Role of inflammation and its mediators in acute ischemic stroke

PubMed Central

Jin, Rong; Liu, Lin; Zhang, Shihao; Nanda, Anil; Li, Guohong

2013-01-01

Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Increasing evidence suggests that inflammatory response is a double-edged sword, as it not only exacerbates secondary brain injury in the acute stage of stroke but also beneficially contributes to brain recovery after stroke. In this article, we provide an overview on the role of inflammation and its mediators in acute ischemic stroke. We discuss various pro-inflammatory and anti-inflammatory responses in different phases after ischemic stroke and the possible reasons for their failures in clinical trials. Undoubtedly, there is still much to be done in order to translate promising pre-clinical findings into clinical practice. A better understanding of the dynamic balance between pro- and anti-inflammatory responses and identifying the discrepancies between pre-clinical studies and clinical trials may serve as a basis for designing effective therapies. PMID:24006091

Head trauma in the cat: 2. assessment and management of traumatic brain injury.

PubMed

Garosi, Laurent; Adamantos, Sophie

2011-11-01

Feline trauma patients are commonly seen in general practice and frequently have sustained some degree of brain injury. Cats with traumatic brain injuries may have a variety of clinical signs, ranging from minor neurological deficits to life-threatening neurological impairment. Appropriate management depends on prompt and accurate patient assessment, and an understanding of the pathophysiology of brain injury. The most important consideration in managing these patients is maintenance of cerebral perfusion and oxygenation. For cats with severe head injury requiring decompressive surgery, early intervention is critical. There is a limited clinical evidence base to support the treatment of traumatic brain injury in cats, despite its relative frequency in general practice. Appropriate therapy is, therefore, controversial in veterinary medicine and mostly based on experimental studies or human head trauma studies. This review, which sets out to describe the specific approach to diagnosis and management of traumatic brain injury in cats, draws on the current evidence, as far as it exists, as well as the authors' clinical experience. Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Brain aromatase: roles in reproduction and neuroprotection.

PubMed

Roselli, Charles F

2007-01-01

It is well established that aromatization constitutes an essential part of testosterone's signaling pathway in brain and that estrogen metabolites, often together with testosterone, organize and activate masculine neural circuits. This paper summarizes the current understanding regarding the distribution, regulation and function of brain aromatase in mammals. Data from our laboratory are presented that highlight the important function of aromatase in the regulation of androgen feedback sensitivity in non-human primates and the possible role that aromatase plays in determining the brain structure and sexual partner preferences of rams. In addition, new data is presented indicating that the capacity for aromatization in cortical astrocytes is associated with cell survival and may be important for neuroprotection. It is anticipated that a better appreciation of the physiological and pathophysiological functions of aromatase will lead to important clinical insights.

Individual brain structure and modelling predict seizure propagation.

PubMed

Proix, Timothée; Bartolomei, Fabrice; Guye, Maxime; Jirsa, Viktor K

2017-03-01

See Lytton (doi:10.1093/awx018) for a scientific commentary on this article.Neural network oscillations are a fundamental mechanism for cognition, perception and consciousness. Consequently, perturbations of network activity play an important role in the pathophysiology of brain disorders. When structural information from non-invasive brain imaging is merged with mathematical modelling, then generative brain network models constitute personalized in silico platforms for the exploration of causal mechanisms of brain function and clinical hypothesis testing. We here demonstrate with the example of drug-resistant epilepsy that patient-specific virtual brain models derived from diffusion magnetic resonance imaging have sufficient predictive power to improve diagnosis and surgery outcome. In partial epilepsy, seizures originate in a local network, the so-called epileptogenic zone, before recruiting other close or distant brain regions. We create personalized large-scale brain networks for 15 patients and simulate the individual seizure propagation patterns. Model validation is performed against the presurgical stereotactic electroencephalography data and the standard-of-care clinical evaluation. We demonstrate that the individual brain models account for the patient seizure propagation patterns, explain the variability in postsurgical success, but do not reliably augment with the use of patient-specific connectivity. Our results show that connectome-based brain network models have the capacity to explain changes in the organization of brain activity as observed in some brain disorders, thus opening up avenues towards discovery of novel clinical interventions. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Biomarker-guided translation of brain imaging into disease pathway models

PubMed Central

Younesi, Erfan; Hofmann-Apitius, Martin

2013-01-01

The advent of state-of-the-art brain imaging technologies in recent years and the ability of such technologies to provide high-resolution information at both structural and functional levels has spawned large efforts to introduce novel non-invasive imaging biomarkers for early prediction and diagnosis of brain disorders; however, their utility in both clinic and drug development at their best resolution remains limited to visualizing and monitoring disease progression. Given the fact that efficient translation of valuable information embedded in brain scans into clinical application is of paramount scientific and public health importance, a strategy is needed to bridge the current gap between imaging and molecular biology, particularly in neurodegenerative diseases. As an attempt to address this issue, we present a novel computational method to link readouts of imaging biomarkers to their underlying molecular pathways with the aim of guiding clinical diagnosis, prognosis and even target identification in drug discovery for Alzheimer's disease. PMID:24287435

Data warehousing methods and processing infrastructure for brain recovery research.

PubMed

Gee, T; Kenny, S; Price, C J; Seghier, M L; Small, S L; Leff, A P; Pacurar, A; Strother, S C

2010-09-01

In order to accelerate translational neuroscience with the goal of improving clinical care it has become important to support rapid accumulation and analysis of large, heterogeneous neuroimaging samples and their metadata from both normal control and patient groups. We propose a multi-centre, multinational approach to accelerate the data mining of large samples and facilitate data-led clinical translation of neuroimaging results in stroke. Such data-driven approaches are likely to have an early impact on clinically relevant brain recovery while we simultaneously pursue the much more challenging model-based approaches that depend on a deep understanding of the complex neural circuitry and physiological processes that support brain function and recovery. We present a brief overview of three (potentially converging) approaches to neuroimaging data warehousing and processing that aim to support these diverse methods for facilitating prediction of cognitive and behavioral recovery after stroke, or other types of brain injury or disease.

Using normalization 3D model for automatic clinical brain quantative analysis and evaluation

NASA Astrophysics Data System (ADS)

Lin, Hong-Dun; Yao, Wei-Jen; Hwang, Wen-Ju; Chung, Being-Tau; Lin, Kang-Ping

2003-05-01

Functional medical imaging, such as PET or SPECT, is capable of revealing physiological functions of the brain, and has been broadly used in diagnosing brain disorders by clinically quantitative analysis for many years. In routine procedures, physicians manually select desired ROIs from structural MR images and then obtain physiological information from correspondent functional PET or SPECT images. The accuracy of quantitative analysis thus relies on that of the subjectively selected ROIs. Therefore, standardizing the analysis procedure is fundamental and important in improving the analysis outcome. In this paper, we propose and evaluate a normalization procedure with a standard 3D-brain model to achieve precise quantitative analysis. In the normalization process, the mutual information registration technique was applied for realigning functional medical images to standard structural medical images. Then, the standard 3D-brain model that shows well-defined brain regions was used, replacing the manual ROIs in the objective clinical analysis. To validate the performance, twenty cases of I-123 IBZM SPECT images were used in practical clinical evaluation. The results show that the quantitative analysis outcomes obtained from this automated method are in agreement with the clinical diagnosis evaluation score with less than 3% error in average. To sum up, the method takes advantage of obtaining precise VOIs, information automatically by well-defined standard 3-D brain model, sparing manually drawn ROIs slice by slice from structural medical images in traditional procedure. That is, the method not only can provide precise analysis results, but also improve the process rate for mass medical images in clinical.

Tractography patterns of subthalamic nucleus deep brain stimulation.

PubMed

Vanegas-Arroyave, Nora; Lauro, Peter M; Huang, Ling; Hallett, Mark; Horovitz, Silvina G; Zaghloul, Kareem A; Lungu, Codrin

2016-04-01

Deep brain stimulation therapy is an effective symptomatic treatment for Parkinson's disease, yet the precise mechanisms responsible for its therapeutic effects remain unclear. Although the targets of deep brain stimulation are grey matter structures, axonal modulation is known to play an important role in deep brain stimulation's therapeutic mechanism. Several white matter structures in proximity to the subthalamic nucleus have been implicated in the clinical benefits of deep brain stimulation for Parkinson's disease. We assessed the connectivity patterns that characterize clinically beneficial electrodes in Parkinson's disease patients, after deep brain stimulation of the subthalamic nucleus. We evaluated 22 patients with Parkinson's disease (11 females, age 57 ± 9.1 years, disease duration 13.3 ± 6.3 years) who received bilateral deep brain stimulation of the subthalamic nucleus at the National Institutes of Health. During an initial electrode screening session, one month after deep brain stimulation implantation, the clinical benefits of each contact were determined. The electrode was localized by coregistering preoperative magnetic resonance imaging and postoperative computer tomography images and the volume of tissue activated was estimated from stimulation voltage and impedance. Brain connectivity for the volume of tissue activated of deep brain stimulation contacts was assessed using probabilistic tractography with diffusion-tensor data. Areas most frequently connected to clinically effective contacts included the thalamus, substantia nigra, brainstem and superior frontal gyrus. A series of discriminant analyses demonstrated that the strength of connectivity to the superior frontal gyrus and the thalamus were positively associated with clinical effectiveness. The connectivity patterns observed in our study suggest that the modulation of white matter tracts directed to the superior frontal gyrus and the thalamus is associated with favourable clinical outcomes and may contribute to the therapeutic effects of deep brain stimulation. Our method can be further developed to reliably identify effective deep brain stimulation contacts and aid in the programming process. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Changes of focal and brainstem neurologic signs in patients with traumatic brain injury and their dependence on the -675 4G/5G polymorphism in the PAI-1 gene].

PubMed

Potapov, O; Kmyta, O

2014-09-01

Regressive course of neurological signs and symptoms is an important factor of evaluating the clinical course and treatment efficacy of traumatic brain injury. This article presents changes evaluation of focal and brainstem symptoms in 200 patients with traumatic brain injury, and determines the association between these changes and the -675 4G/5G polymorphism in the PAI-1 gene. We have found a connection between 4G/4G and 4G/5G genotypes for the studied polymorphism and the changes of focal and brainstem symptoms in patients with traumatic brain injury. Thus, we have demonstrated that the clinical course of traumatic brain injury is influenced by the -675 4G/5G polymorphism in the PAI-1 gene.

[Determination of irreversibility of clinical brain death. Electroencephalography and evoked potentials].

PubMed

Buchner, H; Ferbert, A

2016-02-01

Principally, in the fourth update of the rules for the procedure to finally determine the irreversible cessation of function of the cerebrum, the cerebellum and the brainstem, the importance of an electroencephalogram (EEG), somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) are confirmed. This paper presents the reliability and validity of the electrophysiological diagnosis, discusses the amendments in the fourth version of the guidelines and introduces the practical application, problems and sources of error.An EEG is the best established supplementary diagnostic method for determining the irreversibility of clinical brain death syndrome. It should be noted that residual brain activity can often persist for many hours after the onset of brain death syndrome, particularly in patients with primary brainstem lesions. The derivation and analysis of an EEG requires a high level of expertise to be able to safely distinguish artefacts from primary brain activity. The registration of EEGs to demonstrate the irreversibility of clinical brain death syndrome is extremely time consuming.The BAEPs can only be used to confirm the irreversibility of brain death syndrome in serial examinations or in the rare cases of a sustained wave I or sustained waves I and II. Very often, an investigation cannot be reliably performed because of existing sound conduction disturbances or failure of all potentials even before the onset of clinical brain death syndrome. This explains why BAEPs are only used in exceptional cases.The SEPs of the median nerve can be very reliably derived, are technically simple and with few sources of error. A serial investigation is not required and the time needed for examination is short. For these reasons SEPs are given preference over EEGs and BAEPs for establishing the irreversibility of clinical brain death syndrome.

Clinical, Cognitive, and Genetic Predictors of Change in Job Status Following Traumatic Brain Injury in a Military Population

PubMed Central

Han, S. Duke; Suzuki, Hideo; Drake, Angela I.; Jak, Amy J.; Houston, Wes S.; Bondi, Mark W.

2012-01-01

Objective Traumatic brain injury (TBI) is a risk associated with military duty, and residual effects from TBI may adversely affect a service member's ability to complete duties. It is, therefore, important to identify factors associated with a change in job status following TBI in an active military population. On the basis of previous research, we predicted that apolipoprotein E (APOE) genotype may be 1 factor. Design Cohort study of military personnel who sustained a mild to moderate TBI. Setting Military medical clinics. Patients or Other Participants Fifty-two military participants were recruited through the Defense and Veterans Brain Injury Center, affiliated with Naval Medical Center San Diego and the Defense and Veterans Brain Injury Center Concussion Clinic located at the First Marine Division at Camp Pendleton. Intervention(s) A multivariate statistical classification approach called optimal data analysis allowed for consideration of APOE genotype alongside cognitive, emotional, psychosocial, and physical functioning. Main Outcome Measure(s) APOE genotype, neuropsychological, psychosocial, and clinical outcomes. Results We identified a model of factors that was associated with a change in job status among military personnel who experienced a mild or moderate TBI. Conclusions Factors associated with a change in job status are different when APOE genotype is considered. We conclude that APOE genotype may be an important genetic factor in recovery from mild to moderate head injury. PMID:19158597

The potential role of sensory testing, skin biopsy, and functional brain imaging as biomarkers in chronic pain clinical trials: IMMPACT considerations

PubMed Central

Smith, Shannon M.; Dworkin, Robert H.; Turk, Dennis C.; Baron, Ralf; Polydefkis, Michael; Tracey, Irene; Borsook, David; Edwards, Robert R.; Harris, Richard E.; Wager, Tor D.; Arendt-Nielsen, Lars; Burke, Laurie B.; Carr, Daniel B.; Chappell, Amy; Farrar, John T.; Freeman, Roy; Gilron, Ian; Goli, Veeraindar; Haeussler, Juergen; Jensen, Troels; Katz, Nathaniel P.; Kent, Jeffrey; Kopecky, Ernest A.; Lee, David A.; Maixner, William; Markman, John D.; McArthur, Justin C.; McDermott, Michael P.; Parvathenani, Lav; Raja, Srinivasa N.; Rappaport, Bob A.; Rice, Andrew S. C.; Rowbotham, Michael C.; Tobias, Jeffrey K.; Wasan, Ajay D.; Witter, James

2017-01-01

Valid and reliable biomarkers can play an important role in clinical trials as indicators of biological or pathogenic processes or as a signal of treatment response. Currently, there are no biomarkers for pain qualified by the US Food and Drug Administration or the European Medicines Agency for use in clinical trials. This article summarizes an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) meeting in which 3 potential biomarkers were discussed for use in the development of analgesic treatments: (1) sensory testing, (2), skin punch biopsy, and (3) brain imaging. The empirical evidence supporting the use of these tests is described within the context of the 4 categories of biomarkers: (1) diagnostic, (2) prognostic, (3) predictive, and (4) pharmacodynamic. Although sensory testing, skin punch biopsy, and brain imaging are promising tools for pain in clinical trials, additional evidence is needed to further support and standardize these tests for use as biomarkers in pain clinical trials. PMID:28254585

[Factor structure of regional CBF and CMRglu values as a tool for the study of default mode of the brain].

PubMed

Kataev, G V; Korotkov, A D; Kireev, M V; Medvedev, S V

2013-01-01

In the present article it was shown that the functional connectivity of brain structures, revealed by factor analysis of resting PET CBF and rCMRglu data, is an adequate tool to study the default mode of the human brain. The identification of neuroanatomic systems of default mode (default mode network) during routine clinical PET investigations is important for further studying the functional organization of the normal brain and its reorganizations in pathological conditions.

Neuropsychiatric disorders in persons with severe traumatic brain injury: prevalence, phenomenology, and relationship with demographic, clinical, and functional features.

PubMed

Ciurli, Paola; Formisano, Rita; Bivona, Umberto; Cantagallo, Anna; Angelelli, Paola

2011-01-01

To characterize neuropsychiatric symptoms in a large group of individuals with severe traumatic brain injury (TBI) and to correlate these symptoms with demographic, clinical, and functional features. The Neuropsychiatric Inventory (NPI), a frequently used scale to assess behavioral, emotional, and motivational disorders in persons with neurological diseases, was administered to a sample of 120 persons with severe TBI. Controls were 77 healthy subjects. A wide range of neuropsychiatric symptoms was found in the population with severe TBI: apathy (42%), irritability (37%), dysphoria/depressed mood (29%), disinhibition (28%), eating disturbances (27%), and agitation (24%). A clear relationship was also found with other demographic and clinical variables. Neuropsychiatric disorders constitute an important part of the comorbidity in populations with severe TBI. Our study emphasizes the importance of integrating an overall assessment of cognitive disturbances with a specific neuropsychiatric evaluation to improve clinical understanding and treatment of persons with TBI.

Can the Brain Catch Up?

ERIC Educational Resources Information Center

Tizard, Jack

1974-01-01

The evidence points to the great importance of intra-uterine life and the first two years of childhood for brain growth and development. Follow-up studies of children hospitalized for severe clinical malnutrition in the first two years of life indicate that the ill effects of malnutrition persist; however, their consequences for growth and…

An Intracranial Electroencephalography (iEEG) Brain Function Mapping Tool with an Application to Epilepsy Surgery Evaluation.

PubMed

Wang, Yinghua; Yan, Jiaqing; Wen, Jianbin; Yu, Tao; Li, Xiaoli

2016-01-01

Before epilepsy surgeries, intracranial electroencephalography (iEEG) is often employed in function mapping and epileptogenic foci localization. Although the implanted electrodes provide crucial information for epileptogenic zone resection, a convenient clinical tool for electrode position registration and Brain Function Mapping (BFM) visualization is still lacking. In this study, we developed a BFM Tool, which facilitates electrode position registration and BFM visualization, with an application to epilepsy surgeries. The BFM Tool mainly utilizes electrode location registration and function mapping based on pre-defined brain models from other software. In addition, the electrode node and mapping properties, such as the node size/color, edge color/thickness, mapping method, can be adjusted easily using the setting panel. Moreover, users may manually import/export location and connectivity data to generate figures for further application. The role of this software is demonstrated by a clinical study of language area localization. The BFM Tool helps clinical doctors and researchers visualize implanted electrodes and brain functions in an easy, quick and flexible manner. Our tool provides convenient electrode registration, easy brain function visualization, and has good performance. It is clinical-oriented and is easy to deploy and use. The BFM tool is suitable for epilepsy and other clinical iEEG applications.

An Intracranial Electroencephalography (iEEG) Brain Function Mapping Tool with an Application to Epilepsy Surgery Evaluation

PubMed Central

Wang, Yinghua; Yan, Jiaqing; Wen, Jianbin; Yu, Tao; Li, Xiaoli

2016-01-01

Objects: Before epilepsy surgeries, intracranial electroencephalography (iEEG) is often employed in function mapping and epileptogenic foci localization. Although the implanted electrodes provide crucial information for epileptogenic zone resection, a convenient clinical tool for electrode position registration and Brain Function Mapping (BFM) visualization is still lacking. In this study, we developed a BFM Tool, which facilitates electrode position registration and BFM visualization, with an application to epilepsy surgeries. Methods: The BFM Tool mainly utilizes electrode location registration and function mapping based on pre-defined brain models from other software. In addition, the electrode node and mapping properties, such as the node size/color, edge color/thickness, mapping method, can be adjusted easily using the setting panel. Moreover, users may manually import/export location and connectivity data to generate figures for further application. The role of this software is demonstrated by a clinical study of language area localization. Results: The BFM Tool helps clinical doctors and researchers visualize implanted electrodes and brain functions in an easy, quick and flexible manner. Conclusions: Our tool provides convenient electrode registration, easy brain function visualization, and has good performance. It is clinical-oriented and is easy to deploy and use. The BFM tool is suitable for epilepsy and other clinical iEEG applications. PMID:27199729

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

Aita, J.F.; Keyes, J.W. Jr.

Two cases of acute infantile hemiplegia are presented. The first case is a patient with moyamoya disease with excellent correlation between the brain scan findings and her clinical signs and symptoms and the carotid arteriogram. The second patient had occlusive cerebrovascular disease secondary to thromboemboli with excellent correlation between the brain scan findings and his clinical state and the neuropathologic examination. In both cases the static brain scans and the radionuclide angiogram were comparable to those reported in adults with cerebrovascular disease both in appearance and in temporal sequence. Radionuclide studies can be an important and reliable diagnostic tool inmore » the evaluation of acute infantile hemiplegia. (auth)« less

Clinical correlates of verbal aggression, physical aggression and inappropriate sexual behaviour after brain injury.

PubMed

James, Andrew I W; Young, Andrew W

2013-01-01

To explore the relationships between verbal aggression, physical aggression and inappropriate sexual behaviour following acquired brain injury. Multivariate statistical modelling of observed verbal aggression, physical aggression and inappropriate sexual behaviour utilizing demographic, pre-morbid, injury-related and neurocognitive predictors. Clinical records of 152 participants with acquired brain injury were reviewed, providing an important data set as disordered behaviours had been recorded at the time of occurrence with the Brain Injury Rehabilitation Trust (BIRT) Aggression Rating Scale and complementary measures of inappropriate sexual behaviour. Three behavioural components (verbal aggression, physical aggression and inappropriate sexual behaviour) were identified and subjected to separate logistical regression modelling in a sub-set of 77 participants. Successful modelling was achieved for both verbal and physical aggression (correctly classifying 74% and 65% of participants, respectively), with use of psychotropic medication and poorer verbal function increasing the odds of aggression occurring. Pre-morbid history of aggression predicted verbal but not physical aggression. No variables predicted inappropriate sexual behaviour. Verbal aggression, physical aggression and inappropriate sexual behaviour following acquired brain injury appear to reflect separate clinical phenomena rather than general behavioural dysregulation. Clinical markers that indicate an increased risk of post-injury aggression were not related to inappropriate sexual behaviour.

Brain metastasization of breast cancer.

PubMed

Custódio-Santos, Tânia; Videira, Mafalda; Brito, Maria Alexandra

2017-08-01

Central nervous system metastases have been reported in 15-25% of breast cancer patients, and the incidence is increasing. Moreover, the survival of these patients is generally poor, with reports of a 1-year survival rate of 20%. Therefore, a better knowledge about the determinants of brain metastasization is essential for the improvement of the clinical outcomes. Here, we summarize the current data about the metastatic cascade, ranging from the output of cancer cells from the primary tumour to their colonization in the brain, which involves the epithelial-mesenchymal transition, invasion of mammary tissue, intravasation into circulation, and homing into and extravasation towards the brain. The phenotypic change in malignant cells, and the importance of the microenvironment in the formation of brain metastases are also inspected. Finally, the importance of genetic and epigenetic changes, and the recently disclosed effects of microRNAs in brain metastasization of breast cancer are highlighted. Copyright © 2017 Elsevier B.V. All rights reserved.

Sensorimotor Training in Virtual Reality: A Review

PubMed Central

Adamovich, Sergei V.; Fluet, Gerard G.; Tunik, Eugene; Merians, Alma S.

2010-01-01

Recent experimental evidence suggests that rapid advancement of virtual reality (VR) technologies has great potential for the development of novel strategies for sensorimotor training in neurorehabilitation. We discuss what the adaptive and engaging virtual environments can provide for massive and intensive sensorimotor stimulation needed to induce brain reorganization. Second, discrepancies between the veridical and virtual feedback can be introduced in VR to facilitate activation of targeted brain networks, which in turn can potentially speed up the recovery process. Here we review the existing experimental evidence regarding the beneficial effects of training in virtual environments on the recovery of function in the areas of gait, upper extremity function and balance, in various patient populations. We also discuss possible mechanisms underlying these effects. We feel that future research in the area of virtual rehabilitation should follow several important paths. Imaging studies to evaluate the effects of sensory manipulation on brain activation patterns and the effect of various training parameters on long term changes in brain function are needed to guide future clinical inquiry. Larger clinical studies are also needed to establish the efficacy of sensorimotor rehabilitation using VR approaches in various clinical populations and most importantly, to identify VR training parameters that are associated with optimal transfer into real-world functional improvements. PMID:19713617

Long-Term Consequences of Traumatic Brain Injury: Current Status of Potential Mechanisms of Injury and Neurological Outcomes.

PubMed

Bramlett, Helen M; Dietrich, W Dalton

2015-12-01

Traumatic brain injury (TBI) is a significant clinical problem with few therapeutic interventions successfully translated to the clinic. Increased importance on the progressive, long-term consequences of TBI have been emphasized, both in the experimental and clinical literature. Thus, there is a need for a better understanding of the chronic consequences of TBI, with the ultimate goal of developing novel therapeutic interventions to treat the devastating consequences of brain injury. In models of mild, moderate, and severe TBI, histopathological and behavioral studies have emphasized the progressive nature of the initial traumatic insult and the involvement of multiple pathophysiological mechanisms, including sustained injury cascades leading to prolonged motor and cognitive deficits. Recently, the increased incidence in age-dependent neurodegenerative diseases in this patient population has also been emphasized. Pathomechanisms felt to be active in the acute and long-term consequences of TBI include excitotoxicity, apoptosis, inflammatory events, seizures, demyelination, white matter pathology, as well as decreased neurogenesis. The current article will review many of these pathophysiological mechanisms that may be important targets for limiting the chronic consequences of TBI.

Advances in neuroimaging of traumatic brain injury and posttraumatic stress disorder

PubMed Central

Van Boven, Robert W.; Harrington, Greg S.; Hackney, David B.; Ebel, Andreas; Gauger, Grant; Bremner, J. Douglas; D’Esposito, Mark; Detre, John A.; Haacke, E. Mark; Jack, Clifford R.; Jagust, William J.; Le Bihan, Denis; Mathis, Chester A.; Mueller, Susanne; Mukherjee, Pratik; Schuff, Norbert; Chen, Anthony; Weiner, Michael W.

2011-01-01

Improved diagnosis and treatment of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are needed for our military and veterans, their families, and society at large. Advances in brain imaging offer important biomarkers of structural, functional, and metabolic information concerning the brain. This article reviews the application of various imaging techniques to the clinical problems of TBI and PTSD. For TBI, we focus on findings and advances in neuroimaging that hold promise for better detection, characterization, and monitoring of objective brain changes in symptomatic patients with combat-related, closed-head brain injuries not readily apparent by standard computed tomography or conventional magnetic resonance imaging techniques. PMID:20104401

Brain activity during driving with distraction: an immersive fMRI study

PubMed Central

Schweizer, Tom A.; Kan, Karen; Hung, Yuwen; Tam, Fred; Naglie, Gary; Graham, Simon J.

2013-01-01

Introduction: Non-invasive measurements of brain activity have an important role to play in understanding driving ability. The current study aimed to identify the neural underpinnings of human driving behavior by visualizing the areas of the brain involved in driving under different levels of demand, such as driving while distracted or making left turns at busy intersections. Materials and Methods: To capture brain activity during driving, we placed a driving simulator with a fully functional steering wheel and pedals in a 3.0 Tesla functional magnetic resonance imaging (fMRI) system. To identify the brain areas involved while performing different real-world driving maneuvers, participants completed tasks ranging from simple (right turns) to more complex (left turns at busy intersections). To assess the effects of driving while distracted, participants were asked to perform an auditory task while driving analogous to speaking on a hands-free device and driving. Results: A widely distributed brain network was identified, especially when making left turns at busy intersections compared to more simple driving tasks. During distracted driving, brain activation shifted dramatically from the posterior, visual and spatial areas to the prefrontal cortex. Conclusions: Our findings suggest that the distracted brain sacrificed areas in the posterior brain important for visual attention and alertness to recruit enough brain resources to perform a secondary, cognitive task. The present findings offer important new insights into the scientific understanding of the neuro-cognitive mechanisms of driving behavior and lay down an important foundation for future clinical research. PMID:23450757

Cerebral blood flow and autoregulation: current measurement techniques and prospects for noninvasive optical methods

PubMed Central

Fantini, Sergio; Sassaroli, Angelo; Tgavalekos, Kristen T.; Kornbluth, Joshua

2016-01-01

Abstract. Cerebral blood flow (CBF) and cerebral autoregulation (CA) are critically important to maintain proper brain perfusion and supply the brain with the necessary oxygen and energy substrates. Adequate brain perfusion is required to support normal brain function, to achieve successful aging, and to navigate acute and chronic medical conditions. We review the general principles of CBF measurements and the current techniques to measure CBF based on direct intravascular measurements, nuclear medicine, X-ray imaging, magnetic resonance imaging, ultrasound techniques, thermal diffusion, and optical methods. We also review techniques for arterial blood pressure measurements as well as theoretical and experimental methods for the assessment of CA, including recent approaches based on optical techniques. The assessment of cerebral perfusion in the clinical practice is also presented. The comprehensive description of principles, methods, and clinical requirements of CBF and CA measurements highlights the potentially important role that noninvasive optical methods can play in the assessment of neurovascular health. In fact, optical techniques have the ability to provide a noninvasive, quantitative, and continuous monitor of CBF and autoregulation. PMID:27403447

Developing Brain Vital Signs: Initial Framework for Monitoring Brain Function Changes Over Time

PubMed Central

Ghosh Hajra, Sujoy; Liu, Careesa C.; Song, Xiaowei; Fickling, Shaun; Liu, Luke E.; Pawlowski, Gabriela; Jorgensen, Janelle K.; Smith, Aynsley M.; Schnaider-Beeri, Michal; Van Den Broek, Rudi; Rizzotti, Rowena; Fisher, Kirk; D'Arcy, Ryan C. N.

2016-01-01

Clinical assessment of brain function relies heavily on indirect behavior-based tests. Unfortunately, behavior-based assessments are subjective and therefore susceptible to several confounding factors. Event-related brain potentials (ERPs), derived from electroencephalography (EEG), are often used to provide objective, physiological measures of brain function. Historically, ERPs have been characterized extensively within research settings, with limited but growing clinical applications. Over the past 20 years, we have developed clinical ERP applications for the evaluation of functional status following serious injury and/or disease. This work has identified an important gap: the need for a clinically accessible framework to evaluate ERP measures. Crucially, this enables baseline measures before brain dysfunction occurs, and might enable the routine collection of brain function metrics in the future much like blood pressure measures today. Here, we propose such a framework for extracting specific ERPs as potential “brain vital signs.” This framework enabled the translation/transformation of complex ERP data into accessible metrics of brain function for wider clinical utilization. To formalize the framework, three essential ERPs were selected as initial indicators: (1) the auditory N100 (Auditory sensation); (2) the auditory oddball P300 (Basic attention); and (3) the auditory speech processing N400 (Cognitive processing). First step validation was conducted on healthy younger and older adults (age range: 22–82 years). Results confirmed specific ERPs at the individual level (86.81–98.96%), verified predictable age-related differences (P300 latency delays in older adults, p < 0.05), and demonstrated successful linear transformation into the proposed brain vital sign (BVS) framework (basic attention latency sub-component of BVS framework reflects delays in older adults, p < 0.05). The findings represent an initial critical step in developing, extracting, and characterizing ERPs as vital signs, critical for subsequent evaluation of dysfunction in conditions like concussion and/or dementia. PMID:27242415

[Theory analysis and clinical application of spirit-regulating and pain-relieving acupuncture method].

PubMed

Chen, Liang; Tang, Lewei; Du, Huaibin; Zheng, Hui; Liang, Fanrong

2015-04-01

The theoretical foundation and scientific connotation of spirit-regulating and pain-relieving acupuncture method as well as its clinical application for pain are discussed. During spirit regulation, attention should be paid on regulating heart and brain, while acupoints should be selected mainly from the Heart Meridian, Pericardium Meridian and Governor Vessel. It has significant efficacy for refractory pain in clinical treatment. Spirit-regulating and pain-relieving acupuncture method is development of acupuncture treating spirit, and it is an important method for pain in clinic. Improvement on sensitization of pain center and brain function is considered as one of the mechanisms in spirit-regulating and pain-relieving acupuncture method.

Prevalence of clinically important traumatic brain injuries in children with minor blunt head trauma and isolated severe injury mechanisms.

PubMed

Nigrovic, Lise E; Lee, Lois K; Hoyle, John; Stanley, Rachel M; Gorelick, Marc H; Miskin, Michelle; Atabaki, Shireen M; Dayan, Peter S; Holmes, James F; Kuppermann, Nathan

2012-04-01

To determine the prevalence of clinically important traumatic brain injuries (TBIs) with severe injury mechanisms in children with minor blunt head trauma but with no other risk factors from the Pediatric Emergency Care Applied Research Network (PECARN) TBI prediction rules (defined as isolated severe injury mechanisms). Secondary analysis of a large prospective observational cohort study. Twenty-five emergency departments participating in the PECARN. Children with minor blunt head trauma and Glasgow Coma Scale scores of at least 14. Treating clinicians completed a structured data form that included injury mechanism (severity categories defined a priori). Clinically important TBIs were defined as intracranial injuries resulting in death, neurosurgical intervention, intubation for more than 24 hours, or hospital admission for at least 2 nights. We investigated the rate of clinically important TBIs in children with either severe injury mechanisms or isolated severe injury mechanisms. Of the 42,412 patients enrolled in the overall study, 42,099 (99%) had injury mechanisms recorded, and their data were included for analysis. Of all study patients, 5869 (14%) had severe injury mechanisms, and 3302 (8%) had isolated severe injury mechanisms. Overall, 367 children had clinically important TBIs (0.9%; 95% CI, 0.8%-1.0%). Of the 1327 children younger than 2 years with isolated severe injury mechanisms, 4 (0.3%; 95% CI, 0.1%-0.8%) had clinically important TBIs, as did 12 of the 1975 children 2 years or older (0.6%; 95% CI, 0.3%-1.1%). Children with isolated severe injury mechanisms are at low risk of clinically important TBI, and many do not require emergent neuroimaging.

Systems Neuroscience of Psychosis: Mapping Schizophrenia Symptoms onto Brain Systems.

PubMed

Strik, Werner; Stegmayer, Katharina; Walther, Sebastian; Dierks, Thomas

2017-01-01

Schizophrenia research has been in a deadlock for many decades. Despite important advances in clinical treatment, there are still major concerns regarding long-term psychosocial reintegration and disease management, biological heterogeneity, unsatisfactory predictors of individual course and treatment strategies, and a confusing variety of controversial theories about its etiology and pathophysiological mechanisms. In the present perspective on schizophrenia research, we first discuss a methodological pitfall in contemporary schizophrenia research inherent in the attempt to link mental phenomena with the brain: we claim that the time-honored phenomenological method of defining mental symptoms should not be contaminated with the naturalistic approach of modern neuroscience. We then describe our Systems Neuroscience of Psychosis (SyNoPsis) project, which aims to overcome this intrinsic problem of psychiatric research. Considering schizophrenia primarily as a disorder of interindividual communication, we developed a neurobiologically informed semiotics of psychotic disorders, as well as an operational clinical rating scale. The novel psychopathology allows disentangling the clinical manifestations of schizophrenia into behavioral domains matching the functions of three well-described higher-order corticobasal brain systems involved in interindividual human communication, namely, the limbic, associative, and motor loops, including their corticocortical sensorimotor connections. The results of several empirical studies support the hypothesis that the proposed three-dimensional symptom structure, segregated into the affective, the language, and the motor domain, can be specifically mapped onto structural and functional abnormalities of the respective brain systems. New pathophysiological hypotheses derived from this brain system-oriented approach have helped to develop and improve novel treatment strategies with noninvasive brain stimulation and practicable clinical parameters. In clinical practice, the novel psychopathology allows confining the communication deficits of the individual patient, shifting attention from the symptoms to the intact resources. We have studied this approach and observed important advantages for therapeutic alliances, personalized treatment, and de-escalation strategies. Future studies will further conjoin clinical definitions of psychotic symptoms with brain structures and functions, and disentangle structural and functional deficit patterns within these systems to identify neurobiologically distinct subsyndromes. Neurobiologically homogeneous patient groups may provide new momentum for treatment research. Finally, lessons learned from schizophrenia research may contribute to developing a comprehensive perspective on human experience and behavior that integrates methodologically distinct, but internally consistent, insights from humanities and neuroscience. © 2017 S. Karger AG, Basel.

Mentoring Women in the Frederick Community | Poster

Cancer.gov

Joy Beveridge, clinical project manager III, is all about building relationships. Her work as a clinical project manager requires her to manage teams such as the Coordinating Center for Clinical Trials, Center for Global Health, Brain Tumor Trials Collaborative, and Division of Cancer Treatment and Diagnosis. Equally important are the relationships Beveridge builds through her

Brain death and marginal grafts in liver transplantation.

PubMed

Jiménez-Castro, M B; Gracia-Sancho, J; Peralta, C

2015-06-04

It is well known that most organs for transplantation are currently procured from brain-dead donors; however, the presence of brain death is an important risk factor in liver transplantation. In addition, one of the mechanisms to avoid the shortage of liver grafts for transplant is the use of marginal livers, which may show higher risk of primary non-function or initial poor function. To our knowledge, very few reviews have focused in the field of liver transplantation using brain-dead donors; moreover, reviews that focused on both brain death and marginal grafts in liver transplantation, both being key risk factors in clinical practice, have not been published elsewhere. The present review aims to describe the recent findings and the state-of-the-art knowledge regarding the pathophysiological changes occurring during brain death, their effects on marginal liver grafts and summarize the more controversial topics of this pathology. We also review the therapeutic strategies designed to date to reduce the detrimental effects of brain death in both marginal and optimal livers, attempting to explain why such strategies have not solved the clinical problem of liver transplantation.

[Prosopagnosia and facial expression recognition].

PubMed

Koyama, Shinichi

2014-04-01

This paper reviews clinical neuropsychological studies that have indicated that the recognition of a person's identity and the recognition of facial expressions are processed by different cortical and subcortical areas of the brain. The fusiform gyrus, especially the right fusiform gyrus, plays an important role in the recognition of identity. The superior temporal sulcus, amygdala, and medial frontal cortex play important roles in facial-expression recognition. Both facial recognition and facial-expression recognition are highly intellectual processes that involve several regions of the brain.

COMPLEXITY AND HETEROGENEITY: WHAT DRIVES THE EVER-CHANGING BRAIN IN HUNTINGTONS DISEASE?

PubMed Central

Rosas, H. Diana; Salat, David H; Lee, Stephanie Y; Zaleta, Alexandra K; Hevelone, Nathanael; Hersch, Steven M.

2008-01-01

Significant advances are being made in our understanding of basic pathophyiological and biochemical mechanisms that cause HuntingtonÕs disease (HD). There is increasing reason to believe that pathologic alterations occur in the brain for years before symptoms manifest. The “classic” hallmark of neuropathology in HD is selective neurodegeneration in which vulnerable populations of neurons degenerate while less vulnerable populations are spared. While, the earliest and most striking neuropathologic changes have been found in the neostriatum, neuronal loss has been identified in many other regions of the brain. We report topologically selective, early, and progressive changes in the cortex, striatum, extra-striatal brain structures and white matter throughout the spectrum of disease. Our growing understanding of HD underscores the reality that points to the complexity of HD. A single, well-defined genetic mutation causes a cascade of events whose final result is an aggregate insult of the homeostatic process. We explore possible explanations for the selective vulnerability of the brain in HD. The ultimate goal in HD is to develop disease-modifying therapies that will prevent the onset of clinical symptoms in those individuals who are at risk and slow the progression of symptoms in those individuals already affected with symptoms. Understanding changes in brain morphometry and their relationship to clinical symptoms may provide important new and important insights into basic pathophysiological mechanisms at play in the disease. PMID:19076442

New insight in expression, transport, and secretion of brain-derived neurotrophic factor: Implications in brain-related diseases

PubMed Central

Adachi, Naoki; Numakawa, Tadahiro; Richards, Misty; Nakajima, Shingo; Kunugi, Hiroshi

2014-01-01

Brain-derived neurotrophic factor (BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to develop and maintain normal neuronal circuits in the brain. Given that loss of BDNF function has been reported in the brains of patients with neurodegenerative or psychiatric diseases, understanding basic properties of BDNF and associated intracellular processes is imperative. In this review, we revisit the gene structure, transcription, translation, transport and secretion mechanisms of BDNF. We also introduce implications of BDNF in several brain-related diseases including Alzheimer’s disease, Huntington’s disease, depression and schizophrenia. PMID:25426265

Multimodal brain-tumor segmentation based on Dirichlet process mixture model with anisotropic diffusion and Markov random field prior.

PubMed

Lu, Yisu; Jiang, Jun; Yang, Wei; Feng, Qianjin; Chen, Wufan

2014-01-01

Brain-tumor segmentation is an important clinical requirement for brain-tumor diagnosis and radiotherapy planning. It is well-known that the number of clusters is one of the most important parameters for automatic segmentation. However, it is difficult to define owing to the high diversity in appearance of tumor tissue among different patients and the ambiguous boundaries of lesions. In this study, a nonparametric mixture of Dirichlet process (MDP) model is applied to segment the tumor images, and the MDP segmentation can be performed without the initialization of the number of clusters. Because the classical MDP segmentation cannot be applied for real-time diagnosis, a new nonparametric segmentation algorithm combined with anisotropic diffusion and a Markov random field (MRF) smooth constraint is proposed in this study. Besides the segmentation of single modal brain-tumor images, we developed the algorithm to segment multimodal brain-tumor images by the magnetic resonance (MR) multimodal features and obtain the active tumor and edema in the same time. The proposed algorithm is evaluated using 32 multimodal MR glioma image sequences, and the segmentation results are compared with other approaches. The accuracy and computation time of our algorithm demonstrates very impressive performance and has a great potential for practical real-time clinical use.

Multimodal Brain-Tumor Segmentation Based on Dirichlet Process Mixture Model with Anisotropic Diffusion and Markov Random Field Prior

PubMed Central

Lu, Yisu; Jiang, Jun; Chen, Wufan

2014-01-01

Brain-tumor segmentation is an important clinical requirement for brain-tumor diagnosis and radiotherapy planning. It is well-known that the number of clusters is one of the most important parameters for automatic segmentation. However, it is difficult to define owing to the high diversity in appearance of tumor tissue among different patients and the ambiguous boundaries of lesions. In this study, a nonparametric mixture of Dirichlet process (MDP) model is applied to segment the tumor images, and the MDP segmentation can be performed without the initialization of the number of clusters. Because the classical MDP segmentation cannot be applied for real-time diagnosis, a new nonparametric segmentation algorithm combined with anisotropic diffusion and a Markov random field (MRF) smooth constraint is proposed in this study. Besides the segmentation of single modal brain-tumor images, we developed the algorithm to segment multimodal brain-tumor images by the magnetic resonance (MR) multimodal features and obtain the active tumor and edema in the same time. The proposed algorithm is evaluated using 32 multimodal MR glioma image sequences, and the segmentation results are compared with other approaches. The accuracy and computation time of our algorithm demonstrates very impressive performance and has a great potential for practical real-time clinical use. PMID:25254064

Concussion in the Military: an Evidence-Base Review of mTBI in US Military Personnel Focused on Posttraumatic Headache.

PubMed

Holtkamp, Matthew D; Grimes, Jamie; Ling, Geoffrey

2016-06-01

Traumatic brain injury (TBI) is defined as an alteration in brain function caused by an external force. Mild TBI or concussion is now well recognized to be a risk of military service as well as participation in athletic sports such as football. Posttraumatic headache (PTH) is the most common symptom after mTBI in US service members. PTH most commonly presents with migraine-like headache features. The following is an overview of the epidemiology, pathophysiology, clinical course, prognosis, complications, and treatment of mTBI and associated comorbidities with a focus on PTH. There is a particular emphasis on emerging evidence-based clinical practice. One important medical consequence of the recognition that mTBI is a highly prevalent among military service members is that the Department of Defense (DoD) is dedicating significant financial and intellectual resources to better understanding and developing treatments for TBI. The identification of the importance of TBI among the US military population has had the added benefit of increasing awareness of this condition among civilian populations, particularly those engaged in both professional and youth sports. The NIH and NSF are also supporting important TBI research. President Obama's Brain Initiative is also providing additional impetus for these efforts. Unfortunately, the understanding of the acute and chronic effects of mTBI on the brain remains limited. Gratefully, there is hope that through innovative research, there will be advances in elucidating the underlying pathophysiology, which will lead to clinical and prognostic indicators, ultimately resulting in new treatment options for this very complicated set of disorders.

Insulin transport into the brain.

PubMed

Gray, Sarah M; Barrett, Eugene J

2018-05-30

While there is a growing consensus that insulin has diverse and important regulatory actions on the brain, seemingly important aspects of brain insulin physiology are poorly understood. Examples include: what is the insulin concentration within brain interstitial fluid under normal physiologic conditions; whether insulin is made in the brain and acts locally; does insulin from the circulation cross the blood-brain barrier or the blood-CSF barrier in a fashion that facilitates its signaling in brain; is insulin degraded within the brain; do privileged areas with a "leaky" blood-brain barrier serve as signaling nodes for transmitting peripheral insulin signaling; does insulin action in the brain include regulation of amyloid peptides; whether insulin resistance is a cause or consequence of processes involved in cognitive decline. Heretofore, nearly all studies examining brain insulin physiology have employed techniques and methodologies that do not appreciate the complex fluid compartmentation and flow throughout the brain. This review attempts to provide a status report on historical and recent work that begins to address some of these issues. It is undertaken in an effort to suggest a framework for studies going forward. Such studies are inevitably influenced by recent physiologic and genetic studies of insulin accessing and acting in brain, discoveries relating to brain fluid dynamics and the interplay of cerebrospinal fluid, brain interstitial fluid, and brain lymphatics, and advances in clinical neuroimaging that underscore the dynamic role of neurovascular coupling.

Automatic brain tissue segmentation based on graph filter.

PubMed

Kong, Youyong; Chen, Xiaopeng; Wu, Jiasong; Zhang, Pinzheng; Chen, Yang; Shu, Huazhong

2018-05-09

Accurate segmentation of brain tissues from magnetic resonance imaging (MRI) is of significant importance in clinical applications and neuroscience research. Accurate segmentation is challenging due to the tissue heterogeneity, which is caused by noise, bias filed and partial volume effects. To overcome this limitation, this paper presents a novel algorithm for brain tissue segmentation based on supervoxel and graph filter. Firstly, an effective supervoxel method is employed to generate effective supervoxels for the 3D MRI image. Secondly, the supervoxels are classified into different types of tissues based on filtering of graph signals. The performance is evaluated on the BrainWeb 18 dataset and the Internet Brain Segmentation Repository (IBSR) 18 dataset. The proposed method achieves mean dice similarity coefficient (DSC) of 0.94, 0.92 and 0.90 for the segmentation of white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF) for BrainWeb 18 dataset, and mean DSC of 0.85, 0.87 and 0.57 for the segmentation of WM, GM and CSF for IBSR18 dataset. The proposed approach can well discriminate different types of brain tissues from the brain MRI image, which has high potential to be applied for clinical applications.

How cognitive neuroscience could be more biological—and what it might learn from clinical neuropsychology

PubMed Central

Frisch, Stefan

2014-01-01

Three widespread assumptions of Cognitive-affective Neuroscience are discussed: first, mental functions are assumed to be localized in circumscribed brain areas which can be exactly determined, at least in principle (localizationism). Second, this assumption is associated with the more general claim that these functions (and dysfunctions, such as in neurological or mental diseases) are somehow generated inside the brain (internalism). Third, these functions are seen to be “biological” in the sense that they can be decomposed and finally explained on the basis of elementary biological causes (i.e., genetic, molecular, neurophysiological etc.), causes that can be identified by experimental methods as the gold standard (isolationism). Clinical neuropsychology is widely assumed to support these tenets. However, by making reference to the ideas of Kurt Goldstein (1878–1965), one of its most important founders, I argue that none of these assumptions is sufficiently supported. From the perspective of a clinical-neuropsychological practitioner, assessing and treating brain damage sequelae reveals a quite different picture of the brain as well as of us “brain carriers”, making the organism (or person) in its specific environment the crucial reference point. This conclusion can be further elaborated: all experimental and clinical research on humans presupposes the notion of a situated, reflecting, and interacting subject, which precedes all kinds of scientific decomposition, however useful. These implications support the core assumptions of the embodiment approach to brain and mind, and, as I argue, Goldstein and his clinical-neuropsychological observations are part of its very origin, for both theoretical and historical reasons. PMID:25100981

Not single brain areas but a network is involved in language: Applications in presurgical planning.

