SS with brain metastases is even rarer. Here we present a case of an 11-year-old boy who presented with respiratory complaints, viz. fever and cough for 20 days. Initial impression was lung abscess, however, on histopathological, immunohistochemical and molecular study, the disorder was diagnosed as synovial sarcoma. After a week from the first consult, the child developed neurological symptoms, viz., an episode of convulsion and gradually worsening power of the lower limb. Computed tomography scan and Magnetic Resonance Spectroscopy was suggestive of brain metastases. Given the rarity of primary lung neoplasms in children, clinical detection remains a challenge. Delayed diagnoses are common as respiratory symptoms may be attributed to inflammatory or infective processes. Primary pleuropulmonary synovial sarcoma is a rare tumour and it is not known to commonly metastasise to the brain. Though rare, primary pleuropulmonary SS should be considered an important differential among peadiatric primary lung neoplasms due to its potential for curability if detected early, and more aggressive metastatic pattern, e.g. brain metastases making early detection imperative.

Interaction and the Architecture of the Brain. Perspectives

ERIC Educational Resources Information Center

Friedman, Dorian

2006-01-01

Recent advances in developmental science can teach us a great deal about the value of specific kinds of human interactions in the earliest years of life for the developing brain architecture. Animal experiments indicate that enriched environments with opportunity for frequent interaction and new experiences can help the animals' brains develop…

Primary frontal sinus squamous cell carcinoma in three dogs treated with piroxicam combined with carboplatin or toceranib.

PubMed

de Vos, J; Ramos Vega, S; Noorman, E; de Vos, P

2012-09-01

In human medicine, primary frontal sinus squamous cell carcinoma (pFS-SCC) is not frequently reported. In veterinary medicine, frontal sinus SCC is exclusively described as an extension of nasal cavity SCC. To our knowledge, this is the first publication concerning canine pFS-SCC, diagnosed using histology or cytology and medical imaging, in three dogs. The tumours extended into the orbit or brain cavity, without nasal involvement. Treatment was initiated with piroxicam-carboplatin. Prolongation of carboplatin delivery with a low dose intensity was performed on dogs with a favourable initial response. Dog 1 achieved a complete remission (CR), but was euthanized 344 days after start of therapy. Dog 2, still alive 3 years after start of therapy and in CR, received 14 carboplatin deliveries. In dog 3, after changing the treatment protocol into piroxicam-toceranib, a significant tumour reduction occurred, but the dog was euthanized after 195 days because of a relapse. © 2011 Blackwell Publishing Ltd.

Adult Central Nervous System Tumors Treatment (PDQ®)—Health Professional Version

Cancer.gov

Most primary brain tumors are astrocytomas, glioblastomas, and meningiomas. Most primary spinal tumors are schwannomas, meningiomas, and ependymomas. Metastatic brain tumors have spread to the brain from other parts of the body. Get detailed information about CNS tumors and treatment in this summary for clinicians.

Isolating dividing neural and brain tumour cells for gene expression profiling.

PubMed

Endaya, Berwini; Cavanagh, Brenton; Alowaidi, Faisal; Walker, Tom; de Pennington, Nicholas; Ng, Jin-Ming A; Lam, Paula Y P; Mackay-Sim, Alan; Neuzil, Jiri; Meedeniya, Adrian C B

2016-01-15

The characterisation of dividing brain cells is fundamental for studies ranging from developmental and stem cell biology, to brain cancers. Whilst there is extensive anatomical data on these dividing cells, limited gene transcription data is available due to technical constraints. We focally isolated dividing cells whilst conserving RNA, from culture, primary neural tissue and xenografted glioma tumours, using a thymidine analogue that enables gene transcription analysis. 5-ethynyl-2-deoxyuridine labels the replicating DNA of dividing cells. Once labelled, cultured cells and tissues were dissociated, fluorescently tagged with a revised click chemistry technique and the dividing cells isolated using fluorescence-assisted cell sorting. RNA was extracted and analysed using real time PCR. Proliferation and maturation related gene expression in neurogenic tissues was demonstrated in acutely and 3 day old labelled cells, respectively. An elevated expression of marker and pathway genes was demonstrated in the dividing cells of xenografted brain tumours, with the non-dividing cells showing relatively low levels of expression. BrdU "immune-labelling", the most frequently used protocol for detecting cell proliferation, causes complete denaturation of RNA, precluding gene transcription analysis. This EdU labelling technique, maintained cell integrity during dissociation, minimized copper exposure during labelling and used a cell isolation protocol that avoided cell lysis, thus conserving RNA. The technique conserves RNA, enabling the definition of cell proliferation-related changes in gene transcription of neural and pathological brain cells in cells harvested immediately after division, or following a period of maturation. Copyright © 2015 Elsevier B.V. All rights reserved.

PET Scans Obtained for Evaluation of Cognitive Dysfunction

PubMed Central

Silverman, Daniel H. S.; Mosconi, Lisa; Ercoli, Linda; Chen, W; Small, Gary W.

2015-01-01

The degree of intactness of human cognitive functioning for a given individual spans a wide spectrum, ranging from normal to severely demented. The differential diagnosis for the causes of impairment along that spectrum is also wide, and often difficult to distinguish clinically, which has led to an increasing role for neuroimaging tools in that evaluation. The most frequent causes of dementia are neurodegenerative disorders, Alzheimer's disease being the most prevalent among them, and they produce significant alterations in brain metabolism with devastating neuropathologic, economic, social and clinical consequences. These alterations are detectable through positron emission tomography (PET), even in their earliest stages. The most commonly performed PET studies of the brain are carried out with [18F]fluorodeoxyglucose (FDG) as the imaged radiopharmaceutical. Such scans have demonstrated diagnostic and prognostic utility in evaluating patients with cognitive impairment, and in distinguishing among primary neurodegenerative disorders and other etiologies for cognitive decline. In addition to focusing upon the effects on cerebral metabolism examined with FDG PET, some other changes occurring in the brains of cognitively impaired patients assessable with other radiotracers will be considered. As preventive and disease-modifying treatments are developed, early detection of accurately diagnosed disease processes facilitated by the use of PET has the potential to substantially impact upon the enormous human toll exacted by these diseases. PMID:18514081

Positron emission tomography scans obtained for the evaluation of cognitive dysfunction.

PubMed

Silverman, Daniel H S; Mosconi, Lisa; Ercoli, Linda; Chen, Wei; Small, Gary W

2008-07-01

The degree of intactness of human cognitive functioning for a given individual spans a wide spectrum, ranging from normal to severely demented. The differential diagnosis for the causes of impairment along that spectrum is also wide, and often difficult to distinguish clinically, which has led to an increasing role for neuroimaging tools in that evaluation. The most frequent causes of dementia are neurodegenerative disorders, Alzheimer's disease being the most prevalent among them, and they produce significant alterations in brain metabolism, with devastating neuropathologic, clinical, social, and economic consequences. These alterations are detectable through positron emission tomography (PET), even in their earliest stages. The most commonly performed PET studies of the brain are performed with (18)F-fluorodeoxyglucose as the imaged radiopharmaceutical. Such scans have demonstrated diagnostic and prognostic utility for clinicians evaluating patients with cognitive impairment and in distinguishing among primary neurodegenerative disorders and other etiologies contributing to cognitive decline. In addition to focusing on the effects on cerebral metabolism examined with (18)F-fluorodeoxyglucose PET, some other changes occurring in the brains of cognitively impaired patients assessable with other radiotracers will be considered. As preventive and disease-modifying treatments are developed, early detection of accurately diagnosed disease processes facilitated by the use of PET has the potential to substantially impact on the enormous human toll exacted by these diseases.

Right mesial temporal lobe epilepsy impairs empathy-related brain responses to dynamic fearful faces.

PubMed

Toller, Gianina; Adhimoolam, Babu; Grunwald, Thomas; Huppertz, Hans-Jürgen; Kurthen, Martin; Rankin, Katherine P; Jokeit, Hennric

2015-03-01

Unilateral mesial temporal lobe epilepsy (MTLE) has been associated with reduced amygdala responsiveness to fearful faces. However, the effect of unilateral MTLE on empathy-related brain responses in extra-amygdalar regions has not been investigated. Using functional magnetic resonance imaging, we measured empathy-related brain responses to dynamic fearful faces in 34 patients with unilateral MTLE (18 right sided), in an epilepsy (extra-MTLE; n = 16) and in a healthy control group (n = 30). The primary finding was that right MTLE (RMTLE) was associated with decreased activity predominantly in the right amygdala and also in bilateral periaqueductal gray (PAG) but normal activity in the right anterior insula. The results of the extra-MTLE group demonstrate that these reduced amygdala and PAG responses go beyond the attenuation caused by antiepileptic and antidepressant medication. These findings clearly indicate that RMTLE affects the function of mesial temporal and midbrain structures that mediate basic interoceptive input necessary for the emotional awareness of empathic experiences of fear. Together with the decreased empathic concern found in the RMTLE group, this study provides neurobehavioral evidence that patients with RMTLE are at increased risk for reduced empathy towards others' internal states and sheds new light on the nature of social-cognitive impairments frequently accompanying MTLE.

Prone position for the prevention of lung infection.

PubMed

Beuret, P

2002-04-01

Pulmonary infection is frequent in brain injured patients. It has been identified as an independent predictor of unfavorable neurological outcome, calling for attempts of prevention. We recently evaluated intermittent prone positioning for the prevention of ventilator-associated pneumonia (VAP) in comatose brain injured patients, in a randomized study. 25 patients were included in the prone position (PP) group: they were positioned on prone four hours once daily until they could get up to sit in an armchair; 26 patients were included in the supine position (SP) group. The main characteristics of the patients from the two groups were similar at randomization. The primary end-point was the incidence of lung worsening, defined by an increase in the Lung Injury Score by at least one point since the time of randomization. The incidence of lung worsening was lower in the PP group (12%) than in the SP group (50%) (p=0.003). The incidence of VAP was 38.4% in the SP group and 20% in the PP group (p=0.14). There was no serious complication attributable to prone positioning. In conclusion, the beneficial effect of prone positioning for prevention of lung infection in brain injured patients is not well established. However, in those patients, prone positioning is able to avoid the worsening of pulmonary function, especially in oxygenation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elnahal, Shereef M., E-mail: selnaha1@jhmi.edu; Blackford, Amanda; Smith, Koren

Purpose: To describe radiation therapy cases during which voluntary incident reporting occurred; and identify patient- or treatment-specific factors that place patients at higher risk for incidents. Methods and Materials: We used our institution's incident learning system to build a database of patients with incident reports filed between January 2011 and December 2013. Patient- and treatment-specific data were reviewed for all patients with reported incidents, which were classified by step in the process and root cause. A control group of patients without events was generated for comparison. Summary statistics, likelihood ratios, and mixed-effect logistic regression models were used for group comparisons. Results:more » The incident and control groups comprised 794 and 499 patients, respectively. Common root causes included documentation errors (26.5%), communication (22.5%), technical treatment planning (37.5%), and technical treatment delivery (13.5%). Incidents were more frequently reported in minors (age <18 years) than in adult patients (37.7% vs 0.4%, P<.001). Patients with head and neck (16% vs 8%, P<.001) and breast (20% vs 15%, P=.03) primaries more frequently had incidents, whereas brain (18% vs 24%, P=.008) primaries were less frequent. Larger tumors (17% vs 10% had T4 lesions, P=.02), and cases on protocol (9% vs 5%, P=.005) or with intensity modulated radiation therapy/image guided intensity modulated radiation therapy (52% vs 43%, P=.001) were more likely to have incidents. Conclusions: We found several treatment- and patient-specific variables associated with incidents. These factors should be considered by treatment teams at the time of peer review to identify patients at higher risk. Larger datasets are required to recommend changes in care process standards, to minimize safety risks.« less

The epidemiology of the comorbidity of epilepsy in the general population.

PubMed

Gaitatzis, Athanasios; Carroll, Kevin; Majeed, Azeem; W Sander, Josemir

2004-12-01

To describe the epidemiology of somatic and psychiatric conditions in adults with epilepsy in the community and compare it to that of people without epilepsy. A cross-sectional population-based study extracting data from the UK General Practice Research Database for the period 1995-1998. Age- and sex-standardized prevalence rates were estimated for selected conditions and groups of conditions (categorized by ICD-9 chapters) in adults with epilepsy registered with primary care physicians. Results were compared with those in adults without epilepsy in the cohort, and prevalence ratios were calculated according to two broad age groups (16-64 and older than 64 years). Conditions common in the general population also were common in adults with epilepsy. Psychiatric disorders occurred twice as often, and the risk of somatic disorders was increased in people with epilepsy, with the exception of musculoskeletal and connective tissue disorders in older adults. The prevalence ratio of neoplasia, excluding intracranial tumors, was not increased in epilepsy. The prevalence ratio of brain tumors was particularly increased in young adults [prevalence ratio (PR), 70.7] and of meningiomas in older adults (PR, 91.9). Neurodegenerative conditions, particularly dementias and Alzheimer' disease (PR, 6.3 and 8, respectively) and Parkinson' disease (PR, 3.2), appeared more frequently in people with epilepsy. Upper gastrointestinal bleed occurred more frequently in epilepsy (PR, 4.3), as did cardio- and cerebrovascular disorders, fractures, pneumonia and chronic lung diseases, and diabetes. Eczema, osteoarthritis, and rheumatoid arthritis did not occur more frequently in epilepsy. The prevalence ratio of many common psychiatric and somatic conditions is increased in adults with epilepsy who consult a primary care physician in the U.K. These findings may have implications in the diagnosis and management of epilepsy and coexisting conditions, as well as in health care provision.

[Ischemic stroke in childhood. A complication of tonsillectomy].

PubMed

Matilla Álvarez, A; García Serrano, E; González de la Huebra Labrador, T; Morales Martín, A C; Yusta Martín, G; Vaquero Roncero, L M

2016-02-01

Tonsillectomy is one of the most frequently performed otorhinolaryngological procedures on children. The postoperative complications are classified into primary or intermediate, which generally appear within 24h, and as secondary or delayed, after 48 h. We present the case of an ischemic stroke after performing a tonsillectomy on a 3 year-old boy, which was diagnosed in the immediate postoperative period. Using brain echo-doppler and angio-CT, an intraluminal clot was observed in the left internal carotid artery, probably as a result of direct vessel injury during arterial ligature for hemostasis. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

MDMA, Methylone, and MDPV: Drug-Induced Brain Hyperthermia and Its Modulation by Activity State and Environment.

PubMed

Kiyatkin, Eugene A; Ren, Suelynn E

2017-01-01

Psychomotor stimulants are frequently used by humans to intensify the subjective experience of different types of social interactions. Since psychomotor stimulants enhance metabolism and increase body temperatures, their use under conditions of physiological activation and in warm humid environments could result in pathological hyperthermia, a life-threatening symptom of acute drug intoxication. Here, we will describe the brain hyperthermic effects of MDMA, MDPV, and methylone, three structurally related recreational drugs commonly used by young adults during raves and other forms of social gatherings. After a short introduction on brain temperature and basic mechanisms underlying its physiological fluctuations, we will consider how MDMA, MDPV, and methylone affect brain and body temperatures in awake freely moving rats. Here, we will discuss the role of drug-induced heat production in the brain due to metabolic brain activation and diminished heat dissipation due to peripheral vasoconstriction as two primary contributors to the hyperthermic effects of these drugs. Then, we will consider how the hyperthermic effects of these drugs are modulated under conditions that model human drug use (social interaction and warm ambient temperature). Since social interaction results in brain and body heat production, coupled with skin vasoconstriction that impairs heat loss to the external environment, these physiological changes interact with drug-induced changes in heat production and loss, resulting in distinct changes in the hyperthermic effects of each tested drug. Finally, we present our recent data, in which we compared the efficacy of different pharmacological strategies for reversing MDMA-induced hyperthermia in both the brain and body. Specifically, we demonstrate increased efficacy of the centrally acting atypical neuroleptic compound clozapine over the peripherally acting vasodilator drug, carvedilol. These data could be important for understanding the potential dangers of MDMA in humans and the development of pharmacological tools to alleviate drug-induced hyperthermia - potentially saving the lives of highly intoxicated individuals.

Alterations of brain grey matter density and olfactory bulb volume in patients with olfactory loss after traumatic brain injury.

PubMed

Han, Pengfei; Winkler, Nicole; Hummel, Cornelia; Hähner, Antje; Gerber, Johannes; Hummel, Thomas

2018-04-27

Olfactory loss and traumatic brain injury (TBI) both lead to anatomical brain alterations in humans. Little research has been done on the structural brain changes for TBI patients with olfactory loss. Using voxel-based morphometry, the grey matter (GM) density was examined for twenty-two TBI patients with hyposmia, twenty-four TBI patients with anosmia, and twenty-two age-matched controls. Olfactory bulb (OB) volumes were measured by manual segmentation of acquired T2 weighted coronal slices using a standardized protocol. Brain lesions in the olfactory relevant areas were also examined for TBI patients. Results showed that patients with anosmia have more frequent lesions in the OB, orbitofrontal cortex (OFC) and the temporal lobe pole, as compared to patients with hyposmia. GM density in the primary olfactory area was decreased in both groups of patients. In addition, compared to controls, patients with anosmia showed GM density reduction in several secondary olfactory eloquent regions, including the gyrus rectus, medial OFC, anterior cingulate cortex, insula, and cerebellum. However, patients with hyposmia showed a lesser degree of GM reduction compared to healthy controls. Smaller OB volumes were found for patients with olfactory loss as compared to controls. TBI patients with anosmia had the smallest OB volumes which were caused by the lesions for OB. In addition, post-TBI duration was negatively correlated with GM density in the secondary olfactory areas in patients with hyposmia, but was positively correlated with GM density in the frontal and temporal gyrus in patients with anosmia. The GM density and OB volume reduction among TBI patients with olfactory loss was largely depend on the location and severity of brain lesions in olfactory relevant regions. Longer post-TBI duration had an impact on brain GM density changes, which indicate a decreased olfactory function in patients with hyposmia and possible compensatory mechanisms in patients with anosmia.

Regional brain glucose metabolism in patients with brain tumors before and after radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, G.J.; Volkow, N.D.; Lau, Y.H.

1994-05-01

This study was performed to measure regional glucose metabolism in nonaffected brain regions of patients with primary or metastatic brain tumors. Seven female and four male patients (mean age 51.5{plus_minus}14.0 years old) were compared with eleven age and sex matched normal subjects. None of the patients had hydrocephalus and/or increased intracranial pressure. Brain glucose metabolism was measured using FDG-PET scan. Five of the patients were reevaluated one week after receiving radiation treatment (RT) to the brain. Patients were on Decadron and/or Dilantin at the time of both scan. PET images were analyzed with a template of 115 nonoverlapping regions ofmore » interest and then grouped into eight gray matter regions on each hemisphere. Brain regions with tumors and edema shown in MR imaging were excluded. Z scores were used to compare individual patients` regional values with those of normal subjects. The number of regional values with Z scores of less than - 3.0 were considered abnormal and were quantified. The mean global glucose metabolic rate (mean of all regions) in nonaffected brain regions of patients was significantly lower than that of normal controls (32.1{plus_minus}9.0 versus 44.8{plus_minus}6.3 {mu}mol/100g/min, p<0.001). Analyses of individual subjects revealed that none of the controls and 8 of the 11 patients had at least one abnormal region. In these 8 patients the regions which were abnormal were most frequently localized in right (n=5) and left occipital (n=6) and right orbital frontal cortex (n=7) whereas the basal ganglia was not affected. Five of the patients who had repeated scans following RT showed decrements in tumor metabolism (41{plus_minus}20.5%) and a significant increase in whole brain metabolism (8.6{plus_minus}5.3%, p<0.001). The improvement in whole brain metabolism after RT suggests that the brain metabolic decrements in the patients were related to the presence of tumoral tissue and not just a medication effect.« less

Decoding brain responses to pixelized images in the primary visual cortex: implications for visual cortical prostheses

PubMed Central

Guo, Bing-bing; Zheng, Xiao-lin; Lu, Zhen-gang; Wang, Xing; Yin, Zheng-qin; Hou, Wen-sheng; Meng, Ming

2015-01-01

Visual cortical prostheses have the potential to restore partial vision. Still limited by the low-resolution visual percepts provided by visual cortical prostheses, implant wearers can currently only “see” pixelized images, and how to obtain the specific brain responses to different pixelized images in the primary visual cortex (the implant area) is still unknown. We conducted a functional magnetic resonance imaging experiment on normal human participants to investigate the brain activation patterns in response to 18 different pixelized images. There were 100 voxels in the brain activation pattern that were selected from the primary visual cortex, and voxel size was 4 mm × 4 mm × 4 mm. Multi-voxel pattern analysis was used to test if these 18 different brain activation patterns were specific. We chose a Linear Support Vector Machine (LSVM) as the classifier in this study. The results showed that the classification accuracies of different brain activation patterns were significantly above chance level, which suggests that the classifier can successfully distinguish the brain activation patterns. Our results suggest that the specific brain activation patterns to different pixelized images can be obtained in the primary visual cortex using a 4 mm × 4 mm × 4 mm voxel size and a 100-voxel pattern. PMID:26692860

Brain Cancer—Patient Version

Cancer.gov

Brain cancer refers to growths of malignant cells in tissues of the brain. Tumors that start in the brain are called primary brain tumors. Tumors that spread to the brain are called metastatic brain tumors. Start here to find information on brain cancer treatment, research, and statistics.

Brain Tumors

MedlinePlus

A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

Remediation of information processing following traumatic brain injury: a community-based rehabilitation approach.

PubMed

Ashley, Mark J; Ashley, Jessica; Kreber, Lisa

2012-01-01

Traumatic brain injury (TBI) results in disruption of information processing via damage to primary, secondary, and tertiary cortical regions, as well as, subcortical pathways supporting information flow within and between cortical structures. TBI predominantly affects the anterior frontal poles, anterior temporal poles, white matter tracts and medial temporal structures. Fundamental information processing skills such as attention, perceptual processing, categorization and cognitive distance are concentrated within these same regions and are frequently disrupted following injury. Information processing skills improve in accordance with the extent to which residual frontal and temporal neurons can be encouraged to recruit and bias neuronal networks or the degree to which the functional connectivity of neural networks can be re-established and result in re-emergence or regeneration of specific cognitive skills. Higher-order cognitive processes, i.e., memory, reasoning, problem solving and other executive functions, are dependent upon the integrity of attention, perceptual processing, categorization, and cognitive distance. A therapeutic construct for treatment of attention, perceptual processing, categorization and cognitive distance deficits is presented along with an interventional model for encouragement of re-emergence or regeneration of these fundamental information processing skills.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hussain, Aamir; Brown, Paul D.; Stafford, Scott L.

Purpose: Patients with brainstem metastases have limited treatment options. In this study, we reviewed outcomes after stereotactic radiosurgery (SRS) in the management of patients with brainstem metastases. Methods and Materials: Records were reviewed of 22 consecutive patients presenting with brainstem metastases who underwent SRS. The most frequent primary malignancy was the lung (n = 11), followed by breast (n = 3) and kidney (n = 2). Three patients (14%) also underwent whole-brain radiation therapy (WBRT). The median tumor volume was 0.9 mL (range, 0.1-3.3 mL); the median tumor margin dose was 16 Gy (range, 14-23 Gy). Results: Median survival timemore » after SRS was 8.5 months. Although local tumor control was achieved in all patients with imaging follow-up (n = 19), 5 patients died from development and progression of new brain metastases. Two patients (9%) had symptom improvement after SRS, whereas 1 patient (5%) developed a new hemiparesis after SRS. Conclusions: Radiosurgery is safe and provides a high local tumor control rate for patients with small brainstem metastases. Patients with limited systemic disease and good performance status should be strongly considered for SRS.« less

Three-dimensional Talairach-Tournoux brain atlas

NASA Astrophysics Data System (ADS)

Fang, Anthony; Nowinski, Wieslaw L.; Nguyen, Bonnie T.; Bryan, R. Nick

1995-04-01

The Talairach-Tournoux Stereotaxic Atlas of the human brain is a frequently consulted resource in stereotaxic neurosurgery and computer-based neuroradiology. Its primary application lies in the 2-D analysis and interpretation of neurological images. However, for the purpose of the analysis and visualization of shapes and forms, accurate mensuration of volumes, or 3-D models matching, a 3-D representation of the atlas is essential. This paper proposes and describes, along with its difficulties, a 3-D geometric extension of the atlas. We introduce a `zero-potential' surface smoothing technique, along with a space-dependent convolution kernel and space-dependent normalization. The mesh-based atlas structures are hierarchically organized, and anatomically conform to the original atlas. Structures and their constituents can be independently selected and manipulated in real-time within an integrated system. The extended atlas may be navigated by itself, or interactively registered with patient data with the proportional grid system (piecewise linear) transformation. Visualization of the geometric atlas along with patient data gives a remarkable visual `feel' of the biological structures, not usually perceivable to the untrained eyes in conventional 2-D atlas to image analysis.

Chronophin is a glial tumor modifier involved in the regulation of glioblastoma growth and invasiveness.

PubMed

Schulze, M; Fedorchenko, O; Zink, T G; Knobbe-Thomsen, C B; Kraus, S; Schwinn, S; Beilhack, A; Reifenberger, G; Monoranu, C M; Sirén, A-L; Jeanclos, E; Gohla, A

2016-06-16

Glioblastoma is the most aggressive primary brain tumor in adults. Although the rapid recurrence of glioblastomas after treatment is a major clinical challenge, the relationships between tumor growth and intracerebral spread remain poorly understood. We have identified the cofilin phosphatase chronophin (gene name: pyridoxal phosphatase, PDXP) as a glial tumor modifier. Monoallelic PDXP loss was frequent in four independent human astrocytic tumor cohorts and increased with tumor grade. We found that aberrant PDXP promoter methylation can be a mechanism leading to further chronophin downregulation in glioblastomas, which correlated with shorter glioblastoma patient survival. Moreover, we observed an inverse association between chronophin protein expression and cofilin phosphorylation levels in glioma tissue samples. Chronophin-deficient glioblastoma cells showed elevated cofilin phosphorylation, an increase in polymerized actin, a higher directionality of cell migration, and elevated in vitro invasiveness. Tumor growth of chronophin-depleted glioblastoma cells xenografted into the immunodeficient mouse brain was strongly impaired. Our study suggests a mechanism whereby the genetic and epigenetic alterations of PDXP resulting in altered chronophin expression may regulate the interplay between glioma cell proliferation and invasion.

Systemic therapy of brain metastases: non–small cell lung cancer, breast cancer, and melanoma

PubMed Central

Baik, Christina S.; Gadi, Vijayakrishna K.; Bhatia, Shailender; Chow, Laura Q.M.

2017-01-01

Brain metastases (BM) occur frequently in many cancers, particularly non–small cell lung cancer (NSCLC), breast cancer, and melanoma. The development of BM is associated with poor prognosis and has an adverse impact on survival and quality of life. Commonly used therapies for BM such as surgery or radiotherapy are associated with only modest benefits. However, recent advances in systemic therapy of many cancers have generated considerable interest in exploration of those therapies for treatment of intracranial metastases. This review discusses the epidemiology of BM from the aforementioned primary tumors and the challenges of using systemic therapies for metastatic disease located within the central nervous system. Cumulative data from several retrospective and small prospective studies suggest that molecularly targeted systemic therapies may be an effective option for the treatment of BM from NSCLC, breast cancer, and melanoma, either as monotherapy or in conjunction with other therapies. Larger prospective studies are warranted to further characterize the efficacy and safety profiles of these targeted agents for the treatment of BM. PMID:28031389

Analysis of Time-Dependent Brain Network on Active and MI Tasks for Chronic Stroke Patients

PubMed Central

Chang, Won Hyuk; Kim, Yun-Hee; Lee, Seong-Whan; Kwon, Gyu Hyun

2015-01-01

Several researchers have analyzed brain activities by investigating brain networks. However, there is a lack of the research on the temporal characteristics of the brain network during a stroke by EEG and the comparative studies between motor execution and imagery, which became known to have similar motor functions and pathways. In this study, we proposed the possibility of temporal characteristics on the brain networks of a stroke. We analyzed the temporal properties of the brain networks for nine chronic stroke patients by the active and motor imagery tasks by EEG. High beta band has a specific role in the brain network during motor tasks. In the high beta band, for the active task, there were significant characteristics of centrality and small-worldness on bilateral primary motor cortices at the initial motor execution. The degree centrality significantly increased on the contralateral primary motor cortex, and local efficiency increased on the ipsilateral primary motor cortex. These results indicate that the ipsilateral primary motor cortex constructed a powerful subnetwork by influencing the linked channels as compensatory effect, although the contralateral primary motor cortex organized an inefficient network by using the connected channels due to lesions. For the MI task, degree centrality and local efficiency significantly decreased on the somatosensory area at the initial motor imagery. Then, there were significant correlations between the properties of brain networks and motor function on the contralateral primary motor cortex and somatosensory area for each motor execution/imagery task. Our results represented that the active and MI tasks have different mechanisms of motor acts. Based on these results, we indicated the possibility of customized rehabilitation according to different motor tasks. We expect these results to help in the construction of the customized rehabilitation system depending on motor tasks by understanding temporal functional characteristics on brain network for a stroke. PMID:26656269

Digit ratio (2D:4D) in primary brain tumor patients: A case-control study.

PubMed

Bunevicius, Adomas; Tamasauskas, Sarunas; Deltuva, Vytenis Pranas; Tamasauskas, Arimantas; Sliauzys, Albertas; Bunevicius, Robertas

2016-12-01

The second-to-fourth digit ratio (2D:4D) reflects prenatal estrogen and testosterone exposure, and is established in utero. Sex steroids are implicated in development and progression of primary brain tumors. To investigate whether there is a link between 2D:4D ratio and primary brain tumors, and age at presentation. Digital images of the right and left palms of 85 primary brain tumor patients (age 56.96±13.68years; 71% women) and 106 (age 54.31±13.68years; 68% women) gender and age matched controls were obtained. The most common brain tumor diagnoses were meningioma (41%), glioblastoma (20%) and pituitary adenoma (16%). Right and left 2D:4D ratios, and right minus left 2D:4D (D r-l ) were compared between patients and controls, and were correlated with age. Right and left 2D:4D ratios were significantly lower in primary brain tumor patients relative to controls (t=-4.28, p<0.001 and t=-3.69, p<0.001, respectively). The D r-l was not different between brain tumor patients and controls (p=0.27). In meningioma and glioma patients, age at presentation correlated negatively with left 2D:4D ratio (rho=-0.42, p=0.01 and rho=-0.36, p=0.02, respectively) and positively with D r-l (rho=0.45, p=0.009 and rho=0.65, p=0.04, respectively). Right and left hand 2D:4D ratios are lower in primary brain tumor patients relative to healthy individuals suggesting greater prenatal testosterone and lower prenatal estrogen exposure in brain tumor patients. Greater age at presentation is associated with greater D r-l and with lower left 2D:4D ratio of meningioma and glioma patients. Due to small sample size our results should be considered preliminary and interpreted with caution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Outcome of supratentorial intraaxial extra ventricular primary pediatric brain tumors: A prospective study

PubMed Central

Patibandla, Mohana Rao; Bhattacharjee, Suchanda; Uppin, Megha S.; Purohit, Aniruddh Kumar

2014-01-01

Introduction: Tumors of the central nervous system (CNS) are the second most frequent malignancy of childhood and the most common solid tumor in this age group. CNS tumors represent approximately 17% of all malignancies in the pediatric age range, including adolescents. Glial neoplasms in children account for up to 60% of supratentorial intraaxial tumors. Their histological distribution and prognostic features differ from that of adults. Aims and Objectives: To study clinical and pathological characteristics, and to analyze the outcome using the Engel's classification for seizures, Karnofsky's score during the available follow-up period of minimum 1 year following the surgical and adjuvant therapy of supratentorial intraaxial extraventricular primary pediatric (SIEPP) brain tumors in children equal or less than 18 years. Materials and Methods: The study design is a prospective study done in NIMS from October 2008 to January 2012. All the patients less than 18 years of age operated for SIEPP brain tumors proven histopathologically were included in the study. All the patients with recurrent or residual primary tumors or secondaries were excluded from the study. Post operative CT or magnetic resonance imaging (MRI) is done following surgery. Results and Analysis: There were 2, 8 and 20 patients in the age range of 0-2 years, >2-10 years and 10-18 years, respectively. There were 21 male patients and 9 female patients. Out of 30 patients, 16 had lesion in the temporal lobe, 6 in frontal lobe, 4 in thalamus, 3 in parietal lobe and 1 in occipital lobe. Out of 30 patients, 11 patients had malignant lesions and nineteen patients had benign lesions. Gross total excision could be achieved in 19 patients and subtotal in 11 patients. Seven patients had mortality and four of the remaining 23 patients had increased deficits postoperatively. Remaining 19 patients either improved or remained same. Conclusions: SIEPP brain tumors have male preponderance, occur in 95% of patients in the age range of 7-18 years and have temporal lobe as the most common site of origin. The seizure presentation has good outcome compared to raised intracranial pressure features. The seizure control is quite good irrespective of subtotal or gross total excision in temporal lobe low grade tumors. All PNETs have survival of less than 1 year even with adjuvant chemo and radiotherapy. PMID:25624922

Modeling Autistic Features in Animals

PubMed Central

Patterson, Paul H.

2011-01-01

A variety of features of autism can be simulated in rodents, including the core behavioral hallmarks of stereotyped and repetitive behaviors, and deficits in social interaction and communication. Other behaviors frequently found in autism spectrum disorders (ASD) such as neophobia, enhanced anxiety, abnormal pain sensitivity and eye blink conditioning, disturbed sleep patterns, seizures, and deficits in sensorimotor gating are also present in some of the animal models. Neuropathology and some characteristic neurochemical changes that are frequently seen in autism, as well as alterations in the immune status in the brain and periphery are also found in some of the models. Several known environmental risk factors for autism have been successfully established in rodents, including maternal infection and maternal valproate administration. Also under investigation are a number of mouse models based on genetic variants associated with autism or on syndromic disorders with autistic features. This review briefly summarizes recent developments in this field, highlighting models with face and/or construct validity, and noting the potential for investigation of pathogenesis and early progress towards clinical testing of potential therapeutics. Wherever possible, reference is made to reviews rather than primary articles. PMID:21289542

What is your diagnosis? Intracranial mass in a dog.

PubMed

Harms, N Jane; Dickinson, Ryan M; Nibblett, Belle Marie D; Wobeser, Bruce K

2009-12-01

A 9-year-old, spayed female Chihuahua was presented for evaluation of acute, progressive neurologic disease. On physical examination the dog was depressed and laterally recumbent. The dog had marked neutrophilia with a toxic left shift and monocytosis. Using computed tomography with contrast enhancement a large intracranial mass lesion was identified in the rostral portion of the brain. The mass extended from the central thalamic region rostral to the cribiform plate and obliterated the lateral ventricles. A fine needle aspirate of the mass contained moderately pleomorphic polygonal cells with many intranuclear cytoplasmic pseudoinclusions (ICPs). The primary differential diagnosis was meningioma, based on cell morphology and the presence of ICPs. At necropsy, the mass was well-demarcated, unencapsulated, and densely cellular. Cells were arranged in papillary projections on fibrovascular stalks, and eosinophilic ICPs and nuclear folding were frequently seen. Cavitated areas of necrosis throughout the tumor mass were filled with intact and degenerated neutrophils. The histopathologic diagnosis was malignant papillary meningioma. ICPs are not frequently observed in Wright-stained cytologic preparations but may be found in many types of neoplasms, including meningiomas.

RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases – results and lessons learnt

PubMed Central

Gupta, Avinash; Roberts, Corran; Tysoe, Finn; Goff, Matthew; Nobes, Jenny; Lester, James; Marshall, Ernie; Corner, Carie; Wolstenholme, Virginia; Kelly, Charles; Wise, Adelyn; Collins, Linda; Love, Sharon; Woodward, Martha; Salisbury, Amanda; Middleton, Mark R

2016-01-01

Background: Brain metastases occur in up to 75% of patients with advanced melanoma. Most are treated with whole-brain radiotherapy (WBRT), with limited effectiveness. Vandetanib, an inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and rearranged during transfection tyrosine kinases, is a potent radiosensitiser in xenograft models. We compared WBRT with WBRT plus vandetanib in the treatment of patients with melanoma brain metastases. Methods: In this double-blind, multi-centre, phase 2 trial patients with melanoma brain metastases were randomised to receive WBRT (30 Gy in 10 fractions) plus 3 weeks of concurrent vandetanib 100 mg once daily or placebo. The primary endpoint was progression-free survival in brain (PFS brain). The main study was preceded by a safety run-in phase to confirm tolerability of the combination. A post-hoc analysis and literature review considered barriers to recruiting patients with melanoma brain metastases to clinical trials. Results: Twenty-four patients were recruited, six to the safety phase and 18 to the randomised phase. The study closed early due to poor recruitment. Median PFS brain was 3.3 months (90% confidence interval (CI): 1.6–5.6) in the vandetanib group and 2.5 months (90% CI: 0.2–4.8) in the placebo group (P=0.34). Median overall survival (OS) was 4.6 months (90% CI: 1.6–6.3) and 2.5 months (90% CI: 0.2–7.2), respectively (P=0.54). The most frequent adverse events were fatigue, alopecia, confusion and nausea. The most common barrier to study recruitment was availability of alternative treatments. Conclusions: The combination of WBRT plus vandetanib was well tolerated. Compared with WBRT alone, there was no significant improvement in PFS brain or OS, although we are unable to provide a definitive result due to poor accrual. A review of barriers to trial accrual identified several factors that affect study recruitment in this difficult disease area. PMID:27711083

Brain abscesses associated with right-to-left shunts in adults.

PubMed

Memon, Kashif A; Cleveland, Kerry O; Gelfand, Michael S

2012-04-01

Although brain abscesses are frequently cryptogenic in origin, bacteria must reach the brain either by direct or hematogenous spread. Right-to-left shunts, caused either by intrapulmonary vascular malformations or congenital heart defects, may allow microorganisms to evade the normal host defenses in the lungs and lead to development of brain abscesses. Two patients recently presented with brain abscesses and were found to have conditions associated with right-to-left shunts. The diagnosis of brain abscess should prompt the clinician to consider right-to-left shunts as a possible predisposing condition for brain abscess.

Diffusion Tensor Imaging Reveals White Matter Injury in a Rat Model of Repetitive Blast-Induced Traumatic Brain Injury

PubMed Central

Calabrese, Evan; Du, Fu; Garman, Robert H.; Johnson, G. Allan; Riccio, Cory; Tong, Lawrence C.

2014-01-01

Abstract Blast-induced traumatic brain injury (bTBI) is one of the most common combat-related injuries seen in U.S. military personnel, yet relatively little is known about the underlying mechanisms of injury. In particular, the effects of the primary blast pressure wave are poorly understood. Animal models have proven invaluable for the study of primary bTBI, because it rarely occurs in isolation in human subjects. Even less is known about the effects of repeated primary blast wave exposure, but existing data suggest cumulative increases in brain damage with a second blast. MRI and, in particular, diffusion tensor imaging (DTI), have become important tools for assessing bTBI in both clinical and preclinical settings. Computational statistical methods such as voxelwise analysis have shown promise in localizing and quantifying bTBI throughout the brain. In this study, we use voxelwise analysis of DTI to quantify white matter injury in a rat model of repetitive primary blast exposure. Our results show a significant increase in microstructural damage with a second blast exposure, suggesting that primary bTBI may sensitize the brain to subsequent injury. PMID:24392843

Short desynchronization episodes prevail in synchronous dynamics of human brain rhythms.

PubMed

Ahn, Sungwoo; Rubchinsky, Leonid L

2013-03-01

Neural synchronization is believed to be critical for many brain functions. It frequently exhibits temporal variability, but it is not known if this variability has a specific temporal patterning. This study explores these synchronization/desynchronization patterns. We employ recently developed techniques to analyze the fine temporal structure of phase-locking to study the temporal patterning of synchrony of the human brain rhythms. We study neural oscillations recorded by electroencephalograms in α and β frequency bands in healthy human subjects at rest and during the execution of a task. While the phase-locking strength depends on many factors, dynamics of synchrony has a very specific temporal pattern: synchronous states are interrupted by frequent, but short desynchronization episodes. The probability for a desynchronization episode to occur decreased with its duration. The transition matrix between synchronized and desynchronized states has eigenvalues close to 0 and 1 where eigenvalue 1 has multiplicity 1, and therefore if the stationary distribution between these states is perturbed, the system converges back to the stationary distribution very fast. The qualitative similarity of this patterning across different subjects, brain states and electrode locations suggests that this may be a general type of dynamics for the brain. Earlier studies indicate that not all oscillatory networks have this kind of patterning of synchronization/desynchronization dynamics. Thus, the observed prevalence of short (but potentially frequent) desynchronization events (length of one cycle of oscillations) may have important functional implications for the brain. Numerous short desynchronizations (as opposed to infrequent, but long desynchronizations) may allow for a quick and efficient formation and break-up of functionally significant neuronal assemblies.

Short desynchronization episodes prevail in synchronous dynamics of human brain rhythms

NASA Astrophysics Data System (ADS)

Ahn, Sungwoo; Rubchinsky, Leonid L.

2013-03-01

Neural synchronization is believed to be critical for many brain functions. It frequently exhibits temporal variability, but it is not known if this variability has a specific temporal patterning. This study explores these synchronization/desynchronization patterns. We employ recently developed techniques to analyze the fine temporal structure of phase-locking to study the temporal patterning of synchrony of the human brain rhythms. We study neural oscillations recorded by electroencephalograms in α and β frequency bands in healthy human subjects at rest and during the execution of a task. While the phase-locking strength depends on many factors, dynamics of synchrony has a very specific temporal pattern: synchronous states are interrupted by frequent, but short desynchronization episodes. The probability for a desynchronization episode to occur decreased with its duration. The transition matrix between synchronized and desynchronized states has eigenvalues close to 0 and 1 where eigenvalue 1 has multiplicity 1, and therefore if the stationary distribution between these states is perturbed, the system converges back to the stationary distribution very fast. The qualitative similarity of this patterning across different subjects, brain states and electrode locations suggests that this may be a general type of dynamics for the brain. Earlier studies indicate that not all oscillatory networks have this kind of patterning of synchronization/desynchronization dynamics. Thus, the observed prevalence of short (but potentially frequent) desynchronization events (length of one cycle of oscillations) may have important functional implications for the brain. Numerous short desynchronizations (as opposed to infrequent, but long desynchronizations) may allow for a quick and efficient formation and break-up of functionally significant neuronal assemblies.

Turbo-Proton Echo Planar Spectroscopic Imaging (t-PEPSI) MR technique in the detection of diffuse axonal damage in brain injury. Comparison with Gradient-Recalled Echo (GRE) sequence.

PubMed

Giugni, E; Sabatini, U; Hagberg, G E; Formisano, R; Castriota-Scanderbeg, A

2005-01-01

Diffuse axonal injury (DAI) is a common type of primary neuronal injury in patients with severe traumatic brain injury, and is frequently accompanied by tissue tear haemorrhage. The T2*-weighted gradient-recalled echo (GRE) sequences are more sensitive than T2-weighted spin-echo images for detection of haemorrhage. This study was undertaken to determine whether turbo-PEPSI, an extremely fast multi-echo-planar-imaging sequence, can be used as an alternative to the GRE sequence for detection of DAI. Nineteen patients (mean age 24,5 year) with severe traumatic brain injury (TBI), occurred at least 3 months earlier, underwent a brain MRI study on a 1.5-Tesla scanner. A qualitative evaluation of the turbo-PEPSI sequences was performed by identifying the optimal echo time and in-plane resolution. The number and size of DAI lesions, as well as the signal intensity contrast ratio (SI CR), were computed for each set of GRE and turbo-PEPSI images, and divided according to their anatomic location into lobar and/or deep brain. There was no significant difference between GRE and turbo-PEPSI sequences in the total number of DAI lesions detected (283 vs 225 lesions, respectively). The GRE sequence identified a greater number of hypointense lesions in the temporal lobe compared to the t-PEPSI sequence (72 vs 35, p<0.003), while no significant differences were found for the other brain regions. The SI CR was significantly better (i.e. lower) for the turbo-PEPSI than for the GRE sequence (p<0.00001). Owing to its very short scan time and high sensitivity to the haemorrhage foci, the turbo-PEPSI sequence can be used as an alternative to the GRE to assess brain DAI in severe TBI patients, especially if uncooperative and medically unstable.

The BRAIN Initiative Provides a Unifying Context for Integrating Core STEM Competencies into a Neurobiology Course.

PubMed

Schaefer, Jennifer E

2016-01-01

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative introduced by the Obama Administration in 2013 presents a context for integrating many STEM competencies into undergraduate neuroscience coursework. The BRAIN Initiative core principles overlap with core STEM competencies identified by the AAAS Vision and Change report and other entities. This neurobiology course utilizes the BRAIN Initiative to serve as the unifying theme that facilitates a primary emphasis on student competencies such as scientific process, scientific communication, and societal relevance while teaching foundational neurobiological content such as brain anatomy, cellular neurophysiology, and activity modulation. Student feedback indicates that the BRAIN Initiative is an engaging and instructional context for this course. Course module organization, suitable BRAIN Initiative commentary literature, sample primary literature, and important assignments are presented.

Combined Effects of Primary and Tertiary Blast on Rat Brain: Characterization of a Model of Blast-induced Mild Traumatic Brain Injury

DTIC Science & Technology

2014-03-01

military environments, affected in- dividuals (e.g. football players) often sustain additional mild injuries. mTBI symptoms are typically mild and... concussion andmild traumatic brain injury. PM R 3, S354–358; DOI:10.1016/j.pmrj.2011.07.017 (2011). 2. Hendricks, A. M. et al. Screening for mild traumatic...Mendez, M. F. et al. Mild traumatic brain injury from primary blast vs. blunt forces: post- concussion consequences and functional neuroimaging

Effect of Heterogeneity of Tissues on RF Energy Absorption in the Brain for Exposure Assessment in Epidemiological Studies on Mobile Phone Use and Brain Tumors

NASA Astrophysics Data System (ADS)

Varsier, Nadege; Wake, Kanako; Taki, Masao; Watanabe, Soichi

We compared SAR distributions in major anatomical structures of the brain of a homogeneous and a heterogeneous model using FDTD calculations. Our results proved a good correlation between SAR values in lobes of the brain where tumors may arise more frequently. However SAR values at some specific locations were shown to be under or overestimated.

Residential Radon and Brain Tumour Incidence in a Danish Cohort

PubMed Central

Bräuner, Elvira V.; Andersen, Zorana J.; Andersen, Claus E.; Pedersen, Camilla; Gravesen, Peter; Ulbak, Kaare; Hertel, Ole; Loft, Steffen; Raaschou-Nielsen, Ole

2013-01-01

Background Increased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist. Objective To investigate the long-term effect of exposure to residential radon on the risk of primary brain tumour in a prospective Danish cohort. Methods During 1993–1997 we recruited 57,053 persons. We followed each cohort member for cancer occurrence from enrolment until 31 December 2009, identifying 121 primary brain tumour cases. We traced residential addresses from 1 January 1971 until 31 December 2009 and calculated radon concentrations at each address using information from central databases regarding geology and house construction. Cox proportional hazards models were used to estimate incidence rate-ratios (IRR) and 95% confidence intervals (CI) for the risk of primary brain tumours associated with residential radon exposure with adjustment for age, sex, occupation, fruit and vegetable consumption and traffic-related air pollution. Effect modification by air pollution was assessed. Results Median estimated radon was 40.5 Bq/m3. The adjusted IRR for primary brain tumour associated with each 100 Bq/m3 increment in average residential radon levels was 1.96 (95% CI: 1.07; 3.58) and this was exposure-dependently higher over the four radon exposure quartiles. This association was not modified by air pollution. Conclusions We found significant associations and exposure-response patterns between long-term residential radon exposure radon in a general population and risk of primary brain tumours, adding new knowledge to this field. This finding could be chance and needs to be challenged in future studies. PMID:24066143

Analyzing pitch chroma and pitch height in the human brain.

PubMed

Warren, Jason D; Uppenkamp, Stefan; Patterson, Roy D; Griffiths, Timothy D

2003-11-01

The perceptual pitch dimensions of chroma and height have distinct representations in the human brain: chroma is represented in cortical areas anterior to primary auditory cortex, whereas height is represented posterior to primary auditory cortex.

Amnestic MCI Patients' Perspectives toward Disclosure of Amyloid PET Results in a Research Context.

PubMed

Vanderschaeghe, Gwendolien; Schaeverbeke, Jolien; Vandenberghe, Rik; Dierickx, Kris

2017-01-01

Researchers currently are not obligated to share individual research results (IRR) with participants. This non-disclosure policy has been challenged on the basis of participants' rights to be aware and in control of their personal medical information. Here, we determined how patients view disclosure of research PET results of brain amyloid and why they believe it is advantageous or disadvantageous to disclose. As a part of a larger diagnostic trial, we conducted semi-structured interviews with patients with amnestic Mild Cognitive Impairment (aMCI). Participants had the option to receive their brain amyloid PET scan result (i.e., their IRR). Interviews were conducted before they received their IRR. A total of 38 aMCI patients (100% of study participants) wanted to know their IRR. The two most frequently mentioned reasons for choosing IRR disclosure were to better understand their brain health status and to be better able to make informed decisions about future personal arrangements (e.g., inheritance tax, moving into a smaller house, end-of-life decisions, etc.). Emotional risk was mentioned as the primary disadvantage of knowing one's IRR. On the other hand, non-disclosure was considered to be emotionally difficult also, as patients would be uncertain about their future health condition. Many patients diagnosed clinically with aMCI want to know their brain amyloid test results, even though this knowledge may be disadvantageous to them. Knowing what is going on with their health and the ability to make informed decisions about their future were the two principal advantages mentioned for obtaining their amyloid PET results. Because of the overwhelming consensus of aMCI patients was to disclose their brain amyloid PET scan results, researchers should strongly consider releasing this information to research subjects.

Fast detection of diffuse axonal damage in severe traumatic brain injury: comparison of gradient-recalled echo and turbo proton echo-planar spectroscopic imaging MRI sequences.

PubMed

Giugni, Elisabetta; Sabatini, Umberto; Hagberg, Gisela E; Formisano, Rita; Castriota-Scanderbeg, Alessandro

2005-05-01

Diffuse axonal injury (DAI) is a common type of primary neuronal injury in patients with severe traumatic brain injury (TBI), and is frequently accompanied by tissue tear hemorrhage. T2-weighted gradient-recalled echo (GRE) sequences are more sensitive than T2-weighted spin-echo images for detection of hemorrhage. The purpose of this study is to compare turbo Proton Echo Planar Spectroscopic Imaging (t-PEPSI), an extremely fast sequence, with GRE sequence in the detection of DAI. Twenty-one patients (mean age 26.8 years) with severe TBI occurred at least 3 months earlier, underwent a brain MR Imaging study on a 1.5-T scanner. A qualitative evaluation of the t-PEPSI sequences was performed by identifying the optimal echo time and in-plane resolution. The number and size of DAI lesions, as well as the signal intensity contrast ratio (SI CR), were computed for each set of GRE and t-PEPSI images, and divided according to their anatomic location as lobar and/or deep brain. There was no significant difference between GRE and t-PEPSI sequences in the detection of the total number of DAI lesions (291 vs. 230, respectively). GRE sequence delineated a higher number of DAI in the temporal lobe compared to the t-PEPSI sequence (74 vs. 37, P < .004), while no differences were found for the other regions. The SI CR was significantly lower with the t-PEPSI than the GRE sequence (P < .00001). Owing to its very short scan time and high sensitivity to the hemorrhage foci, the t-PEPSI sequence may be used as an alternative to the GRE to assess brain DAI in severe TBI patients, especially if uncooperative and medically unstable.

Subnetwork mining on functional connectivity network for classification of minimal hepatic encephalopathy.

PubMed

Zhang, Daoqiang; Tu, Liyang; Zhang, Long-Jiang; Jie, Biao; Lu, Guang-Ming

2018-06-01

Hepatic encephalopathy (HE), as a complication of cirrhosis, is a serious brain disease, which may lead to death. Accurate diagnosis of HE and its intermediate stage, i.e., minimal HE (MHE), is very important for possibly early diagnosis and treatment. Brain connectivity network, as a simple representation of brain interaction, has been widely used for the brain disease (e.g., HE and MHE) analysis. However, those studies mainly focus on finding disease-related abnormal connectivity between brain regions, although a large number of studies have indicated that some brain diseases are usually related to local structure of brain connectivity network (i.e., subnetwork), rather than solely on some single brain regions or connectivities. Also, mining such disease-related subnetwork is a challenging task because of the complexity of brain network. To address this problem, we proposed a novel frequent-subnetwork-based method to mine disease-related subnetworks for MHE classification. Specifically, we first mine frequent subnetworks from both groups, i.e., MHE patients and non-HE (NHE) patients, respectively. Then we used the graph-kernel based method to select the most discriminative subnetworks for subsequent classification. We evaluate our proposed method on a MHE dataset with 77 cirrhosis patients, including 38 MHE patients and 39 NHE patients. The results demonstrate that our proposed method can not only obtain the improved classification performance in comparison with state-of-the-art network-based methods, but also identify disease-related subnetworks which can help us better understand the pathology of the brain diseases.

Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance.

PubMed

Saunus, Jodi M; Quinn, Michael C J; Patch, Ann-Marie; Pearson, John V; Bailey, Peter J; Nones, Katia; McCart Reed, Amy E; Miller, David; Wilson, Peter J; Al-Ejeh, Fares; Mariasegaram, Mythily; Lau, Queenie; Withers, Teresa; Jeffree, Rosalind L; Reid, Lynne E; Da Silva, Leonard; Matsika, Admire; Niland, Colleen M; Cummings, Margaret C; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Anderson, Matthew J; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Kassahn, Karin S; Narayanan, Vairavan; Taib, Nur Aishah; Teo, Soo-Hwang; Chow, Yock Ping; kConFab; Jat, Parmjit S; Brandner, Sebastian; Flanagan, Adrienne M; Khanna, Kum Kum; Chenevix-Trench, Georgia; Grimmond, Sean M; Simpson, Peter T; Waddell, Nicola; Lakhani, Sunil R

2015-11-01

Treatment options for patients with brain metastases (BMs) have limited efficacy and the mortality rate is virtually 100%. Targeted therapy is critically under-utilized, and our understanding of mechanisms underpinning metastatic outgrowth in the brain is limited. To address these deficiencies, we investigated the genomic and transcriptomic landscapes of 36 BMs from breast, lung, melanoma and oesophageal cancers, using DNA copy-number analysis and exome- and RNA-sequencing. The key findings were as follows. (a) Identification of novel candidates with possible roles in BM development, including the significantly mutated genes DSC2, ST7, PIK3R1 and SMC5, and the DNA repair, ERBB-HER signalling, axon guidance and protein kinase-A signalling pathways. (b) Mutational signature analysis was applied to successfully identify the primary cancer type for two BMs with unknown origins. (c) Actionable genomic alterations were identified in 31/36 BMs (86%); in one case we retrospectively identified ERBB2 amplification representing apparent HER2 status conversion, then confirmed progressive enrichment for HER2-positivity across four consecutive metastatic deposits by IHC and SISH, resulting in the deployment of HER2-targeted therapy for the patient. (d) In the ERBB/HER pathway, ERBB2 expression correlated with ERBB3 (r(2)  = 0.496; p < 0.0001) and HER3 and HER4 were frequently activated in an independent cohort of 167 archival BM from seven primary cancer types: 57.6% and 52.6% of cases were phospho-HER3(Y1222) or phospho-HER4(Y1162) membrane-positive, respectively. The HER3 ligands NRG1/2 were barely detectable by RNAseq, with NRG1 (8p12) genomic loss in 63.6% breast cancer-BMs, suggesting a microenvironmental source of ligand. In summary, this is the first study to characterize the genomic landscapes of BM. The data revealed novel candidates, potential clinical applications for genomic profiling of resectable BMs, and highlighted the possibility of therapeutically targeting HER3, which is broadly over-expressed and activated in BMs, independent of primary site and systemic therapy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Somatization among older primary care attenders.

PubMed

Sheehan, B; Bass, C; Briggs, R; Jacoby, R

2003-07-01

The importance of somatization among older primary care attenders is unclear. We aimed to establish the prevalence, persistence and associations of somatization among older primary care attenders, and the associations of frequent attendance. One hundred and forty primary care attenders over 65 years were rated twice, 10 months apart, on measures of somatization, psychiatric status, physical health and attendance. The syndrome of GMS hypochondriacal neurosis had a prevalence of 5% but was transient. Somatized symptoms and attributions were persistent and associated with depression, physical illness and perceived poor social support. Frequent attenders (top third) had higher rates of depression, physical illness and somatic symptoms, and lower perceived support. Somatization is common among older primary care attenders and has similar correlates to younger primary care somatizers. Psychological distress among older primary care attenders is associated with frequent attendance. Improved recognition should result in benefits to patients and services.

Brainstem conundrum: the Chiari I malformation.

PubMed

Mueller, D

2001-04-01

To describe the Chairi I Malformation in relation to the anatomy of the brain and spinal cord, the common manifestations of the condition, diagnostic considerations, and management for the primary care provider. Extensive review of the world-wide scientific literature on the condition, supplemented with actual case studies. The adult Chairi I Malformation is an insidious congenital brainstem anomaly that consists of caudal displacement of the cerebellar tonsils, brainstem and fourth ventricle into the upper cervical space, resulting in overcrowding of the posterior fossa. Due to the vague, and often ambiguous presenting symptoms of Chiari I Malformation, many patients are misdiagnosed with conditions such as multiple sclerosis, fibromyalgia, chronic fatigue syndrome, or psychiatric disorders. Patients frequently experience symptoms months to years prior to accurate diagnosis and often incur irreversible neurologic deficits.

Welcome back? Frequent attenders to a pediatric primary care center.

PubMed

Klein, Melissa; Vaughn, Lisa M; Baker, Raymond C; Taylor, Trisha

2011-09-01

This study examines frequent attenders of a pediatric primary care clinic at a large urban children's hospital--who they are and their reasons for frequent attendance to the clinic. The literature suggests that some visits by frequent attenders may not be medically necessary, and these additional appointments may impair others' access to medical care within the same system. The key to eliminating excessive primary care visits is to determine if it is a problem in the primary care practice (quantify the problem), explore the reasons for the visits (from the patients' perspective), and then provide educational interventions that address the various causes for the extra visits and encourage the use of available resources, either ancillary services in the practice itself or resources and agencies available in the community (e.g. social service, legal aid).

A non-aggressive, highly efficient, enzymatic method for dissociation of human brain-tumors and brain-tissues to viable single-cells.

PubMed

Volovitz, Ilan; Shapira, Netanel; Ezer, Haim; Gafni, Aviv; Lustgarten, Merav; Alter, Tal; Ben-Horin, Idan; Barzilai, Ori; Shahar, Tal; Kanner, Andrew; Fried, Itzhak; Veshchev, Igor; Grossman, Rachel; Ram, Zvi

2016-06-01

Conducting research on the molecular biology, immunology, and physiology of brain tumors (BTs) and primary brain tissues requires the use of viably dissociated single cells. Inadequate methods for tissue dissociation generate considerable loss in the quantity of single cells produced and in the produced cells' viability. Improper dissociation may also demote the quality of data attained in functional and molecular assays due to the presence of large quantities cellular debris containing immune-activatory danger associated molecular patterns, and due to the increased quantities of degraded proteins and RNA. Over 40 resected BTs and non-tumorous brain tissue samples were dissociated into single cells by mechanical dissociation or by mechanical and enzymatic dissociation. The quality of dissociation was compared for all frequently used dissociation enzymes (collagenase, DNase, hyaluronidase, papain, dispase) and for neutral protease (NP) from Clostridium histolyticum. Single-cell-dissociated cell mixtures were evaluated for cellular viability and for the cell-mixture dissociation quality. Dissociation quality was graded by the quantity of subcellular debris, non-dissociated cell clumps, and DNA released from dead cells. Of all enzymes or enzyme combinations examined, NP (an enzyme previously not evaluated on brain tissues) produced dissociated cell mixtures with the highest mean cellular viability: 93 % in gliomas, 85 % in brain metastases, and 89 % in non-tumorous brain tissue. NP also produced cell mixtures with significantly less cellular debris than other enzymes tested. Dissociation using NP was non-aggressive over time-no changes in cell viability or dissociation quality were found when comparing 2-h dissociation at 37 °C to overnight dissociation at ambient temperature. The use of NP allows for the most effective dissociation of viable single cells from human BTs or brain tissue. Its non-aggressive dissociative capacity may enable ambient-temperature shipping of tumor pieces in multi-center clinical trials, meanwhile being dissociated. As clinical grade NP is commercially available it can be easily integrated into cell-therapy clinical trials in neuro-oncology. The high quality viable cells produced may enable investigators to conduct more consistent research by avoiding the experimental artifacts associated with the presence dead cells or cellular debris.

Personal Characteristics and Experience of Primary Care Predicting Frequent Use of Emergency Department: A Prospective Cohort Study.

PubMed

Hudon, Catherine; Sanche, Steven; Haggerty, Jeannie L

2016-01-01

A small number of patients frequently using the emergency department (ED) account for a disproportionate amount of the total ED workload and are considered using this service inappropriately. The aim of this study was to identify prospectively personal characteristics and experience of organizational and relational dimensions of primary care that predict frequent use of ED. This study was conducted among parallel cohorts of the general population and primary care patients (N = 1,769). The measures were at baseline (T1), 12 (T2) and 24 months (T3): self-administered questionnaire on current health, health behaviours and primary care experience in the previous year. Use of medical services was confirmed using administrative databases. Mixed effect logistic regression modeling identified characteristics predicting frequent ED utilization. A higher likelihood of frequent ED utilization was predicted by lower socioeconomic status, higher disease burden, lower perceived organizational accessibility, higher number of reported healthcare coordination problems and not having a complete annual check-up, above and beyond adjustment for all independent variables. Personal characteristics such as low socioeconomic status and high disease burden as well as experience of organizational dimensions of primary care such as low accessibility, high healthcare coordination problems and low comprehensiveness of care are prospectively associated with frequent ED utilization. Interventions developed to prevent inappropriate ED visits, such as case management for example, should tailor low socioeconomic status and patients with high disease burden and should aim to improve experience of primary care regarding accessibility, coordination and comprehensiveness.

Human primary mixed brain cultures: preparation, differentiation, characterization and application to neuroscience research.

PubMed

Ray, Balmiki; Chopra, Nipun; Long, Justin M; Lahiri, Debomoy K

2014-09-16

Culturing primary cortical neurons is an essential neuroscience technique. However, most cultures are derived from rodent brains and standard protocols for human brain cultures are sparse. Herein, we describe preparation, maintenance and major characteristics of a primary human mixed brain culture, including neurons, obtained from legally aborted fetal brain tissue. This approach employs standard materials and techniques used in the preparation of rodent neuron cultures, with critical modifications. This culture has distinct differences from rodent cultures. Specifically, a significant numbers of cells in the human culture are derived from progenitor cells, and the yield and survival of the cells grossly depend on the presence of bFGF. In the presence of bFGF, this culture can be maintained for an extended period. Abundant productions of amyloid-β, tau and proteins make this a powerful model for Alzheimer's research. The culture also produces glia and different sub-types of neurons. We provide a well-characterized methodology for human mixed brain cultures useful to test therapeutic agents under various conditions, and to carry forward mechanistic and translational studies for several brain disorders.