PubMed

Alemi, Razieh; Batouli, Seyed Amir Hossein; Behzad, Ebrahim; Ebrahimpoor, Mitra; Oghabian, Mohammad Ali

2018-02-01

Language is an important human function, and is a determinant of the quality of life. In conditions such as brain lesions, disruption of the language function may occur, and lesion resection is a solution for that. Presurgical planning to determine the language-related brain areas would enhance the chances of language preservation after the operation; however, availability of a normative language template is essential. In this study, using data from 60 young individuals who were meticulously checked for mental and physical health, and using fMRI and robust imaging and data analysis methods, functional brain maps for the language production, perception and semantic were produced. The obtained templates showed that the language function should be considered as the product of the collaboration of a network of brain regions, instead of considering only few brain areas to be involved in that. This study has important clinical applications, and extends our knowledge on the neuroanatomy of the language function. Copyright © 2018 Elsevier B.V. All rights reserved.

Atherosclerosis in epilepsy: its causes and implications.

PubMed

Hamed, Sherifa A

2014-12-01

Evidence from epidemiological, longitudinal, prospective, double-blinded clinical trials as well as case reports documents age-accelerated atherosclerosis with increased carotid artery intima media thickness (CA-IMT) in patients with epilepsy. These findings raise concern regarding their implications for age-accelerated cognitive and behavioral changes in midlife and risk of later age-related cognitive disorders including neurodegenerative processes such as Alzheimer's disease (AD). Chronic epilepsy, cerebral atherosclerosis, and age-related cognitive disorders including AD share many clinical manifestations (e.g. characteristic cognitive deficits), risk factors, and structural and pathological brain abnormalities. These shared risk factors include increased CA-IMT, hyperhomocysteinemia (HHcy), lipid abnormalities, weight gain and obesity, insulin resistance (IR), and high levels of inflammatory and oxidative stresses. The resulting brain structural and pathological abnormalities include decreased volume of the hippocampus, increased cortical thinning of the frontal lobe, ventricular expansion and increased white matter ischemic disease, total brain atrophy, and β-amyloid protein deposition in the brain. The knowledge that age-accelerated atherosclerosis may contribute to age-accelerated cognitive and behavioral abnormalities and structural brain pathologies in patients with chronic epilepsy represents an important research path to pursue future clinical and management considerations. Copyright © 2014 Elsevier Inc. All rights reserved.

Coexistence of Multiple Sclerosis and Brain Tumor: An Uncommon Diagnostic Challenge.

PubMed

Abrishamchi, Fatemeh; Khorvash, Fariborz

2017-01-01

Nonneoplastic demyelinating processes of the brain with mass effect on magnetic resonance imaging can cause diagnostic difficulties. It requires differential diagnosis between the tumefactive demyelinating lesion and the coexistence of neoplasm. We document the case of 41-year-old woman with clinical and radiological findings suggestive of multiple sclerosis. Additional investigations confirmed the coexistence of astrocytoma. This report emphasizes the importance of considering brain tumors in the differential diagnosis of primary demyelinating disease presenting with a cerebral mass lesion.

Role of Interleukin-10 in Acute Brain Injuries

PubMed Central

Garcia, Joshua M.; Stillings, Stephanie A.; Leclerc, Jenna L.; Phillips, Harrison; Edwards, Nancy J.; Robicsek, Steven A.; Hoh, Brian L.; Blackburn, Spiros; Doré, Sylvain

2017-01-01

Interleukin-10 (IL-10) is an important anti-inflammatory cytokine expressed in response to brain injury, where it facilitates the resolution of inflammatory cascades, which if prolonged causes secondary brain damage. Here, we comprehensively review the current knowledge regarding the role of IL-10 in modulating outcomes following acute brain injury, including traumatic brain injury (TBI) and the various stroke subtypes. The vascular endothelium is closely tied to the pathophysiology of these neurological disorders and research has demonstrated clear vascular endothelial protective properties for IL-10. In vitro and in vivo models of ischemic stroke have convincingly directly and indirectly shown IL-10-mediated neuroprotection; although clinically, the role of IL-10 in predicting risk and outcomes is less clear. Comparatively, conclusive studies investigating the contribution of IL-10 in subarachnoid hemorrhage are lacking. Weak indirect evidence supporting the protective role of IL-10 in preclinical models of intracerebral hemorrhage exists; however, in the limited number of clinical studies, higher IL-10 levels seen post-ictus have been associated with worse outcomes. Similarly, preclinical TBI models have suggested a neuroprotective role for IL-10; although, controversy exists among the several clinical studies. In summary, while IL-10 is consistently elevated following acute brain injury, the effect of IL-10 appears to be pathology dependent, and preclinical and clinical studies often paradoxically yield opposite results. The pronounced and potent effects of IL-10 in the resolution of inflammation and inconsistency in the literature regarding the contribution of IL-10 in the setting of acute brain injury warrant further rigorously controlled and targeted investigation. PMID:28659854

Air pollution and detrimental effects on children's brain. The need for a multidisciplinary approach to the issue complexity and challenges.

PubMed

Calderón-Garcidueñas, Lilian; Torres-Jardón, Ricardo; Kulesza, Randy J; Park, Su-Bin; D'Angiulli, Amedeo

2014-01-01

Millions of children in polluted cities are showing brain detrimental effects. Urban children exhibit brain structural and volumetric abnormalities, systemic inflammation, olfactory, auditory, vestibular and cognitive deficits v low-pollution controls. Neuroinflammation and blood-brain-barrier (BBB) breakdown target the olfactory bulb, prefrontal cortex and brainstem, but are diffusely present throughout the brain. Urban adolescent Apolipoprotein E4 carriers significantly accelerate Alzheimer pathology. Neurocognitive effects of air pollution are substantial, apparent across all populations, and potentially clinically relevant as early evidence of evolving neurodegenerative changes. The diffuse nature of the neuroinflammation and neurodegeneration forces to employ a weight of evidence approach incorporating current clinical, cognitive, neurophysiological, radiological and epidemiological research. Pediatric air pollution research requires extensive multidisciplinary collaborations to accomplish a critical goal: to protect exposed children through multidimensional interventions having both broad impact and reach. Protecting children and teens from neural effects of air pollution should be of pressing importance for public health.

Air pollution and detrimental effects on children’s brain. The need for a multidisciplinary approach to the issue complexity and challenges

PubMed Central

Calderón-Garcidueñas, Lilian; Torres-Jardón, Ricardo; Kulesza, Randy J.; Park, Su-Bin; D’Angiulli, Amedeo

2014-01-01

Millions of children in polluted cities are showing brain detrimental effects. Urban children exhibit brain structural and volumetric abnormalities, systemic inflammation, olfactory, auditory, vestibular and cognitive deficits v low-pollution controls. Neuroinflammation and blood-brain-barrier (BBB) breakdown target the olfactory bulb, prefrontal cortex and brainstem, but are diffusely present throughout the brain. Urban adolescent Apolipoprotein E4 carriers significantly accelerate Alzheimer pathology. Neurocognitive effects of air pollution are substantial, apparent across all populations, and potentially clinically relevant as early evidence of evolving neurodegenerative changes. The diffuse nature of the neuroinflammation and neurodegeneration forces to employ a weight of evidence approach incorporating current clinical, cognitive, neurophysiological, radiological and epidemiological research. Pediatric air pollution research requires extensive multidisciplinary collaborations to accomplish a critical goal: to protect exposed children through multidimensional interventions having both broad impact and reach. Protecting children and teens from neural effects of air pollution should be of pressing importance for public health. PMID:25161617

A radiologic correlation with the basic functional neuroanatomy of the brain.

PubMed

Bilicka, Z; Liska, M; Bluska, P; Bilicky, J

2014-01-01

Primary cortical areas for motor, sensory and sensitive functions are localized in certain areas of the brain cortex. In clinical practice, cross sectional imaging (computer tomography and magnetic resonance) is wildy used for diagnostics purpose, treatment planning and follow up of the patients. Accurate orientation in brain structures is necessary for the evaluation of radiological images. There are numerable landmark signs, which can be used for precise identification of important brain structures. In this review article, the mostly used anatomical landmarks are described and shown on the cross sectional images (magnetic resonance imaging) (Fig. 14, Ref. 25).

Issues of cultural diversity in acquired brain injury (ABI) rehabilitation.

PubMed

Lequerica, Anthony; Krch, Denise

2014-01-01

With the general population in the United States becoming increasingly diverse, it is important for rehabilitation professionals to develop the capacity to provide culturally sensitive treatment. This is especially relevant when working with minority populations who have a higher risk for brain injury and poorer rehabilitation outcomes. This article presents a number of clinical vignettes to illustrate how cultural factors can influence behavior in patients recovering from brain injury, as well as rehabilitation staff. The main objectives are to raise awareness among clinicians and stimulate research ideas by highlighting some real world examples of situations where a specialized, patient-centered approach needs to consider factors of cultural diversity. Because one's own world view impacts the way we see the world and interpret behavior, it is important to understand one's own ethnocentrism when dealing with a diverse population of patients with brain injury where behavioral sequelae are often expected. Being able to see behavior after brain injury with an open mind and taking into account cultural and contextual factors is an important step in developing culturally competent rehabilitation practices.

Modelling verbal aggression, physical aggression and inappropriate sexual behaviour after acquired brain injury

PubMed Central

James, Andrew I. W.; Böhnke, Jan R.; Young, Andrew W.; Lewis, Gary J.

2015-01-01

Understanding the underpinnings of behavioural disturbances following brain injury is of considerable importance, but little at present is known about the relationships between different types of behavioural disturbances. Here, we take a novel approach to this issue by using confirmatory factor analysis to elucidate the architecture of verbal aggression, physical aggression and inappropriate sexual behaviour using systematic records made across an eight-week observation period for a large sample (n = 301) of individuals with a range of brain injuries. This approach offers a powerful test of the architecture of these behavioural disturbances by testing the fit between observed behaviours and different theoretical models. We chose models that reflected alternative theoretical perspectives based on generalized disinhibition (Model 1), a difference between aggression and inappropriate sexual behaviour (Model 2), or on the idea that verbal aggression, physical aggression and inappropriate sexual behaviour reflect broadly distinct but correlated clinical phenomena (Model 3). Model 3 provided the best fit to the data indicating that these behaviours can be viewed as distinct, but with substantial overlap. These data are important both for developing models concerning the architecture of behaviour as well as for clinical management in individuals with brain injury. PMID:26136449

Molecular, Cellular and Functional Effects of Radiation-Induced Brain Injury: A Review

PubMed Central

Balentova, Sona; Adamkov, Marian

2015-01-01

Radiation therapy is the most effective non-surgical treatment of primary brain tumors and metastases. Preclinical studies have provided valuable insights into pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced brain injury can damage neuronal, glial and vascular compartments of the brain and may lead to molecular, cellular and functional changes. Given its central role in memory and adult neurogenesis, the majority of studies have focused on the hippocampus. These findings suggested that hippocampal avoidance in cranial radiotherapy prevents radiation-induced cognitive impairment of patients. However, multiple rodent studies have shown that this problem is more complex. As the radiation-induced cognitive impairment reflects hippocampal and non-hippocampal compartments, it is of critical importance to investigate molecular, cellular and functional modifications in various brain regions as well as their integration at clinically relevant doses and schedules. We here provide a literature overview, including our previously published results, in order to support the translation of preclinical findings to clinical practice, and improve the physical and mental status of patients with brain tumors. PMID:26610477

All the Vice Chancellor's Neuroscientists: Unity to Achieve Success in Solving Malaysia's Diseases via Upgrading Clinical Services and Neuroscience Research.

PubMed

Abdullah, Jafri Malin

2013-05-01

President Obama of the United States of America announced this April the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN for short) investment, while Professor Henry Markram's team based in the European Union will spend over a billion euros on the Human Brain Project, breaking through the unknowns in the fifth science of the decade: Neuroscience. Malaysia's growth in the same field needs to be augmented, and thus the Universiti Sains Malaysia's vision is to excel in the field of clinical brain sciences, mind sciences and neurosciences. This will naturally bring up the level of research in the country simultaneously. Thus, a center was recently established to coordinate this venture. The four-year Integrated Neuroscience Program established recently will be a sustainable source of neuroscientists for the country. We hope to establish ourselves by 2020 as a global university with neurosciences research as an important flagship.

Brain-Heart Interaction: Cardiac Complications After Stroke.

PubMed

Chen, Zhili; Venkat, Poornima; Seyfried, Don; Chopp, Michael; Yan, Tao; Chen, Jieli

2017-08-04

Neurocardiology is an emerging specialty that addresses the interaction between the brain and the heart, that is, the effects of cardiac injury on the brain and the effects of brain injury on the heart. This review article focuses on cardiac dysfunction in the setting of stroke such as ischemic stroke, brain hemorrhage, and subarachnoid hemorrhage. The majority of post-stroke deaths are attributed to neurological damage, and cardiovascular complications are the second leading cause of post-stroke mortality. Accumulating clinical and experimental evidence suggests a causal relationship between brain damage and heart dysfunction. Thus, it is important to determine whether cardiac dysfunction is triggered by stroke, is an unrelated complication, or is the underlying cause of stroke. Stroke-induced cardiac damage may lead to fatality or potentially lifelong cardiac problems (such as heart failure), or to mild and recoverable damage such as neurogenic stress cardiomyopathy and Takotsubo cardiomyopathy. The role of location and lateralization of brain lesions after stroke in brain-heart interaction; clinical biomarkers and manifestations of cardiac complications; and underlying mechanisms of brain-heart interaction after stroke, such as the hypothalamic-pituitary-adrenal axis; catecholamine surge; sympathetic and parasympathetic regulation; microvesicles; microRNAs; gut microbiome, immunoresponse, and systemic inflammation, are discussed. © 2017 American Heart Association, Inc.

Brain structure in sagittal craniosynostosis

NASA Astrophysics Data System (ADS)

Paniagua, Beatriz; Kim, Sunghyung; Moustapha, Mahmoud; Styner, Martin; Cody-Hazlett, Heather; Gimple-Smith, Rachel; Rumple, Ashley; Piven, Joseph; Gilmore, John; Skolnick, Gary; Patel, Kamlesh

2017-03-01

Craniosynostosis, the premature fusion of one or more cranial sutures, leads to grossly abnormal head shapes and pressure elevations within the brain caused by these deformities. To date, accepted treatments for craniosynostosis involve improving surgical skull shape aesthetics. However, the relationship between improved head shape and brain structure after surgery has not been yet established. Typically, clinical standard care involves the collection of diagnostic medical computed tomography (CT) imaging to evaluate the fused sutures and plan the surgical treatment. CT is known to provide very good reconstructions of the hard tissues in the skull but it fails to acquire good soft brain tissue contrast. This study intends to use magnetic resonance imaging to evaluate brain structure in a small dataset of sagittal craniosynostosis patients and thus quantify the effects of surgical intervention in overall brain structure. Very importantly, these effects are to be contrasted with normative shape, volume and brain structure databases. The work presented here wants to address gaps in clinical knowledge in craniosynostosis focusing on understanding the changes in brain volume and shape secondary to surgery, and compare those with normally developing children. This initial pilot study has the potential to add significant quality to the surgical care of a vulnerable patient population in whom we currently have limited understanding of brain developmental outcomes.

Preliminary investigation of Brain Network Activation (BNA) and its clinical utility in sport-related concussion.

PubMed

Reches, A; Kutcher, J; Elbin, R J; Or-Ly, H; Sadeh, B; Greer, J; McAllister, D J; Geva, A; Kontos, A P

2017-01-01

The clinical diagnosis and management of patients with sport-related concussion is largely dependent on subjectively reported symptoms, clinical examinations, cognitive, balance, vestibular and oculomotor testing. Consequently, there is an unmet need for objective assessment tools that can identify the injury from a physiological perspective and add an important layer of information to the clinician's decision-making process. The goal of the study was to evaluate the clinical utility of the EEG-based tool named Brain Network Activation (BNA) as a longitudinal assessment method of brain function in the management of young athletes with concussion. Athletes with concussion (n = 86) and age-matched controls (n = 81) were evaluated at four time points with symptom questionnaires and BNA. BNA scores were calculated by comparing functional networks to a previously defined normative reference brain network model to the same cognitive task. Subjects above 16 years of age exhibited a significant decrease in BNA scores immediately following injury, as well as notable changes in functional network activity, relative to the controls. Three representative case studies of the tested population are discussed in detail, to demonstrate the clinical utility of BNA. The data support the utility of BNA to augment clinical examinations, symptoms and additional tests by providing an effective method for evaluating objective electrophysiological changes associated with sport-related concussions.

Preliminary investigation of Brain Network Activation (BNA) and its clinical utility in sport-related concussion

PubMed Central

Reches, A.; Kutcher, J.; Elbin, R. J.; Or-Ly, H.; Sadeh, B.; Greer, J.; McAllister, D. J.; Geva, A.; Kontos, A. P.

2017-01-01

ABSTRACT Background: The clinical diagnosis and management of patients with sport-related concussion is largely dependent on subjectively reported symptoms, clinical examinations, cognitive, balance, vestibular and oculomotor testing. Consequently, there is an unmet need for objective assessment tools that can identify the injury from a physiological perspective and add an important layer of information to the clinician’s decision-making process. Objective: The goal of the study was to evaluate the clinical utility of the EEG-based tool named Brain Network Activation (BNA) as a longitudinal assessment method of brain function in the management of young athletes with concussion. Methods: Athletes with concussion (n = 86) and age-matched controls (n = 81) were evaluated at four time points with symptom questionnaires and BNA. BNA scores were calculated by comparing functional networks to a previously defined normative reference brain network model to the same cognitive task. Results: Subjects above 16 years of age exhibited a significant decrease in BNA scores immediately following injury, as well as notable changes in functional network activity, relative to the controls. Three representative case studies of the tested population are discussed in detail, to demonstrate the clinical utility of BNA. Conclusion: The data support the utility of BNA to augment clinical examinations, symptoms and additional tests by providing an effective method for evaluating objective electrophysiological changes associated with sport-related concussions. PMID:28055228

The Potential Role of Sensory Testing, Skin Biopsy, and Functional Brain Imaging as Biomarkers in Chronic Pain Clinical Trials: IMMPACT Considerations.

PubMed

Smith, Shannon M; Dworkin, Robert H; Turk, Dennis C; Baron, Ralf; Polydefkis, Michael; Tracey, Irene; Borsook, David; Edwards, Robert R; Harris, Richard E; Wager, Tor D; Arendt-Nielsen, Lars; Burke, Laurie B; Carr, Daniel B; Chappell, Amy; Farrar, John T; Freeman, Roy; Gilron, Ian; Goli, Veeraindar; Haeussler, Juergen; Jensen, Troels; Katz, Nathaniel P; Kent, Jeffrey; Kopecky, Ernest A; Lee, David A; Maixner, William; Markman, John D; McArthur, Justin C; McDermott, Michael P; Parvathenani, Lav; Raja, Srinivasa N; Rappaport, Bob A; Rice, Andrew S C; Rowbotham, Michael C; Tobias, Jeffrey K; Wasan, Ajay D; Witter, James

2017-07-01

Valid and reliable biomarkers can play an important role in clinical trials as indicators of biological or pathogenic processes or as a signal of treatment response. Currently, there are no biomarkers for pain qualified by the U.S. Food and Drug Administration or the European Medicines Agency for use in clinical trials. This article summarizes an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials meeting in which 3 potential biomarkers were discussed for use in the development of analgesic treatments: 1) sensory testing, 2) skin punch biopsy, and 3) brain imaging. The empirical evidence supporting the use of these tests is described within the context of the 4 categories of biomarkers: 1) diagnostic, 2) prognostic, 3) predictive, and 4) pharmacodynamic. Although sensory testing, skin punch biopsy, and brain imaging are promising tools for pain in clinical trials, additional evidence is needed to further support and standardize these tests for use as biomarkers in pain clinical trials. The applicability of sensory testing, skin biopsy, and brain imaging as diagnostic, prognostic, predictive, and pharmacodynamic biomarkers for use in analgesic treatment trials is considered. Evidence in support of their use and outlining problems is presented, as well as a call for further standardization and demonstrations of validity and reliability. Copyright © 2017 American Pain Society. All rights reserved.

Quantitative assessment of brain stem and cerebellar atrophy in spinocerebellar ataxia types 3 and 6: impact on clinical status.

PubMed

Eichler, L; Bellenberg, B; Hahn, H K; Köster, O; Schöls, L; Lukas, C

2011-05-01

Cerebellar and brain stem atrophy are important features in SCA3, whereas SCA6 has been regarded as a "pure" cerebellar disease. However, recent neuropathologic studies have described additional brain stem involvement in SCA6. We, therefore, aimed to investigate the occurrence and impact of regional infratentorial brain volume differences in patients with SCA3 and SCA6. Thirty-four patients with genetically proved SCA (SCA3, n = 17; SCA6, n = 17) and age-matched healthy control subjects (n = 51) were included. In all subjects, high-resolution T1-weighted images were acquired with a 1.5T MR imaging scanner. Individual brain stem and cerebellar volumes were calculated by using semiautomated volumetry approaches. For all patients with SCA, clinical dysfunction was scored according to the ICARS. Multiple regression analysis was used to identify the contribution of regional volumes to explain the variance in clinical dysfunction in each SCA genotype. Cerebellar volumes were lower in patients with SCA6 compared with controls and with those with SCA3. In contrast to controls, brain stem volume loss was observed in patients with SCA3 (P < .001) and, to a lesser extent, in those with SCA6 (P = .027). Significant linear dependencies were found between ICARS and cerebellum volume (SCA3: R(2) = 0.29, P = .02; SCA6: R(2) = 0.29, P = .03) and between ICARS and brain stem volume (SCA3: R(2) = 0.49, P = .002; SCA6: R(2) = 0.39, P < .01) in both subtypes. Both cerebellar and brain stem atrophy contributed independently to the variance in clinical dysfunction in SCA6, while in SCA3, only brain stem atrophy was of relevance. Our current findings in accordance with recent neuroradiologic and pathoanatomic studies suggest brain stem and cerebellar volume loss as attractive surrogate markers of disease severity in SCA3 and SCA6.

The national DBS brain tissue network pilot study: need for more tissue and more standardization.

PubMed

Vedam-Mai, V; Krock, N; Ullman, M; Foote, K D; Shain, W; Smith, K; Yachnis, A T; Steindler, D; Reynolds, B; Merritt, S; Pagan, F; Marjama-Lyons, J; Hogarth, P; Resnick, A S; Zeilman, P; Okun, M S

2011-08-01

Over 70,000 DBS devices have been implanted worldwide; however, there remains a paucity of well-characterized post-mortem DBS brains available to researchers. We propose that the overall understanding of DBS can be improved through the establishment of a Deep Brain Stimulation-Brain Tissue Network (DBS-BTN), which will further our understanding of DBS and brain function. The objectives of the tissue bank are twofold: (a) to provide a complete (clinical, imaging and pathological) database for DBS brain tissue samples, and (b) to make available DBS tissue samples to researchers, which will help our understanding of disease and underlying brain circuitry. Standard operating procedures for processing DBS brains were developed as part of the pilot project. Complete data files were created for individual patients and included demographic information, clinical information, imaging data, pathology, and DBS lead locations/settings. 19 DBS brains were collected from 11 geographically dispersed centers from across the U.S. The average age at the time of death was 69.3 years (51-92, with a standard deviation or SD of 10.13). The male:female ratio was almost 3:1. Average post-mortem interval from death to brain collection was 10.6 h (SD of 7.17). The DBS targets included: subthalamic nucleus, globus pallidus interna, and ventralis intermedius nucleus of the thalamus. In 16.7% of cases the clinical diagnosis failed to match the pathological diagnosis. We provide neuropathological findings from the cohort, and perilead responses to DBS. One of the most important observations made in this pilot study was the missing data, which was approximately 25% of all available data fields. Preliminary results demonstrated the feasibility and utility of creating a National DBS-BTN resource for the scientific community. We plan to improve our techniques to remedy omitted clinical/research data, and expand the Network to include a larger donor pool. We will enhance sample preparation to facilitate advanced molecular studies and progenitor cell retrieval.

Dementia resulting from traumatic brain injury

PubMed Central

Ramalho, Joana; Castillo, Mauricio

2015-01-01

Traumatic brain injury (TBI) represents a significant public health problem in modern societies. It is primarily a consequence of traffic-related accidents and falls. Other recently recognized causes include sports injuries and indirect forces such as shock waves from battlefield explosions. TBI is an important cause of death and lifelong disability and represents the most well-established environmental risk factor for dementia. With the growing recognition that even mild head injury can lead to neurocognitive deficits, imaging of brain injury has assumed greater importance. However, there is no single imaging modality capable of characterizing TBI. Current advances, particularly in MR imaging, enable visualization and quantification of structural and functional brain changes not hitherto possible. In this review, we summarize data linking TBI with dementia, emphasizing the imaging techniques currently available in clinical practice along with some advances in medical knowledge. PMID:29213985

Brain damage resembling acute necrotizing encephalopathy as a specific manifestation of haemophagocytic lymphohistiocytosis - induced by hypersensitivity.

PubMed

Dai, Dongling; Wen, Feiqiu; Liu, Sixi; Zhou, Shaoming

2016-08-31

Both haemophagocytic lymphohistiocytosis and acute necrotizing encephalopathy are life-threatening condition. It presents major diagnostic difficulties, since it may have a diversity in clinical picture and with many conditions leading to the same clinical presentation. So it is key important to understand the disorders. We report a pediatric case of haemophagocytic lymphohistiocytosis with specific presentation which predominantly featured as acute necrotizing encephalopathy of childhood. We discuss the diagnosis and differential diagnosis, and speculate the etiology of haemophagocytic lymphohistiocytosis is due to hypersensitivity. Haemophagocytic lymphohistiocytosis and brain damage in this case may be induced by hypersensitivity, which have good clinical outcome if diagnosed and treated early.

Thinking through postoperative cognitive dysfunction: How to bridge the gap between clinical and pre-clinical perspectives.

PubMed

Hovens, Iris B; Schoemaker, Regien G; van der Zee, Eddy A; Heineman, Erik; Izaks, Gerbrand J; van Leeuwen, Barbara L

2012-10-01

Following surgery, patients may experience cognitive decline, which can seriously reduce quality of life. This postoperative cognitive dysfunction (POCD) is mainly seen in the elderly and is thought to be mediated by surgery-induced inflammatory reactions. Clinical studies tend to define POCD as a persisting, generalised decline in cognition, without specifying which cognitive functions are impaired. Pre-clinical research mainly describes early hippocampal dysfunction as a consequence of surgery-induced neuroinflammation. These different approaches to study POCD impede translation between clinical and pre-clinical research outcomes and may hamper the development of appropriate interventions. This article analyses which cognitive domains deteriorate after surgery and which brain areas might be involved. The most important outcomes are: (1) POCD encompasses a wide range of cognitive impairments; (2) POCD affects larger areas of the brain; and (3) individual variation in the vulnerability of neuronal networks to neuroinflammatory mechanisms may determine if and how POCD manifests itself. We argue that, for pre-clinical and clinical research of POCD to advance, the effects of surgery on various cognitive functions and brain areas should be studied. Moreover, in addition to general characteristics, research should take inter-relationships between cognitive complaints and physical and mental characteristics into account. Copyright © 2012 Elsevier Inc. All rights reserved.

Psychiatric Brain Banking: Three Perspectives on Current Trends and Future Directions

PubMed Central

Deep-Soboslay, Amy; Benes, Francine M.; Haroutunian, Vahram; Ellis, Justin K.; Kleinman, Joel E.; Hyde, Thomas M.

2011-01-01

Introduction The study of postmortem human brain tissue is central to the advancement of the neurobiological studies of psychiatric illness, particularly for the study of brain-specific isoforms and molecules. Methods The state-of-the-art methods and recommendations for maintaining a successful brain bank for psychiatric disorders are discussed, using the convergence of viewpoints from three brain collections, the National Institute of Mental Health Brain Collection (NIMH), the Harvard Brain Tissue Resource Center (HBTRC), and the Mt. Sinai School of Medicine Brain Bank (MSSM-BB), with diverse research interests and divergent approaches to tissue acquisition. Results While the NIMH obtains donations from medical examiners for its collection, and places particular emphasis on clinical diagnosis, toxicology, and building lifespan control cohorts, the HBTRC is uniquely designed as a repository whose sole purpose is to collect large-volume, high quality brain tissue from community-based donors based on relationships across an expansive nationwide network, and places emphasis on the accessibility of its bank in disseminating tissue and related data to research groups worldwide. The MSSM-BB collection has shown that, with dedication, prospective recruitment is a successful approach to tissue donation, and places particular emphasis on rigorous clinical diagnosis through antemortem contact with donors. The MSSM-BB places great importance on stereological tissue sampling methods for neuroanatomical studies, and frozen tissue sampling approaches that enable multiple assessments (RNA, DNA, protein, enzyme activity, binding, etc.) of the same tissue block. Promising scientific approaches for elucidating the molecular and cellular pathways in brain that may contribute to schizophrenia and/or bipolar disorder, such as cell culture techniques and microarray-based gene expression and genotyping studies are briefly discussed. Conclusions Despite unique perspectives from three established brain collections, there is a consensus that (1) diverse strategies for tissue acquisition, (2) rigor in tissue and diagnostic characterization, (3) the importance of sample accessibility, and (4) continual application of innovative scientific approaches to the study of brain tissue are all integral to the success and future of psychiatric brain banking. The future of neuropsychiatric research depends upon in the availability of high quality brain specimens from large numbers of subjects, including non-psychiatric controls. PMID:20673875

Creating and parameterizing patient-specific deep brain stimulation pathway-activation models using the hyperdirect pathway as an example.

PubMed

Gunalan, Kabilar; Chaturvedi, Ashutosh; Howell, Bryan; Duchin, Yuval; Lempka, Scott F; Patriat, Remi; Sapiro, Guillermo; Harel, Noam; McIntyre, Cameron C

2017-01-01

Deep brain stimulation (DBS) is an established clinical therapy and computational models have played an important role in advancing the technology. Patient-specific DBS models are now common tools in both academic and industrial research, as well as clinical software systems. However, the exact methodology for creating patient-specific DBS models can vary substantially and important technical details are often missing from published reports. Provide a detailed description of the assembly workflow and parameterization of a patient-specific DBS pathway-activation model (PAM) and predict the response of the hyperdirect pathway to clinical stimulation. Integration of multiple software tools (e.g. COMSOL, MATLAB, FSL, NEURON, Python) enables the creation and visualization of a DBS PAM. An example DBS PAM was developed using 7T magnetic resonance imaging data from a single unilaterally implanted patient with Parkinson's disease (PD). This detailed description implements our best computational practices and most elaborate parameterization steps, as defined from over a decade of technical evolution. Pathway recruitment curves and strength-duration relationships highlight the non-linear response of axons to changes in the DBS parameter settings. Parameterization of patient-specific DBS models can be highly detailed and constrained, thereby providing confidence in the simulation predictions, but at the expense of time demanding technical implementation steps. DBS PAMs represent new tools for investigating possible correlations between brain pathway activation patterns and clinical symptom modulation.

Clinically-Important Brain Injury and CT Findings in Pediatric Mild Traumatic Brain Injuries: A Prospective Study in a Chinese Reference Hospital

PubMed Central

Zhu, Huiping; Gao, Qi; Xia, Xin; Xiang, Joe; Yao, Hongli; Shao, Jianbo

2014-01-01

This study investigated injury patterns and the use of computed tomography (CT) among Chinese children with mild traumatic brain injury (MTBI). We enrolled children with MTBI who were treated within 24 hours of head trauma in the emergency department of Wuhan Medical Care Center for Women and Children in Wuhan, China. Characteristics of MTBIs were analyzed by age and gender. Results of cranial CT scan and clinically-important brain injury (ciTBI) for children were obtained. The definition of ciTBI was: death from TBI, intubation for more than 24 h for TBI, neurosurgery, or hospital admission of 2 nights or more. Of 455 eligible patients with MTBI, ciTBI occurred in two, and no one underwent neurosurgical intervention. CT scans were performed for 441 TBI patients (96.9%), and abnormal findings were reported for 147 patients (33.3%, 95% CI 29.0–37.8). Falls were the leading cause of MTBI (61.5%), followed by blows (18.9%) and traffic collisions (14.1%) for children in the 0–2 group and 10–14 group. For children aged between 3 and 9, the top three causes of TBI were falls, traffic collisions and blows. Leisure activity was the most reported activity when injuries occurred for all age groups. Sleeping/resting and walking ranked in the second and third place for children between 0 and 2 years of age, and walking and riding for the other two groups. The places where the majority injuries occurred were the home for the 0–2 and 3–9 years of age groups, and school for the 10–14 years of age group. There was no statistical difference between boys and girls with regard to the activity that caused the MTBI. This study highlights the important roles that parents and school administrators in the development of preventive measures to reduce the risk of traumatic brain injury in children. Also, identifying children who had a head trauma at very low risk of clinically important TBI for whom CT might be unnecessary is a priority area of research in China. PMID:24675642

Intranasal epidermal growth factor treatment rescues neonatal brain injury.

PubMed

Scafidi, Joseph; Hammond, Timothy R; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J; Hyder, Fahmeed; Horvath, Tamas L; Gallo, Vittorio

2014-02-13

There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

Intranasal epidermal growth factor treatment rescues neonatal brain injury

NASA Astrophysics Data System (ADS)

Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

2014-02-01

There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

Brain Tumor Epidemiology – A Hub within Multidisciplinary Neuro-oncology. Report on the 15th Brain Tumor Epidemiology Consortium (BTEC) Annual Meeting, Vienna, 2014

PubMed Central

Woehrer, Adelheid; Lau, Ching C.; Prayer, Daniela; Bauchet, Luc; Rosenfeld, Myrna; Capper, David; Fisher, Paul G.; Kool, Marcel; Müller, Martin; Kros, Johan M.; Kruchko, Carol; Wiemels, Joseph; Wrensch, Margaret; Danysh, Heather E.; Zouaoui, Sonia; Heck, Julia E.; Johnson, Kimberly J.; Qi, Xiaoyang; O’Neill, Brian P.; Afzal, Samina; Scheurer, Michael E.; Bainbridge, Matthew N.; Nousome, Darryl; El Bahassi, Mustapha; Hainfellner, Johannes A.; Barnholtz-Sloan, Jill S.

2015-01-01

The Brain Tumor Epidemiology Consortium (BTEC) is an open scientific forum, which fosters the development of multi-center, international and inter-disciplinary collaborations. BTEC aims to develop a better understanding of the etiology, outcomes, and prevention of brain tumors (http://epi.grants.cancer.gov/btec/). The 15th annual Brain Tumor Epidemiology Consortium Meeting, hosted by the Austrian Societies of Neuropathology and Neuro-oncology, was held on September 9 – 11, 2014 in Vienna, Austria. The meeting focused on the central role of brain tumor epidemiology within multidisciplinary neuro-oncology. Knowledge of disease incidence, outcomes, as well as risk factors is fundamental to all fields involved in research and treatment of patients with brain tumors; thus, epidemiology constitutes an important link between disciplines, indeed the very hub. This was reflected by the scientific program, which included various sessions linking brain tumor epidemiology with clinical neuro-oncology, tissue-based research, and cancer registration. Renowned experts from Europe and the United States contributed their personal perspectives stimulating further group discussions. Several concrete action plans evolved for the group to move forward until next year’s meeting, which will be held at the Mayo Clinic at Rochester, MN, USA. PMID:25518914

Radiation-induced brain structural and functional abnormalities in presymptomatic phase and outcome prediction.

PubMed

Ding, Zhongxiang; Zhang, Han; Lv, Xiao-Fei; Xie, Fei; Liu, Lizhi; Qiu, Shijun; Li, Li; Shen, Dinggang

2018-01-01

Radiation therapy, a major method of treatment for brain cancer, may cause severe brain injuries after many years. We used a rare and unique cohort of nasopharyngeal carcinoma patients with normal-appearing brains to study possible early irradiation injury in its presymptomatic phase before severe, irreversible necrosis happens. The aim is to detect any structural or functional imaging biomarker that is sensitive to early irradiation injury, and to understand the recovery and progression of irradiation injury that can shed light on outcome prediction for early clinical intervention. We found an acute increase in local brain activity that is followed by extensive reductions in such activity in the temporal lobe and significant loss of functional connectivity in a distributed, large-scale, high-level cognitive function-related brain network. Intriguingly, these radiosensitive functional alterations were found to be fully or partially recoverable. In contrast, progressive late disruptions to the integrity of the related far-end white matter structure began to be significant after one year. Importantly, early increased local brain functional activity was predictive of severe later temporal lobe necrosis. Based on these findings, we proposed a dynamic, multifactorial model for radiation injury and another preventive model for timely clinical intervention. Hum Brain Mapp 39:407-427, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Prenatal exposure to drugs: effects on brain development and implications for policy and education

PubMed Central

Thompson, Barbara L.; Levitt, Pat; Stanwood, Gregg D.

2009-01-01

The effects of prenatal exposure to drugs on brain development are complex and are modulated by the timing, dose, and route of drug exposure. It is difficult to assess these effects in clinical cohorts, which are beset with multiple exposures and difficulties in documenting use patterns. This can lead to misinterpretation of research findings by the general public, the media and policy makers, who may mistakenly assume that the legal or illegal status of a drug correlates with its biological impact on fetal brain development and long-term clinical outcomes. It is important to close the gap between what science tells us about the impact of prenatal drug exposure on the fetus and the mother, and what we do programmatically with regard to at-risk populations. PMID:19277053

Diffusion and perfusion weighted magnetic resonance imaging for tumor volume definition in radiotherapy of brain tumors.

PubMed

Guo, Lu; Wang, Gang; Feng, Yuanming; Yu, Tonggang; Guo, Yu; Bai, Xu; Ye, Zhaoxiang

2016-09-21

Accurate target volume delineation is crucial for the radiotherapy of tumors. Diffusion and perfusion magnetic resonance imaging (MRI) can provide functional information about brain tumors, and they are able to detect tumor volume and physiological changes beyond the lesions shown on conventional MRI. This review examines recent studies that utilized diffusion and perfusion MRI for tumor volume definition in radiotherapy of brain tumors, and it presents the opportunities and challenges in the integration of multimodal functional MRI into clinical practice. The results indicate that specialized and robust post-processing algorithms and tools are needed for the precise alignment of targets on the images, and comprehensive validations with more clinical data are important for the improvement of the correlation between histopathologic results and MRI parameter images.

Boomerang sign on MRI.

PubMed

Hirsch, Karen G; Hoesch, Robert E

2012-06-01

Altered mental status and more subtle cognitive and personality changes after traumatic brain injury (TBI) are pervasive problems in patients who survive initial injury. MRI is not necessarily part of the diagnostic evaluation of these patients. Case report with relevant image and review of the literature. Injury to the corpus callosum is commonly described in traumatic brain injury; however, extensive lesions in the splenium are not well described. This image shows an important pattern of brain injury and demonstrates a common clinical syndrome seen in patients with corpus callosum pathology. Injury to the splenium of the corpus callosum due to trauma may be extensive and can cause significant neurologic deficits. MRI is important in the diagnostic evaluation of patients with cognitive changes after TBI.

Towards tailored management of malignant brain tumors with nanotheranostics.

PubMed

Aparicio-Blanco, Juan; Torres-Suárez, Ana-Isabel

2018-06-01

Malignant brain tumors still represent an unmet medical need given their rapid progression and often fatal outcome within months of diagnosis. Given their extremely heterogeneous nature, the assumption that a single therapy could be beneficial for all patients is no longer plausible. Hence, early feedback on drug accumulation at the tumor site and on tumor response to treatment would help tailor therapies to each patient's individual needs for personalized medicine. In this context, at the intersection between imaging and therapy, theranostic nanomedicine is a promising new technique for individualized management of malignant brain tumors. Although brain nanotheranostics has yet to be translated into clinical practice, this field is now a research hotspot due to the growing demand for personalized therapies. In this review, the barriers to the clinical implementation of theranostic nanomedicine for tracking tumor responses to treatment and for guiding stimulus-activated therapies and surgical resection of malignant brain tumors are discussed. Likewise, the criteria that nanotheranostic systems need to fulfil to become clinically relevant formulations are analyzed in depth, focusing on theranostic agents already tested in vivo. Currently, magnetic nanoparticles exploiting brain targeting strategies represent the first generation of preclinical theranostic nanomedicines for the management of malignant brain tumors. The development of nanocarriers that can be used both in imaging studies and the treatment of brain tumors could help identify which patients are most and least likely to respond to a given treatment. This will enable clinicians to adapt the therapy to the needs of the patient and avoid overdosing non-responders. Given the many different approaches to non-invasive techniques for imaging and treating brain tumors, it is important to focus on the strategies most likely to be implemented and to design the most feasible theranostic biomaterials that will bring nanotheranostics one step closer to clinical practice. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Targeting brain metastases in ALK-rearranged non-small-cell lung cancer.

PubMed

Zhang, Isabella; Zaorsky, Nicholas G; Palmer, Joshua D; Mehra, Ranee; Lu, Bo

2015-10-01

The incidence of brain metastases has increased as a result of improved systemic control and advances in imaging. However, development of novel therapeutics with CNS activity has not advanced at the same rate. Research on molecular markers has revealed many potential targets for antineoplastic agents, and a particularly important aberration is translocation in the ALK gene, identified in non-small-cell lung cancer (NSCLC). ALK inhibitors have shown systemic efficacy against ALK-rearranged NSCLC in many clinical trials, but the effectiveness of crizotinib in CNS disease is limited by poor blood-brain barrier penetration and acquired drug resistance. In this Review, we discuss potential pathways to target ALK-rearranged brain metastases, including next generation ALK inhibitors with greater CNS penetration and mechanisms to overcome resistance. Other important mechanisms to control CNS disease include targeting pathways downstream of ALK phosphorylation, increasing the permeability of the blood-brain barrier, modifying the tumour microenvironment, and adding concurrent radiotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Improving the clinical management of traumatic brain injury through the pharmacokinetic modeling of peripheral blood biomarkers.

PubMed

Dadas, Aaron; Washington, Jolewis; Marchi, Nicola; Janigro, Damir

2016-11-30

Blood biomarkers of neurovascular damage are used clinically to diagnose the presence severity or absence of neurological diseases, but data interpretation is confounded by a limited understanding of their dependence on variables other than the disease condition itself. These include half-life in blood, molecular weight, and marker-specific biophysical properties, as well as the effects of glomerular filtration, age, gender, and ethnicity. To study these factors, and to provide a method for markers' analyses, we developed a kinetic model that allows the integrated interpretation of these properties. The pharmacokinetic behaviors of S100B (monomer and homodimer), Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase L1 were modeled using relevant chemical and physical properties; modeling results were validated by comparison with data obtained from healthy subjects or individuals affected by neurological diseases. Brain imaging data were used to model passage of biomarkers across the blood-brain barrier. Our results show the following: (1) changes in biomarker serum levels due to age or disease progression are accounted for by differences in kidney filtration; (2) a significant change in the brain-to-blood volumetric ratio, which is characteristic of infant and adult development, contributes to variation in blood concentration of biomarkers; (3) the effects of extracranial contribution at steady-state are predicted in our model to be less important than suspected, while the contribution of blood-brain barrier disruption is confirmed as a significant factor in controlling markers' appearance in blood, where the biomarkers are typically detected; (4) the contribution of skin to the marker S100B blood levels depends on a direct correlation with pigmentation and not ethnicity; the contribution of extracranial sources for other markers requires further investigation. We developed a multi-compartment, pharmacokinetic model that integrates the biophysical properties of a given brain molecule and predicts its time-dependent concentration in blood, for populations of varying physical and anatomical characteristics. This model emphasizes the importance of the blood-brain barrier as a gatekeeper for markers' blood appearance and, ultimately, for rational clinical use of peripherally-detected brain protein.

Supraependymal cells of hypothalamic third ventricle: identification as resident phagocytes of the brain.

PubMed

Bleier, R; Albrecht, R; Cruce, J A

1975-07-25

Cells lying on the ventricular surface of the hypothalamic ependyma of the tegu lizard exhibit the pseudopodial and flaplike processes characteristic of macrophages found elsewhere. Since they ingest latex beads, they may be considered a resident phagocytic system of the brain. The importance of ependyma and ventricular phagocytes as a first line of defense against viral invasion of the brain, as well as their role in the pathogenesis of certain virus-related diseases, is suggested by a number of experimental and clinical observations.

Interventional programmes to improve cognition during healthy and pathological ageing: Cortical modulations and evidence for brain plasticity.

PubMed

Cespón, Jesús; Miniussi, Carlo; Pellicciari, Maria Concetta

2018-05-01

A growing body of evidence suggests that healthy elderly individuals and patients with Alzheimer's disease retain an important potential for neuroplasticity. This review summarizes studies investigating the modulation of neural activity and structural brain integrity in response to interventions involving cognitive training, physical exercise and non-invasive brain stimulation in healthy elderly and cognitively impaired subjects (including patients with mild cognitive impairment (MCI) and Alzheimer's disease). Moreover, given the clinical relevance of neuroplasticity, we discuss how evidence for neuroplasticity can be inferred from the functional and structural brain changes observed after implementing these interventions. We emphasize that multimodal programmes, which combine several types of interventions, improve cognitive function to a greater extent than programmes that use a single interventional approach. We suggest specific methods for weighting the relative importance of cognitive training, physical exercise and non-invasive brain stimulation according to the functional and structural state of the brain of the targeted subject to maximize the cognitive improvements induced by multimodal programmes. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of the neurological wake-up test on clinical examination, intracranial pressure, brain metabolism and brain tissue oxygenation in severely brain-injured patients

PubMed Central

2012-01-01

Introduction Daily interruption of sedation (IS) has been implemented in 30 to 40% of intensive care units worldwide and may improve outcome in medical intensive care patients. Little is known about the benefit of IS in acutely brain-injured patients. Methods This prospective observational study was performed in a neuroscience intensive care unit in a tertiary-care academic center. Twenty consecutive severely brain-injured patients with multimodal neuromonitoring were analyzed for levels of brain lactate, pyruvate and glucose, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and brain tissue oxygen tension (PbtO2) during IS trials. Results Of the 82 trial days, 54 IS-trials were performed as interruption of sedation and analgesics were not considered safe on 28 days (34%). An increase in the FOUR Score (Full Outline of UnResponsiveness score) was observed in 50% of IS-trials by a median of three (two to four) points. Detection of a new neurologic deficit occurred in one trial (2%), and in one-third of IS-trials the trial had to be stopped due to an ICP-crisis (> 20 mmHg), agitation or systemic desaturation. In IS-trials that had to be aborted, a significant increase in ICP and decrease in PbtO2 (P < 0.05), including 67% with critical values of PbtO2 < 20 mmHg, a tendency to brain metabolic distress (P < 0.07) was observed. Conclusions Interruption of sedation revealed new relevant clinical information in only one trial and a large number of trials could not be performed or had to be stopped due to safety issues. Weighing pros and cons of IS-trials in patients with acute brain injury seems important as related side effects may overcome the clinical benefit. PMID:23186037

Mind-altering with the gut: Modulation of the gut-brain axis with probiotics.

PubMed

Kim, Namhee; Yun, Misun; Oh, Young Joon; Choi, Hak-Jong

2018-03-01

It is increasingly evident that bidirectional interactions exist among the gastrointestinal tract, the enteric nervous system, and the central nervous system. Recent preclinical and clinical trials have shown that gut microbiota plays an important role in these gut-brain interactions. Furthermore, alterations in gut microbiota composition may be associated with pathogenesis of various neurological disorders, including stress, autism, depression, Parkinson's disease, and Alzheimer's disease. Therefore, the concepts of the microbiota-gut-brain axis is emerging. Here, we review the role of gut microbiota in bidirectional interactions between the gut and the brain, including neural, immune-mediated, and metabolic mechanisms. We highlight recent advances in the understanding of probiotic modulation of neurological and neuropsychiatric disorders via the gut-brain axis.

Analysis of Brain Recurrence

NASA Astrophysics Data System (ADS)

Frilot, Clifton; Kim, Paul Y.; Carrubba, Simona; McCarty, David E.; Chesson, Andrew L.; Marino, Andrew A.

Analysis of Brain Recurrence (ABR) is a method for extracting physiologically significant information from the electroencephalogram (EEG), a non-stationary electrical output of the brain, the ultimate complex dynamical system. ABR permits quantification of temporal patterns in the EEG produced by the non-autonomous differential laws that govern brain metabolism. In the context of appropriate experimental and statistical designs, ABR is ideally suited to the task of interpreting the EEG. Present applications of ABR include discovery of a human magnetic sense, increased mechanistic understanding of neuronal membrane processes, diagnosis of degenerative neurological disease, detection of changes in brain metabolism caused by weak environmental electromagnetic fields, objective characterization of the quality of human sleep, and evaluation of sleep disorders. ABR has important beneficial implications for the development of clinical and experimental neuroscience.

Safety of real-time convection-enhanced delivery of liposomes to primate brain: a long-term retrospective.

PubMed

Krauze, Michal T; Vandenberg, Scott R; Yamashita, Yoji; Saito, Ryuta; Forsayeth, John; Noble, Charles; Park, John; Bankiewicz, Krystof S

2008-04-01

Convection-enhanced delivery (CED) is gaining popularity in direct brain infusions. Our group has pioneered the use of liposomes loaded with the MRI contrast reagent as a means to track and quantitate CED in the primate brain through real-time MRI. When co-infused with therapeutic nanoparticles, these tracking liposomes provide us with unprecedented precision in the management of infusions into discrete brain regions. In order to translate real-time CED into clinical application, several important parameters must be defined. In this study, we have analyzed all our cumulative animal data to answer a number of questions as to whether real-time CED in primates depends on concentration of infusate, is reproducible, allows prediction of distribution in a given anatomic structure, and whether it has long term pathological consequences. Our retrospective analysis indicates that real-time CED is highly predictable; repeated procedures yielded identical results, and no long-term brain pathologies were found. We conclude that introduction of our technique to clinical application would enhance accuracy and patient safety when compared to current non-monitored delivery trials.

Detection and mapping of delays in early cortical folding derived from in utero MRI

NASA Astrophysics Data System (ADS)

Habas, Piotr A.; Rajagopalan, Vidya; Scott, Julia A.; Kim, Kio; Roosta, Ahmad; Rousseau, Francois; Barkovich, A. James; Glenn, Orit A.; Studholme, Colin

2011-03-01

Understanding human brain development in utero and detecting cortical abnormalities related to specific clinical conditions is an important area of research. In this paper, we describe and evaluate methodology for detection and mapping of delays in early cortical folding from population-based studies of fetal brain anatomies imaged in utero. We use a general linear modeling framework to describe spatiotemporal changes in curvature of the developing brain and explore the ability to detect and localize delays in cortical folding in the presence of uncertainty in estimation of the fetal age. We apply permutation testing to examine which regions of the brain surface provide the most statistical power to detect a given folding delay at a given developmental stage. The presented methodology is evaluated using MR scans of fetuses with normal brain development and gestational ages ranging from 20.57 to 27.86 weeks. This period is critical in early cortical folding and the formation of the primary and secondary sulci. Finally, we demonstrate a clinical application of the framework for detection and localization of folding delays in fetuses with isolated mild ventriculomegaly.

Poststroke Seizures and Epilepsy: Clinical Studies and Animal Models

PubMed Central

Kelly, Kevin M.

2002-01-01

Poststroke seizures and epilepsy have been described in numerous clinical studies for many years. Most studies are retrospective in design, include relatively small numbers of patients, have limited periods of follow-up, and report a diversity of findings. Well-designed clinical trials and population studies in the recent past addressed several critical clinical issues and generated important findings regarding the occurrence of poststroke seizures and epilepsy. In contrast, the pathophysiologic events of injured brain that establish poststroke epileptogenesis are not well understood, and animal modeling has had limited development. Reviews of several important clinical studies and animal models that hold promise for a better understanding of poststroke epileptogenesis are presented. PMID:15309107

Longitudinal connectome-based predictive modeling for REM sleep behavior disorder from structural brain connectivity

NASA Astrophysics Data System (ADS)

Giancardo, Luca; Ellmore, Timothy M.; Suescun, Jessika; Ocasio, Laura; Kamali, Arash; Riascos-Castaneda, Roy; Schiess, Mya C.

2018-02-01

Methods to identify neuroplasticity patterns in human brains are of the utmost importance in understanding and potentially treating neurodegenerative diseases. Parkinson disease (PD) research will greatly benefit and advance from the discovery of biomarkers to quantify brain changes in the early stages of the disease, a prodromal period when subjects show no obvious clinical symptoms. Diffusion tensor imaging (DTI) allows for an in-vivo estimation of the structural connectome inside the brain and may serve to quantify the degenerative process before the appearance of clinical symptoms. In this work, we introduce a novel strategy to compute longitudinal structural connectomes in the context of a whole-brain data-driven pipeline. In these initial tests, we show that our predictive models are able to distinguish controls from asymptomatic subjects at high risk of developing PD (REM sleep behavior disorder, RBD) with an area under the receiving operating characteristic curve of 0.90 (p<0.001) and a longitudinal dataset of 46 subjects part of the Parkinson's Progression Markers Initiative. By analyzing the brain connections most relevant for the predictive ability of the best performing model, we find connections that are biologically relevant to the disease.

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

Abnormal functional activation and maturation of ventromedial prefrontal cortex and cerebellum during temporal discounting in autism spectrum disorder.

PubMed

Murphy, Clodagh M; Christakou, Anastasia; Giampietro, Vincent; Brammer, Michael; Daly, Eileen M; Ecker, Christine; Johnston, Patrick; Spain, Debbie; Robertson, Dene M; Murphy, Declan G; Rubia, Katya

2017-11-01

People with autism spectrum disorder (ASD) have poor decision-making and temporal foresight. This may adversely impact on their everyday life, mental health, and productivity. However, the neural substrates underlying poor choice behavior in people with ASD, or its' neurofunctional development from childhood to adulthood, are unknown. Despite evidence of atypical structural brain development in ASD, investigation of functional brain maturation in people with ASD is lacking. This cross-sectional developmental fMRI study investigated the neural substrates underlying performance on a temporal discounting (TD) task in 38 healthy (11-35 years old) male adolescents and adults with ASD and 40 age, sex, and IQ-matched typically developing healthy controls. Most importantly, we assessed group differences in the neurofunctional maturation of TD across childhood and adulthood. Males with ASD had significantly poorer task performance and significantly lower brain activation in typical regions that mediate TD for delayed choices, in predominantly right hemispheric regions of ventrolateral/dorsolateral prefrontal cortices, ventromedial prefrontal cortex, striatolimbic regions, and cerebellum. Importantly, differential activation in ventromedial frontal cortex and cerebellum was associated with abnormal functional brain maturation; controls, in contrast to people with ASD, showed progressively increasing activation with increasing age in these regions; which furthermore was associated with performance measures and clinical ASD measures (stereotyped/restricted interests). Findings provide first cross-sectional evidence that reduced activation of TD mediating brain regions in people with ASD during TD is associated with abnormal functional brain development in these regions between childhood and adulthood, and this is related to poor task performance and clinical measures of ASD. Hum Brain Mapp 38:5343-5355, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Clinical Resting-state fMRI in the Preoperative Setting

PubMed Central

Lee, Megan H.; Miller-Thomas, Michelle M.; Benzinger, Tammie L.; Marcus, Daniel S.; Hacker, Carl D.; Leuthardt, Eric C.; Shimony, Joshua S.

2017-01-01

The purpose of this manuscript is to provide an introduction to resting-state functional magnetic resonance imaging (RS-fMRI) and to review the current application of this new and powerful technique in the preoperative setting using our institute’s extensive experience. RS-fMRI has provided important insights into brain physiology and is an increasingly important tool in the clinical setting. As opposed to task-based functional MRI wherein the subject performs a task while being scanned, RS-fMRI evaluates low-frequency fluctuations in the blood oxygen level dependent (BOLD) signal while the subject is at rest. Multiple resting state networks (RSNs) have been identified, including the somatosensory, language, and visual networks, which are of primary importance for presurgical planning. Over the past 4 years, we have performed over 300 RS-fMRI examinations in the clinical setting and these have been used to localize eloquent somatosensory and language cortices before brain tumor resection. RS-fMRI is particularly useful in this setting for patients who are unable to cooperate with the task-based paradigm, such as young children or those who are sedated, paretic, or aphasic. Although RS-fMRI is still investigational, our experience indicates that this method is ready for clinical application in the presurgical setting. PMID:26848556

Influence of N-alkylation on organ distribution of radioiodinated amphetamines

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

Machulla, H.J.; Schmidt, U.; Mehdorn, H.M.

1985-05-01

In spite of numerous animal data and the widespread clinical application of p-(I-123)-N-isopropyl-amphetamine, questions remain open about the role of N-alkylation. Therefore, amphetamine (AP), N-methyl- (MeAP), and N-isopropyl-amphetamine (IsAP) were radioiodinated in the para position and the organ distribution was determined in male mice (Freiburg tribe) 10 weeks of age. In the lungs, all derivatives showed principally the same kinetics. In brain, the maximum uptake was reached after 30 min with 12%/g for AP and MeAP, and 10.5%/g for IsAP. In liver, the radioactivity similarly increased during the first 15 min to approx. 12%/g; afterwards, AP clearly decreased but MeAPmore » remained almost constant up to 120 min and, even more, IsAP increased to a maximum of 18%/g at 30 min. The same brain uptake kinetics for all 3 substances exclude the importance of lipophilicity increased by the N-alkylation. Furthermore, the differences in the liver kinetics of AP and both MeAP and IsAP indicate the importance of liver metabolism on the alkylated amphetamines. The results support the hypothesis that the first important metabolite of the N-alkylated derivatives is the amphetamine which accumulates in the brain as do MeAP and IsAP. On the basis of these findings, AP was applied clinically showing the same efficient brain uptake and distribution in SPECT as IsAP.« less

Integrating some mind and brain views of transference: the phenomena.

PubMed

Levin, F M

1997-01-01

Because understanding the underpinnings of transferential learning allows the analyst to more effectively exploit transference in the clinical situation, as well as to advance psychoanalytic theory, the functions and mechanisms of transference phenomena in learning are subjected to an interdisciplinary analysis. Through transference the brain creates hierarchical databases that make emotional sense of the world, especially the world of human relationships. Transference plays a role in defense and resistance clinically; less explored but equally important is the adaptive potential of transference and its effect on an individual's readiness for structural change through the activation of working memory. Most investigators within psychoanalysis have not considered the importance of similarity judgments and memory priming, especially as these help to explain why transference and its proper handling are effective in treatment. Yet there are complex relationships among transference, similarity judgment, and memory priming that tie together psychoanalysis, cognitive psychology, and neurophysiology. Evidence increasingly suggests a relationship between transference and the transfer of knowledge between various content domains (databases) of mind and brain, which is essential to cognitive and emotional learning. There are indications as well that transference decisively facilitates learning readiness ("windows") in general by means of two of its components: free association and spontaneous (self-initiated) activity. The important question of which mind/brain mechanisms motivate transference is not yet understood comprehensively. However, Vygotsky's work on the zone of proximal development (ZPD), M.Stern's teleonomic theory, schema theory, and neural network theory offer further insights into what motivates transference.

Multimodal characterization of the semantic N400 response within a rapid evaluation brain vital sign framework.

PubMed

Ghosh Hajra, Sujoy; Liu, Careesa C; Song, Xiaowei; Fickling, Shaun D; Cheung, Teresa P L; D'Arcy, Ryan C N

2018-06-04

For nearly four decades, the N400 has been an important brainwave marker of semantic processing. It can be recorded non-invasively from the scalp using electrical and/or magnetic sensors, but largely within the restricted domain of research laboratories specialized to run specific N400 experiments. However, there is increasing evidence of significant clinical utility for the N400 in neurological evaluation, particularly at the individual level. To enable clinical applications, we recently reported a rapid evaluation framework known as "brain vital signs" that successfully incorporated the N400 response as one of the core components for cognitive function evaluation. The current study characterized the rapidly evoked N400 response to demonstrate that it shares consistent features with traditional N400 responses acquired in research laboratory settings-thereby enabling its translation into brain vital signs applications. Data were collected from 17 healthy individuals using magnetoencephalography (MEG) and electroencephalography (EEG), with analysis of sensor-level effects as well as evaluation of brain sources. Individual-level N400 responses were classified using machine learning to determine the percentage of participants in whom the response was successfully detected. The N400 response was observed in both M/EEG modalities showing significant differences to incongruent versus congruent condition in the expected time range (p < 0.05). Also as expected, N400-related brain activity was observed in the temporal and inferior frontal cortical regions, with typical left-hemispheric asymmetry. Classification robustly confirmed the N400 effect at the individual level with high accuracy (89%), sensitivity (0.88) and specificity (0.90). The brain vital sign N400 characteristics were highly consistent with features of the previously reported N400 responses acquired using traditional laboratory-based experiments. These results provide important evidence supporting clinical translation of the rapidly acquired N400 response as a potential tool for assessments of higher cognitive functions.

Addressing safety liabilities of TfR bispecific antibodies that cross the blood-brain barrier.

PubMed

Couch, Jessica A; Yu, Y Joy; Zhang, Yin; Tarrant, Jacqueline M; Fuji, Reina N; Meilandt, William J; Solanoy, Hilda; Tong, Raymond K; Hoyte, Kwame; Luk, Wilman; Lu, Yanmei; Gadkar, Kapil; Prabhu, Saileta; Ordonia, Benjamin A; Nguyen, Quyen; Lin, Yuwen; Lin, Zhonghua; Balazs, Mercedesz; Scearce-Levie, Kimberly; Ernst, James A; Dennis, Mark S; Watts, Ryan J

2013-05-01

Bispecific antibodies using the transferrin receptor (TfR) have shown promise for boosting antibody uptake in brain. Nevertheless, there are limited data on the therapeutic properties including safety liabilities that will enable successful development of TfR-based therapeutics. We evaluate TfR/BACE1 bispecific antibody variants in mouse and show that reducing TfR binding affinity improves not only brain uptake but also peripheral exposure and the safety profile of these antibodies. We identify and seek to address liabilities of targeting TfR with antibodies, namely, acute clinical signs and decreased circulating reticulocytes observed after dosing. By eliminating Fc effector function, we ameliorated the acute clinical signs and partially rescued a reduction in reticulocytes. Furthermore, we show that complement mediates a residual decrease in reticulocytes observed after Fc effector function is eliminated. These data raise important safety concerns and potential mitigation strategies for the development of TfR-based therapies that are designed to cross the blood-brain barrier.

Severe traumatic brain injury management and clinical outcome using the Lund concept.

PubMed

Koskinen, L-O D; Olivecrona, M; Grände, P O

2014-12-26

This review covers the main principles of the Lund concept for treatment of severe traumatic brain injury. This is followed by a description of results of clinical studies in which this therapy or a modified version of the therapy has been used. Unlike other guidelines, which are based on meta-analytical approaches, important components of the Lund concept are based on physiological mechanisms for regulation of brain volume and brain perfusion and to reduce transcapillary plasma leakage and the need for plasma volume expanders. There have been nine non-randomized and two randomized outcome studies with the Lund concept or modified versions of the concept. The non-randomized studies indicated that the Lund concept is beneficial for outcome. The two randomized studies were small but showed better outcome in the groups of patients treated according to the modified principles of the Lund concept than in the groups given a more conventional treatment. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Disruption of astrocyte-vascular coupling and the blood-brain barrier by invading glioma cells

PubMed Central

Watkins, Stacey; Robel, Stefanie; Kimbrough, Ian F.; Robert, Stephanie M.; Ellis-Davies, Graham; Sontheimer, Harald

2014-01-01

Astrocytic endfeet cover the entire cerebral vasculature and serve as exchange sites for ions, metabolites, and energy substrates from the blood to the brain. They maintain endothelial tight junctions that form the blood-brain barrier (BBB) and release vasoactive molecules that regulate vascular tone. Malignant gliomas are highly invasive tumors that use the perivascular space for invasion and co-opt existing vessels as satellite tumors form. Here we use a clinically relevant mouse model of glioma and find that glioma cells, as they populate the perivascular space of pre-existing vessels, displace astrocytic endfeet from endothelial or vascular smooth muscle cells. This causes a focal breach in the BBB. Furthermore, astrocyte-mediated gliovascular coupling is lost, and glioma cells seize control over regulation of vascular tone through Ca2+-dependent release of K+. These findings have important clinical implications regarding blood flow in the tumor-associated brain and the ability to locally deliver chemotherapeutic drugs in disease. PMID:24943270

All the Vice Chancellor’s Neuroscientists: Unity to Achieve Success in Solving Malaysia’s Diseases via Upgrading Clinical Services and Neuroscience Research

PubMed Central

Abdullah, Jafri Malin

2013-01-01

President Obama of the United States of America announced this April the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN for short) investment, while Professor Henry Markram’s team based in the European Union will spend over a billion euros on the Human Brain Project, breaking through the unknowns in the fifth science of the decade: Neuroscience. Malaysia's growth in the same field needs to be augmented, and thus the Universiti Sains Malaysia’s vision is to excel in the field of clinical brain sciences, mind sciences and neurosciences. This will naturally bring up the level of research in the country simultaneously. Thus, a center was recently established to coordinate this venture. The four-year Integrated Neuroscience Program established recently will be a sustainable source of neuroscientists for the country. We hope to establish ourselves by 2020 as a global university with neurosciences research as an important flagship. PMID:23966818

Psychiatry as a Clinical Neuroscience Discipline

PubMed Central

Insel, Thomas R.; Quirion, Remi

2006-01-01

One of the fundamental insights emerging from contemporary neuroscience is that mental illnesses are brain disorders. In contrast to classic neurological illnesses that involve discrete brain lesions, mental disorders need to be addressed as disorders of distributed brain systems with symptoms forged by developmental and social experiences. While genomics will be important for revealing risk, and cellular neuroscience should provide targets for novel treatments for these disorders, it is most likely that the tools of systems neuroscience will yield the biomarkers needed to revolutionize psychiatric diagnosis and treatment. This essay considers the discoveries that will be necessary over the next two decades to translate the promise of modern neuroscience into strategies for prevention and cures of mental disorders. To deliver on this spectacular new potential, clinical neuroscience must be integrated into the discipline of psychiatry, thereby transforming current psychiatric training, tools, and practices. PMID:16264165

Malformations of Cortical Development and Epilepsy

PubMed Central

Barkovich, A. James; Dobyns, William B.; Guerrini, Renzo

2015-01-01

Malformations of cortical development (MCDs) are an important cause of epilepsy and an extremely interesting group of disorders from the perspective of brain development and its perturbations. Many new MCDs have been described in recent years as a result of improvements in imaging, genetic testing, and understanding of the effects of mutations on the ability of their protein products to correctly function within the molecular pathways by which the brain functions. In this review, most of the major MCDs are reviewed from a clinical, embryological, and genetic perspective. The most recent literature regarding clinical diagnosis, mechanisms of development, and future paths of research are discussed. PMID:25934463

Correlates and Prevalence of Aggression at Six Months and One Year After First-Time Traumatic Brain Injury.

PubMed

Roy, Durga; Vaishnavi, Sandeep; Han, Dingfen; Rao, Vani

2017-01-01

Few studies have examined clinical correlates of aggression after first-time traumatic brain injury (TBI) within the first year after injury. The authors aimed to identify the rates of aggression at 6 and 12 months post-TBI and establish clinical and demographic correlates. A total of 103 subjects with first-time TBI were seen within 12 months postinjury and evaluated for aggression. Post-TBI social functioning and new-onset depression (within 3 months of the TBI) may serve as particularly important predictors for aggression within the first year of TBI, as these factors may afford intervention and subsequent decreased risk of aggression.

Multiple cutaneous melanomas associated with gastric and brain metastases*

PubMed Central

Grander, Lara Caroline; Cabral, Fernanda; Lisboa, Alice Paixão; Vale, Gabrielle; Barcaui, Carlos Baptista; Maceira, Juan Manuel Pineiro

2016-01-01

The occurrence of multiple primary melanomas in a single individual is rare. Most commonly, malignant melanocytic lesions subsequent to the initial diagnosis of melanoma are secondary cutaneous metastases. We report a patient with gastrointestinal bleeding from gastric metastasis of cutaneous melanoma. During clinical evaluation and staging, we discovered a brain metastasis associated with 3 synchronous primary cutaneous melanomas. We suggest the research on the mutation in the cyclin-dependent kinase inhibitor 2A (CDKN2A) (INK4a) in such cases. We also emphasize the importance of clinical examination and dermoscopy of the entire tegument, even after a malignant melanocytic lesion is identified. PMID:28300909

St. Louis Encephalitis in Children

PubMed Central

Kaplan, Allen M.; Longhurst, William L.; Randall, Donald L.

1978-01-01

St. Louis encephalitis is not an uncommon cause of seasonal meningoencephalitis in children. The clinical presentation is variable and may range from inapparent infection to a severe illness with diverse neurologic signs. A review of three recent cases of St. Louis encephalitis in children in Phoenix, Arizona, stresses the need to consider this type of encephalitis in patients with signs of brain stem dysfunction or acute cerebellar ataxia. The appearance of these clinical signs is supported by the pathologic changes that have been documented to occur, most frequently in the thalamus and brain stem. The importance of serologic identification to facilitate early vector control is emphasized. PMID:664627

[Effect of RAAS inhibition on stroke prevention].

PubMed

Tanahashi, Norio

2012-09-01

Recently, molecular and experimental studies revealed that the brain possesses its own renin-angiotensin-aldosterone system(RAAS) and the brain angiotensin(Ang) II plays an important role on stroke protection, mediating its effects through stimulation of AT2 and possibly the AT4 receptors. Moreover, the novel ACE2/Ang-(1-7)/Mas receptor axis was found to counterbalance the vasoconstrictive actions of the ACE/Ang II/AT1 receptor. Recent clinical trials indicate that blockade of RAAS has a potential role in stroke prevention, but was not conclusive. More carefully designed large clinical trial are needed to verify blood pressure-independent stroke prevention effect by RAAS inhibition.

Confounding factors in diagnosing brain death: a case report.

PubMed

Burns, Jeffrey M; Login, Ivan S

2002-06-26

Brain death is strictly defined medically and legally. This diagnosis depends on three cardinal neurological features: coma, absent brainstem reflexes, and apnea. The diagnosis can only be made, however, in the absence of intoxication, hypothermia, or certain medical illnesses. A patient with severe hypoxic-ischemic brain injury met the three cardinal neurological features of brain death but concurrent profound hypothyroidism precluded the diagnosis. Our clinical and ethical decisions were further challenged by another facet of this complex case. Although her brain damage indicated a hopeless prognosis, we could not discontinue care based on futility because the only known surrogate was mentally retarded and unable to participate in medical planning. The presence of certain medical conditions prohibits a diagnosis of brain death, which is a medicolegal diagnosis of death, not a prediction or forecast of future outcome. While prognostication is important in deciding to withdraw care, it is not a component in diagnosing brain death.

Magnetic resonance elastography (MRE) of the human brain: technique, findings and clinical applications

NASA Astrophysics Data System (ADS)

Hiscox, Lucy V.; Johnson, Curtis L.; Barnhill, Eric; McGarry, Matt D. J.; Huston 3rd, John; van Beek, Edwin J. R.; Starr, John M.; Roberts, Neil

2016-12-01

Neurological disorders are one of the most important public health concerns in developed countries. Established brain imaging techniques such as magnetic resonance imaging (MRI) and x-ray computerised tomography (CT) have been essential in the identification and diagnosis of a wide range of disorders, although usually are insufficient in sensitivity for detecting subtle pathological alterations to the brain prior to the onset of clinical symptoms—at a time when prognosis for treatment is more favourable. The mechanical properties of biological tissue provide information related to the strength and integrity of the cellular microstructure. In recent years, mechanical properties of the brain have been visualised and measured non-invasively with magnetic resonance elastography (MRE), a particularly sensitive medical imaging technique that may increase the potential for early diagnosis. This review begins with an introduction to the various methods used for the acquisition and analysis of MRE data. A systematic literature search is then conducted to identify studies that have specifically utilised MRE to investigate the human brain. Through the conversion of MRE-derived measurements to shear stiffness (kPa) and, where possible, the loss tangent (rad), a summary of results for global brain tissue and grey and white matter across studies is provided for healthy participants, as potential baseline values to be used in future clinical investigations. In addition, the extent to which MRE has revealed significant alterations to the brain in patients with neurological disorders is assessed and discussed in terms of known pathophysiology. The review concludes by predicting the trends for future MRE research and applications in neuroscience.

Targeting breast to brain metastatic tumours with death receptor ligand expressing therapeutic stem cells

PubMed Central

Bagci-Onder, Tugba; Du, Wanlu; Figueiredo, Jose-Luiz; Martinez-Quintanilla, Jordi

2015-01-01

Characterizing clinically relevant brain metastasis models and assessing the therapeutic efficacy in such models are fundamental for the development of novel therapies for metastatic brain cancers. In this study, we have developed an in vivo imageable breast-to-brain metastasis mouse model. Using real time in vivo imaging and subsequent composite fluorescence imaging, we show a widespread distribution of micro- and macro-metastasis in different stages of metastatic progression. We also show extravasation of tumour cells and the close association of tumour cells with blood vessels in the brain thus mimicking the multi-foci metastases observed in the clinics. Next, we explored the ability of engineered adult stem cells to track metastatic deposits in this model and show that engineered stem cells either implanted or injected via circulation efficiently home to metastatic tumour deposits in the brain. Based on the recent findings that metastatic tumour cells adopt unique mechanisms of evading apoptosis to successfully colonize in the brain, we reasoned that TNF receptor superfamily member 10A/10B apoptosis-inducing ligand (TRAIL) based pro-apoptotic therapies that induce death receptor signalling within the metastatic tumour cells might be a favourable therapeutic approach. We engineered stem cells to express a tumour selective, potent and secretable variant of a TRAIL, S-TRAIL, and show that these cells significantly suppressed metastatic tumour growth and prolonged the survival of mice bearing metastatic breast tumours. Furthermore, the incorporation of pro-drug converting enzyme, herpes simplex virus thymidine kinase, into therapeutic S-TRAIL secreting stem cells allowed their eradication post-tumour treatment. These studies are the first of their kind that provide insight into targeting brain metastasis with stem-cell mediated delivery of pro-apoptotic ligands and have important clinical implications. PMID:25910782

Creating and parameterizing patient-specific deep brain stimulation pathway-activation models using the hyperdirect pathway as an example

PubMed Central

Gunalan, Kabilar; Chaturvedi, Ashutosh; Howell, Bryan; Duchin, Yuval; Lempka, Scott F.; Patriat, Remi; Sapiro, Guillermo; Harel, Noam; McIntyre, Cameron C.

2017-01-01

Background Deep brain stimulation (DBS) is an established clinical therapy and computational models have played an important role in advancing the technology. Patient-specific DBS models are now common tools in both academic and industrial research, as well as clinical software systems. However, the exact methodology for creating patient-specific DBS models can vary substantially and important technical details are often missing from published reports. Objective Provide a detailed description of the assembly workflow and parameterization of a patient-specific DBS pathway-activation model (PAM) and predict the response of the hyperdirect pathway to clinical stimulation. Methods Integration of multiple software tools (e.g. COMSOL, MATLAB, FSL, NEURON, Python) enables the creation and visualization of a DBS PAM. An example DBS PAM was developed using 7T magnetic resonance imaging data from a single unilaterally implanted patient with Parkinson’s disease (PD). This detailed description implements our best computational practices and most elaborate parameterization steps, as defined from over a decade of technical evolution. Results Pathway recruitment curves and strength-duration relationships highlight the non-linear response of axons to changes in the DBS parameter settings. Conclusion Parameterization of patient-specific DBS models can be highly detailed and constrained, thereby providing confidence in the simulation predictions, but at the expense of time demanding technical implementation steps. DBS PAMs represent new tools for investigating possible correlations between brain pathway activation patterns and clinical symptom modulation. PMID:28441410

Exploratory Use of Decision Tree Analysis in Classification of Outcome in Hypoxic-Ischemic Brain Injury.

PubMed

Phan, Thanh G; Chen, Jian; Singhal, Shaloo; Ma, Henry; Clissold, Benjamin B; Ly, John; Beare, Richard

2018-01-01

Prognostication following hypoxic ischemic encephalopathy (brain injury) is important for clinical management. The aim of this exploratory study is to use a decision tree model to find clinical and MRI associates of severe disability and death in this condition. We evaluate clinical model and then the added value of MRI data. The inclusion criteria were as follows: age ≥17 years, cardio-respiratory arrest, and coma on admission (2003-2011). Decision tree analysis was used to find clinical [Glasgow Coma Score (GCS), features about cardiac arrest, therapeutic hypothermia, age, and sex] and MRI (infarct volume) associates of severe disability and death. We used the area under the ROC (auROC) to determine accuracy of model. There were 41 (63.7% males) patients having MRI imaging with the average age 51.5 ± 18.9 years old. The decision trees showed that infarct volume and age were important factors for discrimination between mild to moderate disability and severe disability and death at day 0 and day 2. The auROC for this model was 0.94 (95% CI 0.82-1.00). At day 7, GCS value was the only predictor; the auROC was 0.96 (95% CI 0.86-1.00). Our findings provide proof of concept for further exploration of the role of MR imaging and decision tree analysis in the early prognostication of hypoxic ischemic brain injury.

[Methods of statistical analysis in differential diagnostics of the degree of brain glioma anaplasia during preoperative stage].

PubMed

Glavatskiĭ, A Ia; Guzhovskaia, N V; Lysenko, S N; Kulik, A V

2005-12-01

The authors proposed a possible preoperative diagnostics of the degree of supratentorial brain gliom anaplasia using statistical analysis methods. It relies on a complex examination of 934 patients with I-IV degree anaplasias, which had been treated in the Institute of Neurosurgery from 1990 to 2004. The use of statistical analysis methods for differential diagnostics of the degree of brain gliom anaplasia may optimize a diagnostic algorithm, increase reliability of obtained data and in some cases avoid carrying out irrational operative intrusions. Clinically important signs for the use of statistical analysis methods directed to preoperative diagnostics of brain gliom anaplasia have been defined

The flexible brain. On mind and brain, neural darwinism and psychiatry.

PubMed

den Boer, J A

1997-09-01

A theoretical introduction is given in which several theoretical viewpoints concerning the mind-brain problem are discussed. During the last decade philosophers like Searle, Dennett and the Churchlands have taken a more or less pure materialistic position in explaining mental phenomena. Investigators in biological psychiatry have hardly ever taken a clear position in this discussion, whereas we believe it is important that the conclusions drawn from biological research are embedded in a theoretical framework related to the mind-brain problem. In this article the thesis is defended that the theory of neural darwinism represents a major step forward and may bridge previous distinctions between biological, clinical and social psychiatry.

Disruption to functional networks in neonates with perinatal brain injury predicts motor skills at 8 months.

PubMed

Linke, Annika C; Wild, Conor; Zubiaurre-Elorza, Leire; Herzmann, Charlotte; Duffy, Hester; Han, Victor K; Lee, David S C; Cusack, Rhodri

2018-01-01

Functional connectivity magnetic resonance imaging (fcMRI) of neonates with perinatal brain injury could improve prediction of motor impairment before symptoms manifest, and establish how early brain organization relates to subsequent development. This cohort study is the first to describe and quantitatively assess functional brain networks and their relation to later motor skills in neonates with a diverse range of perinatal brain injuries. Infants ( n  = 65, included in final analyses: n  = 53) were recruited from the neonatal intensive care unit (NICU) and were stratified based on their age at birth (premature vs. term), and on whether neuropathology was diagnosed from structural MRI. Functional brain networks and a measure of disruption to functional connectivity were obtained from 14 min of fcMRI acquired during natural sleep at term-equivalent age. Disruption to connectivity of the somatomotor and frontoparietal executive networks predicted motor impairment at 4 and 8 months. This disruption in functional connectivity was not found to be driven by differences between clinical groups, or by any of the specific measures we captured to describe the clinical course. fcMRI was predictive over and above other clinical measures available at discharge from the NICU, including structural MRI. Motor learning was affected by disruption to somatomotor networks, but also frontoparietal executive networks, which supports the functional importance of these networks in early development. Disruption to these two networks might be best addressed by distinct intervention strategies.

Brain infarction and the clinical expression of Alzheimer disease. The Nun Study.

PubMed

Snowdon, D A; Greiner, L H; Mortimer, J A; Riley, K P; Greiner, P A; Markesbery, W R

1997-03-12

To determine the relationship of brain infarction to the clinical expression of Alzheimer disease (AD). Cognitive function and the prevalence of dementia were determined for participants in the Nun Study who later died. At autopsy, lacunar and larger brain infarcts were identified, and senile plaques and neurofibrillary tangles in the neocortex were quantitated. Participants with abundant senile plaques and some neurofibrillary tangles in the neocortex were classified as having met the neuropathologic criteria for AD. Convents in the Midwestern, Eastern, and Southern United States. A total of 102 college-educated women aged 76 to 100 years. Cognitive function assessed by standard tests and dementia and AD assessed by clinical and neuropathologic criteria. Among 61 participants who met the neuropathologic criteria for AD, those with brain infarcts had poorer cognitive function and a higher prevalence of dementia than those without infarcts. Participants with lacunar infarcts in the basal ganglia, thalamus, or deep white matter had an especially high prevalence of dementia, compared with those without infarcts (the odds ratio [OR] for dementia was 20.7, 95% confidence interval [95% CI], 1.5-288.0). Fewer neuropathologic lesions of AD appeared to result in dementia in those with lacunar infarcts in the basal ganglia, thalamus, or deep white matter than in those without infarcts. In contrast, among 41 participants who did not meet the neuropathologic criteria for AD, brain infarcts were only weakly associated with poor cognitive function and dementia. Among all 102 participants, atherosclerosis of the circle of Willis was strongly associated with lacunar and large brain infarcts. These findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.

[Paralysis, organic brain syndrome, and cardiac dysrhythmias caused by chronic laxative abuse (author's transl)].

PubMed

Dahlmann, W; Volles, E; Lüderitz, B

1977-10-28

A 39-year-old woman developed generalised paralysis, reversible organic brain syndrome, and cardiac dysrhythmias after 15 years of laxative abuse. Under continuous and cautious administration of potassium the cardiac rhythm became normal within four days and two days later the paralysis and organic brain syndrome almost disappeared. The cause of the psychiatric symptoms is thought to be cerebral potassium deficiency and an abnormal sodium/potassium equilibrium. Other clinical signs and symptoms due to extreme potassium depletion are presented. The importance of Na+/K+-activated membrane ATP-ase in myocardium and CNS is discussed.

Non-invasive Brain Stimulation in the Treatment of Post-stroke and Neurodegenerative Aphasia: Parallels, Differences, and Lessons Learned

PubMed Central

Norise, Catherine; Hamilton, Roy H.

2017-01-01

Numerous studies over the span of more than a decade have shown that non-invasive brain stimulation (NIBS) techniques, namely transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can facilitate language recovery for patients who have suffered from aphasia due to stroke. While stroke is the most common etiology of aphasia, neurodegenerative causes of language impairment—collectively termed primary progressive aphasia (PPA)—are increasingly being recognized as important clinical phenotypes in dementia. Very limited data now suggest that (NIBS) may have some benefit in treating PPAs. However, before applying the same approaches to patients with PPA as have previously been pursued in patients with post-stroke aphasia, it will be important for investigators to consider key similarities and differences between these aphasia etiologies that is likely to inform successful approaches to stimulation. While both post-stroke aphasia and the PPAs have clear overlaps in their clinical phenomenology, the mechanisms of injury and theorized neuroplastic changes associated with the two etiologies are notably different. Importantly, theories of plasticity in post-stroke aphasia are largely predicated on the notion that regions of the brain that had previously been uninvolved in language processing may take on new compensatory roles. PPAs, however, are characterized by slow distributed degeneration of cellular units within the language system; compensatory recruitment of brain regions to subserve language is not currently understood to be an important aspect of the condition. This review will survey differences in the mechanisms of language representation between the two etiologies of aphasia and evaluate properties that may define and limit the success of different neuromodulation approaches for these two disorders. PMID:28167904

NeuroRex: A Clinical Neural Interface Roadmap for EEG-based Brain Machine Interfaces to a Lower Body Robotic Exoskeleton*

PubMed Central

Contreras-Vidal, Jose L.; Grossman, Robert G.

2013-01-01

In this communication, a translational clinical brain-machine interface (BMI) roadmap for an EEG-based BMI to a robotic exoskeleton (NeuroRex) is presented. This multi-faceted project addresses important engineering and clinical challenges: It addresses the validation of an intelligent, self-balancing, robotic lower-body and trunk exoskeleton (Rex) augmented with EEG-based BMI capabilities to interpret user intent to assist a mobility-impaired person to walk independently. The goal is to improve the quality of life and health status of wheelchair-bounded persons by enabling standing and sitting, walking and backing, turning, ascending and descending stairs/curbs, and navigating sloping surfaces in a variety of conditions without the need for additional support or crutches. PMID:24110003

The Role of Neuroimaging Techniques in Establishing Diagnosis, Prognosis and Therapy in Disorders of Consciousness

PubMed Central

Gosseries, Olivia; Pistoia, Francesca; Charland-Verville, Vanessa; Carolei, Antonio; Sacco, Simona; Laureys, Steven

2016-01-01

Non-communicative brain damaged patients raise important clinical and scientific issues. Here, we review three major pathological disorders of consciousness: coma, the unresponsive wakefulness syndrome and the minimally conscious state. A number of clinical studies highlight the difficulty in making a correct diagnosis in patients with disorders of consciousness based only on behavioral examinations. The increasing use of neuroimaging techniques allows improving clinical characterization of these patients. Recent neuroimaging studies using positron emission tomography, functional magnetic resonance imaging, electroencephalography and transcranial magnetic stimulation can help assess diagnosis, prognosis, and therapeutic treatment. These techniques, using resting state, passive and active paradigms, also highlight possible dissociations between consciousness and responsiveness, and are facilitating a more accurate understanding of brain function in this challenging population. PMID:27347265

Brain cortical structural differences between non-central nervous system cancer patients treated with and without chemotherapy compared to non-cancer controls: a cross-sectional pilot MRI study using clinically indicated scans

NASA Astrophysics Data System (ADS)

Shiroishi, Mark S.; Gupta, Vikash; Bigjahan, Bavrina; Cen, Steven Y.; Rashid, Faisal; Hwang, Darryl H.; Lerner, Alexander; Boyko, Orest B.; Liu, Chia-Shang Jason; Law, Meng; Thompson, Paul M.; Jahanshad, Neda

2017-11-01

Background: Increases in cancer survival have made understanding the basis of cancer-related cognitive impairment (CRCI) more important. CRCI neuroimaging studies have traditionally used dedicated research brain MRIs in breast cancer survivors with small sample sizes; little is known about other non-CNS cancers. However, there is a wealth of unused data from clinically-indicated MRIs that could be used to study CRCI. Objective: Evaluate brain cortical structural differences in those with non-CNS cancers using clinically-indicated MRIs. Design: Cross-sectional Patients: Adult non-CNS cancer and non-cancer control (C) patients who underwent clinically-indicated MRIs. Methods: Brain cortical surface area and thickness were measured using 3D T1-weighted images. An age-adjusted linear regression model was used and the Benjamini and Hochberg false discovery rate (FDR) corrected for multiple comparisons. Group comparisons were: cancer cases with chemotherapy (Ch+), cancer cases without chemotherapy (Ch-) and subgroup of lung cancer cases with and without chemotherapy vs C. Results: Sixty-four subjects were analyzed: 22 Ch+, 23 Ch- and 19 C patients. Subgroup analysis of 16 LCa was also performed. Statistically significant decreases in either cortical surface area or thickness were found in multiple ROIs primarily within the frontal and temporal lobes for all comparisons. Limitations: Several limitations were apparent including a small sample size that precluded adjustment for other covariates. Conclusions: Our preliminary results suggest that various types of non-CNS cancers, both with and without chemotherapy, may result in brain structural abnormalities. Also, there is a wealth of untapped clinical MRIs that could be used for future CRCI studies.

Workshops of the Fifth International Brain-Computer Interface Meeting: Defining the Future.

PubMed

Huggins, Jane E; Guger, Christoph; Allison, Brendan; Anderson, Charles W; Batista, Aaron; Brouwer, Anne-Marie A-M; Brunner, Clemens; Chavarriaga, Ricardo; Fried-Oken, Melanie; Gunduz, Aysegul; Gupta, Disha; Kübler, Andrea; Leeb, Robert; Lotte, Fabien; Miller, Lee E; Müller-Putz, Gernot; Rutkowski, Tomasz; Tangermann, Michael; Thompson, David Edward

2014-01-01

The Fifth International Brain-Computer Interface (BCI) Meeting met June 3-7 th , 2013 at the Asilomar Conference Grounds, Pacific Grove, California. The conference included 19 workshops covering topics in brain-computer interface and brain-machine interface research. Topics included translation of BCIs into clinical use, standardization and certification, types of brain activity to use for BCI, recording methods, the effects of plasticity, special interest topics in BCIs applications, and future BCI directions. BCI research is well established and transitioning to practical use to benefit people with physical impairments. At the same time, new applications are being explored, both for people with physical impairments and beyond. Here we provide summaries of each workshop, illustrating the breadth and depth of BCI research and high-lighting important issues for future research and development.

Delineation of the Clinical, Molecular and Cellular Aspects of Novel JAM3 Mutations Underlying the Autosomal Recessive Hemorrhagic Destruction of the Brain, Subependymal Calcification and Congenital Cataracts

PubMed Central

Akawi, Nadia A.; Canpolat, Fuat E.; White, Susan M.; Quilis-Esquerra, Josep; Sanchez, Martin Morales; Gamundi, Maria José; Mochida, Ganeshwaran H.; Walsh, Christopher A.; Ali, Bassam R.; Al-Gazali, Lihadh

2014-01-01

We have recently shown that the hemorrhagic destruction of the brain, subependymal calcification and congenital cataracts is caused by biallelic mutations in the gene encoding junctional adhesion molecule 3 (JAM3) protein. Affected members from three new families underwent detailed clinical examination including imaging of the brain. Affected individuals presented with a distinctive phenotype comprising hemorrhagic destruction of the brain, subependymal calcification and congenital cataracts. All patients had a catastrophic clinical course resulting in death in 7 out of 10 affected individuals. Sequencing the coding exons of JAM3 revealed three novel homozygous mutations: c.2T>G (p.M1R), c.346G>A (p.E116K) and c.656G>A (p.C219Y). The p.M1R mutation affects the start codon and therefore is predicted to impair protein synthesis. Cellular studies showed that the p.C219Y mutation resulted in a significant retention of the mutated protein in the endoplasmic reticulum, suggesting a trafficking defect. The p.E116K mutant traffics normally to the plasma membrane as the wild type and may have lost its function due to the lack of interaction with an interacting partner. Our data further support the importance of JAM3 in the development and function of the vascular system and the brain. PMID:23255084

Brain Tumor Image Segmentation in MRI Image

NASA Astrophysics Data System (ADS)

Peni Agustin Tjahyaningtijas, Hapsari

2018-04-01

Brain tumor segmentation plays an important role in medical image processing. Treatment of patients with brain tumors is highly dependent on early detection of these tumors. Early detection of brain tumors will improve the patient’s life chances. Diagnosis of brain tumors by experts usually use a manual segmentation that is difficult and time consuming because of the necessary automatic segmentation. Nowadays automatic segmentation is very populer and can be a solution to the problem of tumor brain segmentation with better performance. The purpose of this paper is to provide a review of MRI-based brain tumor segmentation methods. There are number of existing review papers, focusing on traditional methods for MRI-based brain tumor image segmentation. this paper, we focus on the recent trend of automatic segmentation in this field. First, an introduction to brain tumors and methods for brain tumor segmentation is given. Then, the state-of-the-art algorithms with a focus on recent trend of full automatic segmentaion are discussed. Finally, an assessment of the current state is presented and future developments to standardize MRI-based brain tumor segmentation methods into daily clinical routine are addressed.

Gender Differences in Neurodevelopment and Epigenetics

PubMed Central

Chung, Wilson C.J.; Auger, Anthony P.

2013-01-01

Summary The concept that the brain differs in make-up between males and females is not new. For example, it is well-established that anatomists in the nineteenth century found sex differences in human brain weight. The importance of sex differences in the organization of the brain cannot be overstated as they may directly affect cognitive functions, such as verbal skills and visio-spatial tasks in a sex-dependent fashion. Moreover, the incidence of neurological and psychiatric diseases is also highly dependent on sex. These clinical observations reiterate the importance that gender must be taken into account as a relevant possible contributing factor in order to understand the pathogenesis of neurological and psychiatric disorders. Gender-dependent differentiation of the brain has been detected at every levels of organization: morphological, neurochemical, and functional, and have been shown to be primarily controlled by sex differences in gonadal steroid hormone levels during perinatal development. In this review, we discuss how the gonadal steroid hormone testosterone and its metabolites, affect downstream signaling cascades, including gonadal steroid receptor activation, and epigenetic events in order to differentiate the brain in a gender-dependent fashion. PMID:23503727

Clinical Applications of Resting State Functional Connectivity

PubMed Central

Fox, Michael D.; Greicius, Michael

2010-01-01

During resting conditions the brain remains functionally and metabolically active. One manifestation of this activity that has become an important research tool is spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signal of functional magnetic resonance imaging (fMRI). The identification of correlation patterns in these spontaneous fluctuations has been termed resting state functional connectivity (fcMRI) and has the potential to greatly increase the translation of fMRI into clinical care. In this article we review the advantages of the resting state signal for clinical applications including detailed discussion of signal to noise considerations. We include guidelines for performing resting state research on clinical populations, outline the different areas for clinical application, and identify important barriers to be addressed to facilitate the translation of resting state fcMRI into the clinical realm. PMID:20592951

MRI Segmentation of the Human Brain: Challenges, Methods, and Applications

PubMed Central

Despotović, Ivana

2015-01-01

Image segmentation is one of the most important tasks in medical image analysis and is often the first and the most critical step in many clinical applications. In brain MRI analysis, image segmentation is commonly used for measuring and visualizing the brain's anatomical structures, for analyzing brain changes, for delineating pathological regions, and for surgical planning and image-guided interventions. In the last few decades, various segmentation techniques of different accuracy and degree of complexity have been developed and reported in the literature. In this paper we review the most popular methods commonly used for brain MRI segmentation. We highlight differences between them and discuss their capabilities, advantages, and limitations. To address the complexity and challenges of the brain MRI segmentation problem, we first introduce the basic concepts of image segmentation. Then, we explain different MRI preprocessing steps including image registration, bias field correction, and removal of nonbrain tissue. Finally, after reviewing different brain MRI segmentation methods, we discuss the validation problem in brain MRI segmentation. PMID:25945121

Craniosynostosis in 10q26 deletion patients: A consequence of brain underdevelopment or altered suture biology?