Methylene Blue Protects Astrocytes against Glucose Oxygen Deprivation by Improving Cellular Respiration

PubMed Central

Roy Choudhury, Gourav; Winters, Ali; Rich, Ryan M.; Ryou, Myoung-Gwi; Gryczynski, Zygmunt; Yuan, Fang; Yang, Shao-Hua; Liu, Ran

2015-01-01

Astrocytes outnumber neurons and serve many metabolic and trophic functions in the mammalian brain. Preserving astrocytes is critical for normal brain function as well as for protecting the brain against various insults. Our previous studies have indicated that methylene blue (MB) functions as an alternative electron carrier and enhances brain metabolism. In addition, MB has been shown to be protective against neurodegeneration and brain injury. In the current study, we investigated the protective role of MB in astrocytes. Cell viability assays showed that MB treatment significantly protected primary astrocytes from oxygen-glucose deprivation (OGD) & reoxygenation induced cell death. We also studied the effect of MB on cellular oxygen and glucose metabolism in primary astrocytes following OGD-reoxygenation injury. MB treatment significantly increased cellular oxygen consumption, glucose uptake and ATP production in primary astrocytes. In conclusion our study demonstrated that MB protects astrocytes against OGD-reoxygenation injury by improving astrocyte cellular respiration. PMID:25848957

Using Ferumoxytol-Enhanced MRI to Measure Inflammation in Patients With Brain Tumors or Other Conditions of the CNS

ClinicalTrials.gov

2017-08-30

Brain Injury; Central Nervous System Degenerative Disorder; Central Nervous System Infectious Disorder; Central Nervous System Vascular Malformation; Hemorrhagic Cerebrovascular Accident; Ischemic Cerebrovascular Accident; Primary Brain Neoplasm; Brain Cancer; Brain Tumors

Long-Term Survival in a Patient with Multiple Brain Metastases from Small-Cell Lung Cancer Treated with Gamma Knife Radiosurgery on Four Occasions: A Case Report

PubMed Central

Elaimy, Ameer L.; Thumma, Sudheer R.; Lamm, Andrew F.; Mackay, Alexander R.; Lamoreaux, Wayne T.; Fairbanks, Robert K.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.

2012-01-01

Brain metastases are the most common cancerous neoplasm in the brain. The treatment of these lesions is challenging and often includes a multimodality management approach with whole-brain radiation therapy, stereotactic radiosurgery, and neurosurgery options. Although advances in biomedical imaging technologies and the treatment of extracranial cancer have led to the overall increase in the survival of brain metastases patients, the finding that select patients survive several years remains puzzling. For this reason, we present the case of a 70-year-old patient who was diagnosed with multiple brain metastases from small-cell lung cancer five years ago and is currently alive following treatment with chemotherapy for the primary cancer and whole-brain radiation therapy and Gamma Knife radiosurgery on four separate occasions for the neurological cancer. Since the diagnosis of brain metastases five years ago, the patient's primary cancer has remained controlled. Furthermore, multiple repeat GKRS procedures provided this patient with high levels of local tumor control, which in combination with a stable primary cancer led to an extended period of survival and a highly functional life. Further analysis and clinical research will be valuable in assessing the durability of multiple GKRS for brain metastases patients who experience long-term survival. PMID:23091748

An fMRI investigation into the effect of preceding stimuli during visual oddball tasks.

PubMed

Fajkus, Jiří; Mikl, Michal; Shaw, Daniel Joel; Brázdil, Milan

2015-08-15

This study investigates the modulatory effect of stimulus sequence on neural responses to novel stimuli. A group of 34 healthy volunteers underwent event-related functional magnetic resonance imaging while performing a three-stimulus visual oddball task, involving randomly presented frequent stimuli and two types of infrequent stimuli - targets and distractors. We developed a modified categorization of rare stimuli that incorporated the type of preceding rare stimulus, and analyzed the event-related functional data according to this sequence categorization; specifically, we explored hemodynamic response modulation associated with increasing rare-to-rare stimulus interval. For two consecutive targets, a modulation of brain function was evident throughout posterior midline and lateral temporal cortex, while responses to targets preceded by distractors were modulated in a widely distributed fronto-parietal system. As for distractors that follow targets, brain function was modulated throughout a set of posterior brain structures. For two successive distractors, however, no significant modulation was observed, which is consistent with previous studies and our primary hypothesis. The addition of the aforementioned technique extends the possibilities of conventional oddball task analysis, enabling researchers to explore the effects of the whole range of rare stimuli intervals. This methodology can be applied to study a wide range of associated cognitive mechanisms, such as decision making, expectancy and attention. Copyright © 2015 Elsevier B.V. All rights reserved.

Language, Executive Function and Social Cognition in the Diagnosis of Frontotemporal Dementia Syndromes

PubMed Central

Harciarek, Michał; Cosentino, Stephanie

2015-01-01

Frontotemporal dementia (FTD) represents a spectrum of non-Alzheimer’s degenerative conditions associated with focal atrophy of the frontal and/or temporal lobes. Frontal and temporal regions of the brain have been shown to be strongly involved in executive function, social cognition and language processing and, thus, deficits in these domains are frequently seen in patients with FTD or may even be hallmarks of a specific FTD subtype ( i.e., relatively selective and progressive language impairment in primary progressive aphasia). In this review, we have attempted to delineate how language, executive function, and social cognition may contribute to the diagnosis of FTD syndromes, namely the behavioral variant FTD as well as the language variants of FTD including the three subtypes of primary progressive aphasia (PPA): non-fluent/agrammatic, semantic, and logopenic. This review also addresses the extent to which deficits in these cognitive areas contribute to the differential diagnosis of FTD versus AD. Finally, early clinical determinants of pathology are briefly discussed and contemporary challenges to the diagnosis of FTD are presented. PMID:23611348

Frequent binge drinking after combat-acquired traumatic brain injury among active duty military personnel with a past year combat deployment.

PubMed

Adams, Rachel Sayko; Larson, Mary Jo; Corrigan, John D; Horgan, Constance M; Williams, Thomas V

2012-01-01

To determine whether combat-acquired traumatic brain injury (TBI) is associated with postdeployment frequent binge drinking among a random sample of active duty military personnel. Active duty military personnel who returned home within the past year from deployment to a combat theater of operations and completed a survey health assessment (N = 7155). Cross-sectional observational study with multivariate analysis of responses to the 2008 Department of Defense Survey of Health Related Behaviors Among Active Duty Military Personnel, an anonymous, random, population-based assessment of the armed forces. Frequent binge drinking: 5 or more drinks on the same occasion, at least once per week, in the past 30 days. TBI-AC: self-reported altered consciousness only; loss of consciousness (LOC) of less than 1 minute (TBI-LOC <1); and LOC of 1 minute or greater (TBI-LOC 1+) after combat injury event exposure. Of active duty military personnel who had a past year combat deployment, 25.6% were frequent binge drinkers and 13.9% reported experiencing a TBI on the deployment, primarily TBI-AC (7.5%). In regression models adjusting for demographics and positive screen for posttraumatic stress disorder, active duty military personnel with TBI had increased odds of frequent binge drinking compared with those with no injury exposure or without TBI: TBI-AC (adjusted odds ratio, 1.48; 95% confidence interval, 1.18-1.84); TBI-LOC 1+ (adjusted odds ratio, 1.67; 95% confidence interval, 1.00-2.79). Traumatic brain injury was significantly associated with past month frequent binge drinking after controlling for posttraumatic stress disorder, combat exposure, and other covariates.

Transformation of Primary Hamster Brain Cells with JC Virus and Its DNA

PubMed Central

Frisque, R. J.; Rifkin, D. B.; Walker, D. L.

1980-01-01

We transformed primary hamster brain cells with four isolates of JC virus and JC virus DNA. Several properties of these transformants were characterized and compared to those of simian virus 40 transformants isolated under identical conditions. Images PMID:6251275

Descriptive statistical analysis of a real life cohort of 2419 patients with brain metastases of solid cancers.

PubMed

Berghoff, Anna S; Schur, Sophie; Füreder, Lisa M; Gatterbauer, Brigitte; Dieckmann, Karin; Widhalm, Georg; Hainfellner, Johannes; Zielinski, Christoph C; Birner, Peter; Bartsch, Rupert; Preusser, Matthias

2016-01-01

We provide a descriptive statistical analysis of baseline characteristics and the clinical course of a large real-life cohort of brain metastases (BM) patients. We performed a retrospective chart review for patients treated for BM of solid cancers at the Medical University of Vienna between 1990 and 2011. We identified a total of 2419 BM patients (50.5% male, 49.5% female, median age 59 years). The primary tumour was lung cancer in 43.2%, breast cancer in 15.7%, melanoma in 16.4%, renal cell carcinoma in 9.1%, colorectal cancer in 9.3% and unknown in 1.4% of cases. Rare tumour types associated with BM included genitourinary cancers (4.1%), sarcomas (0.7%). gastro-oesophageal cancer (0.6%) and head and neck cancers (0.2%). 48.7% of patients presented with a singular BM, 27.7% with 2-3 and 23.5% with >3 BM. Time from primary tumour to BM diagnosis was shortest in lung cancer (median 11 months; range 1-162) and longest in breast cancer (median 44 months; 1-443; p<0.001). Multiple BM were most frequent in breast cancer (30.6%) and least frequent in colorectal cancer (8.5%; p<0.001). Patients with breast cancer had the longest median overall survival times (8 months), followed by patients with lung cancer (7 months), renal cell carcinoma (7 months), melanoma (5 months) and colorectal cancer (4 months; p<0.001; log rank test). Recursive partitioning analysis and graded prognostic assessment scores showed significant correlation with overall survival (both p<0.001, log rank test). Evaluation of the disease status in the past 2 months prior to patient death showed intracranial progression in 35.9%, extracranial progression in 27.5% and combined extracranial and intracranial progression in 36.6% of patients. Our data highlight the heterogeneity in presentation and clinical course of BM patients in the everyday clinical setting and may be useful for rational planning of clinical studies.

Cognitive Rehabilitation for Children with Acquired Brain Injury

ERIC Educational Resources Information Center

Slomine, Beth; Locascio, Gianna

2009-01-01

Cognitive deficits are frequent consequences of acquired brain injury (ABI) and often require intervention. We review the theoretical and empirical literature on cognitive rehabilitation in a variety of treatment domains including attention, memory, unilateral neglect, speech and language, executive functioning, and family involvement/education.…

Brain metastasis detection by resonant Raman optical biopsy method

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; Cheng, Gangge; Zhou, Lixin; Zhang, Chunyuan; Pu, Yang; Li, Zhongwu; Liu, Yulong; Li, Qingbo; Wang, Wei; Alfano, Robert R.

2014-03-01

Resonant Raman (RR) spectroscopy provides an effective way to enhance Raman signal from particular bonds associated with key molecules due to changes on a molecular level. In this study, RR is used for detection of human brain metastases of five kinds of primary organs of lung, breast, kidney, rectal and orbital in ex-vivo. The RR spectra of brain metastases cancerous tissues were measured and compared with those of normal brain tissues and the corresponding primary cancer tissues. The differences of five types of brain metastases tissues in key bio-components of carotene, tryptophan, lactate, alanine and methyl/methylene group were investigated. The SVM-KNN classifier was used to categorize a set of RR spectra data of brain metastasis of lung cancerous tissues from normal brain tissue, yielding diagnostic sensitivity and specificity at 100% and 75%, respectively. The RR spectroscopy may provide new moleculebased optical probe tools for diagnosis and classification of brain metastatic of cancers.

Complete prevalence of malignant primary brain tumors registry data in the United States compared with other common cancers, 2010

PubMed Central

Zhang, Adah S.; Ostrom, Quinn T.; Kruchko, Carol; Rogers, Lisa; Peereboom, David M.

2017-01-01

Abstract Background. Complete prevalence proportions illustrate the burden of disease in a population. This study estimates the 2010 complete prevalence of malignant primary brain tumors overall and by Central Brain Tumor Registry of the United States (CBTRUS) histology groups, and compares the brain tumor prevalence estimates to the complete prevalence of other common cancers as determined by the Surveillance, Epidemiology, and End Results Program (SEER) by age at prevalence (2010): children (0–14 y), adolescent and young adult (AYA) (15–39 y), and adult (40+ y). Methods. Complete prevalence proportions were estimated using a novel regression method extended from the Completeness Index Method, which combines survival and incidence data from multiple sources. In this study, two datasets, CBTRUS and SEER, were used to calculate complete prevalence estimates of interest. Results. Complete prevalence for malignant primary brain tumors was 47.59/100000 population (22.31, 48.49, and 57.75/100000 for child, AYA, and adult populations). The most prevalent cancers by age were childhood leukemia (36.65/100000), AYA melanoma of the skin (66.21/100000), and adult female breast (1949.00/100000). The most prevalent CBTRUS histologies in children and AYA were pilocytic astrocytoma (6.82/100000, 5.92/100000), and glioblastoma (12.76/100000) in adults. Conclusions. The relative impact of malignant primary brain tumors is higher among children than any other age group; it emerges as the second most prevalent cancer among children. Complete prevalence estimates for primary malignant brain tumors fills a gap in overall cancer knowledge, which provides critical information toward public health and health care planning, including treatment, decision making, funding, and advocacy programs. PMID:28039365

Traumatic Brain Injury and Blood-Brain Barrier Cross-Talk.

PubMed

Nasser, Mohammad; Bejjani, Fabienne; Raad, Mohamad; Abou-El-Hassan, Hadi; Mantash, Sarah; Nokkari, Amaly; Ramadan, Naify; Kassem, Nouhad; Mondello, Stefania; Hamade, Eva; Darwish, Hala; Zibara, Kazem; Kobeissy, Firas

2016-01-01

Traumatic brain injury, often referred to as the "silent epidemic," is a nondegenerative, non-congenital insult to the brain due to a blow or penetrating object that disrupts the function of the brain leading to permanent or temporary impairment of cognition, physical and psychosocial functions. Traumatic brain injury usually has poor prognosis for long-term treatment and is a major cause of mortality and morbidity worldwide; approximately 10 million deaths and/or hospitalizations annually are directly related to traumatic brain injury. Traumatic brain injury involves primary and secondary insults. Primary injury occurs during the initial insult, and results from direct or indirect force applied to the physical structures of the brain. Secondary injury is characterized by longer-term degeneration of neurons, glial cells, and vascular tissues due to activation of several proteases, glutamate and pro-inflammatory cytokine secretion. In addition, there is growing evidence that the blood-brain barrier is involved in the course of traumatic brain injury pathophysiology and has detrimental effects on the overall pathology of brain trauma, as will be discussed in this work.

Cross-Species Affective Neuroscience Decoding of the Primal Affective Experiences of Humans and Related Animals

PubMed Central

Panksepp, Jaak

2011-01-01

Background The issue of whether other animals have internally felt experiences has vexed animal behavioral science since its inception. Although most investigators remain agnostic on such contentious issues, there is now abundant experimental evidence indicating that all mammals have negatively and positively-valenced emotional networks concentrated in homologous brain regions that mediate affective experiences when animals are emotionally aroused. That is what the neuroscientific evidence indicates. Principal Findings The relevant lines of evidence are as follows: 1) It is easy to elicit powerful unconditioned emotional responses using localized electrical stimulation of the brain (ESB); these effects are concentrated in ancient subcortical brain regions. Seven types of emotional arousals have been described; using a special capitalized nomenclature for such primary process emotional systems, they are SEEKING, RAGE, FEAR, LUST, CARE, PANIC/GRIEF and PLAY. 2) These brain circuits are situated in homologous subcortical brain regions in all vertebrates tested. Thus, if one activates FEAR arousal circuits in rats, cats or primates, all exhibit similar fear responses. 3) All primary-process emotional-instinctual urges, even ones as complex as social PLAY, remain intact after radical neo-decortication early in life; thus, the neocortex is not essential for the generation of primary-process emotionality. 4) Using diverse measures, one can demonstrate that animals like and dislike ESB of brain regions that evoke unconditioned instinctual emotional behaviors: Such ESBs can serve as ‘rewards’ and ‘punishments’ in diverse approach and escape/avoidance learning tasks. 5) Comparable ESB of human brains yield comparable affective experiences. Thus, robust evidence indicates that raw primary-process (i.e., instinctual, unconditioned) emotional behaviors and feelings emanate from homologous brain functions in all mammals (see Appendix S1), which are regulated by higher brain regions. Such findings suggest nested-hierarchies of BrainMind affective processing, with primal emotional functions being foundational for secondary-process learning and memory mechanisms, which interface with tertiary-process cognitive-thoughtful functions of the BrainMind. PMID:21915252

Cross-species affective neuroscience decoding of the primal affective experiences of humans and related animals.

PubMed

Panksepp, Jaak

2011-01-01

The issue of whether other animals have internally felt experiences has vexed animal behavioral science since its inception. Although most investigators remain agnostic on such contentious issues, there is now abundant experimental evidence indicating that all mammals have negatively and positively-valenced emotional networks concentrated in homologous brain regions that mediate affective experiences when animals are emotionally aroused. That is what the neuroscientific evidence indicates. The relevant lines of evidence are as follows: 1) It is easy to elicit powerful unconditioned emotional responses using localized electrical stimulation of the brain (ESB); these effects are concentrated in ancient subcortical brain regions. Seven types of emotional arousals have been described; using a special capitalized nomenclature for such primary process emotional systems, they are SEEKING, RAGE, FEAR, LUST, CARE, PANIC/GRIEF and PLAY. 2) These brain circuits are situated in homologous subcortical brain regions in all vertebrates tested. Thus, if one activates FEAR arousal circuits in rats, cats or primates, all exhibit similar fear responses. 3) All primary-process emotional-instinctual urges, even ones as complex as social PLAY, remain intact after radical neo-decortication early in life; thus, the neocortex is not essential for the generation of primary-process emotionality. 4) Using diverse measures, one can demonstrate that animals like and dislike ESB of brain regions that evoke unconditioned instinctual emotional behaviors: Such ESBs can serve as 'rewards' and 'punishments' in diverse approach and escape/avoidance learning tasks. 5) Comparable ESB of human brains yield comparable affective experiences. Thus, robust evidence indicates that raw primary-process (i.e., instinctual, unconditioned) emotional behaviors and feelings emanate from homologous brain functions in all mammals (see Appendix S1), which are regulated by higher brain regions. Such findings suggest nested-hierarchies of BrainMind affective processing, with primal emotional functions being foundational for secondary-process learning and memory mechanisms, which interface with tertiary-process cognitive-thoughtful functions of the BrainMind.

Modification of existing human motor memories is enabled by primary cortical processing during memory reactivation.

PubMed

Censor, Nitzan; Dimyan, Michael A; Cohen, Leonardo G

2010-09-14

One of the most challenging tasks of the brain is to constantly update the internal neural representations of existing memories. Animal studies have used invasive methods such as direct microfusion of protein inhibitors to designated brain areas, in order to study the neural mechanisms underlying modification of already existing memories after their reactivation during recall [1-4]. Because such interventions are not possible in humans, it is not known how these neural processes operate in the human brain. In a series of experiments we show here that when an existing human motor memory is reactivated during recall, modification of the memory is blocked by virtual lesion [5] of the related primary cortical human brain area. The virtual lesion was induced by noninvasive repetitive transcranial magnetic stimulation guided by a frameless stereotactic brain navigation system and each subject's brain image. The results demonstrate that primary cortical processing in the human brain interacting with pre-existing reactivated memory traces is critical for successful modification of the existing related memory. Modulation of reactivated memories by noninvasive cortical stimulation may have important implications for human memory research and have far-reaching clinical applications. Copyright © 2010 Elsevier Ltd. All rights reserved.

Brain tuberculomas: a case report.

PubMed

Saleh, Maryam; Saeedi, Ali Asghar; Ali Pooran, Ali

2014-07-01

An unusual incidence of tuberculosis in different parts of the body is called tuberculomas. The rate of brain tuberculosis is rare. The following case of tuberculamas of the brain, presented by enhancing rings of meninges, is reported because of its rarity. It was a case of brain tuberculomas in a 15-year-old girl with primary symptoms of headache and general weakness, and no signs of primary pulmonary infection. The subject underwent computerized tomography (CT) and magnetic resonance imaging (MRI) of the brain. Microbiological tests (acid fast bacilli smear-AFB, and culture of biopsy specimen) were applied subsequently. According to the results, the problem was diagnosed as brain tuberculomas. After operation she was completely treated with anti-TB drugs. Although brain tuberculosis is rare, it was diagnosed on the basis of histopathology and the patient's successful response to anti-tuberculous drug treatment.

Intracerebral transplants of primary muscle cells: a potential 'platform' for transgene expression in the brain

NASA Technical Reports Server (NTRS)

Jiao, S.; Schultz, E.; Wolff, J. A.

1992-01-01

After the transplantation of rat primary muscle cells into the caudate or cortex of recipient rats, the muscle cells were able to persist for at least 6 months. Muscle cells transfected with expression plasmids prior to transplantation were able to express reporter genes in the brains for at least 2 months. These results suggest that muscle cells might be a useful 'platform' for transgene expression in the brain.

Lower gingival squamous cell carcinoma with brain metastasis during long-term cetuximab treatment: A case report.

PubMed

Naruse, Tomofumi; Tokuhisa, Mitsuko; Yanamoto, Souichi; Sakamoto, Yuki; Okuyama, Kohei; Tsuchihashi, Hiroki; Umeda, Masahiro

2018-05-01

Long-term cetuximab treatment can lead to acquired resistance, and tumor progression and/or new lesions often occur. The present report describes a case of lower gingival squamous cell carcinoma with brain metastasis during long-term cetuximab treatment in a 60-year-old man, including findings of an immunohistochemical study. The resected primary tumors, biopsy of the lung metastasis before administration of cetuximab, and brain metastasis specimens mediated by cetuximab were immunohistochemically examined. Histologically, the metastatic brain lesion showed hyperkeratinizing tumor cells with deeply stained irregular nuclei with necrotizing tumor cells, and a decrease in cell density was exhibited in part of the tumor nest. Moreover, the brain lesion was less malignant compared with the primary tumor and metastatic lung lesions. Immunohistochemically, the metastatic brain lesions showed low expression of epidermal growth factor receptor (EGFR) and high expression of N-cadherin compared with the primary tumor and metastatic lung lesions. These results suggest that acquired resistance to cetuximab may be associated with low EGFR expression and increased epithelial-to-mesenchymal transition potential.

Cerebellar White Matter Abnormalities following Primary Blast Injury in US Military Personnel

PubMed Central

Mac Donald, Christine; Johnson, Ann; Cooper, Dana; Malone, Thomas; Sorrell, James; Shimony, Joshua; Parsons, Matthew; Snyder, Abraham; Raichle, Marcus; Fang, Raymond; Flaherty, Stephen; Russell, Michael; Brody, David L.

2013-01-01

Little is known about the effects of blast exposure on the human brain in the absence of head impact. Clinical reports, experimental animal studies, and computational modeling of blast exposure have suggested effects on the cerebellum and brainstem. In US military personnel with isolated, primary blast-related ‘mild’ traumatic brain injury and no other known insult, we found diffusion tensor MRI abnormalities consistent with cerebellar white matter injury in 3 of 4 subjects. No abnormalities in other brain regions were detected. These findings add to the evidence supporting the hypothesis that primary blast exposure contributes to brain injury in the absence of head impact and that the cerebellum may be particularly vulnerable. However, the clinical effects of these abnormalities cannot be determined with certainty; none of the subjects had ataxia or other detected evidence of cerebellar dysfunction. The details of the blast events themselves cannot be disclosed at this time, thus additional animal and computational modeling will be required to dissect the mechanisms underlying primary blast-related traumatic brain injury. Furthermore, the effects of possible subconcussive impacts and other military-related exposures cannot be determined from the data presented. Thus many aspects of topic will require further investigation. PMID:23409052

The Role of Hypoxia in Glioblastoma Invasion

PubMed Central

Monteiro, Ana Rita; Pilkington, Geoffrey J.

2017-01-01

Glioblastoma multiforme (GBM), a grade IV astrocytoma, is the most common and deadly type of primary malignant brain tumor, with a patient’s median survival rate ranging from 15 to 17 months. The current treatment for GBM involves tumor resection surgery based on MRI image analysis, followed by radiotherapy and treatment with temozolomide. However, the gradual development of tumor resistance to temozolomide is frequent in GBM patients leading to subsequent tumor regrowth/relapse. For this reason, the development of more effective therapeutic approaches for GBM is of critical importance. Low tumor oxygenation, also known as hypoxia, constitutes a major concern for GBM patients, since it promotes cancer cell spreading (invasion) into the healthy brain tissue in order to evade this adverse microenvironment. Tumor invasion not only constitutes a major obstacle to surgery, radiotherapy, and chemotherapy, but it is also the main cause of death in GBM patients. Understanding how hypoxia triggers the GBM cells to become invasive is paramount to developing novel and more effective therapies against this devastating disease. In this review, we will present a comprehensive examination of the available literature focused on investigating how GBM hypoxia triggers an invasive cancer cell phenotype and the role of these invasive proteins in GBM progression. PMID:29165393

Factors Affecting the Occurrence of Spinal Reflexes in Brain Dead Cases.

PubMed

Hosseini, Mahsa Sadat; Ghorbani, Fariba; Ghobadi, Omid; Najafizadeh, Katayoun

2015-08-01

Brain death is defined as the permanent absence of all cortical and brain stem reflexes. A wide range of spontaneous or reflex movements that are considered medullary reflexes are observed in heart beating cases that appear brain dead, which may create uncertainty about the diagnosis of brain death and cause delays in deceased-donor organ donation process. We determined the frequency and type of medullary reflexes and factors affecting their occurrence in brain dead cases. During 1 year, 122 cases who fulfilled the criteria for brain death were admitted to the special intensive care unit for organ procurement of Masih Daneshvari Hospital. Presence of spinal reflexes was evaluated by trained coordinators and was recorded in a form in addition to other information including demographic characteristics, cause of brain death, time from detection of brain death, history of craniotomy, vital signs, serum electrolyte levels, and parameters of arterial blood gas determination. Most cases (63%) included in this study were male, and mean age was 33 ± 15 y. There was > 1 spinal reflex observed in 40 cases (33%). The most frequent reflex was plantar response (17%) following by myoclonus (10%), triple flexion reflex (9%), pronator extension reflex (8%), and undulating toe reflex (7%). Mean systolic blood pressure was significantly higher in cases who exhibited medullary reflexes than other cases (126 ± 19 mm Hg vs 116 ± 17 mm Hg; P = .007). Spinal reflexes occur frequently in brain dead cases, especially when they become hemodynamically stable after treatment in the organ procurement unit. Observing these movements by caregivers and family members has a negative effect on obtaining family consent and organ donation. Increasing awareness about spinal reflexes is necessary to avoid suspicion about the brain death diagnosis and delays in organ donation.

Brain intrinsic network connectivity in individuals with frequent tanning behavior.

PubMed

Ketcherside, Ariel; Filbey, Francesca M; Aubert, Pamela M; Seibyl, John P; Price, Julianne L; Adinoff, Bryon

2018-05-01

Emergent studies suggest a bidirectional relationship between brain functioning and the skin. This neurocutaneous connection may be responsible for the reward response to tanning and, thus, may contribute to excessive tanning behavior. To date, however, this association has not yet been examined. To explore whether intrinsic brain functional connectivity within the default mode network (DMN) is related to indoor tanning behavior. Resting state functional connectivity (rsFC) was obtained in twenty adults (16 females) with a history of indoor tanning. Using a seed-based [(posterior cingulate cortex (PCC)] approach, the relationship between tanning severity and FC strength was assessed. Tanning severity was measured with symptom count from the Structured Clinical Interview for Tanning Abuse and Dependence (SITAD) and tanning intensity (lifetime indoor tanning episodes/years tanning). rsFC strength between the PCC and other DMN regions (left globus pallidus, left medial frontal gyrus, left superior frontal gyrus) is positively correlated with tanning symptom count. rsFC strength between the PCC and salience network regions (right anterior cingulate cortex, left inferior parietal lobe, left inferior temporal gyrus) is correlated with tanning intensity. Greater connectivity between tanning severity and DMN and salience network connectivity suggests that heightened self-awareness of salient stimuli may be a mechanism that underlies frequent tanning behavior. These findings add to the growing evidence of brain-skin connection and reflect dysregulation in the reward processing networks in those with frequent tanning.

Cerebrovascular Smooth Muscle Actin Is Increased in Non-Demented Subjects with Frequent Senile Plaques at Autopsy: Implications for the Pathogenesis of Alzheimer Disease

PubMed Central

Hulette, Christine M.; Ervin, John F.; Edmonds, Yvette; Antoine, Samantha; Stewart, Nicolas; Szymanski, Mari H.; Hayden, Kathleen M; Pieper, Carl F.; Burke, James R.; Welsh-Bohmer, Kathleen A.

2009-01-01

We previously found that vascular smooth muscle actin (SMA) is reduced in the brains of patients with late stage Alzheimer disease (AD) compared to brains of non-demented, neuropathologically normal subjects. To assess the pathogenetic significance and disease specificity of this finding, we studied 3 additional patient groups: non-demented subjects without significant AD type pathology (“Normal”, n = 20); non-demented subjects with frequent senile plaques at autopsy (“Preclinical AD”, n = 20); and subjects with frontotemporal dementia, (“FTD”, n = 10). The groups were matched for gender and age with those previously reported; SMA immunohistochemistry and image analysis were performed as previously described. Surprisingly, SMA expression in arachnoid, cerebral cortex and white matter arterioles was greater in the Preclinical AD group than in the Normal and FTD groups. The plaques were not associated with amyloid angiopathy or other vascular disease in this group. SMA expression in the brains of the Normal group was intermediate between the Preclinical AD and FTD groups. All 3 groups exhibited much greater SMA expression than in our previous report. The presence of frequent plaques and increased arteriolar SMA expression in the brains of non-demented subjects suggest that increased SMA expression might represent a physiologic response to neurodegeneration that could prevent or delay overt expression dementia in AD. PMID:19287310

An Evolutionary Perspective on Learning Disability in Mathematics

PubMed Central

Geary, David C.

2015-01-01

A distinction between potentially evolved, or biologically-primary forms of cognition, and the culturally-specific, or biologically-secondary forms of cognition that are built from primary systems is used to explore mathematical learning disability (MLD). Using this model, MLD could result from deficits in the brain and cognitive systems that support biologically-primary mathematical competencies, or from the brain and cognitive systems that support the modification of primary systems for the creation of secondary knowledge and secondary cognitive competencies. The former include visuospatial long-term and working memory and the intraparietal sulcus, whereas the latter include the central executive component of working memory and the anterior cingulate cortex and lateral prefrontal cortex. Different forms of MLD are discussed as related to each of the cognitive and brain systems. PMID:17650991

The Relationship between Concussion Knowledge and the High School Athlete's Intention to Report Traumatic Brain Injury Symptoms: A Systematic Review of the Literature

ERIC Educational Resources Information Center

Taylor, Mary Ellen; Sanner, Jennifer E.

2017-01-01

Sports-related concussion or traumatic brain injury (TBI) is a frequent occurrence among high school athletes. Long-term and short-term effects of TBI on the athlete's developing brain can be minimized if the athlete reports and is effectively treated for TBI symptoms. Knowledge of concussion symptoms and a school culture of support are critical…

Treatment of brain metastases: chemotherapy.

PubMed

Grimm, Sean A

2012-02-01

Although systemic therapy is the primary therapeutic modality for disseminated cancer, it plays a limited role in the treatment of brain metastases (BM). This review discusses the blood-brain barrier (BBB), interactions of systemic therapy with supportive care agents used in BM patients, the role of primary tumor sensitivity in the treatment of BM, and unique issues related to the specific primary tumor histologies. The specialized physiology of the brain vasculature that forms the BBB may preclude large and/or water-soluble systemic agents from reaching BM. Once metastases grow larger than 1-2 mm, there is preclinical and clinical evidence that the BBB is at least partially disrupted. Thus, the best treatment strategy in established BM may be to use an agent that is effective against the primary tumor regardless of its apparent BBB permeability. The use of anticonvulsants and corticosteroids must be carefully considered as they can decrease the effectiveness of systemic anti-tumor therapy. Despite the absence of level I data to routinely recommend the use of systemic therapy for solid tumor BM, these treatments should be considered in patients with good performance status and multiple, small metastases, especially if the primary tumor is chemosensitive. The systemic treatment of BM will continue to evolve as effective small-molecule inhibitors are developed and treatment regimens for each specific primary tumor are optimized.

[Some neurologic and psychiatric complications in endocrine disorders: the thyroid gland].

PubMed

Aszalós, Zsuzsa

2007-02-18

Thyroid hormones are of primary importance for the perinatal development of the central nervous system, and for normal function of the adult brain. These hormones primarily regulate the transcription of specific target genes. They increase the cortical serotonergic neurotransmission, and play an important role in regulating central noradrenergic and GABA function. Thyroid deficiency during the perinatal period results in mental retardation. Hypothyroidism of the adults causes most frequently dementia and depression. Other less common clinical pictures include myxoedema coma, dysfunction of cerebellum and cranial nerves. Hypothyroidism also increases predisposition of stroke. Peripheral diseases frequently include polyneuropathy, carpal tunnel syndrome, myalgic state, and rarely myokymia. Nearly all the hyperthyroid patients show minor psychiatric signs, and infrequently psychosis, dementia, confusion state, depression, apathetic thyrotoxicosis, thyrotoxic crisis, seizures, pyramidal signs, or chorea occur. The peripheral complications may be indicated by chronic thyrotoxic myopathy, infiltrative ophthalmopathy, myasthenia gravis, periodic hypokalemic paralysis and polyneuropathy. Generalized resistance to thyroid hormone was confirmed in a number of patients with attention deficit-hyperactivity disorder. Significantly elevated antithyroid antibody titers characterize Hashimoto's encephalopathy. This condition is a rare, acute - subacute, serious, life threatening, but steroid-responsive, relapsing-remitting, autoimmune disease.

Complete prevalence of malignant primary brain tumors registry data in the United States compared with other common cancers, 2010

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Adah S.; Ostrom, Quinn T.; Kruchko, Carol

Complete prevalence proportions illustrate the burden of disease in a population. Here, this study estimates the 2010 complete prevalence of malignant primary brain tumors overall and by Central Brain Tumor Registry of the United States (CBTRUS) histology groups, and compares the brain tumor prevalence estimates to the complete prevalence of other common cancers as determined by the Surveillance, Epidemiology, and End Results Program (SEER) by age at prevalence (2010): children (0–14 y), adolescent and young adult (AYA) (15–39 y), and adult (40+ y).

Complete prevalence of malignant primary brain tumors registry data in the United States compared with other common cancers, 2010

DOE PAGES

Zhang, Adah S.; Ostrom, Quinn T.; Kruchko, Carol; ...

2016-12-29

Complete prevalence proportions illustrate the burden of disease in a population. Here, this study estimates the 2010 complete prevalence of malignant primary brain tumors overall and by Central Brain Tumor Registry of the United States (CBTRUS) histology groups, and compares the brain tumor prevalence estimates to the complete prevalence of other common cancers as determined by the Surveillance, Epidemiology, and End Results Program (SEER) by age at prevalence (2010): children (0–14 y), adolescent and young adult (AYA) (15–39 y), and adult (40+ y).

A model for optimizing delivery of targeted radionuclide therapies into resection cavity margins for the treatment of primary brain cancers.

PubMed

Raghavan, Raghu; Howell, Roger W; Zalutsky, Michael R

2017-06-01

Radionuclides conjugated to molecules that bind specifically to cancer cells are of great interest as a means to increase the specificity of radiotherapy. Currently, the methods to disseminate these targeted radiotherapeutics have been either systemic delivery or by bolus injection into the tumor or tumor resection cavity. Herein we model a potentially more efficient method of delivery, namely pressure-driven fluid flow, called convection-enhanced delivery (CED), where a device infuses the molecules in solution (or suspension) directly into the tissue of interest. In particular, we focus on the setting of primary brain cancer after debulking surgery, where the tissue margins surrounding the surgical resection cavity are infiltrated with tumor cells and the most frequent sites of tumor recurrence. We develop the combination of fluid flow, chemical kinetics, and radiation dose models needed to examine such protocols. We focus on Auger electron-emitting radionuclides (e.g. 67 Ga, 77 Br, 111 In, 125 I, 123 I, 193m Pt, 195m Pt) whose short range makes them ideal for targeted therapy in this setting of small foci of tumor spread within normal tissue. By solving these model equations, we confirm that a CED protocol is promising in allowing sufficient absorbed dose to destroy cancer cells with minimal absorbed dose to normal cells at clinically feasible activity levels. We also show that Auger emitters are ideal for this purpose while the longer range alpha particle emitters fail to meet criteria for effective therapy (as neither would energetic beta particle emitters). The model is used with simplified assumptions on the geometry and homogeneity of brain tissue to allow semi-analytic solutions to be displayed, and with the purpose of a first examination of this new delivery protocol proposed for radionuclide therapy. However, we emphasize that it is immediately extensible to personalized therapy treatment planning as we have previously shown for conventional CED, at the price of requiring a fully numerical computerized approach.

Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy

PubMed Central

Ferrer, Isidro; Grinberg, Lea T.; Alafuzoff, Irina; Attems, Johannes; Budka, Herbert; Cairns, Nigel J.; Crary, John F.; Duyckaerts, Charles; Ghetti, Bernardino; Halliday, Glenda M.; Ironside, James W.; Love, Seth; Mackenzie, Ian R.; Munoz, David G.; Murray, Melissa E.; Nelson, Peter T.; Takahashi, Hitoshi; Trojanowski, John Q.; Ansorge, Olaf; Arzberger, Thomas; Baborie, Atik; Beach, Thomas G.; Bieniek, Kevin F.; Bigio, Eileen H.; Bodi, Istvan; Dugger, Brittany N.; Feany, Mel; Gelpi, Ellen; Gentleman, Stephen M.; Giaccone, Giorgio; Hatanpaa, Kimmo J.; Heale, Richard; Hof, Patrick R.; Hofer, Monika; Hortobágyi, Tibor; Jellinger, Kurt; Jicha, Gregory A.; Ince, Paul; Kofler, Julia; Kövari, Enikö; Kril, Jillian J.; Mann, David M.; Matej, Radoslav; McKee, Ann C.; McLean, Catriona; Milenkovic, Ivan; Montine, Thomas J.; Murayama, Shigeo; Lee, Edward B.; Rahimi, Jasmin; Rodriguez, Roberta D.; Rozemüller, Annemieke; Schneider, Julie A.; Schultz, Christian; Seeley, William; Seilhean, Danielle; Smith, Colin; Tagliavini, Fabrizio; Takao, Masaki; Thal, Dietmar Rudolf; Toledo, Jon B.; Tolnay, Markus; Troncoso, Juan C.; Vinters, Harry V.; Weis, Serge; Wharton, Stephen B.; White, Charles L.; Wisniewski, Thomas; Woulfe, John M.; Yamada, Masahito

2016-01-01

Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators. PMID:26659578

REACH: study protocol of a randomised trial of rehabilitation very early in congenital hemiplegia

PubMed Central

Boyd, Roslyn N; Ziviani, Jenny; Sakzewski, Leanne; Novak, Iona; Badawi, Nadia; Pannek, Kerstin; Elliott, Catherine; Greaves, Susan; Guzzetta, Andrea; Whittingham, Koa; Valentine, Jane; Morgan, Cathy; Wallen, Margaret; Eliasson, Ann-Christin; Findlay, Lisa; Ware, Robert; Fiori, Simona; Rose, Stephen

2017-01-01

Objectives Congenital hemiplegia is the most common form of cerebral palsy (CP). Children with unilateral CP show signs of upper limb asymmetry by 8 months corrected age (ca) but are frequently not referred to therapy until after 12 months ca. This study compares the efficacy of infant-friendly modified constraint-induced movement therapy (Baby mCIMT) to infant friendly bimanual therapy (Baby BIM) on upper limb, cognitive and neuroplasticity outcomes in a multisite randomised comparison trial. Methods and analysis 150 infants (75 in each group), aged between 3 and 6 months ca, with asymmetric brain injury and clinical signs of upper extremity asymmetry will be recruited. Children will be randomised centrally to receive equal doses of either Baby mCIMT or Baby BIM. Baby mCIMT comprises restraint of the unimpaired hand using a simple restraint (eg, glove, sock), combined with intensive parent implemented practice focusing on active use of the impaired hand in a play-based context. In contrast, Baby BIM promotes active play requiring both hands in a play-based context. Both interventions will be delivered by parents at home with monthly home visits and interim telecommunication support by study therapists. Assessments will be conducted at study entry; at 6, 12 months ca immediately postintervention (primary outcome) and 24 months ca (retention). The primary outcome will be the Mini-Assisting Hand Assessment. Secondary outcomes include the Bayley Scale for Infant and Toddler Development (cognitive and motor domains) and the Hand Assessment of Infants. A subset of children will undertake MRI scans at 24 months ca to evaluate brain lesion severity and brain (re)organisation after intervention. Ethics and dissemination Full ethical approvals for this study have been obtained from the relevant sites. The findings will be disseminated in peer-reviewed publications. Trial registration number Australian and New Zealand Clinical Trials Registry: ACTRN12615000180516, Pre results. PMID:28928195

Brain lesion-pattern analysis in patients with olfactory dysfunctions following head trauma

PubMed Central

Lötsch, Jörn; Ultsch, Alfred; Eckhardt, Maren; Huart, Caroline; Rombaux, Philippe; Hummel, Thomas

2016-01-01

The presence of cerebral lesions in patients with neurosensory alterations provides a unique window into brain function. Using a fuzzy logic based combination of morphological information about 27 olfactory-eloquent brain regions acquired with four different brain imaging techniques, patterns of brain damage were analyzed in 127 patients who displayed anosmia, i.e., complete loss of the sense of smell (n = 81), or other and mechanistically still incompletely understood olfactory dysfunctions including parosmia, i.e., distorted perceptions of olfactory stimuli (n = 50), or phantosmia, i.e., olfactory hallucinations (n = 22). A higher prevalence of parosmia, and as a tendency also phantosmia, was observed in subjects with medium overall brain damage. Further analysis showed a lower frequency of lesions in the right temporal lobe in patients with parosmia than in patients without parosmia. This negative direction of the differences was unique for parosmia. In anosmia, and also in phantosmia, lesions were more frequent in patients displaying the respective symptoms than in those without these dysfunctions. In anosmic patients, lesions in the right olfactory bulb region were much more frequent than in patients with preserved sense of smell, whereas a higher frequency of carriers of lesions in the left frontal lobe was observed for phantosmia. We conclude that anosmia, and phantosmia, are the result of lost function in relevant brain areas whereas parosmia is more complex, requiring damaged and intact brain regions at the same time. PMID:26937377

Squamous cell lung carcinoma presenting as melena: a case report and review of the literature.

PubMed

Azar, Ibrahim; Koutroumpakis, Efstratios; Patel, Raina; Mehdi, Syed

2017-10-03

Lung cancer has a predilection to widely metastasize to the liver, bone, brain and adrenal glands. Metastasis of primary lung tumors to the stomach is infrequent, with only sporadic cases reported. Most cases are asymptomatic and diagnosed post-mortem on autopsy. The incidence of symptomatic gastrointestinal metastases is extremely rare. Herein, we describe a case of gastric metastasis by squamous cell lung carcinoma, presenting as melena and diagnosed by esophagogastroduodenoscopy. To the best of our knowledge, only twenty other cases in the English literature have reported symptomatic gastric metastasis of lung cancer diagnosed by endoscopic biopsy. A brief review of the literature shows gastric metastasis of lung cancer to have a predilection to occur most frequently in male smokers with the most common type of tumor likely to be squamous cell carcinoma.

Receptor-Mediated Drug Delivery Systems Targeting to Glioma

PubMed Central

Wang, Shanshan; Meng, Ying; Li, Chengyi; Qian, Min; Huang, Rongqin

2015-01-01

Glioma has been considered to be the most frequent primary tumor within the central nervous system (CNS). The complexity of glioma, especially the existence of the blood-brain barrier (BBB), makes the survival and prognosis of glioma remain poor even after a standard treatment based on surgery, radiotherapy, and chemotherapy. This provides a rationale for the development of some novel therapeutic strategies. Among them, receptor-mediated drug delivery is a specific pattern taking advantage of differential expression of receptors between tumors and normal tissues. The strategy can actively transport drugs, such as small molecular drugs, gene medicines, and therapeutic proteins to glioma while minimizing adverse reactions. This review will summarize recent progress on receptor-mediated drug delivery systems targeting to glioma, and conclude the challenges and prospects of receptor-mediated glioma-targeted therapy for future applications. PMID:28344260

Metabolism, Seizures, and Blood Flow in Brain Following Organophosphate Exposure: Mechanisms of Action and Possible Therapeutic Agents

DTIC Science & Technology

1991-01-31

oxotremorine and arecoline have established the involvement of a cholinergic muscarinic mechanism in OP-induced seizure, but not in OP-induced vasodilation. To...brain transport ofI glc, Ch, leu, and gly, additional influx measurements were made following expssure to carbachol, arecoline, oxotremorine , and AF64a...such as oxotremorine (53, 54). Although the primary effect of OPs on brain ACh levels is well established, their additional primary and secondary

New clinical trial aims to prevent breast cancer from recurring in the brain | Center for Cancer Research

Cancer.gov

In some types of breast cancer, the tumor cells spread more frequently to the brain. A new clinical trial run by CCR investigators will test whether a drug called temozolomide can prevent these deadly lesions from recurring. Read more... 

[Memory engram of brain circuit].

PubMed

Kojima, Hiroto; Sakaguchi, Tetsuya; Ikegaya, Yuji

2015-05-01

How are memories stored in the brain and retrieved on demand? This is a frequently asked question. Indeed, we acquire new memories daily and remember old ones. However, how we can memorize one-time experiences is yet to be investigated. Here, we review possible mechanisms by which memories are maintained in neural networks.

Brain Tuberculomas: A Case Report

PubMed Central

Saleh, Maryam; Saeedi, Ali Asghar; Ali Pooran, Ali

2014-01-01

Introduction: An unusual incidence of tuberculosis in different parts of the body is called tuberculomas. The rate of brain tuberculosis is rare. Case Presentation: The following case of tuberculamas of the brain, presented by enhancing rings of meninges, is reported because of its rarity. It was a case of brain tuberculomas in a 15-year-old girl with primary symptoms of headache and general weakness, and no signs of primary pulmonary infection. Discussion: The subject underwent computerized tomography (CT) and magnetic resonance imaging (MRI) of the brain. Microbiological tests (acid fast bacilli smear-AFB, and culture of biopsy specimen) were applied subsequently. According to the results, the problem was diagnosed as brain tuberculomas. After operation she was completely treated with anti-TB drugs. Although brain tuberculosis is rare, it was diagnosed on the basis of histopathology and the patient's successful response to anti-tuberculous drug treatment. PMID:25368795

C-type natriuretic peptide functions as an innate neuroprotectant in neonatal hypoxic-ischemic brain injury in mouse via natriuretic peptide receptor 2.

PubMed

Ma, Qingyi; Zhang, Lubo

2018-06-01

Neonatal hypoxia-ischemia (HI) is the most common cause of brain injury in neonates, which leads to high neonatal mortality and severe neurological morbidity in later life (Vannucci, 2000; Volpe, 2001). Yet the molecular mechanisms of neuronal death and brain damage induced by neonatal HI remain largely elusive. Herein, using both in vivo and in vitro models, we determine an endogenous neuroprotectant role of c-type natriuretic peptide (CNP) in preserving neuronal survival after HI brain injury in mouse pups. Postnatal day 7 (P7) mouse pups with CNP deficiency (Nppc lbab/lbab ) exhibit increased brain infarct size and worsened long-term locomotor function after neonatal HI compared with wildtype control (Nppc +/+ ). In isolated primary cortical neurons, recombinant CNP dose-dependently protects primary neurons from oxygen-glucose deprivation (OGD) insult. This neuroprotective effect appears to be mediated through its cognate natriuretic peptide receptor 2 (NPR2), in that antagonization of NPR2, but not NPR3, exacerbates neuronal death and counteracts the protective effect of CNP on primary neurons exposed to OGD insult. Immunoblot and confocal microscopy demonstrate the abundant expression of NPR2 in neurons of the neonatal brain and in isolated primary cortical neurons as well. Moreover, similar to CNP deficiency, administration of NPR2 antagonist P19 via intracerebroventricular injection prior to HI results in exacerbated neuronal death and brain injury after HI. Altogether, the present study indicates that CNP and its cognate receptor NPR2 mainly expressed in neurons represent an innate neuroprotective mechanism in neonatal HI brain injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Macrostructural and Microstructural Brain Lesions Relate to Gait Pathology in Children With Cerebral Palsy.

PubMed

Meyns, Pieter; Van Gestel, Leen; Leunissen, Inge; De Cock, Paul; Sunaert, Stefan; Feys, Hilde; Duysens, Jacques; Desloovere, Kaat; Ortibus, Els

2016-10-01

Background Even though lower-limb motor disorders are core features of spastic cerebral palsy (sCP), the relationship with brain lesions remains unclear. Unraveling the relation between gait pathology, lower-limb function, and brain lesions in sCP is complex for several reasons; wide heterogeneity in brain lesions, ongoing brain maturation, and gait depends on a number of primary motor functions/deficits (eg, muscle strength, spasticity). Objective To use a comprehensive approach combining conventional MRI and diffusion tensor imaging (DTI) in children with sCP above 3 years old to relate quantitative parameters of brain lesions in multiple brain areas to gait performance. Methods A total of 50 children with sCP (25 bilateral, 25 unilateral involvement) were enrolled. The investigated neuroradiological parameters included the following: (1) volumetric measures of the corpus callosum (CC) and lateral ventricles (LVs), and (2) DTI parameters of the corticospinal tract (CST). Gait pathology and primary motor deficits, including muscle strength and spasticity, were evaluated by 3D gait analysis and clinical examination. Results In bilateral sCP (n = 25), volume of the LV and the subparts of the CC connecting frontal, (pre)motor, and sensory areas were most related to lower-limb functioning and gait pathology. DTI measures of the CST revealed additional relations with the primary motor deficits (n = 13). In contrast, in unilateral sCP, volumetric (n = 25) and diffusion measures (n = 14) were only correlated to lower-limb strength. Conclusions These results indicate that the combined influence of multiple brain lesions and their impact on the primary motor deficits might explain a large part of the gait pathology in sCP. © The Author(s) 2016.

Adeno-Associated Viral-Mediated Catalase Expression Suppresses Optic Neuritis in Experimental Allergic Encephalomyelitis

NASA Astrophysics Data System (ADS)

Guy, John; Qi, Xiaoping; Hauswirth, William W.

1998-11-01

Suppression of oxidative injury by viral-mediated transfer of the human catalase gene was tested in the optic nerves of animals with experimental allergic encephalomyelitis (EAE). EAE is an inflammatory autoimmune disorder of primary central nervous system demyelination that has been frequently used as an animal model for the human disease multiple sclerosis (MS). The optic nerve is a frequent site of involvement common to both EAE and MS. Recombinant adeno-associated virus containing the human gene for catalase was injected over the right optic nerve heads of SJL/J mice that were simultaneously sensitized for EAE. After 1 month, cell-specific catalase activity, evaluated by quantitation of catalase immunogold, was increased approximately 2-fold each in endothelia, oligodendroglia, astrocytes, and axons of the optic nerve. Effects of catalase on the histologic lesions of EAE were measured by computerized analysis of the myelin sheath area (for demyelination), optic disc area (for optic nerve head swelling), extent of the cellular infiltrate, extravasated serum albumin labeled by immunogold (for blood-brain barrier disruption), and in vivo H2O2 reaction product. Relative to control, contralateral optic nerves injected with the recombinant virus without a therapeutic gene, catalase gene inoculation reduced demyelination by 38%, optic nerve head swelling by 29%, cellular infiltration by 34%, disruption of the blood-brain barrier by 64%, and in vivo levels of H2O2 by 61%. Because the efficacy of potential treatments for MS are usually initially tested in the EAE animal model, this study suggests that catalase gene delivery by using viral vectors may be a therapeutic strategy for suppression of MS.

Profound prevention of experimental brain metastases of breast cancer by temozolomide in an MGMT-dependent manner

PubMed Central

Palmieri, Diane; Duchnowska, Renata; Woditschka, Stephan; Hua, Emily; Qian, Yongzhen; Biernat, Wojciech; Sosińska-Mielcarek, Katarzyna; Gril, Brunilde; Stark, Andreas; Hewitt, Stephen; Liewehr, David J; Steinberg, Seth M; Jassem, Jacek; Steeg, Patricia S

2014-01-01

Purpose Brain metastases of breast cancer cause neurocognitive damage and are incurable. We evaluated a role for temozolomide in the prevention of brain metastases of breast cancer in experimental brain metastasis models. Experimental Design Temozolomide was administered in mice following earlier injection of brain-tropic human epidermal growth factor receptor 2 (HER2)-positive Jimt1-BR3 and triple negative 231-BR-EGFP sublines, the latter with and without expression of 06-methylguanine-DNA methyltransferase (MGMT). Additionally, the percentage of MGMT-positive tumor cells in 62 patient-matched sets of breast cancer primary tumors and resected brain metastases was determined immunohistochemically. Results Temozolomide, when dosed at 50, 25, 10 or 5 mg/kg, 5 days/week, beginning 3 days after inoculation, completely prevented the formation of experimental brain metastases from MGMT-negative 231-BR-EGFP cells. At a 1 mg/kg dose, temozolomide prevented 68% of large brain metastases, and was ineffective at a dose of 0.5 mg/kg. When the 50 mg/kg dose was administered beginning on days 18 or 24, temozolomide efficacy was reduced or absent. Temozolomide was ineffective at preventing brain metastases in MGMT-transduced 231-BR-EGFP and MGMT-expressing Jimt-1-BR3 sublines. In 62 patient-matched sets of primary breast tumors and resected brain metastases, 43.5% of the specimens had concordant low MGMT expression, while in another 14.5% of sets high MGMT staining in the primary tumor corresponded with low staining in the brain metastasis. Conclusions Temozolomide profoundly prevented the outgrowth of experimental brain metastases of breast cancer in an MGMT-dependent manner. These data provide compelling rationale for investigating the preventive efficacy of temozolomide in a clinical setting. PMID:24634373

Profound prevention of experimental brain metastases of breast cancer by temozolomide in an MGMT-dependent manner.

PubMed

Palmieri, Diane; Duchnowska, Renata; Woditschka, Stephan; Hua, Emily; Qian, Yongzhen; Biernat, Wojciech; Sosińska-Mielcarek, Katarzyna; Gril, Brunilde; Stark, Andreas M; Hewitt, Stephen M; Liewehr, David J; Steinberg, Seth M; Jassem, Jacek; Steeg, Patricia S

2014-05-15

Brain metastases of breast cancer cause neurocognitive damage and are incurable. We evaluated a role for temozolomide in the prevention of brain metastases of breast cancer in experimental brain metastasis models. Temozolomide was administered in mice following earlier injection of brain-tropic HER2-positive JIMT-1-BR3 and triple-negative 231-BR-EGFP sublines, the latter with and without expression of O(6)-methylguanine-DNA methyltransferase (MGMT). In addition, the percentage of MGMT-positive tumor cells in 62 patient-matched sets of breast cancer primary tumors and resected brain metastases was determined immunohistochemically. Temozolomide, when dosed at 50, 25, 10, or 5 mg/kg, 5 days per week, beginning 3 days after inoculation, completely prevented the formation of experimental brain metastases from MGMT-negative 231-BR-EGFP cells. At a 1 mg/kg dose, temozolomide prevented 68% of large brain metastases, and was ineffective at a dose of 0.5 mg/kg. When the 50 mg/kg dose was administered beginning on days 18 or 24, temozolomide efficacy was reduced or absent. Temozolomide was ineffective at preventing brain metastases in MGMT-transduced 231-BR-EGFP and MGMT-expressing JIMT-1-BR3 sublines. In 62 patient-matched sets of primary breast tumors and resected brain metastases, 43.5% of the specimens had concordant low MGMT expression, whereas in another 14.5% of sets high MGMT staining in the primary tumor corresponded with low staining in the brain metastasis. Temozolomide profoundly prevented the outgrowth of experimental brain metastases of breast cancer in an MGMT-dependent manner. These data provide compelling rationale for investigating the preventive efficacy of temozolomide in a clinical setting. ©2014 American Association for Cancer Research.

Physiology and molecular biology of barrier mechanisms in the fetal and neonatal brain.

PubMed

Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld; Habgood, Mark D

2018-05-17

Properties of the local internal environment of the adult brain are tightly controlled providing a stable milieu essential for its normal function. The mechanisms involved in this complex control are structural, molecular and physiological (influx and efflux transporters) frequently referred to as the "blood-brain barrier". These mechanisms include regulation of ion levels in brain interstitial fluid essential for normal neuronal function, supply of nutrients, removal of metabolic products and prevention of entry or elimination of toxic agents. A key feature is cerebrospinal fluid secretion and turnover. This is much less during development, allowing greater accumulation of permeating molecules. The overall effect of these mechanisms is to tightly control the exchange of molecules into and out of the brain. This review presents experimental evidence currently available on the status of these mechanisms in developing brain. It has been frequently stated for over nearly a century that the blood-brain barrier is not present or at least is functionally deficient in the embryo, fetus and newborn. We suggest the alternative hypothesis that the barrier mechanisms in developing brain are likely to be appropriately matched to each stage of its development. The contributions of different barrier mechanisms, such as changes in constituents of cerebrospinal fluid in relation to specific features of brain development, for example neurogenesis, are only beginning to be studied. The evidence on this previously neglected aspect of brain barrier function is outlined. We also suggest future directions this field could follow with special emphasis on potential applications in a clinical setting. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Targeting the brain--surmounting or bypassing the blood-brain barrier.

PubMed

Potschka, Heidrun

2010-01-01

The constituents of the blood-brain barrier, including its efflux transporter system, can efficiently limit brain penetration of potential CNS therapeutics. Effective extrusion from the brain by transporters is a frequent reason for the pharmaceutical industry to exclude novel compounds from further development for CNS therapeutics. Moreover, high transporter expression levels that are present in individual patients or may be generally associated with the pathophysiology seem to be a major cause of therapeutic failure in a variety of CNS diseases including brain tumors, epilepsy, brain HIV infection, and psychiatric disorders. Increasing knowledge of the structure and function of the blood-brain barrier creates a basis for the development of strategies which aim to enhance brain uptake of beneficial pharmaceutical compounds. The different strategies discussed in this review aim to modulate blood-brain barrier function or to bypass constituents of the blood-brain barrier.

Tight junction protein expression and barrier properties of immortalized mouse brain microvessel endothelial cells.

PubMed

Brown, Rachel C; Morris, Andrew P; O'Neil, Roger G

2007-01-26

Understanding the molecular and biochemical mechanisms regulating the blood-brain barrier is aided by in vitro model systems. Many studies have used primary cultures of brain microvessel endothelial cells for this purpose. However, primary cultures limit the generation of material for molecular and biochemical assays since cells grow slowly, are prone to contamination by other neurovascular unit cells, and lose blood-brain barrier characteristics when passaged. To address these issues, immortalized cell lines have been generated. In these studies, we assessed the suitability of the immortalized mouse brain endothelial cell line, bEnd3, as a blood-brain barrier model. RT-PCR and immunofluorescence indicated expression of multiple tight junction proteins. bEnd3 cells formed barriers to radiolabeled sucrose, and responded like primary cultures to disrupting stimuli. Exposing cells to serum-free media on their basolateral side significantly decreased paracellular permeability; astrocyte-conditioned media did not enhance barrier properties. The serum-free media-induced decrease in permeability was correlated with an increase in claudin-5 and zonula occludens-1 immunofluorescence at cell-cell contracts. We conclude that bEnd3 cells are an attractive candidate as a model of the blood-brain barrier due to their rapid growth, maintenance of blood-brain barrier characteristics over repeated passages, formation of functional barriers and amenability to numerous molecular interventions.

TIGHT JUNCTION PROTEIN EXPRESSION AND BARRIER PROPERTIES OF IMMORTALIZED MOUSE BRAIN MICROVESSEL ENDOTHELIAL CELLS

PubMed Central

Brown, Rachel C.; Morris, Andrew P.; O’Neil, Roger G.

2007-01-01

Understanding the molecular and biochemical mechanisms regulating the blood-brain barrier is aided by in vitro model systems. Many studies have used primary cultures of brain microvessel endothelial cells for this purpose. However, primary cultures limit the generation of material for molecular and biochemical assays since cells grow slowly, are prone to contamination by other neurovascular unit cells, and lose blood-brain barrier characteristics when passaged. To address these issues, immortalized cell lines have been generated. In these studies, we assessed the suitability of the immortalized mouse brain endothelial cell line, bEnd3, as a blood-brain barrier model. RT-PCR and immunofluorescence indicated expression of multiple tight junction proteins. bEnd3 cells formed barriers to radiolabeled sucrose, and responded like primary cultures to disrupting stimuli. Exposing cells to serum-free media on their basolateral side significantly decreased paracellular permeability; astrocyte-conditioned media did not enhance barrier properties. The serum-free media-induced decrease in permeability was correlated with an increase in claudin-5 and zonula occludens-1 immunofluorescence at cell-cell contracts. We conclude that bEnd3 cells are an attractive candidate as a model of the blood-brain barrier due to their rapid growth, maintenance of blood-brain barrier characteristics over repeated passages, formation of functional barriers and amenability to numerous molecular interventions. PMID:17169347

Human brain metastatic stroma attracts breast cancer cells via chemokines CXCL16 and CXCL12.

PubMed

Chung, Brile; Esmaeili, Ali A; Gopalakrishna-Pillai, Sailesh; Murad, John P; Andersen, Emily S; Kumar Reddy, Naveen; Srinivasan, Gayathri; Armstrong, Brian; Chu, Caleb; Kim, Young; Tong, Tommy; Waisman, James; Yim, John H; Badie, Behnam; Lee, Peter P

2017-01-01

The tumor microenvironment is composed of heterogeneous populations of cells, including cancer, immune, and stromal cells. Progression of tumor growth and initiation of metastasis is critically dependent on the reciprocal interactions between cancer cells and stroma. Through RNA-Seq and protein analyses, we found that cancer-associated fibroblasts derived from human breast cancer brain metastasis express significantly higher levels of chemokines CXCL12 and CXCL16 than fibroblasts from primary breast tumors or normal breast. To further understand the interplay between cancer cells and cancer-associated fibroblasts from each site, we developed three-dimensional organoids composed of patient-derived primary or brain metastasis cancer cells with matching cancer-associated fibroblasts. Three-dimensional CAF aggregates generated from brain metastasis promote migration of cancer cells more effectively than cancer-associated fibroblast aggregates derived from primary tumor or normal breast stromal cells. Treatment with a CXCR4 antagonist and/or CXCL16 neutralizing antibody, alone or in combination, significantly inhibited migration of cancer cells to brain metastatic cancer-associated fibroblast aggregates. These results demonstrate that human brain metastasis cancer-associated fibroblasts potently attract breast cancer cells via chemokines CXCL12 and CXCL16, and blocking CXCR6-CXCL16/CXCR4-CXCL12 receptor-ligand interactions may be an effective therapy for preventing breast cancer brain metastasis.