PubMed

Faria, Ágatha Cristhina; Rabbi-Bortolini, Eliete; Rebouças, Maria R G O; de S Thiago Pereira, Andréia L A; Frasson, Milena G Tonini; Atique, Rodrigo; Lourenço, Naila Cristina V; Rosenberg, Carla; Kobayashi, Gerson S; Passos-Bueno, Maria Rita; Errera, Flávia Imbroisi Valle

2016-02-01

Approximately a hundred patients with terminal 10q deletions have been described. They present with a wide range of clinical features always accompanied by delayed development, intellectual disability and craniofacial dysmorphisms. Here, we report a girl and a boy with craniosynostosis, developmental delay and other congenital anomalies. Karyotyping and molecular analysis including Multiplex Ligation dependent probe amplification (MLPA) and Array Comparative Genomic Hybridization (aCGH) were performed in both patients. We detected a 13.1 Mb pure deletion at 10q26.12-q26.3 in the girl and a 10.9 Mb pure deletion at 10q26.13-q26.3 in the boy, both encompassing about 100 genes. The clinical and molecular findings in these patients reinforce the importance of the DOCK1 smallest region of overlap I (SRO I), previously suggested to explain the clinical signs, and together with a review of the literature suggest a second 3.5 Mb region important for the phenotype (SRO II). Genotype-phenotype correlations and literature data suggest that the craniosynostosis is not directly related to dysregulated signaling in suture development, but may be secondary to alterations in brain development instead. Further, genes at 10q26 may be involved in the molecular crosstalk between brain and cranial vault. © 2015 Wiley Periodicals, Inc.

Deep brain stimulation of the pedunculopontine nucleus for treatment of gait and balance disorder in progressive supranuclear palsy: Effects of frequency modulations and clinical outcome.

PubMed

Galazky, Imke; Kaufmann, Jörn; Lorenzl, Stefan; Ebersbach, Georg; Gandor, Florin; Zaehle, Tino; Specht, Sylke; Stallforth, Sabine; Sobieray, Uwe; Wirkus, Edyta; Casjens, Franziska; Heinze, Hans-Jochen; Kupsch, Andreas; Voges, Jürgen

2018-05-01

The pedunculopontine nucleus has been suggested as a potential deep brain stimulation target for axial symptoms such as gait and balance impairment in idiopathic Parkinson's disease as well as atypical Parkinsonian disorders. Seven consecutive patients with progressive supranuclear palsy received bilateral pedunculopontine nucleus deep brain stimulation. Inclusion criteria comprised of the clinical diagnosis of progressive supranuclear palsy, a levodopa-resistant gait and balance disorder, age <75 years, and absence of dementia or major psychiatric co-morbidities. Effects of stimulation frequencies at 8, 20, 60 and 130 Hz on motor scores and gait were assessed. Motor scores were followed up for two years postoperatively. Activities of daily living, frequency of falls, health-related quality of life, cognition and mood at 12 months were compared to baseline parameters. Surgical and stimulation related adverse events were assessed. Bilateral pedunculopontine nucleus deep brain stimulation at 8 Hz significantly improved axial motor symptoms and cyclic gait parameters, while high frequency stimulation did not ameliorate gait and balance but improved hypokinesia. This improvement however did not translate into clinically relevant benefits. Frequency of falls was not reduced. Activities of daily living, quality of life and frontal cognitive functions declined, while mood remained unchanged. Bilateral pedunculopontine nucleus deep brain stimulation in progressive supranuclear palsy generates frequency-dependent effects with improvement of cyclic gait parameters at low frequency and amelioration of hypokinesia at high frequency stimulation. However, these effects do not translate into a clinically important improvement. Copyright © 2018. Published by Elsevier Ltd.

Functional magnetic resonance imaging in clinical practice: State of the art and science.

PubMed

Barras, Christen D; Asadi, Hamed; Baldeweg, Torsten; Mancini, Laura; Yousry, Tarek A; Bisdas, Sotirios

2016-11-01

Functional magnetic resonance imaging (fMRI) has become a mainstream neuroimaging modality in the assessment of patients being evaluated for brain tumour and epilepsy surgeries. Thus, it is important for doctors in primary care settings to be well acquainted with the present and potential future applications, as well as limitations, of this modality. The objective of this article is to introduce the theoretical principles and state-of-the-art clinical applications of fMRI in brain tumour and epilepsy surgery, with a focus on the implications for clinical primary care. fMRI enables non-invasive functional mapping of specific cortical tasks (eg motor, language, memory-based, visual), revealing information about functional localisation, anatomical variation in cortical function, and disease effects and adaptations, including the fascinating phenomenon of brain plasticity. fMRI is currently ordered by specialist neurologists and neurosurgeons for the purposes of pre-surgical assessment, and within the context of an experienced multidisciplinary team to prepare, conduct and interpret the scan. With an increasing number of patients undergoing fMRI, general practitioners can expect questions about the current and emerging role of fMRI in clinical care from these patients and their families.

Biodegradable brain-penetrating DNA nanocomplexes and their use to treat malignant brain tumors

PubMed Central

Mastorakos, Panagiotis; Zhang, Clark; Song, Eric; Kim, Young Eun; Park, Hee Won; Berry, Sneha; Choi, Won Kyu; Hanes, Justin; Suk, Jung Soo

2018-01-01

The discovery of powerful genetic targets has spurred clinical development of gene therapy approaches to treat patients with malignant brain tumors. However, lack of success in the clinic has been attributed to the inability of conventional gene vectors to achieve gene transfer throughout highly disseminated primary brain tumors. Here, we demonstrate ex vivo that small nanocomplexes composed of DNA condensed by a blend of biodegradable polymer, poly(β-amino ester) (PBAE), with PBAE conjugated with 5 kDa polyethylene glycol (PEG) molecules (PBAE-PEG) rapidly penetrate healthy brain parenchyma and orthotopic brain tumor tissues in rats. Rapid diffusion of these DNA-loaded nanocomplexes observed in fresh tissues ex vivo demonstrated that they avoided adhesive trapping in the brain owing to their dense PEG coating, which was critical to achieving widespread transgene expression throughout orthotopic rat brain tumors in vivo following administration by convection enhanced delivery. Transgene expression with the PBAE/PBAE-PEG blended nanocomplexes (DNA-loaded brain-penetrating nanocomplexes, or DNA-BPN) was uniform throughout the tumor core compared to nanocomplexes composed of DNA with PBAE only (DNA-loaded conventional nanocomplexes, or DNA-CN), and transgene expression reached beyond the tumor edge, where infiltrative cancer cells are found, only for the DNA-BPN formulation. Finally, DNA-BPN loaded with anti-cancer plasmid DNA provided significantly enhanced survival compared to the same plasmid DNA loaded in DNA-CN in two aggressive orthotopic brain tumor models in rats. These findings underscore the importance of achieving widespread delivery of therapeutic nucleic acids within brain tumors and provide a promising new delivery platform for localized gene therapy in the brain. PMID:28694032

Clinical NOE 13C MRS for neuropsychiatric disorders of the frontal lobe

NASA Astrophysics Data System (ADS)

Sailasuta, Napapon; Robertson, Larry W.; Harris, Kent C.; Gropman, Andrea L.; Allen, Peter S.; Ross, Brian D.

2008-12-01

In this communication, a scheme is described whereby in vivo 13C MRS can safely be performed in the frontal lobe, a human brain region hitherto precluded on grounds of SAR, but important in being the seat of impaired cognitive function in many neuropsychiatric and developmental disorders. By combining two well known features of 13C NMR—the use of low power NOE and the focus on 13C carbon atoms which are only minimally coupled to protons, we are able to overcome the obstacle of SAR and develop means of monitoring the 13C fluxes of critically important metabolic pathways in frontal brain structures of normal volunteers and patients. Using a combination of low-power WALTZ decoupling, variants of random noise for nuclear overhauser effect enhancement it was possible to reduce power deposition to 20% of the advised maximum specific absorption rate (SAR). In model solutions 13C signal enhancement achieved with this scheme were comparable to that obtained with WALTZ-4. In human brain, the low power procedure effectively determined glutamine, glutamate and bicarbonate in the posterior parietal brain after [1- 13C] glucose infusion. The same 13C enriched metabolites were defined in frontal brain of human volunteers after administration of [1- 13C] acetate, a recognized probe of glial metabolism. Time courses of incorporation of 13C into cerebral glutamate, glutamine and bicarbonate were constructed. The results suggest efficacy for measurement of in vivo cerebral metabolic rates of the glutamate-glutamine and tricarboxylic acid cycles in 20 min MR scans in previously inaccessible brain regions in humans at 1.5T. We predict these will be clinically useful biomarkers in many human neuropsychiatric and genetic conditions.

Conscious brain-to-brain communication in humans using non-invasive technologies.

PubMed

Grau, Carles; Ginhoux, Romuald; Riera, Alejandro; Nguyen, Thanh Lam; Chauvat, Hubert; Berg, Michel; Amengual, Julià L; Pascual-Leone, Alvaro; Ruffini, Giulio

2014-01-01

Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI) has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI). These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B) communication between subjects (hyperinteraction). Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG) changes with a CBI inducing the conscious perception of phosphenes (light flashes) through neuronavigated, robotized transcranial magnetic stimulation (TMS), with special care taken to block sensory (tactile, visual or auditory) cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues.

Conscious Brain-to-Brain Communication in Humans Using Non-Invasive Technologies

PubMed Central

Grau, Carles; Ginhoux, Romuald; Riera, Alejandro; Nguyen, Thanh Lam; Chauvat, Hubert; Berg, Michel; Amengual, Julià L.; Pascual-Leone, Alvaro; Ruffini, Giulio

2014-01-01

Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI) has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI). These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B) communication between subjects (hyperinteraction). Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG) changes with a CBI inducing the conscious perception of phosphenes (light flashes) through neuronavigated, robotized transcranial magnetic stimulation (TMS), with special care taken to block sensory (tactile, visual or auditory) cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues. PMID:25137064

Electrophysiological Source Imaging: A Noninvasive Window to Brain Dynamics.

PubMed

He, Bin; Sohrabpour, Abbas; Brown, Emery; Liu, Zhongming

2018-06-04

Brain activity and connectivity are distributed in the three-dimensional space and evolve in time. It is important to image brain dynamics with high spatial and temporal resolution. Electroencephalography (EEG) and magnetoencephalography (MEG) are noninvasive measurements associated with complex neural activations and interactions that encode brain functions. Electrophysiological source imaging estimates the underlying brain electrical sources from EEG and MEG measurements. It offers increasingly improved spatial resolution and intrinsically high temporal resolution for imaging large-scale brain activity and connectivity on a wide range of timescales. Integration of electrophysiological source imaging and functional magnetic resonance imaging could further enhance spatiotemporal resolution and specificity to an extent that is not attainable with either technique alone. We review methodological developments in electrophysiological source imaging over the past three decades and envision its future advancement into a powerful functional neuroimaging technology for basic and clinical neuroscience applications.

Toward effective immunotherapy for the treatment of malignant brain tumors.

PubMed

Mitchell, Duane A; Sampson, John H

2009-07-01

The immunologic treatment of cancer has long been heralded as a targeted molecular therapeutic with the promise of eradicating tumor cells with minimal damage to surrounding normal tissues. However, a demonstrative example of the efficacy of immunotherapy in modulating cancer progression is still lacking for most human cancers. Recent breakthroughs in our understanding of the mechanisms leading to full T-cell activation, and recognition of the importance of overcoming tumor-induced immunosuppressive mechanisms, have shed new light on how to generate effective anti-tumor immune responses in humans, and sparked a renewed and enthusiastic effort to realize the full potential of cancer immunotherapy. The immunologic treatment of invasive malignant brain tumors has not escaped this re-invigorated endeavor, and promising therapies are currently under active investigation in dozens of clinical trials at several institutions worldwide. This review will focus on some of the most important breakthroughs in our understanding of how to generate potent anti-tumor immune responses, and some of the clear challenges that lie ahead in achieving effective immunotherapy for the majority of patients with malignant brain tumors. A review of immunotherapeutic strategies currently under clinical evaluation, as well as an outline of promising novel approaches on the horizon, is included to provide perspective on the active and stalwart progress toward effective immunotherapy for the treatment of malignant brain tumors.

A Four-Dimensional Probabilistic Atlas of the Human Brain

PubMed Central

Mazziotta, John; Toga, Arthur; Evans, Alan; Fox, Peter; Lancaster, Jack; Zilles, Karl; Woods, Roger; Paus, Tomas; Simpson, Gregory; Pike, Bruce; Holmes, Colin; Collins, Louis; Thompson, Paul; MacDonald, David; Iacoboni, Marco; Schormann, Thorsten; Amunts, Katrin; Palomero-Gallagher, Nicola; Geyer, Stefan; Parsons, Larry; Narr, Katherine; Kabani, Noor; Le Goualher, Georges; Feidler, Jordan; Smith, Kenneth; Boomsma, Dorret; Pol, Hilleke Hulshoff; Cannon, Tyrone; Kawashima, Ryuta; Mazoyer, Bernard

2001-01-01

The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype– phenotype–behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders. PMID:11522763

Skull metastases detecting on arterial spin labeling perfusion: Three case reports and review of literature.

PubMed

Ryu, Kyeong H; Baek, Hye J; Cho, Soo B; Moon, Jin I; Choi, Bo H; Park, Sung E; An, Hyo J

2017-11-01

Detection of skull metastases is as important as detection of brain metastases because early diagnosis of skull metastases is a crucial determinant of treatment. However, the skull can be a blind spot for assessing metastases on routine brain magnetic resonance imaging (MRI). To the best of our knowledge, the finding of skull metastases on arterial spin labeling (ASL) has not been reported. ASL is a specific MRI sequence for evaluating cerebral blood flow using magnetized endogenous inflow blood. This study uses ASL as a routine sequence of brain MRI protocol and describes 3 clinical cases of skull metastases identified by ASL. The study also highlights the clinical usefulness of ASL in detecting skull metastases. Three patients with known malignancy underwent brain MRI to evaluate for brain metastases. All of the skull metastases were conspicuously depicted on routine ASL images, and the lesions correlated well with other MRI sequences. Three patients received palliative chemotherapy. Three patients are being followed up regularly at the outpatient department. The routine use of ASL may help to detect lesions in blind spots, such as skull metastases, and to facilitate the evaluation of intracranial pathologies without the use of contrast materials in exceptional situations.

Artificial organs: recent progress in artificial hearing and vision.

PubMed

Ifukube, Tohru

2009-01-01

Artificial sensory organs are a prosthetic means of sending visual or auditory information to the brain by electrical stimulation of the optic or auditory nerves to assist visually impaired or hearing-impaired people. However, clinical application of artificial sensory organs, except for cochlear implants, is still a trial-and-error process. This is because how and where the information transmitted to the brain is processed is still unknown, and also because changes in brain function (plasticity) remain unknown, even though brain plasticity plays an important role in meaningful interpretation of new sensory stimuli. This article discusses some basic unresolved issues and potential solutions in the development of artificial sensory organs such as cochlear implants, brainstem implants, artificial vision, and artificial retinas.

AMPK-mediated regulation of neuronal metabolism and function in brain diseases.

PubMed

Liu, Yu-Ju; Chern, Yijuang

2015-01-01

The AMP-activated protein kinase (AMPK) is a serine/threonine kinase that functions as a key energy sensor in a wide variety of tissues. This kinase has been a major drug target for metabolic diseases (e.g., type 2 diabetes) and cancers. For example, metformin (an activator of AMPK) is a first-line diabetes drug that protects against cancers. Abnormal regulation of AMPK has been implicated in several brain diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke. Given the emerging importance of neurodegenerative diseases in our aging societies, this review features the recent studies that have delineated the functions of AMPK in brain diseases and discusses their potential clinical implications or roles as drug targets in brain diseases.

Noninvasive monitoring of treatment response in a rabbit cyanide toxicity model reveals differences in brain and muscle metabolism

NASA Astrophysics Data System (ADS)

Kim, Jae G.; Lee, Jangwoen; Mahon, Sari B.; Mukai, David; Patterson, Steven E.; Boss, Gerry R.; Tromberg, Bruce J.; Brenner, Matthew

2012-10-01

Noninvasive near infrared spectroscopy measurements were performed to monitor cyanide (CN) poisoning and recovery in the brain region and in foreleg muscle simultaneously, and the effects of a novel CN antidote, sulfanegen sodium, on tissue hemoglobin oxygenation changes were compared using a sub-lethal rabbit model. The results demonstrated that the brain region is more susceptible to CN poisoning and slower in endogenous CN detoxification following exposure than peripheral muscles. However, sulfanegen sodium rapidly reversed CN toxicity, with brain region effects reversing more quickly than muscle. In vivo monitoring of multiple organs may provide important clinical information regarding the extent of CN toxicity and subsequent recovery, and facilitate antidote drug development.

Non-ionizing radiofrequency electromagnetic waves traversing the head can be used to detect cerebrovascular autoregulation responses

NASA Astrophysics Data System (ADS)

Oziel, M.; Hjouj, M.; Gonzalez, C. A.; Lavee, J.; Rubinsky, B.

2016-02-01

Monitoring changes in non-ionizing radiofrequency electromagnetic waves as they traverse the brain can detect the effects of stimuli employed in cerebrovascular autoregulation (CVA) tests on the brain, without contact and in real time. CVA is a physiological phenomenon of importance to health, used for diagnosis of a number of diseases of the brain with a vascular component. The technology described here is being developed for use in diagnosis of injuries and diseases of the brain in rural and economically underdeveloped parts of the world. A group of nine subjects participated in this pilot clinical evaluation of the technology. Substantial research remains to be done on correlating the measurements with physiology and anatomy.

[Dementia and small vessel diseases of the brain].

PubMed

Damulin, I V

2014-01-01

Clinical and pathogenetic characteristics of dementia caused by small vessel lesions are presented. It is emphasized that this variant of vascular dementia is the most frequent in clinical practice. Clinical examination, accurate assessment of the disease history and using of modern neuroimaging techniques are important for the diagnosis. The drugs that impact on risk factors, including disaggregants, and metabolic drugs (nicergoline) are widely used in the treatment of dementia. These drugs are highly effective and safe.

Neurogenetics and Nutrigenomics of Neuro-Nutrient Therapy for Reward Deficiency Syndrome (RDS): Clinical Ramifications as a Function of Molecular Neurobiological Mechanisms

PubMed Central

Blum, Kenneth; Oscar-Berman, Marlene; Stuller, Elizabeth; Miller, David; Giordano, John; Morse, Siobhan; McCormick, Lee; Downs, William B; Waite, Roger L; Barh, Debmalya; Neal, Dennis; Braverman, Eric R; Lohmann, Raquel; Borsten, Joan; Hauser, Mary; Han, David; Liu, Yijun; Helman, Manya; Simpatico, Thomas

2013-01-01

In accord with the new definition of addiction published by American Society of Addiction Medicine (ASAM) it is well-known that individuals who present to a treatment center involved in chemical dependency or other documented reward dependence behaviors have impaired brain reward circuitry. They have hypodopaminergic function due to genetic and/or environmental negative pressures upon the reward neuro-circuitry. This impairment leads to aberrant craving behavior and other behaviors such as Substance Use Disorder (SUD). Neurogenetic research in both animal and humans revealed that there is a well-defined cascade in the reward site of the brain that leads to normal dopamine release. This cascade has been termed the “Brain Reward Cascade” (BRC). Any impairment due to either genetics or environmental influences on this cascade will result in a reduced amount of dopamine release in the brain reward site. Manipulation of the BRC has been successfully achieved with neuro-nutrient therapy utilizing nutrigenomic principles. After over four decades of development, neuro-nutrient therapy has provided important clinical benefits when appropriately utilized. This is a review, with some illustrative case histories from a number of addiction professionals, of certain molecular neurobiological mechanisms which if ignored may lead to clinical complications. PMID:23926462

Mechanisms that Underlie Co-variation of the Brain and Face

PubMed Central

Marcucio, Ralph S.; Young, Nathan M.; Hu, Diane; Hallgrimsson, Benedikt

2011-01-01

The effect of the brain on the morphology of the face has long been recognized in both evolutionary biology and clinical medicine. In this paper we describe factors that are active between development of the brain and face and how these might impact craniofacial variation. First, there is the physical influence of the brain, which contributes to overall growth and morphology of the face through direct structural interactions. Second, there is the molecular influence of the brain, which signals to facial tissues to establish signaling centers that regulate patterned growth. Importantly, subtle alterations to these physical or molecular interactions may contribute to both normal and abnormal variation. These interactions are therefore critical to our understanding of how a diversity of facial morphologies can be generated both within species and across evolutionary time. PMID:21381182

Therapeutics with SPION-labeled stem cells for the main diseases related to brain aging: a systematic review.

PubMed

Alvarim, Larissa T; Nucci, Leopoldo P; Mamani, Javier B; Marti, Luciana C; Aguiar, Marina F; Silva, Helio R; Silva, Gisele S; Nucci-da-Silva, Mariana P; DelBel, Elaine A; Gamarra, Lionel F

2014-01-01

The increase in clinical trials assessing the efficacy of cell therapy for structural and functional regeneration of the nervous system in diseases related to the aging brain is well known. However, the results are inconclusive as to the best cell type to be used or the best methodology for the homing of these stem cells. This systematic review analyzed published data on SPION (superparamagnetic iron oxide nanoparticle)-labeled stem cells as a therapy for brain diseases, such as ischemic stroke, Parkinson's disease, amyotrophic lateral sclerosis, and dementia. This review highlights the therapeutic role of stem cells in reversing the aging process and the pathophysiology of brain aging, as well as emphasizing nanotechnology as an important tool to monitor stem cell migration in affected regions of the brain.

Workshops of the Fifth International Brain-Computer Interface Meeting: Defining the Future

PubMed Central

Huggins, Jane E.; Guger, Christoph; Allison, Brendan; Anderson, Charles W.; Batista, Aaron; Brouwer, Anne-Marie (A.-M.); Brunner, Clemens; Chavarriaga, Ricardo; Fried-Oken, Melanie; Gunduz, Aysegul; Gupta, Disha; Kübler, Andrea; Leeb, Robert; Lotte, Fabien; Miller, Lee E.; Müller-Putz, Gernot; Rutkowski, Tomasz; Tangermann, Michael; Thompson, David Edward

2014-01-01

The Fifth International Brain-Computer Interface (BCI) Meeting met June 3–7th, 2013 at the Asilomar Conference Grounds, Pacific Grove, California. The conference included 19 workshops covering topics in brain-computer interface and brain-machine interface research. Topics included translation of BCIs into clinical use, standardization and certification, types of brain activity to use for BCI, recording methods, the effects of plasticity, special interest topics in BCIs applications, and future BCI directions. BCI research is well established and transitioning to practical use to benefit people with physical impairments. At the same time, new applications are being explored, both for people with physical impairments and beyond. Here we provide summaries of each workshop, illustrating the breadth and depth of BCI research and high-lighting important issues for future research and development. PMID:25485284

Exploring the Virchow–Robin spaces function: A unified theory of brain diseases

PubMed Central

Cherian, Iype; Beltran, Margarita; Kasper, Ekkehard M.; Bhattarai, Binod; Munokami, Sunil; Grasso, Giovanni

2016-01-01

Background: Cerebrospinal fluid (CSF) transport across the central nervous system (CNS) is no longer believed to be on the conventional lines. The Virchow–Robin space (VRS) that facilitates CSF transport from the basal cisterns into the brain interstitial fluid (ISF) has gained interest in a whole new array of studies. Moreover, new line of evidence suggests that VRS may be involved in different pathological mechanisms of brain diseases. Methods: Here, we review emerging studies proving the feasible role of VRS in sleep, Alzheimer's disease, chronic traumatic encephalopathy, and traumatic brain injury (TBI). Results: In this study, we have outlined the possible role of VRS in different pathological conditions. Conclusion: The new insights into the physiology of the CSF circulation may have important clinical relevance for understanding the mechanisms underlying brain pathologies and their cure. PMID:27857861

Clinical Application of High-intensity Focused Ultrasound in Cancer Therapy

PubMed Central

Hsiao, Yi-Hsuan; Kuo, Shou-Jen; Tsai, Horng-Der; Chou, Ming-Chih; Yeh, Guang-Perng

2016-01-01

The treatment of cancer is an important issue in both developing and developed countries. Clinical use of ultrasound in cancer is not only for the diagnosis but also for the treatment. Focused ultrasound surgery (FUS) is a noninvasive technique. By using the combination of high-intensity focused ultrasound (HIFU) and imaging method, FUS has the potential to ablate tumor lesions precisely. The main mechanisms of HIFU ablation involve mechanical and thermal effects. Recent advances in HIFU have increased its popularity. Some promising results were achieved in managing various malignancies, including pancreas, prostate, liver, kidney, breast and bone. Other applications include brain tumor ablation and disruption of the blood-brain barrier. We aim at briefly outlining the clinical utility of FUS as a noninvasive technique for a variety of types of cancer treatment. PMID:26918034

Regional brain volumetry and brain function in severely brain-injured patients.

PubMed

Annen, Jitka; Frasso, Gianluca; Crone, Julia Sophia; Heine, Lizette; Di Perri, Carol; Martial, Charlotte; Cassol, Helena; Demertzi, Athena; Naccache, Lionel; Laureys, Steven

2018-04-01

The relationship between residual brain tissue in patients with disorders of consciousness (DOC) and the clinical condition is unclear. This observational study aimed to quantify gray (GM) and white matter (WM) atrophy in states of (altered) consciousness. Structural T1-weighted magnetic resonance images were processed for 102 severely brain-injured and 52 healthy subjects. Regional brain volume was quantified for 158 (sub)cortical regions using Freesurfer. The relationship between regional brain volume and clinical characteristics of patients with DOC and conscious brain-injured patients was assessed using a linear mixed-effects model. Classification of patients with unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) using regional volumetric information was performed and compared to classification using cerebral glucose uptake from fluorodeoxyglucose positron emission tomography. For validation, the T1-based classifier was tested on independent datasets. Patients were characterized by smaller regional brain volumes than healthy subjects. Atrophy occurred faster in UWS compared to MCS (GM) and conscious (GM and WM) patients. Classification was successful (misclassification with leave-one-out cross-validation between 2% and 13%) and generalized to the independent data set with an area under the receiver operator curve of 79% (95% confidence interval [CI; 67-91.5]) for GM and 70% (95% CI [55.6-85.4]) for WM. Brain volumetry at the single-subject level reveals that regions in the default mode network and subcortical gray matter regions, as well as white matter regions involved in long range connectivity, are most important to distinguish levels of consciousness. Our findings suggest that changes of brain structure provide information in addition to the assessment of functional neuroimaging and thus should be evaluated as well. Ann Neurol 2018;83:842-853. © 2018 American Neurological Association.

[Septo-optic dysplasia].

PubMed

Martínez-Sánchez, L; Arce, A; Caritg-Bosch, J; Campistol, J; Pavía, C; Gean-Molins, E

Septo optic syndrome, described by De Morsier in 1956, consists in the hypoplasia of one or both optic nerves, mid line brain malformations and hypothalamohypophysial dysfunction, which is inconstant. It is an infrequent, but treatable, cause of hepatic and neurological damage, and it is important to obtain an early diagnosis and to begin hormone replacement therapy. We report the clinical case of a female baby who was diagnosed early on as suffering from septo?optic dysplasia, after discovery of the existence of cholestatic jaundice. In our case the three components of the syndrome were present: hypothalamohypophysial dysfunction, bilateral hypoplasia of the optic nerves and brain malformations with dysplasia of the transparent septum. All this gives rise to complex clinical features and the predominance of hypernatraemic dehydration secondary to insipid diabetes, nystagmus and serious psychomotor retardation. Our patient died, as in other cases reported in the literature, from an episode of sudden death. Despite the importance of an early diagnosis of this disorder, it is usually late. Most children who present hypopituitarism traits in the neonatal period are not diagnosed at that time, with the subsequent risk of death or brain damage. Some clinical findings, which appear early on and can provide clues which aid us to reach a diagnosis, are the appearance of episodes of hypoglycaemia in the neonatal period, the existence of micropenis and cryptorchidism with hypoplasic testes, jaundice or the appearance of clinical manifestations of insipid diabetes. Later on nystagmus and neurological symptoms may appear. The final diagnosis is performed through the use of neuroimaging techniques (CT or MRI) and hormonal studies.

From inflammation to sickness and depression: when the immune system subjugates the brain.

PubMed

Dantzer, Robert; O'Connor, Jason C; Freund, Gregory G; Johnson, Rodney W; Kelley, Keith W

2008-01-01

In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.

Inferential stereomorphology of human brain lesions

NASA Astrophysics Data System (ADS)

Gedye, John L.

1980-07-01

I very much appreciated the invitation to contribute a paper to this Symposium on Applications of Human Biostereometrics, as it provides a valuable opportunity for me to take a fresh look at a problemâ€""the cerebral localisation of psychological function"â€"in which I have been interested for many years. This interest grew out of considerations of the clinically important problem of how we should go about the task of relating the form of the changes in human behavior consequent upon damage to the human brain following, say, head injury, to the form of the changes in brain morphology which constitute that damage, and related issues.

Diffusion-Weighted Imaging Outside the Brain: Consensus Statement From an ISMRM-Sponsored Workshop

PubMed Central

Taouli, Bachir; Beer, Ambros J.; Chenevert, Thomas; Collins, David; Lehman, Constance; Matos, Celso; Padhani, Anwar R.; Rosenkrantz, Andrew B.; Shukla-Dave, Amita; Sigmund, Eric; Tanenbaum, Lawrence; Thoeny, Harriet; Thomassin-Naggara, Isabelle; Barbieri, Sebastiano; Corcuera-Solano, Idoia; Orton, Matthew; Partridge, Savannah C.; Koh, Dow-Mu

2016-01-01

The significant advances in magnetic resonance imaging (MRI) hardware and software, sequence design, and postprocessing methods have made diffusion-weighted imaging (DWI) an important part of body MRI protocols and have fueled extensive research on quantitative diffusion outside the brain, particularly in the oncologic setting. In this review, we summarize the most up-to-date information on DWI acquisition and clinical applications outside the brain, as discussed in an ISMRM-sponsored symposium held in April 2015. We first introduce recent advances in acquisition, processing, and quality control; then review scientific evidence in major organ systems; and finally describe future directions. PMID:26892827

[Eating disorders].

PubMed

Miyake, Yoshie; Okamoto, Yuri; Jinnin, Ran; Shishida, Kazuhiro; Okamoto, Yasumasa

2015-02-01

Eating disorders are characterized by aberrant patterns of eating behavior, including such symptoms as extreme restriction of food intake or binge eating, and severe disturbances in the perception of body shape and weight, as well as a drive for thinness and obsessive fears of becoming fat. Eating disorder is an important cause for physical and psychosocial morbidity in young women. Patients with eating disorders have a deficit in the cognitive process and functional abnormalities in the brain system. Recently, brain-imaging techniques have been used to identify specific brain areas that function abnormally in patients with eating disorders. We have discussed the clinical and cognitive aspects of eating disorders and summarized neuroimaging studies of eating disorders.

Graph Theoretical Framework of Brain Networks in Multiple Sclerosis: A Review of Concepts.

PubMed

Fleischer, Vinzenz; Radetz, Angela; Ciolac, Dumitru; Muthuraman, Muthuraman; Gonzalez-Escamilla, Gabriel; Zipp, Frauke; Groppa, Sergiu

2017-11-01

Network science provides powerful access to essential organizational principles of the human brain. It has been applied in combination with graph theory to characterize brain connectivity patterns. In multiple sclerosis (MS), analysis of the brain networks derived from either structural or functional imaging provides new insights into pathological processes within the gray and white matter. Beyond focal lesions and diffuse tissue damage, network connectivity patterns could be important for closely tracking and predicting the disease course. In this review, we describe concepts of graph theory, highlight novel issues of tissue reorganization in acute and chronic neuroinflammation and address pitfalls with regard to network analysis in MS patients. We further provide an outline of functional and structural connectivity patterns observed in MS, spanning from disconnection and disruption on one hand to adaptation and compensation on the other. Moreover, we link network changes and their relation to clinical disability based on the current literature. Finally, we discuss the perspective of network science in MS for future research and postulate its role in the clinical framework. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

When "altering brain function" becomes "mind control".

PubMed

Koivuniemi, Andrew; Otto, Kevin

2014-01-01

Functional neurosurgery has seen a resurgence of interest in surgical treatments for psychiatric illness. Deep brain stimulation (DBS) technology is the preferred tool in the current wave of clinical experiments because it allows clinicians to directly alter the functions of targeted brain regions, in a reversible manner, with the intent of correcting diseases of the mind, such as depression, addiction, anorexia nervosa, dementia, and obsessive compulsive disorder. These promising treatments raise a critical philosophical and humanitarian question. "Under what conditions does 'altering brain function' qualify as 'mind control'?" In order to answer this question one needs a definition of mind control. To this end, we reviewed the relevant philosophical, ethical, and neurosurgical literature in order to create a set of criteria for what constitutes mind control in the context of DBS. We also outline clinical implications of these criteria. Finally, we demonstrate the relevance of the proposed criteria by focusing especially on serendipitous treatments involving DBS, i.e., cases in which an unintended therapeutic benefit occurred. These cases highlight the importance of gaining the consent of the subject for the new therapy in order to avoid committing an act of mind control.

Some aspects of clinical relevance in the maturation of respiratory control in infants.

PubMed

Thach, Bradley T

2008-06-01

Two reflex mechanisms important for survival are discussed. Brain stem and cardiovascular mechanisms that are responsible for recovery from severe hypoxia (autoresuscitation) are important for survival in acutely hypoxic infants and adults. Failure of this mechanism may be important in sudden infant death syndrome (SIDS), because brain stem-mediated hypoxic gasping is essential for successful autoresuscitation and because SIDS infants appear to attempt to autoresuscitate just before death. A major function of another mechanism is to protect the airway from fluid aspiration. The various components of the laryngeal chemoreflex (LCR) change during maturation. The LCR is an important cause of prolonged apneic spells in infants. Consequently, it also may have a role in causing SIDS. Maturational changes and/or inadequacy of this reflex may be responsible for pulmonary aspiration and infectious pneumonia in both children and adults.

75 FR 76994 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-10

... Committee: Brain Disorders and Clinical Neuroscience Integrated Review Group Developmental Brain Disorders....gov . Name of Committee: Brain Disorders and Clinical Neuroscience Integrated Review Group, Cell [email protected] . Name of Committee: Brain Disorders and Clinical Neuroscience Integrated Review Group...

Atomoxetine Treatment Strengthens an Anti-Correlated Relationship between Functional Brain Networks in Medication-Naïve Adults with Attention-Deficit Hyperactivity Disorder: A Randomized Double-Blind Placebo-Controlled Clinical Trial

PubMed Central

Lin, Hsiang-Yuan

2016-01-01

Background: Although atomoxetine demonstrates efficacy in individuals with attention-deficit hyperactivity disorder, its treatment effects on brain resting-state functional connectivity remain unknown. Therefore, we aimed to investigate major brain functional networks in medication-naïve adults with attention-deficit hyperactivity disorder and the efficacy of atomoxetine treatment on resting-state functional connectivity. Methods: After collecting baseline resting-state functional MRI scans from 24 adults with attention-deficit hyperactivity disorder (aged 18–52 years) and 24 healthy controls (matched in demographic characteristics), the participants with attention-deficit hyperactivity disorder were randomly assigned to atomoxetine (n=12) and placebo (n=12) arms in an 8-week, double-blind, placebo-controlled trial. The primary outcome was functional connectivity assessed by a resting-state functional MRI. Seed-based functional connectivity was calculated and compared for the affective, attention, default, and cognitive control networks. Results: At baseline, we found atypical cross talk between the default, cognitive control, and dorsal attention networks and hypoconnectivity within the dorsal attention and default networks in adults with attention-deficit hyperactivity disorder. Our first-ever placebo-controlled clinical trial incorporating resting-state functional MRI showed that treatment with atomoxetine strengthened an anticorrelated relationship between the default and task-positive networks and modulated all major brain networks. The strengthened anticorrelations were associated with improving clinical symptoms in the atomoxetine-treated adults. Conclusions: Our results support the idea that atypical default mode network task-positive network interaction plays an important role in the pathophysiology of adult attention-deficit hyperactivity disorder. Strengthening this atypical relationship following atomoxetine treatment suggests an important pathway to treat attention-deficit hyperactivity disorder. PMID:26377368

Atomoxetine Treatment Strengthens an Anti-Correlated Relationship between Functional Brain Networks in Medication-Naïve Adults with Attention-Deficit Hyperactivity Disorder: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

PubMed

Lin, Hsiang-Yuan; Gau, Susan Shur-Fen

2015-09-16

Although atomoxetine demonstrates efficacy in individuals with attention-deficit hyperactivity disorder, its treatment effects on brain resting-state functional connectivity remain unknown. Therefore, we aimed to investigate major brain functional networks in medication-naïve adults with attention-deficit hyperactivity disorder and the efficacy of atomoxetine treatment on resting-state functional connectivity. After collecting baseline resting-state functional MRI scans from 24 adults with attention-deficit hyperactivity disorder (aged 18-52 years) and 24 healthy controls (matched in demographic characteristics), the participants with attention-deficit hyperactivity disorder were randomly assigned to atomoxetine (n=12) and placebo (n=12) arms in an 8-week, double-blind, placebo-controlled trial. The primary outcome was functional connectivity assessed by a resting-state functional MRI. Seed-based functional connectivity was calculated and compared for the affective, attention, default, and cognitive control networks. At baseline, we found atypical cross talk between the default, cognitive control, and dorsal attention networks and hypoconnectivity within the dorsal attention and default networks in adults with attention-deficit hyperactivity disorder. Our first-ever placebo-controlled clinical trial incorporating resting-state functional MRI showed that treatment with atomoxetine strengthened an anticorrelated relationship between the default and task-positive networks and modulated all major brain networks. The strengthened anticorrelations were associated with improving clinical symptoms in the atomoxetine-treated adults. Our results support the idea that atypical default mode network task-positive network interaction plays an important role in the pathophysiology of adult attention-deficit hyperactivity disorder. Strengthening this atypical relationship following atomoxetine treatment suggests an important pathway to treat attention-deficit hyperactivity disorder. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Brain Distribution of a Novel MEK Inhibitor E6201: Implications in the Treatment of Melanoma Brain Metastases.

PubMed

Gampa, Gautham; Kim, Minjee; Cook-Rostie, Nicholas; Laramy, Janice K; Sarkaria, Jann N; Paradiso, Linda; DePalatis, Louis; Elmquist, William F

2018-05-01

Clinically meaningful efficacy in the treatment of brain tumors, including melanoma brain metastases (MBM), requires selection of a potent inhibitor against a suitable target, and adequate drug distribution to target sites in the brain. Deregulated constitutive signaling of mitogen-activated protein kinase (MAPK) pathway has been frequently observed in melanoma, and mitogen-activated protein/extracellular signal-regulated kinase (MEK) has been identified to be an important target. E6201 is a potent synthetic small-molecule MEK inhibitor. The purpose of this study was to evaluate brain distribution of E6201, and examine the impact of active efflux transport at the blood-brain barrier on the central nervous system (CNS) exposure of E6201. In vitro studies utilizing transfected Madin-Darby canine kidney II (MDCKII) cells indicate that E6201 is not a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp). In vivo studies also suggest a minimal involvement of P-gp and Bcrp in E6201's brain distribution. The total concentrations in brain were higher than in plasma, resulting in a brain-to-plasma AUC ratio (Kp) of 2.66 in wild-type mice. The brain distribution was modestly enhanced in Mdr1a/b -/- , Bcrp1 -/- , and Mdr1a/b -/- Bcrp1 -/- knockout mice. The nonspecific binding of E6201 was higher in brain compared with plasma. However, free-drug concentrations in brain following 40 mg/kg intravenous dose reach levels that exceed reported in vitro half-maximal inhibitory concentration (IC 50 ) values, suggesting that E6201 may be efficacious in inhibiting MEK-driven brain tumors. The brain distribution characteristics of E6201 make it an attractive targeted agent for clinical testing in MBM, glioblastoma, and other CNS tumors that may be effectively targeted with inhibition of MEK signaling. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Injury-Related Production of Cysteinyl Leukotrienes Contributes to Brain Damage following Experimental Traumatic Brain Injury

PubMed Central

Farias, Santiago; Frey, Lauren C.; Murphy, Robert C.

2009-01-01

Abstract The leukotrienes belong to a family of biologically active lipids derived from arachidonate that are often involved in inflammatory responses. In the central nervous system, a group of leukotrienes, known as the cysteinyl leukotrienes, is generated in brain tissue in response to a variety of acute brain injuries. Although the exact clinical significance of this excess production remains unclear, the cysteinyl leukotrienes may contribute to injury-related disruption of the brain-blood barrier and exacerbate secondary injury processes. In the present study, the formation and role of cysteinyl leukotrienes was explored in the fluid percussion injury model of traumatic brain injury in rats. The results showed that levels of the cysteinyl leukotrienes were elevated after fluid percussion injury with a maximal formation 1 hour after the injury. Neutrophils contributed to cysteinyl leukotriene formation in the injured brain hemisphere, potentially through a transcellular biosynthetic mechanism. Furthermore, pharmacological reduction of cysteinyl leukotriene formation after the injury, using MK-886, resulted in reduction of brain lesion volumes, suggesting that the cysteinyl leukotrienes play an important role in traumatic brain injury. PMID:19886806

Neuroimaging Studies Illustrate the Commonalities Between Ageing and Brain Diseases.

PubMed

Cole, James H

2018-07-01

The lack of specificity in neuroimaging studies of neurological and psychiatric diseases suggests that these different diseases have more in common than is generally considered. Potentially, features that are secondary effects of different pathological processes may share common neurobiological underpinnings. Intriguingly, many of these mechanisms are also observed in studies of normal (i.e., non-pathological) brain ageing. Different brain diseases may be causing premature or accelerated ageing to the brain, an idea that is supported by a line of "brain ageing" research that combines neuroimaging data with machine learning analysis. In reviewing this field, I conclude that such observations could have important implications, suggesting that we should shift experimental paradigm: away from characterizing the average case-control brain differences resulting from a disease toward methods that place individuals in their age-appropriate context. This will also lead naturally to clinical applications, whereby neuroimaging can contribute to a personalized-medicine approach to improve brain health. © 2018 WILEY Periodicals, Inc.

Role of erythropoietin in the brain

PubMed Central

Noguchi, Constance Tom; Asavaritikrai, Pundit; Teng, Ruifeng; Jia, Yi

2007-01-01

Multi-tissue erythropoietin receptor (EPO-R) expression provides for erythropoietin (EPO) activity beyond its known regulation of red blood cell production. This review highlights the role of EPO and EPO-R in brain development and neuroprotection. EPO-R brain expression includes neural progenitor cells (NPC), neurons, glial cells and endothelial cells. EPO is produced in brain in a hypoxia sensitive manner, stimulates NPC proliferation and differentiation, and neuron survival, and contributes to ischemic preconditioning. Mice lacking EPO or EPO-R exhibit increased neural cell apoptosis during development before embryonic death due to severe anemia. EPO administration provides neural protection in animal models of brain ischemia and trauma, reducing the extent of injury and damage. EPO stimulation of endothelial cells contributes to neuroprotection and is of particular importance since only low levels of EPO appear to cross the blood-brain barrier when administered at high dose intravenously. The therapeutic potential of EPO for brain ischemia/trauma and neurodegenerative diseases has shown promise in early clinical trial and awaits further validation. PMID:17482474

Confounding factors in diagnosing brain death: a case report

PubMed Central

Burns, Jeffrey M; Login, Ivan S

2002-01-01

Background Brain death is strictly defined medically and legally. This diagnosis depends on three cardinal neurological features: coma, absent brainstem reflexes, and apnea. The diagnosis can only be made, however, in the absence of intoxication, hypothermia, or certain medical illnesses. Case presentation A patient with severe hypoxic-ischemic brain injury met the three cardinal neurological features of brain death but concurrent profound hypothyroidism precluded the diagnosis. Our clinical and ethical decisions were further challenged by another facet of this complex case. Although her brain damage indicated a hopeless prognosis, we could not discontinue care based on futility because the only known surrogate was mentally retarded and unable to participate in medical planning. Conclusion The presence of certain medical conditions prohibits a diagnosis of brain death, which is a medicolegal diagnosis of death, not a prediction or forecast of future outcome. While prognostication is important in deciding to withdraw care, it is not a component in diagnosing brain death. PMID:12097152

Comparing Two Processing Pipelines to Measure Subcortical and Cortical Volumes in Patients with and without Mild Traumatic Brain Injury.

PubMed

Reid, Matthew W; Hannemann, Nathan P; York, Gerald E; Ritter, John L; Kini, Jonathan A; Lewis, Jeffrey D; Sherman, Paul M; Velez, Carmen S; Drennon, Ann Marie; Bolzenius, Jacob D; Tate, David F

2017-07-01

To compare volumetric results from NeuroQuant® and FreeSurfer in a service member setting. Since the advent of medical imaging, quantification of brain anatomy has been a major research and clinical effort. Rapid advancement of methods to automate quantification and to deploy this information into clinical practice has surfaced in recent years. NeuroQuant® is one such tool that has recently been used in clinical settings. Accurate volumetric data are useful in many clinical indications; therefore, it is important to assess the intermethod reliability and concurrent validity of similar volume quantifying tools. Volumetric data from 148 U.S. service members across three different experimental groups participating in a study of mild traumatic brain injury (mTBI) were examined. Groups included mTBI (n = 71), posttraumatic stress disorder (n = 22), or a noncranial orthopedic injury (n = 55). Correlation coefficients and nonparametric group mean comparisons were used to assess reliability and concurrent validity, respectively. Comparison of these methods across our entire sample demonstrates generally fair to excellent reliability as evidenced by large intraclass correlation coefficients (ICC = .4 to .99), but little concurrent validity as evidenced by significantly different Mann-Whitney U comparisons for 26 of 30 brain structures measured. While reliability between the two segmenting tools is fair to excellent, volumetric outcomes are statistically different between the two methods. As suggested by both developers, structure segmentation should be visually verified prior to clinical use and rigor should be used when interpreting results generated by either method. Copyright © 2017 by the American Society of Neuroimaging.

Adult Brain Tumors and Pseudotumors: Interesting (Bizarre) Cases.

PubMed

Causil, Lazaro D; Ames, Romy; Puac, Paulo; Castillo, Mauricio

2016-11-01

Some brain tumors results are interesting due to their rarity at presentation and overwhelming imaging characteristics, posing a diagnostic challenge in the eyes of any experienced neuroradiologist. This article focuses on the most important features regarding epidemiology, location, clinical presentation, histopathology, and imaging findings of cases considered "bizarre." A review of the most recent literature dealing with these unusual tumors and pseudotumors is presented, highlighting key points related to the diagnosis, treatments, outcomes, and differential diagnosis. Copyright © 2016 Elsevier Inc. All rights reserved.

A Randomized Clinical Trial of Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorders

DTIC Science & Technology

2015-10-01

This project is focused on conducting the first randomized-controlled trial of Cognitive Enhancement Therapy (CET) in 54 verbal adults with autism ...of the neuroplastic effects of CET on brain function in support of cognitive enhancement in adult autism . Analyses of treatment effects to date...the need and potential for CET to be a significant treatment advance for verbal adults with autism . Importantly, improvements were found in daily life function and in brain circuitry supporting core abilities.

Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson's disease.

PubMed

Hacker, Mallory L; Tonascia, James; Turchan, Maxim; Currie, Amanda; Heusinkveld, Lauren; Konrad, Peter E; Davis, Thomas L; Neimat, Joseph S; Phibbs, Fenna T; Hedera, Peter; Wang, Lily; Shi, Yaping; Shade, David M; Sternberg, Alice L; Drye, Lea T; Charles, David

2015-10-01

The Vanderbilt pilot trial of deep brain stimulation (DBS) in early Parkinson's disease (PD) enrolled patients on medications six months to four years without motor fluctuations or dyskinesias. We conducted a patient-centered analysis based on clinically important worsening of motor symptoms and complications of medical therapy for all subjects and a subset of subjects with a more focused medication duration. Continuous outcomes were also analyzed for this focused cohort. A post hoc analysis was conducted on all subjects from the pilot and a subset of subjects taking PD medications 1-4 years at enrollment. Clinically important worsening is defined as both a ≥ 3 point increase in UPDRS Part III and a ≥ 1 point increase in Part IV. DBS plus optimal drug therapy (DBS + ODT) subjects experienced a 50-80% reduction in the relative risk of worsening after two years. The DBS + ODT group was improved compared to optimal drug therapy (ODT) at each time point on Total UPDRS and Part III (p = 0.04, p = 0.02, respectively, at 24 months). Total UPDRS, Part IV, and PDQ-39 scores significantly worsened in the ODT group after two years (p < 0.003), with no significant change in the DBS + ODT group. DBS + ODT in early PD may reduce the risk of clinically important worsening. These findings further confirm the need to determine if DBS + ODT is superior to medical therapy for managing symptoms, reducing the complications of medications, and improving quality of life. The FDA has approved the conduct of a large-scale, pivotal clinical trial of DBS in early stage PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Brain temperature and its fundamental properties: a review for clinical neuroscientists

PubMed Central

Wang, Huan; Wang, Bonnie; Normoyle, Kieran P.; Jackson, Kevin; Spitler, Kevin; Sharrock, Matthew F.; Miller, Claire M.; Best, Catherine; Llano, Daniel; Du, Rose

2014-01-01

Brain temperature, as an independent therapeutic target variable, has received increasingly intense clinical attention. To date, brain hypothermia represents the most potent neuroprotectant in laboratory studies. Although the impact of brain temperature is prevalent in a number of common human diseases including: head trauma, stroke, multiple sclerosis, epilepsy, mood disorders, headaches, and neurodegenerative disorders, it is evident and well recognized that the therapeutic application of induced hypothermia is limited to a few highly selected clinical conditions such as cardiac arrest and hypoxic ischemic neonatal encephalopathy. Efforts to understand the fundamental aspects of brain temperature regulation are therefore critical for the development of safe, effective, and pragmatic clinical treatments for patients with brain injuries. Although centrally-mediated mechanisms to maintain a stable body temperature are relatively well established, very little is clinically known about brain temperature's spatial and temporal distribution, its physiological and pathological fluctuations, and the mechanism underlying brain thermal homeostasis. The human brain, a metabolically “expensive” organ with intense heat production, is sensitive to fluctuations in temperature with regards to its functional activity and energy efficiency. In this review, we discuss several critical aspects concerning the fundamental properties of brain temperature from a clinical perspective. PMID:25339859

Genetic control of postnatal human brain growth

PubMed Central

van Dyck, Laura I.; Morrow, Eric M.

2017-01-01

Purpose of review Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms. Recent findings Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, postmortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry. Summary In order to understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders. PMID:27898583

Inhibition of type I insulin-like growth factor receptor signaling attenuates the development of breast cancer brain metastasis.

PubMed

Saldana, Sandra M; Lee, Heng-Huan; Lowery, Frank J; Khotskaya, Yekaterina B; Xia, Weiya; Zhang, Chenyu; Chang, Shih-Shin; Chou, Chao-Kai; Steeg, Patricia S; Yu, Dihua; Hung, Mien-Chie

2013-01-01

Brain metastasis is a common cause of mortality in cancer patients, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF-IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that IGF-IR is constitutively autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR results in a decrease of phospho-AKT and phospho-p70s6k, as well as decreased migration and invasion of MDA-MB-231Br brain-seeking cells. In addition, transient ablation of IGFBP3, which is overexpressed in brain-seeking cells, blocks IGF-IR activation. Using an in vivo experimental brain metastasis model, we show that IGF-IR knockdown brain-seeking cells have reduced potential to establish brain metastases. Finally, we demonstrate that the malignancy of brain-seeking cells is attenuated by pharmacological inhibition with picropodophyllin, an IGF-IR-specific tyrosine kinase inhibitor. Together, our data suggest that the IGF-IR is an important mediator of brain metastasis and its ablation delays the onset of brain metastases in our model system.

Evaluation of image quality of MRI data for brain tumor surgery

NASA Astrophysics Data System (ADS)

Heckel, Frank; Arlt, Felix; Geisler, Benjamin; Zidowitz, Stephan; Neumuth, Thomas

2016-03-01

3D medical images are important components of modern medicine. Their usefulness for the physician depends on their quality, though. Only high-quality images allow accurate and reproducible diagnosis and appropriate support during treatment. We have analyzed 202 MRI images for brain tumor surgery in a retrospective study. Both an experienced neurosurgeon and an experienced neuroradiologist rated each available image with respect to its role in the clinical workflow, its suitability for this specific role, various image quality characteristics, and imaging artifacts. Our results show that MRI data acquired for brain tumor surgery does not always fulfill the required quality standards and that there is a significant disagreement between the surgeon and the radiologist, with the surgeon being more critical. Noise, resolution, as well as the coverage of anatomical structures were the most important criteria for the surgeon, while the radiologist was mainly disturbed by motion artifacts.

Renaissance of criticism on the concept of brain death--the role of legal medicine in the context of the interdisciplinary discussion.

PubMed

Markert, L; Bockholdt, B; Verhoff, M A; Heinze, S; Parzeller, M

2016-03-01

In the practice of legal medicine in Germany, the assessment of brain death is of minor importance and attracts little attention. However, since several years, international criticism on the concept of brain death has culminated. By reviewing literature and the results of a questionnaire distributed among the participants of the 93rd Annual Congress of the Germany Society of Legal Medicine, the state of knowledge and the current views on brain death were evaluated. Literature search of recent publications regarding brain death was performed (PubMed database, references of legal medicine, Report of the President's Council on Bioethics, USA 2008). A questionnaire was developed and distributed among the participants of the Congress. The assumption that individual and brain death are synonymous is criticized. Internationally, there are trends to harmonize the very different clinical criteria to assess brain death. The diagnostic advantage of novel techniques such as CT angiography is controversially discussed. It becomes apparent that procedures which record the blood flow and perfusion of the brain will be applied more in the future. Regrettably, these developments are not described in the literature of legal medicine. Moreover, among German forensic scientists, different views concerning brain death exist. The majority favors its equivalent treatment with individual death. The thanatological background can be improved concerning certain aspects of brain death as well as its legal implications. Teaching and research in legal medicine should include the subject brain death. Expertise in forensic science may contribute to the interdisciplinary discussion on brain death. The transfer of actual knowledge, also on disputed ethical aspects of thanatology, to physicians of all disciplines is of great importance.

Mentoring Women in the Frederick Community | Poster

Cancer.gov

Joy Beveridge, clinical project manager III, is all about building relationships. Her work as a clinical project manager requires her to manage teams such as the Coordinating Center for Clinical Trials, Center for Global Health, Brain Tumor Trials Collaborative, and Division of Cancer Treatment and Diagnosis. Equally important are the relationships Beveridge builds through her work with Woman to Woman Mentoring, Inc. (W2WM), a 501(C)3 non-profit organization that seeks to cultivate mentoring relationships that provide women with guidance, support, and connections.

Quantifying brain volumes for Multiple Sclerosis patients follow-up in clinical practice - comparison of 1.5 and 3 Tesla magnetic resonance imaging.

PubMed

Lysandropoulos, Andreas P; Absil, Julie; Metens, Thierry; Mavroudakis, Nicolas; Guisset, François; Van Vlierberghe, Eline; Smeets, Dirk; David, Philippe; Maertens, Anke; Van Hecke, Wim

2016-02-01

There is emerging evidence that brain atrophy is a part of the pathophysiology of Multiple Sclerosis (MS) and correlates with several clinical outcomes of the disease, both physical and cognitive. Consequently, brain atrophy is becoming an important parameter in patients' follow-up. Since in clinical practice both 1.5Tesla (T) and 3T magnetic resonance imaging (MRI) systems are used for MS patients follow-up, questions arise regarding compatibility and a possible need for standardization. Therefore, in this study 18 MS patients were scanned on the same day on a 1.5T and a 3T scanner. For each scanner, a 3D T1 and a 3D FLAIR were acquired. As no atrophy is expected within 1 day, these datasets can be used to evaluate the median percentage error of the brain volume measurement for gray matter (GM) volume and parenchymal volume (PV) between 1.5T and 3T scanners. The results are obtained with MSmetrix, which is developed especially for use in the MS clinical care path, and compared to Siena (FSL), a widely used software for research purposes. The MSmetrix median percentage error of the brain volume measurement between a 1.5T and a 3T scanner is 0.52% for GM and 0.35% for PV. For Siena this error equals 2.99%. When data of the same scanner are compared, the error is in the order of 0.06-0.08% for both MSmetrix and Siena. MSmetrix appears robust on both the 1.5T and 3T systems and the measurement error becomes an order of magnitude higher between scanners with different field strength.

Combined ultrasound and MR imaging to guide focused ultrasound therapies in the brain

NASA Astrophysics Data System (ADS)

Arvanitis, Costas D.; Livingstone, Margaret S.; McDannold, Nathan

2013-07-01

Several emerging therapies with potential for use in the brain, harness effects produced by acoustic cavitation—the interaction between ultrasound and microbubbles either generated during sonication or introduced into the vasculature. Systems developed for transcranial MRI-guided focused ultrasound (MRgFUS) thermal ablation can enable their clinical translation, but methods for real-time monitoring and control are currently lacking. Acoustic emissions produced during sonication can provide information about the location, strength and type of the microbubble oscillations within the ultrasound field, and they can be mapped in real-time using passive imaging approaches. Here, we tested whether such mapping can be achieved transcranially within a clinical brain MRgFUS system. We integrated an ultrasound imaging array into the hemisphere transducer of the MRgFUS device. Passive cavitation maps were obtained during sonications combined with a circulating microbubble agent at 20 targets in the cingulate cortex in three macaques. The maps were compared with MRI-evident tissue effects. The system successfully mapped microbubble activity during both stable and inertial cavitation, which was correlated with MRI-evident transient blood-brain barrier disruption and vascular damage, respectively. The location of this activity was coincident with the resulting tissue changes within the expected resolution limits of the system. While preliminary, these data clearly demonstrate, for the first time, that it is possible to construct maps of stable and inertial cavitation transcranially, in a large animal model, and under clinically relevant conditions. Further, these results suggest that this hybrid ultrasound/MRI approach can provide comprehensive guidance for targeted drug delivery via blood-brain barrier disruption and other emerging ultrasound treatments, facilitating their clinical translation. We anticipate that it will also prove to be an important research tool that will further the development of a broad range of microbubble-enhanced therapies.

Effects of Cognitive-Behavioral Therapy (CBT) on Brain Connectivity Supporting Catastrophizing in Fibromyalgia.

PubMed

Lazaridou, Asimina; Kim, Jieun; Cahalan, Christine M; Loggia, Marco L; Franceschelli, Olivia; Berna, Chantal; Schur, Peter; Napadow, Vitaly; Edwards, Robert R

2017-03-01

Fibromyalgia (FM) is a chronic, common pain disorder characterized by hyperalgesia. A key mechanism by which cognitive-behavioral therapy (CBT) fosters improvement in pain outcomes is via reductions in hyperalgesia and pain-related catastrophizing, a dysfunctional set of cognitive-emotional processes. However, the neural underpinnings of these CBT effects are unclear. Our aim was to assess CBT's effects on the brain circuitry underlying hyperalgesia in FM patients, and to explore the role of treatment-associated reduction in catastrophizing as a contributor to normalization of pain-relevant brain circuitry and clinical improvement. In total, 16 high-catastrophizing FM patients were enrolled in the study and randomized to 4 weeks of individual treatment with either CBT or a Fibromyalgia Education (control) condition. Resting state functional magnetic resonance imaging scans evaluated functional connectivity between key pain-processing brain regions at baseline and posttreatment. Clinical outcomes were assessed at baseline, posttreatment, and 6-month follow-up. Catastrophizing correlated with increased resting state functional connectivity between S1 and anterior insula. The CBT group showed larger reductions (compared with the education group) in catastrophizing at posttreatment (P<0.05), and CBT produced significant reductions in both pain and catastrophizing at the 6-month follow-up (P<0.05). Patients in the CBT group also showed reduced resting state connectivity between S1 and anterior/medial insula at posttreatment; these reductions in resting state connectivity were associated with concurrent treatment-related reductions in catastrophizing. The results add to the growing support for the clinically important associations between S1-insula connectivity, clinical pain, and catastrophizing, and suggest that CBT may, in part via reductions in catastrophizing, help to normalize pain-related brain responses in FM.

Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

PubMed Central

Haldar, Swati; Tripathi, Ajai K.; Horback, Katharine; Wong, Joseph; Sharma, Deepak; Beserra, Amber; Suda, Srinivas; Anbalagan, Charumathi; Dev, Som; Mukhopadhyay, Chinmay K.; Singh, Ajay

2014-01-01

Abstract Iron has emerged as a significant cause of neurotoxicity in several neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), sporadic Creutzfeldt-Jakob disease (sCJD), and others. In some cases, the underlying cause of iron mis-metabolism is known, while in others, our understanding is, at best, incomplete. Recent evidence implicating key proteins involved in the pathogenesis of AD, PD, and sCJD in cellular iron metabolism suggests that imbalance of brain iron homeostasis associated with these disorders is a direct consequence of disease pathogenesis. A complete understanding of the molecular events leading to this phenotype is lacking partly because of the complex regulation of iron homeostasis within the brain. Since systemic organs and the brain share several iron regulatory mechanisms and iron-modulating proteins, dysfunction of a specific pathway or selective absence of iron-modulating protein(s) in systemic organs has provided important insights into the maintenance of iron homeostasis within the brain. Here, we review recent information on the regulation of iron uptake and utilization in systemic organs and within the complex environment of the brain, with particular emphasis on the underlying mechanisms leading to brain iron mis-metabolism in specific neurodegenerative conditions. Mouse models that have been instrumental in understanding systemic and brain disorders associated with iron mis-metabolism are also described, followed by current therapeutic strategies which are aimed at restoring brain iron homeostasis in different neurodegenerative conditions. We conclude by highlighting important gaps in our understanding of brain iron metabolism and mis-metabolism, particularly in the context of neurodegenerative disorders. Antioxid. Redox Signal. 20, 1324–1363. PMID:23815406

Brain iron homeostasis: from molecular mechanisms to clinical significance and therapeutic opportunities.

PubMed

Singh, Neena; Haldar, Swati; Tripathi, Ajai K; Horback, Katharine; Wong, Joseph; Sharma, Deepak; Beserra, Amber; Suda, Srinivas; Anbalagan, Charumathi; Dev, Som; Mukhopadhyay, Chinmay K; Singh, Ajay

2014-03-10

Iron has emerged as a significant cause of neurotoxicity in several neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), sporadic Creutzfeldt-Jakob disease (sCJD), and others. In some cases, the underlying cause of iron mis-metabolism is known, while in others, our understanding is, at best, incomplete. Recent evidence implicating key proteins involved in the pathogenesis of AD, PD, and sCJD in cellular iron metabolism suggests that imbalance of brain iron homeostasis associated with these disorders is a direct consequence of disease pathogenesis. A complete understanding of the molecular events leading to this phenotype is lacking partly because of the complex regulation of iron homeostasis within the brain. Since systemic organs and the brain share several iron regulatory mechanisms and iron-modulating proteins, dysfunction of a specific pathway or selective absence of iron-modulating protein(s) in systemic organs has provided important insights into the maintenance of iron homeostasis within the brain. Here, we review recent information on the regulation of iron uptake and utilization in systemic organs and within the complex environment of the brain, with particular emphasis on the underlying mechanisms leading to brain iron mis-metabolism in specific neurodegenerative conditions. Mouse models that have been instrumental in understanding systemic and brain disorders associated with iron mis-metabolism are also described, followed by current therapeutic strategies which are aimed at restoring brain iron homeostasis in different neurodegenerative conditions. We conclude by highlighting important gaps in our understanding of brain iron metabolism and mis-metabolism, particularly in the context of neurodegenerative disorders.

The temporal pattern of stimulation may be important to the mechanism of deep brain stimulation

PubMed Central

Hess, Christopher W.; Vaillancourt, David E.; Okun, Michael S.

2013-01-01

Deep brain stimulation (DBS) has emerged as an important and potentially powerful treatment option for the management of carefully selected patients with advanced Parkinson's disease (PD) who are not adequately controlled by standard medication therapy. Though considerable advances have been made, the mechanisms underlying the therapeutic effects of DBS remain unclear despite its clinical efficacy. It is now widely held that both excitation and inhibition can occur secondary to stimulation, and it is suspected that abnormal synchronized oscillations may also be important in the mechanism of DBS. Other potentially important processes, including blood flow changes, local and upstream neurogenesis, and the modulation of neurotransmitters through stimulation of bordering astrocytes are also being investigated. Recent research has suggested that the temporal pattern of DBS stimulation is also an important variable in DBS neuromodulation, yet the extent of its influence on DBS efficacy has yet to be determined. As high stimulation frequency alone does not appear to be sufficient for optimal symptom suppression, attention to stimulation pattern might lead to more effective symptom control and reduced side effects, possibly at a lower frequency. Stimulation pattern may be potentially amenable to therapeutic modulation and its role in the clinical efficacy of DBS should be addressed through further focus and research. PMID:23399890

Brain Imaging and Human Nutrition: Which Measures to Use in Intervention Studies?12

PubMed Central

Sizonenko, Stéphane V.; Babiloni, Claudio; Sijben, John W.; Walhovd, Kristine B.

2013-01-01

Throughout the life span, the brain is a metabolically highly active organ that uses a large proportion of total nutrient and energy intake. Furthermore, the development and repair of neural tissue depend on the proper intake of essential structural nutrients, minerals, and vitamins. Therefore, what we eat, or refrain from eating, may have an important impact on our cognitive ability and mental performance. Two of the key areas in which diet is thought to play an important role are in optimizing neurodevelopment in children and in preventing neurodegeneration and cognitive decline during aging. From early development to aging, brain imaging can detect structural, functional, and metabolic changes in humans and modifications due to altered nutrition or to additional nutritional supplementation. Inclusion of imaging measures in clinical studies can increase understanding with regard to the modification of brain structure, metabolism, and functional endpoints and may provide early sensitive measures of long-term effects. In this symposium, the utility of existing brain imaging technologies to assess the effects of nutritional intervention in humans is described. Examples of current research showing the utility of these markers are reviewed. PMID:24038255

Automated brain tumor segmentation in magnetic resonance imaging based on sliding-window technique and symmetry analysis.

PubMed

Lian, Yanyun; Song, Zhijian

2014-01-01

Brain tumor segmentation from magnetic resonance imaging (MRI) is an important step toward surgical planning, treatment planning, monitoring of therapy. However, manual tumor segmentation commonly used in clinic is time-consuming and challenging, and none of the existed automated methods are highly robust, reliable and efficient in clinic application. An accurate and automated tumor segmentation method has been developed for brain tumor segmentation that will provide reproducible and objective results close to manual segmentation results. Based on the symmetry of human brain, we employed sliding-window technique and correlation coefficient to locate the tumor position. At first, the image to be segmented was normalized, rotated, denoised, and bisected. Subsequently, through vertical and horizontal sliding-windows technique in turn, that is, two windows in the left and the right part of brain image moving simultaneously pixel by pixel in two parts of brain image, along with calculating of correlation coefficient of two windows, two windows with minimal correlation coefficient were obtained, and the window with bigger average gray value is the location of tumor and the pixel with biggest gray value is the locating point of tumor. At last, the segmentation threshold was decided by the average gray value of the pixels in the square with center at the locating point and 10 pixels of side length, and threshold segmentation and morphological operations were used to acquire the final tumor region. The method was evaluated on 3D FSPGR brain MR images of 10 patients. As a result, the average ratio of correct location was 93.4% for 575 slices containing tumor, the average Dice similarity coefficient was 0.77 for one scan, and the average time spent on one scan was 40 seconds. An fully automated, simple and efficient segmentation method for brain tumor is proposed and promising for future clinic use. Correlation coefficient is a new and effective feature for tumor location.

The Clinical Management of Multiple Melanoma Brain Metastases: A Systematic Review

PubMed Central

Goyal, Sharad; Silk, Ann W.; Tian, Sibo; Mehnert, Janice; Danish, Shabbar; Ranjan, Sinthu; Kaufman, Howard L.

2017-01-01

Importance The treatment of multiple brain metastases (MBM) from melanoma is controversial and includes surgical resection, stereotactic radiosurgery and whole brain radiation. Several new classes of agents have revolutionized the treatment of metastatic melanoma allowing for subsets of patients to have long-term survival. Given this, management of MBM from melanoma is continually evolving. Objective To review the current evidence regarding the treatment of MBM from melanoma. Evidence Review The Pubmed database was searched using combinations of search terms and synonyms for melanoma, brain metastases, radiation, chemotherapy, immunotherapy and targeted therapy published between January 1, 1995 and January 1, 2015. Articles were selected for inclusion based on targeted keyword searches, manual review of bibliographies, and whether the article was a clinical trial, large observational study, or retrospective study focusing on melanoma brain metastases. Of 2243 articles initially identified, 110 were selected for full review. Of these, the most pertinent 76 articles were included. Findings Patients with newly diagnosed MBM can be treated with various modalities, either alone or in combination. Level 1 evidence supports the use of radiosurgery alone, whole brain radiation therapy (WBRT), and radiosurgery with WBRT. Though the addition of WBRT to SRS improves the overall brain relapse rate, WBRT has no significant impact on overall survival and has detrimental neurocognitive outcomes. Cytotoxic chemotherapy has largely been ineffective; targeted therapies and immunotherapies have reported to have high response rates and deserve further attention in the setting of larger clinical trials. Further studies are needed to fully evaluate the efficacy of these novel regimens in combination with radiation therapy. Conclusions and Relevance At this time, the standard management for patients with MBM from melanoma includes SRS, WBRT, or combination of both. Emerging data exists to support the notion that SRS in combination with targeted therapies or immune therapy may obviate the need for whole brain radiation and prospective studies are required to fully evaluate the efficacy of these novel regimens in combination with radiation therapy. PMID:26181286

The Missing Link in the Pathophysiology of Vascular Cognitive Impairment: Design of the Heart-Brain Study

PubMed Central

Hooghiemstra, Astrid M.; Bertens, Anne Suzanne; Leeuwis, Anna E.; Bron, Esther E.; Bots, Michiel L.; Brunner-La Rocca, Hans-Peter; de Craen, Anton J.M.; van der Geest, Rob J.; Greving, Jacoba P.; Kappelle, L. Jaap; Niessen, Wiro J.; van Oostenbrugge, Robert J.; van Osch, Matthias J.P.; de Roos, Albert; van Rossum, Albert C.; Biessels, Geert Jan; van Buchem, Mark A.; Daemen, Mat J.A.P.; van der Flier, Wiesje M.

2017-01-01

Background Hemodynamic balance in the heart-brain axis is increasingly recognized as a crucial factor in maintaining functional and structural integrity of the brain and thereby cognitive functioning. Patients with heart failure (HF), carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present themselves with complaints attributed to specific parts of the heart-brain axis, but hemodynamic changes often go beyond the part of the axis for which they primarily seek medical advice. The Heart-Brain Study hypothesizes that the hemodynamic status of the heart and the brain is an important but underestimated cause of VCI. We investigate this by studying to what extent hemodynamic changes contribute to VCI and what the mechanisms involved are. Here, we provide an overview of the design and protocol. Methods The Heart-Brain Study is a multicenter cohort study with a follow-up measurement after 2 years among 645 participants (175 VCI, 175 COD, 175 HF, and 120 controls). Enrollment criteria are the following: 1 of the 3 diseases diagnosed according to current guidelines, age ≥50 years, no magnetic resonance contraindications, ability to undergo cognitive testing, and independence in daily life. A core clinical dataset is collected including sociodemographic factors, cardiovascular risk factors, detailed neurologic, cardiac, and medical history, medication, and a physical examination. In addition, we perform standardized neuropsychological testing, cardiac, vascular and brain MRI, and blood sampling. In subsets of participants we assess Alz­heimer biomarkers in cerebrospinal fluid, and assess echocardiography and 24-hour blood pressure monitoring. Follow-up measurements after 2 years include neuropsychological testing, brain MRI, and blood samples for all participants. We use centralized state-of-the-art storage platforms for clinical and imaging data. Imaging data are processed centrally with automated standardized pipelines. Results and Conclusions The Heart-Brain Study investigates relationships between (cardio-)vascular factors, the hemodynamic status of the heart and the brain, and cognitive impairment. By studying the complete heart-brain axis in patient groups that represent components of this axis, we have the opportunity to assess a combination of clinical and subclinical manifestations of disorders of the heart, vascular system and brain, with hemodynamic status as a possible binding factor. PMID:29017156

Ghrelin

PubMed Central

Wu, James T.; Kral, John G.

2004-01-01

Objective: Ghrelin is a novel gastric hormone recognized in 1999 as a mediator of growth hormone release. Since growth hormone is anabolic, an important function of ghrelin may be to coordinate energy needs with the growth process. Newly discovered biologic roles of ghrelin imply that it may have other important physiological functions as well. This is a review of recent clinically relevant, yet less well-known, physiologic actions of ghrelin. Summary Background Data: Ghrelin has profound orexigenic, adipogenic, and somatotrophic properties, increasing food intake and body weight. Secreted predominantly from the stomach, ghrelin is the natural ligand for the growth hormone secretagogue receptor in the pituitary gland, thus fulfilling criteria of a brain-gut peptide. The brain-gut axis is the effector of anabolism by regulating growth, feeding, and metabolism via vagal afferents mediating ghrelin signaling. However, the wide tissue distribution of ghrelin suggests that it may have other functions as well. Methods: Systematic literature review of all PubMed citations between 1999 and August 2003 focusing on clinically relevant biochemical and physiological characteristics of ghrelin. Results: Ghrelin is an important component of an integrated regulatory system of growth and metabolism acting via the vagus nerve, and is implicated in a variety of altered energy states such as obesity, eating disorders, neoplasia, and cachexia. It also enhances immune responses and potentially down-regulates anti-inflammatory molecules. Ghrelin's role as a brain-gut peptide emphasizes the significance of afferent vagal fibers as a major pathway to the brain, serving the purpose of maintaining physiologic homeostasis. Conclusions: The discovery of ghrelin has increased our understanding of feeding regulation, nutritional homeostasis, and metabolic processes. Further characterization of ghrelin's functions will likely generate new pharmacological approaches to diagnose and treat different disease entities including those related to the over-nutrition of obesity and the catabolic response to surgical trauma. PMID:15024307

The right brain is dominant in psychotherapy.

PubMed

Schore, Allan N

2014-09-01

This article discusses how recent studies of the right brain, which is dominant for the implicit, nonverbal, intuitive, holistic processing of emotional information and social interactions, can elucidate the neurobiological mechanisms that underlie the relational foundations of psychotherapy. Utilizing the interpersonal neurobiological perspective of regulation theory, I describe the fundamental role of the early developing right brain in relational processes, throughout the life span. I present interdisciplinary evidence documenting right brain functions in early attachment processes, in emotional communications within the therapeutic alliance, in mutual therapeutic enactments, and in therapeutic change processes. This work highlights the fact that the current emphasis on relational processes is shared by, cross-fertilizing, and indeed transforming both psychology and neuroscience, with important consequences for clinical psychological models of psychotherapeutic change. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Transplantation of embryonic stem cell-derived dopaminergic neurons in MPTP-treated monkeys.

PubMed

Takahashi, Jun; Takagi, Yasushi; Saiki, Hidemoto

2009-01-01

One of the target diseases of cell-replacement therapy is Parkinson's disease. Clinical experiences with fetal dopaminergic cell graft have shown that the therapy is effective, but limited and accompanied by side effects, such as dyskinesia. So, the therapy needs to be further improved and sophisticated. Embryonic stem (ES) cells are expected to be another donor cell for the treatment, because of its proliferative and differentiation capacities. For clinical application, experiments using non-human primates are important, because size, anatomy, and biological characteristics of the brain are different between rodents and primates. Here, we would like to discuss induction of dopaminergic neurons from monkey ES cells and cell transplantation into the brain of monkey Parkinson's disease model.

"Clinical brain profiling": a neuroscientific diagnostic approach for mental disorders.

PubMed

Peled, Abraham; Geva, Amir B

2014-10-01

Clinical brain profiling is an attempt to map a descriptive nosology in psychiatry to underlying constructs in neurobiology and brain dynamics. This paper briefly reviews the motivation behind clinical brain profiling (CBP) and presents some provisional validation using clinical assessments and meta-analyses of neuroscientific publications. The paper has four sections. In the first, we review the nature and motivation for clinical brain profiling. This involves a description of the key aspects of functional anatomy that can lead to psychopathology. These features constitute the dimensions or categories for a profile of brain disorders based upon pathophysiology. The second section describes a mapping or translation matrix that maps from symptoms and signs, of a descriptive sort, to the CBP dimensions that provide a more mechanistic explanation. We will describe how this mapping engenders archetypal diagnoses, referring readers to tables and figures. The third section addresses the construct validity of clinical brain profiling by establishing correlations between profiles based on clinical ratings of symptoms and signs under classical diagnostic categories with the corresponding profiles generated automatically using archetypal diagnoses. We then provide further validation by performing a cluster analysis on the symptoms and signs and showing how they correspond to the equivalent brain profiles based upon clinical and automatic diagnosis. In the fourth section, we address the construct validity of clinical brain profiling by looking for associations between pathophysiological mechanisms (such as connectivity and plasticity) and nosological diagnoses (such as schizophrenia and depression). Based upon the mechanistic perspective offered in the first section, we test some particular hypotheses about double dissociations using a meta-analysis of PubMed searches. The final section concludes with perspectives for the future and outstanding validation issues for clinical brain profiling. Copyright © 2014 Elsevier Ltd. All rights reserved.

PaCER - A fully automated method for electrode trajectory and contact reconstruction in deep brain stimulation.

PubMed

Husch, Andreas; V Petersen, Mikkel; Gemmar, Peter; Goncalves, Jorge; Hertel, Frank

2018-01-01

Deep brain stimulation (DBS) is a neurosurgical intervention where electrodes are permanently implanted into the brain in order to modulate pathologic neural activity. The post-operative reconstruction of the DBS electrodes is important for an efficient stimulation parameter tuning. A major limitation of existing approaches for electrode reconstruction from post-operative imaging that prevents the clinical routine use is that they are manual or semi-automatic, and thus both time-consuming and subjective. Moreover, the existing methods rely on a simplified model of a straight line electrode trajectory, rather than the more realistic curved trajectory. The main contribution of this paper is that for the first time we present a highly accurate and fully automated method for electrode reconstruction that considers curved trajectories. The robustness of our proposed method is demonstrated using a multi-center clinical dataset consisting of N  = 44 electrodes. In all cases the electrode trajectories were successfully identified and reconstructed. In addition, the accuracy is demonstrated quantitatively using a high-accuracy phantom with known ground truth. In the phantom experiment, the method could detect individual electrode contacts with high accuracy and the trajectory reconstruction reached an error level below 100 μm (0.046 ± 0.025 mm). An implementation of the method is made publicly available such that it can directly be used by researchers or clinicians. This constitutes an important step towards future integration of lead reconstruction into standard clinical care.

Measuring iron in the brain using quantitative susceptibility mapping and X-ray fluorescence imaging

PubMed Central

Zheng, Weili; Nichol, Helen; Liu, Saifeng; Cheng, Yu-Chung N.; Haacke, E. Mark

2013-01-01

Measuring iron content in the brain has important implications for a number of neurodegenerative diseases. Quantitative susceptibility mapping (QSM), derived from magnetic resonance images, has been used to measure total iron content in vivo and in post mortem brain. In this paper, we show how magnetic susceptibility from QSM correlates with total iron content measured by X-ray fluorescence (XRF) imaging and by inductively coupled plasma mass spectrometry (ICPMS). The relationship between susceptibility and ferritin iron was estimated at 1.10 ± 0.08 ppb susceptibility per μg iron/g wet tissue, similar to that of iron in fixed (frozen/thawed) cadaveric brain and previously published data from unfixed brains. We conclude that magnetic susceptibility can provide a direct and reliable quantitative measurement of iron content and that it can be used clinically at least in regions with high iron content. PMID:23591072

A proposed role for efflux transporters in the pathogenesis of hydrocephalus

PubMed Central

Krishnamurthy, Satish; Tichenor, Michael D.; Satish, Akhila G.; Lehmann, David B.

2014-01-01

Hydrocephalus is a common brain disorder that is treated only with surgery. The basis for surgical treatment rests on the circulation theory. However, clinical and experimental data to substantiate circulation theory have remained inconclusive. In brain tissue and in the ventricles, we see that osmotic gradients drive water diffusion in water-permeable tissue. As the osmolarity of ventricular CSF increases within the cerebral ventricles, water movement into the ventricles increases and causes hydrocephalus. Macromolecular clearance from the ventricles is a mechanism to establish the normal CSF osmolarity, and therefore ventricular volume. Efflux transporters, (p-glycoprotein), are located along the blood brain barrier and play an important role in the clearance of macromolecules (endobiotics and xenobiotics) from the brain to the blood. There is clinical and experimental data to show that macromolecules are cleared out of the brain in normal and hydrocephalic brains. This article summarizes the existing evidence to support the role of efflux transporters in the pathogenesis of hydrocephalus. The location of p-gp along the pathways of macromolecular clearance and the broad substrate specificity of this abundant transporter to a variety of different macromolecules are reviewed. Involvement of p-gp in the transport of amyloid beta in Alzheimer disease and its relation to normal pressure hydrocephalus is reviewed. Finally, individual variability of p-gp expression might explain the variability in the development of hydrocephalus following intraventricular hemorrhage. PMID:25165050

Factors Influencing Clinical Correlates of Chronic Traumatic Encephalopathy (CTE): A Review

PubMed Central

Asken, Breton M.; Sullan, Molly J.; Snyder, Aliyah R.; Houck, Zachary M.; Bryant, Vaughn E.; Hizel, Loren P.; McLaren, Molly E.; Dede, Duane E.; Jaffee, Michael S.; DeKosky, Steven T.; Bauer, Russell M.

2017-01-01

Chronic traumatic encephalopathy (CTE) is a neuropathologically defined disease reportedly linked to a history of repetitive brain trauma. As such, retired collision sport athletes are likely at heightened risk for developing CTE. Researchers have described distinct pathological features of CTE as well a wide range of clinical symptom presentations, recently termed traumatic encephalopathy syndrome (TES). These clinical symptoms are highly variable, non-specific to individuals described as having CTE pathology in case reports, and are often associated with many other factors. This review describes the cognitive, emotional, and behavioral changes associated with 1) developmental and demographic factors, 2) neurodevelopmental disorders, 3) normal aging, 4) adjusting to retirement, 5) drug and alcohol abuse, 6) surgeries and anesthesia, and 7) sleep difficulties, as well as the relationship between these factors and risk for developing dementia-related neurodegenerative disease. We discuss why some professional athletes may be particularly susceptible to many of these effects and the importance of choosing appropriate controls groups when designing research protocols. We conclude that these factors should be considered as modifiers predominantly of the clinical outcomes associated with repetitive brain trauma within a broader biopsychosocial framework when interpreting and attributing symptom development, though also note potential effects on neuropathological outcomes. Importantly, this could have significant treatment implications for improving quality of life. PMID:27561662

Current Opportunities for Clinical Monitoring of Axonal Pathology in Traumatic Brain Injury

PubMed Central

Tsitsopoulos, Parmenion P.; Abu Hamdeh, Sami; Marklund, Niklas

2017-01-01

Traumatic brain injury (TBI) is a multidimensional and highly complex disease commonly resulting in widespread injury to axons, due to rapid inertial acceleration/deceleration forces transmitted to the brain during impact. Axonal injury leads to brain network dysfunction, significantly contributing to cognitive and functional impairments frequently observed in TBI survivors. Diffuse axonal injury (DAI) is a clinical entity suggested by impaired level of consciousness and coma on clinical examination and characterized by widespread injury to the hemispheric white matter tracts, the corpus callosum and the brain stem. The clinical course of DAI is commonly unpredictable and it remains a challenging entity with limited therapeutic options, to date. Although axonal integrity may be disrupted at impact, the majority of axonal pathology evolves over time, resulting from delayed activation of complex intracellular biochemical cascades. Activation of these secondary biochemical pathways may lead to axonal transection, named secondary axotomy, and be responsible for the clinical decline of DAI patients. Advances in the neurocritical care of TBI patients have been achieved by refinements in multimodality monitoring for prevention and early detection of secondary injury factors, which can be applied also to DAI. There is an emerging role for biomarkers in blood, cerebrospinal fluid, and interstitial fluid using microdialysis in the evaluation of axonal injury in TBI. These biomarker studies have assessed various axonal and neuroglial markers as well as inflammatory mediators, such as cytokines and chemokines. Moreover, modern neuroimaging can detect subtle or overt DAI/white matter changes in diffuse TBI patients across all injury severities using magnetic resonance spectroscopy, diffusion tensor imaging, and positron emission tomography. Importantly, serial neuroimaging studies provide evidence for evolving axonal injury. Since axonal injury may be a key risk factor for neurodegeneration and dementias at long-term following TBI, the secondary injury processes may require prolonged monitoring. The aim of the present review is to summarize the clinical short- and long-term monitoring possibilities of axonal injury in TBI. Increased knowledge of the underlying pathophysiology achieved by advanced clinical monitoring raises hope for the development of novel treatment strategies for axonal injury in TBI. PMID:29209266

Definition, evaluation, and management of brain relaxation during craniotomy.

PubMed

Li, J; Gelb, A W; Flexman, A M; Ji, F; Meng, L

2016-06-01

The term 'brain relaxation' is routinely used to describe the size and firmness of the brain tissue during craniotomy. The status of brain relaxation is an important aspect of neuroanaesthesia practice and is relevant to the operating conditions, retraction injury, and likely patient outcomes. Brain relaxation is determined by the relationship between the volume of the intracranial contents and the capacity of the intracranial space (i.e. a content-space relationship). It is a concept related to, but distinct from, intracranial pressure. The evaluation of brain relaxation should be standardized to facilitate clinical communication and research collaboration. Both advantageous and disadvantageous effects of the various interventions for brain relaxation should be taken into account in patient care. The outcomes that matter the most to patients should be emphasized in defining, evaluating, and managing brain relaxation. To date, brain relaxation has not been reviewed specifically, and the aim of this manuscript is to discuss the current approaches to the definition, evaluation, and management of brain relaxation, knowledge gaps, and targets for future research. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

SRC family kinases as novel therapeutic targets to treat breast cancer brain metastases.

PubMed

Zhang, Siyuan; Huang, Wen-Chien; Zhang, Lin; Zhang, Chenyu; Lowery, Frank J; Ding, Zhaoxi; Guo, Hua; Wang, Hai; Huang, Suyun; Sahin, Aysegul A; Aldape, Kenneth D; Steeg, Patricia S; Yu, Dihua

2013-09-15

Despite better control of early-stage disease and improved overall survival of patients with breast cancer, the incidence of life-threatening brain metastases continues to increase in some of these patients. Unfortunately, other than palliative treatments there is no effective therapy for this condition. In this study, we reveal a critical role for Src activation in promoting brain metastasis in a preclinical model of breast cancer and we show how Src-targeting combinatorial regimens can treat HER2(+) brain metastases in this model. We found that Src was hyperactivated in brain-seeking breast cancer cells derived from human cell lines or from patients' brain metastases. Mechanistically, Src activation promoted tumor cell extravasation into the brain parenchyma via permeabilization of the blood-brain barrier. When combined with the EGFR/HER2 dual-targeting drug lapatinib, an Src-targeting combinatorial regimen prevented outgrowth of disseminated breast cancer cells through the induction of cell-cycle arrest. More importantly, this combinatorial regimen inhibited the outgrowth of established experimental brain metastases, prolonging the survival of metastases-bearing mice. Our results provide a rationale for clinical evaluation of Src-targeting regimens to treat patients with breast cancer suffering from brain metastasis. ©2013 AACR.

Quality of life among parents of children with cancer or brain tumors: the impact of child characteristics and parental psychosocial factors.

PubMed

Litzelman, Kristin; Catrine, Kris; Gangnon, Ronald; Witt, Whitney P

2011-10-01

Understanding the impact of childhood cancer on the family is increasingly important. This study aimed to (1) examine the relationship between child clinical characteristics and health-related quality of life (QOL) among parents of children with cancer or brain tumors, and (2) determine how parental psychosocial factors impact this relationship. Using a within-group approach, this study examined 75 children with cancer or brain tumors and their parent. In-person interviewer-assisted surveys assessed sociodemographics, psychosocial factors, and QOL. Child clinical characteristics were obtained through medical record abstraction. Regressions were performed to determine factors related to parental QOL. Children's activity limitation and active treatment status were associated with worse parental mental QOL (5.4 and 4.4 points lower, respectively; P < 0.05). Adding parental psychosocial characteristics to the model eliminated the relationship between child clinical characteristics and parental mental QOL (P > 0.05 for all child characteristics). While child clinical characteristics appear to be related to poor parental QOL, this relationship was mediated by caregiver burden and stress. Interventions to reduce burden and stress may mitigate the deleterious effects of caregiving. Systematic screening of parents' mental and physical health may facilitate interventions and improve the health and well-being of parents and children.

Cognitive reserve: implications for assessment and intervention.

PubMed

Stern, Yaakov

2013-01-01

The concept of reserve is used to explain the observation that some individuals function better than others in the presence of brain pathology. This article reviews the concept of reserve from its theoretical basis to the implication of reserve for clinical practice. A distinction between brain reserve, referring to individual differences in the anatomic substrate, and cognitive reserve, referring to differences in the flexibility or adaptivity of cognitive networks, is useful. Epidemiologic evidence indicates that a set of life exposures including higher educational and occupational attainment, and engaging in leisure activities is associated with a lower risk of incident dementia, suggesting that these life exposures may enhance cognitive reserve. This provides a basis for controlled clinical studies that can test specific exposures that may enhance reserve. The concept of cognitive reserve also has important implications for clinical practice in terms of diagnosis and prognosis. © 2013 S. Karger AG, Basel.

Cognitive Reserve: Implications for Assessment and Intervention

PubMed Central

Stern, Yaakov

2014-01-01

The concept of reserve is used to explain the observation that some individuals function better than others in the presence of brain pathology. This paper reviews the concept of reserve from its theoretical basis to the implication of reserve for clinical practice. A distinction between brain reserve, referring to individual differences in the anatomic substrate, and cognitive reserve, referring to differences in the flexibility or adaptivity of cognitive networks, is useful. Epidemiologic evidence indicates that a set of life exposures including higher educational and occupational attainment, and engaging in leisure activities is associated with a lower risk of incident dementia, suggesting that these life exposures may enhance cognitive reserve. This provides a basis for controlled clinical studies can test specific exposures that may enhance reserve. The concept of cognitive reserve also has important implications for clinical practice in terms of diagnosis and prognosis. PMID:23941972

Impact of high iron intake on cognition and neurodegeneration in humans and in animal models: a systematic review

PubMed Central

Agrawal, Sonal; Berggren, Kiersten L.; Marks, Eileen; Fox, Jonathan H.

2017-01-01

Abstract Context Accumulation of brain iron is linked to aging and protein-misfolding neurodegenerative diseases. High iron intake may influence important brain health outcomes in later life. Objective The aim of this systematic review was to examine evidence from animal and human studies of the effects of high iron intake or peripheral iron status on adult cognition, brain aging, and neurodegeneration. Data Sources MEDLINE, Scopus, CAB Abstracts, the Cochrane Central Register of Clinical Trials, and OpenGrey databases were searched. Study Selection Studies investigating the effect of elevated iron intake at all postnatal life stages in mammalian models and humans on measures of adult brain health were included. Data Extraction Data were extracted and evaluated by two authors independently, with discrepancies resolved by discussion. Neurodegenerative disease diagnosis and/or behavioral/cognitive, biochemical, and brain morphologic findings were used to study the effects of iron intake or peripheral iron status on brain health. Risk of bias was assessed for animal and human studies. PRISMA guidelines for reporting systematic reviews were followed. Results Thirty-four preclinical and 14 clinical studies were identified from database searches. Thirty-three preclinical studies provided evidence supporting an adverse effect of nutritionally relevant high iron intake in neonates on brain-health-related outcomes in adults. Human studies varied considerably in design, quality, and findings; none investigated the effects of high iron intake in neonates/infants. Conclusions Human studies are needed to verify whether dietary iron intake levels used in neonates/infants to prevent iron deficiency have effects on brain aging and neurodegenerative disease outcomes. PMID:28505363

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

Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer.

PubMed

Yang, Lijun; Kress, Benjamin T; Weber, Harris J; Thiyagarajan, Meenakshisundaram; Wang, Baozhi; Deane, Rashid; Benveniste, Helene; Iliff, Jeffrey J; Nedergaard, Maiken

2013-05-01

Neurodegenerative diseases such as Alzheimer's are associated with the aggregation of endogenous peptides and proteins that contribute to neuronal dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly exchange, has recently been identified as a key contributor to the clearance of interstitial solutes from the brain, including amyloid β. These findings suggest that measuring changes in glymphatic pathway function may be an important prognostic for evaluating neurodegenerative disease susceptibility or progression. However, no clinically acceptable approach to evaluate glymphatic pathway function in humans has yet been developed. Time-sequenced ex vivo fluorescence imaging of coronal rat and mouse brain slices was performed at 30-180 min following intrathecal infusion of CSF tracer (Texas Red- dextran-3, MW 3 kD; FITC- dextran-500, MW 500 kD) into the cisterna magna or lumbar spine. Tracer influx into different brain regions (cortex, white matter, subcortical structures, and hippocampus) in rat was quantified to map the movement of CSF tracer following infusion along both routes, and to determine whether glymphatic pathway function could be evaluated after lumbar intrathecal infusion. Following lumbar intrathecal infusions, small molecular weight TR-d3 entered the brain along perivascular pathways and exchanged broadly with the brain ISF, consistent with the initial characterization of the glymphatic pathway in mice. Large molecular weight FITC-d500 remained confined to the perivascular spaces. Lumbar intrathecal infusions exhibited a reduced and delayed peak parenchymal fluorescence intensity compared to intracisternal infusions. Lumbar intrathecal contrast delivery is a clinically useful approach that could be used in conjunction with dynamic contrast enhanced MRI nuclear imaging to assess glymphatic pathway function in humans.

Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer

PubMed Central

2013-01-01

Background Neurodegenerative diseases such as Alzheimer’s are associated with the aggregation of endogenous peptides and proteins that contribute to neuronal dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly exchange, has recently been identified as a key contributor to the clearance of interstitial solutes from the brain, including amyloid β. These findings suggest that measuring changes in glymphatic pathway function may be an important prognostic for evaluating neurodegenerative disease susceptibility or progression. However, no clinically acceptable approach to evaluate glymphatic pathway function in humans has yet been developed. Methods Time-sequenced ex vivo fluorescence imaging of coronal rat and mouse brain slices was performed at 30–180 min following intrathecal infusion of CSF tracer (Texas Red- dextran-3, MW 3 kD; FITC- dextran-500, MW 500 kD) into the cisterna magna or lumbar spine. Tracer influx into different brain regions (cortex, white matter, subcortical structures, and hippocampus) in rat was quantified to map the movement of CSF tracer following infusion along both routes, and to determine whether glymphatic pathway function could be evaluated after lumbar intrathecal infusion. Results Following lumbar intrathecal infusions, small molecular weight TR-d3 entered the brain along perivascular pathways and exchanged broadly with the brain ISF, consistent with the initial characterization of the glymphatic pathway in mice. Large molecular weight FITC-d500 remained confined to the perivascular spaces. Lumbar intrathecal infusions exhibited a reduced and delayed peak parenchymal fluorescence intensity compared to intracisternal infusions. Conclusion Lumbar intrathecal contrast delivery is a clinically useful approach that could be used in conjunction with dynamic contrast enhanced MRI nuclear imaging to assess glymphatic pathway function in humans. PMID:23635358

Systemic, Local, and Imaging Biomarkers of Brain Injury: More Needed, and Better Use of Those Already Established?