Frequent attendance in primary care: comparison and implications of different definitions

PubMed Central

Luciano, Juan V; Fernández, Ana; Pinto-Meza, Alejandra; Luján, Leila; Bellón, Juan A; García-Campayo, Javier; Peñarrubia, María T; Fernández, Rita; Sanavia, Marta; Blanco, María E; Haro, Josep M; Palao, Diego J; Serrano-Blanco, Antoni

2010-01-01

Background The diversity of definitions of frequent attendance in the literature hampers comparison of their precision, validity, and associated factors. Aim To examine different definitions of frequent attendance in order to identify the sociodemographic and clinical factors associated with frequent attendance in primary care, according to each definition. Design of study One-phase cross-sectional study. Setting Seventy-seven primary care centres in Catalonia, Spain. Method A total of 3815 primary care patients were interviewed between October 2005 and March 2006. Three definitions of frequent attendance were tested: (1) frequent attenders as the top 25% and the top 10% consulting patients; (2) frequent attenders as the top 25% and the top 10% consulting patients stratified by age and sex; and (3) frequent attenders as the top 25% and the top 10% consulting patients stratified by the presence of physical/mental conditions (patients with only mental disorders, with only chronic physical conditions, with comorbid conditions, and with no condition). Multilevel logistic regressions were used. Results The following factors were systematically related to frequent attender status: being on sick leave, being born outside of Spain, reporting mental health problems as the main reason for consulting, and having arthritis/rheumatism, or bronchitis. Major depression was related to frequent attendance in two of the three definitions. The factor ‘GP’ was related to frequent attendance when the top decile cut-off point was used. The models with a 10% cut-off point were more discriminative than those with a 25% cut-off point: the area under the receiver operating characteristic curve for models with a 25% cut-off and a 10% cut-off ranged between 0.71 (95% confidence interval [CI] = 0.70 to 0.73) and 0.75 (95% CI = 0.74 to 0.77) and between 0.79 (95% CI = 0.78 to 0.81) and 0.85 (95% CI = 0.83 to 0.86), respectively. Conclusion The way frequent attendance is defined is of crucial importance. It is recommended that a more discriminative definition of frequent attendance is used (the top 10%). PMID:20132693

Prevention and treatment of venous thromboembolism in patients with solid brain neoplasms: results of a survey among Italian physicians.

PubMed

Mumoli, Nicola; Barco, Stefano; Cei, Marco; Giorgi-Pierfranceschi, Matteo; Campanini, Mauro; Fontanella, Andrea; Ageno, Walter; Dentali, Francesco

2017-06-01

The decision concerning the introduction of primary and secondary prophylaxis of venous thromboembolism (VTE) in patients with solid brain neoplasms and brain metastases is often challenging due to the concomitant increased risk of intracranial hemorrhage and to limited evidence from available literature. A standardized questionnaire composed of nine multiple-choice questions regarding primary VTE prevention in non-surgical patients during high-risk conditions and VTE secondary prevention in patients with a solid brain neoplasm or cerebral metastases was sent via electronic mail to all the members (n = 2420) of the Italian Federation of the Internal Medicine Hospital Executives' Associations (FADOI) in June 2015. Three hundred and fifty two physicians (14.5%) returned it (participants' median age 51 years; females 46.9%). The majority of respondents prescribe primary thromboprophylaxis (usually with heparin) in non-surgical patients with solid brain neoplasms and brain metastases in concomitance with high-risk conditions. Full-dose anticoagulation with either low-molecular-weight heparin or fondaparinux is the preferred option for acute VTE (69.6%), while a reduced dose is chosen by 21.0% of physicians. The presence of a highly vascular brain neoplasm histotype mandates the prescription of a reduced-dose antithrombotic regimen in a minority of respondents. Vena cava filter placement is an option for the treatment of acute VTE in more than 6% of respondents. Anticoagulants are often prescribed for both VTE primary prevention and treatment. In conclusion, physicians' managements are partially in contrast to recent guidelines, reinforcing the need for educational programs and other studies in this setting.

Hominoid visual brain structure volumes and the position of the lunate sulcus.

PubMed

de Sousa, Alexandra A; Sherwood, Chet C; Mohlberg, Hartmut; Amunts, Katrin; Schleicher, Axel; MacLeod, Carol E; Hof, Patrick R; Frahm, Heiko; Zilles, Karl

2010-04-01

It has been argued that changes in the relative sizes of visual system structures predated an increase in brain size and provide evidence of brain reorganization in hominins. However, data about the volume and anatomical limits of visual brain structures in the extant taxa phylogenetically closest to humans-the apes-remain scarce, thus complicating tests of hypotheses about evolutionary changes. Here, we analyze new volumetric data for the primary visual cortex and the lateral geniculate nucleus to determine whether or not the human brain departs from allometrically-expected patterns of brain organization. Primary visual cortex volumes were compared to lunate sulcus position in apes to investigate whether or not inferences about brain reorganization made from fossil hominin endocasts are reliable in this context. In contrast to previous studies, in which all species were relatively poorly sampled, the current study attempted to evaluate the degree of intraspecific variability by including numerous hominoid individuals (particularly Pan troglodytes and Homo sapiens). In addition, we present and compare volumetric data from three new hominoid species-Pan paniscus, Pongo pygmaeus, and Symphalangus syndactylus. These new data demonstrate that hominoid visual brain structure volumes vary more than previously appreciated. In addition, humans have relatively reduced primary visual cortex and lateral geniculate nucleus volumes as compared to allometric predictions from other hominoids. These results suggest that inferences about the position of the lunate sulcus on fossil endocasts may provide information about brain organization. Copyright 2010 Elsevier Ltd. All rights reserved.

Epileptic encephalopathy in children with risk factors for brain damage.

PubMed

Ricardo-Garcell, Josefina; Harmony, Thalía; Porras-Kattz, Eneida; Colmenero-Batallán, Miguel J; Barrera-Reséndiz, Jesús E; Fernández-Bouzas, Antonio; Cruz-Rivero, Erika

2012-01-01

In the study of 887 new born infants with prenatal and perinatal risk factors for brain damage, 11 children with West syndrome that progressed into Lennox-Gastaut syndrome and another 4 children with Lennox-Gastaut syndrome that had not been preceded by West syndrome were found. In this study we present the main findings of these 15 subjects. In all infants multifactor antecedents were detected. The most frequent risk factors were prematurity and severe asphyxia; however placenta disorders, sepsis, and hyperbilirubinemia were also frequent. In all infants MRI direct or secondary features of periventricular leukomalacia were observed. Followup of all infants showed moderate to severe neurodevelopmental delay as well as cerebral palsy. It is concluded that prenatal and perinatal risk factors for brain damage are very important antecedents that should be taken into account to follow up those infants from an early age in order to detect and treat as early as possible an epileptic encephalopathy.

Microglia and macrophages in malignant gliomas: recent discoveries and implications for promising therapies.

PubMed

da Fonseca, Anna Carolina Carvalho; Badie, Behnam

2013-01-01

Malignant gliomas are the most common primary brain tumors. Their deadliest manifestation, glioblastoma multiforme (GBM), accounts for 15% of all primary brain tumors and is associated with a median survival of only 15 months even after multimodal therapy. There is substantial presence of microglia and macrophages within and surrounding brain tumors. These immune cells acquire an alternatively activated phenotype with potent tumor-tropic functions that contribute to glioma growth and invasion. In this review, we briefly summarize recent data that has been reported on the interaction of microglia/macrophages with brain tumors and discuss potential application of these findings to the development of future antiglioma therapies.

Geriatric neuro-oncology: from mythology to biology.

PubMed

Weller, Michael; Platten, Michael; Roth, Patrick; Wick, Wolfgang

2011-12-01

Age has remained one of the most important determinants of risk for the development of certain brain tumors, of benefit from and tolerance of brain tumor treatment, and overall outcome. Regarding these three aspects, there are major differences across the spectrum of primary brain tumors depending on specific histology. Here, we review recent advances in understanding the biological basis of the prognostic marker 'age' in neuro-oncology. Contemporary population-based studies confirm the strong prognostic impact of age in many brain tumors. Elderly patients continue to be treated less aggressively than younger patients with the same tumors. However, biological factors may contribute to the negative prognostic impact of age. For instance, among gliomas, mutations of the isocitrate dehydrogenase genes, which are prognostically favorable, are much more common in younger patients. Moreover, complete responses defined by neuroimaging were much less durable in elderly as opposed to younger patients with primary central nervous system lymphoma in the German Primary Central Nervous System Lymphoma Study Group trial. A combination of age-adapted patterns of care and treatment-independent, tumor-intrinsic factors contributes to the poorer outcome of elderly patients with brain tumors. These factors need to be better distinguished and understood in order to improve outcome in elderly brain tumor patients.

Role of Caspase-9 Gene Ex5+32 G>A (rs1052576) Variant in Susceptibility to Primary Brain Tumors.

PubMed

Ozdogan, Selcuk; Kafadar, Ali; Yilmaz, Seda Gulec; Timirci-Kahraman, Ozlem; Gormus, Uzay; Isbir, Turgay

2017-09-01

This study is the first to evaluate the relationship of caspase-9 (CASP-9) gene polymorphism with the risk for primary brain tumor development. The study group included 43 glioma and 27 meningioma patients and 76 healthy individuals. CASP-9 gene Ex5+32 G>A (rs1052576) polymorphism was analyzed by real-time polymerase chain reaction (RT-PCR). Individuals with the CASP-9 GG genotype had significantly decreased risk of developing a glioma brain tumor (p=0.024). Additionally, the GA genotype was significantly lower in patients with glioma than the control group (p=0.019). A significantly decreased risk of developing glioma was found in the A allele carrier group (p=0.024). However, there was no statistically significant relationship between CASP-9 polymorphism and brain meningioma (p=0.493). CASP-9 (rs1052576) mutant A allele seems to be a protective factor for glioma brain tumor. Future studies with a larger sample size will clarify the possible roles of CASP-9 gene in the etiology and progression of primary brain tumors. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Cognitive behaviour therapy for long-term frequent attenders in primary care: a feasibility case series and treatment development study.

PubMed

Malins, Samuel; Kai, Joe; Atha, Christopher; Avery, Anthony; Guo, Boliang; James, Marilyn; Patel, Shireen; Sampson, Christopher; Stubley, Michelle; Morriss, Richard

2016-10-01

Most frequent attendance in primary care is temporary. Long-term frequent attendance may be suitable for psychological intervention to address health management and service use. To explore the feasibility and acceptability of cognitive behaviour therapy (CBT) for long-term frequent attendance in primary care and obtain preliminary evidence regarding clinical and cost effectiveness. A CBT case series was carried out in five GP practices in the East Midlands. Frequent attenders (FAs) were identified from case notes and invited by their practice for assessment, then offered CBT. Feasibility and acceptability were assessed by CBT session attendance and thematic analysis of semi-structured questionnaires. Clinical and cost effectiveness was assessed by primary care use and clinically important change on a range of health and quality of life instruments. Of 462 FAs invited to interview, 87 (19%) consented to assessment. Thirty-two (7%) undertook CBT over a median of 3 months. Twenty-four (75%) attended at least six sessions. Eighteen FAs (86%, n = 21) reported overall satisfaction with treatment. Patients reported valuing listening without judgement alongside support to develop coping strategies. Thirteen (54%, n = 24), achieved clinically important improvement on the SF-36 Mental-Component Scale at 6-month follow-up and improved quality of life, but no improvement on other outcomes. Primary care use reduced from a median of eight contacts in 3 months at baseline (n = 32) to three contacts in 3 months at 1 year (n = 18). CBT appears feasible and acceptable to a subset of long-term FAs in primary care who halved their primary care use. With improved recruitment strategies, this approach could contribute to decreasing GP workload and merits larger-scale evaluation. © British Journal of General Practice 2016.

Differential learning and memory performance in OEF/OIF veterans for verbal and visual material.

PubMed

Sozda, Christopher N; Muir, James J; Springer, Utaka S; Partovi, Diana; Cole, Michael A

2014-05-01

Memory complaints are particularly salient among veterans who experience combat-related mild traumatic brain injuries and/or trauma exposure, and represent a primary barrier to successful societal reintegration and everyday functioning. Anecdotally within clinical practice, verbal learning and memory performance frequently appears differentially reduced versus visual learning and memory scores. We sought to empirically investigate the robustness of a verbal versus visual learning and memory discrepancy and to explore potential mechanisms for a verbal/visual performance split. Participants consisted of 103 veterans with reported history of mild traumatic brain injuries returning home from U.S. military Operations Enduring Freedom and Iraqi Freedom referred for outpatient neuropsychological evaluation. Findings indicate that visual learning and memory abilities were largely intact while verbal learning and memory performance was significantly reduced in comparison, residing at approximately 1.1 SD below the mean for verbal learning and approximately 1.4 SD below the mean for verbal memory. This difference was not observed in verbal versus visual fluency performance, nor was it associated with estimated premorbid verbal abilities or traumatic brain injury history. In our sample, symptoms of depression, but not posttraumatic stress disorder, were significantly associated with reduced composite verbal learning and memory performance. Verbal learning and memory performance may benefit from targeted treatment of depressive symptomatology. Also, because visual learning and memory functions may remain intact, these might be emphasized when applying neurocognitive rehabilitation interventions to compensate for observed verbal learning and memory difficulties.

White matter changes in early phase schizophrenia and cannabis use: an update and systematic review of diffusion tensor imaging studies.

PubMed

Cookey, Jacob; Bernier, Denise; Tibbo, Philip G

2014-07-01

The impact of cannabis use on the brain tissue is still unclear, both in the healthy developing brain and in people with schizophrenia. The focus of this review is on white matter, the primary connective infrastructure of the brain. We systematically reviewed diffusion tensor imaging (DTI) studies of early phase schizophrenia (illness effect), of cannabis use in otherwise healthy brains (drug effect), and of early phase schizophrenia with cannabis use (combined effects). Studies had to include a healthy, non-cannabis using, control group as well as report on fractional anisotropy as it is the most commonly used DTI index. We excluded cohorts with heavy alcohol or illicit drug use and studies with a sample size of less than 20 in the clinical group. We retained 17 studies of early phase schizophrenia, which together indicate deficits in white matter integrity observed in all fiber tract families, but most frequently in association, callosal and projection fibers. In otherwise healthy cannabis users (2 studies), deficits in white matter tracts were reported mainly in callosal fibers, but also in projection and limbic fibers. In cannabis users with early phase schizophrenia (1 study), deficits in white matter integrity were also observed in all fiber tract families, except for limbic fibers. The current literature points to several families of white matter tracts being differentially affected in early phase schizophrenia. Further work is required to reveal the impact of cannabis use in otherwise healthy people as well as those with schizophrenia. Paucity of available studies as well as restricting analysis to FA values represent the main limitations of this review. Copyright © 2014 Elsevier B.V. All rights reserved.

EpiBrainRad: an epidemiologic study of the neurotoxicity induced by radiotherapy in high grade glioma patients.

PubMed

Durand, Thomas; Jacob, Sophie; Lebouil, Laura; Douzane, Hassen; Lestaevel, Philippe; Rahimian, Amithys; Psimaras, Dimitri; Feuvret, Loïc; Leclercq, Delphine; Brochet, Bruno; Tamarat, Radia; Milliat, Fabien; Benderitter, Marc; Vayatis, Nicolas; Noël, Georges; Hoang-Xuan, Khê; Delattre, Jean-Yves; Ricard, Damien; Bernier, Marie-Odile

2015-12-18

Radiotherapy is one of the most important treatments of primary and metastatic brain tumors. Unfortunately, it can involve moderate to severe complications among which leukoencephalopathy is very frequent and implies cognitive deficits such as memory, attention and executive dysfunctions. However, the incidence of this complication is not well established and the risk factors and process are poorly understood. The main objective of the study is to improve knowledge on radio-induced leukoencephalopathy based on pluridisciplinar approaches combining cognitive, biologic, imagery and dosimetric investigations. The EpiBrainRad study is a prospective cohort study including newly diagnosed high grade gliomas patients treated by radiotherapy and concomitant-adjuvant temozolomide chemotherapy. Patients are included between their surgery and first day of radio-chemotherapy, and the follow-up lasts for 3 years after treatment. Cognitive functioning assessments, specific blood biomarkers measures and magnetic resonance imagery are performed at different moment during the follow-up, and a specific dosimetric assessment of organs involved in the beam fields is performed. Firstly, leukoencephalopathy incidence rate will be estimated in this population. Secondly, correlations between cognitive impairments and dosimetry, biomarkers ranges and anomalies on imagery will be analyzed in order to better understand the onset and evolution of cognitive decrement associated with radiotherapy. Furthermore, a new cognitive test, quickly and easily performed, will be studied to determine its sensibility to detect leukoencephalopathy decrement. With an original multidisciplinary approach, the EpiBrainRad study aims to improve knowledge on radio-induced leukoencephalopathy in order to improve its early diagnosis and prevention. The main challenge is to preserve quality-of-life after cancer treatments which imply to study the incidence of radiation-induced complications and their associated risk factors. NCT02544178.

Lithium treatment elongates primary cilia in the mouse brain and in cultured cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyoshi, Ko, E-mail: miyoshi@cc.okayama-u.ac.jp; Kasahara, Kyosuke; Miyazaki, Ikuko

2009-10-30

The molecular mechanisms underlying the therapeutic effects of lithium, a first-line antimanic mood stabilizer, have not yet been fully elucidated. Treatment of the algae Chlamydomonas reinhardtii with lithium has been shown to induce elongation of their flagella, which are analogous structures to vertebrate cilia. In the mouse brain, adenylyl cyclase 3 (AC3) and certain neuropeptide receptors colocalize to the primary cilium of neuronal cells, suggesting a chemosensory function for the primary cilium in the nervous system. Here we show that lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Brain sections from mice chronically fed withmore » Li{sub 2}CO{sub 3} were subjected to immunofluorescence study. Primary cilia carrying both AC3 and the receptor for melanin-concentrating hormone (MCH) were elongated in the dorsal striatum and nucleus accumbens of lithium-fed mice, as compared to those of control animals. Moreover, lithium-treated NIH3T3 cells and cultured striatal neurons exhibited elongation of the primary cilia. The present results provide initial evidence that a psychotropic agent can affect ciliary length in the central nervous system, and furthermore suggest that lithium exerts its therapeutic effects via the upregulation of cilia-mediated MCH sensing. These findings thus contribute novel insights into the pathophysiology of bipolar mood disorder and other psychiatric diseases.« less

Brain-Derived Neurotrophic Factor Levels in Autism: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Saghazadeh, Amene; Rezaei, Nima

2017-01-01

Brain-derived neurotrophic factor (BDNF) plays an important role in activity-dependent synaptic plasticity. Altered blood BDNF levels have been frequently identified in people with autism spectrum disorders (ASD). There are however wide discrepancies in the evidence. Therefore, we performed the present systematic review and meta-analysis aimed at…

Brain Metastases from Endometrial Carcinoma

PubMed Central

Piura, Ettie; Piura, Benjamin

2012-01-01

This paper will focus on knowledge related to brain metastases from endometrial carcinoma. To date, 115 cases were documented in the literature with an incidence of 0.6% among endometrial carcinoma patients. The endometrial carcinoma was usually an advanced-stage and high-grade tumor. In most patients (~90%), brain metastasis was detected after diagnosis of endometrial carcinoma with a median interval from diagnosis of endometrial carcinoma to diagnosis of brain metastases of 17 months. Brain metastasis from endometrial carcinoma was either an isolated disease limited to the brain only (~50%) or part of a disseminated disease involving also other parts of the body (~50%). Most often, brain metastasis from endometrial carcinoma affected the cerebrum (~75%) and was solitary (~60%). The median survival after diagnosis of brain metastases from endometrial carcinoma was 5 months; however, a significantly better survival was achieved with multimodal therapy including surgical resection or stereotactic radiosurgery followed by whole brain radiotherapy (WBRT) and/or chemotherapy compared to WBRT alone. It is suggested that brain imaging studies should be considered in the routine follow up of patients with endometrial carcinoma and that the search for a primary source in females with brain metastases of unknown primary should include endometrial biopsy. PMID:22523707

Superficial middle cerebral vein connection to the cavernous sinus is not infrequent in brain arteriovenous malformations: an argument against their congenital origin?

PubMed

Shotar, Eimad; Guédon, Alexis; Sourour, Nader; Di Maria, Federico; Gabrieli, Joseph; Nouet, Aurélien; Chiras, Jacques; Clarençon, Frédéric

2016-07-01

The aim of this study was to test the hypothesis that the superficial middle cerebral vein (SMCV) is frequently absent or fails to connect with the cavernous sinus (CS) in the presence of brain arteriovenous malformations (AVMs), a frequently reported argument for the congenital origin of brain AVMs. The SMCV was retrospectively compared between patients with a brain AVM and a control group. The presence or absence of the SMCV, its direct or indirect connection to the CS and its termination in a laterocavernous sinus (LCS), paracavernous sinus (PCS), or directly in the CS was studied on digital subtraction angiography. One hundred twenty-five left or right side carotid angiograms from 70 patients with a brain AVM were compared to 125 angiograms from 74 controls. The SMCV was present in 88 (70.4 %) cases in the brain AVM group and 96 (76.8 %) cases in controls (p = 0.25). The SMCV was connected directly or indirectly to the CS in 65 (52 %) cases in the brain AVM group and 65 (52 %) cases in controls (p = 1). When comparing the subgroup of carotid angiograms ipsilateral to a supratentorial AVM, no statistically significant difference was found with controls. In three of six cases in which a SMCV drained an AVM, the vein terminated directly or indirectly in the CS. No difference of SMCV presence and direct or indirect connection to the CS was found between patients with AVM and a control group. SMCV anatomy does not support the congenital origin of brain AVMs.

Distribution and severity of hypoxic-ischaemic lesions on brain MRI following therapeutic cooling: selective head versus whole body cooling.

PubMed

Sarkar, Subrata; Donn, Steven M; Bapuraj, Jayapalli R; Bhagat, Indira; Barks, John D

2012-09-01

Whole body cooling (WBC) cools different parts of the brain uniformly, and selective head cooling (SHC) cools the superficial brain more than the deeper brain structures. In this study, the authors hypothesised that the hypoxic-ischaemic lesions on brain MRI following cooling would differ between modalities of cooling. To compare the frequency, distribution and severity of hypoxic-ischaemic lesions on brain MRI between SHC or WBC. In a single centre retrospective study, 83 infants consecutively cooled using either SHC (n=34) or WBC (n=49) underwent brain MRI. MRI images were evaluated by a neuroradiologist, who was masked to clinical parameters and outcomes, using a basal ganglia/watershed (BG/W) scoring system. Higher scores (on a scale of 0 to 4) were given for more extensive injury. The score has been reported to be predictive of neuromotor and cognitive outcome at 12 months. The two groups were similar for severity of depression as assessed by a history of an intrapartum sentinel event, Apgar scores, initial blood pH and base deficit and early neurological examination. However, abnormal MRI was more frequent in the SHC group (SHC 25 of 34, 74% vs WBC 22 of 49, 45%; p=0.0132, OR 3.4, 95% CI 1.3 to 8.8). Infants from the SHC group also had more severe hypoxic-ischaemic lesions (median BG/W score: SHC 2 vs WBC 0, p=0.0014). Hypoxic-ischaemic lesions on brain MRI following therapeutic cooling were more frequent and more severe with SHC compared with WBC.

Bradycardia in frontotemporal dementia.

PubMed

Robles Bayón, A; Gude Sampedro, F; Torregrosa Quesada, J M

2014-03-01

Numerous regions of the brain, such as the medial frontal cortex, orbitofrontal cortex, insula, and amygdala, participate in the autonomic control of cardiovascular functions such as heart rate. The degenerative process in frontotemporal dementia (FTD) involves the listed anatomical structures and may therefore produce dysautonomic cardiovascular symptoms. To observe whether or not non-cardiogenic bradycardia was more frequent in a group of patients with FTD than in subjects with mild cognitive impairment or dementia of a different aetiology. Once patients with primary cardiac arrhythmia were excluded, we registered the heart rates of 258 patients with cognitive symptoms (36 with FTD, 22 with Alzheimer disease, 23 with vascular dementia, 10 with other dementias, and 167 with non-dementia cognitive impairment). Bradycardia (<60 beats/minute) was significantly more frequent in patients with FTD. This difference remained significant after excluding subjects undergoing treatment with a potentially bradycardic effect. Bradycardia was more prevalent in behavioural FTD cases than in cases of the aphasic variant, and we detected a trend toward higher frequency among patients with more pronounced right hemisphere atrophy. Moreover, mean systolic blood pressure in FTD patients was lower than in other participants, and systolic hypotension (<120 and <100mm Hg) was more prevalent. Bradycardia was more frequent in the FTD sample than in other patients with cognitive symptoms. Further investigations will be necessary before we may consider bradycardia to be a sign supporting diagnosis of FTD or its behavioural variant. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Brain and visceral involvement during congenital cytomegalovirus infection of guinea pigs.

PubMed

Griffith, B P; Lucia, H L; Hsiung, G D

1982-06-01

The virologic and histologic characteristics of congenital cytomegalovirus infection (CMV) were defined in 65 neonatal guinea pigs born from 27 mothers infected pregnancy. Infectious virus or tissue lesions were present in 54% of the neonates tested. Guinea pig CMV was detected most often in the salivary glands (72%) and spleen (33%) of infected guinea pigs. Less frequently, virus was also detected in the brain, lung, pancreas and liver. Tissue lesions were most frequently observed in the brain and kidney, but also occurred in the salivary glands, liver, pancreas, thymus and spleen. The histopathology was identical to that observed in infants with congenital CMV infection. Infectious virus and histopathology were present in newborn guinea pigs born from mothers infected at any time during gestation. Newborns from mothers infected during early stages of gestation and virus present most frequently in the salivary glands, whereas offspring of mothers infected in late pregnancy had virus present in several tissues. Acute maternal guinea pig CMV infection produced generalized CMV infection of the offspring which was followed by persistent infection in neonatal salivary glands. Lesions remained present in several neonatal tissues including the brain. The long term consequences of such lesions in affected guinea pigs remain to be determined. The results of the study emphasize the similarities between human congenital CMV infection and congenital guinea pig CMV infection, thereby underlining the utility of this animal model as a means of understanding human congenital CMV infection.

Brain imaging before primary lung cancer resection: a controversial topic.

PubMed

Hudson, Zoe; Internullo, Eveline; Edey, Anthony; Laurence, Isabel; Bianchi, Davide; Addeo, Alfredo

2017-01-01

International and national recommendations for brain imaging in patients planned to undergo potentially curative resection of non-small-cell lung cancer (NSCLC) are variably implemented throughout the United Kingdom [Hudson BJ, Crawford MB, and Curtin J et al (2015) Brain imaging in lung cancer patients without symptoms of brain metastases: a national survey of current practice in England Clin Radiol https://doi.org/10.1016/j.crad.2015.02.007]. However, the recommendations are not based on high-quality evidence and do not take into account cost implications and local resources. Our aim was to determine local practice based on historic outcomes in this patient cohort. This retrospective study took place in a regional thoracic surgical centre in the United Kingdom. Pathology records for all patients who had undergone lung resection with curative intent during the time period January 2012-December 2014 were analysed in October 2015. Electronic pathology and radiology reports were accessed for each patient and data collected about their histological findings, TNM stage, resection margins, and the presence of brain metastases on either pre-operative or post-operative imaging. From the dates given on imaging, we calculated the number of days post-resection that the brain metastases were detected. 585 patients were identified who had undergone resection of their lung cancer. Of these, 471 had accessible electronic radiology records to assess for the radiological evidence of brain metastases. When their electronic records were evaluated, 25/471 (5.3%) patients had radiological evidence of brain metastasis. Of these, five patients had been diagnosed with a brain metastasis at initial presentation and had undergone primary resection of the brain metastasis followed by resection of the lung primary. One patient had been diagnosed with both a primary lung and a primary bowel adenocarcinoma; on review of the case, it was felt that the brain metastasis was more likely to have originated from the bowel cancer. One had been clinically diagnosed with a cerebral abscess while the radiology had been reported as showing a metastatic deposit. Of the remaining 18/471 (3.8%) patients who presented with brain metastases after their surgical resection, 12 patients had adenocarcinoma, four patients had squamous cell carcinoma, one had basaloid, and one had large-cell neuroendocrine. The mean number of days post-resection that the brain metastases were identified was 371 days, range 14-1032 days, median 295 days (date of metastases not available for two patients). The rate of brain metastases identified in this study was similar to previous studies. This would suggest that preoperative staging of the central nervous system may change the management pathway in a small group of patients. However, for this group of patients, the change would be significant either sparing them non-curative surgery or allowing aggressive management of oligometastatic disease. Therefore, we would recommend pre-operative brain imaging with MRI for all patients undergoing potentially curative lung resection.

Voxelwise distribution of acute ischemic stroke lesions in patients with newly diagnosed atrial fibrillation: Trigger of arrhythmia or only target of embolism?

PubMed Central

Johnson, Timothy D.; Dittgen, Felix; Nichols, Thomas E.; Malzahn, Uwe; Veltkamp, Roland

2017-01-01

Objective Atrial fibrillation (AF) is frequently detected after ischemic stroke for the first time, and brain regions involved in autonomic control have been suspected to trigger AF. We examined whether specific brain regions are associated with newly detected AF after ischemic stroke. Methods Patients with acute cerebral infarctions on diffusion-weighted magnetic resonance imaging were included in this lesion mapping study. Lesions were mapped and modeled voxelwise using Bayesian Spatial Generalised Linear Mixed Modeling to determine differences in infarct locations between stroke patients with new AF, without AF and with AF already known before the stroke. Results 582 patients were included (median age 68 years; 63.2% male). AF was present in 109/582 patients [(18.7%); new AF: 39/109 (35.8%), known AF: 70/109 (64.2%)]. AF patients had larger infarct volumes than patients without AF (mean: 29.7 ± 45.8 ml vs. 15.2 ± 35.1 ml; p<0.001). Lesions in AF patients accumulated in the right central middle cerebral artery territory. Increasing stroke size predicted progressive cortical but not pontine and thalamic involvement. Patients with new AF had more frequently lesions in the right insula compared to patients without AF when stroke size was not accounted for, but no specific brain region was more frequently involved after adjustment for infarct volume. Controlled for stroke size, left parietal involvement was less likely for patients with new AF than for those without AF or with known AF. Conclusions In the search for brain areas potentially triggering cardiac arrhythmias infarct size should be accounted for. After controlling for infarct size, there is currently no evidence that ischemic stroke lesions of specific brain areas are associated with new AF compared to patients without AF. This challenges the neurogenic hypothesis of AF according to which a relevant proportion of new AF is triggered by ischemic brain lesions of particular locations. PMID:28542605

Primary cardiac sarcoma complicated with cerebral infarction and brain metastasis: A case report and literature review.

PubMed

Sun, Yun-Peng; Wang, Xuan; Gao, Yong-Sheng; Zhao, Song; Bai, Yang

2017-12-12

In large autopsy series, the estimated frequency of primary tumors of the heart ranges from 0.0017% to 0.33%. Approximately 25% of primary cardiac tumors are malignant, and nearly 20% of these are sarcomas. To date, a completely feasible surgical resection remains the major treatment measure of cardiac sarcoma, especially for recurrent focal cardiac sarcoma and the recurrence of a restrictive metastasis. Although characteristically medical treatments are recommended, there is no consistent opinion for adjuvant radiotherapy and chemotherapy following an operation. Since these tumors usually undergo extensive spread by the time that the diagnosis is established, the prognosis of cardiac sarcoma remains poor. In this report, we described a case who underwent initial cardiac tumor resection, and was confirmed to be a pleomorphic undifferentiated sarcoma based on pathological findings. However, the patient complicated with cerebral infarction and subsequent brain metastasis sarcoma after the initial surgery, which was confirmed by brain tissue pathology. During the course of therapy, the patient underwent three surgical operations and refused to accept any chemotherapy and radiotherapy intervention. To the best of our knowledge, this is the first case report describing a primary cardiac sarcoma complicated with cerebral infarction and brain metastasis. The management of primary cardiac sarcoma is also discussed.

Donepezil in Treating Young Patients With Primary Brain Tumors Previously Treated With Radiation Therapy to the Brain

ClinicalTrials.gov

2017-07-31

Brain and Central Nervous System Tumors; Cognitive/Functional Effects; Long-term Effects Secondary to Cancer Therapy in Children; Neurotoxicity; Psychosocial Effects of Cancer and Its Treatment; Radiation Toxicity

Primary brain tumors, neural stem cell, and brain tumor cancer cells: where is the link?

PubMed Central

Germano, Isabelle; Swiss, Victoria; Casaccia, Patrizia

2010-01-01

The discovery of brain tumor-derived cells (BTSC) with the properties of stem cells has led to the formulation of the hypothesis that neural stem cells could be the cell of origin of primary brain tumors (PBT). In this review we present the most common molecular changes in PBT, define the criteria of identification of BTSC and discuss the similarities between the characteristics of these cells and those of the endogenous population of neural stem cells (NPCs) residing in germinal areas of the adult brain. Finally, we propose possible mechanisms of cancer initiation and progression and suggest a model of tumor initiation that includes intrinsic changes of resident NSC and potential changes in the microenvironment defining the niche where the NSC reside. PMID:20045420

Congenital heart disease affects cerebral size but not brain growth.

PubMed

Ortinau, Cynthia; Inder, Terrie; Lambeth, Jennifer; Wallendorf, Michael; Finucane, Kirsten; Beca, John

2012-10-01

Infants with congenital heart disease (CHD) have delayed brain maturation and alterations in brain volume. Brain metrics is a simple measurement technique that can be used to evaluate brain growth. This study used brain metrics to test the hypothesis that alterations in brain size persist at 3 months of age and that infants with CHD have slower rates of brain growth than control infants. Fifty-seven infants with CHD underwent serial brain magnetic resonance imaging (MRI). To evaluate brain growth across the first 3 months of life, brain metrics were undertaken using 19 tissue and fluid spaces shown on MRIs performed before surgery and again at 3 months of age. Before surgery, infants with CHD have smaller frontal, parietal, cerebellar, and brain stem measures (p < 0.001). At 3 months of age, alterations persisted in all measures except the cerebellum. There was no difference between control and CHD infants in brain growth. However, the cerebellum trended toward greater growth in infants with CHD. Somatic growth was the primary factor that related to brain growth. Presence of focal white matter lesions before and after surgery did not relate to alterations in brain size or growth. Although infants with CHD have persistent alterations in brain size at 3 months of age, rates of brain growth are similar to that of healthy term infants. Somatic growth was the primary predictor of brain growth, emphasizing the importance of optimal weight gain in this population.

Primary intranasal melanoma with brain invasion in a dog.

PubMed

Lemetayer, Julie; Al-Dissi, Ahmad; Tryon, Kim; MacDonald-Dickinson, Valerie

2017-04-01

A 6-year-old castrated male boxer dog with right-sided dark purulent nasal discharge and acute bilateral blindness was diagnosed on magnetic resonance imaging (MRI) and then on necropsy with primary nasal malignant melanoma that extended into the brain, as well as concurrent ocular melanosis. There was no evidence of metastasis in other organs.

Primary intranasal melanoma with brain invasion in a dog

PubMed Central

Lemetayer, Julie; Al-Dissi, Ahmad; Tryon, Kim; MacDonald-Dickinson, Valerie

2017-01-01

A 6-year-old castrated male boxer dog with right-sided dark purulent nasal discharge and acute bilateral blindness was diagnosed on magnetic resonance imaging (MRI) and then on necropsy with primary nasal malignant melanoma that extended into the brain, as well as concurrent ocular melanosis. There was no evidence of metastasis in other organs. PMID:28373733

Synchronous glioblastoma multiforme and chondrosarcoma: A case report and review of the literature.

PubMed

Li, Charles Xin; Goldenberg, Yoni; McLean, Catriona; Savio Gomes, Keith

2018-06-01

This case report describes the rare occurrence of two individually uncommon tumours found in synchronous manner in an otherwise healthy patient with no history of malignancy. We believe this to be the first reported case of synchronous glioblastoma and chondrosarcoma. While primary rib lesions metastasising to brain are rarely reported and primary brain lesions metastasising to rib are even rarer still, there were no previous reports in the literature of synchronous brain and rib dual primary pathology that we could identify. Unrelated dual pathology, while rare, must be considered amongst the list of differential diagnoses in patients who present with multiple lesions, and highlights the importance of separate histological confirmation prior to integrated management. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Would the Screening of Common Mental Disorders in Primary-Care Health Services Hyper-Frequent Patients Be Useful?].

PubMed

Rincón-Hoyos, Hernán G; López, Mérida R Rodríguez; Ruiz, Ana María Villa; Hernández, Carlos Augusto; Ramos, Martha Lucía

2012-12-01

Hyper-frequentation in health services is a problem for patients, their families and the institutions. This study is aimed at determining the frequency and characteristics of common mental disorders in hyper-frequent patients showing vague symptoms and signs at a primary healthcare service during the year 2007 in the city of Cali (Colombia). Cross sectional. The most frequent mental disorders in hyper-frequent patients were detected through a telephone interview which included several modules of the PRIME MD instrument. In general, healthcare service hyper-frequenters are working women, 38,7-year old in average. Basically, the consultation is due to cephalalgia but they also exhibit a high prevalence of common mental disorders (somatization, depression and anxiety) not easily diagnosed by physicians in primary care. Expenses for additional health activities generated by these patients are attributed basically to medical consultation and required procedures. Considering hyper-frequenters in health care services as a risk group in terms of common mental disorders involves screening as an efficient strategy to prevent abuse in service use and to improve satisfaction with the attention received. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Brain composition and olfactory learning in honey bees

PubMed Central

Gronenberg, Wulfila; Couvillon, Margaret J.

2015-01-01

Correlations between brain or brain component size and behavioral measures are frequently studied by comparing different animal species, which sometimes introduces variables that complicate interpretation in terms of brain function. Here, we have analyzed the brain composition of honey bees (Apis mellifera) that have been individually tested in an olfactory learning paradigm. We found that the total brain size correlated with the bees’ learning performance. Among different brain components, only the mushroom body, a structure known to be involved in learning and memory, showed a positive correlation with learning performance. In contrast, visual neuropils were relatively smaller in bees that performed better in the olfactory learning task, suggesting modality-specific behavioral specialization of individual bees. This idea is also supported by inter-individual differences in brain composition. Some slight yet statistically significant differences in the brain composition of European and Africanized honey bees are reported. Larger bees had larger brains, and by comparing brains of different sizes, we report isometric correlations for all brain components except for a small structure, the central body. PMID:20060918

Analysis of tumor- and stroma-supplied proteolytic networks reveals a brain metastasis-promoting role for cathepsin S

PubMed Central

Sevenich, Lisa; Bowman, Robert L.; Mason, Steven D.; Quail, Daniela F.; Rapaport, Franck; Elie, Benelita T.; Brogi, Edi; Brastianos, Priscilla K.; Hahn, William C.; Holsinger, Leslie J.; Massagué, Joan; Leslie, Christina S.; Joyce, Johanna A.

2014-01-01

Metastasis remains the most common cause of death in most cancers, with limited therapies for combating disseminated disease. While the primary tumor microenvironment is an important regulator of cancer progression, it is less well understood how different tissue environments influence metastasis. We analyzed tumor-stroma interactions that modulate organ tropism of brain, bone and lung metastasis in xenograft models. We identified a number of potential modulators of site-specific metastasis, including cathepsin S as a regulator of breast-to-brain metastasis. High cathepsin S expression at the primary site correlated with decreased brain metastasis-free survival in breast cancer patients. Both macrophages and tumor cells produce cathepsin S, and only the combined depletion significantly reduced brain metastasis in vivo. Cathepsin S specifically mediates blood-brain barrier transmigration via proteolytic processing of the junctional adhesion molecule (JAM)-B. Pharmacological inhibition of cathepsin S significantly reduced experimental brain metastasis, supporting its consideration as a therapeutic target for this disease. PMID:25086747

Prevalence estimates for primary brain tumors in the United States by age, gender, behavior, and histology.

PubMed

Porter, Kimberly R; McCarthy, Bridget J; Freels, Sally; Kim, Yoonsang; Davis, Faith G

2010-06-01

Prevalence is the best indicator of cancer survivorship in the population, but few studies have focused on brain tumor prevalence because of previous data limitations. Hence, the full impact of primary brain tumors on the healthcare system in the United States is not completely described. The present study provides an estimate of the prevalence of disease in the United States, updating an earlier prevalence study. Incidence data for 2004 and survival data for 1985-2005 were obtained by the Central Brain Tumor Registry of the United States from selected regions, modeled under 2 different survival assumptions, to estimate prevalence rates for the year 2004 and projected estimates for 2010. The overall incidence rate for primary brain tumors was 18.1 per 100 000 person-years with 2-, 5-, 10-, and 20-year observed survival rates of 62%, 54%, 45%, and 30%, respectively. On the basis of the sum of nonmalignant and averaged malignant estimates, the overall prevalence rate of individuals with a brain tumor was estimated to be 209.0 per 100 000 in 2004 and 221.8 per 100 000 in 2010. The female prevalence rate (264.8 per 100 000) was higher than that in males (158.7 per 100 000). The averaged prevalence rate for malignant tumors (42.5 per 100 000) was lower than the prevalence for nonmalignant tumors (166.5 per 100 000). This study provides estimates of the 2004 (n = 612 770) and 2010 (n = 688 096) expected number of individuals living with primary brain tumor diagnoses in the United States, providing more current and robust estimates for aiding healthcare planning and patient advocacy for an aging US population.

The isoform A of reticulon-4 (Nogo-A) in cerebrospinal fluid of primary brain tumor patients: influencing factors.

PubMed

Koper, Olga Martyna; Kamińska, Joanna; Milewska, Anna; Sawicki, Karol; Mariak, Zenon; Kemona, Halina; Matowicka-Karna, Joanna

2018-05-18

The influence of isoform A of reticulon-4 (Nogo-A), also known as neurite outgrowth inhibitor, on primary brain tumor development was reported. Therefore the aim was the evaluation of Nogo-A concentrations in cerebrospinal fluid (CSF) and serum of brain tumor patients compared with non-tumoral individuals. All serum results, except for two cases, obtained both in brain tumors and non-tumoral individuals, were below the lower limit of ELISA detection. Cerebrospinal fluid Nogo-A concentrations were significantly lower in primary brain tumor patients compared to non-tumoral individuals. The univariate linear regression analysis found that if white blood cell count increases by 1 × 10 3 /μL, the mean cerebrospinal fluid Nogo-A concentration value decreases 1.12 times. In the model of multiple linear regression analysis predictor variables influencing cerebrospinal fluid Nogo-A concentrations included: diagnosis, sex, and sodium level. The mean cerebrospinal fluid Nogo-A concentration value was 1.9 times higher for women in comparison to men. In the astrocytic brain tumor group higher sodium level occurs with lower cerebrospinal fluid Nogo-A concentrations. We found the opposite situation in non-tumoral individuals. Univariate linear regression analysis revealed, that cerebrospinal fluid Nogo-A concentrations change in relation to white blood cell count. In the created model of multiple linear regression analysis we found, that within predictor variables influencing CSF Nogo-A concentrations were diagnosis, sex, and sodium level. Results may be relevant to the search for cerebrospinal fluid biomarkers and potential therapeutic targets in primary brain tumor patients. Nogo-A concentrations were tested by means of enzyme-linked immunosorbent assay (ELISA).

Correlation of Tumor and Peritumoral Edema Volumes with Survival in Patients with Cerebral Metastases.

PubMed

Kerschbaumer, Johannes; Bauer, Marlies; Popovscaia, Marina; Grams, Astrid E; Thomé, Claudius; Freyschlag, Christian F

2017-02-01

Surgical resection in combination with radiotherapy in selected cases remains the best option for patients with cerebral metastases. Postoperative relapse of brain metastases occurs frequently and can be reduced by postoperative whole-brain radiotherapy (WBRT). Continuous spread of tumor cells from the primary lesions is debated as a cause of recurrence. It is well known that in gliomas, infiltration takes place within the surrounding edema. Obviously, most brain metastases are usually associated with peritumoral edema, which may act as an indicator of infiltration and more aggressive tumor biology. Therefore, we aimed to investigate the correlation of tumor and edema volumes with overall survival in patients with cerebral metastases. A total of 143 patients diagnosed with brain metastasis (male:female=1.1:1) who underwent surgical resection were included retrospectively in this analysis. Clinical data were retrieved from electronic patient files. The volumes of tumor and edema calculated by manual delineation. The ratio of edema to tumor volume was calculated, leading to dichotomization of the patients. The median tumor volume was 20.1 cc (range=0.8-90.8 cc) and the median volume of edema 49.5 cc (range=0-179.9 cc). The volume of metastases did not significantly correlate with overall survival. The ratio of edema to tumor volume was also not a prognostic factor in terms of overall survival. Only surgical resection, preoperative recursive partitioning analysis class, and postoperative addition of WBRT, as well as female sex, demonstrated beneficial effects. The extent of edema surrounding cerebral metastases does not appear to influence overall survival in patients suffering from brain metastases, although it seems to be responsible for most of the patients' symptoms. The hypothesis that the extent of edema was disadvantageous concerning survival was supported by our data. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Tentative Evidence for Striatal Hyperactivity in Adolescent Cannabis Using Boys: A Cross-Sectional Multicenter fMRI Study

PubMed Central

Jager, Gerry; Block, Robert I.; Luijten, Maartje; Ramsey, Nick F.

2013-01-01

Adolescents' risk-taking behavior has been linked to a maturational imbalance between reward (“go”) and inhibitory-control (“stop”) related brain circuitry. This may drive adolescent drug-taking, such as cannabis use. In this study we assessed the non-acute effects of adolescent cannabis use on reward-related brain function. We performed a two-site (United States and Netherlands; pooled data) functional magnetic resonance imaging (fMRI) study with a cross-sectional design. Twenty-one abstinent but frequent cannabis-using boys were compared with 24 non-using peers on reward-related brain function, using a monetary incentive delay task with fMRI. Focus was on anticipatory and response stages of reward and brain areas critically involved in reward processing like the striatum. Performance in users was normal. Region-of-interest analysis indicated striatal hyperactivity during anticipatory stages of reward in users. Intriguingly, this effect was most pronounced during non-rewarding events. Striatal hyperactivity in adolescent cannabis users may signify an overly sensitive motivational brain circuitry. Frequent cannabis use during adolescence may induce diminished ability to disengage the motivational circuit when no reward can be obtained. This could strengthen the search for reinforcements like drugs of abuse, even when facing the negative (non-rewarding) consequences. PMID:23909003

Tentative evidence for striatal hyperactivity in adolescent cannabis-using boys: a cross-sectional multicenter fMRI study.

PubMed

Jager, Gerry; Block, Robert I; Luijten, Maartje; Ramsey, Nick F

2013-01-01

Adolescents' risk-taking behavior has been linked to a maturational imbalance between reward ("go") and inhibitory-control ("stop")-related brain circuitry. This may drive adolescent drug-taking, such as cannabis use. In this study, we assessed the non-acute effects of adolescent cannabis use on reward-related brain function. We performed a two-site (United States and Netherlands; pooled data) functional magnetic resonance imaging (fMRI) study with a cross-sectional design. Twenty-one abstinent but frequent cannabis-using boys were compared with 24 non-using peers on reward-related brain function, using a monetary incentive delay task with fMRI. Focus was on anticipatory and response stages of reward and brain areas critically involved in reward processing like the striatum. Performance in users was normal. Region-of-interest analysis indicated striatal hyperactivity during anticipatory stages of reward in users. Intriguingly, this effect was most pronounced during non-rewarding events. Striatal hyperactivity in adolescent cannabis users may signify an overly sensitive motivational brain circuitry. Frequent cannabis use during adolescence may induce diminished ability to disengage the motivational circuit when no reward can be obtained. This could strengthen the search for reinforcements like drugs of abuse, even when facing the negative (non-rewarding) consequences.

Microglia and Macrophages in Malignant Gliomas: Recent Discoveries and Implications for Promising Therapies

PubMed Central

Carvalho da Fonseca, Anna Carolina; Badie, Behnam

2013-01-01

Malignant gliomas are the most common primary brain tumors. Their deadliest manifestation, glioblastoma multiforme (GBM), accounts for 15% of all primary brain tumors and is associated with a median survival of only 15 months even after multimodal therapy. There is substantial presence of microglia and macrophages within and surrounding brain tumors. These immune cells acquire an alternatively activated phenotype with potent tumor-tropic functions that contribute to glioma growth and invasion. In this review, we briefly summarize recent data that has been reported on the interaction of microglia/macrophages with brain tumors and discuss potential application of these findings to the development of future antiglioma therapies. PMID:23864876

Electrochemical Analysis of Neurotransmitters

NASA Astrophysics Data System (ADS)

Bucher, Elizabeth S.; Wightman, R. Mark

2015-07-01

Chemical signaling through the release of neurotransmitters into the extracellular space is the primary means of communication between neurons. More than four decades ago, Ralph Adams and his colleagues realized the utility of electrochemical methods for the study of easily oxidizable neurotransmitters, such as dopamine, norepinephrine, and serotonin and their metabolites. Today, electrochemical techniques are frequently coupled to microelectrodes to enable spatially resolved recordings of rapid neurotransmitter dynamics in a variety of biological preparations spanning from single cells to the intact brain of behaving animals. In this review, we provide a basic overview of the principles underlying constant-potential amperometry and fast-scan cyclic voltammetry, the most commonly employed electrochemical techniques, and the general application of these methods to the study of neurotransmission. We thereafter discuss several recent developments in sensor design and experimental methodology that are challenging the current limitations defining the application of electrochemical methods to neurotransmitter measurements.

The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes.

PubMed

Xie, Yuan; Bergström, Tobias; Jiang, Yiwen; Johansson, Patrik; Marinescu, Voichita Dana; Lindberg, Nanna; Segerman, Anna; Wicher, Grzegorz; Niklasson, Mia; Baskaran, Sathishkumar; Sreedharan, Smitha; Everlien, Isabelle; Kastemar, Marianne; Hermansson, Annika; Elfineh, Lioudmila; Libard, Sylwia; Holland, Eric Charles; Hesselager, Göran; Alafuzoff, Irina; Westermark, Bengt; Nelander, Sven; Forsberg-Nilsson, Karin; Uhrbom, Lene

2015-10-01

Glioblastoma (GBM) is the most frequent and malignant form of primary brain tumor. GBM is essentially incurable and its resistance to therapy is attributed to a subpopulation of cells called glioma stem cells (GSCs). To meet the present shortage of relevant GBM cell (GC) lines we developed a library of annotated and validated cell lines derived from surgical samples of GBM patients, maintained under conditions to preserve GSC characteristics. This collection, which we call the Human Glioblastoma Cell Culture (HGCC) resource, consists of a biobank of 48 GC lines and an associated database containing high-resolution molecular data. We demonstrate that the HGCC lines are tumorigenic, harbor genomic lesions characteristic of GBMs, and represent all four transcriptional subtypes. The HGCC panel provides an open resource for in vitro and in vivo modeling of a large part of GBM diversity useful to both basic and translational GBM research.

The Potential of Cellular- and Viral-Based Immunotherapies for Malignant Glioma-Dendritic Cell Vaccines, Adoptive Cell Transfer, and Oncolytic Viruses.

PubMed

Maxwell, Russell; Luksik, Andrew S; Garzon-Muvdi, Tomas; Lim, Michael

2017-06-01

Malignant gliomas, including glioblastoma and anaplastic astrocytoma, are the most frequent primary brain tumors and present with many treatment challenges. In this review, we discuss the potential of cellular- and viral-based immunotherapies in the treatment of malignant glioma, specifically focusing on dendritic cell vaccines, adoptive cell therapy, and oncolytic viruses. Diverse cellular- and viral-based strategies have been engineered and optimized to generate either a specific or broad antitumor immune response in malignant glioma. Due to their successes in the preclinical arena, many of these therapies have undergone phase I and II clinical testing. These early clinical trials have demonstrated the feasibility, safety, and efficacy of these immunotherapies. Dendritic cell vaccines, adoptive cell transfer, and oncolytic viruses may have a potential role in the treatment of malignant glioma. However, these modalities must be investigated in well-designed phase III trials to prove their efficacy.

A mathematical model describes the malignant transformation of low grade gliomas: Prognostic implications.

PubMed

Bogdańska, Magdalena U; Bodnar, Marek; Piotrowska, Monika J; Murek, Michael; Schucht, Philippe; Beck, Jürgen; Martínez-González, Alicia; Pérez-García, Víctor M

2017-01-01

Gliomas are the most frequent type of primary brain tumours. Low grade gliomas (LGGs, WHO grade II gliomas) may grow very slowly for the long periods of time, however they inevitably cause death due to the phenomenon known as the malignant transformation. This refers to the transition of LGGs to more aggressive forms of high grade gliomas (HGGs, WHO grade III and IV gliomas). In this paper we propose a mathematical model describing the spatio-temporal transition of LGGs into HGGs. Our modelling approach is based on two cellular populations with transitions between them being driven by the tumour microenvironment transformation occurring when the tumour cell density grows beyond a critical level. We show that the proposed model describes real patient data well. We discuss the relationship between patient prognosis and model parameters. We approximate tumour radius and velocity before malignant transformation as well as estimate the onset of this process.

Electrochemical Analysis of Neurotransmitters

PubMed Central

Bucher, Elizabeth S.; Wightman, R. Mark

2016-01-01

Chemical signaling through the release of neurotransmitters into the extracellular space is the primary means of communication between neurons. More than four decades ago, Ralph Adams and his colleagues realized the utility of electrochemical methods for the study of easily oxidizable neurotransmitters, such as dopamine, norepinephrine, and serotonin and their metabolites. Today, electrochemical techniques are frequently coupled to microelectrodes to enable spatially resolved recordings of rapid neurotransmitter dynamics in a variety of biological preparations spanning from single cells to the intact brain of behaving animals. In this review, we provide a basic overview of the principles underlying constant-potential amperometry and fast-scan cyclic voltammetry, the most commonly employed electrochemical techniques, and the general application of these methods to the study of neurotransmission. We thereafter discuss several recent developments in sensor design and experimental methodology that are challenging the current limitations defining the application of electrochemical methods to neurotransmitter measurements. PMID:25939038

Neuroscientists’ Classroom Visits Positively Impact Student Attitudes

PubMed Central

Fitzakerley, Janet L.; Michlin, Michael L.; Paton, John; Dubinsky, Janet M.

2013-01-01

The primary recommendation of the 2010 President’s Council of Advisors on Science and Technology report on K-12 education was to inspire more students so that they are motivated to study science. Scientists’ visits to classrooms are intended to inspire learners and increase their interest in science, but verifications of this impact are largely qualitative. Our primary goal was to evaluate the impact of a longstanding Brain Awareness classroom visit program focused on increasing learners understanding of their own brains. Educational psychologists have established that neuroscience training sessions can improve academic performance and shift attitudes of students from a fixed mindset to a growth mindset. Our secondary goal was to determine whether short interactive Brain Awareness scientist-in-the-classroom sessions could similarly alter learners’ perceptions of their own potential to learn. Teacher and student surveys were administered in 4th-6th grade classrooms throughout Minnesota either before or after one-hour Brain Awareness sessions that engaged students in activities related to brain function. Teachers rated the Brain Awareness program as very valuable and said that the visits stimulated students’ interest in the brain and in science. Student surveys probed general attitudes towards science and their knowledge of neuroscience concepts (particularly the ability of the brain to change). Significant favorable improvements were found on 10 of 18 survey statements. Factor analyses of 4805 responses demonstrated that Brain Awareness presentations increased positive attitudes toward science and improved agreement with statements related to growth mindset. Overall effect sizes were small, consistent with the short length of the presentations. Thus, the impact of Brain Awareness presentations was positive and proportional to the efforts expended, demonstrating that short, scientist-in-the-classroom visits can make a positive contribution to primary school students’ attitudes toward science and learning. PMID:24358325

Neuroscientists' classroom visits positively impact student attitudes.

PubMed

Fitzakerley, Janet L; Michlin, Michael L; Paton, John; Dubinsky, Janet M

2013-01-01

The primary recommendation of the 2010 President's Council of Advisors on Science and Technology report on K-12 education was to inspire more students so that they are motivated to study science. Scientists' visits to classrooms are intended to inspire learners and increase their interest in science, but verifications of this impact are largely qualitative. Our primary goal was to evaluate the impact of a longstanding Brain Awareness classroom visit program focused on increasing learners understanding of their own brains. Educational psychologists have established that neuroscience training sessions can improve academic performance and shift attitudes of students from a fixed mindset to a growth mindset. Our secondary goal was to determine whether short interactive Brain Awareness scientist-in-the-classroom sessions could similarly alter learners' perceptions of their own potential to learn. Teacher and student surveys were administered in 4(th)-6(th) grade classrooms throughout Minnesota either before or after one-hour Brain Awareness sessions that engaged students in activities related to brain function. Teachers rated the Brain Awareness program as very valuable and said that the visits stimulated students' interest in the brain and in science. Student surveys probed general attitudes towards science and their knowledge of neuroscience concepts (particularly the ability of the brain to change). Significant favorable improvements were found on 10 of 18 survey statements. Factor analyses of 4805 responses demonstrated that Brain Awareness presentations increased positive attitudes toward science and improved agreement with statements related to growth mindset. Overall effect sizes were small, consistent with the short length of the presentations. Thus, the impact of Brain Awareness presentations was positive and proportional to the efforts expended, demonstrating that short, scientist-in-the-classroom visits can make a positive contribution to primary school students' attitudes toward science and learning.

Complementary and Integrative Interventions for Chronic Neurologic Conditions Encountered in the Primary Care Office.

PubMed

Bega, Danny

2017-06-01

Chronic neurologic conditions are frequently managed in the primary care setting, and patients with these conditions are increasingly seeking nonconventional treatment options. This article provides a review and summary of the evidence for some of the most commonly studied and most frequently used complementary and integrative interventions for 3 conditions managed every day in primary care offices - diabetic neuropathy, migraine, and dementia. Copyright © 2017 Elsevier Inc. All rights reserved.

Spoken Persuasive Discourse Abilities of Adolescents with Acquired Brain Injury

ERIC Educational Resources Information Center

Moran, Catherine; Kirk, Cecilia; Powell, Emma

2012-01-01

Purpose: The aim of this study was to examine the performance of adolescents with acquired brain injury (ABI) during a spoken persuasive discourse task. Persuasive discourse is frequently used in social and academic settings and is of importance in the study of adolescent language. Method: Participants included 8 adolescents with ABI and 8 peers…

Didelphis marsupialis: a primary reservoir of Trypanosoma cruzi in urban areas of Caracas, Venezuela.

PubMed

Herrera, L; Urdaneta-Morales, S

1992-12-01

Direct blood examination and xenodiagnosis of 45 sylvatic, peridomestic or domestic mammals from the Caracas valley, Venezuela, revealed trypanosome infection in six of the 24 opossums, Didelphis marsupialis, collected in urban areas. Isolates were successfully made of trypanosomes from four of the opossums, using the parasites which developed in Rhodnius prolixus fed on the infected opossums to infect NMRI mice. The prepatent period, course of parasitaemia, morphology of bloodstream trypomastigotes, tissue tropism of parasites in the opossums and/or mice, host mortality, morphology of parasites in the bugs, and infectivity to mice of parasites in the faeces of infected bugs, were all characteristic of Trypanosoma (Schizotrypanum) cruzi. In mice, the parasites showed marked myotropism; the heart, skeletal muscle and the smooth muscle of the urinary bladder, penis, prostate, seminal vesicle, lung, stomach, jejunum and colon were frequently invaded, and pseudocyts were also occasionally found in the liver, brain and pancreas. The significance of the invasion of the genito-urinary structures as a possible alternative parasite transmission route is discussed. The possible role of D. marsupialis, as a primary reservoir of T. cruzi, in the establishment of foci of Chagas' disease in Caracas and other Latin American cities, is emphasized.

Switching benchmarks in cancer of unknown primary: from autopsy to microarray.

PubMed

Pentheroudakis, George; Golfinopoulos, Vassilios; Pavlidis, Nicholas

2007-09-01

Cancer of unknown primary (CUP) is associated with unknown biology and dismal prognosis. Information on the primary site of origin is scant and has never been analysed. We systematically reviewed all published evidence on the CUP primary site identified by two different approaches, either autopsy or microarray gene expression profiling. Published reports on identification of CUP primary site by autopsy or microarray-based multigene expression platforms were retrieved and analysed for year of publication, primary site, patient age, gender, histology, rate of primary identification, manifestations and metastatic deposits, microarray chip technology, training and validation sets, mathematical modelling, classification accuracy and number of classifying genes. From 1944 to 2000, a total of 884 CUP patients (66% males) underwent autopsy in 12 studies after presenting with metastatic or systemic symptoms and succumbing to their disease. A primary was identified in 644 (73%) of them, mostly in the lung (27%), pancreas (24%), hepatobiliary tree (8%), kidneys (8%), bowel, genital system and stomach, as a small focus of adenocarcinoma or poorly differentiated carcinoma. An unpredictable systemic dissemination was evident with high frequency of lung (46%), nodal (35%), bone (17%), brain (16%) and uncommon (18%) deposits. Between the 1944-1980 and the 1980-2000 series, female representation increased, 'undetermined neoplasm' diagnosis became rarer, pancreatic primaries were found less often while colonic ones were identified more frequently. Four studies using microarray technology profiled more than 500 CUP cases using classifier set of genes (ranging from 10 to 495) and reported strikingly dissimilar frequencies of assigned primary sites (lung 11.5%, pancreas 12.5%, bowel 12%, breast 15%, hepatobiliary tree 8%, kidneys 6%, genital system 9%, bladder 5%) in 75-90% of the cases. Evolution in medical imaging technology, diet and lifestyle habits probably account for changing epidemiology of CUP primaries in autopsies. Discrepant assignment of primary sites by microarrays may be due to the presence of 'sanctuary sites' in autopsies, molecular misclassification and the postulated presence of a pro-metastatic genetic signature. In view of the absence of patient therapeutic or prognostic benefit with primary identification, gene expression profiling should be re-orientated towards unraveling the complex pathophysiology of metastases.

Hydroxyurea-mediated neuroblast ablation establishes birthdates of secondary lineages and addresses neuronal interactions in the developing Drosophila brain

PubMed Central

Lovick, Jennifer K.; Hartenstein, Volker

2015-01-01

The Drosophila brain is comprised of neurons formed by approximately 100 lineages, each of which is derived from a stereotyped, asymmetrically dividing neuroblast. Lineages serve as structural and developmental units of Drosophila brain anatomy and reconstruction of lineage projection patterns represents a suitable map of Drosophila brain circuitry at the level of neuron populations (“macro-circuitry”). Two phases of neuroblast proliferation, the first in the embryo and the second during the larval phase (following a period of mitotic quiescence), produce primary and secondary lineages, respectively. Using temporally controlled pulses of hydroxyurea (HU) to ablate neuroblasts and their corresponding secondary lineages during the larval phase, we analyzed the effect on development of primary and secondary lineages in the late larval and adult brain. Our findings indicate that timing of neuroblast re-activation is highly stereotyped, allowing us to establish “birth dates” for all secondary lineages. Furthermore, our results demonstrate that, whereas the trajectory and projection pattern of primary and secondary lineages is established in a largely independent manner, the final branching pattern of secondary neurons is dependent upon the presence of appropriate neuronal targets. Taken together, our data provide new insights into the degree of neuronal plasticity during Drosophila brain development. PMID:25773365

Brainstem involvement in subacute sclerosing panencephalitis.

PubMed

Sharma, Pawan; Singh, Dileep; Singh, Maneesh Kumar; Garg, Ravindra Kumar; Kohli, Neera

2011-01-01

The parieto-occipital region of the brain is most frequently and severely affected in subacute sclerosing panencephalitis (SSPE). The basal ganglia, cerebellum and corpus callosum are less commonly involved. Brainstem involvement is rarely described in SSPE, and usually there is involvement of other regions of the brain. We describe a patient with subacute sclerosing panencephalitis with brain magnetic resonance imaging showing extensive brainstem involvement without significant involvement of other cortical structures. Though rarely described in SSPE, one should be aware of such brainstem and cerebellum involvement, and SSPE should be kept in mind when brainstem signal changes are seen in brain MRI with or without involvement of other regions of brain to avoid erroneous reporting.

TNF-α enhancement of CD62E mediates adhesion of non-small cell lung cancer cells to brain endothelium via CD15 in lung-brain metastasis.

PubMed

Jassam, Samah A; Maherally, Zaynah; Smith, James R; Ashkan, Keyoumars; Roncaroli, Federico; Fillmore, Helen L; Pilkington, Geoffrey J

2016-05-01

CD15, which is overexpressed on various cancers, has been reported as a cell adhesion molecule that plays a key role in non-CNS metastasis. However, the role of CD15 in brain metastasis is largely unexplored. This study provides a better understanding of CD15/CD62E interaction, enhanced by tumor necrosis factor-α (TNF-α), and its correlation with brain metastasis in non-small cell lung cancer (NSCLC). CD15 and E-selectin (CD62E) expression was demonstrated in both human primary and metastatic NSCLC cells using flow cytometry, immunofluorescence, and Western blotting. The role of CD15 was investigated using an adhesion assay under static and physiological flow live-cell conditions. Human tissue sections were examined using immunohistochemistry. CD15, which was weakly expressed on hCMEC/D3 human brain endothelial cells, was expressed at high levels on metastatic NSCLC cells (NCI-H1299, SEBTA-001, and SEBTA-005) and at lower levels on primary NSCLC (COR-L105 and A549) cells (P < .001). The highest expression of CD62E was observed on hCMEC/D3 cells activated with TNF-α, with lower levels on metastatic NSCLC cells followed by primary NSCLC cells. Metastatic NSCLC cells adhered most strongly to hCMEC/D3 compared with primary NSCLC cells. CD15 immunoblocking decreased cancer cell adhesion to brain endothelium under static and shear stress conditions (P < .0001), confirming a correlation between CD15 and cerebral metastasis. Both CD15 and CD62E expression were detected in lung metastatic brain biopsies. This study enhances the understanding of cancer cell-brain endothelial adhesion and confirms that CD15 plays a crucial role in adhesion in concert with TNF-α activation of its binding partner, CD62E. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

TNF-α enhancement of CD62E mediates adhesion of non–small cell lung cancer cells to brain endothelium via CD15 in lung-brain metastasis

PubMed Central

Jassam, Samah A.; Maherally, Zaynah; Smith, James R.; Ashkan, Keyoumars; Roncaroli, Federico; Fillmore, Helen L.; Pilkington, Geoffrey J.

2016-01-01

Background CD15, which is overexpressed on various cancers, has been reported as a cell adhesion molecule that plays a key role in non-CNS metastasis. However, the role of CD15 in brain metastasis is largely unexplored. This study provides a better understanding of CD15/CD62E interaction, enhanced by tumor necrosis factor-α (TNF-α), and its correlation with brain metastasis in non–small cell lung cancer (NSCLC). Methods CD15 and E-selectin (CD62E) expression was demonstrated in both human primary and metastatic NSCLC cells using flow cytometry, immunofluorescence, and Western blotting. The role of CD15 was investigated using an adhesion assay under static and physiological flow live-cell conditions. Human tissue sections were examined using immunohistochemistry. Results CD15, which was weakly expressed on hCMEC/D3 human brain endothelial cells, was expressed at high levels on metastatic NSCLC cells (NCI-H1299, SEBTA-001, and SEBTA-005) and at lower levels on primary NSCLC (COR-L105 and A549) cells (P < .001). The highest expression of CD62E was observed on hCMEC/D3 cells activated with TNF-α, with lower levels on metastatic NSCLC cells followed by primary NSCLC cells. Metastatic NSCLC cells adhered most strongly to hCMEC/D3 compared with primary NSCLC cells. CD15 immunoblocking decreased cancer cell adhesion to brain endothelium under static and shear stress conditions (P < .0001), confirming a correlation between CD15 and cerebral metastasis. Both CD15 and CD62E expression were detected in lung metastatic brain biopsies. Conclusion This study enhances the understanding of cancer cell-brain endothelial adhesion and confirms that CD15 plays a crucial role in adhesion in concert with TNF-α activation of its binding partner, CD62E. PMID:26472821

Clinical characteristics of persistent frequent attenders in primary care: case-control study.

PubMed

Patel, Shireen; Kai, Joe; Atha, Christopher; Avery, Anthony; Guo, Boliang; James, Marilyn; Malins, Samuel; Sampson, Christopher; Stubley, Michelle; Morriss, Richard

2015-12-01

Most frequent attendance in primary care is temporary, but persistent frequent attendance is expensive and may be suitable for psychological intervention. To plan appropriate intervention and service delivery, there is a need for research involving standardized psychiatric interviews with assessment of physical health and health status. To compare the mental and physical health characteristics and health status of persistent frequent attenders (FAs) in primary care, currently and over the preceding 2 years, with normal attenders (NAs) matched by age, gender and general practice. Case-control study of 71 FAs (30 or more GP or practice nurse consultations in 2 years) and 71 NAs, drawn from five primary care practices, employing standardized psychiatric interview, quality of life, health anxiety and primary care electronic record review over the preceding 2 years. Compared to NAs, FAs were more likely to report a lower quality of life (P < 0.001), be unmarried (P = 0.03) and have no educational qualifications (P = 0.009) but did not differ in employment status. FAs experienced greater health anxiety (P < 0.001), morbid obesity (P = 0.02), pain (P < 0.001) and long-term pathological and ill-defined physical conditions (P < 0.001). FAs had more depression including dysthymia, anxiety and somatoform disorders (all P < 0.001). Persistent frequent attendance in primary care was associated with poor quality of life and high clinical complexity characterized by diverse and often persistent physical and mental multimorbidity. A brokerage model with GPs working in close liaison with skilled psychological therapists is required to manage such persistent complexity. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of nifedipine and atosiban on perinatal brain injury: secondary analysis of the APOSTEL-III trial.

PubMed

Nijman, T A J; Goedhart, M M; Naaktgeboren, C N; de Haan, T R; Vijlbrief, D C; Mol, B W; Benders, M J N; Franx, A; Oudijk, M A

2018-06-01

Brain injury in neonates born prematurely is associated strongly with poor neurodevelopmental outcome. The aim of this study was to evaluate whether tocolysis with nifedipine or atosiban in women with threatened preterm birth can reduce the incidence of overall brain injury in neonates born prematurely. This was a secondary analysis of the APOSTEL-III trial (Dutch Clinical Trial Registry, no. NTR2947), a randomized clinical trial in which women with threatened preterm labor between 25 and 34 weeks of gestation were allocated to treatment with nifedipine or atosiban. In this secondary analysis, women delivered at ≤ 32 weeks of gestational age in the two main contributing centers were included. Primary outcome was the presence of neonatal brain injury, which was defined as presence of abnormalities on ultrasound investigation and classified into mild and severe. To evaluate type and severity of brain injury, all neonatal ultrasounds performed during neonatal intensive and medium care admission were analyzed. To test the robustness of our results, a sensitivity analysis was performed assessing differences in baseline or known risk factors for brain injury. A total of 117 neonates (from 102 women) were studied, of which 51 had been exposed to nifedipine and 66 to atosiban. Brain injury was observed in 22 (43.1%) neonates in the nifedipine group compared with 37 (56.1%) in the atosiban group (OR, 0.60; 95% CI, 0.29-1.24). Presence of mild brain injury was comparable between the nifedipine (33.3%) and atosiban (48.5%) groups (OR, 0.53; 95% CI, 0.25-1.13). Severe brain injury was also comparable between the groups, observed in 9.8% of neonates in the nifedipine vs 7.6% of those in the atosiban group (OR, 1.33; 95% CI, 0.36-4.85). Intraventricular hemorrhage (≥ Grade I) was the most frequently seen ultrasound abnormality, observed in 18 (35.3%) neonates in the nifedipine group vs 25 (37.9%) in the atosiban group (OR, 0.90; 95% CI, 0.42-1.91). The sensitivity analysis, with adjustment for maternal age and gestational age at randomization, showed no statistical difference between the groups for presence of brain injury (OR, 0.58; 95% CI, 0.27-1.27). In children born before 32 weeks of gestation after the use of tocolytics, the prevalence of brain injury was high. No significant differences were found with respect to overall brain injury between neonates exposed to nifedipine and those exposed to atosiban. However, as this study was a secondary analysis of the APOSTEL III trial, it was underpowered for brain injury. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Multiple bone metastases from glioblastoma multiforme without local brain relapse: a case report and review of the literature.

PubMed

Takanen, Silvia; Bangrazi, Caterina; Caiazzo, Rossella; Raffetto, Nicola; Tombolini, Vincenzo

2013-01-01

Extracranial metastases from glioblastoma multiforme (GBM) are a very rare event, even if an increasing incidence has been documented. We report the case of a young woman with primary GBM who developed bone metastases without local brain relapse. Because of persistent headache and visual disturbances, in March 2011 the patient underwent magnetic resonance imaging (MRI) evidencing a temporoparietal mass, which was surgically resected. Histology revealed GBM. She was given concomitant chemoradiotherapy according to the Stupp regimen. After a 4-week break, the patient received 6 cycles of adjuvant temozolomide according to the standard 5-day schedule every 28 days. In December 2011 she complained of progressive low back pain, and MRI showed multiple bone metastases from primary GBM, confirmed by histology. Cases of metastatic GBM in concurrence with a primary brain tumor or local relapse are more common in the literature; only a few cases have been reported where extracranial metastases from GBM occurred without any relapse in the brain. Here we report our experience.

Long-term cognitive effects of human stem cell transplantation in the irradiated brain.

PubMed

Acharya, Munjal M; Martirosian, Vahan; Christie, Lori-Ann; Limoli, Charles L

2014-09-01

Radiotherapy remains a primary treatment modality for the majority of central nervous system tumors, but frequently leads to debilitating cognitive dysfunction. Given the absence of satisfactory solutions to this serious problem, we have used human stem cell therapies to ameliorate radiation-induced cognitive impairment. Here, past studies have been extended to determine whether engrafted cells provide even longer-term benefits to cognition. Athymic nude rats were cranially irradiated (10 Gy) and subjected to intrahippocampal transplantation surgery 2 days later. Human embryonic stem cells (hESC) or human neural stem cells (hNSC) were transplanted, and animals were subjected to cognitive testing on a novel place recognition task 8 months later. Grafting of hNSC was found to provide long lasting cognitive benefits over an 8-month post-irradiation interval. At this protracted time, hNSC grafting improved behavioral performance on a novel place recognition task compared to irradiated animals not receiving stem cells. Engrafted hESC previously shown to be beneficial following a similar task, 1 and 4 months after irradiation, were not found to provide cognitive benefits at 8 months. Our findings suggest that hNSC transplantation promotes the long-term recovery of the irradiated brain, where intrahippocampal stem cell grafting helps to preserve cognitive function.

Role of the cathelicidin-related antimicrobial peptide in inflammation and mortality in a mouse model of bacterial meningitis.

PubMed

Merres, Julika; Höss, Jonas; Albrecht, Lea-Jessica; Kress, Eugenia; Soehnlein, Oliver; Jansen, Sandra; Pufe, Thomas; Tauber, Simone C; Brandenburg, Lars-Ove

2014-01-01

Antimicrobial peptides (AP) are important components of the innate immune system, yet little is known about their expression and function in the brain. Our previous work revealed upregulated gene expression of cathelicidin-related AP (CRAMP) following bacterial meningitis in primary rat glial cells as well as bactericidal activity against frequent meningitis-causing bacteria. However, the effect of cathelicidin expression on the progression of inflammation and mortality in bacterial meningitis remains unknown. Therefore, we used CRAMP-deficient mice to investigate the effect of CRAMP on bacterial growth, inflammatory responses and mortality in meningitis. Meningitis was induced by intracerebral injection of type 3 Streptococcus pneumoniae. The degree of inflammation was analyzed in various brain regions by means of immunohistochemistry and real-time RT-PCR. CRAMP deficiency led to a higher mortality rate that was associated with increased bacterial titers in the cerebellum, blood and spleen as well as decreased meningeal neutrophil infiltration. CRAMP-deficient mice displayed a higher degree of glial cell activation that was accompanied by a more pronounced proinflammatory response. Taken together, this work provides insight into the important role of CRAMP as part of the innate immune defense against pathogens in bacterial CNS infections. Copyright © 2013 S. Karger AG, Basel

Rethinking stimulation of brain in stroke rehabilitation: Why higher-motor areas might be better alternatives for patients with greater impairments

PubMed Central

Plow, Ela B; Cunningham, David; Varnerin, Nicole; Machado, Andre

2015-01-01

Stimulating the brain to drive its adaptive plastic potential is promising to accelerate rehabilitative outcomes in stroke. Ipsilesional Primary Motor Cortex (M1) is invariably facilitated. However, evidence supporting its efficacy is divided, indicating we may have over-generalized its potential. Since M1 and its corticospinal output are frequently damaged, in patients with serious lesions and impairments, ipsilesional premotor areas (PMA) could be useful alternates instead. We base our premise on their higher probability of survival, greater descending projections, and an adaptive potential, which is causal for recovery across the seriously impaired. Using a conceptual model, we describe how chronically stimulating PMA would strongly affect key mechanisms of stroke motor recovery, such as facilitating plasticity of alternate descending output, restoring inter-hemispheric balance, and establishing widespread connectivity. Although at this time it is difficult to predict whether PMA would be ‘better’, it is important to at least investigate whether they are reasonable substitutes for M1. Even if stimulation of M1 may benefit those with maximum recovery potential, while that of PMA may only help the more disadvantaged, it may still be reasonable to achieve some recovery across the majority rather than stimulate a single locus fated to be inconsistently effective across all. PMID:24951091

Inter-subject Functional Correlation Reveal a Hierarchical Organization of Extrinsic and Intrinsic Systems in the Brain.

PubMed

Ren, Yudan; Nguyen, Vinh Thai; Guo, Lei; Guo, Christine Cong

2017-09-07

The brain is constantly monitoring and integrating both cues from the external world and signals generated intrinsically. These extrinsically and intrinsically-driven neural processes are thought to engage anatomically distinct regions, which are thought to constitute the extrinsic and intrinsic systems of the brain. While the specialization of extrinsic and intrinsic system is evident in primary and secondary sensory cortices, a systematic mapping of the whole brain remains elusive. Here, we characterized the extrinsic and intrinsic functional activities in the brain during naturalistic movie-viewing. Using a novel inter-subject functional correlation (ISFC) analysis, we found that the strength of ISFC shifts along the hierarchical organization of the brain. Primary sensory cortices appear to have strong inter-subject functional correlation, consistent with their role in processing exogenous information, while heteromodal regions that attend to endogenous processes have low inter-subject functional correlation. Those brain systems with higher intrinsic tendency show greater inter-individual variability, likely reflecting the aspects of brain connectivity architecture unique to individuals. Our study presents a novel framework for dissecting extrinsically- and intrinsically-driven processes, as well as examining individual differences in brain function during naturalistic stimulation.

Management of parturients in active labor with Arnold Chiari malformation, tonsillar herniation, and syringomyelia

PubMed Central

Ghaly, Ramsis F.; Tverdohleb, Tatiana; Candido, Kenneth D.; Knezevic, Nebojsa Nick

2017-01-01

Background: Arnold-Chiari malformation Type 1 (ACM-1) in parturients is a topic of ongoing discussion between obstetricians and anesthesiologists. The primary unanswered question remains; How should the anesthesia provider proceed with labor analgesia and anesthesia for cesarean section when confronted with an advanced, asymptomatic, or minimally symptomatic case of ACM-1 during labor? Case Description: A 24-year-old, ASA II, G1P0 full-term parturient presented to Labor and Delivery for vaginal delivery. A diagnosis of ACM-1 was made 12 years ago when a brain magnetic resonance imaging (MRI) was performed for right-sided numbness following a rear-end motor vehicle collision. The patient had been asymptomatic since then and had been seen by an outside neurologist frequently for the past 10 years. During the anesthesia evaluation, it was noted that she had an exaggerated patellar reflex, and a questionable left-sided Babinski; subsequently, an MRI study was requested. Review of a brain MRI demonstrated an advanced form of ACM with a 1.7 cm transtonsillar herniation and a large syrinx extending from C1 down to C5. Following a discussion with the patient, family, and primary OB team, a plan for elective cesarean section was made per neurosurgical recommendations. This was conducted uneventfully under general anesthesia. The patient had no complaints in the post-anesthesia care unit. Conclusion: Unfamiliarity of health care providers with regards to ACM-1 parturients can be countered by increasing awareness of this condition throughout medical specialties involved in their care. The Ghaly Obstetric Guide to Arnold-Chiari malformation Type 1, along with proper training of anesthesia care providers regarding the specificities of ACM-1 parturients aids in better management and understanding of this complex condition. PMID:28217389

Management of parturients in active labor with Arnold Chiari malformation, tonsillar herniation, and syringomyelia.

PubMed

Ghaly, Ramsis F; Tverdohleb, Tatiana; Candido, Kenneth D; Knezevic, Nebojsa Nick

2017-01-01

Arnold-Chiari malformation Type 1 (ACM-1) in parturients is a topic of ongoing discussion between obstetricians and anesthesiologists. The primary unanswered question remains; How should the anesthesia provider proceed with labor analgesia and anesthesia for cesarean section when confronted with an advanced, asymptomatic, or minimally symptomatic case of ACM-1 during labor? A 24-year-old, ASA II, G1P0 full-term parturient presented to Labor and Delivery for vaginal delivery. A diagnosis of ACM-1 was made 12 years ago when a brain magnetic resonance imaging (MRI) was performed for right-sided numbness following a rear-end motor vehicle collision. The patient had been asymptomatic since then and had been seen by an outside neurologist frequently for the past 10 years. During the anesthesia evaluation, it was noted that she had an exaggerated patellar reflex, and a questionable left-sided Babinski; subsequently, an MRI study was requested. Review of a brain MRI demonstrated an advanced form of ACM with a 1.7 cm transtonsillar herniation and a large syrinx extending from C1 down to C5. Following a discussion with the patient, family, and primary OB team, a plan for elective cesarean section was made per neurosurgical recommendations. This was conducted uneventfully under general anesthesia. The patient had no complaints in the post-anesthesia care unit. Unfamiliarity of health care providers with regards to ACM-1 parturients can be countered by increasing awareness of this condition throughout medical specialties involved in their care. The Ghaly Obstetric Guide to Arnold-Chiari malformation Type 1, along with proper training of anesthesia care providers regarding the specificities of ACM-1 parturients aids in better management and understanding of this complex condition.

Premature primary tooth eruption in cognitive/motor-delayed ADNP-mutated children

PubMed Central

Gozes, I; Van Dijck, A; Hacohen-Kleiman, G; Grigg, I; Karmon, G; Giladi, E; Eger, M; Gabet, Y; Pasmanik-Chor, M; Cappuyns, E; Elpeleg, O; Kooy, R F; Bedrosian-Sermone, S

2017-01-01

A major flaw in autism spectrum disorder (ASD) management is late diagnosis. Activity-dependent neuroprotective protein (ADNP) is a most frequent de novo mutated ASD-related gene. Functionally, ADNP protects nerve cells against electrical blockade. In mice, complete Adnp deficiency results in dysregulation of over 400 genes and failure to form a brain. Adnp haploinsufficiency results in cognitive and social deficiencies coupled to sex- and age-dependent deficits in the key microtubule and ion channel pathways. Here, collaborating with parents/caregivers globally, we discovered premature tooth eruption as a potential early diagnostic biomarker for ADNP mutation. The parents of 44/54 ADNP-mutated children reported an almost full erupted dentition by 1 year of age, including molars and only 10 of the children had teeth within the normal developmental time range. Looking at Adnp-deficient mice, by computed tomography, showed significantly smaller dental sacs and tooth buds at 5 days of age in the deficient mice compared to littermate controls. There was only trending at 2 days, implicating age-dependent dysregulation of teething in Adnp-deficient mice. Allen Atlas analysis showed Adnp expression in the jaw area. RNA sequencing (RNAseq) and gene array analysis of human ADNP-mutated lymphoblastoids, whole-mouse embryos and mouse brains identified dysregulation of bone/nervous system-controlling genes resulting from ADNP mutation/deficiency (for example, BMP1 and BMP4). AKAP6, discovered here as a major gene regulated by ADNP, also links cognition and bone maintenance. To the best of our knowledge, this is the first time that early primary (deciduous) teething is related to the ADNP syndrome, providing for early/simple diagnosis and paving the path to early intervention/specialized treatment plan. PMID:28221363

The effect of modafinil on fatigue, cognitive functioning, and mood in primary brain tumor patients: a multicenter randomized controlled trial

PubMed Central

Boele, Florien W.; Douw, Linda; de Groot, Marjolein; van Thuijl, Hinke F.; Cleijne, Wilmy; Heimans, Jan J.; Taphoorn, Martin J.B.; Reijneveld, Jaap C.; Klein, Martin

2013-01-01

Background Fatigue, cognitive deficits, and depression are frequently reported but often undertreated symptoms that can profoundly affect daily life in patients with primary brain tumors (PBTs). To evaluate the effects of the psychostimulant modafinil on fatigue, depression, health-related quality of life (HRQOL), and cognitive functioning in PBT patients, we performed a multicenter, double-blind placebo-controlled crossover trial. Methods Patients randomly received either 6 weeks of treatment with modafinil (up to 400 mg/day) or 6 weeks with placebo. After a 1-week washout period, the opposite treatment was provided. Assessments took place at baseline and immediately after the first and second condition. Patients completed self-report questionnaires on fatigue (Checklist Individual Strength [CIS]), depression (Center for Epidemiologic Studies Depression Scale [CES-D]), HRQOL (Short-Form Health Survey [SF-36]), and self-perceived cognitive functioning (Medical Outcomes Study [MOS]). They also underwent comprehensive neurocognitive testing. Results In total, 37 patients participated. Relative to baseline, patients reported lower fatigue severity (CIS) and better motivation (CIS) in both the modafinil (P = .010 and P = .021, respectively) and the placebo condition (P < .001 and P = .027, respectively). The same held for physical health (SF-36 Physical Component Summary score; P = .001 and P = .008, respectively), working memory (P = .040 and P = .043), and information processing capacity (P = .036 and P = .040). No improvement in depressive symptoms was found in either condition. Conclusions Modafinil did not exceed the effects of placebo with respect to symptom management. Patient accrual was slow, and relatively many patients dropped out during the trial, due mostly to side effects. Other, preferably nonpharmacologic intervention studies should be considered to improve symptom management of PBT patients. PMID:23925452

Building a neuroscience of pleasure and well-being

PubMed Central

Berridge, Kent C; Kringelbach, Morten L

2012-01-01

Background How is happiness generated via brain function in lucky individuals who have the good fortune to be happy? Conceptually, well-being or happiness has long been viewed as requiring at least two crucial ingredients: positive affect or pleasure (hedonia) and a sense of meaningfulness or engagement in life (eudaimonia). Science has recently made progress in relating hedonic pleasure to brain function, and so here we survey new insights into how brains generate the hedonic ingredient of sustained or frequent pleasure. We also briefly discuss how brains might connect hedonia states of pleasure to eudaimonia assessments of meaningfulness, and so create balanced states of positive well-being. Results Notable progress has been made in understanding brain bases of hedonic processing, producing insights into that brain systems that cause and/or code sensory pleasures. Progress has been facilitated by the recognition that hedonic brain mechanisms are largely shared between humans and other mammals, allowing application of conclusions from animal studies to a better understanding of human pleasures. In the past few years, evidence has also grown to indicate that for humans, brain mechanisms of higher abstract pleasures strongly overlap with more basic sensory pleasures. This overlap may provide a window into underlying brain circuitry that generates all pleasures, including even the hedonic quality of pervasive well-being that detaches from any particular sensation to apply to daily life in a more sustained or frequent fashion. Conclusions Hedonic insights are applied to understanding human well-being here. Our strategy combines new findings on brain mediators that generate the pleasure of sensations with evidence that human brains use many of the same hedonic circuits from sensory pleasures to create the higher pleasures. This in turn may be linked to how hedonic systems interact with other brain systems relevant to self-understanding and the meaning components of eudaimonic happiness. Finally, we speculate a bit about how brains that generate hedonia states might link to eudaimonia assessments to create properly balanced states of positive well-being that approach true happiness. PMID:22328976

Origins of Brain Tumor Macrophages.

PubMed

De Palma, Michele

2016-12-12

The ontogeny of brain-tumor-associated macrophages is poorly understood. New findings indicate that both resident microglia and blood-derived monocytes generate the pool of macrophages that infiltrate brain tumors of either primary or metastatic origin. Copyright © 2016 Elsevier Inc. All rights reserved.

Neuropathologic findings after organ transplantation. An autopsy study.

PubMed

Schwechheimer, K; Hashemian, A

1995-05-01

Since 1972 organ transplantations of kidney, bone marrow, liver, heart and lung have been performed at the University Hospital of Essen, Germany. Out of 2535 transplantations until September 1993, autopsies were performed in 157 patients In 25 patients (15.9%) neuropathologic findings (n = 26) were found. In 97 autopsies after bone marrow transplantation, 9 patients (9.3%) exhibited a severe neuropathologic alteration. In six patients (6/9; 66.6%), necrotisizing toxoplasmose encephalitis was found. Other cases showed a septic-metastatic mycotic encephalitis with crypto-coccus neoformans and candida albicans (n = 2) and leucemia infiltrates (n = 1). Massive cerebral hemorrhage was the most frequent neuropathologic finding after liver (4/8) and kidney transplantation (3/6). In addition liver-transplanted patients exhibited septic-metastatic encephalitis (3/8) and embolic brain infarct (1/8) as well as cerebral metastases (2/6) and primary malignant cerebral lymphoma in kidney transplantation (1/6). CNS findings in five autopsies after heart-lung-transplantation were diverse. They comprised intracerebral hemorrhage, intravasal lymphoma and septic-metastatic encephalitis, respectively. In summary, neuropathologic autopsy findings after organ transplantation are diverse and preferentially comprise infections, cerebral hemorrhages, and malignant lymphomas. After bone marrow transplantation, the most frequent neuropathologic autopsy finding was toxoplasmose encephalitis and massive cerebral hemorrhages after liver and kidney transplantations.

Acute lymphoblastic leukemia and lymphoma in the context of constitutional mismatch repair deficiency syndrome.

PubMed

Ripperger, Tim; Schlegelberger, Brigitte

2016-03-01

Constitutional mismatch repair deficiency (CMMRD) syndrome is one of the rare diseases associated with a high risk of cancer. Causative mutations are found in DNA mismatch repair genes PMS2, MSH6, MSH2 or MLH1 that are well known in the context of Lynch syndrome. CMMRD follows an autosomal recessive inheritance trait and is characterized by childhood brain tumors and hematological malignancies as well as gastrointestinal cancer in the second and third decades of life. There is a high risk of multiple cancers, occurring synchronously and metachronously. In general, the prognosis is poor. About one third of CMMRD patients develop hematological malignancies as primary (sometimes the only) malignancy or as secondary neoplasm. T-cell non-Hodgkin lymphomas, mainly of mediastinal origin, are the most frequent hematological malignancies. Besides malignant diseases, non-neoplastic features are frequently observed, e.g. café-au-lait spots sometimes resembling neurofibromatosis type I, hypopigmented skin lesions, numerous adenomatous polyps, multiple pilomatricomas, or impaired immunoglobulin class switch recombination. Within the present review, we summarize previously published CMMRD patients with at least one hematological malignancy, provide an overview of steps necessary to substantiate the diagnosis of CMMRD, and refer to the recent most relevant literature. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Frequent users of rural primary care: comparisons with randomly selected users.

PubMed

Mehl-Madrona, L E

1998-01-01

Frequent users of primary care have not been adequately characterized. The unique characteristics of this population was sought--why they come so often, what their care costs, and whether psychosocial factors play a role in their high utilization of health care. The billing system of a rural primary care clinic was used to find the frequency of visits for all patients attending the clinic for the previous 12 months. The 211 most frequent visitors were selected. A comparison group of 250 patients was drawn from the billing records using a random number generator. Charts were reviewed to compare diagnoses (by frequency), number of procedures, amount billed for care, amount received from those billings, number of psychotropic medications prescribed, and response to medication. A subgroup of each group was interviewed to confirm chart review findings and to inquire about personal reasons for coming to the clinic. Compared with patients who were random users, patients who were frequent users were more likely to come from the younger and older age groups, they averaged significantly more emergency department visits and visits to other specialists (P < 0.0001), and they had more mental health problems diagnosed (P < 0.01). Significantly more frequent users were insured by Medicaid and fewer were insured by Medicare. They had more detailed office visits and more laboratory tests. They received twice as much psychotherapy and had a higher percentage of problem-focused office visits. Chart audits and interviews of selected patients revealed that many nonmedical reasons were related to visits in addition to psychosocial stressors. Nonmedical factors are important among the most frequent users of a primary care clinic. Proposals to improve care for frequent users should consider the psychosocial needs of this population.

The Developmental Course of Sleep Disturbances Across Childhood Relates to Brain Morphology at Age 7: The Generation R Study.

PubMed

Kocevska, Desana; Muetzel, Ryan L; Luik, Annemarie I; Luijk, Maartje P C M; Jaddoe, Vincent W; Verhulst, Frank C; White, Tonya; Tiemeier, Henning

2017-01-01

Little is known about the impact of sleep disturbances on the structural properties of the developing brain. This study explored associations between childhood sleep disturbances and brain morphology at 7 years. Mothers from the Generation R cohort reported sleep disturbances in 720 children at ages 2 months, 1.5, 2, 3, and 6 years. T1-weighted Magnetic Resonance Imaging (MRI) images were used to assess brain structure at 7 years. Associations of sleep disturbances at each age and of sleep disturbance trajectories with brain volumes (total brain volume, cortical and subcortical grey matter, white matter) were tested with linear regressions. To assess regional differences, sleep disturbance trajectories were tested as determinants for cortical thickness in whole-brain analyses. Sleep disturbances followed a declining trend from toddlerhood onwards. Infant sleep was not associated with brain morphology at age 7. Per SD sleep disturbances (one frequent symptom or two less frequent symptoms) at 2 and 3 years of age, children had -6.3 (-11.7 to -0.8) cm3 and -6.4 (-11.7 to -1.7) cm3 smaller grey matter volumes, respectively. Sleep disturbances at age 6 years were associated with global brain morphology (grey matter: -7.3 (-12.1 to -2.6), p value = .01). Consistently, trajectory analyses showed that more adverse developmental course of childhood sleep disturbances are associated with smaller grey matter volumes and thinner dorsolateral prefrontal cortex. Sleep disturbances from age 2 years onwards are associated with smaller grey matter volumes. Thinner prefrontal cortex in children with adverse sleep disturbance trajectories may reflect effects of sleep disturbances on brain maturation. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Transiently increased colocalization of vesicular glutamate transporters 1 and 2 at single axon terminals during postnatal development of mouse neocortex: a quantitative analysis with correlation coefficient.

PubMed

Nakamura, Kouichi; Watakabe, Akiya; Hioki, Hiroyuki; Fujiyama, Fumino; Tanaka, Yasuyo; Yamamori, Tetsuo; Kaneko, Takeshi

2007-12-01

Vesicular glutamate transporter 1 (VGLUT1) and VGLUT2 show complementary distribution in neocortex; VGLUT1 is expressed mainly in axon terminals of neocortical neurons, whereas VGLUT2 is located chiefly in thalamocortical axon terminals. However, we recently reported a frequent colocalization of VGLUT1 and VGLUT2 at a subset of axon terminals in postnatal developing neocortex. We here quantified the frequency of colocalization between VGLUT1 and VGLUT2 immunoreactivities at single axon terminals by using the correlation coefficient (CC) as an indicator in order to determine the time course and spatial extent of the colocalization during postnatal development of mouse neocortex. The colocalization was more frequent in the primary somatosensory (S1) area than in both the primary visual (V1) and the motor areas; of area S1 cortical layers, colocalization was most evident in layer IV barrels at postnatal day (P) 7 and in adulthood. CC in layer IV showed a peak at P7 in area S1, and at P10 in area V1 though the latter peak was much smaller than the former. These results suggest that thalamocortical axon terminals contained not only VGLUT2 but also VGLUT1, especially at P7-10. Double fluorescence in situ hybridization confirmed coexpression of VGLUT1 and VGLUT2 mRNAs at P7 in the somatosensory thalamic nuclei and later in the thalamic dorsal lateral geniculate nucleus. As VGLUT1 is often used in axon terminals that show synaptic plasticity in adult brain, the present findings suggest that VGLUT1 is used in thalamocortical axons transiently during the postnatal period when plasticity is required.

Determinants of Glasgow outcome scale in patients with severe traumatic brain injury for better quality of life

NASA Astrophysics Data System (ADS)

Dharmajaya, R.; Sari, D. K.; Ganie, R. A.

2018-03-01

Primary and secondary brain injury may occur with severe traumatic brain injury. Secondary traumatic brain injury results in a more severe effect compared to primary traumatic brain injury. Therefore, prevention of secondary traumatic brain injury is necessary to obtain maximum therapeutic results and accurate determination of prognosis and better quality of life. This study aimed to determine accurate and noninvasive prognostic factors in patients with severe traumatic brain injury. It was a cohort study on 16 subjects. Intracranial pressure was monitored within the first 24 hours after traumatic brain injury. Examination of Brain-Derived Neurotrophic Factor (BDNF) and S100B protein were conducted four times. The severity of outcome was evaluated using Glasgow Outcome Scale (GOS) three months after traumatic brain injury. Intracranial pressure measurement performed 24 hours after traumatic brain injury, low S100B protein (<2μg/L) 120 hours after injury and increased BDNF (>6.16pg/ml) 48 hours after injury indicate good prognosis and were shown to be significant predictors (p<0.05) for determining the quality of GOS. The conclusion is patient with a moderate increase in intracranial pressure Intracranial pressure S100B protein, being inexpensive and non-invasive, can substitute BDNF and intracranial pressure measurements as a tool for determining prognosis 120 hours following traumatic brain injury.

Predictors for long-term survival free from whole brain radiation therapy in patients treated with radiosurgery for limited brain metastases.

PubMed

Gorovets, Daniel; Rava, Paul; Ebner, Daniel K; Tybor, David J; Cielo, Deus; Puthawala, Yakub; Kinsella, Timothy J; DiPetrillo, Thomas A; Wazer, David E; Hepel, Jaroslaw T

2015-01-01

To identify predictors for prolonged survival free from salvage whole brain radiation therapy (WBRT) in patients with brain metastases treated with stereotactic radiosurgery (SRS) as their initial radiotherapy approach. Patients with brain metastases treated with SRS from 2001 to 2013 at our institution were identified. SRS without WBRT was typically offered to patients with 1-4 brain metastases, Karnofsky performance status ≥70, and life expectancy ≥3 months. Three hundred and eight patients met inclusion criteria for analysis. Medical records were reviewed for patient, disease, and treatment information. Two comparison groups were identified: those with ≥1-year WBRT-free survival (N = 104), and those who died or required salvage WBRT within 3 months of SRS (N = 56). Differences between these groups were assessed by univariate and multivariate analyses. Median survival for all patients was 11 months. Among patients with ≥1-year WBRT-free survival, median survival was 33 months (12-107 months) with only 21% requiring salvage WBRT. Factors significantly associated with prolonged WBRT-free survival on univariate analysis (p < 0.05) included younger age, asymptomatic presentation, RTOG RPA class I, fewer brain metastases, surgical resection, breast primary, new or controlled primary, absence of extracranial metastatic disease, and oligometastatic disease burden (≤5 metastatic lesions). After controlling for covariates, asymptomatic presentation, breast primary, single brain metastasis, absence of extracranial metastases, and oligometastatic disease burden remained independent predictors for favorable WBRT-free survival. A subset of patients with brain metastases can achieve long-term survival after upfront SRS without the need for salvage WBRT. Predictors identified in this study can help select patients that might benefit most from a treatment strategy of SRS alone.

CD15s/CD62E Interaction Mediates the Adhesion of Non-Small Cell Lung Cancer Cells on Brain Endothelial Cells: Implications for Cerebral Metastasis

PubMed Central

Jassam, Samah A.; Maherally, Zaynah; Ashkan, Keyoumars; Roncaroli, Federico; Fillmore, Helen L.; Pilkington, Geoffrey J.

2017-01-01

Expression of the cell adhesion molecule (CAM), Sialyl Lewis X (CD15s) correlates with cancer metastasis, while expression of E-selectin (CD62E) is stimulated by TNF-α. CD15s/CD62E interaction plays a key role in the homing process of circulating leukocytes. We investigated the heterophilic interaction of CD15s and CD62E in brain metastasis-related cancer cell adhesion. CD15s and CD62E were characterised in human brain endothelium (hCMEC/D3), primary non-small cell lung cancer (NSCLC) (COR-L105 and A549) and metastatic NSCLC (SEBTA-001 and NCI-H1299) using immunocytochemistry, Western blotting, flow cytometry and immunohistochemistry in human brain tissue sections. TNF-α (25 pg/mL) stimulated extracellular expression of CD62E while adhesion assays, under both static and physiological flow live-cell conditions, explored the effect of CD15s-mAb immunoblocking on adhesion of cancer cell–brain endothelium. CD15s was faintly expressed on hCMEC/D3, while high levels were observed on primary NSCLC cells with expression highest on metastatic NSCLC cells (p < 0.001). CD62E was highly expressed on hCMEC/D3 cells activated with TNF-α, with lower levels on primary and metastatic NSCLC cells. CD15s and CD62E were expressed on lung metastatic brain biopsies. CD15s/CD62E interaction was localised at adhesion sites of cancer cell–brain endothelium. CD15s immunoblocking significantly decreased cancer cell adhesion to brain endothelium under static and shear stress conditions (p < 0.001), highlighting the role of CD15s–CD62E interaction in brain metastasis. PMID:28698503

CD15s/CD62E Interaction Mediates the Adhesion of Non-Small Cell Lung Cancer Cells on Brain Endothelial Cells: Implications for Cerebral Metastasis.

PubMed

Jassam, Samah A; Maherally, Zaynah; Smith, James R; Ashkan, Keyoumars; Roncaroli, Federico; Fillmore, Helen L; Pilkington, Geoffrey J

2017-07-10

Expression of the cell adhesion molecule (CAM), Sialyl Lewis X (CD15s) correlates with cancer metastasis, while expression of E-selectin (CD62E) is stimulated by TNF-α. CD15s/CD62E interaction plays a key role in the homing process of circulating leukocytes. We investigated the heterophilic interaction of CD15s and CD62E in brain metastasis-related cancer cell adhesion. CD15s and CD62E were characterised in human brain endothelium (hCMEC/D3), primary non-small cell lung cancer (NSCLC) (COR-L105 and A549) and metastatic NSCLC (SEBTA-001 and NCI-H1299) using immunocytochemistry, Western blotting, flow cytometry and immunohistochemistry in human brain tissue sections. TNF-α (25 pg/mL) stimulated extracellular expression of CD62E while adhesion assays, under both static and physiological flow live-cell conditions, explored the effect of CD15s-mAb immunoblocking on adhesion of cancer cell-brain endothelium. CD15s was faintly expressed on hCMEC/D3, while high levels were observed on primary NSCLC cells with expression highest on metastatic NSCLC cells ( p < 0.001). CD62E was highly expressed on hCMEC/D3 cells activated with TNF-α, with lower levels on primary and metastatic NSCLC cells. CD15s and CD62E were expressed on lung metastatic brain biopsies. CD15s/CD62E interaction was localised at adhesion sites of cancer cell-brain endothelium. CD15s immunoblocking significantly decreased cancer cell adhesion to brain endothelium under static and shear stress conditions ( p < 0.001), highlighting the role of CD15s-CD62E interaction in brain metastasis.

3D printing of layered brain-like structures using peptide modified gellan gum substrates.

PubMed

Lozano, Rodrigo; Stevens, Leo; Thompson, Brianna C; Gilmore, Kerry J; Gorkin, Robert; Stewart, Elise M; in het Panhuis, Marc; Romero-Ortega, Mario; Wallace, Gordon G

2015-10-01

The brain is an enormously complex organ structured into various regions of layered tissue. Researchers have attempted to study the brain by modeling the architecture using two dimensional (2D) in vitro cell culturing methods. While those platforms attempt to mimic the in vivo environment, they do not truly resemble the three dimensional (3D) microstructure of neuronal tissues. Development of an accurate in vitro model of the brain remains a significant obstacle to our understanding of the functioning of the brain at the tissue or organ level. To address these obstacles, we demonstrate a new method to bioprint 3D brain-like structures consisting of discrete layers of primary neural cells encapsulated in hydrogels. Brain-like structures were constructed using a bio-ink consisting of a novel peptide-modified biopolymer, gellan gum-RGD (RGD-GG), combined with primary cortical neurons. The ink was optimized for a modified reactive printing process and developed for use in traditional cell culturing facilities without the need for extensive bioprinting equipment. Furthermore the peptide modification of the gellan gum hydrogel was found to have a profound positive effect on primary cell proliferation and network formation. The neural cell viability combined with the support of neural network formation demonstrated the cell supportive nature of the matrix. The facile ability to form discrete cell-containing layers validates the application of this novel printing technique to form complex, layered and viable 3D cell structures. These brain-like structures offer the opportunity to reproduce more accurate 3D in vitro microstructures with applications ranging from cell behavior studies to improving our understanding of brain injuries and neurodegenerative diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adolescent Condom Use and Connectivity in the Social-Planful Brain.

PubMed

Caouette, Justin D; Hudson, Karen A; Bryan, Angela D; Feldstein Ewing, Sarah W

2018-05-14

To reduce rates of sexually transmitted infections (STIs) and unwanted pregnancy among adolescents, it is critical to investigate brain connectivity that may underlie adolescents' sexual health decision-making in the context of intercourse. This study explored relationships between adolescent condom use frequency and the brain's resting-state functional connectivity, to identify differential patterns of social-affective processing among sexually active youth. In this study, N = 143 sexually active adolescents (68.5% male, Mage = 16.2 years, SD = 1.06) completed magnetic resonance imaging and reported past 3-month frequency of condom use. Resting-state connectivity, seeded on a social region of the brain, the temporoparietal junction (TPJ), was assessed to determine its correspondence with protected sex (condom use). Condom use was associated with positive connectivity between the left TPJ and bilateral inferior frontal gyrus (IFG). This relationship was observed in adolescent males only; no connectivity differences were observed with adolescent females. This study reflects functional synchrony between nodes of the "social brain," including the TPJ, and a region of planfulness and control, the IFG. The relationship between these regions suggests that adolescents who have more coordinated systems of communication between these critical components of the brain are more likely to be successful in planning and engaging in safer sexual decision-making; for young males, this differentiated more frequent from less frequent condom use. In turn, interventions designed to reduce STIs/human immunodeficiency virus may benefit from targeting social-planfulness dimensions to help youth implement safer sex behaviors.

Brevibacterium casei as a cause of brain abscess in an immunocompetent patient.

PubMed

Kumar, V Anil; Augustine, Deepthi; Panikar, Dilip; Nandakumar, Aswathy; Dinesh, Kavitha R; Karim, Shamsul; Philip, Rosamma

2011-12-01

Coryneform bacteria belonging to the genus Brevibacterium have emerged as opportunistic pathogens. Of the nine known species of Brevibacterium isolated from human clinical samples, Brevibacterium casei is the most frequently reported species from clinical specimens. We report the first case of B. casei brain abscess in an immunocompetent patient successfully treated by surgery and antimicrobial therapy.

JaK/STAT Inhibition to Prevent Post-Traumatic Epileptogenesis

DTIC Science & Technology

2014-09-01

Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Traumatic Brain Injury (TBI) is a well-established inducer of temporal lobe epilepsy (TLE...INTRODUCTION: This research addresses the FY10 PRMRP topic area of Epilepsy . Traumatic Brain Injury (TBI) is a well- established etiology of temporal ... lobe epilepsy (TLE), a frequently medically intractable and often progressive epilepsy syndrome. Much evidence indicates that abnormalities in

Transfection of brain capillary endothelial cells in primary culture with defined blood-brain barrier properties.

PubMed

Burkhart, Annette; Thomsen, Louiza Bohn; Thomsen, Maj Schneider; Lichota, Jacek; Fazakas, Csilla; Krizbai, István; Moos, Torben

2015-08-07

Primary brain capillary endothelial cells (BCECs) are a promising tool to study the blood-brain barrier (BBB) in vitro, as they maintain many important characteristics of the BBB in vivo, especially when co-cultured with pericytes and/or astrocytes. A novel strategy for drug delivery to the brain is to transform BCECs into protein factories by genetic modifications leading to secretion of otherwise BBB impermeable proteins into the central nervous system. However, a huge challenge underlying this strategy is to enable transfection of non-mitotic BCECs, taking a non-viral approach. We therefore aimed to study transfection in primary, non-mitotic BCECs cultured with defined BBB properties without disrupting the cells' integrity. Primary cultures of BCECs, pericytes and astrocytes were generated from rat brains and used in three different in vitro BBB experimental arrangements, which were characterised based on a their expression of tight junction proteins and other BBB specific proteins, high trans-endothelial electrical resistance (TEER), and low passive permeability to radiolabeled mannitol. Recombinant gene expression and protein synthesis were examined in primary BCECs. The BCECs were transfected using a commercially available transfection agent Turbofect™ to express the red fluorescent protein HcRed1-C1. The BCECs were transfected at different time points to monitor transfection in relation to mitotic or non-mitotic cells, as indicated by fluorescence-activated cell sorting analysis after 5-and 6-carboxylfluorescein diacetate succinidyl ester incorporation. The cell cultures exhibited important BBB characteristics judged from their expression of BBB specific proteins, high TEER values, and low passive permeability. Among the three in vitro BBB models, co-culturing with BCECs and astrocytes was well suited for the transfection studies. Transfection was independent of cell division and with equal efficacy between the mitotic and non-mitotic BCECs. Importantly, transfection of BCECs exhibiting BBB characteristics did not alter the integrity of the BCECs cell layer. The data clearly indicate that non-viral gene therapy of BCECs is possible in primary culture conditions with an intact BBB.

Investigations of primary blast-induced traumatic brain injury

NASA Astrophysics Data System (ADS)

Sawyer, T. W.; Josey, T.; Wang, Y.; Villanueva, M.; Ritzel, D. V.; Nelson, P.; Lee, J. J.

2018-01-01

The development of an advanced blast simulator (ABS) has enabled the reproducible generation of single-pulse shock waves that simulate free-field blast with high fidelity. Studies with rodents in the ABS demonstrated the necessity of head restraint during head-only exposures. When the head was not restrained, violent global head motion was induced by pressures that would not produce similar movement of a target the size and mass of a human head. This scaling artefact produced changes in brain function that were reminiscent of traumatic brain injury (TBI) due to impact-acceleration effects. Restraint of the rodent head eliminated these, but still produced subtle changes in brain biochemistry, showing that blast-induced pressure waves do cause brain deficits. Further experiments were carried out with rat brain cell aggregate cultures that enabled the conduct of studies without the gross movement encountered when using rodents. The suspension nature of this model was also exploited to minimize the boundary effects that complicate the interpretation of primary blast studies using surface cultures. Using this system, brain tissue was found not only to be sensitive to pressure changes, but also able to discriminate between the highly defined single-pulse shock waves produced by underwater blast and the complex pressure history exposures experienced by aggregates encased within a sphere and subjected to simulated air blast. The nature of blast-induced primary TBI requires a multidisciplinary research approach that addresses the fidelity of the blast insult, its accurate measurement and characterization, as well as the limitations of the biological models used.

Glucose metabolism in the developing brain.

PubMed

Vannucci, R C; Vannucci, S J

2000-04-01

As in adults, glucose is the predominant cerebral energy fuel for the fetus and newborn. Studies in experimental animals and humans indicate that cerebral glucose utilization initially is low and increases with maturation with increasing regional heterogeneity. The increases in cerebral glucose utilization with advancing age occurs as a consequence of increasing functional activity and cerebral energy demands. The levels of expression of the 2 primary facilitative glucose transporter proteins in brain, GLUT1 (blood-brain barrier and glia) and GLUT3 (neuronal), display a similar maturational pattern. Alternate cerebral energy fuels, specifically the ketone bodies and lactate, can substitute for glucose, especially during hypoglycemia, thereby protecting the immature brain from potential untoward effects of hypoglycemia. Unlike adults, glucose supplementation during hypoxia-ischemia is protective in the immature brain, whereas hypoglycemia is deleterious. Accordingly, glucose plays a critical role in the developing brain, not only as the primary substrate for energy production but also to allow for normal biosynthetic processes to proceed.

Glioblastoma and chemoresistance to alkylating agents: Involvement of apoptosis, autophagy, and unfolded protein response.

PubMed

Hombach-Klonisch, Sabine; Mehrpour, Maryam; Shojaei, Shahla; Harlos, Craig; Pitz, Marshall; Hamai, Ahmed; Siemianowicz, Krzysztof; Likus, Wirginia; Wiechec, Emilia; Toyota, Brian D; Hoshyar, Reyhane; Seyfoori, Amir; Sepehri, Zahra; Ande, Sudharsana R; Khadem, Forough; Akbari, Mohsen; Gorman, Adrienne M; Samali, Afshin; Klonisch, Thomas; Ghavami, Saeid

2018-04-01

Despite advances in neurosurgical techniques and radio-/chemotherapy, the treatment of brain tumors remains a challenge. This is particularly true for the most frequent and fatal adult brain tumor, glioblastoma (GB). Upon diagnosis, the average survival time of GB patients remains only approximately 15months. The alkylating drug temozolomide (TMZ) is routinely used in brain tumor patients and induces apoptosis, autophagy and unfolded protein response (UPR). Here, we review these cellular mechanisms and their contributions to TMZ chemoresistance in brain tumors, with a particular emphasis on TMZ chemoresistance in glioma stem cells and GB. Copyright © 2017 Elsevier Inc. All rights reserved.

Immunotherapy targeting immune check-point(s) in brain metastases.

PubMed

Di Giacomo, Anna Maria; Valente, Monica; Covre, Alessia; Danielli, Riccardo; Maio, Michele

2017-08-01

Immunotherapy with monoclonal antibodies (mAb) directed to different immune check-point(s) is showing a significant clinical impact in a growing number of human tumors of different histotype, both in terms of disease response and long-term survival patients. In this rapidly changing scenario, treatment of brain metastases remains an high unmeet medical need, and the efficacy of immunotherapy in these highly dismal clinical setting remains to be largely demonstrated. Nevertheless, up-coming observations are beginning to suggest a clinical potential of cancer immunotherapy also in brain metastases, regardless the underlying tumor histotype. These observations remain to be validated in larger clinical trials eventually designed also to address the efficacy of therapeutic mAb to immune check-point(s) within multimodality therapies for brain metastases. Noteworthy, the initial proofs of efficacy on immunotherapy in central nervous system metastases are already fostering clinical trials investigating its therapeutic potential also in primary brain tumors. We here review ongoing immunotherapeutic approaches to brain metastases and primary brain tumors, and the foreseeable strategies to overcome their main biologic hurdles and clinical challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

Family History of Cancer in Benign Brain Tumor Subtypes Versus Gliomas

PubMed Central

Ostrom, Quinn T.; McCulloh, Christopher; Chen, Yanwen; Devine, Karen; Wolinsky, Yingli; Davitkov, Perica; Robbins, Sarah; Cherukuri, Rajesh; Patel, Ashokkumar; Gupta, Rajnish; Cohen, Mark; Barrios, Jaime Vengoechea; Brewer, Cathy; Schilero, Cathy; Smolenski, Kathy; McGraw, Mary; Denk, Barbara; Naska, Theresa; Laube, Frances; Steele, Ruth; Greene, Dale; Kastl, Alison; Bell, Susan; Aziz, Dina; Chiocca, E. A.; McPherson, Christopher; Warnick, Ronald; Barnett, Gene H.; Sloan, Andrew E.; Barnholtz-Sloan, Jill S.

2012-01-01

Purpose: Family history is associated with gliomas, but this association has not been established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%), 78 meningioma (65%), 49 pituitary adenoma (73.1%), and 152 glioma patients (58.2%). The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs) and 95% confidence intervals. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusion: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases. PMID:22649779

Traumatic brain injury: an overview of pathobiology with emphasis on military populations

PubMed Central

Cernak, Ibolja; Noble-Haeusslein, Linda J

2010-01-01

This review considers the pathobiology of non-impact blast-induced neurotrauma (BINT). The pathobiology of traumatic brain injury (TBI) has been historically studied in experimental models mimicking features seen in the civilian population. These brain injuries are characterized by primary damage to both gray and white matter and subsequent evolution of secondary pathogenic events at the cellular, biochemical, and molecular levels, which collectively mediate widespread neurodegeneration. An emerging field of research addresses brain injuries related to the military, in particular blast-induced brain injuries. What is clear from the effort to date is that the pathobiology of military TBIs, particularly BINT, has characteristics not seen in other types of brain injury, despite similar secondary injury cascades. The pathobiology of primary BINT is extremely complex. It comprises systemic, local, and cerebral responses interacting and often occurring in parallel. Activation of the autonomous nervous system, sudden pressure-increase in vital organs such as lungs and liver, and activation of neuroendocrine-immune system are among the most important mechanisms significantly contributing to molecular changes and cascading injury mechanisms in the brain. PMID:19809467

Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia

PubMed Central

Kim, Jae Hwan; Lee, Yong Woo; Park, Kyung Ah; Lee, Won Taek; Lee, Jong Eun

2010-01-01

Brain edema is frequently shown after cerebral ischemia. It is an expansion of brain volume because of increasing water content in brain. It causes to increase mortality after stroke. Agmatine, formed by the decarboxylation of -arginine by arginine decarboxylase, has been shown to be neuroprotective in trauma and ischemia models. The purpose of this study was to investigate the effect of agmatine for brain edema in ischemic brain damage and to evaluate the expression of aquaporins (AQPs). Results showed that agmatine significantly reduced brain swelling volume 22 h after 2 h middle cerebral artery occlusion in mice. Water content in brain tissue was clearly decreased 24 h after ischemic injury by agmatine treatment. Blood–brain barrier (BBB) disruption was diminished with agmatine than without. The expressions of AQPs-1 and -9 were well correlated with brain edema as water channels, were significantly decreased by agmatine treatment. It can thus be suggested that agmatine could attenuate brain edema by limitting BBB disruption and blocking the accumulation of brain water content through lessening the expression of AQP-1 after cerebral ischemia. PMID:20029450

Separation of rare oligodendrocyte progenitor cells from brain using a high-throughput multilayer thermoplastic-based microfluidic device.

PubMed

Didar, Tohid Fatanat; Li, Kebin; Veres, Teodor; Tabrizian, Maryam

2013-07-01

Despite the advances made in the field of regenerative medicine, the progress in cutting-edge technologies for separating target therapeutic cells are still at early stage of development. These cells are often rare, such as stem cells or progenitor cells that their overall properties should be maintained during the separation process for their subsequent application in regenerative medicine. This work, presents separation of oligodendrocyte progenitor cells (OPCs) from rat brain primary cultures using an integrated thermoplastic elastomeric (TPE)- based multilayer microfluidic device fabricated using hot-embossing technology. OPCs are frequently used in recovery, repair and regeneration of central nervous system after injuries. Indeed, their ability to differentiate in vitro into myelinating oligodendrocytes, are extremely important for myelin repair. OPCs form 5-10% of the glial cells population. The traditional macroscale techniques for OPCs separation require pre-processing of cells and/or multiple time consuming steps with low efficiency leading very often to alteration of their properties. The proposed methodology implies to separate OPCs based on their smaller size compared to other cells from the brain tissue mixture. Using aforementioned microfluidic chip embedded with a 5 μm membrane pore size and micropumping system, a separation efficiency more than 99% was achieved. This microchip was able to operate at flow rates up to 100 μl/min, capable of separating OPCs from a confluent 75 cm(2) cell culture flask in less than 10 min, which provides us with a high-throughput and highly efficient separation expected from any cell sorting techniques. Copyright © 2013 Elsevier Ltd. All rights reserved.

Patterns of coordinated cortical remodeling during adolescence and their associations with functional specialization and evolutionary expansion.

PubMed

Sotiras, Aristeidis; Toledo, Jon B; Gur, Raquel E; Gur, Ruben C; Satterthwaite, Theodore D; Davatzikos, Christos

2017-03-28

During adolescence, the human cortex undergoes substantial remodeling to support a rapid expansion of behavioral repertoire. Accurately quantifying these changes is a prerequisite for understanding normal brain development, as well as the neuropsychiatric disorders that emerge in this vulnerable period. Past accounts have demonstrated substantial regional heterogeneity in patterns of brain development, but frequently have been limited by small samples and analytics that do not evaluate complex multivariate imaging patterns. Capitalizing on recent advances in multivariate analysis methods, we used nonnegative matrix factorization (NMF) to uncover coordinated patterns of cortical development in a sample of 934 youths ages 8-20, who completed structural neuroimaging as part of the Philadelphia Neurodevelopmental Cohort. Patterns of structural covariance (PSCs) derived by NMF were highly reproducible over a range of resolutions, and differed markedly from common gyral-based structural atlases. Moreover, PSCs were largely symmetric and showed correspondence to specific large-scale functional networks. The level of correspondence was ordered according to their functional role and position in the evolutionary hierarchy, being high in lower-order visual and somatomotor networks and diminishing in higher-order association cortex. Furthermore, PSCs showed divergent developmental associations, with PSCs in higher-order association cortex networks showing greater changes with age than primary somatomotor and visual networks. Critically, such developmental changes within PSCs were significantly associated with the degree of evolutionary cortical expansion. Together, our findings delineate a set of structural brain networks that undergo coordinated cortical thinning during adolescence, which is in part governed by evolutionary novelty and functional specialization.

Primary Blast-Induced Traumatic Brain Injury in Rats Leads to Increased Prion Protein in Plasma: A Potential Biomarker for Blast-Induced Traumatic Brain Injury

PubMed Central

Pham, Nam; Sawyer, Thomas W.; Wang, Yushan; Jazii, Ferdous Rastgar; Vair, Cory

2015-01-01

Abstract Traumatic brain injury (TBI) is deemed the “signature injury” of recent military conflicts in Afghanistan and Iraq, largely because of increased blast exposure. Injuries to the brain can often be misdiagnosed, leading to further complications in the future. Therefore, the use of protein biomarkers for the screening and diagnosis of TBI is urgently needed. In the present study, we have investigated the plasma levels of soluble cellular prion protein (PrPC) as a novel biomarker for the diagnosis of primary blast-induced TBI (bTBI). We hypothesize that the primary blast wave can disrupt the brain and dislodge extracellular localized PrPC, leading to a rise in concentration within the systemic circulation. Adult male Sprague–Dawley rats were exposed to single pulse shockwave overpressures of varying intensities (15-30 psi or 103.4–206.8 kPa] using an advanced blast simulator. Blood plasma was collected 24 h after insult, and PrPC concentration was determined with a modified commercial enzyme-linked immunosorbent assay (ELISA) specific for PrPC. We provide the first report that mean PrPC concentration in primary blast exposed rats (3.97 ng/mL±0.13 SE) is significantly increased compared with controls (2.46 ng/mL±0.14 SE; two tailed test p<0.0001). Furthermore, we report a mild positive rank correlation between PrPC concentration and increasing blast intensity (psi) reflecting a plateaued response at higher pressure magnitudes, which may have implications for all military service members exposed to blast events. In conclusion, it appears that plasma levels of PrPC may be a novel biomarker for the detection of primary bTBI. PMID:25058115

Revised and updated recommendations for the establishment of primary stroke centers: a summary statement from the brain attack coalition.

PubMed

Alberts, Mark J; Latchaw, Richard E; Jagoda, Andy; Wechsler, Lawrence R; Crocco, Todd; George, Mary G; Connolly, E S; Mancini, Barbara; Prudhomme, Stephen; Gress, Daryl; Jensen, Mary E; Bass, Robert; Ruff, Robert; Foell, Kathy; Armonda, Rocco A; Emr, Marian; Warren, Margo; Baranski, Jim; Walker, Michael D

2011-09-01

The formation and certification of Primary Stroke Centers has progressed rapidly since the Brain Attack Coalition's original recommendations in 2000. The purpose of this article is to revise and update our recommendations for Primary Stroke Centers to reflect the latest data and experience. We conducted a literature review using MEDLINE and PubMed from March 2000 to January 2011. The review focused on studies that were relevant for acute stroke diagnosis, treatment, and care. Original references as well as meta-analyses and other care guidelines were also reviewed and included if found to be valid and relevant. Levels of evidence were added to reflect current guideline development practices. Based on the literature review and experience at Primary Stroke Centers, the importance of some elements has been further strengthened, and several new areas have been added. These include (1) the importance of acute stroke teams; (2) the importance of Stroke Units with telemetry monitoring; (3) performance of brain imaging with MRI and diffusion-weighted sequences; (4) assessment of cerebral vasculature with MR angiography or CT angiography; (5) cardiac imaging; (6) early initiation of rehabilitation therapies; and (7) certification by an independent body, including a site visit and disease performance measures. Based on the evidence, several elements of Primary Stroke Centers are particularly important for improving the care of patients with an acute stroke. Additional elements focus on imaging of the brain, the cerebral vasculature, and the heart. These new elements may improve the care and outcomes for patients with stroke cared for at a Primary Stroke Center.

The Complexity of Biomechanics Causing Primary Blast-Induced Traumatic Brain Injury: A Review of Potential Mechanisms

PubMed Central

Courtney, Amy; Courtney, Michael

2015-01-01

Primary blast-induced traumatic brain injury (bTBI) is a prevalent battlefield injury in recent conflicts, yet biomechanical mechanisms of bTBI remain unclear. Elucidating specific biomechanical mechanisms is essential to developing animal models for testing candidate therapies and for improving protective equipment. Three hypothetical mechanisms of primary bTBI have received the most attention. Because translational and rotational head accelerations are primary contributors to TBI from non-penetrating blunt force head trauma, the acceleration hypothesis suggests that blast-induced head accelerations may cause bTBI. The hypothesis of direct cranial transmission suggests that a pressure transient traverses the skull into the brain and directly injures brain tissue. The thoracic hypothesis of bTBI suggests that some combination of a pressure transient reaching the brain via the thorax and a vagally mediated reflex result in bTBI. These three mechanisms may not be mutually exclusive, and quantifying exposure thresholds (for blasts of a given duration) is essential for determining which mechanisms may be contributing for a level of blast exposure. Progress has been hindered by experimental designs, which do not effectively expose animal models to a single mechanism and by over-reliance on poorly validated computational models. The path forward should be predictive validation of computational models by quantitative confirmation with blast experiments in animal models, human cadavers, and biofidelic human surrogates over a range of relevant blast magnitudes and durations coupled with experimental designs, which isolate a single injury mechanism. PMID:26539158

Long-term disability progression in primary progressive multiple sclerosis: a 15-year study.