PubMed Central

Carpenter, Keri L. H.; Czosnyka, Marek; Jalloh, Ibrahim; Newcombe, Virginia F. J.; Helmy, Adel; Shannon, Richard J.; Budohoski, Karol P.; Kolias, Angelos G.; Kirkpatrick, Peter J.; Carpenter, Thomas Adrian; Menon, David K.; Hutchinson, Peter J.

2015-01-01

Much progress has been made over the past two decades in the treatment of severe acute brain injury, including traumatic brain injury and subarachnoid hemorrhage, resulting in a higher proportion of patients surviving with better outcomes. This has arisen from a combination of factors. These include improvements in procedures at the scene (pre-hospital) and in the hospital emergency department, advances in neuromonitoring in the intensive care unit, both continuously at the bedside and intermittently in scans, evolution and refinement of protocol-driven therapy for better management of patients, and advances in surgical procedures and rehabilitation. Nevertheless, many patients still experience varying degrees of long-term disabilities post-injury with consequent demands on carers and resources, and there is room for improvement. Biomarkers are a key aspect of neuromonitoring. A broad definition of a biomarker is any observable feature that can be used to inform on the state of the patient, e.g., a molecular species, a feature on a scan, or a monitoring characteristic, e.g., cerebrovascular pressure reactivity index. Biomarkers are usually quantitative measures, which can be utilized in diagnosis and monitoring of response to treatment. They are thus crucial to the development of therapies and may be utilized as surrogate endpoints in Phase II clinical trials. To date, there is no specific drug treatment for acute brain injury, and many seemingly promising agents emerging from pre-clinical animal models have failed in clinical trials. Large Phase III studies of clinical outcomes are costly, consuming time and resources. It is therefore important that adequate Phase II clinical studies with informative surrogate endpoints are performed employing appropriate biomarkers. In this article, we review some of the available systemic, local, and imaging biomarkers and technologies relevant in acute brain injury patients, and highlight gaps in the current state of knowledge. PMID:25741315

fMRI reveals neural activity overlap between adult and infant pain

PubMed Central

Goksan, Sezgi; Hartley, Caroline; Emery, Faith; Cockrill, Naomi; Poorun, Ravi; Moultrie, Fiona; Rogers, Richard; Campbell, Jon; Sanders, Michael; Adams, Eleri; Clare, Stuart; Jenkinson, Mark; Tracey, Irene; Slater, Rebeccah

2015-01-01

Limited understanding of infant pain has led to its lack of recognition in clinical practice. While the network of brain regions that encode the affective and sensory aspects of adult pain are well described, the brain structures involved in infant nociceptive processing are less well known, meaning little can be inferred about the nature of the infant pain experience. Using fMRI we identified the network of brain regions that are active following acute noxious stimulation in newborn infants, and compared the activity to that observed in adults. Significant infant brain activity was observed in 18 of the 20 active adult brain regions but not in the infant amygdala or orbitofrontal cortex. Brain regions that encode sensory and affective components of pain are active in infants, suggesting that the infant pain experience closely resembles that seen in adults. This highlights the importance of developing effective pain management strategies in this vulnerable population. DOI: http://dx.doi.org/10.7554/eLife.06356.001 PMID:25895592

The brain commission of the international association of academies: the first international society of neurosciences.

PubMed

Richter, J

2000-08-01

International associations of scientists, set up to organize cooperative scientific investigations in an international scope and to lay down global binding standards of research, are of great and still growing importance for the advancement of science. This was also recognized at the beginning of the 20th century by the community of researchers in basic and clinical neurological sciences, who created their first international organization following the trend initiated by scholars in astronomy and geophysics. Thus, the so-called "Brain Commission" of the International Association of Academies was founded in 1903 and was active until the outbreak of the First World War. The Brain Commission had no successor for nearly half a century, until the "International Brain Research Organization" (IBRO) was founded in 1961. Although the Brain Commission could exert an impact on neurosciences only for one decade, this international scientific association inspired and promoted the foundation of a series of Brain Research Institutes, which in part still exist in Europe, and long-lasting innovations in the neurosciences.

Clinical neuropsychology within adolescent and young-adult psychiatry: conceptualizing theory and practice.

PubMed

Allott, Kelly; Proffitt, Tina-Marie; McGorry, Patrick D; Pantelis, Christos; Wood, Stephen J; Cumner, Marnie; Brewer, Warrick J

2013-01-01

Historically, clinical neuropsychology has made significant contributions to the understanding of brain-behavior relationships, particularly in neurological conditions. During the past several decades, neuropsychology has also become established as an important discipline in psychiatric settings. Cognition is increasingly recognized as being core to psychiatric illnesses and predictive of functional outcomes, augmenting theories regarding symptomatology and illness progression. Adult-type psychiatric disorders (including schizophrenia and other psychotic, mood, anxiety, eating, substance-related, and personality disorders) typically emerge during adolescence or young adulthood, a critical neurodevelopmental period. Clinical neuropsychological assessment in adolescent psychiatric patients is particularly valuable in informing clinical formulation and intervention and can be therapeutic across a number of levels. This article articulates the theoretical considerations and practical challenges and applications of clinical neuropsychology within adolescent and young-adult psychiatry. The importance of considering the neurodevelopmental context and its relationship to current theoretical models underpinning clinical practice are discussed.

Critical Evaluation of the Lund Concept for Treatment of Severe Traumatic Head Injury, 25 Years after Its Introduction.

PubMed

Grände, Per-Olof

2017-01-01

When introduced in 1992, the Lund concept (LC) was the first complete guideline for treatment of severe traumatic brain injury (s-TBI). It was a theoretical approach, based mainly on general physiological principles-i.e., of brain volume control and optimization of brain perfusion and oxygenation of the penumbra zone. The concept gave relatively strict outlines for cerebral perfusion pressure, fluid therapy, ventilation, sedation, nutrition, the use of vasopressors, and osmotherapy. The LC strives for treatment of the pathophysiological mechanisms behind symptoms rather than just treating the symptoms. The treatment is standardized, with less need for individualization. Alternative guidelines published a few years later (e.g., the Brain Trauma Foundation guidelines and European guidelines) were mainly based on meta-analytic approaches from clinical outcome studies and to some extent from systematic reviews. When introduced, they differed extensively from the LC. We still lack any large randomized outcome study comparing the whole concept of BTF guidelines with other guidelines including the LC. From that point of view, there is limited clinical evidence favoring any of the s-TBI guidelines used today. In principle, the LC has not been changed since its introduction. Some components of the alternative guidelines have approached those in the LC. In this review, I discuss some important principles of brain hemodynamics that have been lodestars during formulation of the LC. Aspects of ventilation, nutrition, and temperature control are also discussed. I critically evaluate the most important components of the LC 25 years after its introduction, based on hemodynamic principles and on the results of own an others experimental and human studies that have been published since then.

Critical Evaluation of the Lund Concept for Treatment of Severe Traumatic Head Injury, 25 Years after Its Introduction

PubMed Central

Grände, Per-Olof

2017-01-01

When introduced in 1992, the Lund concept (LC) was the first complete guideline for treatment of severe traumatic brain injury (s-TBI). It was a theoretical approach, based mainly on general physiological principles—i.e., of brain volume control and optimization of brain perfusion and oxygenation of the penumbra zone. The concept gave relatively strict outlines for cerebral perfusion pressure, fluid therapy, ventilation, sedation, nutrition, the use of vasopressors, and osmotherapy. The LC strives for treatment of the pathophysiological mechanisms behind symptoms rather than just treating the symptoms. The treatment is standardized, with less need for individualization. Alternative guidelines published a few years later (e.g., the Brain Trauma Foundation guidelines and European guidelines) were mainly based on meta-analytic approaches from clinical outcome studies and to some extent from systematic reviews. When introduced, they differed extensively from the LC. We still lack any large randomized outcome study comparing the whole concept of BTF guidelines with other guidelines including the LC. From that point of view, there is limited clinical evidence favoring any of the s-TBI guidelines used today. In principle, the LC has not been changed since its introduction. Some components of the alternative guidelines have approached those in the LC. In this review, I discuss some important principles of brain hemodynamics that have been lodestars during formulation of the LC. Aspects of ventilation, nutrition, and temperature control are also discussed. I critically evaluate the most important components of the LC 25 years after its introduction, based on hemodynamic principles and on the results of own an others experimental and human studies that have been published since then. PMID:28725211

[18F]-Fluoro-Deoxy-Glucose Positron Emission Tomography Scan Should Be Obtained Early in Cases of Autoimmune Encephalitis

PubMed Central

Sarwal, A.; Hantus, S.

2016-01-01

Introduction. Autoimmune encephalitis (AE) is a clinically challenging diagnosis with nonspecific neurological symptoms. Prompt diagnosis is important and often relies on neuroimaging. We present a case series of AE highlighting the importance of an early [18F]-fluoro-deoxy-glucose positron emission tomography (FDG-PET) scan. Methods. Retrospective review of seven consecutive cases of autoimmune encephalitis. Results. All patients had both magnetic resonance imaging (MRI) and FDG-PET scans. Initial clinical presentations included altered mental status and/or new onset seizures. Six cases had serum voltage-gated potassium channel (VGKC) antibody and one had serum N-methyl-D-aspartate (NMDA) antibody. MRI of brain showed mesial temporal lobe hyperintensity in five cases of VGKC. The other two patients with VGKC or NMDA AE had restiform body hyperintensity on MRI brain or a normal MRI, respectively. Mesial temporal lobe hypermetabolism was noted in three cases on FDG-PET, despite initial unremarkable MRI. Malignancy workup was negative in all patients. Conclusion. A high index of suspicion for AE should be maintained in patients presenting with cognitive symptoms, seizures, and limbic changes on neuroimaging. In cases with normal initial brain MRI, FDG-PET can be positive. Additionally, extralimbic hyperintensity on MRI may also be observed. PMID:27559482

Multiprotocol MR image segmentation in multiple sclerosis: experience with over 1000 studies

NASA Astrophysics Data System (ADS)

Udupa, Jayaram K.; Nyul, Laszlo G.; Ge, Yulin; Grossman, Robert I.

2000-06-01

Multiple Sclerosis (MS) is an acquired disease of the central nervous system. Subjective cognitive and ambulatory test scores on a scale called EDSS are currently utilized to assess the disease severity. Various MRI protocols are being investigated to study the disease based on how it manifests itself in the images. In an attempt to eventually replace EDSS by an objective measure to assess the natural course of the disease and its response to therapy, we have developed image segmentation methods based on fuzzy connectedness to quantify various objects in multiprotocol MRI. These include the macroscopic objects such as lesions, the gray matter (GM), white matter (WM), cerebrospinal fluid (CSF), and brain parenchyma as well as the microscopic aspects of the diseased WM. Over 1000 studies have been processed to date. By far the strongest correlations with the clinical measures were demonstrated by the Magnetization Transfer Ratio (MTR) histogram parameters obtained for the various segmented tissue regions emphasizing the importance of considering the microscopic/diffused nature of the disease in the individual tissue regions. Brain parenchymal volume also demonstrated a strong correlation with the clinical measures indicating that brain atrophy is an important indicator of the disease. Fuzzy connectedness is a viable segmentation method for studying MS.

Immoral behaviour following brain damage: A review.

PubMed

Roberts, Stefanie; Henry, Julie D; Molenberghs, Pascal

2018-04-16

Despite the apparent sociability of human kind, immoral behaviour is ever present in society. The term 'immoral behaviour' represents a complex array of conduct, ranging from insensitivity to topics of conversation through to violent assault and murder. To better understand the neuroscience of immoral behaviour, this review investigates two clinical populations that commonly present with changes in moral behaviour - behavioural-variant frontotemporal dementia and acquired brain injuries. Based on evidence from these groups, it is argued that rather than a single underlying cause, immoral behaviour can result from three distinct types of cognitive failure: (1) problems understanding others; (2) difficulties controlling behaviour; or (3) deficits in the capacity to make appropriate emotional contributions. Each of these failures is associated with damage to different brain regions. A more nuanced approach to the neuroscience of immoral behaviour has important implications for our understanding of immoral behaviour in a wide range of clinical groups, as well as human society more broadly. © 2018 The British Psychological Society.

A Neuropsychological Profile for Agenesis of the Corpus Callosum? Cognitive, Academic, Executive, Social, and Behavioral Functioning in School-Age Children.

PubMed

Siffredi, Vanessa; Anderson, Vicki; McIlroy, Alissandra; Wood, Amanda G; Leventer, Richard J; Spencer-Smith, Megan M

2018-05-01

Agenesis of the corpus callosum (AgCC), characterized by developmental absence of the corpus callosum, is one of the most common congenital brain malformations. To date, there are limited data on the neuropsychological consequences of AgCC and factors that modulate different outcomes, especially in children. This study aimed to describe general intellectual, academic, executive, social and behavioral functioning in a cohort of school-aged children presenting for clinical services to a hospital and diagnosed with AgCC. The influences of age, social risk and neurological factors were examined. Twenty-eight school-aged children (8 to 17 years) diagnosed with AgCC completed tests of general intelligence (IQ) and academic functioning. Executive, social and behavioral functioning in daily life, and social risk, were estimated from parent and teacher rated questionnaires. MRI findings reviewed by a pediatric neurologist confirmed diagnosis and identified brain characteristics. Clinical details including the presence of epilepsy and diagnosed genetic condition were obtained from medical records. In our cohort, ~50% of children experienced general intellectual, academic, executive, social and/or behavioral difficulties and ~20% were functioning at a level comparable to typically developing children. Social risk was important for understanding variability in neuropsychological outcomes. Brain anomalies and complete AgCC were associated with lower mathematics performance and poorer executive functioning. This is the first comprehensive report of general intellectual, academic, executive social and behavioral consequences of AgCC in school-aged children. The findings have important clinical implications, suggesting that support to families and targeted intervention could promote positive neuropsychological functioning in children with AgCC who come to clinical attention. (JINS, 2018, 24, 445-455).

Atrophied Brain Lesion Volume: A New Imaging Biomarker in Multiple Sclerosis.

PubMed

Dwyer, Michael G; Bergsland, Niels; Ramasamy, Deepa P; Jakimovski, Dejan; Weinstock-Guttman, Bianca; Zivadinov, Robert

2018-06-01

Lesion accrual in multiple sclerosis (MS) is an important and clinically relevant measure, used extensively as an imaging trial endpoint. However, lesions may also shrink or disappear entirely due to atrophy. Although generally ignored or treated as a nuisance, this phenomenon may actually be an important stand-alone imaging biomarker. Therefore, we investigated the rate of brain lesion loss due to atrophy (atrophied lesion volume) in MS subtypes compared to baseline lesion volume and to new and enlarging lesion volumes, and evaluated the independent predictive value of this phenomenon for clinical disability. A total of 192 patients (18 clinically isolated syndrome, 126 relapsing-remitting MS, and 48 progressive) received 3T magnetic resonance imaging at baseline and 5 years. Lesions were quantified at baseline, and new/enlarging lesion volumes were calculated over the study interval. Atrophied lesion volume was calculated by combining baseline lesion masks with follow-up SIENAX-derived cerebrospinal fluid partial volume maps. Measures were compared between disease subgroups, and correlations with disability change (Expanded Disability Status Scale [EDSS]) were evaluated. Hierarchical regression was employed to determine the unique additive value of atrophied lesion volume. Atrophied lesion volume was different between MS subtypes (P = .02), and exceeded new lesion volume accumulation in progressive MS (298.1 vs. 75.5 mm 3 ). Atrophied lesion volume was the only significant correlate of EDSS change (r = .192 relapsing, r = .317 progressive, P < .05), and explained significant additional variance when controlling for brain atrophy and new/enlarging lesion volume (R 2 .092 vs. .045, P = .003). Atrophied lesion volume is a unique and clinically relevant imaging marker in MS, with particular promise in progressive MS. Copyright © 2018 by the American Society of Neuroimaging.

Evolving knowledge of sex differences in brain structure, function, and chemistry.

PubMed

Cosgrove, Kelly P; Mazure, Carolyn M; Staley, Julie K

2007-10-15

Clinical and epidemiologic evidence demonstrates sex differences in the prevalence and course of various psychiatric disorders. Understanding sex-specific brain differences in healthy individuals is a critical first step toward understanding sex-specific expression of psychiatric disorders. Here, we evaluate evidence on sex differences in brain structure, chemistry, and function using imaging methodologies, including functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), and structural magnetic resonance imaging (MRI) in mentally healthy individuals. MEDLINE searches of English-language literature (1980-November 2006) using the terms sex, gender, PET, SPECT, MRI, fMRI, morphometry, neurochemistry, and neurotransmission were performed to extract relevant sources. The literature suggests that while there are many similarities in brain structure, function, and neurotransmission in healthy men and women, there are important differences that distinguish the male from the female brain. Overall, brain volume is greater in men than women; yet, when controlling for total volume, women have a higher percentage of gray matter and men a higher percentage of white matter. Regional volume differences are less consistent. Global cerebral blood flow is higher in women than in men. Sex-specific differences in dopaminergic, serotonergic, and gamma-aminobutyric acid (GABA)ergic markers indicate that male and female brains are neurochemically distinct. Insight into the etiology of sex differences in the normal living human brain provides an important foundation to delineate the pathophysiological mechanisms underlying sex differences in neuropsychiatric disorders and to guide the development of sex-specific treatments for these devastating brain disorders.

Social anxiety following traumatic brain injury: an exploration of associated factors.

PubMed

Curvis, William; Simpson, Jane; Hampson, Natalie

2018-06-01

Social anxiety (SA) following traumatic brain injury (TBI) has the potential to affect an individual's general psychological well-being and social functioning, however little research has explored factors associated with its development. The present study used hierarchical multiple regression to investigate the demographic, clinical and psychological factors associated with SA following TBI. A sample of 85 people who experienced TBI were recruited through social media websites and brain injury services across the North-West of England. The overall combined biopsychosocial model was significant, explaining 52-54.3% of the variance in SA (across five imputations of missing data). The addition of psychological variables (self-esteem, locus of control, self-efficacy) made a significant contribution to the overall model, accounting for an additional 12.2-13% of variance in SA above that explained by demographic and clinical variables. Perceived stigma was the only significant independent predictor of SA (B = .274, p = .005). The findings suggest that psychological variables are important in the development of SA following TBI and must be considered alongside clinical factors. Furthermore, the significant role of stigma highlights the need for intervention at both an individualised and societal level.

Bodily illusions in health and disease: physiological and clinical perspectives and the concept of a cortical 'body matrix'.

PubMed

Moseley, G Lorimer; Gallace, Alberto; Spence, Charles

2012-01-01

Illusions that induce a feeling of ownership over an artificial body or body-part have been used to explore the complex relationships that exist between the brain's representation of the body and the integrity of the body itself. Here we discuss recent findings in both healthy volunteers and clinical populations that highlight the robust relationship that exists between a person's sense of ownership over a body part, cortical processing of tactile input from that body part, and its physiological regulation. We propose that a network of multisensory and homeostatic brain areas may be responsible for maintaining a 'body-matrix'. That is, a dynamic neural representation that not only extends beyond the body surface to integrate both somatotopic and peripersonal sensory data, but also integrates body-centred spatial sensory data. The existence of such a 'body-matrix' allows our brain to adapt to even profound anatomical and configurational changes to our body. It also plays an important role in maintaining homeostatic control over the body. Its alteration can be seen to have both deleterious and beneficial effects in various clinical populations. Copyright © 2011 Elsevier Ltd. All rights reserved.

Language-related Cntnap2 gene is differentially expressed in sexually dimorphic song nuclei essential for vocal learning in songbirds

PubMed Central

Panaitof, S. Carmen; Abrahams, Brett S.; Dong, Hongmei; Geschwind, Daniel H.; White, Stephanie A.

2010-01-01

Multiple studies, involving distinct clinical populations, implicate contactin associated protein-like 2 (CNTNAP2) in aspects of language development and performance. While CNTNAP2 is broadly distributed in developing rodent brain, it shows a striking gradient of frontal cortical enrichment in developing human brain, consistent with a role in patterning circuits that subserve higher cognition and language. To test the hypothesis that CNTNAP2 may be important for learned vocal communication in additional species, we employed in situ hybridization to characterize transcript distribution in the zebra finch, an experimentally tractable songbird for which the neural substrate of this behavior is well-established. Consistent with an important role in learned vocalization, Cntnap2 was enriched or diminished in key song control nuclei relative to adjacent brain tissue. Importantly, this punctuated expression was observed in males, but not females, in accord with the sexual dimorphism of neural circuitry and vocal learning in this species. Ongoing functional work will provide important insights into the relationship between Cntnap2 and vocal communication in songbirds and thereby clarify mechanisms at play in disorders of human cognition and language. PMID:20394055

Noninvasive Brain Stimulation: Challenges and Opportunities for a New Clinical Specialty.

PubMed

Boes, Aaron D; Kelly, Michael S; Trapp, Nicholas T; Stern, Adam P; Press, Daniel Z; Pascual-Leone, Alvaro

2018-04-24

Noninvasive brain stimulation refers to a set of technologies and techniques with which to modulate the excitability of the brain via transcranial stimulation. Two major modalities of noninvasive brain stimulation are transcranial magnetic stimulation (TMS) and transcranial current stimulation. Six TMS devices now have approved uses by the U.S. Food and Drug Administration and are used in clinical practice: five for treating medication refractory depression and the sixth for presurgical mapping of motor and speech areas. Several large, multisite clinical trials are currently underway that aim to expand the number of clinical applications of noninvasive brain stimulation in a way that could affect multiple clinical specialties in the coming years, including psychiatry, neurology, pediatrics, neurosurgery, physical therapy, and physical medicine and rehabilitation. In this article, the authors review some of the anticipated challenges facing the incorporation of noninvasive brain stimulation into clinical practice. Specific topics include establishing efficacy, safety, economics, and education. In discussing these topics, the authors focus on the use of TMS in the treatment of medication refractory depression when possible, because this is the most widely accepted clinical indication for TMS to date. These challenges must be thoughtfully considered to realize the potential of noninvasive brain stimulation as an emerging specialty that aims to enhance the current ability to diagnose and treat disorders of the brain.

Functional and clinical neuroanatomy of morality.

PubMed

Fumagalli, Manuela; Priori, Alberto

2012-07-01

Morality is among the most sophisticated features of human judgement, behaviour and, ultimately, mind. An individual who behaves immorally may violate ethical rules and civil rights, and may threaten others' individual liberty, sometimes becoming violent and aggressive. In recent years, neuroscience has shown a growing interest in human morality, and has advanced our understanding of the cognitive and emotional processes involved in moral decisions, their anatomical substrates and the neurology of abnormal moral behaviour. In this article, we review research findings that have provided a key insight into the functional and clinical neuroanatomy of the brain areas involved in normal and abnormal moral behaviour. The 'moral brain' consists of a large functional network including both cortical and subcortical anatomical structures. Because morality is a complex process, some of these brain structures share their neural circuits with those controlling other behavioural processes, such as emotions and theory of mind. Among the anatomical structures implicated in morality are the frontal, temporal and cingulate cortices. The prefrontal cortex regulates activity in subcortical emotional centres, planning and supervising moral decisions, and when its functionality is altered may lead to impulsive aggression. The temporal lobe is involved in theory of mind and its dysfunction is often implicated in violent psychopathy. The cingulate cortex mediates the conflict between the emotional and the rational components of moral reasoning. Other important structures contributing to moral behaviour include the subcortical nuclei such as the amygdala, hippocampus and basal ganglia. Brain areas participating in moral processing can be influenced also by genetic, endocrine and environmental factors. Hormones can modulate moral behaviour through their effects on the brain. Finally, genetic polymorphisms can predispose to aggressivity and violence, arguing for a genetic-based predisposition to morality. Because abnormal moral behaviour can arise from both functional and structural brain abnormalities that should be diagnosed and treated, the neurology of moral behaviour has potential implications for clinical practice and raises ethical concerns. Last, since research has developed several neuromodulation techniques to improve brain dysfunction (deep brain stimulation, transcranial magnetic stimulation and transcranial direct current stimulation), knowing more about the 'moral brain' might help to develop novel therapeutic strategies for neurologically based abnormal moral behaviour.

Advanced neuroimaging techniques for the term newborn with encephalopathy.

PubMed

Chau, Vann; Poskitt, Kenneth John; Miller, Steven Paul

2009-03-01

Neonatal encephalopathy is associated with a high risk of morbidity and mortality in the neonatal period and of long-term neurodevelopmental disability in survivors. Advanced magnetic resonance techniques now play a major role in the clinical care of newborns with encephalopathy and in research addressing this important condition. From conventional magnetic resonance imaging, typical patterns of injury have been defined in neonatal encephalopathy. When applied in contemporary cohorts of newborns with encephalopathy, the patterns of brain injury on magnetic resonance imaging distinguish risk factors, clinical presentation, and risk of abnormal outcome. Advanced magnetic resonance techniques such as magnetic resonance spectroscopy, diffusion-weighted imaging, and diffusion tensor imaging provide novel perspectives on neonatal brain metabolism, microstructure, and connectivity. With the application of these imaging tools, it is increasingly apparent that brain injury commonly occurs at or near the time of birth and evolves over the first weeks of life. These observations have complemented findings from trials of emerging strategies of brain protection, such as hypothermia. Application of these advanced magnetic resonance techniques may enable the earliest possible identification of newborns at risk of neurodevelopmental impairment, thereby ensuring appropriate follow-up with rehabilitation and psychoeducational resources.

White matter injury in term newborns with neonatal encephalopathy.

PubMed

Li, Amanda M; Chau, Vann; Poskitt, Kenneth J; Sargent, Michael A; Lupton, Brian A; Hill, Alan; Roland, Elke; Miller, Steven P

2009-01-01

White matter injury (WMI) is the characteristic pattern of brain injury detected on magnetic resonance imaging in the premature newborn. Focal noncystic WMI is increasingly recognized in populations of term newborns. The aim of this study was to describe the occurrence of focal noncystic WMI in a cohort of 48 term newborns with encephalopathy studied with magnetic resonance imaging at 72 +/- 12 h of life, and to identify clinical risk factors for this pattern of injury. Eleven newborns (23%; 95% CI 11-35) were found to have WMI (four minimal, three moderate, and four severe). In 10 of the 11 newborns, the WMI was associated with restricted diffusion on apparent diffusion coefficient maps. An increasing severity of WMI was associated with lower gestational age at birth (p = 0.05), but not lower birth weight. Newborns with WMI had milder encephalopathy and fewer clinical seizures relative to other newborns in the cohort. Other brain injuries were seen in three of the 11 newborns: basal nuclei predominant pattern of injury in one and cortical strokes in two. These findings suggest that WMI in the term newborn is acquired near birth and that the state of brain maturation is an important determinant of this pattern of brain injury.

Cognitive reserve and preinjury educational attainment: effects on outcome of community-based rehabilitation for longer-term individuals with acquired brain injury.

PubMed

Fortune, Dónal G; Walsh, R Stephen; Richards, Helen L

2016-09-01

The cognitive reserve hypothesis has been proposed to account for the mismatch between brain pathology and its clinical expression. The aim of the current research was to explore, in a longitudinal data set, the effects of level of educational attainment before brain injury (cognitive reserve) and clinical factors on the level of rehabilitation-induced changes in disability and community integration. Participants in receipt of postacute rehabilitation were assessed at induction to the service and again at between 14 and 18 months of follow-up while still in service on changes in aspects of their abilities, adjustment and participation (Mayo Portland Adaptability Indices) and community integration (Community Integration Questionnaire). Controlling for type and severity of injury, age at onset of injury and duration of time since injury, participants with higher previous educational attainment showed significantly greater changes over the course of rehabilitation on adjustment to their injury and participation, but not on abilities, or community integration following postacute rehabilitation. Level of education would appear to be an important element of cognitive reserve in brain injury that serves to aid responses to postacute rehabilitation in terms of an individual's adjustment to disability and participation.

The pathophysiology of post-stroke aphasia: A network approach.

PubMed

Thiel, Alexander; Zumbansen, Anna

2016-06-13

Post-stroke aphasia syndromes as a clinical entity arise from the disruption of brain networks specialized in language production and comprehension due to permanent focal ischemia. This approach to post-stroke aphasia is based on two pathophysiological concepts: 1) Understanding language processing in terms of distributed networks rather than language centers and 2) understanding the molecular pathophysiology of ischemic brain injury as a dynamic process beyond the direct destruction of network centers and their connections. While considerable progress has been made in the past 10 years to develop such models on a systems as well as a molecular level, the influence of these approaches on understanding and treating clinical aphasia syndromes has been limited. In this article, we review current pathophysiological concepts of ischemic brain injury, their relationship to altered information processing in language networks after ischemic stroke and how these mechanisms may be influenced therapeutically to improve treatment of post-stroke aphasia. Understanding the pathophysiological mechanism of post-stroke aphasia on a neurophysiological systems level as well as on the molecular level becomes more and more important for aphasia treatment, as the field moves from standardized therapies towards more targeted individualized treatment strategies comprising behavioural therapies as well as non-invasive brain stimulation (NIBS).

Reliability of in vitro and in vivo methods for predicting P-glycoprotein effect on antidepressants delivery to the brain

PubMed Central

Zheng, Yi; Chen, Xijing; Benet, Leslie Z.

2017-01-01

As P-glycoprotein (P-gp) transport on antidepressant delivery has been extensively evaluated using in vitro cellular and in vivo rodent models, an increasing number of publications addressed the effect of P-gp in limiting brain penetration of antidepressants and causing treatment-resistant depression in current clinical therapies. However, contradictory results were observed in different systems. It is of vital importance to understand the potential for drug interactions related to P-gp at the blood-brain barrier (BBB), and whether co-administration of a P-gp inhibitor together with an antidepressant is a good clinical strategy for dosing of patients with treatment-resistant depression. In this review, the complicated construction of the BBB, the transport mechanisms for compounds that cross the BBB, and the basic characteristics of antidepressants are illustrated. Further, the reliability of different systems related to antidepressant brain delivery, including in vitro bidirectional transport cell lines, in vivo Mdr1 knock-out mice, and chemical inhibition studies in rodents are analyzed, supporting a low possibility that P-gp affects currently marketed antidepressants when these results are extrapolated to human BBB. These findings can also be applied to other central nervous system drugs. PMID:26293617

Multiscale CNNs for Brain Tumor Segmentation and Diagnosis.

PubMed

Zhao, Liya; Jia, Kebin

2016-01-01

Early brain tumor detection and diagnosis are critical to clinics. Thus segmentation of focused tumor area needs to be accurate, efficient, and robust. In this paper, we propose an automatic brain tumor segmentation method based on Convolutional Neural Networks (CNNs). Traditional CNNs focus only on local features and ignore global region features, which are both important for pixel classification and recognition. Besides, brain tumor can appear in any place of the brain and be any size and shape in patients. We design a three-stream framework named as multiscale CNNs which could automatically detect the optimum top-three scales of the image sizes and combine information from different scales of the regions around that pixel. Datasets provided by Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized by MICCAI 2013 are utilized for both training and testing. The designed multiscale CNNs framework also combines multimodal features from T1, T1-enhanced, T2, and FLAIR MRI images. By comparison with traditional CNNs and the best two methods in BRATS 2012 and 2013, our framework shows advances in brain tumor segmentation accuracy and robustness.

Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis.

PubMed

Jenkins, Trisha A; Nguyen, Jason C D; Polglaze, Kate E; Bertrand, Paul P

2016-01-20

The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. Manipulation of tryptophan levels, acutely or chronically, by depletion or supplementation, is an experimental procedure for modifying peripheral and central serotonin levels. These studies have allowed us to establish the role of serotonin in higher order brain function in both preclinical and clinical situations and have precipitated the finding that low brain serotonin levels are associated with poor memory and depressed mood. The gut-brain axis is a bi-directional system between the brain and gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. An influence of gut microbiota on behaviour is becoming increasingly evident, as is the extension to tryptophan and serotonin, producing a possibility that alterations in the gut may be important in the pathophysiology of human central nervous system disorders. In this review we will discuss the effect of manipulating tryptophan on mood and cognition, and discuss a possible influence of the gut-brain axis.

MicroRNAs in brain metastases: potential role as diagnostics and therapeutics.

PubMed

Alsidawi, Samer; Malek, Ehsan; Driscoll, James J

2014-06-11

Brain metastases remain a daunting adversary that negatively impact patient survival. Metastatic brain tumors affect up to 45% of all cancer patients with systemic cancer and account for ~20% of all cancer-related deaths. A complex network of non-coding RNA molecules, microRNAs (miRNAs), regulate tumor metastasis. The brain micro-environment modulates metastatic tumor growth; however, defining the precise genetic events that promote metastasis in the brain niche represents an important, unresolved problem. Understanding these events will reveal disease-based targets and offer effective strategies to treat brain metastases. Effective therapeutic strategies based upon the biology of brain metastases represent an urgent, unmet need with immediate potential for clinical impact. Studies have demonstrated the ability of miRNAs to distinguish normal from cancerous cells, primary from secondary brain tumors, and correctly categorize metastatic brain tumor tissue of origin based solely on miRNA profiles. Interestingly, manipulation of miRNAs has proven effective in cancer treatment. With the promise of reduced toxicity, increased efficacy and individually directed personalized anti-cancer therapy, using miRNA in the treatment of metastatic brain tumors may prove very useful and improve patient outcome. In this review, we focus on the potential of miRNAs as diagnostic and therapeutic targets for the treatment of metastatic brain lesions.

Hyper- and viscoelastic modeling of needle and brain tissue interaction.

PubMed

Lehocky, Craig A; Yixing Shi; Riviere, Cameron N

2014-01-01

Deep needle insertion into brain is important for both diagnostic and therapeutic clinical interventions. We have developed an automated system for robotically steering flexible needles within the brain to improve targeting accuracy. In this work, we have developed a finite element needle-tissue interaction model that allows for the investigation of safe parameters for needle steering. The tissue model implemented contains both hyperelastic and viscoelastic properties to simulate the instantaneous and time-dependent responses of brain tissue. Several needle models were developed with varying parameters to study the effects of the parameters on tissue stress, strain and strain rate during needle insertion and rotation. The parameters varied include needle radius, bevel angle, bevel tip fillet radius, insertion speed, and rotation speed. The results will guide the design of safe needle tips and control systems for intracerebral needle steering.

[Complex application 2-ethyl-6-methyl-3-hydroxypyridine-succinate and vinpocetine in cerebrovascular disorder.

PubMed

Solovyeva, E Yu; Karneev, A N; Chekanov, A V; Baranova, O A; Choi, I V

Developing brain ischemia due to cerebral vascularization leads to disruption of brain metabolism. Chronic cerebral hypoperfusion leads to irreversible brain damage and plays an important role in the development of some types of dementia. Early use of antioxidants such as ethyl ether apovincamine acid (vinpocetine) and 2-ethyl-6-methyl-3-hydroxypyridine-succinate in the treatment of this pathology is seen as a real pathogenetically based method of correction of cerebral metabolism with cerebral vascular disorders, demonstrating the increase in cerebral blood flow and also neuroprotective effects. Clinical studies and studies on biological models show that the main mechanisms of action of vinpocetine and 2-ethyl-6-methyl-3-hydroxypyridine-succinate, although have a similar focus, but implementing neuroprotective and nootropic effects via various links in the pathogenesis of ischemic brain damage.

Neurocognitive and Family Functioning and Quality of Life Among Young Adult Survivors of Childhood Brain Tumors

PubMed Central

Hocking, Matthew C.; Hobbie, Wendy L.; Deatrick, Janet A.; Lucas, Matthew S.; Szabo, Margo M.; Volpe, Ellen M.; Barakat, Lamia P.

2012-01-01

Many childhood brain tumor survivors experience significant neurocognitive late effects across multiple domains that negatively affect quality of life. A theoretical model of survivorship suggests that family functioning and survivor neurocognitive functioning interact to affect survivor and family outcomes. This paper reviews the types of neurocognitive late effects experienced by survivors of pediatric brain tumors. Quantitative and qualitative data from three case reports of young adult survivors and their mothers are analyzed according to the theoretical model and presented in this paper to illustrate the importance of key factors presented in the model. The influence of age at brain tumor diagnosis, family functioning, and family adaptation to illness on survivor quality of life and family outcomes are highlighted. Future directions for research and clinical care for this vulnerable group of survivors are discussed. PMID:21722062

The Traumatic Brain Injury Endpoints Development (TED) Initiative: Progress on a Public-Private Regulatory Collaboration to Accelerate Diagnosis and Treatment of Traumatic Brain Injury.

PubMed

Manley, Geoffrey T; MacDonald, Christine L; Markowitz, Amy; Stephenson, Diane; Robbins, Ann; Gardner, Raquel C; Winkler, Ethan A; Bodien, Yelena; Taylor, Sabrina; Yue, John K; Kannan, Lakshmi; Kumar, Allison; McCrea, Michael; Wang, Kevin K W

2017-03-31

The Traumatic Brain Injury Endpoints Development (TED) Initiative is a 5-year, Department of Defense (DoD) funded project that is working toward the ultimate goal of developing better designed clinical trials, leading to more precise diagnosis, and effective treatments for traumatic brain injury (TBI). TED is comprised of leading academic clinician-scientists, along with innovative industry leaders in biotechnology and imaging technology, patient advocacy organizations, and philanthropists, working collaboratively with regulatory authorities, specifically the US Food and Drug Administration (FDA). The goals of the TED Initiative are to gain consensus and validation of TBI clinical outcome assessment measures and biomarkers for endorsement by global regulatory agencies for use in drug and device development processes. This manuscript summarizes the Initiative's Stage 1 progress over the first 18 months, including intensive engagement with a number of FDA divisions responsible for review and validation of biomarkers and clinical outcome assessments, progression into the prequalification phase of FDA's Medical Device Development Tool program for a candidate set of neuroimaging biomarkers, and receipt of FDA's Recognition of Research Importance Letter regarding TBI. Other signal achievements relate to the creation of the TED Metadataset, harmonizing study measures across eight major TBI studies, and the leadership role played by TED investigators in the conversion of the NINDS TBI Common Data Elements (CDEs) to Clinical Data Interchange Standards Consortium (CDISC) standards. This paper frames both the near-term expectations and the Initiative's long-term vision to accelerate approval of treatments for patients affected by TBI in urgent need of effective therapies.

Assessment of a brain-tumour-specific Patient Concerns Inventory in the neuro-oncology clinic.

PubMed

Rooney, Alasdair G; Netten, Anouk; McNamara, Shanne; Erridge, Sara; Peoples, Sharon; Whittle, Ian; Hacking, Belinda; Grant, Robin

2014-04-01

Brain tumour patients may struggle to express their concerns in the outpatient clinic, creating a physician-focused rather than a shared agenda. We created a simple, practical brain-tumour-specific holistic needs assessment (HNA) tool for use in the neuro-oncology outpatient clinic. We posted the brain tumour Patient Concerns Inventory (PCI) to a consecutive sample of adult brain tumour attendees to a neuro-oncology outpatient clinic. Participants brought the completed PCI to their clinic consultation. Patients and staff provided feedback. Seventy seven patients were eligible and 53 participated (response rate = 68%). The PCI captured many problems absent from general cancer checklists. The five most frequent concerns were fatigue, fear of tumour coming back, memory, concentration, and low mood. Respondents used the PCI to formulate 105 specific questions, usually about the meaning of physical or psychological symptoms. Patients and staff found the PCI to be useful, and satisfaction with the instrument was high. This study demonstrates the clinical utility of the brain tumour PCI in a neuro-oncology clinic. The combination of a brain-tumour-specific concerns checklist and an intervention to focus patient agenda creates a simple and efficient HNA tool.

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.

A Diagnostic Model for Dementia in Clinical Practice-Case Methodology Assisting Dementia Diagnosis.

PubMed

Londos, Elisabet

2015-04-02

Dementia diagnosis is important for many different reasons. Firstly, to separate dementia, or major neurocognitive disorder, from MCI (mild cognitive impairment), mild neurocognitive disorder. Secondly, to define the specific underlying brain disorder to aid treatment, prognosis and decisions regarding care needs and assistance. The diagnostic method of dementias is a puzzle of different data pieces to be fitted together in the best possible way to reach a clinical diagnosis. Using a modified case methodology concept, risk factors affecting cognitive reserve and symptoms constituting the basis of the brain damage hypothesis, can be visualized, balanced and reflected against test results as well as structural and biochemical markers. The model's origin is the case method initially described in Harvard business school, here modified to serve dementia diagnostics.

A Diagnostic Model for Dementia in Clinical Practice—Case Methodology Assisting Dementia Diagnosis

PubMed Central

Londos, Elisabet

2015-01-01

Dementia diagnosis is important for many different reasons. Firstly, to separate dementia, or major neurocognitive disorder, from MCI (mild cognitive impairment), mild neurocognitive disorder. Secondly, to define the specific underlying brain disorder to aid treatment, prognosis and decisions regarding care needs and assistance. The diagnostic method of dementias is a puzzle of different data pieces to be fitted together in the best possible way to reach a clinical diagnosis. Using a modified case methodology concept, risk factors affecting cognitive reserve and symptoms constituting the basis of the brain damage hypothesis, can be visualized, balanced and reflected against test results as well as structural and biochemical markers. The model’s origin is the case method initially described in Harvard business school, here modified to serve dementia diagnostics. PMID:26854146

Beyond the Curriculum: Creating the Conditions for Learning.

ERIC Educational Resources Information Center

Grauer, Stuart

Using current mind/brain research, this paper explores the "hidden curriculum" in the contexts of teaching, learning and supervision. It explains ways in which current research on the nature of learning can fit into today's typical, "clinical" teaching techniques. The importance of respecting individual modes of learning is stressed; further to…

Cortical brain structure and sexual orientation in adult females with bipolar disorder or attention deficit hyperactivity disorder.

PubMed

Abé, Christoph; Rahman, Qazi; Långström, Niklas; Rydén, Eleonore; Ingvar, Martin; Landén, Mikael

2018-05-29

Nonheterosexual individuals have higher risk of psychiatric morbidity. Together with growing evidence for sexual orientation-related brain differences, this raises the concern that sexual orientation may be an important factor to control for in neuroimaging studies of neuropsychiatric disorders. We studied sexual orientation in adult psychiatric patients with bipolar disorder (BD) or ADHD in a large clinical cohort (N = 154). We compared cortical brain structure in exclusively heterosexual women (HEW, n = 29) with that of nonexclusively heterosexual women (nHEW, n = 37) using surface-based reconstruction techniques provided by FreeSurfer. The prevalence of nonheterosexual sexual orientation was tentatively higher than reported in general population samples. Consistent with previously reported cross-sex shifted brain patterns among homosexual individuals, nHEW patients showed significantly larger cortical volumes than HEW in medial occipital brain regions. We found evidence for a sex-reversed difference in cortical volume among nonheterosexual female patients, which provides insights into the neurobiology of sexual orientation, and may provide the first clues toward a better neurobiological understanding of the association between sexual orientation and mental health. We also suggest that sexual orientation is an important factor to consider in future neuroimaging studies of populations with certain mental health disorders. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

A gut feeling: Microbiome-brain-immune interactions modulate social and affective behaviors.

PubMed

Sylvia, Kristyn E; Demas, Gregory E

2018-03-01

The expression of a wide range of social and affective behaviors, including aggression and investigation, as well as anxiety- and depressive-like behaviors, involves interactions among many different physiological systems, including the neuroendocrine and immune systems. Recent work suggests that the gut microbiome may also play a critical role in modulating behavior and likely functions as an important integrator across physiological systems. Microbes within the gut may communicate with the brain via both neural and humoral pathways, providing numerous avenues of research in the area of the gut-brain axis. We are now just beginning to understand the intricate relationships among the brain, microbiome, and immune system and how they work in concert to influence behavior. The effects of different forms of experience (e.g., changes in diet, immune challenge, and psychological stress) on the brain, gut microbiome, and the immune system have often been studied independently. Though because these systems do not work in isolation, it is essential to shift our focus to the connections among them as we move forward in our investigations of the gut-brain axis, the shaping of behavioral phenotypes, and the possible clinical implications of these interactions. This review summarizes the recent progress the field has made in understanding the important role the gut microbiome plays in the modulation of social and affective behaviors, as well as some of the intricate mechanisms by which the microbiome may be communicating with the brain and immune system. Copyright © 2018 Elsevier Inc. All rights reserved.

A computational framework for the detection of subcortical brain dysmaturation in neonatal MRI using 3D Convolutional Neural Networks.

PubMed

Ceschin, Rafael; Zahner, Alexandria; Reynolds, William; Gaesser, Jenna; Zuccoli, Giulio; Lo, Cecilia W; Gopalakrishnan, Vanathi; Panigrahy, Ashok

2018-05-21

Deep neural networks are increasingly being used in both supervised learning for classification tasks and unsupervised learning to derive complex patterns from the input data. However, the successful implementation of deep neural networks using neuroimaging datasets requires adequate sample size for training and well-defined signal intensity based structural differentiation. There is a lack of effective automated diagnostic tools for the reliable detection of brain dysmaturation in the neonatal period, related to small sample size and complex undifferentiated brain structures, despite both translational research and clinical importance. Volumetric information alone is insufficient for diagnosis. In this study, we developed a computational framework for the automated classification of brain dysmaturation from neonatal MRI, by combining a specific deep neural network implementation with neonatal structural brain segmentation as a method for both clinical pattern recognition and data-driven inference into the underlying structural morphology. We implemented three-dimensional convolution neural networks (3D-CNNs) to specifically classify dysplastic cerebelli, a subset of surface-based subcortical brain dysmaturation, in term infants born with congenital heart disease. We obtained a 0.985 ± 0. 0241-classification accuracy of subtle cerebellar dysplasia in CHD using 10-fold cross-validation. Furthermore, the hidden layer activations and class activation maps depicted regional vulnerability of the superior surface of the cerebellum, (composed of mostly the posterior lobe and the midline vermis), in regards to differentiating the dysplastic process from normal tissue. The posterior lobe and the midline vermis provide regional differentiation that is relevant to not only to the clinical diagnosis of cerebellar dysplasia, but also genetic mechanisms and neurodevelopmental outcome correlates. These findings not only contribute to the detection and classification of a subset of neonatal brain dysmaturation, but also provide insight to the pathogenesis of cerebellar dysplasia in CHD. In addition, this is one of the first examples of the application of deep learning to a neuroimaging dataset, in which the hidden layer activation revealed diagnostically and biologically relevant features about the clinical pathogenesis. The code developed for this project is open source, published under the BSD License, and designed to be generalizable to applications both within and beyond neonatal brain imaging. Copyright © 2018 Elsevier Inc. All rights reserved.

Animal modelling of traumatic brain injury in preclinical drug development: where do we go from here?

PubMed Central

Marklund, Niklas; Hillered, Lars

2011-01-01

Traumatic brain injury (TBI) is the leading cause of death and disability in young adults. Survivors of TBI frequently suffer from long-term personality changes and deficits in cognitive and motor performance, urgently calling for novel pharmacological treatment options. To date, all clinical trials evaluating neuroprotective compounds have failed in demonstrating clinical efficacy in cohorts of severely injured TBI patients. The purpose of the present review is to describe the utility of animal models of TBI for preclinical evaluation of pharmacological compounds. No single animal model can adequately mimic all aspects of human TBI owing to the heterogeneity of clinical TBI. To successfully develop compounds for clinical TBI, a thorough evaluation in several TBI models and injury severities is crucial. Additionally, brain pharmacokinetics and the time window must be carefully evaluated. Although the search for a single-compound, ‘silver bullet’ therapy is ongoing, a combination of drugs targeting various aspects of neuroprotection, neuroinflammation and regeneration may be needed. In summary, finding drugs and prove clinical efficacy in TBI is a major challenge ahead for the research community and the drug industry. For a successful translation of basic science knowledge to the clinic to occur we believe that a further refinement of animal models and functional outcome methods is important. In the clinical setting, improved patient classification, more homogenous patient cohorts in clinical trials, standardized treatment strategies, improved central nervous system drug delivery systems and monitoring of target drug levels and drug effects is warranted. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21175576

Progress and roadblocks in the search for brain-based biomarkers of autism and attention-deficit/hyperactivity disorder.