PubMed

Rocca, Maria A; Sormani, Maria Pia; Rovaris, Marco; Caputo, Domenico; Ghezzi, Angelo; Montanari, Enrico; Bertolotto, Antonio; Laroni, Alice; Bergamaschi, Roberto; Martinelli, Vittorio; Comi, Giancarlo; Filippi, Massimo

2017-11-01

Prognostic markers of primary progressive multiple sclerosis evolution are needed. We investigated the added value of magnetic resonance imaging measures of brain and cervical cord damage in predicting long-term clinical worsening of primary progressive multiple sclerosis compared to simple clinical assessment. In 54 patients, conventional and diffusion tensor brain scans and cervical cord T1-weighted scans were acquired at baseline and after 15 months. Clinical evaluation was performed after 5 and 15 years in 49 patients. Lesion load, brain and cord atrophy, mean diffusivity and fractional anisotropy values from the brain normal-appearing white matter and grey matter were obtained. Using linear regression models, we screened the clinical and imaging variables as independent predictors of 15-year disability change (measured on the expanded disability status scale). At 15 years, 90% of the patients had disability progression. Integrating clinical and imaging variables at 15 months predicted disability changes at 15 years better than clinical factors at 5 years (R2 = 61% versus R2 = 57%). The model predicted long-term disability change with a precision within one point in 38 of 49 patients (77.6%). Integration of clinical and imaging measures allows identification of primary progressive multiple sclerosis patients at risk of long-term disease progression 4 years earlier than when using clinical assessment alone. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Look again: effects of brain images and mind-brain dualism on lay evaluations of research.

PubMed

Hook, Cayce J; Farah, Martha J

2013-09-01

Brain scans have frequently been credited with uniquely seductive and persuasive qualities, leading to claims that fMRI research receives a disproportionate share of public attention and funding. It has been suggested that functional brain images are fascinating because they contradict dualist beliefs regarding the relationship between the body and the mind. Although previous research has indicated that brain images can increase judgments of an article's scientific reasoning, the hypotheses that brain scans make research appear more interesting, surprising, or worthy of funding have not been tested. Neither has the relation between the allure of brain imaging and dualism. In the following three studies, laypersons rated both fictional research descriptions and real science news articles accompanied by brain scans, bar charts, or photographs. Across 988 participants, we found little evidence of neuroimaging's seductive allure or of its relation to self-professed dualistic beliefs. These results, taken together with other recent null findings, suggest that brain images are less powerful than has been argued.

Association of subdural hematoma with increased mortality in lobar intracerebral hemorrhage.

PubMed

Patel, Pratik V; FitzMaurice, Emilie; Nandigam, R N Kaveer; Auluck, Pavan; Viswanathan, Anand; Goldstein, Joshua N; Rosand, Jonathan; Greenberg, Steven M; Smith, Eric E

2009-01-01

To determine the prevalence of subdural hematoma (SDH) in patients presenting with primary nontraumatic lobar intracerebral hemorrhage (ICH) and characteristics associated with the presence of SDH. Retrospective analysis of data collected in a prospective cohort study. Hospital. Consecutive sample of 200 patients with primary lobar ICH and 75 patients with deep hemispheric ICH. Presence of SDH and mortality. Subdural hematoma was present in 40 of 200 patients (20%) with primary lobar ICH. By contrast, SDH was not present in any of 75 consecutive patients with deep hemispheric ICH (P < .001 for comparison with lobar ICH). Intracerebral hemorrhage volume higher than 60 cm3 was the only independent predictor of SDH (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.14-6.34; P = .02). Subdural hematoma thickness more than 5 mm was an independent predictor of increased 30-day mortality (OR, 7.60; 95% CI, 1.86-30.99; P = .005) after controlling for other factors including ICH volume. Further analysis showed that the effect of SDH on mortality depended on ICH volume, with larger odds for mortality in those with low ICH volume (OR, 12.85; 95% CI, 2.42-68.23; P = .003 for those with ICH volume <30 cm3). Cerebral amyloid angiopathy was present in 8 of 9 patients with pathological specimens. Nontraumatic SDH frequently accompanies primary lobar ICH and is associated with higher 30-day mortality, particularly when the ICH volume is relatively low. Rupture of an amyloid-laden leptomeningeal vessel, with extravasation into the brain parenchyma and subdural space, may be the pathogenic mechanism.

[Frequency of neurologic diseases in cattle].

PubMed

Heim, D; Fatzer, R; Hörnlimann, B; Vandevelde, M

1997-01-01

The cases of neurological diseases at the Institute of Animal Neurology, University of Berne, from 1985-1994 were assessed. During this period 532 cattle with neurological symptoms were examined. After 1980 differential diagnostic investigation of rabies negative brains were not pursued anymore and the number of examined cattle brains had declined to 25-30 per year. With the occurrence of bovine spongiform encephalopathy (BSE) in 1990 in Switzerland the number of cattle brains examined has increased to 75-80 yearly. The most frequently diagnosed neurological diseases found are BSE, followed by listeriosis and viral encephalitides.

Isolation and molecular typing of Naegleria fowleri from the brain of a cow that died of primary amebic meningoencephalitis.

PubMed

Visvesvara, Govinda S; De Jonckheere, Johan F; Sriram, Rama; Daft, Barbara

2005-08-01

Naegleria fowleri causes an acute and rapidly fatal central nervous system infection called primary amebic meningoencephalitis (PAM) in healthy children and young adults. We describe here the identification of N. fowleri isolated from the brain of one of several cows that died of PAM based on sequencing of the internal transcribed spacers, including the 5.8S rRNA genes.

Multimodality cellular and molecular imaging of concomitant tumour enhancement in a syngeneic mouse model of breast cancer metastasis.

PubMed

Parkins, Katie M; Dubois, Veronica P; Hamilton, Amanda M; Makela, Ashley V; Ronald, John A; Foster, Paula J

2018-06-12

The mechanisms that influence metastatic growth rates are poorly understood. One mechanism of interest known as concomitant tumour resistance (CTR) can be defined as the inhibition of metastasis by existing tumour mass. Conversely, the presence of a primary tumour has also been shown to increase metastatic outgrowth, termed concomitant tumour enhancement (CTE). The majority of studies evaluating CTR/CTE in preclinical models have relied on endpoint histological evaluation of tumour burden. The goal of this research was to use conventional magnetic resonance imaging (MRI), cellular MRI, and bioluminescence imaging to study the impact of a primary tumour on the development of brain metastases in a syngeneic mouse model. Here, we report that the presence of a 4T1 primary tumour significantly enhances total brain tumour burden in Balb/C mice. Using in vivo BLI/MRI we could determine this was not related to differences in initial arrest or clearance of viable cells in the brain, which suggests that the presence of a primary tumour can increase the proliferative growth of brain metastases in this model. The continued application of our longitudinal cellular and molecular imaging tools will yield a better understanding of the mechanism(s) by which this physiological inhibition (CTR) and/or enhancement (CTE) occurs.

Systematic Review of Interventions to Improve the Provision of Information for Adults with Primary Brain Tumors and Their Caregivers

PubMed Central

Langbecker, Danette; Janda, Monika

2014-01-01

Background: Adults with primary brain tumors and their caregivers have significant information needs. This review assessed the effect of interventions to improve information provision for adult primary brain tumor patients and/or their caregivers. Methods: We included randomized or non-randomized trials testing educational interventions that had outcomes of information provision, knowledge, understanding, recall, or satisfaction with the intervention, for adults diagnosed with primary brain tumors and/or their family or caregivers. PubMed, MEDLINE, EMBASE, and Cochrane Reviews databases were searched for studies published between 1980 and June 2014. Results: Two randomized controlled, 1 non-randomized controlled, and 10 single group pre–post trials enrolled more than 411 participants. Five group, four practice/process change, and four individual interventions assessed satisfaction (12 studies), knowledge (4 studies), and information provision (2 studies). Nine studies reported high rates of satisfaction. Three studies showed statistically significant improvements over time in knowledge and two showed greater information was provided to intervention than control group participants, although statistical testing was not performed. Discussion: The trials assessed intermediate outcomes such as satisfaction, and only 4/13 reported on knowledge improvements. Few trials had a randomized controlled design and risk of bias was either evident or could not be assessed in most domains. PMID:25667919

Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial.

PubMed

Brown, Paul D; Ballman, Karla V; Cerhan, Jane H; Anderson, S Keith; Carrero, Xiomara W; Whitton, Anthony C; Greenspoon, Jeffrey; Parney, Ian F; Laack, Nadia N I; Ashman, Jonathan B; Bahary, Jean-Paul; Hadjipanayis, Costas G; Urbanic, James J; Barker, Fred G; Farace, Elana; Khuntia, Deepak; Giannini, Caterina; Buckner, Jan C; Galanis, Evanthia; Roberge, David

2017-08-01

Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis. In this randomised, controlled, phase 3 trial, adult patients (aged 18 years or older) from 48 institutions in the USA and Canada with one resected brain metastasis and a resection cavity less than 5·0 cm in maximal extent were randomly assigned (1:1) to either postoperative SRS (12-20 Gy single fraction with dose determined by surgical cavity volume) or WBRT (30 Gy in ten daily fractions or 37·5 Gy in 15 daily fractions of 2·5 Gy; fractionation schedule predetermined for all patients at treating centre). We randomised patients using a dynamic allocation strategy with stratification factors of age, duration of extracranial disease control, number of brain metastases, histology, maximal resection cavity diameter, and treatment centre. Patients and investigators were not masked to treatment allocation. The co-primary endpoints were cognitive-deterioration-free survival and overall survival, and analyses were done by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT01372774. Between Nov 10, 2011, and Nov 16, 2015, 194 patients were enrolled and randomly assigned to SRS (98 patients) or WBRT (96 patients). Median follow-up was 11·1 months (IQR 5·1-18·0). Cognitive-deterioration-free survival was longer in patients assigned to SRS (median 3·7 months [95% CI 3·45-5·06], 93 events) than in patients assigned to WBRT (median 3·0 months [2·86-3·25], 93 events; hazard ratio [HR] 0·47 [95% CI 0·35-0·63]; p<0·0001), and cognitive deterioration at 6 months was less frequent in patients who received SRS than those who received WBRT (28 [52%] of 54 evaluable patients assigned to SRS vs 41 [85%] of 48 evaluable patients assigned to WBRT; difference -33·6% [95% CI -45·3 to -21·8], p<0·00031). Median overall survival was 12·2 months (95% CI 9·7-16·0, 69 deaths) for SRS and 11·6 months (9·9-18·0, 67 deaths) for WBRT (HR 1·07 [95% CI 0·76-1·50]; p=0·70). The most common grade 3 or 4 adverse events reported with a relative frequency greater than 4% were hearing impairment (three [3%] of 93 patients in the SRS group vs eight [9%] of 92 patients in the WBRT group) and cognitive disturbance (three [3%] vs five [5%]). There were no treatment-related deaths. Decline in cognitive function was more frequent with WBRT than with SRS and there was no difference in overall survival between the treatment groups. After resection of a brain metastasis, SRS radiosurgery should be considered one of the standards of care as a less toxic alternative to WBRT for this patient population. National Cancer Institute. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metastatic brain tumor

MedlinePlus

... the brain, the type of tissue involved, the original location of the tumor, and other factors. In rare cases, doctors do not know the original location. This is called cancer of unknown primary ( ...

Working Memory Performance Is Correlated with Local Brain Morphology in the Medial Frontal and Anterior Cingulate Cortex in Fibromyalgia Patients: Structural Correlates of Pain-Cognition Interaction

ERIC Educational Resources Information Center

Luerding, R.; Weigand, T.; Bogdahn, U.; Schmidt-Wilcke, T.

2008-01-01

Fibromyalgia (FM) is a disorder of unknown aetiology, characterized by chronic widespread pain, stiffness and sleep disturbances. In addition, patients frequently complain of memory and attention deficits. Accumulating evidence suggests that FM is associated with CNS dysfunction and with an altered brain morphology. However, few studies have…

Hardware-based Artificial Neural Networks for Size, Weight, and Power Constrained Platforms (Preprint)

DTIC Science & Technology

2012-11-01

few sensors/complex computations, and many sensors/simple computation. II. CHALLENGES WITH NANO-ENABLED NEUROMORPHIC CHIPS A wide variety of...scenarios. Neuromorphic processors, which are based on the highly parallelized computing architecture of the mammalian brain, show great promise in...in the brain. This fundamentally different approach, frequently referred to as neuromorphic computing, is thought to be better able to solve fuzzy

Combined brain Fe, Cu, Zn and neurometabolite analysis - a new methodology for unraveling the efficacy of transcranial direct current stimulation (tDCS) in appetite control.

PubMed

Ziomber, Agata; Surowka, Artur Dawid; Antkiewicz-Michaluk, Lucyna; Romanska, Irena; Wrobel, Pawel; Szczerbowska-Boruchowska, Magdalena

2018-03-01

Obesity is a chronic, multifactorial origin disease that has recently become one of the most frequent lifestyle disorders. Unfortunately, current obesity treatments seem to be ineffective. At present, transcranial direct current brain stimulation (tDCS) represents a promising novel treatment methodology that seems to be efficient, well-tolerated and safe for a patient. Unfortunately, the biochemical action of tDCS remains unknown, which prevents its widespread use in the clinical arena, although neurobiochemical changes in brain signaling and metal metabolism are frequently reported. Therefore, our research aimed at exploring the biochemical response to tDCS in situ, in the brain areas triggering feeding behavior in obese animals. The objective was to propose a novel neurochemical (serotoninergic and dopaminergic signaling) and trace metal analysis of Fe, Cu and Zn. In doing so, we used energy-dispersive X-ray fluorescence (EDXRF) and high-performance liquid chromatography (HPLC). Anodal-type stimulation (atDCS) of the right frontal cortex was utilized to down-regulate food intake and body weight gain in obese rats. EDXRF was coupled with the external standard method in order to quantify the chemical elements within appetite-triggering brain areas. Major dopamine metabolites were assessed in the brains, based on the HPLC assay utilizing the external standard assay. Our study confirms that elemental analysis by EDXRF and brain metabolite assay by HPLC can be considered as a useful tool for the in situ investigation of the interplay between neurochemical and Fe/Cu/Zn metabolism in the brain upon atDCS. With this methodology, an increase in both Cu and Zn in the satiety center of the stimulated group could be reported. In turn, the most significant neurochemical changes involved dopaminergic and serotoninergic signaling in the brain reward system.

Association of general psychological factors with frequent attendance in primary care: a population-based cross-sectional observational study.

PubMed

Hajek, André; Bock, Jens-Oliver; König, Hans-Helmut

2017-03-24

Whereas several studies have examined the association between frequent attendance in primary care and illness-specific psychological factors, little is known about the relation between frequent attendance and general psychological factors. Thus, the aim of this study was to investigate the association between being a frequent attender in primary care and general psychological factors. Data were used from a large, population-based sample of community-dwelling individuals aged 40 and above in Germany in 2014 (n = 7,446). Positive and negative affect, life satisfaction, optimism, self-esteem, self-efficacy, and self-regulation were included as general psychological factors. The number of self-reported GP visits in the past twelve months was used to quantify frequency of attendance; individuals with more than 9 visits (highest decile) were defined as frequent attenders. Multiple logistic regressions showed that being a frequent attender was positively associated with less life satisfaction [OR: 0.79 (0.70-0.89)], higher negative affect [OR: 1.38 (1.17-1.62)], less self-efficacy [OR: 0.74 (0.63-0.86)], less self-esteem [OR: 0.65 (0.54-0.79)], less self-regulation [OR: 0.74 (0.60-0.91)], and higher perceived stress [OR: 1.46 (1.28-1.66)], after adjusting for sociodemographic factors, morbidity and lifestyle factors. However, frequent attendance was not significantly associated with positive affect and self-regulation. The present study highlights the association between general psychological factors and frequent attendance. As frequent GP visits produce high health care costs and are potentially associated with increased referrals and use of secondary health care services, this knowledge might help to address these individuals with high needs.

Childhood Brain and Spinal Cord Tumors Treatment Overview (PDQ®)—Health Professional Version

Cancer.gov

Pediatric primary brain and CNS tumors are a diverse group of diseases that together constitute the most common solid tumor of childhood. Get detailed information about the diagnosis, classification, prognosis, and treatment of childhood brain and spinal cord tumors in this comprehensive summary for clinicians.

Perfusion MRI: The Five Most Frequently Asked Clinical Questions

PubMed Central

Essig, Marco; Nguyen, Thanh Binh; Shiroishi, Mark S.; Saake, Marc; Provenzale, James M.; Enterline, David S.; Anzalone, Nicoletta; Dörfler, Arnd; Rovira, Àlex; Wintermark, Max; Law, Meng

2013-01-01

OBJECTIVE This article addresses questions that radiologists frequently ask when planning, performing, processing, and interpreting MRI perfusion studies in CNS imaging. CONCLUSION Perfusion MRI is a promising tool in assessing stroke, brain tumors, and neurodegenerative diseases. Most of the impediments that have limited the use of perfusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols. PMID:23971482

Functional MRI and intraoperative brain mapping to evaluate brain plasticity in patients with brain tumours and hemiparesis

PubMed Central

Roux, F; Boulanouar, K; Ibarrola, D; Tremoulet, M; Chollet, F; Berry, I

2000-01-01

OBJECTIVE—To support the hypothesis about the potential compensatory role of ipsilateral corticofugal pathways when the contralateral pathways are impaired by brain tumours.
METHODS—Retrospective analysis was carried out on the results of functional MRI (fMRI) of a selected group of five paretic patients with Rolandic brain tumours who exhibited an abnormally high ipsilateral/contralateral ratio of activation—that is, movements of the paretic hand activated predominately the ipsilateral cortex. Brain activation was achieved with a flexion extension of the fingers. Statistical parametric activation was obtained using a t test and a threshold of p<0.001. These patients, candidates for tumour resection, also underwent cortical intraoperative stimulation that was correlated to the fMRI spatial data using three dimensional reconstructions of the brain. Three patients also had postoperative control fMRI.
RESULTS—The absence of fMRI activation of the primary sensorimotor cortex normally innervating the paretic hand for the threshold chosen, was correlated with completely negative cortical responses of the cortical hand area during the operation. The preoperative fMRI activation of these patients predominantly found in the ipsilateral frontal and primary sensorimotor cortices could be related to the residual ipsilateral hand function. Postoperatively, the fMRI activation returned to more classic patterns of activation, reflecting the consequences of therapy.
CONCLUSION—In paretic patients with brain tumours, ipsilateral control could be implicated in the residual hand function, when the normal primary pathways are impaired. The possibility that functional tissue still remains in the peritumorous sensorimotor cortex even when the preoperative fMRI and the cortical intraoperative stimulations are negative, should be taken into account when planning the tumour resection and during the operation.

 PMID:10990503

Trends and Outcomes in the Treatment of Gliomas Based on Data during 2001–2004 from the Brain Tumor Registry of Japan

PubMed Central

NARITA, Yoshitaka; SHIBUI, Soichiro

2015-01-01

The committee of Brain Tumor Registry of Japan (BTRJ) was founded in 1973 and conducts surveys and analyses of incidence, therapeutic methods, and treatment outcomes of primary and metastatic brain tumors with the cooperation of the Japan Neurosurgical Society members. Newly diagnosed 3,000–4,000 primary brain tumors and 600–1,000 brain metastases patients were enrolled in each year. This report describes the trends and treatment outcomes of gliomas from BTRJ volume 13, including 13,431 patients with primary brain tumors who newly started treatment from 2001 to 2004. Data from 382 diffuse astrocytomas (DAs), 121 oligodendrogliomas (OLs), 90 oligoastrocytomas (OAs), 513 anaplastic astrocytomas (AAs), 126 anaplastic oligodendrogliomas (AOs), 106 anaplastic oligoastrocytomas (AOAs), and 1,489 glioblastomas (GBMs) were analyzed for overall survival (OS) and progression free survival (PFS) depending on age, symptoms, Karnofsky performance status, location of the tumor, extent of resection (EOR), initial radiotherapy and chemotherapy. The 5-year PFS rates of the patients with DA, OL + OA, AA, AO + AOA, and GBM were 57.0%, 74.6%, 28.7%, 54.0%, and 9.2%, and the 5-year OS rates were 75.0%, 90.0%, 41.1%, 68.2%, and 10.1%, respectively. Higher EOR ≥ 75% in DA and OL + OA and that ≥ 50% in AA, AO + AOA, and GBM significantly prolonged OS. Complications and cause of death were also reported. BTRJ had been edited for all the patients, researchers, and especially for clinicians at bedside to give useful information about brain tumors and to contribute to the advances in brain tumor treatment. This report revealed various clinical problematic issues pertaining to the diagnosis and treatment of gliomas. PMID:25797780

Chronic Intake of Commercial Sweeteners Induces Changes in Feeding Behavior and Signaling Pathways Related to the Control of Appetite in BALB/c Mice.

PubMed

Barrios-Correa, Alberto A; Estrada, José A; Martel, Caroline; Olivier, Martin; López-Santiago, Rubén; Contreras, Irazú

2018-01-01

Nonnutritive sweetener use is a common practice worldwide. Although considered safe for human consumption, accumulating evidence suggests these compounds may affect metabolic homeostasis; however, there is no consensus on the role of frequent sweetener intake in appetite and weight loss. We sought to determine whether frequent intake of commercial sweeteners induces changes in the JAK2/STAT3 signaling pathway in the brain of mice, as it is involved in the regulation of appetite and body composition. We supplemented adult BALB/c mice with sucrose, steviol glycosides (SG), or sucralose, daily, for 6 weeks. After supplementation, we evaluated body composition and expression of total and phosphorylated JAK2, STAT3, and Akt, as well as SOCS3 and ObRb, in brain tissue. Our results show that frequent intake of commercial SG decreases energy intake, adiposity, and weight gain in male animals, while increasing the expression of pJAK2 and pSTAT3 in the brain, whereas sucralose increases weight gain and pJAK2 expression in females. Our results suggest that chronic intake of commercial sweeteners elicits changes in signaling pathways that have been related to the control of appetite and energy balance in vivo , which may have relevant consequences for the nutritional state and long term health of the organism.

Chronic Intake of Commercial Sweeteners Induces Changes in Feeding Behavior and Signaling Pathways Related to the Control of Appetite in BALB/c Mice

PubMed Central

Barrios-Correa, Alberto A.; Martel, Caroline; Olivier, Martin; López-Santiago, Rubén

2018-01-01

Nonnutritive sweetener use is a common practice worldwide. Although considered safe for human consumption, accumulating evidence suggests these compounds may affect metabolic homeostasis; however, there is no consensus on the role of frequent sweetener intake in appetite and weight loss. We sought to determine whether frequent intake of commercial sweeteners induces changes in the JAK2/STAT3 signaling pathway in the brain of mice, as it is involved in the regulation of appetite and body composition. We supplemented adult BALB/c mice with sucrose, steviol glycosides (SG), or sucralose, daily, for 6 weeks. After supplementation, we evaluated body composition and expression of total and phosphorylated JAK2, STAT3, and Akt, as well as SOCS3 and ObRb, in brain tissue. Our results show that frequent intake of commercial SG decreases energy intake, adiposity, and weight gain in male animals, while increasing the expression of pJAK2 and pSTAT3 in the brain, whereas sucralose increases weight gain and pJAK2 expression in females. Our results suggest that chronic intake of commercial sweeteners elicits changes in signaling pathways that have been related to the control of appetite and energy balance in vivo, which may have relevant consequences for the nutritional state and long term health of the organism. PMID:29789785

Implementing a Primary Healthcare Framework: The Importance of Nursing Leadership in Developing and Maintaining a Brain Tumor Support Group.

PubMed

Nichols, Linda J; Wright, Kylie M

2015-08-01

Although brain tumor support groups have been available internationally for many years, Liverpool Hospital in Australia has not traditionally provided this service. As a leadership initiative, the development of a brain tumor support group that incorporates a primary healthcare framework is a sustainable approach that showcases the role of nursing leaders in changing attitudes and improving outcomes. The purpose of this review of the literature and reflection of clinical experience is to explore nursing leadership within brain tumor-specific support groups. This article will showcase a nurse-led group that incorporated a coordinated approach to delivering patient-centered care. The initiation of activities and interventions that reflected the five tenets of primary health care resulted in improved outcomes for individuals and their family caregivers throughout the trajectory of their illness. Vital to the success of this project was moving from a standalone leader to building collective and collaborative leadership more conducive to facilitating change. The support group successfully demonstrated that individuals and family caregivers may see ongoing and long-term improvements during and following treatment.

Epilepsy in patients with primary brain tumors: The impact on mood, cognition, and HRQOL.

PubMed

Rahman, Z; Wong, C H; Dexter, M; Olsson, G; Wong, M; Gebsky, V; Nahar, N; Wood, A; Byth, K; King, M; Bleasel, A B

2015-07-01

A primary brain tumor (PBT) is often a fatal disease of the nervous system and has a serious impact on health-related quality of life (HRQOL). Presence of epilepsy and adverse reactions from tumor and epilepsy treatments may cause additional decline in HRQOL. We aimed to study the impact of epileptic seizures on cognition, mood, and HRQOL in patients with brain tumor-related epilepsy. Patients were grouped on an ordinal scale according to epilepsy burden from none to severe based on the presence of epileptic seizures and seizure frequency: L1, no epilepsy; L2, with epilepsy, seizure-free in the last 6 months with antiepileptic drugs; and L3, with epilepsy, at least one seizure in the last 6 months with AEDs. Health-related quality of life was measured by Functional Assessment of Cancer Therapy-Brain (FACT-Br) and Quality of Life in Epilepsy-31 (QOLIE-31) tools, cognition by the Montreal Cognitive Assessment (MoCA) tool and Frontal Assessment Battery (FAB), mood by the Hospital Anxiety and Depression Scale (HADS), activities of daily living (ADLs) by the Barthel Index (BI), and performance status by the Karnofsky Performance Status (KPS) scale in patients with primary brain tumors at least one month following neurosurgery with or without radiotherapy and chemotherapy. Eighty-one patients with a diagnosis of primary brain tumors were recruited. Sixty-eight percent of patients were diagnosed with primary brain tumor-related epilepsy, 50.61% patients had cognitive impairment, 33% had abnormal scores in the anxiety scale, and 34% had abnormal scores in the depression scale. There were no statistically significant differences in these scores among L1, L2, and L3 groups. There were statistically significant differences in duration of disease and KPS and BI scores between L1 and L3 groups. The L3 group has significantly longer duration of disease and scored low in both the BI and KPS scale when compared to the L1 group. All patients with primary brain tumors scored significantly low in FACT-Br 'physical well-being' (PWB) and 'emotional well-being' (EWB) and high in 'social well-being' (SWB) when compared to healthy controls. When scores of each group were individually compared to healthy controls, the L3 group showed the lowest scores in PWB, EWB, and 'functional well-being'. In SWB, L1 and L2 groups showed statistically significantly high scores when compared to normative data. The QOLIE-31 applied to groups with epilepsy showed statistically significantly lower scores in the L3 group when compared to the L2 group in 'cognitive' and 'social functioning' domains. On multivariate analysis, both poor performance status and frequency of seizures were found to be independent risk factors for poor HRQOL when FACT-Br mean scores were compared. Level of seizures was found to be an independent risk factor for poor HRQOL when QOLIE-31 scores were compared between L2 and L3 groups. Presence of brain tumors could be attributed to cognitive impairment irrespective of the presence of epilepsy in our cohort. High seizure burden is an independent risk factor for poor HRQOL in patients with primary brain tumors. The QOLIE-31 is a more sensitive tool than the FACT-Br because of the presence of a seizure-related questionnaire. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Relationship between orientation to a blast and pressure wave propagation inside the rat brain.

PubMed

Chavko, Mikulas; Watanabe, Tomas; Adeeb, Saleena; Lankasky, Jason; Ahlers, Stephen T; McCarron, Richard M

2011-01-30

Exposure to a blast wave generated during an explosion may result in brain damage and related neurological impairments. Several mechanisms by which the primary blast wave can damage the brain have been proposed, including: (1) a direct effect of the shock wave on the brain causing tissue damage by skull flexure and propagation of stress and shear forces; and (2) an indirect transfer of kinetic energy from the blast, through large blood vessels and cerebrospinal fluid (CSF), to the central nervous system. To address a basic question related to the mechanisms of blast brain injury, pressure was measured inside the brains of rats exposed to a low level of blast (~35kPa), while positioned in three different orientations with respect to the primary blast wave; head facing blast, right side exposed to blast and head facing away from blast. Data show different patterns and durations of the pressure traces inside the brain, depending on the rat orientation to blast. Frontal exposures (head facing blast) resulted in pressure traces of higher amplitude and longer duration, suggesting direct transmission and reflection of the pressure inside the brain (dynamic pressure transfer). The pattern of the pressure wave inside the brain in the head facing away from blast exposures assumes contribution of the static pressure, similar to hydrodynamic pressure to the pressure wave inside the brain. Published by Elsevier B.V.

An analysis of the effects of Mn{sup 2+} on oxidative phosphorylation in liver, brain, and heart mitochondria using state 3 oxidation rate assays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gunter, Thomas E., E-mail: thomas_gunter@urmc.rochester.ed; Gerstner, Brent, E-mail: brent_gerstner@urmc.rochester.ed; Lester, Tobias, E-mail: Tlester200@gmail.co

2010-11-15

Manganese (Mn) toxicity is partially mediated by reduced ATP production. We have used oxidation rate assays-a measure of ATP production-under rapid phosphorylation conditions to explore sites of Mn{sup 2+} inhibition of ATP production in isolated liver, brain, and heart mitochondria. This approach has several advantages. First, the target tissue for Mn toxicity in the basal ganglia is energetically active and should be studied under rapid phosphorylation conditions. Second, Mn may inhibit metabolic steps which do not affect ATP production rate. This approach allows identification of inhibitions that decrease this rate. Third, mitochondria from different tissues contain different amounts of themore » components of the metabolic pathways potentially resulting in different patterns of ATP inhibition. Our results indicate that Mn{sup 2+} inhibits ATP production with very different patterns in liver, brain, and heart mitochondria. The primary Mn{sup 2+} inhibition site in liver and heart mitochondria, but not in brain mitochondria, is the F{sub 1}F{sub 0} ATP synthase. In mitochondria fueled by either succinate or glutamate + malate, ATP production is much more strongly inhibited in brain than in liver or heart mitochondria; moreover, Mn{sup 2+} inhibits two independent sites in brain mitochondria. The primary site of Mn-induced inhibition of ATP production in brain mitochondria when succinate is substrate is either fumarase or complex II, while the likely site of the primary inhibition when glutamate plus malate are the substrates is either the glutamate/aspartate exchanger or aspartate aminotransferase.« less

Quantitative Folding Pattern Analysis of Early Primary Sulci in Human Fetuses with Brain Abnormalities.

PubMed

Im, K; Guimaraes, A; Kim, Y; Cottrill, E; Gagoski, B; Rollins, C; Ortinau, C; Yang, E; Grant, P E

2017-07-01

Aberrant gyral folding is a key feature in the diagnosis of many cerebral malformations. However, in fetal life, it is particularly challenging to confidently diagnose aberrant folding because of the rapid spatiotemporal changes of gyral development. Currently, there is no resource to measure how an individual fetal brain compares with normal spatiotemporal variations. In this study, we assessed the potential for automatic analysis of early sulcal patterns to detect individual fetal brains with cerebral abnormalities. Triplane MR images were aligned to create a motion-corrected volume for each individual fetal brain, and cortical plate surfaces were extracted. Sulcal basins were automatically identified on the cortical plate surface and compared with a combined set generated from 9 normal fetal brain templates. Sulcal pattern similarities to the templates were quantified by using multivariate geometric features and intersulcal relationships for 14 normal fetal brains and 5 fetal brains that were proved to be abnormal on postnatal MR imaging. Results were compared with the gyrification index. Significantly reduced sulcal pattern similarities to normal templates were found in all abnormal individual fetuses compared with normal fetuses (mean similarity [normal, abnormal], left: 0.818, 0.752; P < .001; right: 0.810, 0.753; P < .01). Altered location and depth patterns of sulcal basins were the primary distinguishing features. The gyrification index was not significantly different between the normal and abnormal groups. Automated analysis of interrelated patterning of early primary sulci could outperform the traditional gyrification index and has the potential to quantitatively detect individual fetuses with emerging abnormal sulcal patterns. © 2017 by American Journal of Neuroradiology.

Epidemiology of primary brain tumors: current concepts and review of the literature.

PubMed Central

Wrensch, Margaret; Minn, Yuriko; Chew, Terri; Bondy, Melissa; Berger, Mitchel S.

2002-01-01

The purpose of this review is to provide a sufficiently detailed perspective on epidemiologic studies of primary brain tumors to encourage multidisciplinary etiologic and prognostic studies among surgeons, neuro-oncologists, epidemiologists, and molecular scientists. Molecular tumor markers that predict survival and treatment response are being identified with hope of even greater gains in this area from emerging array technologies. Regarding risk factors, studies of inherited susceptibility and constitutive polymorphisms in genes pertinent to carcinogenesis (for example, DNA repair and detoxification genes and mutagen sensitivity) have revealed provocative findings. Inverse associations of the history of allergies with glioma risk observed in 3 large studies and reports of inverse associations of glioma with common infections suggest a possible role of immune factors in glioma genesis or progression. Studies continue to suggest that brain tumors might result from workplace, dietary, and other personal and residential exposures, but studies of cell phone use and power frequency electromagnetic fields have found little to support a causal connection with brain tumors; caveats remain. The only proven causes of brain tumors (that is, rare hereditary syndromes, therapeutic radiation, and immune suppression giving rise to brain lymphomas) account for a small proportion of cases. Progress in understanding primary brain tumors might result from studies of well-defined histologic and molecular tumor types incorporating assessment of potentially relevant information on subject susceptibility and environmental and noninherited endogenous factors (viruses, radiation, and carcinogenic or protective chemical exposures through diet, workplace, oxidative metabolism, or other sources). Such studies will require the cooperation of researchers from many disciplines. PMID:12356358

Study Protocol for a Randomized Controlled Trial Evaluating the Efficacy of an Evidence-Based iPad-App for Cognitive Rehabilitation in Patients with Primary Brain Tumors.

PubMed

van der Linden, Sophie Dorothee; Sitskoorn, Margriet Maria; Rutten, Geert-Jan Maria; Gehring, Karin

2018-06-16

Many patients with primary brain tumors suffer from cognitive deficits, which negatively impact their quality of life. However, cognitive rehabilitation programs for these patients are scarce. We developed an iPad-based cognitive rehabilitation program for brain tumor patients, which was based on our effective face-to-face cognitive rehabilitation program. After successful completion of a feasibility study, a randomized controlled trial has been started. To evaluate the immediate and long-term effects of the iPad-based program on cognitive performance and patient-reported outcome measures (PROMs) in patients with primary brain tumors in an early stage of the disease. Prior to surgery, patients with presumed low-grade glioma and meningioma are included. Before surgery and 3 mo after surgery, neuropsychological assessments are conducted. After the second neuropsychological assessment, patients are assigned to the intervention group or waiting-list control group. The intervention consists of psychoeducation, compensation training, and retraining. Patients are advised to spend 3 h per week on the program for 10 wk. Immediately after completion of the program and a half-year thereafter, postintervention assessments take place. Patients in the control group are offered the opportunity to follow the program after all study assessments. We expect that early cognitive rehabilitation has beneficial effects on cognitive performance and PROMs in brain tumor patients. The iPad-based program allows brain tumor patients to follow a cognitive rehabilitation program from their homes. Forthcoming results may contribute to further improvement of supportive care for brain tumor patients.

Brain-lung crosstalk in critical care: how protective mechanical ventilation can affect the brain homeostasis.

PubMed

Mazzeo, A T; Fanelli, V; Mascia, L

2013-03-01

The maintenance of brain homeostasis against multiple internal and external challenges occurring during the acute phase of acute brain injury may be influenced by critical care management, especially in its respiratory, hemodynamic and metabolic components. The occurrence of acute lung injury represents the most frequent extracranial complication after brain injury and deserves special attention in daily practice as optimal ventilatory strategy for patients with acute brain and lung injury are potentially in conflict. Protecting the lung while protecting the brain is thus a new target in the modern neurointensive care. This article discusses the essentials of brain-lung crosstalk and focuses on how mechanical ventilation may exert an active role in the process of maintaining or treatening brain homeostasis after acute brain injury, highlighting the following points: 1) the role of inflammation as common pathomechanism of both acute lung and brain injury; 2) the recognition of ventilatory induced lung injury as determinant of systemic inflammation affecting distal organs, included the brain; 3) the possible implication of protective mechanical ventilation strategy on the patient with an acute brain injury as an undiscovered area of research in both experimental and clinical settings.

Neuroendocrine Disturbances One to Five or More Years after Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage: Data from the German Database on Hypopituitarism.

PubMed

Krewer, Carmen; Schneider, Manfred; Schneider, Harald Jörn; Kreitschmann-Andermahr, Ilonka; Buchfelder, Michael; Faust, Michael; Berg, Christian; Wallaschofski, Henri; Renner, Caroline; Uhl, Eberhard; Koenig, Eberhard; Jordan, Martina; Stalla, Günter Karl; Kopczak, Anna

2016-08-15

Neuroendocrine disturbances are common after traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH), but only a few data exist on long-term anterior pituitary deficiencies after brain injury. We present data from the Structured Data Assessment of Hypopituitarism after TBI and SAH, a multi-center study including 1242 patients. We studied a subgroup of 351 patients, who had sustained a TBI (245) or SAH (106) at least 1 year before endocrine assessment (range 1-55 years) in a separate analysis. The highest prevalence of neuroendocrine disorders was observed 1-2 years post-injury, and it decreased over time only to show another maximum in the long-term phase in patients with brain injury occurring ≥5 years prior to assessment. Gonadotropic and somatotropic insufficiencies were most common. In the subgroup from 1 to 2 years after brain injury (n = 126), gonadotropic insufficiency was the most common hormonal disturbance (19%, 12/63 men) followed by somatotropic insufficiency (11.5%, 7/61), corticotropic insufficiency (9.2%, 11/119), and thyrotropic insufficiency (3.3%, 4/122). In patients observed ≥ 5 years after brain injury, the prevalence of somatotropic insufficiency increased over time to 24.1%, whereas corticotropic and thyrotrophic insufficiency became less frequent (2.5% and 0%, respectively). The prevalence differed regarding the diagnostic criteria (laboratory values vs. physician`s diagnosis vs. stimulation tests). Our data showed that neuroendocrine disturbances are frequent even years after TBI or SAH, in a cohort of patients who are still on medical treatment.

A comprehensive picture of 4-year outcome of severe brain injuries. Results from the PariS-TBI study.

PubMed

Jourdan, C; Bayen, E; Pradat-Diehl, P; Ghout, I; Darnoux, E; Azerad, S; Vallat-Azouvi, C; Charanton, J; Aegerter, P; Ruet, A; Azouvi, P

2016-04-01

Survivors of severe traumatic brain injury have a great variety of impairments and participation restrictions. Detailed descriptions of their long-term outcome are critical. We aimed to assess brain injury outcome for subjects with traumatic brain injury in terms of the International classification of functioning, disability and health. Four-year follow-up of an inception cohort of adults with severe traumatic brain injury by using face-to-face interviews with patients and proxies. Among 245 survivors at 4 years, 147 were evaluated (80% male, mean age: 32.5±14.2 years at injury); 46 (32%) presented severe disability, 58 (40%) moderate disability, and 40 (28%) good recovery. Most frequent somatic problems were fatigue, headaches, other pain, and balance. One quarter of subjects had motor impairments. Rates of cognitive complaints ranged from 25 to 68%, the most frequent being memory, irritability, slowness and concentration. With the Hospital Anxiety and Depression Scale, 43% had anxiety and 25% depression. Overall, 79% were independent in daily living activities and 40 to 50% needed help for outdoor or organizational activities on the BICRO-39. Most had regular contacts with relatives or close friends but few contacts with colleagues or new acquaintances. Subjects spent little time in productive activities such as working, studying, looking after children or voluntary work. Quality of life on the QOLIBRI scale was associated with disability level (P<0.0001). Management of late brain injury needs to focus on cognitive difficulties, particularly social skills, to enhance patient participation in life. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

[Frequent attendance: the primary care professional's perceptions on the influence of social factors and health care system organisation].

PubMed

Sandín-Vázquez, M; Conde-Espejo, P

2011-01-01

FREQUENT ATTENDANCE: The primary care professional's perceptions on the influence of social factors and health care system organisation. To find out the primary care (PC) professional's perceptions on the social factors and healthcare system organisation that influence frequent attendance. A qualitative study using semi-structured interviews in Primary Care Centres of six Health Areas in the Community of Madrid. Eighteen interviews were conducted, three per area (two physicians and one nurse). Structural sampling was carried out with regards to the variables that could influence the discourse: health area, occupation, sex and number of years worked. The transcriptions were analysed by two investigators and an agreement of interpretation was reached. Among the social factors, health professionals perceived as determining factors: the influence of the media and the medicalization of society, lack of health education and self-care abilities of the population and contextual factors of the patient (social, work and family). Among the health care organisation factors that could influence frequent attendance were, system saturation, appointment on demand, fear of potential lawsuits by the patient, chronic patients protocols, administrative consultations, professional behaviour, and poor coordination with specialised care. According to PC professionals, there are multiple environmental factors, both social and healthcare system organisational factors that encourage frequent attendance. Within the scope of health care system, organisational actions (such as teamwork and coordination with specialists) would help to manage demand. Copyright © 2010 SECA. Published by Elsevier Espana. All rights reserved.

Basal ganglia lesions in subacute sclerosing panencephalitis

PubMed Central

Almeida, Kelson James; Brucki, Sonia Maria Dozzi; Duarte, Maria Irma Seixas; Pasqualucci, Carlos Augusto Gonçalves; Rosemberg, Sérgio; Nitrini, Ricardo

2012-01-01

The parieto-occipital region of the brain is the most frequently and severely affected in subacute sclerosing panencephalitis (SSPE). The basal ganglia, cerebellum and corpus callosum are less commonly involved. We describe a patient with SSPE confirmed by neuropathology based on brain magnetic resonance imaging showing extensive basal ganglia involvement and no significant involvement of other cortical structures. Though rarely described in SSPE, clinicians should be aware of this involvement. SSPE should be kept in mind when changes in basal ganglia signal are seen on brain magnetic resonance imaging with or without involvement of other regions of the human brain to avoid erroneous etiological diagnosis of other pathologies causing rapidly progressive dementia. PMID:29213810

Dietary intake of plant sterols stably increases plant sterol levels in the murine brain.

PubMed

Vanmierlo, Tim; Weingärtner, Oliver; van der Pol, Susanne; Husche, Constanze; Kerksiek, Anja; Friedrichs, Silvia; Sijbrands, Eric; Steinbusch, Harry; Grimm, Marcus; Hartmann, Tobias; Laufs, Ulrich; Böhm, Michael; de Vries, Helga E; Mulder, Monique; Lütjohann, Dieter

2012-04-01

Plant sterols such as sitosterol and campesterol are frequently administered as cholesterol-lowering supplements in food. Recently, it has been shown in mice that, in contrast to the structurally related cholesterol, circulating plant sterols can enter the brain. We questioned whether the accumulation of plant sterols in murine brain is reversible. After being fed a plant sterol ester-enriched diet for 6 weeks, C57BL/6NCrl mice displayed significantly increased concentrations of plant sterols in serum, liver, and brain by 2- to 3-fold. Blocking intestinal sterol uptake for the next 6 months while feeding the mice with a plant stanol ester-enriched diet resulted in strongly decreased plant sterol levels in serum and liver, without affecting brain plant sterol levels. Relative to plasma concentrations, brain levels of campesterol were higher than sitosterol, suggesting that campesterol traverses the blood-brain barrier more efficiently. In vitro experiments with brain endothelial cell cultures showed that campesterol crossed the blood-brain barrier more efficiently than sitosterol. We conclude that, over a 6-month period, plant sterol accumulation in murine brain is virtually irreversible.

Isolation and Molecular Typing of Naegleria fowleri from the Brain of a Cow That Died of Primary Amebic Meningoencephalitis

PubMed Central

Visvesvara, Govinda S.; De Jonckheere, Johan F.; Sriram, Rama; Daft, Barbara

2005-01-01

Naegleria fowleri causes an acute and rapidly fatal central nervous system infection called primary amebic meningoencephalitis (PAM) in healthy children and young adults. We describe here the identification of N. fowleri isolated from the brain of one of several cows that died of PAM based on sequencing of the internal transcribed spacers, including the 5.8S rRNA genes. PMID:16081978

Time-resolved fluorescence spectroscopy of human brain tumors

NASA Astrophysics Data System (ADS)

Marcu, Laura; Thompson, Reid C.; Garde, Smita; Sedrak, Mark; Black, Keith L.; Yong, William H.

2002-05-01

Fluorescence spectroscopy of the endogenous emission of brain tumors has been researched as a potentially important method for the intraoperative localization of brain tumor margins. In this study, we investigate the use of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) for demarcation of primary brain tumors by studying the time-resolved spectra of gliomas of different histologic grades. Time-resolved fluorescence (3 ns, 337 nm excitation) from excised human brain tumor show differences between the time-resolved emission of malignant glioma and normal brain tissue (gray and white matter). Our findings suggest that brain tumors can be differentiated from normal brain tissue based upon unique time-resolved fluorescence signature.

Frequent Binge Drinking After Combat-Acquired Traumatic Brain Injury Among Active Duty Military Personnel with a Past Year Combat Deployment

PubMed Central

Adams, Rachel Sayko; Larson, Mary Jo; Corrigan, John D.; Horgan, Constance M.; Williams, Thomas V.

2013-01-01

Objective To determine whether combat-acquired traumatic brain injury (TBI) is associated with post-deployment frequent binge drinking among a random sample of active duty military personnel (ADMP). Participants ADMP who returned home within the past year from deployment to a combat theater of operations and completed a survey health assessment (N = 7,155). Methods Cross-sectional observational study with multivariate analysis of responses to the 2008 Department of Defense Survey of Health Related Behaviors among Active Duty Military Personnel, an anonymous, random population-based assessment of the Armed Forces. Main Measures Frequent binge drinking: five or more drinks on the same occasion, at least once per week, in the past 30 days. TBI-AC: self-reported altered consciousness only; loss of consciousness of less than 1 minute (TBI-LOC<1); and LOC of 1 minute or greater (TBI-LOC 1+) after combat injury event exposure. Results Of ADMP who had a past year combat deployment, 25.6% were frequent binge drinkers and 13.9% reported experiencing a TBI on the deployment, primarily TBI-AC (7.5%). In regression models adjusting for demographics and positive screen for posttraumatic stress disorder, ADMP with TBI had increased odds of frequent binge drinking compared to those with no injury exposure or without TBI: TBI-AC (AOR 1.48, 95% CI, 1.18–1.84); TBI-LOC 1+ (AOR 1.67, 95% CI, 1.00–2.79). Conclusions TBI was significantly associated with past month frequent binge drinking after controlling for posttraumatic stress disorder, combat exposure, and other covariates. PMID:22955100

Induction of specific micro RNA (miRNA) species by ROS-generating metal sulfates in primary human brain cells

PubMed Central

Lukiw, Walter J.; Pogue, Aileen I.

2007-01-01

Iron- and aluminum-sulfate together, at nanomolar concentrations, trigger the production of reactive oxygen species (ROS) in cultures of human brain cells. Previous studies have shown that following ROS induction, a family of pathogenic brain genes that promote inflammatory signalling, cellular apoptosis and brain cell death is significantly over-expressed. Notably, iron- and aluminum-sulfate induce genes in cultured human brain cells that exhibit expression patterns similar to those observed to be up-regulated in moderate- to late-stage Alzheimer's disease (AD). In this study we have extended our investigations to analyze the expression of micro RNA (miRNA) populations in iron- and aluminum-sulfate treated human neural cells in primary culture. The main finding was that these ROS-generating neurotoxic metal sulfates also up-regulate a specific set of miRNAs that includes miR-9, miR-125b and miR-128. Notably, these same miRNAs are up-regulated in AD brain. These findings further support the idea that iron- and aluminum-sulfates induce genotoxicity via a ROS-mediated up-regulation of specific regulatory elements and pathogenic genes that redirect brain cell fate towards progressive dysfunction and apoptotic cell death. PMID:17629564

The endocranial cast of an early miocene edentate, Hapalops indifferens Ameghino (Mammalia, Edentata, Tardigrada, Megatheriidae). Comparative study with brains of recent sloths.

PubMed

Dozo, M T

1987-01-01

A natural endocranial cast which represents a complete brain of a specimen of Hapalops indifferens is described. Comparing this cast to brains of actual Tardigrada, it shows a telencephalic morphology and a pattern of neocortical sulci that resemble more the brain of Bradypus rather than that of Choloepus. The neocortical sulci homologate the lateral or corono-lateral, suprasylvian and pseudosylvian sulci. Taking into account the studies of cortical maps in Bradypus and the notable similitude of the pattern of neocortical sulci between Bradypus and H. indifferens, the possible representation of the primary sensitive and motor somatic areas, secondary sensitive somatic area, visual and auditory areas are inferred. As in Bradypus, the primary sensitive and motor somatotopic organizations would be overlapped and would not be mirror images; they would show a predominance of the area of the forelimb. The relative brain size of H. indifferens is similar or higher than that of sloths of the genus Bradypus. The close resemblance between Bradypus and Hapalops, with respect to its brain morphology and relative brain size. is congruent with the current hypothesis of the phylogenetic relations between fossil and recent Tardigrada.

Brain imaging research in autism spectrum disorders: in search of neuropathology and health across the lifespan.

PubMed

Lainhart, Janet E

2015-03-01

Advances in brain imaging research in autism spectrum disorders (ASD) are rapidly occurring, and the amount of neuroimaging research has dramatically increased over the past 5 years. In this review, advances during the past 12 months and longitudinal studies are highlighted. Cross-sectional neuroimaging research provides evidence that the neural underpinnings of the behavioral signs of ASD involve not only dysfunctional integration of information across distributed brain networks but also basic dysfunction in primary cortices.Longitudinal studies of ASD show abnormally enlarged brain volumes and increased rates of brain growth during early childhood in only a small minority of ASD children. There is evidence of disordered development of white matter microstructure and amygdala growth, and at 2 years of age, network inefficiencies in posterior cerebral regions.From older childhood into adulthood, atypical age-variant and age-invariant changes in the trajectories of total and regional brain volumes and cortical thickness are apparent at the group level. There is evidence of abnormalities in posterior lobes and posterior brain networks during the first 2 years of life in ASD and, even in older children and adults, dysfunction in primary cortical areas.

Chronic traumatic encephalopathy.

PubMed

Omalu, Bennet

2014-01-01

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative syndrome, which is caused by single, episodic, or repetitive blunt force impacts to the head and transfer of acceleration-deceleration forces to the brain. CTE presents clinically as a composite syndrome of mood disorders and behavioral and cognitive impairment, with or without sensorimotor impairment. Symptoms of CTE may begin with persistent symptoms of acute traumatic brain injury (TBI) following a documented episode of brain trauma or after a latent period that may range from days to weeks to months and years, up to 40 years following a documented episode of brain trauma or cessation of repetitive TBI. Posttraumatic encephalopathy is distinct from CTE, can be comorbid with CTE, and is a clinicopathologic syndrome induced by focal and/or diffuse, gross and/or microscopic destruction of brain tissue following brain trauma. The brain of a CTE sufferer may appear grossly unremarkable, but shows microscopic evidence of primary and secondary proteinopathies. The primary proteinopathy of CTE is tauopathy, while secondary proteinopathies may include, but are not limited to, amyloidopathy and TDP proteinopathy. Reported prevalence rates of CTE in cohorts exposed to TBI ranges from 3 to 80% across age groups. © 2014 S. Karger AG, Basel.

His Brain, Her Brain: A Conversation with Richard M. Restak.

ERIC Educational Resources Information Center

Zakariya, Sally Banks

1981-01-01

Neurologist Richard M. Restak discusses empirical research that demonstrates significant brain-sex differences between males and females. He asserts that the typical primary classroom is geared to skills that come naturally to girls but develop slowly in boys, while the reverse is true in higher level science classes. (Author/WD)

Ganging Up on Brain Metastases | Center for Cancer Research

Cancer.gov

When primary tumors metastasize to the brain, the prognosis for patients is poor. The currently accepted treatment is whole-brain radiation therapy, and the median survival time is several months. Since these types of tumors form in 10 to 30 percent of adult cancer patients, improvements in treatment methods are a necessity.  

JaK/STAT Inhibition to Prevent Post-Traumatic Epileptogenesis

DTIC Science & Technology

2013-07-01

temporal lobe epilepsy (TLE), a frequently medically intractable and permanent epilepsy syndrome. Unlike many TLE models, which cause global brain injury...addresses the FY10 PRMRP topic area of Epilepsy . Traumatic Brain Injury (TBI) is a well-established etiology of temporal lobe epilepsy (TLE), a...is one of the most common causes of temporal lobe epilepsy (TLE). Changes in inhibitory signaling after CCI include hilar inhibitory neuron loss

Emotional Face Identification in Youths with Primary Bipolar Disorder or Primary Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Seymour, Karen E.; Pescosolido, Matthew F.; Reidy, Brooke L.; Galvan, Thania; Kim, Kerri L.; Young, Matthew; Dickstein, Daniel P.

2013-01-01

Objective: Bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) are often comorbid or confounded; therefore, we evaluated emotional face identification to better understand brain/behavior interactions in children and adolescents with either primary BD, primary ADHD, or typically developing controls (TDC). Method: Participants…

Primary meningeal rhabdomyosarcoma.

PubMed

Palta, Manisha; Riedel, Richard F; Vredenburgh, James J; Cummings, Thomas J; Green, Scott; Chang, Zheng; Kirkpatrick, John P

2011-01-01

Primary meningeal rhabdomyosarcoma is a rare primary brain malignancy, with scant case reports. While most reports of primary intracranial rhabdomyosarcoma occur in pediatric patients, a handful of cases in adult patients have been reported in the medical literature. We report the case of a 44-year-old male who developed primary meningeal rhabdomyosarcoma. After developing episodes of right lower extremity weakness, word finding difficulty, and headaches, a brain magnetic resonance imaging (MRI) demonstrated a vertex lesion with radiographic appearance of a meningeal-derived tumor. Subtotal surgical resection was performed due to sagittal sinus invasion and initial pathology was interpreted as an anaplastic meningioma. Re-review of pathology demonstrated rhabdomyosarcoma negative for alveolar translocation t(2;13). Staging studies revealed no evidence of disseminated disease. He was treated with stereotactic radiotherapy with concurrent temozolamide to be followed by vincristine, actinomycin-D, and cyclophosphamide (VAC) systemic therapy.

Where Do Neurologists Look When Viewing Brain CT Images? An Eye-Tracking Study Involving Stroke Cases

PubMed Central

Matsumoto, Hideyuki; Terao, Yasuo; Yugeta, Akihiro; Fukuda, Hideki; Emoto, Masaki; Furubayashi, Toshiaki; Okano, Tomoko; Hanajima, Ritsuko; Ugawa, Yoshikazu

2011-01-01

The aim of this study was to investigate where neurologists look when they view brain computed tomography (CT) images and to evaluate how they deploy their visual attention by comparing their gaze distribution with saliency maps. Brain CT images showing cerebrovascular accidents were presented to 12 neurologists and 12 control subjects. The subjects' ocular fixation positions were recorded using an eye-tracking device (Eyelink 1000). Heat maps were created based on the eye-fixation patterns of each group and compared between the two groups. The heat maps revealed that the areas on which control subjects frequently fixated often coincided with areas identified as outstanding in saliency maps, while the areas on which neurologists frequently fixated often did not. Dwell time in regions of interest (ROI) was likewise compared between the two groups, revealing that, although dwell time on large lesions was not different between the two groups, dwell time in clinically important areas with low salience was longer in neurologists than in controls. Therefore it appears that neurologists intentionally scan clinically important areas when reading brain CT images showing cerebrovascular accidents. Both neurologists and control subjects used the “bottom-up salience” form of visual attention, although the neurologists more effectively used the “top-down instruction” form. PMID:22174928

Women and Mathematics: Fact and Fiction.

ERIC Educational Resources Information Center

Luchins, Edith H.

1981-01-01

Frequently cited sex differences in general psychology texts are noted, with such "differences" specified even when scientific evidence did not exist. Research on brain lateralization and sex difference is reviewed. (MP)

Chemotherapy - what to ask your doctor

MedlinePlus

... More Brain tumor - children Brain tumor - primary - adults Breast cancer Chemotherapy Colon cancer Hodgkin lymphoma Lung cancer - small cell Non-Hodgkin lymphoma Ovarian cancer Testicular cancer Patient Instructions After chemotherapy - discharge Bleeding during cancer treatment ...

Cystic echinococcosis of lung and heart coupled with repeated echinococcosis of brain--a case report.

PubMed

Busić, Zeljko; Bradarić, Nikola; Ledenko, Vlatko; Pavlek, Goran

2011-12-01

Echinococcosis is rarely encountered as a cystic brain disease. In this article we are presenting a case of a young woman repeatedly operated due to echinococcosis of lung, heart and brain. Recurrent brain ecchinococcosis developed despite preoperative and postoperative albendazol therapy after first and combined therapy with albendazol and praziquantel after the second brain surgery. The mechanism of recurrence remains unclear (primary infestation, dissemination after spontaneous or intraoperative cyst rupture or new infestation).

Effects of Methylphenidate on Attention Deficits in Childhood Cancer Survivors

ClinicalTrials.gov

2015-03-16

ALL, Childhood; Leukemia, Lymphoblastic; Leukemia, Lymphoblastic, Acute; Leukemia, Lymphoblastic, Acute, L1; Leukemia, Lymphoblastic, Acute, L2; Leukemia, Lymphoblastic, Acute, Philadelphia-Positive; Leukemia, Lymphocytic, Acute; Leukemia, Lymphocytic, Acute, L1; Leukemia, Lymphocytic, Acute, L2; Lymphoblastic Leukemia; Lymphoblastic Leukemia, Acute; Lymphoblastic Leukemia, Acute, Childhood; Lymphoblastic Leukemia, Acute, L1; Lymphoblastic Leukemia, Acute, L2; Lymphoblastic Lymphoma; Lymphocytic Leukemia, Acute; Lymphocytic Leukemia, L1; Lymphocytic Leukemia, L2; Brain Tumors; Cancer of the Brain; Cancer of Brain; Malignant Primary Brain Tumors; Brain Neoplasms, Malignant

Isolated cortical visual loss with subtle brain MRI abnormalities in a case of hypoxic-ischemic encephalopathy.

PubMed

Margolin, Edward; Gujar, Sachin K; Trobe, Jonathan D

2007-12-01

A 16-year-old boy who was briefly asystolic and hypotensive after a motor vehicle accident complained of abnormal vision after recovering consciousness. Visual acuity was normal, but visual fields were severely constricted without clear hemianopic features. The ophthalmic examination was otherwise normal. Brain MRI performed 11 days after the accident showed no pertinent abnormalities. At 6 months after the event, brain MRI demonstrated brain volume loss in the primary visual cortex and no other abnormalities. One year later, visual fields remained severely constricted; neurologic examination, including formal neuropsychometric testing, was normal. This case emphasizes the fact that hypoxic-ischemic encephalopathy (HIE) may cause enduring damage limited to primary visual cortex and that the MRI abnormalities may be subtle. These phenomena should be recognized in the management of patients with HIE.

Comparative Analysis of Human and Rodent Brain Primary Neuronal Culture Spontaneous Activity Using Micro-Electrode Array Technology.

PubMed

Napoli, Alessandro; Obeid, Iyad

2016-03-01

Electrical activity in embryonic brain tissue has typically been studied using Micro Electrode Array (MEA) technology to make dozens of simultaneous recordings from dissociated neuronal cultures, brain stem cell progenitors, or brain slices from fetal rodents. Although these rodent neuronal primary culture electrical properties are mostly investigated, it has not been yet established to what extent the electrical characteristics of rodent brain neuronal cultures can be generalized to those of humans. A direct comparison of spontaneous spiking activity between rodent and human primary neurons grown under the same in vitro conditions using MEA technology has never been carried out before and will be described in the present study. Human and rodent dissociated fetal brain neuronal cultures were established in-vitro by culturing on a glass grid of 60 planar microelectrodes neurons under identical conditions. Three different cultures of human neurons were produced from tissue sourced from a single aborted fetus (at 16-18 gestational weeks) and these were compared with seven different cultures of embryonic rat neurons (at 18 gestational days) originally isolated from a single rat. The results show that the human and rodent cultures behaved significantly differently. Whereas the rodent cultures demonstrated robust spontaneous activation and network activity after only 10 days, the human cultures required nearly 40 days to achieve a substantially weaker level of electrical function. These results suggest that rat neuron preparations may yield inferences that do not necessarily transfer to humans. © 2015 Wiley Periodicals, Inc.

Gamma Knife Surgery for Metastatic Brain Tumors from Gynecologic Cancer.

PubMed

Matsunaga, Shigeo; Shuto, Takashi; Sato, Mitsuru

2016-05-01

The incidences of metastatic brain tumors from gynecologic cancer have increased. The results of Gamma Knife surgery (GKS) for the treatment of patients with brain metastases from gynecologic cancer (ovarian, endometrial, and uterine cervical cancers) were retrospectively analyzed to identify the efficacy and prognostic factors for local tumor control and survival. The medical records were retrospectively reviewed of 70 patients with 306 tumors who underwent GKS for brain metastases from gynecologic cancer between January 1995 and December 2013 in our institution. The primary cancers were ovarian in 33 patients with 147 tumors and uterine in 37 patients with 159 tumors. Median tumor volume was 0.3 cm(3). Median marginal prescription dose was 20 Gy. The local tumor control rates were 96.4% at 6 months and 89.9% at 1 year. There was no statistically significant difference between ovarian and uterine cancers. Higher prescription dose and smaller tumor volume were significantly correlated with local tumor control. Median overall survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and solitary brain metastasis were significantly correlated with satisfactory overall survival. Median activities of daily living (ADL) preservation survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and higher Karnofsky Performance Status score were significantly correlated with better ADL preservation. GKS is effective for control of tumor progression in patients with brain metastases from gynecologic cancer, and may provide neurologic benefits and preservation of the quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.

Expression of amyloid-β protein and amyloid-β precursor protein after primary brain-stem injury in rats.

PubMed

Yang, Shudong; Sun, Rongchao; Zhou, Zhiyi; Zhou, Jing; Liang, Jiabei; Mu, Huijun

2014-09-01

Amyloid-β (Aβ) protein and its precursor, amyloid-β precursor protein (β-APP), have traditionally been used in the diagnosis of Alzheimer disease. Their use in diagnosis of traumatic brain injury by forensic analysis is becoming more widespread. However, to date, no reliable small animal model exists to evaluate these brain injury indicators. To address this, we have studied primary brain-stem injury in rats to assess the appearance of diffuse axonal injury in brain sections and correlate these findings with appearance of Aβ and relative β-APP mRNA levels. Using an EnVision 2-step immunohistochemical staining method to measure axon diameter, we found that there was significant difference in axon diameters within the medulla oblongata and several time points after brain injury, ranging from 3 to 24 hours. In addition, mRNA expression levels of β-APP increased following brain injury, peaking 3 hours following injury and decreasing back to baseline levels by 24 hours after injury. These results suggest that using immunohistochemistry and reverse transcription-polymerase chain reaction to detect changes in Aβ-associated axonal changes and β-APP mRNA levels, respectively, can be useful for the diagnosis of diffuse axonal injury during autopsy at early time points following fatal brain injury.

Abnormal neural activities of directional brain networks in patients with long-term bilateral hearing loss.

PubMed

Xu, Long-Chun; Zhang, Gang; Zou, Yue; Zhang, Min-Feng; Zhang, Dong-Sheng; Ma, Hua; Zhao, Wen-Bo; Zhang, Guang-Yu

2017-10-13

The objective of the study is to provide some implications for rehabilitation of hearing impairment by investigating changes of neural activities of directional brain networks in patients with long-term bilateral hearing loss. Firstly, we implemented neuropsychological tests of 21 subjects (11 patients with long-term bilateral hearing loss, and 10 subjects with normal hearing), and these tests revealed significant differences between the deaf group and the controls. Then we constructed the individual specific virtual brain based on functional magnetic resonance data of participants by utilizing effective connectivity and multivariate regression methods. We exerted the stimulating signal to the primary auditory cortices of the virtual brain and observed the brain region activations. We found that patients with long-term bilateral hearing loss presented weaker brain region activations in the auditory and language networks, but enhanced neural activities in the default mode network as compared with normally hearing subjects. Especially, the right cerebral hemisphere presented more changes than the left. Additionally, weaker neural activities in the primary auditor cortices were also strongly associated with poorer cognitive performance. Finally, causal analysis revealed several interactional circuits among activated brain regions, and these interregional causal interactions implied that abnormal neural activities of the directional brain networks in the deaf patients impacted cognitive function.

Training communication partners of people with severe traumatic brain injury improves everyday conversations: a multicenter single blind clinical trial.

PubMed

Togher, Leanne; McDonald, Skye; Tate, Robyn; Power, Emma; Rietdijk, Rachael

2013-07-01

To determine effectiveness of communication training for partners of people with severe traumatic brain injury. Three arm non-randomized controlled trial comparing communication partner training (JOINT) with individual treatment (TBI SOLO) and a waitlist control group with 6 month follow-up. Forty-four outpatients with severe chronic traumatic brain injuries were recruited. Ten-week conversational skills treatment program encompassing weekly group and individual sessions for both treatment groups. The JOINT condition focused on both the partner and the person with traumatic brain injury while the TBI SOLO condition focused on the individual with TBI only. Primary outcomes were blind ratings of the person with traumatic brain injury's level of participation during conversation on the Measure of Participation in Communication Adapted Kagan scales. Communication partner training improved conversational performance relative to training the person with traumatic brain injury alone and a waitlist control group on the primary outcome measures. Results were maintained at six months post-training. Training communication partners of people with chronic severe traumatic brain injury was more efficacious than training the person with traumatic brain injury alone. The Adapted Kagan scales proved to be a robust and sensitive outcome measure for a conversational skills training program.

An open-label multicenter study to assess the safety of dextromethorphan/quinidine in patients with pseudobulbar affect associated with a range of underlying neurological conditions.

PubMed

Pattee, Gary L; Wymer, James P; Lomen-Hoerth, Catherine; Appel, Stanley H; Formella, Andrea E; Pope, Laura E

2014-11-01

Pseudobulbar affect (PBA) is associated with neurological disorders or injury affecting the brain, and characterized by frequent, uncontrollable episodes of crying and/or laughing that are exaggerated or unrelated to the patient's emotional state. Clinical trials establishing dextromethorphan and quinidine (DM/Q) as PBA treatment were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This trial evaluated DM/Q safety in patients with PBA secondary to any neurological condition affecting the brain. To evaluate the safety and tolerability of DM/Q during long-term administration to patients with PBA associated with multiple neurological conditions. Fifty-two-week open-label study of DM/Q 30/30 mg twice daily. Safety measures included adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. #NCT00056524. A total of 553 PBA patients with >30 different neurological conditions enrolled; 296 (53.5%) completed. The most frequently reported treatment-related AEs (TRAEs) were nausea (11.8%), dizziness (10.5%), headache (9.9%), somnolence (7.2%), fatigue (7.1%), diarrhea (6.5%), and dry mouth (5.1%). TRAEs were mostly mild/moderate, generally transient, and consistent with previous controlled trials. Serious AEs (SAEs) were reported in 126 patients (22.8%), including 47 deaths, mostly due to ALS progression and respiratory failure. No SAEs were deemed related to DM/Q treatment by investigators. ECG results suggested no clinically meaningful effect of DM/Q on myocardial repolarization. Differences in AEs across neurological disease groups appeared consistent with the known morbidity of the primary neurological conditions. Study interpretation is limited by the small size of some disease groups, the lack of a specific efficacy measure and the use of a DM/Q dose higher than the eventually approved dose. DM/Q was generally well tolerated over this 52 week trial in patients with PBA associated with a wide range of neurological conditions.

Alkamides from Echinacea angustifolia Interact with P-glycoprotein of primary brain capillary endothelial cells isolated from porcine brain blood vessels.

PubMed

Mahringer, Anne; Ardjomand-Woelkart, Karin; Bauer, Rudolf; Fricker, Gert; Efferth, Thomas

2013-03-01

The blood-brain barrier prevents the passage of toxic compounds from blood circulation into brain tissue. Unfortunately, drugs for the treatment of neurodegenerative diseases, brain tumors, and other diseases also do not cross the blood-brain barrier. In the present investigation, we used isolated porcine brain capillary endothelial cells and a flow cytometric calcein-AM assay to analyze inhibition of P-glycoprotein, a major constituent of the blood-brain barrier. We tested 8 alkamides isolated from Echinacea angustifolia and found that four of them inhibited P-glycoprotein-mediated calcein transport in porcine brain capillary endothelial cells. Georg Thieme Verlag KG Stuttgart · New York.

An Investigation of the Mechanism of Traumatic Brain Injury Caused by Blast in the Open Field

NASA Astrophysics Data System (ADS)

Feng, Ke

Blast-induced traumatic brain injury (bTBI) is a signature wound of modern warfare. The current incomplete understanding of its injury mechanism impedes the development of strategies for effective protection of bTBI. Despite a considerable amount of experimental animal studies focused on the evaluation of brain neurotrauma caused by blast exposure, there is very limited knowledge on the biomechanical responses of the gyrenecephalic brain subjected to primary free-field blast waves imposed in vivo, and the correlation analysis between the biomechanical responses and its injury outcomes. Such information is crucial to the development of injury criteria of bTBI. This study aims to evaluate the external and internal mechanical responses of the brain against different levels of blast loading with Yucatan swine in free field, and to conduct correlational studies with brain tissue damage. To better understand primary bTBI, we have implemented an open field experimental model to apply controlled shock waves on swine head. The applied pressure levels of shock waves were predicted by finite element modeling and verified with calibrated testing. Biomechanical responses of primary blasts such as intracranial pressure (ICP), head kinetics, strain rate of skull, were measured in vivo during the blasts. A positive correlation between incident overpressure (IOP) and its corresponding biomechanical responses of the brain was observed. A parallel group of non-instrumented animals were used to collect injury data 72 hours post experiment. Cellular responses governed by primary blasts, such as neuronal degeneration and apoptosis were studied via immunohistochemistry. Representative fluorescent-stained images were examined under microscope. A positive correlation was found between the amount of degenerative neurons and the blast level. Significant elevation of apoptosis was found in the high-level blast. Comparisons between brains with varies ICP readings demonstrate differences of the numbers of neuronal degeneration and apoptosis within the imaged volume. Additionally, comparisons between sections at different locations of the head did not show spatial changes for cellular responses. These metrics provide a pathway for direct connection between the cellular damage and the measured biomechanical responses of the brain within the same experimental model, and could be critical in understanding the mechanisms of bTBI. This experimental data can be used to validate computer models of bTBI.

Co-evolution of breast-to-brain metastasis and neural progenitor cells.

PubMed

Neman, Josh; Choy, Cecilia; Kowolik, Claudia M; Anderson, Athena; Duenas, Vincent J; Waliany, Sarah; Chen, Bihong T; Chen, Mike Y; Jandial, Rahul

2013-08-01

Brain colonization by metastatic tumor cells offers a unique opportunity to investigate microenvironmental influences on the neoplastic process. The bi-directional interplay of breast cancer cells (mesodermal origin) and brain cells (neuroectodermal origin) is poorly understood and rarely investigated. In our patients undergoing neurosurgical resection of breast-to-brain metastases, specimens from the tumor/brain interface exhibited increased active gliosis as previously described. In addition, our histological characterization revealed infiltration of neural progenitor cells (NPCs) both outside and inside the tumor margin, leading us to investigate the cellular and molecular interactions between NPCs and metastases. Since signaling by the TGF-β superfamily is involved in both developmental neurobiology and breast cancer pathogenesis, we examined the role of these proteins in the context of brain metastases. The brain-metastatic breast cancer cell line MDA-MB-231Br (231Br) expressed BMP-2 at significantly higher levels compared to its matched primary breast cancer cell line MDA-MB-231 (231). Co-culturing was used to examine bi-directional cellular effects and the relevance of BMP-2 overexpression. When co-cultured with NPCs, 231 (primary) tumor cells failed to proliferate over 15 days. However, 231Br (brain metastatic) tumor cells co-cultured with NPCs escaped growth inhibition after day 5 and proliferated, occurring in parallel with NPC differentiation into astrocytes. Using shRNA and gene knock-in, we then demonstrated BMP-2 secreted by 231Br cells mediated NPC differentiation into astrocytes and concomitant tumor cell proliferation in vitro. In xenografts, overexpression of BMP-2 in primary breast cancer cells significantly enhanced their ability to engraft and colonize the brain, thereby creating a metastatic phenotype. Conversely, BMP-2 knockdown in metastatic breast cancer cells significantly diminished engraftment and colonization. The results suggest metastatic tumor cells create a permissive neural niche by steering NPC differentiation toward astrocytes through paracrine BMP-2 signaling.

Co-evolution of breast-to-brain metastasis and neural progenitor cells

PubMed Central

Neman, Josh; Choy, Cecilia; Kowolik, Claudia M.; Anderson, Athena; Duenas, Vincent J.; Waliany, Sarah; Chen, Bihong T.; Chen, Mike Y.

2013-01-01

Brain colonization by metastatic tumor cells offers a unique opportunity to investigate microenvironmental influences on the neoplastic process. The bi-directional interplay of breast cancer cells (mesodermal origin) and brain cells (neuroectodermal origin) is poorly understood and rarely investigated. In our patients undergoing neurosurgical resection of breast-to-brain metastases, specimens from the tumor/brain interface exhibited increased active gliosis as previously described. In addition, our histological characterization revealed infiltration of neural progenitor cells (NPCs) both outside and inside the tumor margin, leading us to investigate the cellular and molecular interactions between NPCs and metastases. Since signaling by the TGF-β superfamily is involved in both developmental neurobiology and breast cancer pathogenesis, we examined the role of these proteins in the context of brain metastases. The brain-metastatic breast cancer cell line MDA-MB-231Br (231Br) expressed BMP-2 at significantly higher levels compared to its matched primary breast cancer cell line MDA-MB-231 (231). Co-culturing was used to examine bi-directional cellular effects and the relevance of BMP-2 overexpression. When co-cultured with NPCs, 231 (primary) tumor cells failed to proliferate over 15 days. However, 231Br (brain meta-static) tumor cells co-cultured with NPCs escaped growth inhibition after day 5 and proliferated, occurring in parallel with NPC differentiation into astrocytes. Using shRNA and gene knock-in, we then demonstrated BMP-2 secreted by 231Br cells mediated NPC differentiation into astrocytes and concomitant tumor cell proliferation in vitro. In xenografts, overexpression of BMP-2 in primary breast cancer cells significantly enhanced their ability to engraft and colonize the brain, thereby creating a metastatic phenotype. Conversely, BMP-2 knockdown in metastatic breast cancer cells significantly diminished engraftment and colonization. The results suggest metastatic tumor cells create a permissive neural niche by steering NPC differentiation toward astrocytes through paracrine BMP-2 signaling. PMID:23456474

Altering Iron Oxide Nanoparticle Surface Properties Induce Cortical Neuron Cytotoxicity

PubMed Central

Rivet, Christopher J.; Yuan, Yuan; Borca-Tasciuc, Diana-Andra; Gilbert, Ryan J.

2014-01-01

Superparamagnetic iron oxide nanoparticles, with diameters in the range of a few tens of nanometers, display the ability to cross the blood-brain barrier and are envisioned as diagnostic and therapeutic tools in neuro-medicine. However, despite the numerous applications being explored, insufficient information is available on their potential toxic effect on neurons. While iron oxide has been shown to pose a decreased risk of toxicity, surface functionalization, often employed for targeted delivery, can significantly alter the biological response. This aspect is addressed in the present study, which investigates the response of primary cortical neurons to iron oxide nanoparticles with coatings frequently used in biomedical applications: aminosilane, dextran, and polydimethylamine. Prior to administering the particles to neuronal cultures, each particle type was thoroughly characterized to assess the (1) size of individual nanoparticles, (2) concentration of the particles in solution and (3) agglomeration size and morphology. Culture results show that polydimethylamine functionalized nanoparticles induce cell death at all concentrations tested by swift and complete removal of the plasma membrane. Aminosilane coated particles affected metabolic activity only at higher concentrations while leaving the membrane intact and dextran-coated nanoparticles partially altered viability at higher concentrations. These findings suggest that nanoparticle characterization and primary cell-based cytotoxicity evaluation should be completed prior to applying nanomaterials to the nervous system. PMID:22111864

Decreasing GSH and increasing ROS in chemosensitivity gliomas with IDH1 mutation.

PubMed

Shi, Jinlong; Sun, Baolan; Shi, Wei; Zuo, Hao; Cui, Daming; Ni, Lanchun; Chen, Jian

2015-02-01

Gliomas are the most malignant and aggressive primary brain tumor in adults. Despite concerted efforts to improve therapies, their prognosis remains very poor. Isocitrate dehydrogenase 1 (IDH1) mutations have been discovered frequently in glioma patients and are strongly correlated with improved survival. However, the effect of IDH1 mutations on the chemosensitivity of gliomas remains unclear. In this study, we generated clonal U87 and U251 glioma cell lines overexpressing the R132H mutant protein (IDH1-R132H). Compared with control cells and cells overexpressing IDH wild type (IDH1-WT), both types of IDH1-R132H cells were more sensitive to temozolomide (TMZ) and cis-diamminedichloroplatinum (CDDP) in a time- and dose-dependent manner. The IDH1-R132H-induced higher chemosensitivity was associated with nicotine adenine disphosphonucleotide (NADPH), glutathione (GSH) depletion, and reactive oxygen species (ROS) generation. Accordingly, this IDH1-R132H-induced growth inhibition was effectively abrogated by GSH in vitro and in vivo. Our study provides direct evidence that the improved survival in patients with IDH1-R132H tumors may partly result from the effects of the IDH1-R132H protein on chemosensitivity. The primary cellular events associated with improved survival are the GSH depletion and increased ROS generation.

Use of complementary and alternative medicine by a sample of Turkish primary headache patients.

PubMed

Karakurum Göksel, Başak; Coşkun, Özlem; Ucler, Serap; Karatas, Mehmet; Ozge, Aynur; Ozkan, Secil

2014-01-01

Complementary and alternative medicine (CAM) is increasingly being used as adjunctive treatment in primary headache syndromes in many countries. In the Turkish population, no epidemiologic data have been reported about awareness and usage of these treatments in patients with headache. One hundred and ten primary headache patients attending three headache clinics completed a questionnaire regarding their headaches, the known modalities and the use and effect of CAM procedures for their headaches. The mean age of the patients was 34.7±9.6 years (32.8-36.5). Almost two-thirds of patients had completed high school and university, and one-third of patients were housewives. Migraine without aura (45.5%) was the most frequently diagnosed type of headache followed by migraine with aura (19.1%) and tension-type headache (18.2%). In 43.6% of the patients, headache frequency was 5-10 per month. The most frequently known CAM modalities were massage (74.5%), acupuncture (44.5%), yoga (31.8%), exercise (28.2%), psychotherapy (25.5%), and rosemary (23.6%). The most frequently used CAM treatments were massage (51%) and exercise (11%). Only massage was reported to be beneficial in one-third of the primary headache patients; the other modalities were not. Our findings suggest that the subgroup of primary headache patients in Turkey seek and use alternative treatments, frequently in combination with standard treatments. Neurologists should become more knowledgeable regarding CAM therapies; further randomized and controlled clinical researches with large sample sizes are needed.

The organ transplantation act and recent trends in Korea.

PubMed

Joo, Ho No

2013-03-01

The Organ Transplantation Act, including transplantation of organs from brain-dead donors, entered into force in Korea on February 9, 2000. This article introduces the Organ Transplantation Act, focusing on scope of the Act, determination of brain death, removal of organs from brain-dead or deceased donors, removal from living donors, organ allocation, and prohibition of trade in human organs. Especially, some primary ethical dilemmas surrounding organ allocation arise from the shortage of available organs. The primary ethical problems surrounding organ allocation are as follows. A key purpose of the organ donation incentive system is to increase the number of organ transplants from brain-dead donors. In particular, the priority for kidney patient was allowed in consideration of doctor's strong desire to increase the brain-dead donors. Also, the organ allocation criteria based on the organ donation incentive system appear unfair, especially for the kidney patient, because the criteria do not fit the principles of distributive justice. In the future, the organ donation incentive system itself may need to be reexamined.

Motor deficits correlate with resting state motor network connectivity in patients with brain tumours

PubMed Central

Mikell, Charles B.; Youngerman, Brett E.; Liston, Conor; Sisti, Michael B.; Bruce, Jeffrey N.; Small, Scott A.; McKhann, Guy M.

2012-01-01

While a tumour in or abutting primary motor cortex leads to motor weakness, how tumours elsewhere in the frontal or parietal lobes affect functional connectivity in a weak patient is less clear. We hypothesized that diminished functional connectivity in a distributed network of motor centres would correlate with motor weakness in subjects with brain masses. Furthermore, we hypothesized that interhemispheric connections would be most vulnerable to subtle disruptions in functional connectivity. We used task-free functional magnetic resonance imaging connectivity to probe motor networks in control subjects and patients with brain tumours (n = 22). Using a control dataset, we developed a method for automated detection of key nodes in the motor network, including the primary motor cortex, supplementary motor area, premotor area and superior parietal lobule, based on the anatomic location of the hand-motor knob in the primary motor cortex. We then calculated functional connectivity between motor network nodes in control subjects, as well as patients with and without brain masses. We used this information to construct weighted, undirected graphs, which were then compared to variables of interest, including performance on a motor task, the grooved pegboard. Strong connectivity was observed within the identified motor networks between all nodes bilaterally, and especially between the primary motor cortex and supplementary motor area. Reduced connectivity was observed in subjects with motor weakness versus subjects with normal strength (P < 0.001). This difference was driven mostly by decreases in interhemispheric connectivity between the primary motor cortices (P < 0.05) and between the left primary motor cortex and the right premotor area (P < 0.05), as well as other premotor area connections. In the subjects without motor weakness, however, performance on the grooved pegboard did not relate to interhemispheric connectivity, but rather was inversely correlated with connectivity between the left premotor area and left supplementary motor area, for both the left and the right hands (P < 0.01). Finally, two subjects who experienced severe weakness following surgery for their brain tumours were followed longitudinally, and the subject who recovered showed reconstitution of her motor network at follow-up. The subject who was persistently weak did not reconstitute his motor network. Motor weakness in subjects with brain tumours that do not involve primary motor structures is associated with decreased connectivity within motor functional networks, particularly interhemispheric connections. Motor networks become weaker as the subjects become weaker, and may become strong again during motor recovery. PMID:22408270

Impact of persistent, frequent regurgitation on quality of life in heartburn responders treated with acid suppression: a multinational primary care study.

PubMed

Kahrilas, P J; Howden, C W; Wernersson, B; Denison, H; Nuevo, J; Gisbert, J P

2013-05-01

In gastro-oesophageal reflux disease (GERD), heartburn responds well to acid suppression, but regurgitation is a common cause of incomplete treatment response. To assess the prevalence and burden of persistent, frequent regurgitation in primary care patients with GERD treated with acid suppression. We analysed observational data from 134 sites across six European countries in patients diagnosed with GERD. Within 3 months of the index visit, symptoms were assessed using the Reflux Disease Questionnaire, and their impact on sleep and work productivity with the Quality of Life in Reflux and Dyspepsia questionnaire and the Work Productivity and Activity Impairment Questionnaire, respectively. Patients provided information on concomitant over-the-counter (OTC) GERD medication use. Persistent, frequent (3-7 days/week) regurgitation was reported by 13.2% (153/1156) of GERD patients with no heartburn on acid suppression; the prevalence was very similar for patients with up to 2 days/week of ongoing mild heartburn. Among patients without heartburn, sleep disturbance of any type was reported by 50.7-60.1% with persistent, frequent regurgitation, compared with 38.1-51.1% and 14.4-19.2% of those with less frequent or no regurgitation respectively. Persistent, frequent regurgitation was associated with increased use of OTC medication and more hours of work missed, whether mild, infrequent heartburn was present or not. Frequent regurgitation, which persisted in 12-13% of patients with no or infrequent, mild heartburn on acid suppression, negatively affected sleep and work productivity, and increased use of OTC medication. Persistent, frequent regurgitation is problematic for primary care patients with GERD. © 2013 Blackwell Publishing Ltd.

Inferior frontal cortex activity is modulated by reward sensitivity and performance variability.

PubMed

Fuentes-Claramonte, Paola; Ávila, César; Rodríguez-Pujadas, Aina; Costumero, Víctor; Ventura-Campos, Noelia; Bustamante, Juan Carlos; Rosell-Negre, Patricia; Barrós-Loscertales, Alfonso

2016-02-01

High reward sensitivity has been linked with motivational and cognitive disorders related with prefrontal and striatal brain function during inhibitory control. However, few studies have analyzed the interaction among reward sensitivity, task performance and neural activity. Participants (N=57) underwent fMRI while performing a Go/No-go task with Frequent-go (77.5%), Infrequent-go (11.25%) and No-go (11.25%) stimuli. Task-associated activity was found in inhibition-related brain regions, with different activity patterns for right and left inferior frontal gyri (IFG): right IFG responded more strongly to No-go stimuli, while left IFG responded similarly to all infrequent stimuli. Reward sensitivity correlated with omission errors in Go trials and reaction time (RT) variability, and with increased activity in right and left IFG for No-go and Infrequent-go stimuli compared with Frequent-go. Bilateral IFG activity was associated with RT variability, with reward sensitivity mediating this association. These results suggest that reward sensitivity modulates behavior and brain function during executive control. Copyright © 2016 Elsevier B.V. All rights reserved.

[Loss of motivation in the elderly].

PubMed

Thomas, Philippe; Hazif-Thomas, Cyril; Clément, Jean-Pierre

2008-06-30

The loss of motivation is frequent in aged person and sometimes is difficult to assess. It is associated with depression but not exclusively. It overlaps with frontal brain aging consequences. Moreover, somatic problems can interfere with a loss of motivation; loss of motivation is frequent with exhausting chronic diseases, cognitive impairment and it facilitates the social withdrawal. In elderly, loss of motivation blunts the intensity of moral pain. Depressions with conative disorders can move in a dysexecutive syndrome. Even if, owing to the treatment, the cognitive disorders disappear, several years after, an authentic dementia can be diagnosed. With aging process, elderly must cope with losses, less or more balanced: affective, physical and financial losses, triggering the reject of any personal commitment. Aging process also concerns brain amines, especially dopamine, exposing old persons to depression. It alters by a similar way others brain neuro-mediator, such acetylcholine, involved in dementia. Both loss motivation and executive disorders have to be systematically assessed. An antidepressant therapeutic is necessary in case of doubt, improving patients thymic status, quality of life of patients and their family, and sometime of frontal dysfunctions.

Localized intestinal perforations as a potential complication of brain hypothermic therapy for perinatal asphyxia.

PubMed

Nishizaki, Naoto; Maiguma, Atsuko; Obinata, Kaoru; Okazaki, Tadaharu; Shimizu, Toshiaki

2016-01-01

Brain hypothermic therapy (BHT) is becoming a frequently used standard of care for perinatal asphyxia. Although cardiovascular side effects, coagulation disorders, renal impairment, electrolyte abnormalities, impaired liver function, opportunistic infections, and skin lesions are well-known adverse effects of BHT in newborns, little information is available on the clinical features of intestinal perforation-related BHT. We herein report a case of therapeutic brain cooling for perinatal asphyxia complicated by localized intestinal perforation. In practice, the neonatologist should be aware that intestinal perforation in an infant with perinatal asphyxia is possible, particularly following BHT.

Targetable genetic features of primary testicular and primary central nervous system lymphomas

PubMed Central

Chapuy, Bjoern; Roemer, Margaretha G. M.; Stewart, Chip; Tan, Yuxiang; Abo, Ryan P.; Zhang, Liye; Dunford, Andrew J.; Meredith, David M.; Thorner, Aaron R.; Jordanova, Ekaterina S.; Liu, Gang; Feuerhake, Friedrich; Ducar, Matthew D.; Illerhaus, Gerald; Gusenleitner, Daniel; Linden, Erica A.; Sun, Heather H.; Homer, Heather; Aono, Miyuki; Pinkus, Geraldine S.; Ligon, Azra H.; Ligon, Keith L.; Ferry, Judith A.; Freeman, Gordon J.; van Hummelen, Paul; Golub, Todd R.; Getz, Gad; Rodig, Scott J.; de Jong, Daphne; Monti, Stefano

2016-01-01

Primary central nervous system lymphomas (PCNSLs) and primary testicular lymphomas (PTLs) are extranodal large B-cell lymphomas (LBCLs) with inferior responses to current empiric treatment regimens. To identify targetable genetic features of PCNSL and PTL, we characterized their recurrent somatic mutations, chromosomal rearrangements, copy number alterations (CNAs), and associated driver genes, and compared these comprehensive genetic signatures to those of diffuse LBCL and primary mediastinal large B-cell lymphoma (PMBL). These studies identify unique combinations of genetic alterations in discrete LBCL subtypes and subtype-selective bases for targeted therapy. PCNSLs and PTLs frequently exhibit genomic instability, and near-uniform, often biallelic, CDKN2A loss with rare TP53 mutations. PCNSLs and PTLs also use multiple genetic mechanisms to target key genes and pathways and exhibit near-uniform oncogenic Toll-like receptor signaling as a result of MYD88 mutation and/or NFKBIZ amplification, frequent concurrent B-cell receptor pathway activation, and deregulation of BCL6. Of great interest, PCNSLs and PTLs also have frequent 9p24.1/PD-L1/PD-L2 CNAs and additional translocations of these loci, structural bases of immune evasion that are shared with PMBL. PMID:26702065

Sports-related Head Injury

MedlinePlus

... The force of a professional boxer's fist is equivalent to being hit with a 13-pound bowling ... concussions frequently affect athletes in both contact and non-contact sports. Cerebral concussions are considered diffuse brain ...

Airway Management Strategies for Brain-injured Patients Meeting Standard Criteria to Consider Extubation. A Prospective Cohort Study.

PubMed

McCredie, Victoria A; Ferguson, Niall D; Pinto, Ruxandra L; Adhikari, Neill K J; Fowler, Robert A; Chapman, Martin G; Burrell, Althea; Baker, Andrew J; Cook, Deborah J; Meade, Maureen O; Scales, Damon C

2017-01-01

Patients with acute brain injury are frequently capable of breathing spontaneously with minimal ventilatory support despite persistent neurological impairment. We sought to describe factors associated with extubation timing, success, and primary tracheostomy in these patients. We conducted a prospective multicenter observational cohort study in three academic hospitals in Toronto, Canada. Consecutive brain-injured adults receiving mechanical ventilation for at least 24 hours in three intensive care units were screened by study personnel daily for extubation consideration criteria. We monitored all patients until hospital discharge and used logistic regression models to examine associations with extubation failure and delayed extubation. Of 192 patients included, 152 (79%) were extubated and 40 (21%) received a tracheostomy without an extubation attempt. The rate of extubation failure within 72 hours was 32 of 152 (21%), which did not vary significantly between those extubated before (early; 6 of 37; 16.2%), within 24 hours (timely; 14 of 70; 20.0%), or more than 24 hours after meeting criteria to consider extubation (delayed; 12 of 45; 26.7%; P = 0.49). Delayed extubation was associated with lower a Glasgow Coma Scale (GCS) score at the time of consideration of extubation, absence of cough, and new positive sputum cultures. Factors independently associated with successful extubation were presence of cough (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.42-9.09), fluid balance in prior 24 hours (OR, 0.75 per 1-L increase; 95% CI, 0.57-0.98), and age (OR, 0.97 per 10-yr increase; 95% CI, 0.95-0.99). A higher GCS score was not associated with successful extubation. Extubation success was predicted by younger age, presence of cough, and negative fluid balance, rather than GCS score at extubation. These results do not support prolonging intubation solely for low GCS score in brain-injured patients.

Top-cited articles in traumatic brain injury.

PubMed

Sharma, Bhanu; Lawrence, David Wyndham

2014-01-01

A review of the top-cited articles in a scientific discipline can identify areas of research that are well established and those in need of further development, and may, as a result, inform and direct future research efforts. Our objective was to identify and characterize the top-cited articles in traumatic brain injury (TBI). We used publically available software to identify the 50 TBI articles with the most lifetime citations, and the 50 TBI articles with the highest annual citation rates. A total of 73 articles were included in this review, with 27 of the 50 papers with the highest annual citation rates common to the cohort of 50 articles with the most lifetime citations. All papers were categorized by their primary topic or focus, namely: predictor of outcome, pathology/natural history, treatment, guidelines and consensus statements, epidemiology, assessment measures, or experimental model of TBI. The mean year of publication of the articles with the most lifetime citations and highest annual citation rates was 1990 ± 14.9 years and 2003 ± 6.7 years, respectively. The 50 articles with the most lifetime citations typically studied predictors of outcome (34.0%, 17/50) and were specific to severe TBI (38.0%, 19/50). In contrast, the most common subject of papers with the highest annual citation rates was treatment of brain injury (22.0%, 11/50), and these papers most frequently investigated mild TBI (36.0%, 18/50). These findings suggest an intensified focus on mild TBI, which is perhaps a response to the dedicated attention these injuries are currently receiving in the context of sports and war, and because of their increasing incidence in developing nations. Our findings also indicate increased focus on treatment of TBI, possibly due to the limited efficacy of current interventions for brain injury. This review provides a cross-sectional summary of some of the most influential articles in TBI, and a bibliometric examination of the current status of TBI research.

Intensive versus conventional glucose control in critically ill patients with traumatic brain injury: long-term follow-up of a subgroup of patients from the NICE-SUGAR study.

PubMed

Finfer, Simon; Chittock, Dean; Li, Yang; Foster, Denise; Dhingra, Vinay; Bellomo, Rinaldo; Cook, Deborah; Dodek, Peter; Hebert, Paul; Henderson, William; Heyland, Daren; Higgins, Alisa; McArthur, Colin; Mitchell, Imogen; Myburgh, John; Robinson, Bruce; Ronco, Juan

2015-06-01

To compare the effect of intensive versus conventional blood glucose control in patients with traumatic brain injury. In a large international randomized trial patients were randomly assigned to a target blood glucose (BG) range of either 4.5-6.0 mmol/L (intensive control) or <10 mmol/L (conventional control). Patients with traumatic brain injury (TBI) were identified at randomization and data were collected to examine the extended Glasgow outcome score (includes mortality) at 24 months. Of the 6104 randomized patients, 391 satisfied diagnostic criteria for TBI; 203 (51.9%) were assigned to intensive and 188 (48.1%) to conventional control; the primary outcome was available for 166 (81.8%) and 149 (79.3%) patients, respectively. The two groups had similar baseline characteristics. At 2 years 98 (58.7%) patients in the intensive group and 79 (53.0%) in the conventional group had a favorable neurological outcome (odds ratio [OR] 1.26, 95% CI 0.81-1.97; P = 0.3); 35 patients (20.9%) in the intensive group and 34 (22.8%) in the conventional group had died (OR 0.90, 95% CI 0.53-1.53; P = 0.7); moderate hypoglycemia (BG 2.3-3.9 mmol/L; 41-70 mg/dL) occurred in 160/202 (79.2%) and 17/188 (9.0%), respectively (OR 38.3, 95% CI 21.0-70.1; P < 0.0001); severe hypoglycemia (BG ≤ 2.2 mmol/L; ≤40 mg/dL) in 10 (4.9%) and 0 (0.0%), respectively (OR 20.5 95% CI 1.2-351.6, P = 0.003). Although patients with traumatic brain injury randomly assigned to intensive compared to conventional glucose control experienced moderate and severe hypoglycemia more frequently, we found no significant difference in clinically important outcomes.

Large-scale cortical volume correlation networks reveal disrupted small world patterns in Parkinson's disease.

PubMed

Wu, Qiong; Gao, Yang; Liu, Ai-Shi; Xie, Li-Zhi; Qian, Long; Yang, Xiao-Guang

2018-01-01

To date, the most frequently reported neuroimaging biomarkers in Parkinson's disease (PD) are direct brain imaging measurements focusing on local disrupted regions. However, the notion that PD is related to abnormal functional and structural connectivity has received support in the past few years. Here, we employed graph theory to analyze the structural co-variance networks derived from 50 PD patients and 48 normal controls (NC). Then, the small world properties of brain networks were assessed in the structural networks that were constructed based on cortical volume data. Our results showed that both the PD and NC groups had a small world architecture in brain structural networks. However, the PD patients had a higher characteristic path length and clustering coefficients compared with the NC group. With regard to the nodal centrality, 11 regions, including 3 association cortices, 5 paralimbic cortices, and 3 subcortical regions were identified as hubs in the PD group. In contrast, 10 regions, including 7 association cortical regions, 2 paralimbic cortical regions, and the primary motor cortex region, were identified as hubs. Moreover, the regional centrality was profoundly affected in PD patients, including decreased nodal centrality in the right inferior occipital gyrus and the middle temporal gyrus and increased nodal centrality in the right amygdala, the left caudate and the superior temporal gyrus. In addition, the structural cortical network of PD showed reduced topological stability for targeted attacks. Together, this study shows that the coordinated patterns of cortical volume network are widely altered in PD patients with a decrease in the efficiency of parallel information processing. These changes provide structural evidence to support the concept that the core pathophysiology of PD is associated with disruptive alterations in the coordination of large-scale brain networks that underlie high-level cognition. Copyright © 2017. Published by Elsevier B.V.

Hippocampus-sparing radiotherapy using volumetric modulated arc therapy (VMAT) to the primary brain tumor: the result of dosimetric study and neurocognitive function assessment.

PubMed

Kim, Kyung Su; Wee, Chan Woo; Seok, Jin-Yong; Hong, Joo Wan; Chung, Jin-Beom; Eom, Keun-Yong; Kim, Jae-Sung; Kim, Chae-Yong; Park, Young Ho; Kim, Yu Jung; Kim, In Ah

2018-02-20

We hypothesized that hippocampal-sparing radiotherapy via volumetric modulated arc therapy (VMAT) could preserve the neurocognitive function (NCF) of patients with primary brain tumors treated with radiotherapy. We reviewed data from patients with primary brain tumors who underwent hippocampal-sparing brain radiotherapy via VMAT between February 2014 and December 2015. The optimization criteria for the contralateral hippocampus was a maximum dose (D max ) of less than 17 Gy. For NCF evaluations, the Seoul Verbal Learning Test for total recall, delayed recall, and recognition (SVLT-TR, DR, and Recognition) was performed at baseline and at seven months after radiotherapy. A total of 26 patients underwent NCF testing seven months after radiotherapy. Their median age was 49.5 years (range 26-77 years), and 14 (53.8%) had grade III/IV tumors. The median D max to the contralateral hippocampus was 16.4 Gy (range 3.5-63.4). The median mean dose to the contralateral hippocampus, expressed as equivalent to a 2-Gy dose (EQD 2/2 ), was 7.4 Gy 2 (0.7-13.1). The mean relative changes in SVLT-TR, SVLT-DR, and SVLT-Recognition at seven months compared to the baseline were - 7.7% (95% confidence interval [CI], - 19.6% to 4.2%), - 9.2% (95% CI, - 25.4% to 7.0%), and - 3.4% (- 12.7% to 5.8%), respectively. Two patients (7.7%) showed deteriorated NCF in the SVLT-TR and SVLT-DR, and three (11.5%) in the SVLT-Recognition. The mean dose of the left hippocampus and bilateral hippocampi were significantly higher in patients showing deterioration of the SVLT-TR and SVLT-Recognition than in those without deterioration. The contralateral hippocampus could be effectively spared in patients with primary brain tumor via VMAT to preserve the verbal memory function. Further investigation is needed to identify those patients who will most benefit from hippocampal-sparing radiotherapy of the primary brain tumor.

Unruptured Brain Arteriovenous Malformations: Primary ONYX Embolization in ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations)-Eligible Patients.

PubMed

Singfer, Uri; Hemelsoet, Dimitri; Vanlangenhove, Peter; Martens, Frederic; Verbeke, Luc; Van Roost, Dirk; Defreyne, Luc

2017-12-01

In light of evidence from ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations), neurovascular specialists had to reconsider deliberate treatment of unruptured brain arteriovenous malformations (uBAVMs). Our objective was to determine the outcomes of uBAVM treated with primary embolization using ethylene vinyl alcohol (ONYX). Patients with uBAVM who met the inclusion criteria of ARUBA and were treated with primary Onyx embolization were assigned to this retrospective study. The primary outcome was the modified Rankin Scale score. Secondary outcomes were stroke or death because of uBAVM or intervention and uBAVM obliteration. Sixty-one patients (mean age, 38 years) were included. The median observation period was 60 months. Patients were treated by embolization alone (41.0%), embolization and radiosurgery (57.4%), or embolization and excision (1.6%). Occlusion was achieved in 44 of 57 patients with completed treatment (77.2%). Forty-seven patients (77.1%) had no clinical impairment at the end of observation (modified Rankin Scale score of <2). Twelve patients (19.7%) reached the outcome of stroke or death because of uBAVM or intervention. Treatment-related mortality was 6.6% (4 patients). In uBAVM, Onyx embolization alone or combined with stereotactic radiosurgery achieves a high occlusion rate. Morbidity remains a challenge, even if it seems lower than in the ARUBA trial. © 2017 American Heart Association, Inc.

Simultaneous 11C-Methionine Positron Emission Tomography/Magnetic Resonance Imaging of Suspected Primary Brain Tumors

PubMed Central

Deuschl, Cornelius; Goericke, Sophia; Grueneisen, Johannes; Sawicki, Lino Morris; Goebel, Juliane; El Hindy, Nicolai; Wrede, Karsten; Binse, Ina; Poeppel, Thorsten; Quick, Harald; Forsting, Michael; Hense, Joerg; Umutlu, Lale; Schlamann, Marc

2016-01-01

Introduction The objective of this study was to assess the diagnostic value of integrated 11C- methionine PET/MRI for suspected primary brain tumors, in comparison to MRI alone. Material and Methods Forty-eight consecutive patients with suspected primary brain tumor were prospectively enrolled for an integrated 11C-methionine PET/MRI. Two neuro-radiologists separately evaluated the MRI alone and the integrated PET/MRI data sets regarding most likely diagnosis and diagnostic confidence on a 5-point scale. Reference standard was histopathology or follow-up imaging. Results Fifty-one suspicious lesions were detected: 16 high-grade glioma and 25 low-grade glioma. Ten non-malignant cerebral lesions were described by the reference standard. MRI alone and integrated PET/MRI each correctly classified 42 of the 51 lesions (82.4%) as neoplastic lesions (WHO grade II, III and IV) or non-malignant lesions (infectious and neoplastic lesions). Diagnostic confidence for all lesions, low-grade astrocytoma and high-grade astrocytoma (3.7 vs. 4.2, 3,1 vs. 3.8, 4.0 vs. 4,7) were significantly (p < 0.05) better with integrated PET/MRI than in MRI alone. Conclusions The present study demonstrates the high potential of integrated 11C-methionine-PET/MRI for the assessment of suspected primary brain tumors. Although integrated methionine PET/MRI does not lead to an improvement of correct diagnoses, diagnostic confidence is significantly improved. PMID:27907162

Variation in promptness of presentation among 10,297 patients subsequently diagnosed with one of 18 cancers: Evidence from a National Audit of Cancer Diagnosis in Primary Care

PubMed Central

Keeble, Stuart; Abel, Gary A; Saunders, Catherine L; McPhail, Sean; Walter, Fiona M; Neal, Richard D; Rubin, Gregory P; Lyratzopoulos, Georgios

2014-01-01

Cancer awareness public campaigns aim to shorten the interval between symptom onset and presentation to a doctor (the ‘patient interval’). Appreciating variation in promptness of presentation can help to better target awareness campaigns. We explored variation in patient intervals recorded in consultations with general practitioners among 10,297 English patients subsequently diagnosed with one of 18 cancers (bladder, brain, breast, colorectal, endometrial, leukaemia, lung, lymphoma, melanoma, multiple myeloma, oesophageal, oro-pharyngeal, ovarian, pancreatic, prostate, renal, stomach, and unknown primary) using data from of the National Audit of Cancer Diagnosis in Primary Care (2009–2010). Proportions of patients with ‘prompt’/‘non-prompt’ presentation (0–14 or 15+ days from symptom onset, respectively) were described and respective odds ratios were calculated by multivariable logistic regression. The overall median recorded patient interval was 10 days (IQR 0–38). Of all patients, 56% presented promptly. Prompt presentation was more frequent among older or housebound patients (p < 0.001). Prompt presentation was most frequent for bladder and renal cancer (74% and 70%, respectively); and least frequent for oro-pharyngeal and oesophageal cancer (34% and 39%, respectively, p <.001). Using lung cancer as reference, the adjusted odds ratios of non-prompt presentation were 2.26 (95% confidence interval 1.57–3.25) and 0.42 (0.34–0.52) for oro-pharyngeal and bladder cancer, respectively. Sensitivity analyses produced similar findings. Routinely recorded patient interval data reveal considerable variation in the promptness of presentation. These findings can help to prioritise public awareness initiatives and research focusing on symptoms of cancers associated with greater risk of non-prompt presentation, such as oro-pharyngeal and oesophageal cancer. What's new? A critical aspect of cancer diagnosis is how promptly patients consult a doctor after they first notice initial symptoms. Here, the authors examine differences in this so-called patient interval in English patients subsequently diagnosed with one of 18 cancers. On average, patients with bladder and renal cancer as well as older and housebound patients consulted a doctor relatively promptly while patients with oro-pharyngeal and oesophageal cancer took the longest until first presenting to a general practitioner. The authors point out that cancer awareness campaigns should encompass symptoms of oro-pharyngeal and oesophageal cancer aiming to shorten the patient interval for these cancers. PMID:24515930

Impairment of Glymphatic Pathway Function Promotes Tau Pathology after Traumatic Brain Injury

PubMed Central

Chen, Michael J.; Plog, Benjamin A.; Zeppenfeld, Douglas M.; Soltero, Melissa; Yang, Lijun; Singh, Itender; Deane, Rashid; Nedergaard, Maiken

2014-01-01

Traumatic brain injury (TBI) is an established risk factor for the early development of dementia, including Alzheimer's disease, and the post-traumatic brain frequently exhibits neurofibrillary tangles comprised of aggregates of the protein tau. We have recently defined a brain-wide network of paravascular channels, termed the “glymphatic” pathway, along which CSF moves into and through the brain parenchyma, facilitating the clearance of interstitial solutes, including amyloid-β, from the brain. Here we demonstrate in mice that extracellular tau is cleared from the brain along these paravascular pathways. After TBI, glymphatic pathway function was reduced by ∼60%, with this impairment persisting for at least 1 month post injury. Genetic knock-out of the gene encoding the astroglial water channel aquaporin-4, which is importantly involved in paravascular interstitial solute clearance, exacerbated glymphatic pathway dysfunction after TBI and promoted the development of neurofibrillary pathology and neurodegeneration in the post-traumatic brain. These findings suggest that chronic impairment of glymphatic pathway function after TBI may be a key factor that renders the post-traumatic brain vulnerable to tau aggregation and the onset of neurodegeneration. PMID:25471560

Anticipatory Processing in the Brain on the Perception of Müller-Lyer Illusionary Figures—A Brain Potential Study

NASA Astrophysics Data System (ADS)

Nomura, Shusaku; Sasaki, Shuntaro; Hirakawa, Masato; Hiwaki, Osamu

2010-11-01

We investigated the brain potential in relation with the recognition of Müller-Lyer (ML) illusionary figure, which was a famous optical illusion. Although it is frequently assumed that the ML illusionary effect could be derived from its geometrical construction, it derives the same length miss-estimation effect on the sense of touch; haptic illusion. Moreover it occurs in people who are blindfolded or congenital blind. Thus somehow higher information processing than the optical one within the brain could be expected to involve with the recognition of ML figure while few brain studies have demonstrated it. We then investigated the brain waves under subjects' perceiving ML illusionary figure. As a result the marked difference of the brain potential between ML and the control condition around the midline of parietal brain, where the multi-modal perception information was thought to associate within the brain, was observed. This result implies that the anticipatory processing on the perception of ML illusionary figures would be derived by integrating multi-sensory information.

Promoter methylation of AREG, HOXA11, hMLH1, NDRG2, NPTX2 and Tes genes in glioblastoma.

PubMed

Skiriutė, Daina; Vaitkienė, Paulina; Ašmonienė, Virginija; Steponaitis, Giedrius; Deltuva, Vytenis Pranas; Tamašauskas, Arimantas

2013-07-01

Epigenetic alterations alone or in combination with genetic mechanisms play a key role in brain tumorigenesis. Glioblastoma is one of the most common, lethal and poor clinical outcome primary brain tumors with extraordinarily miscellaneous epigenetic alterations profile. The aim of this study was to investigate new potential prognostic epigenetic markers such as AREG, HOXA11, hMLH1, NDRG2, NTPX2 and Tes genes promoter methylation, frequency and value for patients outcome. We examined the promoter methylation status using methylation-specific polymerase chain reaction in 100 glioblastoma tissue samples. The value for clinical outcome was calculated using Kaplan-Meier estimation with log-rank test. DNA promoter methylation was frequent event appearing more than 45 % for gene. AREG and HOXA11 methylation status was significantly associated with patient age. HOXA11 showed the tendency to be associated with patient outcome in glioblastomas. AREG gene promoter methylation showed significant correlation with poor patient outcome. AREG methylation remained significantly associated with patient survival in a Cox multivariate model including MGMT promoter methylation status. This study of new epigenetic targets has shown considerably high level of analyzed genes promoter methylation variability in glioblastoma tissue. AREG gene might be valuable marker for glioblastoma patient survival prognosis, however further analysis is needed to clarify the independence and appropriateness of the marker.

Profile of effective donors from organ and tissue procurement services

PubMed Central

Rodrigues, Simey de Lima Lopes; Ferraz Neto, Jose Ben-Hur de Escobar; Sardinha, Luiz Antonio da Costa; Araujo, Sebastião; Zambelli, Helder Jose Lessa; Boin, Ilka de Fátima Santana Ferreira; Athayde, Maria Valeria de Omena; Montone, Eliete Bombarda Bachega; Panunto, Marcia Raquel

2014-01-01

Objective To characterize the profile of effective organ and tissue donors and to understand which organs and tissues were donated for transplantation. Methods This was a quantitative, descriptive, exploratory, retrospective study that analyzed clinical data from 305 donors between January 2006 to December 2010. The data were then analyzed using descriptive analyses, generating frequency tables, measures of position (mean, minimum and maximum) and measures of dispersion (standard deviation) for data that was social and clinical in nature. Results There was an overall predominance of white (72%) and male (55%) individuals between the ages of 41 and 60 years (44%). The primary cause of brain death was cerebrovascular accident (55%). In the patient history, 31% of the patients were classified as overweight, 27% as hypertensive and only 4.3% as having diabetes mellitus. Vasoactive drugs were used in 92.7% of the donors, and the main drug of choice was noradrenaline (81.6%). Hyperglycemia and hypernatremia were diagnosed in 78% and 71% of the donors, respectively. Conclusion Significant hemodynamic changes were found, and the results indicate that the use of vasoactive drugs was the main strategy used to control these changes. Furthermore, most donors presented with hyperglycemia and hypernatremia, which were frequently reported in association with brain death. The persistent nature of these findings suggests that the organ donors were inadequately maintained. PMID:24770685

Glioblastoma with oligodendroglioma component (GBM-O): molecular genetic and clinical characteristics.

PubMed

Appin, Christina L; Gao, Jingjing; Chisolm, Candace; Torian, Mike; Alexis, Dianne; Vincentelli, Cristina; Schniederjan, Matthew J; Hadjipanayis, Costas; Olson, Jeffrey J; Hunter, Stephen; Hao, Chunhai; Brat, Daniel J

2013-07-01

Glioblastoma (GBM) is an aggressive primary brain tumor with an average survival of approximately 1 year. A recently recognized subtype, glioblastoma with oligodendroglioma component (GBM-O), was designated by the World Health Organization (WHO) in 2007. We investigated GBM-Os for their clinical and molecular characteristics as compared to other forms of GBM. Tissue samples were used to determine EGFR, PTEN, and 1p and 19q status by fluorescence in situ hybridization (FISH); p53 and mutant IDH1 protein expression by immunohistochemistry (IHC); and MGMT promoter status by methylation-specific polymerase chain reaction (PCR). GBM-Os accounted for 11.9% of all GBMs. GBM-Os arose in younger patients compared to other forms of GBMs (50.7 years vs. 58.7 years, respectively), were more frequently secondary neoplasms, had a higher frequency of IDH1 mutations and had a lower frequency of PTEN deletions. Survival was longer in patients with GBM-Os compared to those with other GBMs, with median survivals of 16.2 and 8.1 months, respectively. Most of the survival advantage for GBM-O appeared to be associated with a younger age at presentation. Among patients with GBM-O, younger age at presentation and 1p deletion were most significant in conferring prolonged survival. Thus, GBM-O represents a subset of GBMs with distinctive morphologic, clinical and molecular characteristics. © 2013 The Authors; Brain Pathology © 2013 International Society of Neuropathology.

Molecular Characterization of Coccidia Associated with an Epizootic in Green Sea Turtles (Chelonia mydas) in South East Queensland, Australia

PubMed Central

Chapman, Phoebe A.; Owen, Helen; Flint, Mark; Traub, Rebecca J.; Cribb, Thomas H.; Mills, Paul C.

2016-01-01

In the spring of 2014, mass mortalities among wild green sea turtles occurred off the coast of south-east Queensland, Australia. The suspected causative agent was Caryospora cheloniae, an eimeriid coccidian implicated in previous epizootics. Necropsies were undertaken on a subset of 11 dead turtles, with subsequent histopathology and molecular analyses. All turtles returned positive PCR results for coccidial infection in various tissues; these included the brain, gastrointestinal tract, lung, kidney and thyroid. Granulomatous encephalitis was consistently observed, as well as enteritis and, less frequently, thyroiditis and nephritis. Sequencing and phylogenetic analyses indicated the presence of two distinct coccidian genotypes, presumably separate species—one associated with the brain, gastrointestinal tract and lung, and the second with the thyroid and kidney. Maximum likelihood and Bayesian inference analyses placed the first genotype closest to the lankesterellid genus Schellackia, rather than in the Eimeriidae, while the second was paraphyletic to the eimeriids. Presence of coccidial stages in extra-intestinal tissues of the primary host raises questions about the potential presence of intermediate or paratenic hosts within the life cycles, as well as their current placement relative to the genus Caryospora. This study represents the first genetic characterization of this emerging disease agent in green sea turtles, an endangered species, and has relevance for life-cycle elucidation and future development of diagnostics. PMID:26901786

Molecular Characterization of Coccidia Associated with an Epizootic in Green Sea Turtles (Chelonia mydas) in South East Queensland, Australia.

PubMed

Chapman, Phoebe A; Owen, Helen; Flint, Mark; Traub, Rebecca J; Cribb, Thomas H; Mills, Paul C

2016-01-01

In the spring of 2014, mass mortalities among wild green sea turtles occurred off the coast of south-east Queensland, Australia. The suspected causative agent was Caryospora cheloniae, an eimeriid coccidian implicated in previous epizootics. Necropsies were undertaken on a subset of 11 dead turtles, with subsequent histopathology and molecular analyses. All turtles returned positive PCR results for coccidial infection in various tissues; these included the brain, gastrointestinal tract, lung, kidney and thyroid. Granulomatous encephalitis was consistently observed, as well as enteritis and, less frequently, thyroiditis and nephritis. Sequencing and phylogenetic analyses indicated the presence of two distinct coccidian genotypes, presumably separate species-one associated with the brain, gastrointestinal tract and lung, and the second with the thyroid and kidney. Maximum likelihood and Bayesian inference analyses placed the first genotype closest to the lankesterellid genus Schellackia, rather than in the Eimeriidae, while the second was paraphyletic to the eimeriids. Presence of coccidial stages in extra-intestinal tissues of the primary host raises questions about the potential presence of intermediate or paratenic hosts within the life cycles, as well as their current placement relative to the genus Caryospora. This study represents the first genetic characterization of this emerging disease agent in green sea turtles, an endangered species, and has relevance for life-cycle elucidation and future development of diagnostics.

RasGRP3 regulates the migration of glioma cells via interaction with Arp3

PubMed Central

Lee, Hae Kyung; Finniss, Susan; Cazacu, Simona; Xiang, Cunli; Poisson, Laila M.; Blumberg, Peter M.; Brodie, Chaya

2015-01-01

Glioblastoma (GBM), the most aggressive primary brain tumors, are highly infiltrative. Although GBM express high Ras activity and Ras proteins have been implicated in gliomagenesis, Ras-activating mutations are not frequent in these tumors. RasGRP3, an important signaling protein responsive to diacylglycerol (DAG), increases Ras activation. Here, we examined the expression and functions of RasGRP3 in GBM and glioma cells. RasGRP3 expression was upregulated in GBM specimens and glioma stem cells compared with normal brains and neural stem cells, respectively. RasGRP3 activated Ras and Rap1 in glioma cells and increased cell migration and invasion partially via Ras activation. Using pull-down assay and mass spectroscopy we identified the actin-related protein, Arp3, as a novel interacting protein of RasGRP3. The interaction of RasGRP3 and Arp3 was validated by immunofluorescence staining and co-immunoprecipitation, and PMA, which activates RasGRP3 and induces its translocation to the peri-nuclear region, increased the association of Arp3 and RasGRP3. Arp3 was upregulated in GBM, regulated cell spreading and migration and its silencing partially decreased these effects of RasGRP3 in glioma cells. In summary, RasGRP3 acts as an important integrating signaling protein of the DAG and Ras signaling pathways and actin polymerization and represents an important therapeutic target in GBM. PMID:25682201

Prospective memory rehabilitation using smartphones in patients with TBI: What do participants report?

PubMed

Evald, Lars

2015-01-01

Use of assistive devices has been shown to be beneficial as a compensatory memory strategy among brain injury survivors, but little is known about possible advantages and disadvantages of the technology. As part of an intervention study participants were interviewed about their experiences with the use of low-cost, off-the-shelf, unmodified smartphones combined with Internet calendars as a compensatory memory strategy. Thirteen community-dwelling patients with traumatic brain injury (TBI) received a 6-week group-based instruction in the systematic use of a smartphone as a memory compensatory aid followed by a brief structured open-ended interview regarding satisfaction with and advantages and disadvantages of the compensatory strategy. Ten of 13 participants continued to use a smartphone as their primary compensatory strategy. Audible and visual reminders were the most frequently mentioned advantages of the smartphone, and, second, the capability as an all-in-one memory device. In contrast, battery life was the most often mentioned disadvantage, followed by concerns about loss or failure of the device. Use of a smartphone seems to be a satisfactory compensatory memory strategy to many patients with TBI and smartphones come with features that are advantageous to other compensatory strategies. However, some benefits come hand-in-hand with drawbacks, such as the feeling of dependency. These aspects should be taken into account when choosing assistive technology as a memory compensatory strategy.

Effect of binasal occlusion (BNO) on the visual-evoked potential (VEP) in mild traumatic brain injury (mTBI).

PubMed

Ciuffreda, Kenneth J; Yadav, Naveen K; Ludlam, Diana P

2013-01-01

The purpose of the experiment was to assess the effect of binasal occlusion (BNO) on the visually-evoked potential (VEP) in visually-normal (VN) individuals and in those with mild traumatic brain injury (mTBI) for whom BNO frequently reduces their primary symptoms related to abnormally-increased visual motion sensitivity (VMS). Subjects were comprised of asymptomatic VN adults (n = 10) and individuals with mTBI (n = 10) having the symptom of VMS. Conventional full-field VEP testing was employed under two conditions: without BNO and with opaque BNO which blocked regions on either side of the VEP test stimulus. Subjective impressions were also assessed. In VN, the mean VEP amplitude decreased significantly with BNO in all subjects. In contrast, in mTBI, the mean VEP amplitude increased significantly with BNO in all subjects. Latency was normal and unaffected in all cases. Repeat VEP testing in three subjects from each group revealed similar test-re-test findings. Visuomotor activities improved, with reduced symptoms, with BNO in the mTBI group. It is speculated that individuals with mTBI habitually attempt to suppress visual information in the near retinal periphery to reduce their abnormal VMS, with addition of the BNO negating the suppressive influence and thus producing a widespread disinhibition effect and resultant increase in VEP amplitude.

High-intensity erotic visual stimuli de-activate the primary visual cortex in women.

PubMed

Huynh, Hieu K; Beers, Caroline; Willemsen, Antoon; Lont, Erna; Laan, Ellen; Dierckx, Rudi; Jansen, Monique; Sand, Michael; Weijmar Schultz, Willibrord; Holstege, Gert

2012-06-01

The primary visual cortex, Brodmann's area (BA 17), plays a vital role in basic survival mechanisms in humans. In most neuro-imaging studies in which the volunteers have to watch pictures or movies, the primary visual cortex is similarly activated independent of the content of the pictures or movies. However, in case the volunteers perform demanding non-visual tasks, the primary visual cortex becomes de-activated, although the amount of incoming visual sensory information is the same. Do low- and high-intensity erotic movies, compared to neutral movies, produce similar de-activation of the primary visual cortex? Brain activation/de-activation was studied by Positron Emission Tomography scanning of the brains of 12 healthy heterosexual premenopausal women, aged 18-47, who watched neutral, low- and high-intensity erotic film segments. We measured differences in regional cerebral blood flow (rCBF) in the primary visual cortex during watching neutral, low-intensity erotic, and high-intensity erotic film segments. Watching high-intensity erotic, but not low-intensity erotic movies, compared to neutral movies resulted in strong de-activation of the primary (BA 17) and adjoining parts of the secondary visual cortex. The strong de-activation during watching high-intensity erotic film might represent compensation for the increased blood supply in the brain regions involved in sexual arousal, also because high-intensity erotic movies do not require precise scanning of the visual field, because the impact is clear to the observer. © 2012 International Society for Sexual Medicine.

Japanese Encephalitis: Frequently Asked Questions

MedlinePlus

... the vaccine, what should I do? What is Japanese encephalitis? Japanese encephalitis (JE) is a potentially severe ... cause inflammation of the brain (encephalitis). Where does Japanese encephalitis occur? JE occurs in Asia and parts ...

The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs

PubMed Central

Carhart-Harris, Robin L.; Leech, Robert; Hellyer, Peter J.; Shanahan, Murray; Feilding, Amanda; Tagliazucchi, Enzo; Chialvo, Dante R.; Nutt, David

2014-01-01

Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of “primary states” is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit “criticality,” i.e., the property of being poised at a “critical” point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state. PMID:24550805

The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs.

PubMed

Carhart-Harris, Robin L; Leech, Robert; Hellyer, Peter J; Shanahan, Murray; Feilding, Amanda; Tagliazucchi, Enzo; Chialvo, Dante R; Nutt, David

2014-01-01

Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of "primary states" is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit "criticality," i.e., the property of being poised at a "critical" point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state.

Teaching Sport Skills to Brain-Injury Students: An Example in Swimming

ERIC Educational Resources Information Center

Driver, Simon; Kelly, Luke

2005-01-01

The number of people who experience a brain injury increases every year, and 40 percent of all cases involve children (Hill, 1999). In fact, this high rate has led brain injury to become the most commonly acquired disability among children (Bigge, Best, & Heller, 2001), leading to a variety of primary disabilities that affect cognition,…

Depression in adult patients with primary brain tumours: a review of independent risk factors.

PubMed

Pidani, Anum Sadruddin; Rao, Aaida Mumtaz; Shamim, Muhammad Shahzad

2018-04-01

Depression is considered an under-diagnosed problem, especially in patients with malignancies. Patients with brain tumours in particular, have a relatively higher risk of developing depression, which is multifactorial. Herein, the authors review the recent literature on the prevalence of depression in patients with brain tumours, and explore the various risk factors involved. .

Application of Lateral Brain Research to the Employability Quotient of Core Black Youth: Implications for Occupational Futuring.

ERIC Educational Resources Information Center

Toldson, Ivory L.

Lateral brain research can be used to develop an understanding and appreciation of the vocational and occupational significance of black expressive behavior manifested in some blacks. Historically, employers have placed primary emphasis on cognitive abilities--functions of the left side of the brain. Research has shown, however, that the right…

Delivery of Nano-Tethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

DTIC Science & Technology

2015-10-01

tomography images. The CT image densities in Hounsfield units (HU) of the brain were translated into corresponding optical properties (absorption...derived the Hounsfield units and optical properties of brain tissues such as white/gray matter. 13-15 The segmentation software generated an optical map...treatment protocol. Head CT image densities (in Hounsfield Units /HU) are segmented and translated into optical properties of the brain tissue

Regional differences in actomyosin contraction shape the primary vesicles in the embryonic chicken brain

NASA Astrophysics Data System (ADS)

Filas, Benjamen A.; Oltean, Alina; Majidi, Shabnam; Bayly, Philip V.; Beebe, David C.; Taber, Larry A.

2012-12-01

In the early embryo, the brain initially forms as a relatively straight, cylindrical epithelial tube composed of neural stem cells. The brain tube then divides into three primary vesicles (forebrain, midbrain, hindbrain), as well as a series of bulges (rhombomeres) in the hindbrain. The boundaries between these subdivisions have been well studied as regions of differential gene expression, but the morphogenetic mechanisms that generate these constrictions are not well understood. Here, we show that regional variations in actomyosin-based contractility play a major role in vesicle formation in the embryonic chicken brain. In particular, boundaries did not form in brains exposed to the nonmuscle myosin II inhibitor blebbistatin, whereas increasing contractile force using calyculin or ATP deepened boundaries considerably. Tissue staining showed that contraction likely occurs at the inner part of the wall, as F-actin and phosphorylated myosin are concentrated at the apical side. However, relatively little actin and myosin was found in rhombomere boundaries. To determine the specific physical mechanisms that drive vesicle formation, we developed a finite-element model for the brain tube. Regional apical contraction was simulated in the model, with contractile anisotropy and strength estimated from contractile protein distributions and measurements of cell shapes. The model shows that a combination of circumferential contraction in the boundary regions and relatively isotropic contraction between boundaries can generate realistic morphologies for the primary vesicles. In contrast, rhombomere formation likely involves longitudinal contraction between boundaries. Further simulations suggest that these different mechanisms are dictated by regional differences in initial morphology and the need to withstand cerebrospinal fluid pressure. This study provides a new understanding of early brain morphogenesis.

Brain glucose metabolism during hypoglycemia in type 1 diabetes: insights from functional and metabolic neuroimaging studies.

PubMed

Rooijackers, Hanne M M; Wiegers, Evita C; Tack, Cees J; van der Graaf, Marinette; de Galan, Bastiaan E

2016-02-01

Hypoglycemia is the most frequent complication of insulin therapy in patients with type 1 diabetes. Since the brain is reliant on circulating glucose as its main source of energy, hypoglycemia poses a threat for normal brain function. Paradoxically, although hypoglycemia commonly induces immediate decline in cognitive function, long-lasting changes in brain structure and cognitive function are uncommon in patients with type 1 diabetes. In fact, recurrent hypoglycemia initiates a process of habituation that suppresses hormonal responses to and impairs awareness of subsequent hypoglycemia, which has been attributed to adaptations in the brain. These observations sparked great scientific interest into the brain's handling of glucose during (recurrent) hypoglycemia. Various neuroimaging techniques have been employed to study brain (glucose) metabolism, including PET, fMRI, MRS and ASL. This review discusses what is currently known about cerebral metabolism during hypoglycemia, and how findings obtained by functional and metabolic neuroimaging techniques contributed to this knowledge.