PubMed

Uddin, L Q; Dajani, D R; Voorhies, W; Bednarz, H; Kana, R K

2017-08-22

Children with neurodevelopmental disorders benefit most from early interventions and treatments. The development and validation of brain-based biomarkers to aid in objective diagnosis can facilitate this important clinical aim. The objective of this review is to provide an overview of current progress in the use of neuroimaging to identify brain-based biomarkers for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), two prevalent neurodevelopmental disorders. We summarize empirical work that has laid the foundation for using neuroimaging to objectively quantify brain structure and function in ways that are beginning to be used in biomarker development, noting limitations of the data currently available. The most successful machine learning methods that have been developed and applied to date are discussed. Overall, there is increasing evidence that specific features (for example, functional connectivity, gray matter volume) of brain regions comprising the salience and default mode networks can be used to discriminate ASD from typical development. Brain regions contributing to successful discrimination of ADHD from typical development appear to be more widespread, however there is initial evidence that features derived from frontal and cerebellar regions are most informative for classification. The identification of brain-based biomarkers for ASD and ADHD could potentially assist in objective diagnosis, monitoring of treatment response and prediction of outcomes for children with these neurodevelopmental disorders. At present, however, the field has yet to identify reliable and reproducible biomarkers for these disorders, and must address issues related to clinical heterogeneity, methodological standardization and cross-site validation before further progress can be achieved.

Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging.

PubMed

Voss, Michelle W; Weng, Timothy B; Burzynska, Agnieszka Z; Wong, Chelsea N; Cooke, Gillian E; Clark, Rachel; Fanning, Jason; Awick, Elizabeth; Gothe, Neha P; Olson, Erin A; McAuley, Edward; Kramer, Arthur F

2016-05-01

Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the default mode network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks. Copyright © 2015 Elsevier Inc. All rights reserved.

Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging

PubMed Central

Voss, Michelle W.; Weng, Timothy B.; Burzynska, Agnieszka Z.; Wong, Chelsea N.; Cooke, Gillian E.; Clark, Rachel; Fanning, Jason; Awick, Elizabeth; Gothe, Neha P.; Olson, Erin A.; McAuley, Edward; Kramer, Arthur F.

2015-01-01

Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the Default Mode Network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks. PMID:26493108

Test-retest reliability of functional connectivity networks during naturalistic fMRI paradigms.

PubMed

Wang, Jiahui; Ren, Yudan; Hu, Xintao; Nguyen, Vinh Thai; Guo, Lei; Han, Junwei; Guo, Christine Cong

2017-04-01

Functional connectivity analysis has become a powerful tool for probing the human brain function and its breakdown in neuropsychiatry disorders. So far, most studies adopted resting-state paradigm to examine functional connectivity networks in the brain, thanks to its low demand and high tolerance that are essential for clinical studies. However, the test-retest reliability of resting-state connectivity measures is moderate, potentially due to its low behavioral constraint. On the other hand, naturalistic neuroimaging paradigms, an emerging approach for cognitive neuroscience with high ecological validity, could potentially improve the reliability of functional connectivity measures. To test this hypothesis, we characterized the test-retest reliability of functional connectivity measures during a natural viewing condition, and benchmarked it against resting-state connectivity measures acquired within the same functional magnetic resonance imaging (fMRI) session. We found that the reliability of connectivity and graph theoretical measures of brain networks is significantly improved during natural viewing conditions over resting-state conditions, with an average increase of almost 50% across various connectivity measures. Not only sensory networks for audio-visual processing become more reliable, higher order brain networks, such as default mode and attention networks, but also appear to show higher reliability during natural viewing. Our results support the use of natural viewing paradigms in estimating functional connectivity of brain networks, and have important implications for clinical application of fMRI. Hum Brain Mapp 38:2226-2241, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Source-based neurofeedback methods using EEG recordings: training altered brain activity in a functional brain source derived from blind source separation

PubMed Central

White, David J.; Congedo, Marco; Ciorciari, Joseph

2014-01-01

A developing literature explores the use of neurofeedback in the treatment of a range of clinical conditions, particularly ADHD and epilepsy, whilst neurofeedback also provides an experimental tool for studying the functional significance of endogenous brain activity. A critical component of any neurofeedback method is the underlying physiological signal which forms the basis for the feedback. While the past decade has seen the emergence of fMRI-based protocols training spatially confined BOLD activity, traditional neurofeedback has utilized a small number of electrode sites on the scalp. As scalp EEG at a given electrode site reflects a linear mixture of activity from multiple brain sources and artifacts, efforts to successfully acquire some level of control over the signal may be confounded by these extraneous sources. Further, in the event of successful training, these traditional neurofeedback methods are likely influencing multiple brain regions and processes. The present work describes the use of source-based signal processing methods in EEG neurofeedback. The feasibility and potential utility of such methods were explored in an experiment training increased theta oscillatory activity in a source derived from Blind Source Separation (BSS) of EEG data obtained during completion of a complex cognitive task (spatial navigation). Learned increases in theta activity were observed in two of the four participants to complete 20 sessions of neurofeedback targeting this individually defined functional brain source. Source-based EEG neurofeedback methods using BSS may offer important advantages over traditional neurofeedback, by targeting the desired physiological signal in a more functionally and spatially specific manner. Having provided preliminary evidence of the feasibility of these methods, future work may study a range of clinically and experimentally relevant brain processes where individual brain sources may be targeted by source-based EEG neurofeedback. PMID:25374520

Impact of high iron intake on cognition and neurodegeneration in humans and in animal models: a systematic review.

PubMed

Agrawal, Sonal; Berggren, Kiersten L; Marks, Eileen; Fox, Jonathan H

2017-06-01

Accumulation of brain iron is linked to aging and protein-misfolding neurodegenerative diseases. High iron intake may influence important brain health outcomes in later life. The aim of this systematic review was to examine evidence from animal and human studies of the effects of high iron intake or peripheral iron status on adult cognition, brain aging, and neurodegeneration. MEDLINE, Scopus, CAB Abstracts, the Cochrane Central Register of Clinical Trials, and OpenGrey databases were searched. Studies investigating the effect of elevated iron intake at all postnatal life stages in mammalian models and humans on measures of adult brain health were included. Data were extracted and evaluated by two authors independently, with discrepancies resolved by discussion. Neurodegenerative disease diagnosis and/or behavioral/cognitive, biochemical, and brain morphologic findings were used to study the effects of iron intake or peripheral iron status on brain health. Risk of bias was assessed for animal and human studies. PRISMA guidelines for reporting systematic reviews were followed. Thirty-four preclinical and 14 clinical studies were identified from database searches. Thirty-three preclinical studies provided evidence supporting an adverse effect of nutritionally relevant high iron intake in neonates on brain-health-related outcomes in adults. Human studies varied considerably in design, quality, and findings; none investigated the effects of high iron intake in neonates/infants. Human studies are needed to verify whether dietary iron intake levels used in neonates/infants to prevent iron deficiency have effects on brain aging and neurodegenerative disease outcomes. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute.

Zika Virus Infection in Pregnancy, Microcephaly, and Maternal and Fetal Health: What We Think, What We Know, and What We Think We Know.

PubMed

Alvarado, Maria Gabriela; Schwartz, David A

2017-01-01

-The global epidemic of Zika virus (ZIKV) infection has emerged as an important public health problem affecting pregnant women and their infants. -To review the causal association between ZIKV infection during pregnancy and intrauterine fetal infection, microcephaly, brain damage, congenital malformation syndrome, and experimental laboratory models of fetal infection. Many questions remain regarding the risk factors, pathophysiology, epidemiology, and timing of maternal-fetal transmission and disease. These include mechanisms of fetal brain damage and microcephaly; the role of covariables, such as viral burden, duration of viremia, and host genetics, on vertical transmission; and the clinical and pathologic spectrum of congenital Zika syndrome. Additional questions include defining the potential long-term physical and neurobehavioral outcomes for infected infants, whether maternal or fetal host genetics influence the clinical outcome, and whether ZIKV infection can cause maternal morbidity. Finally, are experimental laboratory and animal models of ZIKV infection helpful in addressing maternal-fetal viral transmission and the development of congenital microcephaly? This communication provides current information and attempts to address some of these important questions. -Comprehensive review of published scientific literature. -Recent advances in epidemiology, clinical medicine, pathology, and experimental studies have provided a great amount of new information regarding vertical ZIKV transmission and the mechanisms of congenital microcephaly, brain damage, and congenital Zika syndrome in a relatively short time. However, much work still needs to be performed to more completely understand the maternal and fetal aspects of this new and emerging viral disease.

Brain profiling and clinical-neuroscience.

PubMed

Peled, Avi

2006-01-01

The current psychiatric diagnostic system, the diagnostic statistic manual, has recently come under increasing criticism. The major reason for the shortcomings of the current psychiatric diagnosis is the lack of a scientific brain-related etiological knowledge about mental disorders. The advancement toward such knowledge is further hampered by the lack of a theoretical framework or "language" that translates clinical findings of mental disorders to brain disturbances and insufficiencies. Here such a theoretical construct is proposed based on insights from neuroscience and neural-computation models. Correlates between clinical manifestations and presumed neuronal network disturbances are proposed in the form of a practical diagnostic system titled "Brain Profiling". Three dimensions make-up brain profiling, "neural complexity disorders", "neuronal resilience insufficiency", and "context-sensitive processing decline". The first dimension relates to disturbances occurring to fast neuronal activations in the millisecond range, it incorporates connectivity and hierarchical imbalances appertaining typically to psychotic and schizophrenic clinical manifestations. The second dimension relates to disturbances that alter slower changes namely long-term synaptic modulations, and incorporates disturbances to optimization and constraint satisfactions within relevant neuronal circuitry. Finally, the level of internal representations related to personality disorders is presented by a "context-sensitive process decline" as the third dimension. For practical use of brain profiling diagnosis a consensual list of psychiatric clinical manifestations provides a "diagnostic input vector", clinical findings are coded 1 for "detection" and 0 for "non-detection", 0.5 is coded for "questionable". The entries are clustered according to their presumed neuronal dynamic relationships and coefficients determine their relevance to the specific related brain disturbance. Relevant equations calculate and normalize the different values attributed to relevant brain disturbances culminating in a three-digit estimation representing the three diagnostic dimensions. brain profiling has the promise for a future brain-related diagnosis. It offers testable predictions about the etiology of mental disorders because being brain-related it lends readily to brain imaging investigations. Being presented also as a one-point representation in a three-dimensional space, multiple follow-up diagnoses trace a trajectory representing an easy-to-see clinical history of the patient. Additional, more immediate, advantages involve reduced stigma because it relaters the disorder to the brain not the person, in addition the three-digit diagnostic code is clinically informative unlike the DSM codes that have no clinical relevance. To conclude, brain profiling diagnosis of mental disorders could be a bold new step toward a "clinical-neuroscience" substituting "psychiatry".

Unusual developmental pattern of brain lateralization in young boys with autism spectrum disorder: Power analysis with child-sized magnetoencephalography.

PubMed

Hiraishi, Hirotoshi; Kikuchi, Mitsuru; Yoshimura, Yuko; Kitagawa, Sachiko; Hasegawa, Chiaki; Munesue, Toshio; Takesaki, Natsumi; Ono, Yasuki; Takahashi, Tsutomu; Suzuki, Michio; Higashida, Haruhiro; Asada, Minoru; Minabe, Yoshio

2015-03-01

Autism spectrum disorder (ASD) is often described as comprising an unusual brain growth pattern and aberrant brain lateralization. Although it is important to study the pathophysiology of the developing ASD cortex, examples of physiological brain lateralization in young children with ASD have yet to be well examined. Thirty-eight boys with ASD (aged 3-7 years) and 38 typically developing (TD) boys (aged 3-8 years) concentrated on video programs and their brain activities were measured non-invasively. We employed a customized child-sized magnetoencephalography system in which the sensors were located as close to the brain as possible for optimal recording in young children. To produce a credible laterality index of the brain oscillations, we defined two clusters of sensors corresponding to the right and left hemispheres. We focused on the laterality index ([left - right]/[left+right]) of the relative power band in seven frequency bands. The TD group displayed significantly rightward lateralized brain oscillations in the theta-1 frequency bands compared to the ASD group. This is the first study to demonstrate unusual brain lateralization of brain oscillations measured by magnetoencephalography in young children with ASD. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Pediatric Brain Tumors: Genomics and Epigenomics Pave the Way.

PubMed

Fontebasso, Adam M; Jabado, Nada

2015-01-01

Primary malignant brain tumors remain a disproportionate cause of morbidity and mortality in humans. A number of studies exploring the cancer genome of brain tumors across ages using integrated genetics and epigenetics and next-generation sequencing technologies have recently emerged. This has led to considerable advances in the understanding of the basic biology and pathogenesis of brain tumors, including the most malignant and common variants in children: gliomas and medulloblastoma. Notably, studies of pediatric brain tumors have identified unexpected oncogenic pathways implicated in tumorigenesis. These range from a single pathway/molecule defect such as abnormalities of the mitogen-activated protein kinase pathway, considered to be a hallmark of pilocytic astrocytomas, to alterations in the epigenome as a critical component altered in many subgroups of high-grade brain tumors. Importantly, the type, timing, and spatial clustering of these molecular alterations provide a better understanding of the pathogenesis of the respective brain tumor they target and critical markers for therapy that will help refine pathological grading. We summarize these novel findings in pediatric brain tumors, which also are put in the context of the evolving notion of molecular pathology, now a mandated tool for proper classification and therapy assignment in the clinical setting.

The development, past achievements, and future directions of brain PET

PubMed Central

Jones, Terry; Rabiner, Eugenii A

2012-01-01

The early developments of brain positron emission tomography (PET), including the methodological advances that have driven progress, are outlined. The considerable past achievements of brain PET have been summarized in collaboration with contributing experts in specific clinical applications including cerebrovascular disease, movement disorders, dementia, epilepsy, schizophrenia, addiction, depression and anxiety, brain tumors, drug development, and the normal healthy brain. Despite a history of improving methodology and considerable achievements, brain PET research activity is not growing and appears to have diminished. Assessments of the reasons for decline are presented and strategies proposed for reinvigorating brain PET research. Central to this is widening the access to advanced PET procedures through the introduction of lower cost cyclotron and radiochemistry technologies. The support and expertize of the existing major PET centers, and the recruitment of new biologists, bio-mathematicians and chemists to the field would be important for such a revival. New future applications need to be identified, the scope of targets imaged broadened, and the developed expertize exploited in other areas of medical research. Such reinvigoration of the field would enable PET to continue making significant contributions to advance the understanding of the normal and diseased brain and support the development of advanced treatments. PMID:22434067

Growth and development of the brain and impact on cognitive outcomes.

PubMed

Hüppi, Petra S

2010-01-01

Understanding human brain development from the fetal life to adulthood is of great clinical importance as many neurological and neurobehavioral disorders have their origin in early structural and functional cerebral maturation. The developing brain is particularly prone to being affected by endogenous and exogenous events through the fetal and early postnatal life. The concept of 'developmental plasticity or disruption of the developmental program' summarizes these events. Increases in white matter, which speed up communication between brain cells, growing complexity of neuronal networks suggested by gray and white matter changes, and environmentally sensitive plasticity are all essential aspects in a child's ability to mentalize and maintain the adaptive flexibility necessary for achieving high sociocognitive functioning. Advancement in neuroimaging has opened up new ways for examining the developing human brain in vivo, the study of the effects of early antenatal, perinatal and neonatal events on later structural and functional brain development resulting in developmental disabilities or developmental resilience. In this review, methods of quantitative assessment of human brain development, such as 3D-MRI with image segmentation, diffusion tensor imaging to assess connectivity and functional MRI to visualize brain function will be presented. Copyright (c) 2010 S. Karger AG, Basel.

Recent advances in fetal near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

D'Antona, Donato; Aldrich, Clive J.; O'Brien, Patrick; Lawrence, Sally; Delpy, David T.; Wyatt, John S.

1997-01-01

Fetal brain injury resulting from hypoxia and ischemia during labor remains an important cause of death and long- term disability. However, little is known about fetal brain oxygenation and hemodynamics. There are currently no satisfactory clinical techniques for fetal monitoring and there remains a need for a new method to assess brain oxygenation. Fetal near infrared spectroscopy (NIRS) is a new technique that allows noninvasive observation of changes in the cerebral concentrations of oxyhemoglobin and deoxyhemoglobin to be made during labor. A specially designed optical probe is inserted through the dilated cervix and placed against the fetal head. It is then possible to compare changes in NIRS data with other observations of fetal conditions, such as fetal heart rate and acid-base status.

Fat embolism syndrome: Clinical and imaging considerations: Case report and review of literature

PubMed Central

Shaikh, Nissar; Parchani, Ashok; Bhat, Venkatraman; Kattren, Marie Anne

2008-01-01

Fat embolism syndrome (FES) is a serious clinical disorder occurring after trauma, orthopedic procedures and rarely in non-traumatic patients. Fat emboli develop in nearly all patients with bone fractures, but they are usually asymptomatic. Small number of patients develop signs and symptoms of various organ system dysfunction due to either mechanical obstruction of capillaries by fat emboli or due to hydrolysis of fat to fatty acids. A triad of lung, brain and skin involvement develop after an asymptomatic period of 24 to 72 hours. This symptom complex is called FES. The incidence reported is up to 30%, but many mild cases may recover unnoticed. Diagnosis of fat embolism is clinical with nonspecific, insensitive diagnostic test results. Treatment of fat embolism syndrome remains supportive and in most cases can be prevented by early fixation of large bone factures. Here we report two cases of traumatic fat embolism, which were diagnosed initially by Gurd's criteria and subsequently confirmed by typical appearance on magnetic resonance imaging (MRI) of the brain in these patients. These patients were successfully treated with supportive management. In conclusion, diagnosis of FES needs high index of suspicion, exclusion of other conditions and use of clinical criteria in combination with imaging. Magnetic resonance imaging of the brain is of great importance in diagnosis and management of these patients. PMID:19826589

Role of Epidermal Growth Factor Receptor (EGFR) Inhibitors and Radiation in the Management of Brain Metastases from EGFR Mutant Lung Cancers.

PubMed

Khandekar, Melin J; Piotrowska, Zofia; Willers, Henning; Sequist, Lecia V

2018-04-27

The growth of genotype-directed targeted therapies, such as inhibitors of the epidermal growth factor receptor (EGFR), has revolutionized treatment for some patients with oncogene-addicted lung cancer. However, as systemic control for these patients has improved, brain metastases remain an important source of morbidity and mortality. Traditional treatment for brain metastases has been radiotherapy, either whole-brain radiation or stereotactic radiosurgery. The growing availability of drugs that can cross the blood-brain barrier and have activity in the central nervous system (CNS) has led to many studies investigating whether targeted therapy can be used in combination with or in lieu of radiation. In this review, we summarize the key literature about the incidence and nature of EGFR-mutant brain metastases (EGFR BMs), the data about the activity of EGFR inhibitors in the CNS, and whether they can be used as front-line therapy for brain metastases. Although initial use of tyrosine kinase inhibitors for EGFR BMs can often be an effective treatment strategy, multidisciplinary evaluation is critical, and prospective studies are needed to clarify which patients may benefit from early radiotherapy. Management of brain metastases in epidermal growth factor receptor (EGFR) mutant lung cancer is a common clinical problem. The question of whether to start initial therapy with an EGFR inhibitor or radiotherapy (either whole-brain radiotherapy or stereotactic radiosurgery) is controversial. The development of novel EGFR inhibitors with enhanced central nervous system (CNS) penetration is an important advance in the treatment of CNS disease. Multidisciplinary evaluation and evaluation of extracranial disease status are critical to choosing the best treatment option for each patient. © AlphaMed Press 2018.

77 FR 297 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-04

... of Committee: Brain Disorders and Clinical Neuroscience Integrated Review Group, Developmental Brain...- 9866, [email protected] . Name of Committee: Brain Disorders and Clinical Neuroscience Integrated...

Nuclear emission-based imaging in the study of brain function

NASA Astrophysics Data System (ADS)

Sossi, Vesna

2016-09-01

Nuclear emission - based imaging has been used in medicine for decades either in the form of Single Photon Emission Computerized Tomography (SPECT) or Positron Emission Tomography (PET). Both techniques are based on radiolabelling molecules of biological interest (radiotracers) with either a gamma (SPECT) or a positron (PET) emitting radionuclide. By detecting radiation from the radiolabels and reconstructing the acquired data it is possible to form an image of the radiotracer distribution in the body and thus obtain information on the biological process that the radiotracer is tagging. While most of the clinical applications of PET are in oncology, where the glucose analogue 18F-flurodeoxyglocose (FDG) is the most commonly used radiotracer, the importance of PET imaging for brain applications is rapidly increasing. Numerous radiotracers exist that can tag different neurotransmitter systems as well as abnormal protein aggregations that are known to underlie several brain diseases: amyloid deposition, a characteristic of Alzheimer's, and, more recently, tau deposition, which is deemed abnormal not only in dementia, but also in Parkinson's syndrome and traumatic brain injury. Imaging has shown that may brain diseases start decades before clinical symptoms, in part explaining the difficulty of developing adequate treatments. This talk will briefly summarize the role of PET imaging in the study of neurodegeneration and discuss the upcoming hybrid PET/MRI imaging instrumentation. NSERC, CIHR, MJFF.

The utilization of fluorescein in brain tumor surgery: a systematic review.

PubMed

Cavallo, Claudio; De Laurentis, Camilla; Vetrano, Ignazio G; Falco, Jacopo; Broggi, Morgan; Schiariti, Marco; Ferroli, Paolo; Acerbi, Francesco

2018-05-22

Sodium Fluorescein (SF) is a green, water-soluble dye with the capacity to accumulate in cerebral areas as a result of damaged blood-brain barrier (BBB); this property allows SF to concentrate specifically at the tumor site of various types of brain neoplasms, making the tumor tissue more clearly visible. A literature search (1947-2018) was conducted with the keywords "fluorescein neurosurgery", "YELLOW neurosurgery", "fluorescein brain tumor", "YELLOW brain tumor". We included clinical studies, clinical trials, observational studies, only conducted on humans and concerning surgery; in addition, we have included 3 articles derived from the analysis of the references of other papers. Ultimately, 57 articles were included for further analysis. Fluorescein as a fluorescent tracer in neuro-oncology is gaining a wider acceptance in the neurosurgical literature: until February 1st, 2018, at least 1099 neuro-oncological patients have been operated through fluorescein-assistance, mostly only after 2012. The most important application remains the aim to improve tumor visualization and extent of resection for high-grade gliomas (HGG), but the nonspecific mechanism of action is the theoretical base for its use also for tumors different from HGG. Nevertheless, no homogenous protocol of fluorescein utilization in neurosurgical oncology can be found in literature. Fluorescein-guided surgery is a safe and effective technique to improve visualization and resection of different CNS tumors and conditions, based on BBB alteration, with a growing evidence-based background.

Emotional and personality changes following brain tumour resection.

PubMed

Jenkins, Lisanne M; Drummond, Katharine J; Andrewes, David G

2016-07-01

Psychological distress has a high prevalence in brain tumour patients, and understanding the emotional and personality changes that may follow neurosurgery is important for clinical management of these patients. We aimed to characterise these emotional and personality changes using subjective, observer-rated and clinical measures. We examined subjective changes in emotional experience and observer-rated changes to personality disturbances following neurosurgery for brain tumours (n=44), compared to a control group that had undergone spinal surgery (n=26). Participants completed the Hospital Anxiety and Depression Scale and a Subjective Emotional Change Questionnaire. Observers who knew the patients well also completed the Iowa Rating Scale of Personality Change. Compared to controls, patients with tumours reported significantly more changes to their subjective experience of emotions following neurosurgery, particularly anger, disgust and sadness. For the observer-ratings, tumour patients were described as having significant changes in the personality disturbances of irritability, impulsivity, moodiness, inflexibility, and being easily overwhelmed. Anxiety and depression were not significantly different between groups. Neurosurgical resection of a brain tumour is a major life event that changes patients' subjective experiences of different emotions, and leads to observer-rated changes in personality. In this study, these changes were not accompanied by increases in anxiety or depression. We conclude with a discussion of biological and psychosocial mechanisms that can impact emotional functioning and personality in patients with brain tumours. Copyright © 2015 Elsevier Ltd. All rights reserved.

76 FR 72957 - 4th Annual Trauma Spectrum Conference: Bridging the Gap Between Research and Clinical Practice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-28

... Brain Injury: Prevention, Diagnosis, Treatment and Recovery for the Iraq and Afghanistan Cohort Notice... Clinical Practice of Psychological Health and Traumatic Brain Injury: Prevention, Diagnosis, Treatment and... clinical practices for psychological health and traumatic brain injury (TBI) health concerns for returning...

Finding language in the matter of the brain: origins of the clinical aphasia examination.

PubMed

Roth, Heidi L

2002-12-01

The origins of the aphasia examination can be traced back to the 19th century when physicians and scientists began to understand how higher mental functions such as language could be localized in the brain. Paul Broca, Carl Wernicke, and Hughlings Jackson developed different models of brain function, and each contributed important insights to the study of aphasia. Broca's contributions were influenced by the fundamental question of whether higher mental function could be localized in the brain at all; Wernicke's contributions were influenced by an attempt to unite more mechanistic and physiological principles to a model of higher brain functions; and Jackson's contributions were influenced by British association psychology. In addition to reviewing the origins of the aphasia examination, this article reviews the historical context in which these contributors worked, the factors that affected the reception of their views, and the manner in which their views have affected the aphasia examination and understanding of aphasia today.

TuMore: generation of synthetic brain tumor MRI data for deep learning based segmentation approaches

NASA Astrophysics Data System (ADS)

Lindner, Lydia; Pfarrkirchner, Birgit; Gsaxner, Christina; Schmalstieg, Dieter; Egger, Jan

2018-03-01

Accurate segmentation and measurement of brain tumors plays an important role in clinical practice and research, as it is critical for treatment planning and monitoring of tumor growth. However, brain tumor segmentation is one of the most challenging tasks in medical image analysis. Since manual segmentations are subjective, time consuming and neither accurate nor reliable, there exists a need for objective, robust and fast automated segmentation methods that provide competitive performance. Therefore, deep learning based approaches are gaining interest in the field of medical image segmentation. When the training data set is large enough, deep learning approaches can be extremely effective, but in domains like medicine, only limited data is available in the majority of cases. Due to this reason, we propose a method that allows to create a large dataset of brain MRI (Magnetic Resonance Imaging) images containing synthetic brain tumors - glioblastomas more specifically - and the corresponding ground truth, that can be subsequently used to train deep neural networks.

Clinical applications of modern imaging technology: stereo image formation and location of brain cancer

NASA Astrophysics Data System (ADS)

Wang, Dezong; Wang, Jinxiang

1994-05-01

It is very important to locate the tumor for a patient, who has cancer in his brain. If he only gets X-CT or MRI pictures, the doctor does not know the size, shape location of the tumor and the relation between the tumor and other organs. This paper presents the formation of stereo images of cancer. On the basis of color code and color 3D reconstruction. The stereo images of tumor, brain and encephalic truncus are formed. The stereo image of cancer can be round on X, Y, Z-coordinates to show the shape from different directions. In order to show the location of tumor, stereo image of tumor and encephalic truncus are provided on different angles. The cross section pictures are also offered to indicate the relation of brain, tumor and encephalic truncus on cross sections. In this paper the calculating of areas, volume and the space between cancer and the side of the brain are also described.

An oscillopathic approach to developmental dyslexia: From genes to speech processing.

PubMed

Jiménez-Bravo, Miguel; Marrero, Victoria; Benítez-Burraco, Antonio

2017-06-30

Developmental dyslexia is a heterogeneous condition entailing problems with reading and spelling. Several genes have been linked or associated to the disease, many of which contribute to the development and function of brain areas important for auditory and phonological processing. Nonetheless, a clear link between genes, the brain, and the symptoms of dyslexia is still pending. The goal of this paper is contributing to bridge this gap. With this aim, we have focused on how the dyslexic brain fails to process speech sounds and reading cues. We have adopted an oscillatory perspective, according to which dyslexia may result from a deficient integration of different brain rhythms during reading/spellings tasks. Moreover, we show that some candidate genes for this condition are related to brain rhythms. This fresh approach is expected to provide a better understanding of the aetiology and the clinical presentation of developmental dyslexia, but also to achieve an earlier and more accurate diagnosis of the disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Imaging biomarkers of angiogenesis and the microvascular environment in cerebral tumours

PubMed Central

Thompson, G; Mills, S J; Coope, D J; O’connor, J P B; Jackson, A

2011-01-01

Conventional contrast-enhanced CT and MRI are now in routine clinical use for the diagnosis, treatment and monitoring of diseases in the brain. The presence of contrast enhancement is a proxy for the pathological changes that occur in the normally highly regulated brain vasculature and blood-brain barrier. With recognition of the limitations of these techniques, and a greater appreciation for the nuanced mechanisms of microvascular change in a variety of pathological processes, novel techniques are under investigation for their utility in further interrogating the microvasculature of the brain. This is particularly important in tumours, where the reliance on angiogenesis (new vessel formation) is crucial for tumour growth, and the resulting microvascular configuration and derangement has profound implications for diagnosis, treatment and monitoring. In addition, novel therapeutic approaches that seek to directly modify the microvasculature require more sensitive and specific biological markers of baseline tumour behaviour and response. The currently used imaging biomarkers of angiogenesis and brain tumour microvascular environment are reviewed. PMID:22433824

Cytokine-mediated blood brain barrier disruption as a conduit for cancer/chemotherapy-associated neurotoxicity and cognitive dysfunction.

PubMed

Wardill, Hannah R; Mander, Kimberley A; Van Sebille, Ysabella Z A; Gibson, Rachel J; Logan, Richard M; Bowen, Joanne M; Sonis, Stephen T

2016-12-15

Neurotoxicity is a common side effect of chemotherapy treatment, with unclear molecular mechanisms. Clinical studies suggest that the most frequent neurotoxic adverse events affect memory and learning, attention, concentration, processing speeds and executive function. Emerging preclinical research points toward direct cellular toxicity and induction of neuroinflammation as key drivers of neurotoxicity and subsequent cognitive impairment. Emerging data now show detectable levels of some chemotherapeutic agents within the CNS, indicating potential disruption of blood brain barrier integrity or transport mechanisms. Blood brain barrier disruption is a key aspect of many neurocognitive disorders, particularly those characterized by a proinflammatory state. Importantly, many proinflammatory mediators able to modulate the blood brain barrier are generated by tissues and organs that are targets for chemotherapy-associated toxicities. This review therefore aims to explore the hypothesis that peripherally derived inflammatory cytokines disrupt blood brain barrier permeability, thereby increasing direct access of chemotherapeutic agents into the CNS to facilitate neuroinflammation and central neurotoxicity. © 2016 UICC.

Tau elevations in the brain extracellular space correlate with reduced amyloid-β levels and predict adverse clinical outcomes after severe traumatic brain injury.

PubMed

Magnoni, Sandra; Esparza, Thomas J; Conte, Valeria; Carbonara, Marco; Carrabba, Giorgio; Holtzman, David M; Zipfel, Greg J; Stocchetti, Nino; Brody, David L

2012-04-01

Axonal injury is believed to be a major determinant of adverse outcomes following traumatic brain injury. However, it has been difficult to assess acutely the severity of axonal injury in human traumatic brain injury patients. We hypothesized that microdialysis-based measurements of the brain extracellular fluid levels of tau and neurofilament light chain, two low molecular weight axonal proteins, could be helpful in this regard. To test this hypothesis, 100 kDa cut-off microdialysis catheters were placed in 16 patients with severe traumatic brain injury at two neurological/neurosurgical intensive care units. Tau levels in the microdialysis samples were highest early and fell over time in all patients. Initial tau levels were >3-fold higher in patients with microdialysis catheters placed in pericontusional regions than in patients in whom catheters were placed in normal-appearing right frontal lobe tissue (P = 0.005). Tau levels and neurofilament light-chain levels were positively correlated (r = 0.6, P = 0.013). Neurofilament light-chain levels were also higher in patients with pericontusional catheters (P = 0.04). Interestingly, initial tau levels were inversely correlated with initial amyloid-β levels measured in the same samples (r = -0.87, P = 0.000023). This could be due to reduced synaptic activity in areas with substantial axonal injury, as amyloid-β release is closely coupled with synaptic activity. Importantly, high initial tau levels correlated with worse clinical outcomes, as assessed using the Glasgow Outcome Scale 6 months after injury (r = -0.6, P = 0.018). Taken together, our data add support for the hypothesis that axonal injury may be related to long-term impairments following traumatic brain injury. Microdialysis-based measurement of tau levels in the brain extracellular space may be a useful way to assess the severity of axonal injury acutely in the intensive care unit. Further studies with larger numbers of patients will be required to assess the reproducibility of these findings and to determine whether this approach provides added value when combined with clinical and radiological information.

[The role of arteriovenous interrelations in the formation of clinical-pathogenetic variants of hypertonic encephalopathy].

PubMed

Belova, L A

2012-01-01

We studied 209 patients with chronic brain ischemia due to arterial hypertension (hypertonic encephalopathy). 93 patients (44.5%) had clinical-anamnestic features of constitutional phlebopathy and 116 (55.5%) had not. Based on the conception of 5 functional-morphological levels of the vascular brain system, a complex ultrasound study was conducted. The control group included 30 people without cerebrovascular pathology. In hypertonic encephalopathy, pathological processes developing in the 1st and 2nd structural-functional levels (extra- and intracerebral arteries) correspond to remodeling, that is characteristic of arterial hypertension, and do not depend on the presence of the constitutional venous insufficiency. Changes in parameters of the blood flow in the 3rd, 4th and 5th structural-functional levels of the brain's blood supply (microcirculatory bed, head venous system, jugular and spine veins) form a dopplerographic pattern of the cerebral venous dyscirculation which is mostly pronounced in constitutional phlebopathy in patients with hypertonic encephalopathy. This pattern includes the reduction of linear blood flow velocity in nitroglycerine test, lower values of the resistance index and the increase in the linear blood flow velocity in the sinus transversus and Rosenthal vein, lack of ostial valves of the inner jugular veinas well as the decrease of linear and increase in the volume blood flow velocity along it. The methodology of the system approach based on using clinical and instrumental method in the study of cerebral hemodynamics is important for treatment optimization in patients with chronic brain ischemia.

Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection

PubMed Central

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments. PMID:28928987

Armored brain in patients with hydrocephalus after shunt surgery: review of the literatures.

PubMed

Taha, Mahmoud M

2012-01-01

Armored brain or chronic calcified subdural hematoma is a rare complication of cerebrospinal fluid diversion with few cases reported in the literature. Seventeen patients with this pathology have been published. A complete review of the literatures regarding this topic has been collected and discussed. The author also presents a 12- year old boy with triventricular hydrocephalus who had undergone ventriculoperitoneal medium pressure shunt system since birth. The patient presented to our clinic with a 2-year history of seizures. The patient was conscious and without neurological deficits on examination. Computed tomography of the brain showed bilateral high density mass with surface calcification. X ray skull and MRI confirmed the calcified subdural hematoma bilaterally. We preferred conservative treatment and the patient continued his antiepileptic treatment. At one year follow up, the patient had the same neurological state. The case highlights the importance of frequent follow up CT brain after shunt surgery.

Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection.

PubMed

Phillips, Cristy

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments.

Effects of Sex Steroids in the Human Brain.

PubMed

Nguyen, Tuong-Vi; Ducharme, Simon; Karama, Sherif

2017-11-01

Sex steroids are thought to play a critical developmental role in shaping both cortical and subcortical structures in the human brain. Periods of profound changes in sex steroids invariably coincide with the onset of sex differences in mental health vulnerability, highlighting the importance of sex steroids in determining sexual differentiation of the brain. Yet, most of the evidence for the central effects of sex steroids relies on non-human studies, as several challenges have limited our understanding of these effects in humans: the lack of systematic assessment of the human sex steroid metabolome, the different developmental trajectories of specific sex steroids, the impact of genetic variation and epigenetic changes, and the plethora of interactions between sex steroids, sex chromosomes, neurotransmitters, and other hormonal systems. Here we review how multimodal strategies may be employed to bridge the gap between the basic and clinical understanding of sex steroid-related changes in the human brain.

Brain-Computer Interfaces: A Neuroscience Paradigm of Social Interaction? A Matter of Perspective

PubMed Central

Mattout, Jérémie

2012-01-01

A number of recent studies have put human subjects in true social interactions, with the aim of better identifying the psychophysiological processes underlying social cognition. Interestingly, this emerging Neuroscience of Social Interactions (NSI) field brings up challenges which resemble important ones in the field of Brain-Computer Interfaces (BCI). Importantly, these challenges go beyond common objectives such as the eventual use of BCI and NSI protocols in the clinical domain or common interests pertaining to the use of online neurophysiological techniques and algorithms. Common fundamental challenges are now apparent and one can argue that a crucial one is to develop computational models of brain processes relevant to human interactions with an adaptive agent, whether human or artificial. Coupled with neuroimaging data, such models have proved promising in revealing the neural basis and mental processes behind social interactions. Similar models could help BCI to move from well-performing but offline static machines to reliable online adaptive agents. This emphasizes a social perspective to BCI, which is not limited to a computational challenge but extends to all questions that arise when studying the brain in interaction with its environment. PMID:22675291

Lactate shuttling and lactate use as fuel after traumatic brain injury: metabolic considerations

PubMed Central

Dienel, Gerald A

2014-01-01

Lactate is proposed to be generated by astrocytes during glutamatergic neurotransmission and shuttled to neurons as ‘preferred' oxidative fuel. However, a large body of evidence demonstrates that metabolic changes during activation of living brain disprove essential components of the astrocyte–neuron lactate shuttle model. For example, some glutamate is oxidized to generate ATP after its uptake into astrocytes and neuronal glucose phosphorylation rises during activation and provides pyruvate for oxidation. Extension of the notion that lactate is a preferential fuel into the traumatic brain injury (TBI) field has important clinical implications, and the concept must, therefore, be carefully evaluated before implementation into patient care. Microdialysis studies in TBI patients demonstrate that lactate and pyruvate levels and lactate/pyruvate ratios, along with other data, have important diagnostic value to distinguish between ischemia and mitochondrial dysfunction. Results show that lactate release from human brain to blood predominates over its uptake after TBI, and strong evidence for lactate metabolism is lacking; mitochondrial dysfunction may inhibit lactate oxidation. Claims that exogenous lactate infusion is energetically beneficial for TBI patients are not based on metabolic assays and data are incorrectly interpreted. PMID:25204393

Combined Ultrasound and MR Imaging to Guide Focused Ultrasound Therapies in the Brain

PubMed Central

Arvanitis, Costas D.; Livingstone, Margaret S.; McDannold, Nathan

2013-01-01

Purpose Several emerging therapies with potential for use in the brain harness effects produced by acoustic cavitation – the interaction between ultrasound and microbubbles either generated during sonication or introduced into the vasculature. Systems developed for transcranial MRI-guided focused ultrasound (MRgFUS) thermal ablation can enable their clinical translation, but methods for real-time monitoring and control are currently lacking. Acoustic emissions produced during sonication can provide information about the location, strength, and type of the microbubble oscillations within the ultrasound field, and they can be mapped in real-time using passive imaging approaches. Here, we tested whether such mapping can be achieved transcranially within a clinical brain MRgFUS system. Materials and Methods We integrated an ultrasound imaging array into the hemisphere transducer of the MRgFUS device. Passive cavitation maps were obtained during sonications combined with a circulating microbubble agent at 20 targets in the cingulate cortex in three macaques. The maps were compared with MRI-evident tissue effects. Results The system successfully mapped microbubble activity during both stable and inertial cavitation, which was correlated with MRI-evident transient blood-brain barrier disruption and vascular damage, respectively. The location of this activity was coincident with the resulting tissue changes within the expected resolution limits of the system. Conclusion While preliminary, these data clearly demonstrate, for the first time, that is possible to construct maps of stable and inertial cavitation transcranially, in a large animal model, and under clinically relevant conditions. Further, these results suggest that this hybrid ultrasound/MRI approach can provide comprehensive guidance for targeted drug delivery via blood-brain barrier disruption and other emerging ultrasound treatments, facilitating their clinical translation. We anticipate it will also prove to be an important research tool that will further the development of a broad range of microbubble-enhanced therapies. PMID:23788054

"My child doesn't have a brain injury, he only has a concussion".

PubMed

Dematteo, Carol A; Hanna, Steven E; Mahoney, William J; Hollenberg, Robert D; Scott, Louise A; Law, Mary C; Newman, Anne; Lin, Chia-Yu A; Xu, Liqin

2010-02-01

The term "concussion" is frequently used in clinical records to describe a traumatic head injury; however, there are no standard definitions of this term, particularly in how it is used with children. The goals of this study were to examine the clinical correlates of the concussion diagnosis and to identify the factors that lead to the use of this term in a regional pediatric center. Medical data were prospectively collected from 434 children with traumatic brain injury who were admitted to a Canadian children's hospital. A proportional hazards regression was used to examine the association of the concussion diagnosis and the times until discharge and school return. A classification-tree analysis modeled the clinical correlates of patients who received a concussion diagnosis. The concussion label was significantly more likely to be applied to children with mild Glasgow Coma Scale scores of 13 to 15 (P = .03). The concussion label was strongly predictive of earlier hospital discharge (odds ratio [OR]: 1.5; 95% confidence interval [CI]: 1.2-1.9; P = .003) and earlier return to school (OR: 2.4 [95% CI: 1.6-3.7]; P < .001). A diagnosis of a concussion was significantly more likely when the computed-tomography results were normal and the child had lost consciousness. Children with mild traumatic brain injuries have an increased frequency of receiving the concussion label, although the label may also be applied to children with more-severe injuries. The concussion diagnosis is associated with important clinical outcomes. Its typical use in hospital settings likely refers to an impact-related mild brain injury, in the absence of indicators other than a loss of consciousness. Clinicians may use the concussion label because it is less alarming to parents than the term mild brain injury, with the intent of implying that the injury is transient with no significant long-term health consequences.

Brain abscess due to Aggregatibacter aphrophilus and Bacteroides uniformis.

PubMed

Bogdan, Maja; Zujić Atalić, Vlasta; Hećimović, Ivan; Vuković, Dubravka

2015-01-01

The aim of this report was to describe the occurrence of a bacterial brain abscess in a healthy individual, without any predisposing condition. A thirteen-year old boy was admitted to the Department of Neurosurgery after the onset of vomiting, headache and dizziness. A neurological deficit was detected during the physical examination so urgent magnetic resonance imaging of the brain was performed, revealing an intrahemispheric, right positioned solitary expansive mass with ring enhancement. Purulent material was obtained during osteoplastic craniotomy with total extirpation of the brain abscess. Aggregatibacter aphrophilus and Bacteroides uniformis were isolated. The patient's general condition improved and the neurological deficit subsided as a result of the prompt recognition and treatment of this life threatening condition. To achieve a favourable clinical outcome, prompt recognition and surgical treatment of a brain abscess are of primary importance,followed by administration of appropriate antimicrobial therapy. To our best knowledge, this is the first report of this combination of microorganisms as the cause of a brain abscess. Copyright © 2015 by Academy of Sciences and Arts of Bosnia and Herzegovina.

Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

NASA Astrophysics Data System (ADS)

Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

2013-05-01

Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report.

PubMed

Themistocleous, Marios S; Boviatsis, Efstathios J; Stavrinou, Lampis C; Stathis, Pantelis; Sakas, Damianos E

2011-06-29

The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti-parkinsonian drugs during the pre-operative preparation for deep brain stimulation surgery for Parkinson's disease. We present the first case of neuroleptic malignant syndrome associated with discontinuation of anti-parkinsonian medication prior to deep brain stimulation surgery in a 54-year-old Caucasian man. The characteristic neuroleptic malignant syndrome symptoms can be attributed to other, more common causes associated with deep brain stimulation treatment for Parkinson's disease, thus requiring a high index of clinical suspicion to timely establish the correct diagnosis. As more centers become eligible to perform deep brain stimulation, neurologists and neurosurgeons alike should be aware of this potentially fatal complication. Timely activation of the deep brain stimulation system may be important in accelerating the patient's recovery.

Losing protein in the brain: the case of progranulin.

PubMed

Ghidoni, Roberta; Paterlini, Anna; Albertini, Valentina; Binetti, Giuliano; Benussi, Luisa

2012-10-02

It is well known that progranulin protein is involved in wound repair, inflammation, and tumor formation. The wedding between progranulin and brain was celebrated in 2006 with the involvement of progranulin gene (GRN) in Frontotemporal lobar degeneration (FTLD), the most common form of early-onset dementia: up to date, 75 mutations have been detected in FTLD patients as well as in patients with widely variable clinical phenotypes. All pathogenic GRN mutations identified thus far cause the disease through a uniform mechanism, i.e. loss of functional progranulin or haploinsufficiency. Studies on GRN knockout mice suggest that progranulin-related neurodegenerative diseases may result from lifetime depletion of neurotrophic support together with cumulative damage in association with dysregulated inflammation, thus highlighting possible new molecular targets for GRN-related FTLD treatment. Recently, the dosage of plasma progranulin has been proposed as a useful tool for a quick and inexpensive large-scale screening of affected and unaffected carriers of GRN mutations. Before it is systematically translated into clinical practice and, more importantly, included into diagnostic criteria for dementias, further standardization of plasma progranulin test and harmonization of its use are required. Once a specific treatment becomes available for these pathologies, this test - being applicable on large scale - will represent an important step towards personalized healthcare. This article is part of a Special Issue entitled: Brain Integration. Copyright © 2012 Elsevier B.V. All rights reserved.

Brain invasion assessability in meningiomas is related to meningioma size and grade, and can be improved by extensive sampling of the surgically removed meningioma specimen.

PubMed

Pizem, Joze; Velnar, Tomaz; Prestor, Borut; Mlakar, Jernej; Popovic, Mara

2014-01-01

Despite the important prognostic value of brain invasion in meningiomas, little attention has been paid to its massessment, and the parameters associated with brain invasion assessability (identification of brain tissue in the surgical specimen) are not well characterized. The aim of our study was to determine the parameters that are associated with brain invasion assessability and brain invasion in meningiomas. By binary logistic regression analysis, we studied the association of various clinical and pathologic parameters with brain invasion assessabilitym and brain invasion in 294 meningiomas: 149 unselected consecutive meningiomas with extensive sampling, diagnosed in 2009 and 2010, collected prospectively, and 145 meningiomas diagnosed in 1999 and 2000 when little attention was paid to brain invasion assessment. Meningioma grade, size and number of tissue blocks were independent predictors of brain invasion assessability. Brain tissue was identified in 78 of 233 (33%) benign, 33 of 51 (65%) atypical, and 10 of 10 (100%) malignant meningiomas. In univariate analysis, group (prospective vs.retrospective), type (recurrent vs. primary), cleavability, meningioma grade and mitotic count were predictors of brain invasion, while only meningioma grade, and group retained predictive value in multivariate analysis. Brain invasion, when assessable, was identified in 22 of 78 (28%) benign, 21 of 33 (64%) atypical, and 10 of 10 (100%) malignant meningiomas. Brain invasion assessability is related to meningioma grade and size and can be improved by extensive sampling of meningioma surgical.

Nerve Growth Factor: Early Studies And Recent Clinical Trials.