State-of-the-art considerations in small cell lung cancer brain metastases

PubMed Central

Lukas, Rimas V.; Gondi, Vinai; Kamson, David O.; Kumthekar, Priya; Salgia, Ravi

2017-01-01

Background Small cell lung cancer (SCLC) frequently leads to development of brain metastases. These unfortunately continue to be associated with short survival. Substantial advances have been made in our understanding of the underlying biology of disease. This understanding on the background of previously evaluated and currently utilized therapeutic treatments can help guide the next steps in investigations into this disease with the potential to influence future treatments. Design A comprehensive review of the literature covering epidemiology, pathophysiology, imaging characteristics, prognosis, and therapeutic management of SCLC brain metastases was performed. Results SCLC brain metastases continue to have a poor prognosis. Both unique aspects of SCLC brain metastases as well as features seen more universally across other solid tumor brain metastases are discussed. Systemic therapeutic studies and radiotherapeutic approaches are reviewed. Conclusions A clearer understanding of SCLC brain metastases will help lay the framework for studies which will hopefully translate into meaningful therapeutic options for these patients. PMID:29050358

Transferrin-appended PEGylated nanoparticles for temozolomide delivery to brain: in vitro characterisation.

PubMed

Jain, Aviral; Chasoo, Gousia; Singh, Shashank K; Saxena, Ajit K; Jain, Sanjay K

2011-01-01

Polymer-based nanotechnologies are proposed to be an alternative for drug administration, delivery and targeting to those of conventional formulations. The blood brain barrier is frequently a rate-limiting factor in determining permeation of a drug into brain. In this study, the surface-engineered long-circulating PLGA nanoparticles (NPs) were assessed for brain-specific delivery. Long circulating NPs of PLGA- and PEG-synthesised copolymer were prepared by emulsification solvent evaporation method. Further, the surface of PEGylated NPs was modified by anchoring transferrin (Tf) ligand for receptor-mediated targeting to brain. NPs were characterised for shape and size, zeta potential, entrapment efficiency and in vitro drug release. In vitro cytotoxicity studies were performed on human cancer cell lines. Confocal Laser Scanning Microscopy studies show the enhanced uptake of Tf-appended PEGylated NPs and their localisation in the brain tissues. Hence, the specific role of Tf ligand on PEGylated NPs for brain delivery was confirmed.

The microenvironmental landscape of brain tumors

PubMed Central

Quail, Daniela F.; Joyce, Johanna A.

2017-01-01

The brain tumor microenvironment (TME) is emerging as a critical regulator of cancer progression in primary and metastatic brain malignancies. The unique properties of this organ require a specific framework for designing TME-targeted interventions. Here we discuss a number of these distinct features, including brain-resident cell types, the blood-brain barrier, and various aspects of the immune-suppressive environment. We also highlight recent advances in therapeutically targeting the brain TME in cancer. By developing a comprehensive understanding of the complex and interconnected microenvironmental landscape of brain malignancies we will greatly expand the range of therapeutic strategies available to target these deadly diseases. PMID:28292436

Persistent frequent attenders in primary care: costs, reasons for attendance, organisation of care and potential for cognitive behavioural therapeutic intervention.

PubMed

Morriss, Richard; Kai, Joe; Atha, Christopher; Avery, Anthony; Bayes, Sara; Franklin, Matthew; George, Tracey; James, Marilyn; Malins, Samuel; McDonald, Ruth; Patel, Shireen; Stubley, Michelle; Yang, Min

2012-07-06

The top 3% of frequent attendance in primary care is associated with 15% of all appointments in primary care, a fivefold increase in hospital expenditure, and more mental disorder and functional somatic symptoms compared to normal attendance. Although often temporary if these rates of attendance last more than two years, they may become persistent (persistent frequent or regular attendance). However, there is no long-term study of the economic impact or clinical characteristics of regular attendance in primary care. Cognitive behaviour formulation and treatment (CBT) for regular attendance as a motivated behaviour may offer an understanding of the development, maintenance and treatment of regular attendance in the context of their health problems, cognitive processes and social context. A case control design will compare the clinical characteristics, patterns of health care use and economic costs over the last 10 years of 100 regular attenders (≥30 appointments with general practitioner [GP] over 2 years) with 100 normal attenders (6-22 appointments with GP over 2 years), from purposefully selected primary care practices with differing organisation of care and patient demographics. Qualitative interviews with regular attending patients and practice staff will explore patient barriers, drivers and experiences of consultation, and organisation of care by practices with its challenges. Cognitive behaviour formulation analysed thematically will explore the development, maintenance and therapeutic opportunities for management in regular attenders. The feasibility, acceptability and utility of CBT for regular attendance will be examined. The health care costs, clinical needs, patient motivation for consultation and organisation of care for persistent frequent or regular attendance in primary care will be explored to develop training and policies for service providers. CBT for regular attendance will be piloted with a view to developing this approach as part of a multifaceted intervention.

Primary microglia isolation from mixed glial cell cultures of neonatal rat brain tissue.

PubMed

Tamashiro, Tami T; Dalgard, Clifton Lee; Byrnes, Kimberly R

2012-08-15

Microglia account for approximately 12% of the total cellular population in the mammalian brain. While neurons and astrocytes are considered the major cell types of the nervous system, microglia play a significant role in normal brain physiology by monitoring tissue for debris and pathogens and maintaining homeostasis in the parenchyma via phagocytic activity. Microglia are activated during a number of injury and disease conditions, including neurodegenerative disease, traumatic brain injury, and nervous system infection. Under these activating conditions, microglia increase their phagocytic activity, undergo morpohological and proliferative change, and actively secrete reactive oxygen and nitrogen species, pro-inflammatory chemokines and cytokines, often activating a paracrine or autocrine loop. As these microglial responses contribute to disease pathogenesis in neurological conditions, research focused on microglia is warranted. Due to the cellular heterogeneity of the brain, it is technically difficult to obtain sufficient microglial sample material with high purity during in vivo experiments. Current research on the neuroprotective and neurotoxic functions of microglia require a routine technical method to consistently generate pure and healthy microglia with sufficient yield for study. We present, in text and video, a protocol to isolate pure primary microglia from mixed glia cultures for a variety of downstream applications. Briefly, this technique utilizes dissociated brain tissue from neonatal rat pups to produce mixed glial cell cultures. After the mixed glial cultures reach confluency, primary microglia are mechanically isolated from the culture by a brief duration of shaking. The microglia are then plated at high purity for experimental study. The principle and protocol of this methodology have been described in the literature. Additionally, alternate methodologies to isolate primary microglia are well described. Homogenized brain tissue may be separated by density gradient centrifugation to yield primary microglia. However, the centrifugation is of moderate length (45 min) and may cause cellular damage and activation, as well as, cause enriched microglia and other cellular populations. Another protocol has been utilized to isolate primary microglia in a variety of organisms by prolonged (16 hr) shaking while in culture. After shaking, the media supernatant is centrifuged to isolate microglia. This longer two-step isolation method may also perturb microglial function and activation. We chiefly utilize the following microglia isolation protocol in our laboratory for a number of reasons: (1) primary microglia simulate in vivo biology more faithfully than immortalized rodent microglia cell lines, (2) nominal mechanical disruption minimizes potential cellular dysfunction or activation, and (3) sufficient yield can be obtained without passage of the mixed glial cell cultures. It is important to note that this protocol uses brain tissue from neonatal rat pups to isolate microglia and that using older rats to isolate microglia can significantly impact the yield, activation status, and functional properties of isolated microglia. There is evidence that aging is linked with microglia dysfunction, increased neuroinflammation and neurodegenerative pathologies, so previous studies have used ex vivo adult microglia to better understand the role of microglia in neurodegenerative diseases where aging is important parameter. However, ex vivo microglia cannot be kept in culture for prolonged periods of time. Therefore, while this protocol extends the life of primary microglia in culture, it should be noted that the microglia behave differently from adult microglia and in vitro studies should be carefully considered when translated to an in vivo setting.

αB-crystallin: a Novel Regulator of Breast Cancer Metastasis to the Brain

PubMed Central

Malin, Dmitry; Strekalova, Elena; Petrovic, Vladimir; Deal, Allison M.; Ahmad, Abraham Al; Adamo, Barbara; Miller, C. Ryan; Ugolkov, Andrey; Livasy, Chad; Fritchie, Karen; Hamilton, Erika; Blackwell, Kimberly; Geradts, Joseph; Ewend, Matt; Carey, Lisa; Shusta, Eric V.; Anders, Carey K.; Cryns, Vincent L.

2013-01-01

Purpose Basal-like breast tumors are typically (ER/PR/HER2) triple-negative and are associated with a high incidence of brain metastases and poor clinical outcomes. The molecular chaperone αB-crystallin is predominantly expressed in triple-negative breast cancer (TNBC) and contributes to an aggressive tumor phenotype in preclinical models. We investigated the potential role of αB-crystallin in brain metastasis in TNBC. Experimental Design αB-crystallin expression in primary breast carcinomas and brain metastases was analyzed by immunohistochemistry among breast cancer patients with brain metastases. αB-crystallin was overexpressed or silenced in two different TNBC cell lines. The effects on cell adhesion to human brain microvascular endothelial cells (HBMECs) or extracellular matrix proteins, transendothelial migration, and transmigration across a HBMEC/astrocyte co-culture blood-brain barrier (BBB) model were examined. Additionally, the effects of overexpressing or silencing αB-crystallin on brain metastasis in vivo were investigated using orthotopic TNBC models. Results In a cohort of women with breast cancer brain metastasis, αB-crystallin expression in primary breast carcinomas was associated with poor overall survival and poor survival after brain metastasis, even among TNBC patients. Stable overexpression of αB-crystallin in TNBC cells enhanced adhesion to HBMECs, transendothelial migration, and BBB transmigration in vitro, while silencing αB-crystallin inhibited these events. αB-crystallin promoted adhesion of TNBC cells to HBMECs at least in part through an α3β1 integrin-dependent mechanism. αB-crystallin overexpression promoted brain metastasis, while silencing αB-crystallin inhibited brain metastasis in orthotopic TNBC models. Conclusion αB-crystallin is a novel regulator of brain metastasis in TNBC and represents a potential biomarker and drug target for this aggressive disease. PMID:24132917

αB-crystallin: a novel regulator of breast cancer metastasis to the brain.

PubMed

Malin, Dmitry; Strekalova, Elena; Petrovic, Vladimir; Deal, Allison M; Al Ahmad, Abraham; Adamo, Barbara; Miller, C Ryan; Ugolkov, Andrey; Livasy, Chad; Fritchie, Karen; Hamilton, Erika; Blackwell, Kimberly; Geradts, Joseph; Ewend, Matt; Carey, Lisa; Shusta, Eric V; Anders, Carey K; Cryns, Vincent L

2014-01-01

Basal-like breast tumors are typically (ER/PR/HER2) triple-negative and are associated with a high incidence of brain metastases and poor clinical outcomes. The molecular chaperone αB-crystallin is predominantly expressed in triple-negative breast cancer (TNBC) and contributes to an aggressive tumor phenotype in preclinical models. We investigated the potential role of αB-crystallin in brain metastasis in TNBCs. αB-crystallin expression in primary breast carcinomas and brain metastases was analyzed by immunohistochemistry among patients with breast cancer with brain metastases. αB-crystallin was overexpressed or silenced in two different TNBC cell lines. The effects on cell adhesion to human brain microvascular endothelial cells (HBMEC) or extracellular matrix proteins, transendothelial migration, and transmigration across a HBMEC/astrocyte coculture blood-brain barrier (BBB) model were examined. In addition, the effects of overexpressing or silencing αB-crystallin on brain metastasis in vivo were investigated using orthotopic TNBC models. In a cohort of women with breast cancer brain metastasis, αB-crystallin expression in primary breast carcinomas was associated with poor overall survival and poor survival after brain metastasis, even among patients with TNBC. Stable overexpression of αB-crystallin in TNBC cells enhanced adhesion to HBMECs, transendothelial migration, and BBB transmigration in vitro, whereas silencing αB-crystallin inhibited these events. αB-crystallin promoted adhesion of TNBC cells to HBMECs, at least in part, through an α3β1 integrin-dependent mechanism. αB-crystallin overexpression promoted brain metastasis, whereas silencing αB-crystallin inhibited brain metastasis in orthotopic TNBC models. αB-crystallin is a novel regulator of brain metastasis in TNBC and represents a potential biomarker and drug target for this aggressive disease.

Genetic Alterations in Glioma

PubMed Central

Bralten, Linda B. C.; French, Pim J.

2011-01-01

Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma). This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Apart from frequent mutations in the IDH1/2 gene, much less is known about the causal genetic changes of grade II and III (anaplastic) gliomas. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively. In this review, we provide an update on all common events involved in the initiation and/or progression across the different subtypes of glioma and provide future directions for research into the genetic changes. PMID:24212656

Common High Altitudes Illnesses a Primer for Healthcare Provider

PubMed Central

Mohsenin, Vahid

2015-01-01

Exposure to high altitude imposes significant strain on cardiopulmonary system and the brain. As a consequence, sojourners to high altitude frequently experience sleep disturbances, often reporting restless and sleepless nights. At altitudes above 3,000 meters (9,800 ft) almost all healthy subjects develop periodic breathing especially during NREM sleep. Sleep architecture gradually improves with increased NREM and REM sleep despite persistence of periodic breathing. The primary reason for periodic breathing at high altitude is a hypoxic-induced increase in chemoreceptor sensitivity to changes in PaCO2 – both above and below eupnea, leading to periods of apnea and hyperpnea. Acetazolamide improves sleep by reducing the periodic breathing through development of metabolic acidosis and induced hyperventilation decreasing the plant gain and widening the PCO2 reserve. This widening of the PCO2 reserve impedes development of central apneas during sleep. Benzodiazepines and GABA receptor antagonist such as zolpidem improve sleep without affecting breathing pattern or cognitive functions. PMID:27057512

Role of surgery in brain metastases.

PubMed

Laghari, Altaf Ali; Ahmed, Syed Ijlal; Shamim, Muhammad Shahzad

2017-08-01

Brain metastases remain the commonest type of brain tumour, being four times more common than primary brain tumours. Although surgical intervention may be recommended for one of various reasons in the management of these tumours, including but not limited to conformation of diagnosis, relief of mass effect, improvement of neurological status and prolongation of survival, the guidelines for management of brain metastases remain largely subjective and therefore controversial. Herein the authors have attempted to review some of the existing evidence on role of surgery in the management of brain metastases and have presented their selected guidelines for the readers.

Whole-Brain DTI Assessment of White Matter Damage in Children with Bilateral Cerebral Palsy: Evidence of Involvement beyond the Primary Target of the Anoxic Insult.

PubMed

Arrigoni, F; Peruzzo, D; Gagliardi, C; Maghini, C; Colombo, P; Iammarrone, F Servodio; Pierpaoli, C; Triulzi, F; Turconi, A C

2016-07-01

Cerebral palsy is frequently associated with both motor and nonmotor symptoms. DTI can characterize the damage at the level of motor tracts but provides less consistent results in nonmotor areas. We used a standardized pipeline of analysis to describe and quantify the pattern of DTI white matter abnormalities of the whole brain in a group of children with chronic bilateral cerebral palsy and periventricular leukomalacia. We also explored potential correlations between DTI and clinical scale metrics. Twenty-five patients (mean age, 11.8 years) and 25 healthy children (mean age, 11.8 years) were studied at 3T with a 2-mm isotropic DTI sequence. Differences between patients and controls were assessed both voxelwise and in ROIs obtained from an existing DTI atlas. Clinical metrics included the Gross Motor Function Classification System, the Manual Ability Classification System, and intelligence quotient. The voxel-level and ROI-level analyses demonstrated highly significant (P < .001) modifications of DTI measurements in patients at several levels: cerebellar peduncles, corticospinal tracts and posterior thalamic radiations, posterior corpus callosum, external capsule, anterior thalamic radiation, superior longitudinal fasciculi and corona radiata, optic nerves, and chiasm. The reduction of fractional anisotropy values in significant tracts was between 8% and 30%. Statistically significant correlations were found between motor impairment and fractional anisotropy in corticospinal tracts and commissural and associative tracts of the supratentorial brain. We demonstrated the involvement of several motor and nonmotor areas in the chronic damage associated with periventricular leukomalacia and showed new correlations between motor skills and DTI metrics. © 2016 by American Journal of Neuroradiology.

Different shades of default mode disturbance in schizophrenia: Subnodal covariance estimation in structure and function.

PubMed

Lefort-Besnard, Jérémy; Bassett, Danielle S; Smallwood, Jonathan; Margulies, Daniel S; Derntl, Birgit; Gruber, Oliver; Aleman, Andre; Jardri, Renaud; Varoquaux, Gaël; Thirion, Bertrand; Eickhoff, Simon B; Bzdok, Danilo

2018-02-01

Schizophrenia is a devastating mental disease with an apparent disruption in the highly associative default mode network (DMN). Interplay between this canonical network and others probably contributes to goal-directed behavior so its disturbance is a candidate neural fingerprint underlying schizophrenia psychopathology. Previous research has reported both hyperconnectivity and hypoconnectivity within the DMN, and both increased and decreased DMN coupling with the multimodal saliency network (SN) and dorsal attention network (DAN). This study systematically revisited network disruption in patients with schizophrenia using data-derived network atlases and multivariate pattern-learning algorithms in a multisite dataset (n = 325). Resting-state fluctuations in unconstrained brain states were used to estimate functional connectivity, and local volume differences between individuals were used to estimate structural co-occurrence within and between the DMN, SN, and DAN. In brain structure and function, sparse inverse covariance estimates of network coupling were used to characterize healthy participants and patients with schizophrenia, and to identify statistically significant group differences. Evidence did not confirm that the backbone of the DMN was the primary driver of brain dysfunction in schizophrenia. Instead, functional and structural aberrations were frequently located outside of the DMN core, such as in the anterior temporoparietal junction and precuneus. Additionally, functional covariation analyses highlighted dysfunctional DMN-DAN coupling, while structural covariation results highlighted aberrant DMN-SN coupling. Our findings reframe the role of the DMN core and its relation to canonical networks in schizophrenia. We thus underline the importance of large-scale neural interactions as effective biomarkers and indicators of how to tailor psychiatric care to single patients. © 2017 Wiley Periodicals, Inc.

Cognitive performance in transient global hypoxic brain injury due to moderate drowning.

PubMed

Nucci, Mariana Penteado; Lukasova, Katerina; Vieira, Gilson; Sato, João Ricardo; Amaro Júnior, Edson

2018-06-01

Drowning is a serious and frequently neglected public health threat. Primary respiratory impairment after submersion often leads to brain dysfunction. Depending on the period of global hypoxia (respiratory failure), clinical aspects of neurological dysfunction are evident on the first evaluation after the water rescue. Nowadays, many neuropsychological assessments after drowning are inconclusive, with some studies reporting only minor neurological or cognitive impairments. The aim of this study is to identify measures in neuropsychological tests that most contribute to classify volunteers as moderate drowning subjects or healthy controls. To the best of our knowledge, this study is the first neuropsychological prospective case-control study of moderate drowning in a country with large coastal cities. Fifteen moderate drowning patients (DP), who met the inclusion criteria, were compared with 18 healthy controls (HC). All subjects were assessed on memory, learning, visual spatial ability, executive function, attention, and general intellectual functioning and underwent structural magnetic resonance (MR) imaging of the brain at 3.0 T, in order to exclude subjects with anatomic abnormalities. Neuropsychological tests assessing learning, execution function, and verbal fluency-Rey Auditory Verbal Learning Test (RAVLT) general learning ability, Digit Span total, Phonological Verbal Fluency (total FAS correct), and Brief Visuospatial Memory Test Revised (BVMT) correct recognition-have the strongest discriminating ability, using predictive models via the partial least squares (PLS) approach for data classification, while the other tests have shown similar predictive values between groups. Learning, execution function, and verbal fluency domains were the most critically affected domains. Serious impairments in the same domains have already been reported in severe drowning cases, and we hypothesize that subtle alterations found in moderate drowning cases, although not sufficient to be detected in daily routine, may possibly have a negative impact on cognitive reserve.

The Intracranial Volume Pressure Response in Increased Intracranial Pressure Patients: Clinical Significance of the Volume Pressure Indicator.

PubMed

Lai, Hung-Yi; Lee, Ching-Hsin; Lee, Ching-Yi

2016-01-01

For patients suffering from primary brain injury, monitoring intracranial pressure alone is not enough to reflect the dynamic intracranial condition. In our previous study, a segment of the pressure-volume curve can be expressed by the parabolic regression model with single indicator "a". The aim of this study is to evaluate if the indicator "a" can reflect intracranial conditions. Patients with traumatic brain injury, spontaneous intracranial hemorrhage, and/or hydrocephalus who had external ventricular drainage from January 2009 to February 2010 were included. The successive volume pressure response values were obtained by successive drainage of cerebral spinal fluid from intracranial pressure 20-25 mm Hg to 10 mm Hg. The relationship between withdrawn cerebral spinal fluid volume and intracranial pressure was analyzed by the parabolic regression model with single parameter "a". The overall mean for indicator "a" was 0.422 ± 0.046. The mean of "a" in hydrocephalus was 0.173 ± 0.024 and in severe intracranial mass with slender ventricle, it was 0.663 ± 0.062. The two extreme intracranial conditions had a statistical significant difference (p<0.001). The indicator "a" of a pressure-volume curve can reflect the dynamic intracranial condition and is comparable in different situations. A significantly larger indicator "a" with increased intracranial pressure is always observed in severe intracranial mass lesions with cerebral edema. A significantly smaller indicator "a" with increased intracranial pressure is observed in hydrocephalus. Brain computed tomography should be performed early if a rapid elevation of indicator "a" is detected, as it can reveal some ongoing intracranial pathology prior to clinical deterioration. Increased intracranial pressure was frequently observed in patients with intracranial pathology. The progression can be differentiated using the pattern of the volume pressure indicator.

HIV and drug abuse mediate astrocyte senescence in a β-catenin-dependent manner leading to neuronal toxicity.

PubMed

Yu, Chunjiang; Narasipura, Srinivas D; Richards, Maureen H; Hu, Xiu-Ti; Yamamoto, Bryan; Al-Harthi, Lena

2017-10-01

Emerging evidence suggests that cell senescence plays an important role in aging-associated diseases including neurodegenerative diseases. HIV leads to a spectrum of neurologic diseases collectively termed HIV-associated neurocognitive disorders (HAND). Drug abuse, particularly methamphetamine (meth), is a frequently abused psychostimulant among HIV+ individuals and its abuse exacerbates HAND. The mechanism by which HIV and meth lead to brain cell dysregulation is not entirely clear. In this study, we evaluated the impact of HIV and meth on astrocyte senescence using in vitro and several animal models. Astrocytes constitute up to 50% of brain cells and play a pivotal role in marinating brain homeostasis. We show here that HIV and meth induce significant senescence of primary human fetal astrocytes, as evaluated by induction of senescence markers (β-galactosidase and p16 INK 4A ), senescence-associated morphologic changes, and cell cycle arrest. HIV- and meth-mediated astrocyte senescence was also demonstrated in three small animal models (humanized mouse model of HIV/NSG-huPBMCs, HIV-transgenic rats, and in a meth administration rat model). Senescent astrocytes in turn mediated neuronal toxicity. Further, we show that β-catenin, a pro-survival/proliferation transcriptional co-activator, is downregulated by HIV and meth in human astrocytes and this downregulation promotes astrocyte senescence while induction of β-catenin blocks HIV- and meth-mediated astrocyte senescence. These studies, for the first time, demonstrate that HIV and meth induce astrocyte senescence and implicate the β-catenin pathway as potential therapeutic target to overcome astrocyte senescence. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Compression Stiffening of Brain and its Effect on Mechanosensing by Glioma Cells

NASA Astrophysics Data System (ADS)

Pogoda, Katarzyna

The stiffness of tissues, often characterized by their time-dependent elastic properties, is tightly controlled under normal condition and central nervous system tissue is among the softest tissues. Changes in tissue and organ stiffness occur in some physiological conditions and are frequently symptoms of diseases such as fibrosis, cardiovascular disease and many forms of cancer. Primary cells isolated from various tissues often respond to changes in the mechanical properties of their substrates, and the range of stiffness over which these responses occur appear to be limited to the tissue elastic modulus from which they are derived. Our goal was to test the hypotheses that the stiffness of tumors derived from CNS tissue differs from that of normal brain, and that transformed cells derived from such tumors exhibit mechanical responses that differ from those of normal glial cells. Unlike breast and some other cancers where the stroma and the tumor itself is substantially stiffer than the surrounding normal tissue, our data suggest that gliomas can arise without a gross change in the macroscopic tissue stiffness when measured at low strains without compression. However, both normal brain and glioma samples stiffen with compression, but not in elongation and increased shear strains. On the other hand, different classes of immortalized cells derived from human glioblastoma show substantially different responses to the stiffness of substrates in vitrowhen grown on soft polyacrylamide and hyaluronic acid gels. This outcome supports the hypothesis that compression stiffening, which might occur with increased vascularization and interstitial pressure gradients that are characteristic of tumors, effectively stiffens the environment of glioma cells, and that in situ, the elastic resistance these cells sense might be sufficient to trigger the same responses that are activated in vitro by increased substrate stiffness.

[Cancer chemotherapy with special reference to pharmacokinetics of nitrosoureas].

PubMed

Wakui, A

1982-08-01

This paper provides an overview of cancer chemotherapy with special reference to the pharmacokinetics of the nitrosoureas. At physiological PH, the chloroethylnitrosoureas can be decomposed into an isocyanate and 2-chloroethyl diazene hydroxide. Therefore, it is clear that they have both alkylation and carbamoylation actions. In addition to the spontaneous chemical dissociation, the nitrosoureas can be metabolized by liver microsomal enzymes to more polar hydroxylated products, and certain nitrosoureas can be denitrosated by these enzymes to the parent urea. Since the lipid-soluble nitrosoureas and some of the water-soluble nitrosoureas such as ACNU and MCNU demonstrated to cross the blood-brain barrier, they have been used in the treatment of primary brain tumors and tumors and tumors of metastatic origin. It has been demonstrated from the results of our study and other reports that the alkylation of DNA by ACNU progresses more slowly as compared with that of other alkylating agents. This is an important finding in relation to the appearance of delayed myelosuppression of the nitrosoureas and in the design of dose schedules of these agents. The major clinical emphasis has been directed towards the more active chloroethylnitrosoureas with reduced myelosuppression, and attempts are now made for this purpose. Unfortunately, the results of phase I and II trials of the newly developed nitrosoureas suggest that these agents produce delayed and cumulative bone marrow toxicity. Antitumor activity of the nitrosoureas is frequestly observed in chronic myelocytic leukemia, malignant lymphoma, brain tumors and small cell carcinoma of the lung, and less frequently in gastrointestinal carcinoma, multiple myeloma and malignant melanoma. In order to enhance clinical effects of the nitrosoureas, further investigation of the design in therapeutic schedules on the basis of their pharmacokinetic characteristics will be needed.

O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction.

PubMed

Brell, Marta; Ibáñez, Javier; Tortosa, Avelina

2011-01-26

The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP) the most commonly used for promoter methylation study, while immunohistochemistry (IHC) has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP. A computer-aided search of MEDLINE (1950-October 2009), EBSCO (1966-October 2009) and EMBASE (1974-October 2009) was performed for relevant publications. Studies meeting inclusion criteria were those comparing MGMT protein expression by IHC with MGMT promoter methylation by MSP in the same cohort of patients. Methodological quality was assessed by using the QUADAS and STARD instruments. Previously published guidelines were followed for meta-analysis performance. Of 254 studies identified as eligible for full-text review, 52 (20.5%) met the inclusion criteria. The review showed that results of MGMT protein expression by IHC are not in close agreement with those obtained with MSP. Moreover, type of tumour (primary brain tumour vs others) was an independent covariate of accuracy estimates in the meta-regression analysis beyond the cut-off value. Protein expression assessed by IHC alone fails to reflect the promoter methylation status of MGMT. Thus, in attempts at clinical diagnosis the two methods seem to select different groups of patients and should not be used interchangeably.

Spatial organization of neurons in the frontal pole sets humans apart from great apes.

PubMed

Semendeferi, Katerina; Teffer, Kate; Buxhoeveden, Dan P; Park, Min S; Bludau, Sebastian; Amunts, Katrin; Travis, Katie; Buckwalter, Joseph

2011-07-01

Few morphological differences have been identified so far that distinguish the human brain from the brains of our closest relatives, the apes. Comparative analyses of the spatial organization of cortical neurons, including minicolumns, can aid our understanding of the functionally relevant aspects of microcircuitry. We measured horizontal spacing distance and gray-level ratio in layer III of 4 regions of human and ape cortex in all 6 living hominoid species: frontal pole (Brodmann area [BA] 10), and primary motor (BA 4), primary somatosensory (BA 3), and primary visual cortex (BA 17). Our results identified significant differences between humans and apes in the frontal pole (BA 10). Within the human brain, there were also significant differences between the frontal pole and 2 of the 3 regions studied (BA 3 and BA 17). Differences between BA 10 and BA 4 were present but did not reach significance. These findings in combination with earlier findings on BA 44 and BA 45 suggest that human brain evolution was likely characterized by an increase in the number and width of minicolumns and the space available for interconnectivity between neurons in the frontal lobe, especially the prefrontal cortex.

Sleep and Psychiatric Disorders in Persons With Mild Traumatic Brain Injury.

PubMed

Mollayeva, Tatyana; D'Souza, Andrea; Mollayeva, Shirin

2017-08-01

Mild traumatic brain injury (mTBI) frequently challenges the integrity of sleep function by affecting multiple brain areas implicated in controlling the switch between wakefulness and sleep and those involved in circadian and homeostatic processes; the malfunction of each causes a variety of disorders. In this review, we discuss recent data on the dynamics between disorders of sleep and mental/psychiatric disorders in persons with mTBI. This analysis sets the stage for understanding how a variety of physiological, emotional and environmental influences affect sleep and mental activities after injury to the brain. Consideration of the intricate links between sleep and mental functions in future research can increase understanding on the underlying mechanisms of sleep-related and psychiatric comorbidity in mTBI.

[Quantitative evaluation of visual gnosis in children with focal brain lesions].

PubMed

Pencheva, S; Zaprianova, L

1983-01-01

Bearing in mind the opinion of many authors on a great plasticity and interchangeability of the brain cortical functional systems in children the authors have carried out an experiment with 40 children with focal damages of the brain hemispheres, in 20 of whom the right, and in the other 20 the left hemisphere was affected. Use was made of the method of visual gnosis quantitative assessment in the modification of Pencheva and Mavlov (1975). In the children with the focal damages, more or less marked disturbances of the visual gnosis were revealed, however, no statistically significant relationship between the disturbances and the brain side were disclosed. The agnostic disorders were equally frequent in the children of both groups.

Drowning stars: Reassessing the role of astrocytes in brain edema

PubMed Central

Thrane, Alexander S.; Thrane, Vinita Rangroo; Nedergaard, Maiken

2014-01-01

Edema formation frequently complicates brain infarction, tumors and trauma. Despite the significant mortality of this condition, current treatment options are often ineffective or incompletely understood. Recent studies have revealed the existence of a brain-wide paravascular pathway for cerebrospinal (CSF) and interstitial fluid (ISF) exchange. The current review critically examines the contribution of this ‘glymphatic’ system to the main types of brain edema. We propose that in cytotoxic edema, energy depletion enhances glymphatic CSF influx, whilst suppressing ISF efflux. We also argue that paravascular inflammation or ‘paravasculitis’ plays a critical role in vasogenic edema. Finally, recent advances in diagnostic imaging of glymphatic function may hold the key to defining the edema profile of individual patients and thus enable more targeted therapy. PMID:25236348

A pragmatic clinicopathobiological grouping/staging system for gliomas: proposal of the Indian TNM subcommittee on brain tumors.

PubMed

Gupta, Tejpal; Sarin, Rajiv; Jalali, Rakesh; Sharma, Suash; Kurkure, Purna; Goel, Atul

2009-01-01

There is no universally accepted staging system for primary brain tumors wherein prognostication is mainly based on complex composite indices. To develop a simple, pragmatic, and widely applicable grouping/staging system for gliomas, the most common primary brain tumor. An expert neurooncology panel with representation from radiation oncology, neurosurgery, pathology, radiology, and medical oncology had several rounds of discussion on issues pertinent to brain tumor staging. The trade off was between the accuracy of prognostic categorization and a pragmatic, widely applicable approach. The Tumor-Node-Metastasis staging was considered irrelevant for gliomas that seldom metastasize to lymphatics or outside the neuraxis. Instead, a 4-point staging/grouping system is proposed, using histological grade as the main prognostic variable and at least one stage migration based on other unfavorable features such as tumor location (brainstem); age (<5 years for all grades, >50 years for high-grade, and >40 years for low-grade gliomas); poor neurological performance status (NPS 2-4); multicentricity and/or gliomatosis; and adverse biological parameters (proliferative index, angiogenesis markers, apoptotic index, cytogenetic abnormalities, and molecular markers). In absence of a grouping/staging system for primary brain tumors, prognostification is mostly based on complex composite indices. The proposed clinicopathobiological grouping/staging system for gliomas is a simple, pragmatic, and user-friendly tool with a potential to fulfill the objectives of staging classification.

Multiple Primary and Histology Coding Rules - SEER

Cancer.gov

Download the coding manual and training resources for cases diagnosed from 2007 to 2017. Sites included are lung, breast, colon, melanoma of the skin, head and neck, kidney, renal pelvis/ureter/bladder, benign brain, and malignant brain.

Brain Vulnerability to Repeated Blast Overpressure and Polytrauma

DTIC Science & Technology

2012-05-01

shock tube: distinguishing primary and tertiary blast injury mechanisms in rat TBI - Roles of polyunsaturated fatty acids in traumatic brain injury...vulnerabilities and resilience: evaluation of salutary effects of DHA supplementation using neurolipidomics and functional outcome assessments

Memory Impairment in Korsakoff's Psychosis: A Correlation with Brain Noradrenergic Activity.

ERIC Educational Resources Information Center

McEntee, William J.; Mair, Robert G.

1978-01-01

The concentration of the primary brain metabolite of norepinephrine is diminished in the lumbar spinal fluid of patients with Korsakoff's syndrome. The extent of its reduction is correlated with measures of memory impairment. (BB)

Association of Subdural Hematoma With Increased Mortality in Lobar Intracerebral Hemorrhage

PubMed Central

Patel, Pratik V.; FitzMaurice, Emilie; Kaveer Nandigam, R. N.; Auluck, Pavan; Viswanathan, Anand; Goldstein, Joshua N.; Rosand, Jonathan; Greenberg, Steven M.; Smith, Eric E.

2011-01-01

Objective To determine the prevalence of subdural hematoma (SDH) in patients presenting with primary non-traumatic lobar intracerebral hemorrhage (ICH) and characteristics associated with the presence of SDH. Design Retrospective analysis of data collected in a prospective cohort study. Setting Hospital. Patients Consecutive sample of 200 patients with primary lobar ICH and 75 patients with deep hemispheric ICH. Main Outcome Measures Presence of SDH and mortality. Results Subdural hematoma was present in 40 of 200 patients (20%) with primary lobar ICH. By contrast, SDH was not present in any of 75 consecutive patients with deep hemispheric ICH (P<.001 for comparison with lobar ICH). Intracerebral hemorrhage volume higher than 60 cm3 was the only independent predictor of SDH (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.14–6.34; P=.02). Subdural hematoma thickness more than 5 mm was an independent predictor of increased 30-day mortality (OR, 7.60; 95% CI, 1.86–30.99; P=.005) after controlling for other factors including ICH volume. Further analysis showed that the effect of SDH on mortality depended on ICH volume, with larger odds for mortality in those with low ICH volume (OR, 12.85; 95% CI, 2.42–68.23; P=.003 for those with ICH volume <30 cm3). Cerebral amyloid angiopathy was present in 8 of 9 patients with pathological specimens. Conclusions Nontraumatic SDH frequently accompanies primary lobar ICH and is associated with higher 30-day mortality, particularly when the ICH volume is relatively low. Rupture of an amyloid-laden leptomeningeal vessel, with extravasation into the brain parenchyma and subdural space, may be the pathogenic mechanism. PMID:19139303

Validation of DTI Tractography-Based Measures of Primary Motor Area Connectivity in the Squirrel Monkey Brain

PubMed Central

Gao, Yurui; Choe, Ann S.; Stepniewska, Iwona; Li, Xia; Avison, Malcolm J.; Anderson, Adam W.

2013-01-01

Diffusion tensor imaging (DTI) tractography provides noninvasive measures of structural cortico-cortical connectivity of the brain. However, the agreement between DTI-tractography-based measures and histological ‘ground truth’ has not been quantified. In this study, we reconstructed the 3D density distribution maps (DDM) of fibers labeled with an anatomical tracer, biotinylated dextran amine (BDA), as well as DTI tractography-derived streamlines connecting the primary motor (M1) cortex to other cortical regions in the squirrel monkey brain. We evaluated the agreement in M1-cortical connectivity between the fibers labeled in the brain tissue and DTI streamlines on a regional and voxel-by-voxel basis. We found that DTI tractography is capable of providing inter-regional connectivity comparable to the neuroanatomical connectivity, but is less reliable measuring voxel-to-voxel variations within regions. PMID:24098365

Diagnostic Value of 68Ga PSMA-11 PET/CT Imaging of Brain Tumors-Preliminary Analysis.

PubMed

Sasikumar, Arun; Joy, Ajith; Pillai, M R A; Nanabala, Raviteja; Anees K, Muhammed; Jayaprakash, P G; Madhavan, Jayaprakash; Nair, Suresh

2017-01-01

To evaluate the feasibility of using Ga PSMA-11 PET/CT for imaging brain lesions and its comparison with F-FDG. Ten patients with brain lesions were included in the study. Five patients were treated cases of glioblastoma with suspected recurrence. F-FDG and Ga PSMA-11 brain scans were done for these patients. Five patients were sent for assessing the nature (primary lesion/metastasis) of space occupying lesion in brain. They underwent whole body F-FDG PET/CT scan and a primary site elsewhere in the body was ruled out. Subsequently they underwent Ga PSMA-11 brain PET/CT imaging. Target to background ratios (TBR) for the brain lesions were calculated using contralateral cerebellar uptake as background. In five treated cases of glioblastoma with suspected recurrence the findings of Ga PSMA-11 PET/CT showed good correlation with that of F-FDG PET/CT scan. Compared to the F-FDG, Ga PSMA-11 PET/CT showed better visualization of the recurrent lesion (presence/absence) owing to its significantly high TBR. Among the five cases evaluated for lesion characterization glioma and atypical meningioma patients showed higher SUVmax in the lesion with Ga PSMA-11 than with F-FDG and converse in cases of lymphoma. TBR was better with Ga PSMA PET/CT in all cases. Ga PSMA-11 PET/CT brain imaging is a potentially useful imaging tool in the evaluation of brain lesions. Absence of physiological uptake of Ga PSMA-11 in the normal brain parenchyma results in high TBR values and consequently better visualization of metabolically active disease in brain.

Perfusion MRI: The Five Most Frequently Asked Technical Questions

PubMed Central

Essig, Marco; Shiroishi, Mark S.; Nguyen, Thanh Binh; Saake, Marc; Provenzale, James M.; Enterline, David; Anzalone, Nicoletta; Dörfler, Arnd; Rovira, Àlex; Wintermark, Max; Law, Meng

2013-01-01

OBJECTIVE This and its companion article address the 10 most frequently asked questions that radiologists face when planning, performing, processing, and interpreting different MR perfusion studies in CNS imaging. CONCLUSION Perfusion MRI is a promising tool in assessing stroke, brain tumors, and patients with neurodegenerative diseases. Most of the impediments that have limited the use of perfusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols. PMID:23255738

Classifying brain metastases by their primary site of origin using a radiomics approach based on texture analysis: a feasibility study.

PubMed

Ortiz-Ramón, Rafael; Larroza, Andrés; Ruiz-España, Silvia; Arana, Estanislao; Moratal, David

2018-05-14

To examine the capability of MRI texture analysis to differentiate the primary site of origin of brain metastases following a radiomics approach. Sixty-seven untreated brain metastases (BM) were found in 3D T1-weighted MRI of 38 patients with cancer: 27 from lung cancer, 23 from melanoma and 17 from breast cancer. These lesions were segmented in 2D and 3D to compare the discriminative power of 2D and 3D texture features. The images were quantized using different number of gray-levels to test the influence of quantization. Forty-three rotation-invariant texture features were examined. Feature selection and random forest classification were implemented within a nested cross-validation structure. Classification was evaluated with the area under receiver operating characteristic curve (AUC) considering two strategies: multiclass and one-versus-one. In the multiclass approach, 3D texture features were more discriminative than 2D features. The best results were achieved for images quantized with 32 gray-levels (AUC = 0.873 ± 0.064) using the top four features provided by the feature selection method based on the p-value. In the one-versus-one approach, high accuracy was obtained when differentiating lung cancer BM from breast cancer BM (four features, AUC = 0.963 ± 0.054) and melanoma BM (eight features, AUC = 0.936 ± 0.070) using the optimal dataset (3D features, 32 gray-levels). Classification of breast cancer and melanoma BM was unsatisfactory (AUC = 0.607 ± 0.180). Volumetric MRI texture features can be useful to differentiate brain metastases from different primary cancers after quantizing the images with the proper number of gray-levels. • Texture analysis is a promising source of biomarkers for classifying brain neoplasms. • MRI texture features of brain metastases could help identifying the primary cancer. • Volumetric texture features are more discriminative than traditional 2D texture features.

TMOD-05. MOLECULAR CHARACTERIZATION OF ORTHOTOPIC PATIENT-DERIVED XENOGRAFT MODELS OF PEDIATRIC BRAIN TUMORS AND THEIR USE IN PRECLINICAL EXPERIMENTS

PubMed Central

Brabetz, Sebastian; Schmidt, Christin; Groebner, Susanne N.; Mack, Norman; Seker-Cin, Huriye; Jones, David T.W.; Chavez, Lukas; Milde, Till; Witt, Olaf; Leary, Sarah E.; Li, Xiao-Nan; Wechsler-Reya, Robert J.; Olson, James M.; Pfister, Stefan M.; Kool, Marcel

2017-01-01

Abstract Genomic studies have shown that multiple molecular subtypes of pediatric brain tumors exist that are biologically and clinically highly distinct. These findings ask for novel subtype specific treatments. To develop these we need more and better preclinical models that correctly reflect the proper tumor (sub)type. Orthotopic patient-derived xenograft (PDX) models generated by intracranial injection of primary patient material into the brain of NSG mice offer the unique possibility to test novel substances in primary patient tissue in an in vivo environment. Prior to drug selection and testing, extensive molecular characterizations of PDX and matching primary tumor/blood (DNA methylation, DNA sequencing, and gene expression) are needed to see how the PDX represents the original disease and to learn about targetable oncogenic drivers in each model. In collaboration with several groups around the world we have generated and fully characterized thus far 75 PDX models reflecting 15 distinct subtypes of pediatric brain cancer. PDX models always retain their molecular subtype and in the vast majority of cases also mutations and copy number alterations compared to matching primary tumors. Most aggressive tumors, harboring MYC(N) amplifications, are overrepresented in the cohort, but also subtypes which have not been available for preclinical testing before due to lack of genetically engineered mouse models or suitable cell lines, such as Group 4 medulloblastoma, are included. All models and corresponding molecular data will become available for the community for preclinical research. Examples of such preclinical experiments will be presented. PDX models of pediatric brain tumors are still quite rare. Our repertoire of PDX models and corresponding molecular characterizations allow researchers all over the world to find the right models for their specific scientific questions. It will provide an unprecedented resource to study tumor biology and pave the way for improving treatment strategies for children with malignant brain tumors.

Differential coding of hyperalgesia in the human brain: a functional MRI study.

PubMed

Maihöfner, Christian; Handwerker, Hermann O

2005-12-01

Neuropathic pain can be both ongoing or stimulus-induced. Stimulus-induced pain, also known as hyperalgesia, can be differentiated into primary and secondary hyperalgesia. The former results from sensitization of peripheral nociceptive structures, the latter involves sensitization processes within the central nervous system (CNS). Hypersensitivity towards heat stimuli, i.e. thermal hyperalgesia, is a key feature of primary hyperalgesia, whereas secondary hyperalgesia is characterized by hypersensitivity towards mechanical (e.g. pin-prick) stimulation. Using functional magnetic resonance imaging (fMRI), we investigated if brain activation patterns associated with primary and secondary hyperalgesia might differ. Thermal and pin-prick hyperalgesia were induced on the left forearm in 12 healthy subjects by topical capsaicin (2.5%, 30 min) application. Equal pain intensities of both hyperalgesia types were applied during fMRI experiments, based on previous quantitative sensory testing. Simultaneously, subjects had to rate the unpleasantness of stimulus-related pain. Pin-prick hyperalgesia (i.e. subtraction of brain activations during pin-prick stimulation before and after capsaicin exposure) led to activations of primary and secondary somatosensory cortices (S1 and S2), associative-somatosensory cortices, insula and superior and inferior frontal cortices (SFC, IFC). Brain areas activated during thermal hyperalgesia (i.e. subtraction of brain activations during thermal stimulation before and after capsaicin exposure) were S1 and S2, insula, associative-somatosensory cortices, cingulate cortex (GC), SFC, middle frontal cortex (MFC) and IFC. When compared to pin-prick hyperalgesia, thermal hyperalgesia led to an increased activation of bilateral anterior insular cortices, MFC, GC (Brodmann area 24' and 32') and contralateral SFC and IFC, despite equal pain intensities. Interestingly, stronger activations of GC, contralateral MFC and anterior insula significantly correlated to higher ratings of the stimulus-related unpleasantness. We conclude that thermal and mechanical hyperalgesia produce substantially different brain activation patterns. This is linked to different psychophysical properties.

Combination of blood flow asymmetry in the cerebral and cerebellar hemispheres on brain perfusion SPECT predicts 5-year outcome in patients with symptomatic unilateral major cerebral artery occlusion.

PubMed

Nomura, Jun-ichi; Ogasawara, Kuniaki; Saito, Hideo; Terasaki, Kazunori; Matsumoto, Yoshiyasu; Takahashi, Yoshihiro; Ogasawara, Yasushi; Saura, Hiroaki; Yoshida, Koji; Sato, Yuiko; Kubo, Yoshitaka; Ogawa, Akira

2014-03-01

Misery perfusion increases the risk of stroke recurrence in patients with symptomatic major cerebral artery occlusion. The ratio of brain perfusion contralateral-to-affected asymmetry in the cerebellar hemisphere to brain perfusion affected-to-contralateral asymmetry in the cerebral hemisphere (CblPR/CbrPR) indicates affected-to-contralateral asymmetry of oxygen extraction fraction (OEF) in the cerebral hemisphere. The purpose of the present study was to determine whether the CblPR/CbrPR on brain perfusion single-photon emission computed tomography (SPECT) predicts 5-year outcomes in patients with symptomatic unilateral occlusion of the middle cerebral artery (MCA) or internal carotid artery (ICA). Brain perfusion was assessed using N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) SPECT in 70 patients. A region of interest (ROI) was manually placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres, and the CblPR/CbrPR was calculated. All patients were prospectively followed for 5 years. The primary end points were stroke recurrence or death. A total of 17 patients exhibited the primary end points, 11 of whom experienced subsequent ipsilateral strokes. Multivariate analysis revealed that only high CblPR/CbrPR was significantly associated with the development of the primary end point or subsequent ipsilateral strokes (95% confidential limits [CIs], 1.130-3.145; P  =  0.0114 or 95% CIs, 2.558-5.140; P  =  0.0045, respectively). The CblPR/CbrPR provided 65% (11/17) or 91% (10/11) sensitivity and 88% (47/53) or 88% (52/59) specificity in predicting the primary end point or subsequent ipsilateral strokes, respectively. The CblPR/CbrPR on brain perfusion SPECT predicts 5-year outcomes in patients with symptomatic unilateral occlusion of the MCA or ICA.

BrainPhys® increases neurofilament levels in CNS cultures, and facilitates investigation of axonal damage after a mechanical stretch-injury in vitro.

PubMed

Jackson, Travis C; Kotermanski, Shawn E; Jackson, Edwin K; Kochanek, Patrick M

2018-02-01

Neurobasal®/B27 is a gold standard culture media used to study primary neurons in vitro. An alternative media (BrainPhys®/SM1) was recently developed which robustly enhances neuronal activity vs. Neurobasal® or DMEM. To the best of our knowledge BrainPhys® has not been explored in the setting of neuronal injury. Here we characterized the utility of BrainPhys® in a model of in vitro mechanical-stretch injury. Primary rat cortical neurons were maintained in classic Neurobasal®, or sequentially maintained in Neurocult® followed by BrainPhys® (hereafter simply referred to as "BrainPhys® maintained neurons"). The levels of axonal markers and proteins involved in neurotransmission were compared on day in vitro 10 (DIV10). BrainPhys® maintained neurons had higher levels of GluN2B, GluR1, Neurofilament light/heavy chain (NF-L & NF-H), and protein phosphatase 2 A (PP2A) vs. neurons in Neurobasal®. Mechanical stretch-injury (50ms/54% biaxial stretch) to BrainPhys® maintained neurons modestly (albeit significantly) increased 24h lactate dehydrogenase (LDH) levels but markedly decreased axonal NF-L levels post-injury vs. uninjured controls or neurons given a milder 38% stretch-injury. Furthermore, two 54% stretch-injuries (in tandem) exacerbated 24h LDH release, increased α-spectrin breakdown products (SBDPs), and decreased Tau levels. Also, BrainPhys® maintained cultures had decreased markers of cell damage 24h after a single 54% stretch-injury vs. neurons in Neurobasal®. Finally, we tested the hypothesis that lentivirus mediated overexpression of the pro-death protein RBM5 exacerbates neuronal and/or axonal injury in primary CNS cultures. RBM5 overexpression vs. empty-vector controls increased 24h LDH release, and SBDP levels, after a single 54% stretch-injury but did not affect NF-L levels or Tau. BrainPhys® is a promising new reagent which facilities the investigation of molecular targets involved in axonal and/or neuronal injury in vitro. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Detection of Blast-Related Traumatic Brain Injury in U.S. Military Personnel

PubMed Central

Mac Donald, Christine L.; Johnson, Ann M.; Cooper, Dana; Nelson, Elliot C.; Werner, Nicole J.; Shimony, Joshua S.; Snyder, Abraham Z.; Raichle, Marcus E.; Witherow, John R.; Fang, Raymond; Flaherty, Stephen F.; Brody, David L.

2011-01-01

BACKGROUND Blast-related traumatic brain injuries have been common in the Iraq and Afghanistan wars, but fundamental questions about the nature of these injuries remain unanswered. METHODS We tested the hypothesis that blast-related traumatic brain injury causes traumatic axonal injury, using diffusion tensor imaging (DTI), an advanced form of magnetic resonance imaging that is sensitive to axonal injury. The subjects were 63 U.S. military personnel who had a clinical diagnosis of mild, uncomplicated traumatic brain injury. They were evacuated from the field to the Landstuhl Regional Medical Center in Landstuhl, Germany, where they underwent DTI scanning within 90 days after the injury. All the subjects had primary blast exposure plus another, blast-related mechanism of injury (e.g., being struck by a blunt object or injured in a fall or motor vehicle crash). Controls consisted of 21 military personnel who had blast exposure and other injuries but no clinical diagnosis of traumatic brain injury. RESULTS Abnormalities revealed on DTI were consistent with traumatic axonal injury in many of the subjects with traumatic brain injury. None had detectible intracranial injury on computed tomography. As compared with DTI scans in controls, the scans in the subjects with traumatic brain injury showed marked abnormalities in the middle cerebellar peduncles (P<0.001), in cingulum bundles (P = 0.002), and in the right orbitofrontal white matter (P = 0.007). In 18 of the 63 subjects with traumatic brain injury, a significantly greater number of abnormalities were found on DTI than would be expected by chance (P<0.001). Follow-up DTI scans in 47 subjects with traumatic brain injury 6 to 12 months after enrollment showed persistent abnormalities that were consistent with evolving injuries. CONCLUSIONS DTI findings in U.S. military personnel support the hypothesis that blast-related mild traumatic brain injury can involve axonal injury. However, the contribution of primary blast exposure as compared with that of other types of injury could not be determined directly, since none of the subjects with traumatic brain injury had isolated primary blast injury. Furthermore, many of these subjects did not have abnormalities on DTI. Thus, traumatic brain injury remains a clinical diagnosis. (Funded by the Congressionally Directed Medical Research Program and the National Institutes of Health; ClinicalTrials.gov number, NCT00785304.) PMID:21631321

Impact of microRNA-134 on neural cell survival against ischemic injury in primary cultured neuronal cells and mouse brain with ischemic stroke by targeting HSPA12B.

PubMed

Chi, Wenying; Meng, Fanjun; Li, Yan; Li, Peilong; Wang, Guizhi; Cheng, Hong; Han, Song; Li, Junfa

2014-12-10

As a newly discovered member of the HSP70 family, heat shock protein A12B (HSPA12B) is involved in brain ischemic injury. According to our previous study, microRNA-134 (miR-134) could target HSPA12B by binding to its 3'-untranslated region (UTR). However, the regulation of miR-134 on HSPA12B and their role in protecting neuronal cells from ischemic injury are unclear. In this study, the miR-134 expression level was manipulated, and the HSPA12B protein levels were also determined in oxygen-glucose deprivation (OGD)-treated primary cultured neuronal cells in vitro and mouse brain after middle cerebral artery occlusion (MCAO)-induced ischemic stroke in vivo. The results showed that miR-134 expression levels increased in primary cultured neuronal cells and mouse brain from 12h to 7 day reoxygenation/reperfusion after 1h OGD or 1h MCAO treatment. miR-134 overexpression promoted neuronal cell death and apoptosis by decreasing HSPA12B protein levels. Conversely, downregulating miR-134 reduced neuronal cell death and apoptosis by enhancing HSPA12B protein levels. Also, HSPA12B siRNA could block miR-134 inhibitor-mediated neuroprotection against OGD-induced neuronal cell injury in vitro. Taken together, miR-134 might influence neuronal cell survival against ischemic injury in primary cultured neuronal cells and mouse brain with ischemic stroke by negatively modulating HSPA12B protein expression in a posttranscriptional manner. Copyright © 2014 Elsevier B.V. All rights reserved.

[Neurological disorders and the blood-brain barrier. Strategies and limitations for drug delivery to the brain].

PubMed

Domínguez, Alazne; Álvarez, Antonia; Suárez-Merino, Blanca; Goñi-de-Cerio, Felipe

2014-03-01

The incidence in the central nervous system diseases has increased with a growing elderly population. Unfortunately, conventional treatments used to treat the mentioned diseases are frequently ineffective due to the presence of the blood brain barrier. To illustrate the blood-brain barrier properties that limit drug transport into the brain and the main strategies employed to treat neurologic disorders. The blood-brain barrier is mainly composed of a specialized microvascular endothelium and of glial cells. It constitutes a valuable tool to separate the central nervous system from the rest of the body. Nevertheless, it also represents an obstacle to the delivery of therapeutic drugs to the brain. To be effective, drugs must reach their target in the brain. On one hand, therapeutic agents could be designed to be able to cross the blood brain barrier. On the other hand, drug delivery systems could be employed to facilitate the therapeutic agents' entry into the central nervous system. In vivo models of neurological diseases, in addition to in vitro models of the blood brain barrier, have been widely employed for the evaluation of drugs utilized to treat central nervous system diseases.

Expression of Shiga toxin 2e glycosphingolipid receptors of primary porcine brain endothelial cells and toxin-mediated breakdown of the blood-brain barrier.

PubMed

Meisen, Iris; Rosenbrück, Regina; Galla, Hans-Joachim; Hüwel, Sabine; Kouzel, Ivan U; Mormann, Michael; Karch, Helge; Müthing, Johannes

2013-06-01

Shiga toxin (Stx) 2e, released by certain Stx-producing Escherichia coli, is presently the best characterized virulence factor responsible for pig edema disease, which is characterized by hemorrhagic lesions, neurological disorders and often fatal outcomes. Although Stx2e-mediated brain vascular injury is the key event in development of neurologic signs, the glycosphingolipid (GSL) receptors of Stx2e and toxin-mediated impairment of pig brain endothelial cells have not been investigated so far. Here, we report on the detailed structural characterization of Stx2e receptors globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer), which make up the major neutral GSLs in primary porcine brain capillary endothelial cells (PBCECs). Various Gb3Cer and Gb4Cer lipoforms harboring sphingenine (d18:1) or sphinganine (d18:0) and mostly a long-chain fatty acid (C20-C24) were detected. A notable batch-to-batch heterogeneity of primary endothelial cells was observed regarding the extent of ceramide hydroxylation of Gb3Cer or Gb4Cer species. Gb3Cer, Gb4Cer and sphingomyelin preferentially distribute to detergent-resistant membrane fractions and can be considered lipid raft markers in PBCECs. Moreover, we employed an in vitro model of the blood-brain barrier (BBB), which exhibited strong cytotoxic effects of Stx2e on the endothelial monolayer and a rapid collapse of the BBB. These data strongly suggest the involvement of Stx2e in cerebral vascular damage with resultant neurological disturbance characteristic of edema disease.

Gene expression profiles help identify the tissue of origin for metastatic brain cancers.

PubMed

Wu, Alan H B; Drees, Julia C; Wang, Hangpin; VandenBerg, Scott R; Lal, Anita; Henner, William D; Pillai, Raji

2010-04-26

Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA) is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3%) cases. This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers.

Gene expression profiles help identify the Tissue of Origin for metastatic brain cancers

PubMed Central

2010-01-01

Background Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork® Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA) is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Methods Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Results Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3%) cases. Discussion This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers. PMID:20420692

Secondary brain injuries in thalamus and hippocampus after focal ischemia caused by mild, transient extradural compression of the somatosensori cortex in the rat.

PubMed

Holmberg, Per; Liljequist, Sture; Wägner, Anna

2009-02-01

The development and distribution of secondary brain lesions, subsequent to ischemic stroke, are of considerable clinical interest but so far only a limited number of studies have investigated the distribution and development of these secondary lesions in detail. In this study, we used an animal model of focal ischemia caused by extradural compression of the sensorimotor cortex. This paradigm of focal ischemia was shown to produce a consistent pattern of secondary lesions located distally from the primary lesion. Functionally the primary brain lesion produced a transient neurological deficit, which was evaluated by daily beam walking tests. Morphological changes were assessed in parallel after the ischemic event using Fluoro-Jade (FJ) staining as a marker of neuronal cell death. Secondary brain lesions were observed in the thalamus as well as in the hippocampus. The first sign of the slowly developing secondary brain lesions was present on day 3 with subsequent lesions being identified until day 16 after the primary ischemia. In addition to the identification of neuronal cell death by the FJ assays, immunostaining for parvalbumin (PA), a marker of GABAergic interneurons, revealed a loss of PA-staining in the pyramidal layer of CA1 on day 3, thus showing a similar time pattern for loss of PA-staining as for the loss of FJ stained cells. Based upon our present results, we suggest that the current animal model of focal ischemia represents a valuable tool for studies concerning the development of secondary remote brain lesions and their association to impaired motor and cognitive functions.

Spinal Cord Injury Disrupts Resting-State Networks in the Human Brain.

PubMed

Hawasli, Ammar H; Rutlin, Jerrel; Roland, Jarod L; Murphy, Rory K J; Song, Sheng-Kwei; Leuthardt, Eric C; Shimony, Joshua S; Ray, Wilson Z

2018-03-15

Despite 253,000 spinal cord injury (SCI) patients in the United States, little is known about how SCI affects brain networks. Spinal MRI provides only structural information with no insight into functional connectivity. Resting-state functional MRI (RS-fMRI) quantifies network connectivity through the identification of resting-state networks (RSNs) and allows detection of functionally relevant changes during disease. Given the robust network of spinal cord afferents to the brain, we hypothesized that SCI produces meaningful changes in brain RSNs. RS-fMRIs and functional assessments were performed on 10 SCI subjects. Blood oxygen-dependent RS-fMRI sequences were acquired. Seed-based correlation mapping was performed using five RSNs: default-mode (DMN), dorsal-attention (DAN), salience (SAL), control (CON), and somatomotor (SMN). RSNs were compared with normal control subjects using false-discovery rate-corrected two way t tests. SCI reduced brain network connectivity within the SAL, SMN, and DMN and disrupted anti-correlated connectivity between CON and SMN. When divided into separate cohorts, complete but not incomplete SCI disrupted connectivity within SAL, DAN, SMN and DMN and between CON and SMN. Finally, connectivity changed over time after SCI: the primary motor cortex decreased connectivity with the primary somatosensory cortex, the visual cortex decreased connectivity with the primary motor cortex, and the visual cortex decreased connectivity with the sensory parietal cortex. These unique findings demonstrate the functional network plasticity that occurs in the brain as a result of injury to the spinal cord. Connectivity changes after SCI may serve as biomarkers to predict functional recovery following an SCI and guide future therapy.

Surgery for brain metastases: An analysis of outcomes and factors affecting survival.

PubMed

Sivasanker, Masillamany; Madhugiri, Venkatesh S; Moiyadi, Aliasgar V; Shetty, Prakash; Subi, T S

2018-05-01

For patients who develop brain metastases from solid tumors, age, KPS, primary tumor status and presence of extracranial metastases have been identified as prognostic factors. However, the factors that affect survival in patients who are deemed fit to undergo resection of brain metastases have not been clearly elucidated hitherto. This is a retrospective analysis of a prospectively maintained database. All patients who underwent resection of intracranial metastases from solid tumors were included. Various patient, disease and treatment related factors were analyzed to assess their impact on survival. Overall, 124 patients had undergone surgery for brain metastases from various primary sites. The median age and pre-operative performance score were 53 years and 80 respectively. Synchronous metastases were resected in 17.7% of the patients. The postoperative morbidity and mortality rates were 17.7% and 2.4% respectively. Adjuvant whole brain radiation was received by 64 patients. At last follow-up, 8.1% of patients had fresh post-surgical neurologic deficits. The median progression free and overall survival were 6.91 was 8.56 months respectively. Surgical resection of for brain metastases should be considered in carefully selected patients. Gross total resection and receiving adjuvant whole brain RT significantly improves survival in these patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Active tactile exploration using a brain-machine-brain interface.

PubMed

O'Doherty, Joseph E; Lebedev, Mikhail A; Ifft, Peter J; Zhuang, Katie Z; Shokur, Solaiman; Bleuler, Hannes; Nicolelis, Miguel A L

2011-10-05

Brain-machine interfaces use neuronal activity recorded from the brain to establish direct communication with external actuators, such as prosthetic arms. It is hoped that brain-machine interfaces can be used to restore the normal sensorimotor functions of the limbs, but so far they have lacked tactile sensation. Here we report the operation of a brain-machine-brain interface (BMBI) that both controls the exploratory reaching movements of an actuator and allows signalling of artificial tactile feedback through intracortical microstimulation (ICMS) of the primary somatosensory cortex. Monkeys performed an active exploration task in which an actuator (a computer cursor or a virtual-reality arm) was moved using a BMBI that derived motor commands from neuronal ensemble activity recorded in the primary motor cortex. ICMS feedback occurred whenever the actuator touched virtual objects. Temporal patterns of ICMS encoded the artificial tactile properties of each object. Neuronal recordings and ICMS epochs were temporally multiplexed to avoid interference. Two monkeys operated this BMBI to search for and distinguish one of three visually identical objects, using the virtual-reality arm to identify the unique artificial texture associated with each. These results suggest that clinical motor neuroprostheses might benefit from the addition of ICMS feedback to generate artificial somatic perceptions associated with mechanical, robotic or even virtual prostheses.

Developmental analysis of the dopamine-containing neurons of the Drosophila brain

PubMed Central

Hartenstein, Volker; Cruz, Louie; Lovick, Jennifer K.; Guo, Ming

2016-01-01

The Drosophila dopaminergic (DA) system consists of a relatively small number of neurons clustered throughout the brain and ventral nerve cord. Previous work shows that clusters of DA neurons innervate different brain compartments, which in part accounts for functional diversity of the DA system. In this paper, we analyzed the association between DA neuron clusters and specific brain lineages, developmental and structural units of the Drosophila brain which provide a framework of connections that can be followed throughout development. The hatching larval brain contains six groups of primary DA neurons (born in the embryo), which we assign to six distinct lineages. We can show that all larval DA clusters persist into the adult brain. Some clusters increase in cell number during late larval stages while others do not become DA-positive until early pupa. Ablating neuroblasts with hydroxyurea (HU) prior to onset of larval proliferation (generates secondary neurons) confirms these added DA clusters are primary neurons born in the embryo, rather than secondary neurons. A single cluster that becomes DA-positive in the late pupa, PAM1/lineage DALcm1/2, forms part of a secondary lineage which can be ablated by larval HU application. By supplying lineage information for each DA cluster, our analysis promotes further developmental and functional analyses of this important system of neurons. PMID:27350102

Glucose-Coated Gold Nanoparticles Transfer across Human Brain Endothelium and Enter Astrocytes In Vitro

PubMed Central

Gromnicova, Radka; Davies, Heather A.; Sreekanthreddy, Peddagangannagari; Romero, Ignacio A.; Lund, Torben; Roitt, Ivan M.; Phillips, James B.; Male, David K.

2013-01-01

The blood-brain barrier prevents the entry of many therapeutic agents into the brain. Various nanocarriers have been developed to help agents to cross this barrier, but they all have limitations, with regard to tissue-selectivity and their ability to cross the endothelium. This study investigated the potential for 4 nm coated gold nanoparticles to act as selective carriers across human brain endothelium and subsequently to enter astrocytes. The transfer rate of glucose-coated gold nanoparticles across primary human brain endothelium was at least three times faster than across non-brain endothelia. Movement of these nanoparticles occurred across the apical and basal plasma membranes via the cytosol with relatively little vesicular or paracellular migration; antibiotics that interfere with vesicular transport did not block migration. The transfer rate was also dependent on the surface coating of the nanoparticle and incubation temperature. Using a novel 3-dimensional co-culture system, which includes primary human astrocytes and a brain endothelial cell line hCMEC/D3, we demonstrated that the glucose-coated nanoparticles traverse the endothelium, move through the extracellular matrix and localize in astrocytes. The movement of the nanoparticles through the matrix was >10 µm/hour and they appeared in the nuclei of the astrocytes in considerable numbers. These nanoparticles have the correct properties for efficient and selective carriers of therapeutic agents across the blood-brain barrier. PMID:24339894

Mind, Brain, and Education: Building a Scientific Groundwork for Learning and Teaching

ERIC Educational Resources Information Center

Fischer, Kurt W.

2009-01-01

The primary goal of the emerging field of Mind, Brain, and Education is to join biology, cognitive science, development, and education in order to create a sound grounding of education in research. The growing, worldwide movement needs to avoid the myths and distortions of popular conceptions of brain and genetics and build on the best integration…

Allostasis and the Human Brain: Integrating Models of Stress from the Social and Life Sciences

ERIC Educational Resources Information Center

Ganzel, Barbara L.; Morris, Pamela A.; Wethington, Elaine

2010-01-01

We draw on the theory of allostasis to develop an integrative model of the current stress process that highlights the brain as a dynamically adapting interface between the changing environment and the biological self. We review evidence that the core emotional regions of the brain constitute the primary mediator of the well-established association…

If You Had My Brain, Where Would I Be? Children's Understanding of the Brain and Identity.

ERIC Educational Resources Information Center

Johnson, Carl Nils

1990-01-01

Reveals that during the elementary school years, children acquire a firm understanding of the brain as the primary locus of psychological attributes and identity. The early school years, when children are five to seven years old, appear to be a transitional phase, when performance is variable and subject to task conditions. (RH)

Comparison of a Rat Primary Cell-Based Blood-Brain Barrier Model With Epithelial and Brain Endothelial Cell Lines: Gene Expression and Drug Transport.

PubMed

Veszelka, Szilvia; Tóth, András; Walter, Fruzsina R; Tóth, Andrea E; Gróf, Ilona; Mészáros, Mária; Bocsik, Alexandra; Hellinger, Éva; Vastag, Monika; Rákhely, Gábor; Deli, Mária A

2018-01-01

Cell culture-based blood-brain barrier (BBB) models are useful tools for screening of CNS drug candidates. Cell sources for BBB models include primary brain endothelial cells or immortalized brain endothelial cell lines. Despite their well-known differences, epithelial cell lines are also used as surrogate models for testing neuropharmaceuticals. The aim of the present study was to compare the expression of selected BBB related genes including tight junction proteins, solute carriers (SLC), ABC transporters, metabolic enzymes and to describe the paracellular properties of nine different culture models. To establish a primary BBB model rat brain capillary endothelial cells were co-cultured with rat pericytes and astrocytes (EPA). As other BBB and surrogate models four brain endothelial cells lines, rat GP8 and RBE4 cells, and human hCMEC/D3 cells with or without lithium treatment (D3 and D3L), and four epithelial cell lines, native human intestinal Caco-2 and high P-glycoprotein expressing vinblastine-selected VB-Caco-2 cells, native MDCK and MDR1 transfected MDCK canine kidney cells were used. To test transporter functionality, the permeability of 12 molecules, glucopyranose, valproate, baclofen, gabapentin, probenecid, salicylate, rosuvastatin, pravastatin, atorvastatin, tacrine, donepezil, was also measured in the EPA and epithelial models. Among the junctional protein genes, the expression level of occludin was high in all models except the GP8 and RBE4 cells, and each model expressed a unique claudin pattern. Major BBB efflux (P-glycoprotein or ABCB1) and influx transporters (GLUT-1, LAT-1) were present in all models at mRNA levels. The transcript of BCRP (ABCG2) was not expressed in MDCK, GP8 and RBE4 cells. The absence of gene expression of important BBB efflux and influx transporters BCRP, MRP6, -9, MCT6, -8, PHT2, OATPs in one or both types of epithelial models suggests that Caco-2 or MDCK models are not suitable to test drug candidates which are substrates of these transporters. Brain endothelial cell lines GP8, RBE4, D3 and D3L did not form a restrictive paracellular barrier necessary for screening small molecular weight pharmacons. Therefore, among the tested culture models, the primary cell-based EPA model is suitable for the functional analysis of the BBB.

A BRCA1 deficient-like signature is enriched in breast cancer brain metastases and predicts DNA damage-induced poly (ADP-ribose) polymerase inhibitor sensitivity.

PubMed

McMullin, Ryan P; Wittner, Ben S; Yang, Chuanwei; Denton-Schneider, Benjamin R; Hicks, Daniel; Singavarapu, Raj; Moulis, Sharon; Lee, Jeongeun; Akbari, Mohammad R; Narod, Steven A; Aldape, Kenneth D; Steeg, Patricia S; Ramaswamy, Sridhar; Sgroi, Dennis C

2014-03-14

There is an unmet clinical need for biomarkers to identify breast cancer patients at an increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with human epidermal growth factor receptor 2-positive (HER2+) brain metastasis. We combined laser capture microdissection and gene expression microarrays to analyze malignant epithelium from HER2+ breast cancer brain metastases with that from HER2+ nonmetastatic primary tumors. Differential gene expression was performed including gene set enrichment analysis (GSEA) using publicly available breast cancer gene expression data sets. In a cohort of HER2+ breast cancer brain metastases, we identified a gene expression signature that anti-correlates with overexpression of BRCA1. Sequence analysis of the HER2+ brain metastases revealed no pathogenic mutations of BRCA1, and therefore the aforementioned signature was designated BRCA1 Deficient-Like (BD-L). Evaluation of an independent cohort of breast cancer metastases demonstrated that BD-L values are significantly higher in brain metastases as compared to other metastatic sites. Although the BD-L signature is present in all subtypes of breast cancer, it is significantly higher in BRCA1 mutant primary tumors as compared with sporadic breast tumors. Additionally, BD-L signature values are significantly higher in HER2-/ER- primary tumors as compared with HER2+/ER + and HER2-/ER + tumors. The BD-L signature correlates with breast cancer cell line pharmacologic response to a combination of poly (ADP-ribose) polymerase (PARP) inhibitor and temozolomide, and the signature outperformed four published gene signatures of BRCA1/2 deficiency. A BD-L signature is enriched in HER2+ breast cancer brain metastases without pathogenic BRCA1 mutations. Unexpectedly, elevated BD-L values are found in a subset of primary tumors across all breast cancer subtypes. Evaluation of pharmacological sensitivity in breast cancer cell lines representing all breast cancer subtypes suggests the BD-L signature may serve as a biomarker to identify sporadic breast cancer patients who might benefit from a therapeutic combination of PARP inhibitor and temozolomide and may be indicative of a dysfunctional BRCA1-associated pathway.

A BRCA1 deficient-like signature is enriched in breast cancer brain metastases and predicts DNA damage-induced poly (ADP-ribose) polymerase inhibitor sensitivity

PubMed Central

2014-01-01

Introduction There is an unmet clinical need for biomarkers to identify breast cancer patients at an increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with human epidermal growth factor receptor 2-positive (HER2+) brain metastasis. Methods We combined laser capture microdissection and gene expression microarrays to analyze malignant epithelium from HER2+ breast cancer brain metastases with that from HER2+ nonmetastatic primary tumors. Differential gene expression was performed including gene set enrichment analysis (GSEA) using publicly available breast cancer gene expression data sets. Results In a cohort of HER2+ breast cancer brain metastases, we identified a gene expression signature that anti-correlates with overexpression of BRCA1. Sequence analysis of the HER2+ brain metastases revealed no pathogenic mutations of BRCA1, and therefore the aforementioned signature was designated BRCA1 Deficient-Like (BD-L). Evaluation of an independent cohort of breast cancer metastases demonstrated that BD-L values are significantly higher in brain metastases as compared to other metastatic sites. Although the BD-L signature is present in all subtypes of breast cancer, it is significantly higher in BRCA1 mutant primary tumors as compared with sporadic breast tumors. Additionally, BD-L signature values are significantly higher in HER2-/ER- primary tumors as compared with HER2+/ER + and HER2-/ER + tumors. The BD-L signature correlates with breast cancer cell line pharmacologic response to a combination of poly (ADP-ribose) polymerase (PARP) inhibitor and temozolomide, and the signature outperformed four published gene signatures of BRCA1/2 deficiency. Conclusions A BD-L signature is enriched in HER2+ breast cancer brain metastases without pathogenic BRCA1 mutations. Unexpectedly, elevated BD-L values are found in a subset of primary tumors across all breast cancer subtypes. Evaluation of pharmacological sensitivity in breast cancer cell lines representing all breast cancer subtypes suggests the BD-L signature may serve as a biomarker to identify sporadic breast cancer patients who might benefit from a therapeutic combination of PARP inhibitor and temozolomide and may be indicative of a dysfunctional BRCA1-associated pathway. PMID:24625110

Epicenters of dynamic connectivity in the adaptation of the ventral visual system.

PubMed

Prčkovska, Vesna; Huijbers, Willem; Schultz, Aaron; Ortiz-Teran, Laura; Peña-Gomez, Cleofe; Villoslada, Pablo; Johnson, Keith; Sperling, Reisa; Sepulcre, Jorge

2017-04-01

Neuronal responses adapt to familiar and repeated sensory stimuli. Enhanced synchrony across wide brain systems has been postulated as a potential mechanism for this adaptation phenomenon. Here, we used recently developed graph theory methods to investigate hidden connectivity features of dynamic synchrony changes during a visual repetition paradigm. Particularly, we focused on strength connectivity changes occurring at local and distant brain neighborhoods. We found that connectivity reorganization in visual modal cortex-such as local suppressed connectivity in primary visual areas and distant suppressed connectivity in fusiform areas-is accompanied by enhanced local and distant connectivity in higher cognitive processing areas in multimodal and association cortex. Moreover, we found a shift of the dynamic functional connections from primary-visual-fusiform to primary-multimodal/association cortex. These findings suggest that repetition-suppression is made possible by reorganization of functional connectivity that enables communication between low- and high-order areas. Hum Brain Mapp 38:1965-1976, 2017. © 2017 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Comparison of FIM™ communication ratings for English versus non-English speakers in the traumatic brain injury model systems (TBIMS) national database.

PubMed

Lequerica, Anthony; Krch, Denise; Lengenfelder, Jean; Chiaravalloti, Nancy; Arango-Lasprilla, Juan Carlos; Hammond, Flora M; O'Neil-Pirozzi, Therese M; Perrin, Paul B; Sander, Angelle M

2015-01-01

To examine the effect of primary language on admission and discharge FIM™ communication ratings in a sample of individuals with moderate-to-severe traumatic brain injury (TBI). Secondary data analysis of rehabilitation admission and discharge FIM™ communication ratings of 2795 individuals hospitalized at a Traumatic Brain Injury Model Systems (TBIMS) centre between 2007-2012. Individuals who spoke no English were rated worse on functional communication outcomes at inpatient rehabilitation discharge relative to individuals whose primary language was English. These findings may reflect systematic bias in FIM™ communication ratings of non-English-speaking individuals with TBI and/or TBI-induced communication difficulties in non-English-speaking individuals. Clinical and research implications are discussed.

Progranulin Is a Chemoattractant for Microglia and Stimulates Their Endocytic Activity

PubMed Central

Pickford, Fiona; Marcus, Jacob; Camargo, Luiz Miguel; Xiao, Qiurong; Graham, Danielle; Mo, Jan-Rung; Burkhardt, Matthew; Kulkarni, Vinayak; Crispino, Jamie; Hering, Heike; Hutton, Michael

2011-01-01

Mutations resulting in progranulin haploinsufficiency cause disease in patients with a subset of frontotemporal lobar degeneration; however, the biological functions of progranulin in the brain remain unknown. To address this subject, the present study initially assessed changes in gene expression and cytokine secretion in rat primary cortical neurons treated with progranulin. Molecular pathways enriched in the progranulin gene set included cell adhesion and cell motility pathways and pathways involved in growth and development. Secretion of cytokines and several chemokines linked to chemoattraction but not inflammation were also increased from progranulin-treated primary neurons. Therefore, whether progranulin is involved in recruitment of immune cells in the brain was investigated. Localized lentiviral expression of progranulin in C57BL/6 mice resulted in an increase of Iba1-positive microglia around the injection site. Moreover, progranulin alone was sufficient to promote migration of primary mouse microglia in vitro. Primary microglia and C4B8 cells demonstrated more endocytosis of amyloid β1-42 when treated with progranulin. These data demonstrate that progranulin acts as a chemoattractant in the brain to recruit or activate microglia and can increase endocytosis of extracellular peptides such as amyloid β. PMID:21224065

Neural dynamics in Parkinsonian brain: The boundary between synchronized and nonsynchronized dynamics

NASA Astrophysics Data System (ADS)

Park, Choongseok; Worth, Robert M.; Rubchinsky, Leonid L.

2011-04-01

Synchronous oscillatory dynamics is frequently observed in the human brain. We analyze the fine temporal structure of phase-locking in a realistic network model and match it with the experimental data from Parkinsonian patients. We show that the experimentally observed intermittent synchrony can be generated just by moderately increased coupling strength in the basal ganglia circuits due to the lack of dopamine. Comparison of the experimental and modeling data suggest that brain activity in Parkinson's disease resides in the large boundary region between synchronized and nonsynchronized dynamics. Being on the edge of synchrony may allow for easy formation of transient neuronal assemblies.

Inhibiting 4EBP1 in Glioblastoma. | Office of Cancer Genomics

Cancer.gov

Glioblastoma is the most common and aggressive adult brain cancer. Tumors show frequent dysregulation of the PI3K-mTOR pathway. Although a number of small molecules target the PI3K-AKT-mTOR axis, their preclinical and clinical efficacy has been limited. Reasons for treatment failure include poor penetration of agents into the brain and observations that blockade of PI3K or AKT minimally affects downstream mTOR activity in glioma.

Frontal and Temporal Structural Connectivity Is Associated with Social Communication Impairment Following Traumatic Brain Injury

PubMed Central

Rigon, Arianna; Voss, Michelle W.; Turkstra, Lyn S.; Mutlu, Bilge; Duff, Melissa C.

2018-01-01

Objectives Although it has been well documented that traumatic brain injury (TBI) can result in communication impairment, little work to date has examined the relationship between social communication skills and structural brain integrity in patients with TBI. The aim of the current study was to investigate the association between self- and other-perceived communication problems and white matter integrity in patients with mild to severe TBI. Methods Forty-four individuals (TBI = 24) and people with whom they frequently communicate, as well as demographically matched normal healthy comparisons (NC) and their frequent communication partners, were administered, respectively, the La-Trobe Communication Questionnaire Self form (LCQ-SELF) and Other form (LCQ-OTHER). In addition, diffusion tensor imaging data were collected, and fractional anisotropy (FA) measures were extracted for each lobe in both hemispheres. Results Within the TBI group, but not within the NC group, participants who were perceived by their close others as having more communication problems had lower FA in the left frontal and temporal lobes (p < .01), but not in other brain regions. Conclusions Frontotemporal white matter microstructural integrity is associated with social communication abilities in adults with TBI. This finding contributes to our understanding of the mechanisms leading to communication impairment following TBI and can inform the development of new neuromodulation therapies as well as diagnostic tools. PMID:27405965

Exploring the relationship between frequent internet use and health and social care resource use in a community-based cohort of older adults: an observational study in primary care

PubMed Central

Round, Jeff; Morris, Stephen; Kharicha, Kalpa; Ford, John; Manthorpe, Jill; Iliffe, Steve; Goodman, Claire; Walters, Kate

2017-01-01

Objectives Given many countries’ ageing populations, policymakers must consider how to mitigate or reduce health problems associated with old age, within budgetary constraints. Evidence of use of digital technology in delaying the onset of illness and reducing healthcare service use is mixed, with no clear consensus as yet. Our aim was to investigate the relationship between frequent internet use and patterns of health or social care resource use in primary care attendees who took part in a study seeking to improve the health of older adults. Methods Participants recruited from primary care, aged >65 and living in semirural or urban areas in the south of England, were followed up at 3 and 6 months after completing a comprehensive questionnaire with personalised feedback on their health and well-being. We performed logistic regression analyses to investigate relationships between frequent internet use and patterns of service use, controlling for confounding factors, and clustering by general practitioner practice. Four categories of service use data were gathered: use of primary National Health Service (NHS) care; secondary NHS care; other community health and social care services; and assistance with washing, shopping and meals. Results Our results show, in this relatively healthy population, a positive relationship (OR 1.72, 95% CI 1.33 to 2.23) between frequent internet use and use of any other community-based health services (physiotherapist, osteopath/chiropractor, dentist, optician/optometrist, counselling service, smoking cessation service, chiropodist/podiatrist, emergency services, other non-specific health services) and no relationship with the other types of care. No causal relationship can be postulated due to the study’s design. Conclusions No observed relationship between frequent internet use and primary or secondary care use was found, suggesting that older adults without internet access are not disadvantaged regarding healthcare use. Further research should explore how older people use the internet to access healthcare and the impact on health. PMID:28733300

Indications for laboratory tests in primary care: assessment of the most frequent indications and requests with blank clinical information

PubMed Central

Salinas, Maria; López-Garrigós, Maite; Flores, Emilio; Leiva-Salinas, Maria; Esteban, Patricia; Ahumada, Miguel; Leiva-Salinas, Carlos

2016-01-01

Introduction The aim of this work is twofold. Firstly, to study the temporal evolution in the number of laboratory requests from primary care without clinical indication, and to analyse the number of such requests before and after the implementation of an automated requesting procedure. Secondly, to investigate what are the most frequent clinical indications that prompted laboratory testing. Materials and methods This is a retrospective observational study conducted from January 2009 to December 2015. We counted the requests without clinical question, calculated the number of such requests per total number of requests and listed the most frequent indications. Results The number of tests requests with a blank clinical indication was significantly higher in 2009 when compared to 2015 (80% vs. 20%; P < 0.001). For every year in this 7-year period, dyslipidemia, essential hypertension and diabetes were the most prevalent diagnoses that prompted a laboratory test in primary care, accounting for more than 20% of all indications. Conclusions The number of primary care requests without patient clinical question has decreased after the implementation of an automated requesting procedure. Disorders of lipid metabolism, essential hypertension and diabetes mellitus were the most prevalent diagnoses that prompted a laboratory test in primary care. PMID:27812310

Evaluation of anxiety and depression prevalence in patients with primary severe hyperhidrosis*

PubMed Central

Bragança, Gleide Maria Gatto; Lima, Sonia Oliveira; Pinto, Aloisio Ferreira; Marques, Lucas Menezes; de Melo, Enaldo Vieira; Reis, Francisco Prado

2014-01-01

BACKGROUND Primary hyperhidrosis (PH) can lead to mood changes due to the inconveniences it causes. OBJECTIVE This study aimed to examine the existence of anxiety and depression in patients with severe primary hyperhidrosis who sought treatment at a medical office. METHODS The questionnaire "Hospital Anxiety and Depression Scale" was used for 197 individuals, in addition to the chi square test and Fisher exact test, p <0.05. RESULTS There was an increased prevalence of anxiety (49.6%) but not of depression (11.2%) among patients with PH, with no link to gender, age or amount of affected areas. Palmar and plantar primary hyperhidrosis were the most frequent but when associated with the presence of anxiety, the most frequent were the axillary (p = 0.02) and craniofacial (p = 0.02) forms. There was an association between patients with depression and anxiety (p = 0.001). CONCLUSIONS the involvement of Primary hyperhidrosis was responsible for a higher prevalence of anxiety than that described among the general population and patients with other chronic diseases. Depression had a low prevalence rate, while mild and moderate forms were the most common and frequently associated with anxiety. The degree of anxiety was higher in mild and moderate types than in the severe form. PMID:24770497

Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex.

PubMed

Scott, Gregory D; Karns, Christina M; Dow, Mark W; Stevens, Courtney; Neville, Helen J

2014-01-01

Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl's gyrus. In addition to reorganized auditory cortex (cross-modal plasticity), a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case), as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral vs. perifoveal visual stimulation (11-15° vs. 2-7°) in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl's gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl's gyrus) indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral vs. perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory, and multisensory and/or supramodal regions, such as posterior parietal cortex (PPC), frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal, and multisensory regions, to altered visual processing in congenitally deaf adults.

Rationale for the Use of Upfront Whole Brain Irradiation in Patients with Brain Metastases from Breast Cancer

PubMed Central

Tallet, Agnes V.; Azria, David; Le Rhun, Emilie; Barlesi, Fabrice; Carpentier, Antoine F.; Gonçalves, Antony; Taillibert, Sophie; Dhermain, Frédéric; Spano, Jean-Philippe; Metellus, Philippe

2014-01-01

Breast cancer is the second most common cause of brain metastases and deserves particular attention in relation to current prolonged survival of patients with metastatic disease. Advances in both systemic therapies and brain local treatments (surgery and stereotactic radiosurgery) have led to a reappraisal of brain metastases management. With respect to this, the literature review presented here was conducted in an attempt to collect medical evidence-based data on the use of whole-brain radiotherapy for the treatment of brain metastases from breast cancer. In addition, this study discusses here the potential differences in outcomes between patients with brain metastases from breast cancer and those with brain metastases from other primary malignancies and the potential implications within a treatment strategy. PMID:24815073

Rationale for the use of upfront whole brain irradiation in patients with brain metastases from breast cancer.

PubMed

Tallet, Agnes V; Azria, David; Le Rhun, Emilie; Barlesi, Fabrice; Carpentier, Antoine F; Gonçalves, Antony; Taillibert, Sophie; Dhermain, Frédéric; Spano, Jean-Philippe; Metellus, Philippe

2014-05-08

Breast cancer is the second most common cause of brain metastases and deserves particular attention in relation to current prolonged survival of patients with metastatic disease. Advances in both systemic therapies and brain local treatments (surgery and stereotactic radiosurgery) have led to a reappraisal of brain metastases management. With respect to this, the literature review presented here was conducted in an attempt to collect medical evidence-based data on the use of whole-brain radiotherapy for the treatment of brain metastases from breast cancer. In addition, this study discusses here the potential differences in outcomes between patients with brain metastases from breast cancer and those with brain metastases from other primary malignancies and the potential implications within a treatment strategy.

Predictors of longitudinal outcome and recovery of pragmatic language and its relation to externalizing behaviour after pediatric traumatic brain injury.

PubMed

Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Coleman, Lee; Ditchfield, Michael; Crossley, Louise; Beauchamp, Miriam H; Anderson, Vicki A

2015-03-01

The purpose of the present investigation was to evaluate the contribution of age-at-insult and brain pathology on longitudinal outcome and recovery of pragmatic language in a sample of children and adolescents with traumatic brain injury (TBI). Children and adolescents with mild to severe TBI (n=112) were categorized according to timing of brain insult: (i) Middle Childhood (5-9 years; n=41); (ii) Late Childhood (10-11 years; n=39); and (iii) Adolescence (12-15 years; n=32) and group-matched for age, gender and socio-economic status (SES) to a typically developing (TD) control group (n=43). Participants underwent magnetic resonance imaging (MRI) including a susceptibility weighted imaging (SWI) sequence 2-8 weeks after injury and were assessed on measures of pragmatic language and behavioural functioning at 6- and 24-months after injury. Children and adolescents with TBI of all severity levels demonstrated impairments in these domains at 6-months injury before returning to age-expected levels at 2-years post-TBI. However, while adolescent TBI was associated with post-acute disruption to skills that preceded recovery to age-expected levels by 2-years post injury, the middle childhood TBI group demonstrated impairments at 6-months post-injury that were maintained at 2-year follow up. Reduced pragmatic communication was associated with frontal, temporal and corpus callosum lesions, as well as more frequent externalizing behaviour at 24-months post injury. Findings show that persisting pragmatic language impairment after pediatric TBI is related to younger age at brain insult, as well as microhemorrhagic pathology in brain regions that contribute to the anatomically distributed social brain network. Relationships between reduced pragmatic communication and more frequent externalizing behavior underscore the need for context-sensitive rehabilitation programs that aim to increase interpersonal effectiveness and reduce risk for maladaptive behavior trajectories into the long-term post injury. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical outcomes of gastrointestinal brain metastases treated with radiotherapy.

PubMed

Sanghvi, Samrat M; Lischalk, Jonathan W; Cai, Ling; Collins, Sean; Nair, Mani; Collins, Brain; Unger, Keith

2017-02-28

Brain metastases of gastrointestinal origin are a rare occurrence. Radiation therapy (RT) in the form of stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) is an effective established treatment modality in either the definitive or adjuvant setting. The aim of this study is to assess the long-term clinical outcomes of patients with gastrointestinal (GI) brain metastases treated with SRS or WBRT. In this single institutional retrospective review, we detail the outcomes of patients diagnosed with metastatic brain tumors from an adenocarcinoma gastrointestinal primary. Patients were treated using stereotactic radiosurgery or whole brain radiation therapy. Initial site control (defined as lesions visualized on imaging at time of treatment), new site control (defined as new intracranial lesions visualized on follow-up imaging), and overall survival were calculated using the Kaplan-Meier method. Thirty-three patients were treated from August 2008 to December 2015. Primary malignancy locations were as follows: 18 colon, 6 esophagus, 4 rectum, 5 other. Median total dose delivered was 25 Gy (18-35 Gy) in a median of 4 fractions for SRS and 30 Gy (10.8-40 Gy) in 10 fractions for WBRT. Crude initial site control at last radiographic follow-up was 64.3% after SRS and 41.7% after WBRT. Eleven of the 28 brain lesions (39.3%) treated with SRS had resection of the SRS-treated lesion prior to radiation therapy. Five of the twelve patients (41.7%) undergoing WBRT underwent cranial resection prior to radiation therapy. Crude new site control at last radiographic follow-up was 46.4% after SRS and 83.3% after WBRT. Kaplan-Meier analysis of overall survival did not show any statistically significant difference between WBRT and SRS (p = 0.424). Median overall survival for SRS patients was 5.2 months (0.5-57.5) and for WBRT patients 4.4 months (0-15). Kaplan-Meier analysis of new site control was significantly improved with WBRT versus SRS (p = 0.017). Total dose, treatment with WBRT, and active extracranial disease were statistically significant on multivariate analysis for new site control (p < 0.05). Survival and intracranial disease control are poor following RT for brain metastases from GI primaries. In this small series, outcomes are worse than published series for other primary malignancies metastatic to the brain and further research into methods of local control improvement is warranted. Future studies should explore the utility of dose escalation or radiosensitization in this patient population.

The frequently used intraperitoneal hyponatraemia model induces hypovolaemic hyponatraemia with possible model-dependent brain sodium loss.

PubMed

Overgaard-Steensen, Christian; Stødkilde-Jørgensen, Hans; Larsson, Anders; Tønnesen, Else; Frøkiaer, Jørgen; Ring, Troels

2016-07-01

What is the central question of this study? The brain response to acute hyponatraemia is usually studied in rodents by intraperitoneal instillation of hypotonic fluids (i.p. model). The i.p. model is described as 'dilutional' and 'syndrome of inappropriate ADH (SIADH)', but the mechanism has not been explored systematically and might affect the brain response. Therefore, in vivo brain and muscle response were studied in pigs. What is the main finding and its importance? The i.p. model induces hypovolaemic hyponatraemia attributable to sodium redistribution, not dilution. A large reduction in brain sodium is observed, probably because of the specific mechanism causing the hyponatraemia. This is not accounted for in current understanding of the brain response to acute hyponatraemia. Hyponatraemia is common clinically, and if it develops rapidly, brain oedema evolves, and severe morbidity and even death may occur. Experimentally, acute hyponatraemia is most frequently studied in small animal models, in which the hyponatraemia is produced by intraperitoneal instillation of hypotonic fluids (i.p. model). This hyponatraemia model is described as 'dilutional' or 'syndrome of inappropriate ADH (SIADH)', but seminal studies contradict this interpretation. To confront this issue, we developed an i.p. model in a large animal (the pig) and studied water and electrolyte responses in brain, muscle, plasma and urine. We hypothesized that hyponatraemia was induced by simple water dilution, with no change in organ sodium content. Moderate hypotonic hyponatraemia was induced by a single i.v. dose of desmopressin and intraperitoneal instillation of 2.5% glucose. All animals were anaesthetized and intensively monitored. In vivo brain and muscle water was determined by magnetic resonance imaging and related to the plasma sodium concentration. Muscle water content increased less than expected as a result of pure dilution, and muscle sodium content decreased significantly (by 28%). Sodium was redistributed to the peritoneal fluid, resulting in a significantly reduced plasma volume. This shows that the i.p. model induces hypovolaemic hyponatraemia and not dilutional/SIADH hyponatraemia. Brain oedema evolved, but brain sodium content decreased significantly (by 21%). To conclude, the i.p. model induces hypovolaemic hyponatraemia attributable to sodium redistribution and not water dilution. The large reduction in brain sodium is probably attributable to the specific mechanism that causes the hyponatraemia. This is not accounted for in the current understanding of the brain response to acute hyponatraemia. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Investigation of the cortical activation by touching fabric actively using fingers.

PubMed

Wang, Q; Yu, W; He, N; Chen, K

2015-11-01

Human subjects can tactually estimate the perception of touching fabric. Although many psychophysical and neurophysiological experiments have elucidated the peripheral neural mechanisms that underlie fabric hand estimation, the associated cortical mechanisms are not well understood. To identify the brain regions responsible for the tactile stimulation of fabric against human skin, we used the technology of functional magnetic resonance imaging (fMRI), to observe brain activation when the subjects touched silk fabric actively using fingers. Consistent with previous research about brain cognition on sensory stimulation, large activation in the primary somatosensory cortex (SI), the secondary somatosensory cortex (SII) and moto cortex, and little activation in the posterior insula cortex and Broca's Area were observed when the subjects touched silk fabric. The technology of fMRI is a promising tool to observe and characterize the brain cognition on the tactile stimulation of fabric quantitatively. The intensity and extent of activation in the brain regions, especially the primary somatosensory cortex (SI) and the secondary somatosensory cortex (SII), can represent the perception of stimulation of fabric quantitatively. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Secondary instabilities modulate cortical complexity in the mammalian brain

NASA Astrophysics Data System (ADS)

Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

2015-10-01

Disclosing the origin of convolutions in the mammalian brain remains a scientific challenge. Primary folds form before we are born: they are static, well defined and highly preserved across individuals. Secondary folds occur and disappear throughout our entire lifetime: they are dynamic, irregular and highly variable among individuals. While extensive research has improved our understanding of primary folding in the mammalian brain, secondary folding remains understudied and poorly understood. Here, we show that secondary instabilities can explain the increasing complexity of our brain surface as we age. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we explore the critical conditions for secondary instabilities. We show that with continuing growth, our brain surface continues to bifurcate into increasingly complex morphologies. Our results suggest that even small geometric variations can have a significant impact on surface morphogenesis. Secondary bifurcations, and with them morphological changes during childhood and adolescence, are closely associated with the formation and loss of neuronal connections. Understanding the correlation between neuronal connectivity, cortical thickness, surface morphology and ultimately behaviour, could have important implications on the diagnostics, classification and treatment of neurological disorders.

Multiple cortical brain abscesses due to Listeria monocytogenes in an immunocompetent patient.

PubMed

Khan, Sadia; Kumar, Anil; Kale, Satyajit; Kurkure, Nitin; Nair, Gulsiv; Dinesh, Kavitha

2018-04-01

Listeria monocytogenes is an intracellular organism which is well recognised for its ability to cause meningeal infections in neonates, immunosuppressed, debilitated and elderly individuals. 1 Other less common central nervous system (CNS) infections caused by Listeria spp. include rhomboencephalitis, cerebritis and abscesses in the brain, brain stem and spinal cord. The neuroradiological appearance of Listeria brain abscesses is similar to other types and may also mimic primary or metastatic brain tumours. 2 , 3 We report a case of Listeria brain abscesses in a patient who was being treated for atypical parkinsonism. A good clinical outcome was achieved after appropriate antimicrobial therapy.

Structural covariance mapping delineates medial and medio-lateral temporal networks in déjà vu.

PubMed

Shaw, Daniel Joel; Mareček, Radek; Brázdil, Milan

2016-12-01

Déjà vu (DV) is an eerie phenomenon experienced frequently as an aura of temporal lobe epilepsy, but also reported commonly by healthy individuals. The former pathological manifestation appears to result from aberrant neural activity among brain structures within the medial temporal lobes. Recent studies also implicate medial temporal brain structures in the non-pathological experience of DV, but as one element of a diffuse neuroanatomical correlate; it remains to be seen if neural activity among the medial temporal lobes also underlies this benign manifestation. The present study set out to investigate this. Due to its unpredictable and infrequent occurrence, however, non-pathological DV does not lend itself easily to functional neuroimaging. Instead, we draw on research showing that brain structure covaries among regions that interact frequently as nodes of functional networks. Specifically, we assessed whether grey-matter covariance among structures implicated in non-pathological DV differs according to the frequency with which the phenomenon is experienced. This revealed two diverging patterns of structural covariation: Among the first, comprised primarily of medial temporal structures and the caudate, grey-matter volume becomes more positively correlated with higher frequency of DV experience. The second pattern encompasses medial and lateral temporal structures, among which greater DV frequency is associated with more negatively correlated grey matter. Using a meta-analytic method of co-activation mapping, we demonstrate a higher probability of functional interactions among brain structures constituting the former pattern, particularly during memory-related processes. Our findings suggest that altered neural signalling within memory-related medial temporal brain structures underlies both pathological and non-pathological DV.

Vision's Brain.

ERIC Educational Resources Information Center

Miller, Julie Ann

1978-01-01

The functional architecture of the primary visual cortex has been explored by monitoring the responses of individual brain cells to visual stimuli. A combination of anatomical and physiological techniques reveals groups of functionally related cells, juxtaposed and superimposed, in a sometimes complex, but presumably efficient, structure. (BB)

[A case of primary central nervous system anaplastic lymphoma kinase positive anaplastic large cell lymphoma manifested as a unilateral pachymeningits].

PubMed

Fujisawa, Etsuco; Shibayama, Hidehiro; Mitobe, Fumi; Katada, Fumiaki; Sato, Susumu; Fukutake, Toshio

2017-11-25

There have been 23 reports of primary central nervous system anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma in the literature. Here we report the 24th case of a 40-year-old man who presented with occipital headache for one month. His contrast-enhanced brain MRI showed enhancement around the right temporal lobe, which suggested a diagnosis of hypertrophic pachymeningitis. He improved with steroid therapy. After discharge, however, he was readmitted with generalized convulsive seizures. Finally, he was diagnosed as primary central nervous system ALK-positive anaplastic large cell lymphoma by brain biopsy. Primary central nervous system lymphoma invading dura matter can rarely manifests as a unilateral pachymeningitis. Therefore, in case of pachymeningitis, we should pay attention to the possibility of infiltration of lymophoma with meticulous clinical follow-up.

Coping and adaptive strategies of traumatic brain injury survivors and primary caregivers.

PubMed

Adams, Deana; Dahdah, Marie

2016-06-27

Qualitative research methods allowed the investigator to contribute to the development of new theories and to examine change in processes over time, which added rich detail to existing knowledge of the use of coping and adaptive strategies by traumatic brain injury survivors and their primary caregivers (Ponsford, Sloan, & Snow, 2013). The advantages of phenomenological study were that it allows flexibility to explore and understand meanings attached by people to well-studied concepts such as coping, resiliency, and adaptation or compensation. Phenomenological study was sensitive to contextual factors. It also permitted the study of in-depth dynamics of coping and adaptive strategies of TBI survivors and primary caregivers, while understanding the social and psychological implications of the phenomenon. To explore the needs and deficits of adult traumatic brain injury (TBI) survivors and primary caregivers; and to identify their self-initiated coping and adaptive strategies. Significant to this study was the development of coping and adaptive strategies by the participants after their discharge from inpatient and rehabilitation treatment. The compensatory skills taught in treatment settings did not transfer to the home environment. Therefore, these strategies developed independently from previous treatment recommendations contributed to the development of theory related to rehabilitation and counseling. Distinctive to this study was the similarity of coping and adaptive strategies developed from both mild and severe traumatic brain injury survivors. This study consisted of eleven with TBI and six primary caregivers (N = 17), who participated in a series of semi-structured interviews aimed at discovering the coping and adaptive strategies utilized in dealing with the effects of brain injury. A Qualitative Phenomenological design was employed. Patience and understanding, support, and professional help were identified by TBI survivors and caregivers as being their most relevant needs. Self-reported deficits included short-term memory loss (STM), fatigue, anger, and personality changes, and the strategies that TBI survivors and caregivers identified tended to address their problems with these specific day-to-day deficits. Problem focused, emotion focused, and avoidant coping were utilized to some degree in their adjustment to home life and activities of daily living. Participants offered suggestions for mental health professionals addressing how to more effectively work with brain injury survivors and their primary caregivers. TBI survivors and caregivers had multiple self-reported unaddressed needs following their discharge from facility-based treatment. They reported spontaneously engaging in various coping and adaptive strategies to address their needs and deficits. However, further education regarding potential post-TBI challenges and strategies for addressing them are needed, including a need for community and mental health resources.

Genetics Home Reference: early-onset primary dystonia

MedlinePlus

... such as seizures or a loss of intellectual function (dementia). Early-onset primary dystonia does not affect a person's intelligence. On ... of torsinA. The altered protein's effect on the function of nerve cells in the brain ... with early-onset primary dystonia do not have a loss of nerve ...

Microbleeds in postmortem brains of patients with Alzheimer disease: a T2*-weighted gradient-echo 7.0 T magnetic resonance imaging study.

PubMed

De Reuck, Jacques L; Cordonnier, Charlotte; Deramecourt, Vincent; Auger, Florent; Durieux, Nicolas; Bordet, Regis; Maurage, Claude-Alain; Leys, Didier; Pasquier, Florence

2013-01-01

This study aims to determine the distribution and to quantify microbleeds (MBs) in postmortem brains of patients with Alzheimer disease (AD) on T2*-weighted gradient-echo 7.0 T magnetic resonance imaging. Twenty-eight AD brains were compared with 5 controls. The AD brains were subdivided further: 18 without and 10 with additional severe cerebral amyloid angiopathy (AD-CAA). The distribution and the number of cortical focal signal intensity losses, representing MBs, were assessed on coronal sections at the frontal, the central, and the occipital level of a cerebral hemisphere. MBs prevailed in the central sections (P=0.005) of AD brains without CAA, whereas in AD-CAA brains, they were more frequent in all coronal sections (P≤0.002). They prevailed in the deep cortical layers of the AD brains and of the controls (P≤0.03). They were significantly increased in all cortical layers of the AD-CAA brains (P≤0.04), compared with the controls. MBs prevalence in brains of AD patients had a different topographic distribution according to the absence or presence of severe CAA.

miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF α

PubMed Central

Xing, Fei; Sharma, Sambad; Liu, Yin; Mo, Yin-Yuan; Wu, Kerui; Zhang, Ying-Yu; Pochampally, Radhika; Martinez, Luis A; Lo, Hui-wen; Watabe, Kounosuke

2014-01-01

The median survival time of breast cancer patients with brain metastasis is less than 6 months, and even a small metastatic lesion often causes severe neurological disabilities. Because of the location of metastatic lesions, a surgical approach is limited and most chemotherapeutic drugs are ineffective due to the blood brain barrier (BBB). Despite this clinical importance, the molecular basis of the brain metastasis is poorly understood. In this study, we have isolated RNA from samples obtained from primary breast tumors and also from brain metastatic lesions followed by microRNA profiling analysis. Our results revealed that the miR-509 is highly expressed in the primary tumors, while the expression of this microRNA is significantly decreased in the brain metastatic lesions. MicroRNA target prediction and the analysis of cytokine array for the cells ectopically expressed with miR-509 demonstrated that this microRNA was capable of modulating two genes essential for brain invasion, RhoC and TNFα that affect the invasion of cancer cells and permeability of BBB, respectively. Importantly, high levels of TNFα and RhoC-induced MMP9 were significantly correlated with brain metastasis-free survival of breast cancer patients. Furthermore, the results of our in vivo experiments indicate that miR-509 significantly suppressed the ability of cancer cells to metastasize to the brain. These findings suggest that miR-509 plays a critical role in brain metastasis of breast cancer by modulating the RhoC-TNFα network and that this miR-509 axis may represent a potential therapeutic target or serve as a prognostic tool for brain metastasis. PMID:25659578

Efficiency, capacity, compensation, maintenance, plasticity: emerging concepts in cognitive reserve

PubMed Central

Barulli, Daniel; Stern, Yaakov

2013-01-01

Cognitive reserve (CR) is a concept meant to account for the frequent discrepancy between an individual’s measured level of brain pathology and her expected cognitive performance. It is particularly important within the context of aging and dementia, but has wider applicability to all forms of brain damage. As such, it has intimate links to related compensatory and neuroprotective concepts, as well as to the related notion of brain reserve. In this article, we introduce the concept of cognitive reserve and explicate its potential cognitive neural implementation. We conclude that cognitive reserve is compatible and complementary with many related concepts, but that each much draw sharper conceptual boundaries in order to truly explain preserved cognitive function in the face of aging or brain damage. PMID:24018144

Abnormality of circadian rhythm accompanied by an increase in frontal cortex serotonin in animal model of autism.

PubMed

Tsujino, Naohisa; Nakatani, Yasushi; Seki, Yoshinari; Nakasato, Akane; Nakamura, Michiko; Sugawara, Michiya; Arita, Hideho

2007-02-01

Several clinical reports have indicated that autistic patients often show disturbance of the circadian rhythm, which may be related to dysfunction of the serotonergic system in the brain. Using rats exposed prenatally to valproic acid (VPA) as an animal model of autism, we examined locomotor activity and feeding under a reversed 12-h light/dark cycle, and found disturbance of the circadian rhythm characterized by frequent arousal during the light/sleep phase. In addition, measurement of brain serotonin (5-HT) level using in vivo microdialysis showed that the brain 5-HT level in VPA-exposed rats was significantly higher than that in control rats. These results suggest that a higher brain 5-HT level might be responsible for the irregular sleep/awake rhythm in autism.

Drowning stars: reassessing the role of astrocytes in brain edema.

PubMed

Thrane, Alexander S; Rangroo Thrane, Vinita; Nedergaard, Maiken

2014-11-01

Edema formation frequently complicates brain infarction, tumors, and trauma. Despite the significant mortality of this condition, current treatment options are often ineffective or incompletely understood. Recent studies have revealed the existence of a brain-wide paravascular pathway for cerebrospinal (CSF) and interstitial fluid (ISF) exchange. The current review critically examines the contribution of this 'glymphatic' system to the main types of brain edema. We propose that in cytotoxic edema, energy depletion enhances glymphatic CSF influx, whilst suppressing ISF efflux. We also argue that paravascular inflammation or 'paravasculitis' plays a critical role in vasogenic edema. Finally, recent advances in diagnostic imaging of glymphatic function may hold the key to defining the edema profile of individual patients, and thus enable more targeted therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Isolated brain stem lesion in children: is it acute disseminated encephalomyelitis or not?

PubMed

Alper, G; Sreedher, G; Zuccoli, G

2013-01-01

Isolated brain stem lesions presenting with acute neurologic findings create a major diagnostic dilemma in children. Although the brain stem is frequently involved in ADEM, solitary brain stem lesions are unusual. We performed a retrospective review in 6 children who presented with an inflammatory lesion confined to the brain stem. Two children were diagnosed with connective tissue disorder, CNS lupus, and localized scleroderma. The etiology could not be determined in 1, and clinical features suggested monophasic demyelination in 3. In these 3 children, initial lesions demonstrated vasogenic edema; all showed dramatic response to high-dose corticosteroids and made a full clinical recovery. Follow-up MRI showed complete resolution of lesions, and none had relapses at >2 years of follow-up. In retrospect, these cases are best regarded as a localized form of ADEM. We conclude that though ADEM is typically a disseminated disease with multifocal lesions, it rarely presents with monofocal demyelination confined to the brain stem.

The biology and therapeutic management of melanoma brain metastases.

PubMed

Abate-Daga, Daniel; Ramello, Maria C; Smalley, Inna; Forsyth, Peter A; Smalley, Keiran S M

2018-07-01

The recent years have seen significant progress in the development of systemic therapies to treat patients with advanced melanoma. Use of these new treatment modalities, which include immune checkpoint inhibitors and small molecule BRAF inhibitors, lead to increased overall survival and better outcomes. Although revolutionary, these therapies are often less effective against melanoma brain metastases, and frequently the CNS is the major site of treatment failure. The development of brain metastases remains a serious complication of advanced melanoma that is associated with significant morbidity and mortality. New approaches to both prevent the development of brain metastases and treat established disease are urgently needed. In this review we will outline the mechanisms underlying the development of melanoma brain metastases and will discuss how new insights into metastasis biology are driving the development of new therapeutic strategies. Finally, we will describe the latest data from the ongoing clinical trials for patients with melanoma brain metastases. Copyright © 2018 Elsevier Inc. All rights reserved.

The influence of brain abnormalities on psychosocial development, criminal history and paraphilias in sexual murderers.

PubMed

Briken, Peer; Habermann, Niels; Berner, Wolfgang; Hill, Andreas

2005-09-01

The aim of this study was to investigate the number and type of brain abnormalities and their influence on psychosocial development, criminal history and paraphilias in sexual murderers. We analyzed psychiatric court reports of 166 sexual murderers and compared a group with notable signs of brain abnormalities (N = 50) with those without any signs (N = 116). Sexual murderers with brain abnormalities suffered more from early behavior problems. They were less likely to cohabitate with the victim at the time of the homicide and had more victims at the age of six years or younger. Psychiatric diagnoses revealed a higher total number of paraphilias: Transvestic fetishism and paraphilias not otherwise specified were more frequent in offenders with brain abnormalities. A binary logistic regression identified five predictors that accounted for 46.8% of the variance explaining the presence of brain abnormalities. Our results suggest the importance of a comprehensive neurological and psychological examination of this special offender group.

Influence of neonatal vitamin A or vitamin D treatment on the concentration of biogenic amines and their metabolites in the adult rat brain.

PubMed

Tekes, K; Gyenge, M; Folyovich, A; Csaba, G

2009-04-01

Newborn male rats were treated with a single dose of 3 mg vitamin A (retinol) or 0.05 mg vita-min D (cholecalciferol), and three months later five brain regions (frontopolar cortex, hypothalamus, hippocampus, striatum, and brainstem) were studied for tissue levels of dopamine (DA), serotonin (5HT), and metabolites such as homovanillic acid (HVA), as well as 5-hydroxyindole-3-acetic acid (5HIAA). Vitamin A treatment as hormonal imprinting significantly decreased 5HIAA levels in each brain region. Vitamin D imprinting significantly elevated DA only in the brainstem and HVA levels in striatum and hypothalamus. Present and earlier brain-imprinting results (with brain-produced substances), show that the profound and life-long effect of neonatal hormonal imprinting on neurotransmitter production of the adult brain seems to be well established. As prophylactic treatment with these vitamins is frequent in the perinatal period, the imprinting effect of vitamin A and vitamin D must be taken into consideration.

Establishing Mouse Models for Zika Virus-induced Neurological Disorders Using Intracerebral Injection Strategies: Embryonic, Neonatal, and Adult.

PubMed

Herrlinger, Stephanie A; Shao, Qiang; Ma, Li; Brindley, Melinda; Chen, Jian-Fu

2018-04-26

The Zika virus (ZIKV) is a flavivirus currently endemic in North, Central, and South America. It is now established that the ZIKV can cause microcephaly and additional brain abnormalities. However, the mechanism underlying the pathogenesis of ZIKV in the developing brain remains unclear. Intracerebral surgical methods are frequently used in neuroscience research to address questions about both normal and abnormal brain development and brain function. This protocol utilizes classical surgical techniques and describes methods that allow one to model ZIKV-associated human neurological disease in the mouse nervous system. While direct brain inoculation does not model the normal mode of virus transmission, the method allows investigators to ask targeted questions concerning the consequence after ZIKV infection of the developing brain. This protocol describes embryonic, neonatal, and adult stages of intraventricular inoculation of ZIKV. Once mastered, this method can become a straightforward and reproducible technique that only takes a few hours to perform.

Is Dyslexia a Brain Disorder?

PubMed Central

Parrila, Rauno

2018-01-01

Specific word reading difficulty, commonly termed ‘developmental dyslexia’, refers to the low end of the word reading skill distribution but is frequently considered to be a neurodevelopmental disorder. This term implies that brain development is thought to be disrupted, resulting in an abnormal and dysfunctional brain. We take issue with this view, pointing out that there is no evidence of any obvious neurological abnormality in the vast majority of cases of word reading difficulty cases. The available relevant evidence from neuroimaging studies consists almost entirely of correlational and group-differences studies. However, differences in brains are certain to exist whenever differences in behavior exist, including differences in ability and performance. Therefore, findings of brain differences do not constitute evidence for abnormality; rather, they simply document the neural substrate of the behavioral differences. We suggest that dyslexia is best viewed as one of many expressions of ordinary ubiquitous individual differences in normal developmental outcomes. Thus, terms such as “dysfunctional” or “abnormal” are not justified when referring to the brains of persons with dyslexia. PMID:29621138

Frequent users of the Royal Flying Doctor Service primary clinic and aeromedical services in remote New South Wales: a quality study.

PubMed

Garne, David L; Perkins, David A; Boreland, Frances T; Lyle, David M

To examine activity patterns of the Royal Flying Doctor Service of Australia (RFDS) in far western New South Wales and to determine whether frequent use of RFDS services, particularly emergency evacuations, is a useful indicator of patients who may benefit from care planning and review. We conducted a retrospective audit of the RFDS South Eastern Section's Broken Hill patient database. Patients with a residential address in the study area who had accessed at least one RFDS medical service between 1 July 2000 and 30 June 2005 were included in the study. Number of evacuations, clinic consultations and remote consultations; clinic usage by frequent evacuees; number of primary diagnoses recorded for frequent evacuees; number of frequent users who might benefit from multidisciplinary care or specialist shared care. Between July 2000 and June 2005, the number of residents requiring evacuation or remote consultations declined by 26% and 19%, respectively, and the number of residents accessing clinics declined by 6%. (Over the same period, the population of the study area fell by about 24%.) Of the 78 patients who were identified as frequent users of the evacuation service (> or = 3 evacuations/year), 34 had three or more primary diagnoses recorded; 15 were infrequent or non-users of the clinics (< or = 3 attendances/year); 53 may have benefited from multidisciplinary care, and 41 from specialist shared care. Simple, practical clinical review systems can help health care organisations in rural and remote communities to achieve better outcomes by identifying patients who may benefit from planned care.

Vascular targeting of LIGHT normalizes blood vessels in primary brain cancer and induces intratumoural high endothelial venules.

PubMed

He, Bo; Jabouille, Arnaud; Steri, Veronica; Johansson-Percival, Anna; Michael, Iacovos P; Kotamraju, Venkata Ramana; Junckerstorff, Reimar; Nowak, Anna K; Hamzah, Juliana; Lee, Gabriel; Bergers, Gabriele; Ganss, Ruth

2018-06-01

High-grade brain cancer such as glioblastoma (GBM) remains an incurable disease. A common feature of GBM is the angiogenic vasculature, which can be targeted with selected peptides for payload delivery. We assessed the ability of micelle-tagged, vascular homing peptides RGR, CGKRK and NGR to specifically bind to blood vessels in syngeneic orthotopic GBM models. By using the peptide CGKRK to deliver the tumour necrosis factor (TNF) superfamily member LIGHT (also known as TNF superfamily member 14; TNFSF14) to angiogenic tumour vessels, we have generated a reagent that normalizes the brain cancer vasculature by inducing pericyte contractility and re-establishing endothelial barrier integrity. LIGHT-mediated vascular remodelling also activates endothelia and induces intratumoural high endothelial venules (HEVs), which are specialized blood vessels for lymphocyte infiltration. Combining CGKRK-LIGHT with anti-vascular endothelial growth factor and checkpoint blockade amplified HEV frequency and T-cell accumulation in GBM, which is often sparsely infiltrated by immune effector cells, and reduced tumour burden. Furthermore, CGKRK and RGR peptides strongly bound to blood vessels in freshly resected human GBM, demonstrating shared peptide-binding activities in mouse and human primary brain tumour vessels. Thus, peptide-mediated LIGHT targeting is a highly translatable approach in primary brain cancer to reduce vascular leakiness and enhance immunotherapy. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

INFLAMMATORY INDEX AND TREATMENT OF BRAIN ABSCESS

PubMed Central

OYAMA, HIROFUMI; KITO, AKIRA; MAKI, HIDEKI; HATTORI, KENICHI; NODA, TOMOYUKI; WADA, KENTARO

2012-01-01

ABSTRACT This study retrospectively analyzed 12 patients with brain abscesses. Half of the patients were diagnosed inaccurately in the initial stage, and 7.2 days were required to achieve the final diagnosis of brain abscess. The patients presented only with a moderately elevated leukocyte count, serum CRP levels, or body temperatures during the initial stage. These markers changed, first with an increase in the leukocyte count, followed by the CRP and body temperature. The degree of elevation tended to be less prominent, and the time for each inflammatory index to reach its maximum value tended to be longer in the patients without ventriculitis than in those with it. The causative organisms of a brain abscess were detected in 10 cases. The primary causative organisms from dental caries were Streptococcus viridians or milleri, and Fusobacterium nucleatum. Nocardia sp. or farcinica were common when the abscess was found in other regions. The primary causative organisms of unrecognized sources of infection were Streptococcus milleri and Prolionibacterium sp. Nocardia is resistant to many antibiotics. However, carbapenem, tetracycline and quinolone were effective for Nocardia as well as many other kinds of bacteria. In summary, the brain abscesses presented with only mildly elevated inflammatory markers of body temperature, leukocyte and CRP. These inflammatory markers were less obvious in the patients without ventriculitis and/or meningitis. The source of infection tended to suggest some specific primary causative organism. It was reasonable to initiate therapy with carbapenem. PMID:23092104

Posterior fossa tumor

MedlinePlus

... Most tumors of the posterior fossa are primary brain cancers. They start in the brain, rather than spreading from somewhere else in the ... nausea, vomiting, or vision changes. Alternative Names ... JF, Hollander AB, Alonso-Basanta M, et al. Cancer of the central nervous system. In: Niederhuber JE, ...

Affective neuroscience of the emotional BrainMind: evolutionary perspectives and implications for understanding depression

PubMed Central

Panksepp, Jaak

2010-01-01

Cross-species affective neuroscience studies confirm that primary-process emotional feelings are organized within primitive subcortical regions of the brain that are anatomically, neurochemically, and functionally homologous in all mammals that have been studied. Emotional feelings (affects) are intrinsic values that inform animals how they are faring in the quest to survive. The various positive affects indicate that animals are returning to “comfort zones” that support survival, and negative affects reflect “discomfort zones” that indicate that animals are in situations that may impair survival. They are ancestral tools for living - evolutionary memories of such importance that they were coded into the genome in rough form (as primary brain processes), which are refined by basic learning mechanisms (secondary processes) as well as by higher-order cognitions/thoughts (tertiary processes). To understand why depression feels horrible, we must fathom the affective infrastructure of the mammalian brain. Advances in our understanding of the nature of primary-process emotional affects can promote the development of better preclinical models of psychiatric disorders and thereby also allow clinicians new and useful ways to understand the foundational aspects of their clients' problems. These networks are of clear importance for understanding psychiatric disorders and advancing psychiatric practice. PMID:21319497

Primary cultures of astrocytes from fetal bovine brain.

PubMed

Ballarin, Cristina; Peruffo, Antonella

2012-01-01

We describe here a method to obtain primary cell cultures from the cerebral cortex and the hypothalamus of bovine fetuses. We report how tissue origin, developmental stages, and culture medium conditions influence cell differentiation and the prevalence of glial cells vs. neurons. We compare explants from early, middle, and late stages of development and two different fetal calf serum concentrations (1 and 10%) to identify the best conditions to obtain and grow viable astrocytes in culture. In addition, we describe how to cryopreserve and obtain viable cortical astrocytes from frozen fetal bovine brain samples.

Ex vivo micro-CT imaging of murine brain models using non-ionic iodinated contrast

NASA Astrophysics Data System (ADS)

Salas Bautista, N.; Martínez-Dávalos, A.; Rodríguez-Villafuerte, M.; Murrieta-Rodríguez, T.; Manjarrez-Marmolejo, J.; Franco-Pérez, J.; Calvillo-Velasco, M. E.

2014-11-01

Preclinical investigation of brain tumors is frequently carried out by means of intracranial implantation of brain tumor xenografts or allografts, with subsequent analysis of tumor growth using conventional histopathology. However, very little has been reported on the use contrast-enhanced techniques in micro-CT imaging for the study of malignant brain tumors in small animal models. The aim of this study has been to test a protocol for ex vivo imaging of murine brain models of glioblastoma multiforme (GBM) after treatment with non-ionic iodinated solution, using an in-house developed laboratory micro-CT. We have found that the best compromise between acquisition time and image quality is obtained using a 50 kVp, 0.5 mAs, 1° angular step on a 360 degree orbit acquisition protocol, with 70 μm reconstructed voxel size using the Feldkamp algorithm. With this parameters up to 4 murine brains can be scanned in tandem in less than 15 minutes. Image segmentation and analysis of three sample brains allowed identifying tumor volumes as small as 0.4 mm3.

What can we learn from a two-brain approach to verbal interaction?

PubMed

Schoot, Lotte; Hagoort, Peter; Segaert, Katrien

2016-09-01

Verbal interaction is one of the most frequent social interactions humans encounter on a daily basis. In the current paper, we zoom in on what the multi-brain approach has contributed, and can contribute in the future, to our understanding of the neural mechanisms supporting verbal interaction. Indeed, since verbal interaction can only exist between individuals, it seems intuitive to focus analyses on inter-individual neural markers, i.e. between-brain neural coupling. To date, however, there is a severe lack of theoretically-driven, testable hypotheses about what between-brain neural coupling actually reflects. In this paper, we develop a testable hypothesis in which between-pair variation in between-brain neural coupling is of key importance. Based on theoretical frameworks and empirical data, we argue that the level of between-brain neural coupling reflects speaker-listener alignment at different levels of linguistic and extra-linguistic representation. We discuss the possibility that between-brain neural coupling could inform us about the highest level of inter-speaker alignment: mutual understanding. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nanobiomaterials' applications in neurodegenerative diseases.

PubMed

Silva Adaya, Daniela; Aguirre-Cruz, Lucinda; Guevara, Jorge; Ortiz-Islas, Emma

2017-02-01

The blood-brain barrier is the interface between the blood and brain, impeding the passage of most circulating cells and molecules, protecting the latter from foreign substances, and maintaining central nervous system homeostasis. However, its restrictive nature constitutes an obstacle, preventing therapeutic drugs from entering the brain. Usually, a large systemic dose is required to achieve pharmacological therapeutic levels in the brain, leading to adverse effects in the body. As a consequence, various strategies are being developed to enhance the amount and concentration of therapeutic compounds in the brain. One such tool is nanotechnology, in which nanostructures that are 1-100 nm are designed to deliver drugs to the brain. In this review, we examine many nanotechnology-based approaches to the treatment of neurodegenerative diseases. The review begins with a brief history of nanotechnology, followed by a discussion of its definition, the properties of most reported nanomaterials, their biocompatibility, the mechanisms of cell-material interactions, and the current status of nanotechnology in treating Alzheimer's, Parkinson's diseases, and amyotrophic lateral sclerosis. Of all strategies to deliver drug to the brain that are used in nanotechnology, drug release systems are the most frequently reported.

Hemispheric asymmetry of electroencephalography-based functional brain networks.

PubMed

Jalili, Mahdi

2014-11-12

Electroencephalography (EEG)-based functional brain networks have been investigated frequently in health and disease. It has been shown that a number of graph theory metrics are disrupted in brain disorders. EEG-based brain networks are often studied in the whole-brain framework, where all the nodes are grouped into a single network. In this study, we studied the brain networks in two hemispheres and assessed whether there are any hemispheric-specific patterns in the properties of the networks. To this end, resting state closed-eyes EEGs from 44 healthy individuals were processed and the network structures were extracted separately for each hemisphere. We examined neurophysiologically meaningful graph theory metrics: global and local efficiency measures. The global efficiency did not show any hemispheric asymmetry, whereas the local connectivity showed rightward asymmetry for a range of intermediate density values for the constructed networks. Furthermore, the age of the participants showed significant direct correlations with the global efficiency of the left hemisphere, but only in the right hemisphere, with local connectivity. These results suggest that only local connectivity of EEG-based functional networks is associated with brain hemispheres.