PubMed

Rocco, Maria Luisa; Soligo, Marzia; Manni, Luigi; Aloe, Luigi

2018-04-11

Since its discovery, nerve growth factor (NGF) has long occupied a critical role in developmental and adult neurobiology for its many important regulatory functions on the survival, growth and differentiation of nerve cells in the peripheral and central nervous system. NGF is the first discovered member of a family of neurotrophic factors, collectively indicated as neurotrophins, (which include brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin 4/5). NGF was discovered for its action on the survival and differentiation of selected populations of peripheral neurons. Since then, an enormous number of basic and human studies were undertaken to explore the role of purified NGF to prevent the death of NGF-receptive cells. These studies revealed that NGF possesses important therapeutic properties, after topical administration, on human cutaneous pressure ulcer, corneal ulcers, glaucoma, retinal maculopathy, Retinitis Pigmentosa and in pediatric optic gliomas and brain traumas. The aim of this review is to present our previous, recent and ongoing clinical studies on the therapeutic properties of NGF. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cognitive impairment in a young marmoset reveals lateral ventriculomegaly and a mild hippocampal atrophy: a case report

PubMed Central

Sadoun, A.; Strelnikov, K.; Bonté, E.; Fonta, C.; Girard, P.

2015-01-01

The number of studies that use the common marmoset (Callithrix jacchus) in various fields of neurosciences is increasing dramatically. In general, animals enter the study when their health status is considered satisfactory on the basis of classical clinical investigations. In behavioral studies, variations of score between individuals are frequently observed, some of them being considered as poor performers or outliers. Experimenters rarely consider the fact that it could be related to some brain anomaly. This raises the important issue of the reliability of such classical behavioral approaches without using complementary imaging, especially in animals lacking striking external clinical signs. Here we report the case of a young marmoset which presented a set of cognitive impairments in two different tasks compared to other age-matched animals. Brain imaging revealed a patent right lateral ventricular enlargement with a mild hippocampal atrophy. This abnormality could explain the cognitive impairments of this animal. Such a case points to the importance of complementing behavioral studies by imaging explorations to avoid experimental bias. PMID:26527211

Heterogeneous patterns of brain atrophy in Alzheimer's disease.

PubMed

Poulakis, Konstantinos; Pereira, Joana B; Mecocci, Patrizia; Vellas, Bruno; Tsolaki, Magda; Kłoszewska, Iwona; Soininen, Hilkka; Lovestone, Simon; Simmons, Andrew; Wahlund, Lars-Olof; Westman, Eric

2018-05-01

There is increasing evidence showing that brain atrophy varies between patients with Alzheimer's disease (AD), suggesting that different anatomical patterns might exist within the same disorder. We investigated AD heterogeneity based on cortical and subcortical atrophy patterns in 299 AD subjects from 2 multicenter cohorts. Clusters of patients and important discriminative features were determined using random forest pairwise similarity, multidimensional scaling, and distance-based hierarchical clustering. We discovered 2 typical (72.2%) and 3 atypical (28.8%) subtypes with significantly different demographic, clinical, and cognitive characteristics, and different rates of cognitive decline. In contrast to previous studies, our unsupervised random forest approach based on cortical and subcortical volume measures and their linear and nonlinear interactions revealed more typical AD subtypes with important anatomically discriminative features, while the prevalence of atypical cases was lower. The hippocampal-sparing and typical AD subtypes exhibited worse clinical progression in visuospatial, memory, and executive cognitive functions. Our findings suggest there is substantial heterogeneity in AD that has an impact on how patients function and progress over time. Copyright © 2018 Elsevier Inc. All rights reserved.

Imported human rabies in Switzerland, 2012: a diagnostic conundrum.

PubMed

Deubelbeiss, A N; Trachsel, Ch; Bachli, E B; Kuffer, A; Budka, H; Eniseyskiy, P; Zimmermann, H; Wallace, R M; Farley, S; Zanoni, R G

2013-06-01

Human rabies is rare in Western Europe. It is not easily recognized in the absence of a history of exposure. We describe the clinical course, diagnosis and follow-up of an imported human rabies case in Switzerland. The patient, a U.S. citizen, presented at an outpatient clinic in Iraq with pain in his right shoulder on July 5, 2012. On July 8 he was transferred to a hospital in the United Arab Emirates, where he exhibited progressive encephalitis with coma. On July 29, he was transferred to a hospital in Switzerland, where he died on July 31, 2012. The autopsy showed severe encephalitis. Rabies was diagnosed by the rapid fluorescent focus inhibition test (RFFIT) and confirmed by fluorescence antibody testing (FAT) in brain smears and immunohistochemistry on paraffin-embedded brain sections. The viral strain was characterized by RT-PCR followed by sequencing and phylogenetic analysis as an American bat rabies strain associated with Tadarida brasiliensis. Close contacts and exposed health care workers received postexposure prophylaxis (PEP). Copyright © 2013 Elsevier B.V. All rights reserved.

Improved spatial coverage for brain 3D PRESS MRSI by automatic placement of outer-volume suppression saturation bands.

PubMed

Ozhinsky, Eugene; Vigneron, Daniel B; Nelson, Sarah J

2011-04-01

To develop a technique for optimizing coverage of brain 3D (1) H magnetic resonance spectroscopic imaging (MRSI) by automatic placement of outer-volume suppression (OVS) saturation bands (sat bands) and to compare the performance for point-resolved spectroscopic sequence (PRESS) MRSI protocols with manual and automatic placement of sat bands. The automated OVS procedure includes the acquisition of anatomic images from the head, obtaining brain and lipid tissue maps, calculating optimal sat band placement, and then using those optimized parameters during the MRSI acquisition. The data were analyzed to quantify brain coverage volume and data quality. 3D PRESS MRSI data were acquired from three healthy volunteers and 29 patients using protocols that included either manual or automatic sat band placement. On average, the automatic sat band placement allowed the acquisition of PRESS MRSI data from 2.7 times larger brain volumes than the conventional method while maintaining data quality. The technique developed helps solve two of the most significant problems with brain PRESS MRSI acquisitions: limited brain coverage and difficulty in prescription. This new method will facilitate routine clinical brain 3D MRSI exams and will be important for performing serial evaluation of response to therapy in patients with brain tumors and other neurological diseases. Copyright © 2011 Wiley-Liss, Inc.

Multiple Schwannomas of the Spine: Review of the Schwannomatosis or Congenital Neurilemmomatosis: A Case Report.

PubMed

Lee, Sang-Hoon; Kim, Se-Hoon; Kim, Bum-Joon; Lim, Dong-Jun

2015-06-01

Schwannomas are the most common benign nerve sheath tumors originating in Schwann cells. With special conditions like neurofibromatosis type 2 or entity called schwannomatosis, patients develop multiple schwannomas. But in clinical setting, distinguishing schwannomatosis from neurofibromatosis type 2 is challengeable. We describe 58-year-old male who presented with severe neuropathic pain, from schwannomatosis featuring multiple schwannomas of spine and trunk, and underwent surgical treatment. We demonstrate his radiologic and clinical findings, and discuss about important clinical features of this condition. To confirm schwannomatosis, we performed brain magnetic resonance imaging, and took his familial history. Staged surgery was done for pathological confirmation and relief of the pain. Schwannomatosis and neurofibromatosis type 2 are similar but different disease. There are diagnostic hallmarks of these conditions, including familial history, pathology, and brain imaging. Because of different prognosis, the two diseases must be distinguished, so diagnostic tests that are mentioned above should be performed in caution.

Multiple Schwannomas of the Spine: Review of the Schwannomatosis or Congenital Neurilemmomatosis: A Case Report

PubMed Central

Lee, Sang-Hoon; Kim, Bum-Joon; Lim, Dong-Jun

2015-01-01

Schwannomas are the most common benign nerve sheath tumors originating in Schwann cells. With special conditions like neurofibromatosis type 2 or entity called schwannomatosis, patients develop multiple schwannomas. But in clinical setting, distinguishing schwannomatosis from neurofibromatosis type 2 is challengeable. We describe 58-year-old male who presented with severe neuropathic pain, from schwannomatosis featuring multiple schwannomas of spine and trunk, and underwent surgical treatment. We demonstrate his radiologic and clinical findings, and discuss about important clinical features of this condition. To confirm schwannomatosis, we performed brain magnetic resonance imaging, and took his familial history. Staged surgery was done for pathological confirmation and relief of the pain. Schwannomatosis and neurofibromatosis type 2 are similar but different disease. There are diagnostic hallmarks of these conditions, including familial history, pathology, and brain imaging. Because of different prognosis, the two diseases must be distinguished, so diagnostic tests that are mentioned above should be performed in caution. PMID:26217390

Confounding Brain Stem Function During Pediatric Brain Death Determination: Two Case Reports.

PubMed

Hansen, Gregory; Joffe, Ari R

2017-06-01

A patient who has been declared brain dead is considered to be both legally and clinically dead. However, we report 2 pediatric cases in which the patients demonstrated clinical signs of brain stem function that are not recognized or tested in current Canadian or US guidelines.

Assaultive behavior. Does provocation begin in the front office?

PubMed

Blair, D T

1991-05-01

1. Provocation is an important risk predictor because these issues can be recognized, assessed, and appropriate interventions can be implemented to reduce the associated risks. It is only by the reduction of such "non-fixed" risk factors that any reduction of assaults can be accomplished. 2. Involuntary admission, patients with dementia or organic brain disorder, physical or verbal limits, staff attitude, denial of the possibility of assaults, and the educational level and clinical experience of the staff may help provoke an assaultive episode. 3. An important step is assessing the assault to identify provocation due to certain medical causes, and to document the extent of degeneration in patients with dementia or organic brain disorder. Medical intervention would be indicated and would appropriately address the causes of some violent episodes.

A Systematic Review of Randomized Controlled Trials Comparing Hypertonic Sodium Solutions and Mannitol for Traumatic Brain Injury: Implications for Emergency Department Management.

PubMed

Burgess, Sarah; Abu-Laban, Riyad B; Slavik, Richard S; Vu, Erik N; Zed, Peter J

2016-04-01

To comparatively evaluate hypertonic sodium (HTS) and mannitol in patients following acute traumatic brain injury (TBI) on the outcomes of all-cause mortality, neurological disability, intracranial pressure (ICP) change from baseline, ICP treatment failure, and serious adverse events. PubMed, EMBASE, CENTRAL, Cochrane Database of Systematic Reviews, ClinicalTrials.gov, and WHO ICTRP (World Health Organization International Clinical Trials Registry Platform) were searched (inception to November 2015) using hypertonic saline solutions, sodium chloride, mannitol, osmotic diuretic, traumatic brain injury, brain injuries, and head injury. Searches were limited to humans. Clinical practice guidelines and bibliographies were reviewed. Prospective, randomized trials comparing HTS and mannitol in adults (≥16 years) with severe TBI (Glasgow Coma Scale score ≤8) and elevated ICP were included. ICP elevation, ICP reduction, and treatment failure were defined using study definitions. Of 326 articles screened, 7 trials enrolling a total of 191 patients met inclusion criteria. Studies were underpowered to detect a significant difference in mortality or neurological outcomes. Due to significant heterogeneity and differences in reporting ICP change from baseline, this outcome was not meta-analyzed. No difference between HTS and mannitol was observed for mean ICP reduction; however, risk of ICP treatment failure favored HTS (risk ratio [RR] = 0.39; 95% CI = 0.18-0.81). Serious adverse events were not reported. Based on limited data, clinically important differences in mortality, neurological outcomes, and ICP reduction were not observed between HTS or mannitol in the management of severe TBI. HTS appears to lead to fewer ICP treatment failures. © The Author(s) 2016.

The use and impact of quality of life assessment tools in clinical care settings for cancer patients, with a particular emphasis on brain cancer: insights from a systematic review and stakeholder consultations.

PubMed

King, Sarah; Exley, Josephine; Parks, Sarah; Ball, Sarah; Bienkowska-Gibbs, Teresa; MacLure, Calum; Harte, Emma; Stewart, Katherine; Larkin, Jody; Bottomley, Andrew; Marjanovic, Sonja

2016-09-01

Patient-reported data are playing an increasing role in health care. In oncology, data from quality of life (QoL) assessment tools may be particularly important for those with limited survival prospects, where treatments aim to prolong survival while maintaining or improving QoL. This paper examines the use and impact of using QoL measures on health care of cancer patients within a clinical setting, particularly those with brain cancer. It also examines facilitators and challenges, and provides implications for policy and practice. We conducted a systematic literature review, 15 expert interviews and a consultation at an international summit. The systematic review found no relevant intervention studies specifically in brain cancer patients, and after expanding our search to include other cancers, 15 relevant studies were identified. The evidence on the effectiveness of using QoL tools was inconsistent for patient management, but somewhat more consistent in favour of improving patient-physician communication. Interviews identified unharnessed potential and growing interest in QoL tool use and associated challenges to address. Our findings suggest that the use of QoL tools in cancer patients may improve patient-physician communication and have the potential to improve care, but the tools are not currently widely used in clinical practice (in brain cancer nor some other cancer contexts) although they are in clinical trials. There is a need for further research and stakeholder engagement on how QoL tools can achieve most impact across cancer and patient contexts. There is also a need for policy, health professional, research and patient communities to strengthen information exchange and debate, support awareness raising and provide training on tool design, use and interpretation.

Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability.

PubMed

Giorgio, Antonio; Zhang, Jian; Stromillo, Maria Laura; Rossi, Francesca; Battaglini, Marco; Nichelli, Lucia; Mortilla, Marzia; Portaccio, Emilio; Hakiki, Bahia; Amato, Maria Pia; De Stefano, Nicola

2017-01-01

Pediatric-onset multiple sclerosis (POMS) may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS) patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability ( n  = 15) in comparison with age- and disability-matched AOMS patients ( n  = 14) and to normal controls (NC, n  = 20). We used a multimodal MRI approach by modeling, using FSL, voxelwise measures of microstructural integrity of white matter tracts and gray matter volumes with those of intra- and internetwork functional connectivity (FC) (analysis of variance, p  ≤ 0.01, corrected for multiple comparisons across space). POMS patients showed, when compared with both NC and AOMS patients, altered measures of diffusion tensor imaging (reduced fractional anisotropy and/or increased diffusivities) and higher probability of lesion occurrence in a clinically eloquent region for physical disability such as the posterior corona radiata. In addition, POMS patients showed, compared with the other two groups, reduced long-range FC, assessed from resting functional MRI, between default mode network and secondary visual network, whose interaction subserves important cognitive functions such as spatial attention and visual learning. Overall, this pattern of structural damage and brain connectivity disruption in early adult POMS patients with no or minimal clinical disability might explain their unfavorable clinical outcome in the long term.

The CCLM contribution to improvements in quality and patient safety.

PubMed

Plebani, Mario

2013-01-01

Clinical laboratories play an important role in improving patient care. The past decades have seen unbelievable, often unpredictable improvements in analytical performance. Although the seminal concept of the brain-to-brain laboratory loop has been described more than four decades ago, there is now a growing awareness about the importance of extra-analytical aspects in laboratory quality. According to this concept, all phases and activities of the testing cycle should be assessed, monitored and improved in order to decrease the total error rates thereby improving patients' safety. Clinical Chemistry and Laboratory Medicine (CCLM) not only has followed the shift in perception of quality in the discipline, but has been the catalyst for promoting a large debate on this topic, underlining the value of papers dealing with errors in clinical laboratories and possible remedies, as well as new approaches to the definition of quality in pre-, intra-, and post-analytical steps. The celebration of the 50th anniversary of the CCLM journal offers the opportunity to recall and mention some milestones in the approach to quality and patient safety and to inform our readers, as well as laboratory professionals, clinicians and all the stakeholders of the willingness of the journal to maintain quality issues as central to its interest even in the future.

The role of the posterior cingulate cortex in cognition and disease

PubMed Central

Sharp, David J.

2014-01-01

The posterior cingulate cortex is a highly connected and metabolically active brain region. Recent studies suggest it has an important cognitive role, although there is no consensus about what this is. The region is typically discussed as having a unitary function because of a common pattern of relative deactivation observed during attentionally demanding tasks. One influential hypothesis is that the posterior cingulate cortex has a central role in supporting internally-directed cognition. It is a key node in the default mode network and shows increased activity when individuals retrieve autobiographical memories or plan for the future, as well as during unconstrained ‘rest’ when activity in the brain is ‘free-wheeling’. However, other evidence suggests that the region is highly heterogeneous and may play a direct role in regulating the focus of attention. In addition, its activity varies with arousal state and its interactions with other brain networks may be important for conscious awareness. Understanding posterior cingulate cortex function is likely to be of clinical importance. It is well protected against ischaemic stroke, and so there is relatively little neuropsychological data about the consequences of focal lesions. However, in other conditions abnormalities in the region are clearly linked to disease. For example, amyloid deposition and reduced metabolism is seen early in Alzheimer’s disease. Functional neuroimaging studies show abnormalities in a range of neurological and psychiatric disorders including Alzheimer’s disease, schizophrenia, autism, depression and attention deficit hyperactivity disorder, as well as ageing. Our own work has consistently shown abnormal posterior cingulate cortex function following traumatic brain injury, which predicts attentional impairments. Here we review the anatomy and physiology of the region and how it is affected in a range of clinical conditions, before discussing its proposed functions. We synthesize key findings into a novel model of the region’s function (the ‘Arousal, Balance and Breadth of Attention’ model). Dorsal and ventral subcomponents are functionally separated and differences in regional activity are explained by considering: (i) arousal state; (ii) whether attention is focused internally or externally; and (iii) the breadth of attentional focus. The predictions of the model can be tested within the framework of complex dynamic systems theory, and we propose that the dorsal posterior cingulate cortex influences attentional focus by ‘tuning’ whole-brain metastability and so adjusts how stable brain network activity is over time. PMID:23869106

[Stab injuries of the skull and brain].

PubMed

Ritter, C; Adebahr, G

1986-01-01

A few cases of skull and brain stab wounds are described and the clinicodiagnostic problems discussed. The injuries often remain unrecognized because the external wound often appears harmless, there are no neurological symptoms, or the clinical picture is interpreted as drunkenness, blunt injury or as another disease. The importance of a precise physical examination of the whole patient's head is pointed out. The refined methods used in modern radiodiagnostics of the skull are the most helpful in correctly recognizing these injuries; there are reports of patients with severe injuries who recovered when the correct diagnosis had been established.

Resting and reactive frontal brain electrical activity (EEG) among a non-clinical sample of socially anxious adults: Does concurrent depressive mood matter?

PubMed Central

Beaton, Elliott A; Schmidt, Louis A; Ashbaugh, Andrea R; Santesso, Diane L; Antony, Martin M; McCabe, Randi E

2008-01-01

A number of studies have noted that the pattern of resting frontal brain electrical activity (EEG) is related to individual differences in affective style in healthy infants, children, and adults and some clinical populations when symptoms are reduced or in remission. We measured self-reported trait shyness and sociability, concurrent depressive mood, and frontal brain electrical activity (EEG) at rest and in anticipation of a speech task in a non-clinical sample of healthy young adults selected for high and low social anxiety. Although the patterns of resting and reactive frontal EEG asymmetry did not distinguish among individual differences in social anxiety, the pattern of resting frontal EEG asymmetry was related to trait shyness after controlling for concurrent depressive mood. Individuals who reported a higher degree of shyness were likely to exhibit greater relative right frontal EEG activity at rest. However, trait shyness was not related to frontal EEG asymmetry measured during the speech-preparation task, even after controlling for concurrent depressive mood. These findings replicate and extend prior work on resting frontal EEG asymmetry and individual differences in affective style in adults. Findings also highlight the importance of considering concurrent emotional states of participants when examining psychophysiological correlates of personality. PMID:18728822

Neural correlates of brain state in chronic ischemia and stroke: combined resting state electroencephalogram and transcranial Doppler ultrasonographic study.

PubMed

Martynova, Olga V; Portnova, Galina V; Gladun, Ksenya V

2017-02-08

Clinical neurology is constantly searching for reliable indices of ischemic brain damage to prevent a possible development of stroke. We suggest that resting state electroencephalogram (rsEEG) with respect to other clinical data may provide important information about the severity of ischemia. We carried out correlation analysis of rsEEG, data of transcranial Doppler ultrasonography of head vessels, and clinical assessment scores collected from healthy volunteers and four groups of patients with mild chronic microvascular ischemia (CMI-1), moderate CMI (CMI-2), severe atrophy of the cerebral hemisphere, ischemic stroke in the left middle cerebral artery stroke, and ischemic stroke in the right middle cerebral artery stroke. Using independent component analysis and k-mean clustering of EEG data, we observed prominent changes in rsEEG reflected in specific distributions of spectral peaks in all groups of patients. We found a significant correlation of EEG spectral distribution and the blood flow velocity in coronal arteries, which was also affected by the severity of ischemia and the localization of stroke. Moreover, EEG spectral distribution was more indicative of early stages of ischemia than the blood flow velocity. Our data support the hypothesis that rsEEG may reflect altered neural activity caused by ischemic brain damage.

Functional magnetic resonance imaging.

PubMed

Buchbinder, Bradley R

2016-01-01

Functional magnetic resonance imaging (fMRI) maps the spatiotemporal distribution of neural activity in the brain under varying cognitive conditions. Since its inception in 1991, blood oxygen level-dependent (BOLD) fMRI has rapidly become a vital methodology in basic and applied neuroscience research. In the clinical realm, it has become an established tool for presurgical functional brain mapping. This chapter has three principal aims. First, we review key physiologic, biophysical, and methodologic principles that underlie BOLD fMRI, regardless of its particular area of application. These principles inform a nuanced interpretation of the BOLD fMRI signal, along with its neurophysiologic significance and pitfalls. Second, we illustrate the clinical application of task-based fMRI to presurgical motor, language, and memory mapping in patients with lesions near eloquent brain areas. Integration of BOLD fMRI and diffusion tensor white-matter tractography provides a road map for presurgical planning and intraoperative navigation that helps to maximize the extent of lesion resection while minimizing the risk of postoperative neurologic deficits. Finally, we highlight several basic principles of resting-state fMRI and its emerging translational clinical applications. Resting-state fMRI represents an important paradigm shift, focusing attention on functional connectivity within intrinsic cognitive networks. © 2016 Elsevier B.V. All rights reserved.

Induction of neuroplasticity and recovery in post-stroke aphasia by non-invasive brain stimulation

PubMed Central

Shah, Priyanka P.; Szaflarski, Jerzy P.; Allendorfer, Jane; Hamilton, Roy H.

2013-01-01

Stroke victims tend to prioritize speaking, writing, and walking as the three most important rehabilitation goals. Of note is that two of these goals involve communication. This underscores the significance of developing successful approaches to aphasia treatment for the several hundred thousand new aphasia patients each year and over 1 million stroke survivors with chronic aphasia in the U.S. alone. After several years of growth as a research tool, non-invasive brain stimulation (NBS) is gradually entering the arena of clinical aphasiology. In this review, we first examine the current state of knowledge of post-stroke language recovery including the contributions from the dominant and non-dominant hemispheres. Next, we briefly discuss the methods and the physiologic basis of the use of inhibitory and excitatory repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) as research tools in patients who experience post-stroke aphasia. Finally, we provide a critical review of the most influential evidence behind the potential use of these two brain stimulation methods as clinical rehabilitative tools. PMID:24399952

Penfield's ceiling: Seeing brain injury through Galen's eyes.

PubMed

Adams, Zoe M; Fins, Joseph J

2017-08-22

The cathedral ceiling located in the entrance hall of the Montreal Neurological Institute, planned by its founder Wilder Penfield, has intrigued visitors since it was erected in 1934. Central to its charm is a cryptic comment by the ancient physician Galen of Pergamum, which refutes a dire Hippocratic aphorism about prognosis in brain injury. Galen's optimism, shared by Penfield, is curious from a fellow ancient. In this article, we use primary sources in Ancient Greek as well as secondary sources to not only examine the origins of Galen's epistemology but also, using a methodology in classics scholarship known as reception studies , illustrate how an awareness of this ancient debate can illuminate contemporary clinical contexts. While Galen based his prognostications on direct clinical observations like the Hippocratics, he also engaged in experimental and anatomic work in both animals and humans, which informed his views on neurologic states and outcomes. Penfield's memorialization of Galen is representative of the evolution of the neurosciences and the ongoing importance of evidence-based prognostication in severe brain injury. © 2017 American Academy of Neurology.

Statistical Analysis of Organ Morphometric Parameters and Weights in South Iranian Adult Autopsies.

PubMed

Gholamzadeh, Saeid; Zarenezhad, Mohammad; Montazeri, Mahmoud; Zareikordshooli, Marzieh; Sadeghi, Ghazaleh; Malekpour, Abdorrasoul; Hoseni, Sanaz; Bahrani, Mohammadreza; Hajatmand, Razieh

2017-05-01

Organ weight is one important indicator to discern normal from abnormal condition in forensic pathology as well as in clinical medicine. The present study aimed to investigate morphometric parameters and organ weights of southern Iranian adults, which can be fundamental sources to be compared to abnormal cases.Morphometric parameters and weights of 6 organs (heart, liver, kidney, spleen, appendix, and brain), which were harvested from 501 southern Iranian adults (385 males and 116 females) during ordinary postmortem examination, were measured.All the organs were heavier in males than in females. Heart, brain, spleen, and right kidney were significantly heavier in males compared to females, but no significant difference was observed between the 2 sexes regarding the weights of the rest of the organs. Moreover, brain and heart became heavier as one got older and most organs were heavier in middle-aged individuals compared to other age groups. Furthermore, various types of correlations were observed between different organs' weights and body parameters.These results can be useful anatomical data for autopsy investigations, clinical practices, and research in southern Iran.

Quality of life of victims of traumatic brain injury six months after the trauma.

PubMed

Vieira, Rita de Cássia Almeida; Hora, Edilene Curvelo; de Oliveira, Daniel Vieira de; Ribeiro, Maria do Carmo de Oliveira; de Sousa, Regina Márcia Cardoso

2013-01-01

to describe the quality of life of victims of traumatic brain injury six months after the event and to show the relationship between the results observed and the clinical, sociodemographic and return to productivity data. data were analyzed from 47 victims assisted in a trauma reference hospital in the municipality of Aracaju and monitored in an outpatient neurosurgery clinic. The data were obtained through analysis of the patient records and structured interviews, with the application of the World Health Organization Quality of Life, brief version, questionnaire. the victims presented positive perceptions of their quality of life, and the physical domain presented the highest mean value (68.4±22.9). Among the sociodemographic characteristics, a statistically significant correlation was found between marital status and the psychological domain. However, the return to productivity was related to all the domains. the return to productivity was an important factor for the quality of life of the victims of traumatic brain injury and should direct the public policies in promoting the health of these victims.

Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity.

PubMed

Ballard, Peter; Yates, James W T; Yang, Zhenfan; Kim, Dong-Wan; Yang, James Chih-Hsin; Cantarini, Mireille; Pickup, Kathryn; Jordan, Angela; Hickey, Mike; Grist, Matthew; Box, Matthew; Johnström, Peter; Varnäs, Katarina; Malmquist, Jonas; Thress, Kenneth S; Jänne, Pasi A; Cross, Darren

2016-10-15

Approximately one-third of patients with non-small cell lung cancer (NSCLC) harboring tumors with EGFR-tyrosine kinase inhibitor (TKI)-sensitizing mutations (EGFRm) experience disease progression during treatment due to brain metastases. Despite anecdotal reports of EGFR-TKIs providing benefit in some patients with EGFRm NSCLC brain metastases, there is a clinical need for novel EGFR-TKIs with improved efficacy against brain lesions. We performed preclinical assessments of brain penetration and activity of osimertinib (AZD9291), an oral, potent, irreversible EGFR-TKI selective for EGFRm and T790M resistance mutations, and other EGFR-TKIs in various animal models of EGFR-mutant NSCLC brain metastases. We also present case reports of previously treated patients with EGFRm-advanced NSCLC and brain metastases who received osimertinib in the phase I/II AURA study (NCT01802632). Osimertinib demonstrated greater penetration of the mouse blood-brain barrier than gefitinib, rociletinib (CO-1686), or afatinib, and at clinically relevant doses induced sustained tumor regression in an EGFRm PC9 mouse brain metastases model; rociletinib did not achieve tumor regression. Under positron emission tomography micro-dosing conditions, [ 11 C]osimertinib showed markedly greater exposure in the cynomolgus monkey brain than [ 11 C]rociletinib and [ 11 C]gefitinib. Early clinical evidence of osimertinib activity in previously treated patients with EGFRm-advanced NSCLC and brain metastases is also reported. Osimertinib may represent a clinically significant treatment option for patients with EGFRm NSCLC and brain metastases. Further investigation of osimertinib in this patient population is ongoing. Clin Cancer Res; 22(20); 5130-40. ©2016 AACR. ©2016 American Association for Cancer Research.

[Mild head injury in children and adults: Diagnostic challenges in the emergency department].

PubMed

Leidel, B A; Lindner, T; Wolf, S; Bogner, V; Steinbeck, A; Börner, N; Peiser, C; Audebert, H J; Biberthaler, P; Kanz, K-G

2015-06-01

Mild head injuries are one of the most frequent reasons for attending emergency departments and are particularly challenging in different ways. While clinically important injuries are infrequent, delayed or missed injuries may lead to fatal consequences. The initial mostly inconspicuous appearance may not reflect the degree of intracranial injury and computed tomography (CT) is necessary to rule out covert injuries. Furthermore, infants and young children with a lack of or rudimentary cognitive and language development are challenging, especially for those examiners not familiar with pediatric care. Established check lists of clinical risk factors for children and adults regarding traumatic brain injuries allow specific and rational decision-making for cranial CT imaging. Clinically important intracranial injuries can be reliably detected and unnecessary radiation exposure avoided at the same time.

[Mild head injury in children and adults. Diagnostic challenges in the emergency department].

PubMed

Leidel, B A; Lindner, T; Wolf, S; Bogner, V; Steinbeck, A; Börner, N; Peiser, C; Audebert, H J; Biberthaler, P; Kanz, K-G

2015-01-01

Mild head injuries are one of the most frequent reasons for attending emergency departments and are particularly challenging in different ways. While clinically important injuries are infrequent, delayed or missed injuries may lead to fatal consequences. The initial mostly inconspicuous appearance may not reflect the degree of intracranial injury and computed tomography (CT) is necessary to rule out covert injuries. Furthermore, infants and young children with a lack of or rudimentary cognitive and language development are challenging, especially for those examiners not familiar with pediatric care. Established check lists of clinical risk factors for children and adults regarding traumatic brain injuries allow specific and rational decision-making for cranial CT imaging. Clinically important intracranial injuries can be reliably detected and unnecessary radiation exposure avoided at the same time.

In silico cancer modeling: is it ready for primetime?

PubMed Central

Deisboeck, Thomas S; Zhang, Le; Yoon, Jeongah; Costa, Jose

2011-01-01

SUMMARY At the dawn of the era of personalized, systems-driven medicine, computational or in silico modeling and the simulation of disease processes is becoming increasingly important for hypothesis generation and data integration in both experiment and clinics alike. Arguably, this is nowhere more visible than in oncology. To illustrate the field’s vast potential as well as its current limitations we briefly review selected works on modeling malignant brain tumors. Implications for clinical practice, including trial design and outcome prediction are also discussed. PMID:18852721

Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis

PubMed Central

Jenkins, Trisha A.; Nguyen, Jason C. D.; Polglaze, Kate E.; Bertrand, Paul P.

2016-01-01

The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. Manipulation of tryptophan levels, acutely or chronically, by depletion or supplementation, is an experimental procedure for modifying peripheral and central serotonin levels. These studies have allowed us to establish the role of serotonin in higher order brain function in both preclinical and clinical situations and have precipitated the finding that low brain serotonin levels are associated with poor memory and depressed mood. The gut-brain axis is a bi-directional system between the brain and gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. An influence of gut microbiota on behaviour is becoming increasingly evident, as is the extension to tryptophan and serotonin, producing a possibility that alterations in the gut may be important in the pathophysiology of human central nervous system disorders. In this review we will discuss the effect of manipulating tryptophan on mood and cognition, and discuss a possible influence of the gut-brain axis. PMID:26805875

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.

Intelligence deficits in Chinese patients with brain tumor: the impact of tumor resection.

PubMed

Shen, Chao; Xie, Rong; Cao, Xiaoyun; Bao, Weimin; Yang, Bojie; Mao, Ying; Gao, Chao

2013-01-01

Intelligence is much important for brain tumor patients after their operation, while the reports about surgical related intelligence deficits are not frequent. It is not only theoretically important but also meaningful for clinical practice. Wechsler Adult Intelligence Scale was employed to evaluate the intelligence of 103 patients with intracranial tumor and to compare the intelligence quotient (IQ), verbal IQ (VIQ), and performance IQ (PIQ) between the intracerebral and extracerebral subgroups. Although preoperative intelligence deficits appeared in all subgroups, IQ, VIQ, and PIQ were not found to have any significant difference between the intracerebral and extracerebral subgroups, but with VIQ lower than PIQ in all the subgroups. An immediate postoperative follow-up demonstrated a decline of IQ and PIQ in the extracerebral subgroup, but an improvement of VIQ in the right intracerebral subgroup. Pituitary adenoma resection exerted no effect on intelligence. In addition, age, years of education, and tumor size were found to play important roles. Brain tumors will impair IQ, VIQ, and PIQ. The extracerebral tumor resection can deteriorate IQ and PIQ. However, right intracerebral tumor resection is beneficial to VIQ, and transsphenoidal pituitary adenoma resection performs no effect on intelligence.

Cerebral Amyloid Angiopathy: An Important Differential Diagnosis of Stroke in the Elderly

PubMed Central

AZMIN, Shahrul; OSMAN, Syazarina Sharis; MUKARI, Shahizon; SAHATHEVAN, Ramesh

2015-01-01

Cerebral amyloid angiopathy (CAA) accounts for approximately 10–20% of spontaneous intracerebral haemorrhage (ICH). This figure is thought to be higher in the elderly population. With the increasing life expectancy of our population, we anticipate that the prevalence of CAA- related ICH will increase in tandem. Although CAA-related ICH and hypertension-related ICH are distinct entities based on histopathology and imaging, the clinical presentation of the two conditions is similar. The use of brain computed tomography (CT) scans remain the ICH imaging modality of choice in Malaysia due to its availability, cost, and sensitivity in detecting acute bleeds. On the other hand, the use of brain magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) sequencing enables the clinician to determine the presence of chronic blood products in the brain, especially clinically silent microbleeds associated with CAA. However, the use of brain MRI scans in our country is limited and leads to a blurring of lines when differentiating between hypertension-related ICH and CAA-related ICH. How this misrepresentation affects the management of these conditions is unclear. In this study, we present two cases of ICH to illustrate this point and to serve as a springboard to question current practice and promote discussion. PMID:25892953

Hydrogen sulfide therapy in brain diseases: from bench to bedside

PubMed Central

Zhang, Ju-yi; Ding, Yi-ping; Wang, Zhong; Kong, Yan; Gao, Rong; Chen, Gang

2017-01-01

Hydrogen sulfide (H2S) has been recognized and studied for nearly 300 years, but past researches mainly focus on its toxicity effect. During the past two decades, the majority of researches have reported that H2S is a novel endogenous gaseous signal molecule in organisms, and play an important role in various systems and diseases. H2S is mainly produced by three enzymes, including cystathionine β-synthase, cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase along with cysteine aminotransferase. H2S had been firstly reported as a neuromodulator in the brain, because of its essential role in the facilitating hippocampal long-term potentiation at physiological concentration. It is subsequently reported that H2S may have relevance to neurologic disorders through antioxidative, anti-inflammatory, anti-apoptotic and additional effects. Recent basic medical studies and preclinical studies on neurologic diseases have demonstrated that the administration of H2S at physiological or pharmacological levels attenuates brain injury. However, the neuroprotective effect of H2S is concentration-dependent, only a comparatively low dose of H2S can provide beneficial effect. Herein, we review the neuroprotevtive role of H2S therapy in brain diseases from its mechanism to clinical application in animal and human subjects, and therefore provide the potential strategies for further clinical treatment. PMID:28744364

PET evaluation of late cerebral effect in advanced radiation therapy techniques for cranial base tumors.

PubMed

Alongi, Pierpaolo; Iaccarino, Leonardo; Losa, Marco; Del Vecchio, Antonella; Gerevini, Simonetta; Plebani, Valentina; Di Muzio, Nadia; Mortini, Pietro; Gianolli, Luigi; Perani, Daniela

2018-05-25

Even though the benefits of radiation therapy are well established, it is important to recognize the broad spectrum of radiation-induced changes, particularly in the central nervous system. The possible damage to the brain parenchyma may have clinical consequences and in particular cognitive impairment might be one of the major complication of radiotherapy. To date, no studies have investigated the effects of focal radiation therapy on brain structure and function together with the assessment of their clinical outcomes at a long follow-up. In this prospective study, we evaluated in six patients the possible brain late effects after radiation therapy, using a standardized neuropsychological battery, MRI and 18F-FDG PET using SPM and semi-quantitative methods, in patients affected by cranial base tumors who underwent gamma knife or tomotherapy. Neuropsychological examinations showed no cognitive impairment after the treatment. In all patients, both MRI assessment and 18F-FDG-PET did not reveal any local or distant anatomical and metabolic late effects. The present study support the safety of advanced radiation therapy techniques. 18F-FDG-PET, using SPM and semi-quantitative methods, might be a valuable tool to evaluate the cerebral radiotoxicity in patients treated for brain neoplasms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Disclosing incidental findings in brain research: the rights of minors in decision-making.

PubMed

Di Pietro, Nina C; Illes, Judy

2013-11-01

MRI is used routinely in research with children to generate new knowledge about brain development. The detection of unexpected brain abnormalities (incidental findings; IFs) in these studies presents unique challenges. While key issues surrounding incidence and significance, duty of care, and burden of disclosure have been addressed substantially for adults, less empirical data and normative analyses exist for minors who participate in minimal risk research. To identify ethical concerns and fill existing gaps, we conducted a comprehensive review of papers that focused explicitly on the discovery of IFs in minors. The discourse in the 21 papers retrieved for this analysis amply covered practical issues such as informed consent and screening, difficulties in ascertaining clinical significance, the economic costs and burden of responsibility on researchers, and risks (physical or psychological). However, we found little discussion about the involvement of minors in decisions about disclosure of IFs in the brain, especially for IFs of low clinical significance. In response, we propose a framework for managing IFs that integrates practical considerations with explicit appreciation of rights along the continuum of maturity. This capacity-adjusted framework emphasizes the importance of involving competent minors and respecting their right to make decisions about disclosure. Copyright © 2013 Wiley Periodicals, Inc.

Clinical Correlates and Prognostic Significance of Lateralized Periodic Discharges in Patients Without Acute or Progressive Brain Injury: A Case-Control Study.

PubMed

Sainju, Rup K; Manganas, Louis N; Gilmore, Emily J; Petroff, Ognen A; Rampal, Nishi; Hirsch, Lawrence J; Gaspard, Nicolas

2015-12-01

Lateralized periodic discharges (LPDs, also known as periodic lateralized epileptiform discharges) in conjunction with acute brain injuries are known to be associated with worse prognosis but little is known about their importance in absence of such acute injuries. We studied the clinical correlates and outcome of patients with LPDs in the absence of acute or progressive brain injury. This is a case-control study of 74 patients with no acute brain injury undergoing continuous EEG monitoring, half with LPDs and half without, matched for age and etiology of remote brain injury, if any, or history of epilepsy. Lateralized periodic discharges were found in 145/1785 (8.1%) of subjects; 37/145 (26%) had no radiologic evidence of acute or progressive brain injury. Those with LPDs were more likely to have abnormal consciousness (86% vs. 57%; P = 0.005), seizures (70% vs. 24%; P = 0.0002), and functional decline (62% vs. 27%; P = 0.005), and were less likely to be discharged home (24% vs. 62%; P = 0.002). On multivariate analysis, LPDs and status epilepticus were associated with abnormal consciousness (P = 0.009; odds ratio = 5.2, 95% CI = 1.60-20.00 and P = 0.017; odds ratio = 5.0, 95% CI = 1.4-21.4); and LPDs were independently associated with functional decline (P = 0.001; odds ratio = 4.8, 95% CI = 1.6-15.4) and lower likelihood of being discharged home (P = 0.009; odds ratio = 0.2, 95% CI = 0.04-0.6). Despite absence of acute or progressive brain injury, LPDs were independently associated with abnormal consciousness and worse outcome at hospital discharge.

[Introduction of neuroethics: out of clinic, beyond academia in human brain research].

PubMed

Fukushi, Tamami; Sakura, Osamu

2008-11-01

Higher cognitive function in human brain is one of well-developed fields of neuroscience research in the 21st century. Especially functional magnetic resonance imaging (fMRI) and near infrared recording system have brought so many non-clinical researchers whose background is such as cognitive psychology, economics, politics, pedagogy, and so on, to the human brain mapping study. Authors have introduced the ethical issues related to incidental findings during the fMRI recording for non-clinical purpose, which is a typical problem derived from such expanded human brain research under non clinical condition, that is, neuroethics. In the present article we would introduce neuroethical issues in contexts of "out of clinic" and "beyond academia".

PET evaluation of the dopamine system of the human brain

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

Volkow, N.D.; Fowler, J.S.; Gatley, S.

1996-07-01

Dopamine plays a pivotal role in the regulation and control of movement, motivation and cognition. It also is closely linked to reward, reinforcement and addiction. Abnormalities in brain dopamine are associated with many neurological and psychiatric disorders including Parkinson`s disease, schizophrenia and substance abuse. This close association between dopamine and neurological and psychiatric diseases and with substance abuse make it an important topic in research in the neurosciences and an important molecular target in drug development. PET enables the direct measurement of components of the dopamine system in the living human brain. It relies on radiotracers which label dopamine receptors,more » dopamine transporters, precursors of dopamine or compounds which have specificity for the enzymes which degrade dopamine. Additionally, by using tracers that provide information on regional brain metabolism or blood flow as well as neurochemically specific pharmacological interventions, PET can be used to assess the functional consequences of change in brain dopamine activity. PET dopamine measurements have been used to investigate the normal human brain and its involvement in psychiatric and neurological diseases. It has also been used in psychopharmacological research to investigate dopamine drugs used in the treatment of Parkinson`s disease and of schizophrenia as well as to investigate the effects of drugs of abuse on the dopamine system. Since various functional and neurochemical parameters can be studied in the same subject, PET enables investigation of the functional integrity of the dopamine system in the human brain and investigation of the interactions of dopamine with other neurotransmitters. This paper summarizes the different tracers and experimental strategies developed to evaluate the various elements of the dopamine system in the human brain with PET and their applications to clinical research. 254 refs., 7 figs., 3 tabs.« less

Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate.

PubMed

Bondulich, Marie K; Guo, Tong; Meehan, Christopher; Manion, John; Rodriguez Martin, Teresa; Mitchell, Jacqueline C; Hortobagyi, Tibor; Yankova, Natalia; Stygelbout, Virginie; Brion, Jean-Pierre; Noble, Wendy; Hanger, Diane P

2016-08-01

Human neurodegenerative tauopathies exhibit pathological tau aggregates in the brain along with diverse clinical features including cognitive and motor dysfunction. Post-translational modifications including phosphorylation, ubiquitination and truncation, are characteristic features of tau present in the brain in human tauopathy. We have previously reported an N-terminally truncated form of tau in human brain that is associated with the development of tauopathy and is highly phosphorylated. We have generated a new mouse model of tauopathy in which this human brain-derived, 35 kDa tau fragment (Tau35) is expressed in the absence of any mutation and under the control of the human tau promoter. Most existing mouse models of tauopathy overexpress mutant tau at levels that do not occur in human neurodegenerative disease, whereas Tau35 transgene expression is equivalent to less than 10% of that of endogenous mouse tau. Tau35 mice recapitulate key features of human tauopathies, including aggregated and abnormally phosphorylated tau, progressive cognitive and motor deficits, autophagic/lysosomal dysfunction, loss of synaptic protein, and reduced life-span. Importantly, we found that sodium 4-phenylbutyrate (Buphenyl®), a drug used to treat urea cycle disorders and currently in clinical trials for a range of neurodegenerative diseases, reverses the observed abnormalities in tau and autophagy, behavioural deficits, and loss of synapsin 1 in Tau35 mice. Our results show for the first time that, unlike other tau transgenic mouse models, minimal expression of a human disease-associated tau fragment in Tau35 mice causes a profound and progressive tauopathy and cognitive changes, which are rescued by pharmacological intervention using a clinically approved drug. These novel Tau35 mice therefore represent a highly disease-relevant animal model in which to investigate molecular mechanisms and to develop novel treatments for human tauopathies. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Development of clinical recommendations for progressive return to activity after military mild traumatic brain injury: guidance for rehabilitation providers.

PubMed

McCulloch, Karen L; Goldman, Sarah; Lowe, Lynn; Radomski, Mary Vining; Reynolds, John; Shapiro, Rita; West, Therese A

2015-01-01

Previously published mild traumatic brain injury (mTBI) management guidelines provide very general recommendations to return individuals with mTBI to activity. This lack of specific guidance creates variation in military rehabilitation. The Office of the Army Surgeon General in collaboration with the Defense and Veterans Brain Injury Center, a component center of the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury, convened an expert working group to review the existing literature and propose clinical recommendations that standardize rehabilitation activity progression following mTBI. A Progressive Activity Working Group consisted of 11 Department of Defense representatives across all service branches, 7 Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury representatives, and 8 academic/research/civilian experts with experience assessing and treating individuals with mTBI for return to activity. An expert working group meeting included the Progressive Activity Working Group and 15 additional subject matter experts. In February 2012, the Progressive Activity Working Group was established to determine the need and purpose of the rehabilitation recommendations. Following literature review, a table was created on the basis of the progression from the Zurich consensus statement on concussion in sport. Issues were identified for discussion with a meeting of the larger expert group during a July 2012 conference. Following development of rehabilitation guidance, the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury coordinated a similar process for military primary care providers. End products for rehabilitation and primary care providers include specific recommendations for return to activity after concussion. A 6-stage progression specifies activities in physical, cognitive, and balance/vestibular domains and allows for resumption of activity for those with low-level or preinjury symptom complaints. The clinical recommendations for progressive return to activity represent an important effort to standardize activity progression across functional domains and offer providers duty-specific activities to incorporate into intervention. Recommendations were released in January 2014.

Resected Brain Tissue, Seizure Onset Zone and Quantitative EEG Measures: Towards Prediction of Post-Surgical Seizure Control

PubMed Central

Andrzejak, Ralph G.; Hauf, Martinus; Pollo, Claudio; Müller, Markus; Weisstanner, Christian; Wiest, Roland; Schindler, Kaspar

2015-01-01

Background Epilepsy surgery is a potentially curative treatment option for pharmacoresistent patients. If non-invasive methods alone do not allow to delineate the epileptogenic brain areas the surgical candidates undergo long-term monitoring with intracranial EEG. Visual EEG analysis is then used to identify the seizure onset zone for targeted resection as a standard procedure. Methods Despite of its great potential to assess the epileptogenicty of brain tissue, quantitative EEG analysis has not yet found its way into routine clinical practice. To demonstrate that quantitative EEG may yield clinically highly relevant information we retrospectively investigated how post-operative seizure control is associated with four selected EEG measures evaluated in the resected brain tissue and the seizure onset zone. Importantly, the exact spatial location of the intracranial electrodes was determined by coregistration of pre-operative MRI and post-implantation CT and coregistration with post-resection MRI was used to delineate the extent of tissue resection. Using data-driven thresholding, quantitative EEG results were separated into normally contributing and salient channels. Results In patients with favorable post-surgical seizure control a significantly larger fraction of salient channels in three of the four quantitative EEG measures was resected than in patients with unfavorable outcome in terms of seizure control (median over the whole peri-ictal recordings). The same statistics revealed no association with post-operative seizure control when EEG channels contributing to the seizure onset zone were studied. Conclusions We conclude that quantitative EEG measures provide clinically relevant and objective markers of target tissue, which may be used to optimize epilepsy surgery. The finding that differentiation between favorable and unfavorable outcome was better for the fraction of salient values in the resected brain tissue than in the seizure onset zone is consistent with growing evidence that spatially extended networks might be more relevant for seizure generation, evolution and termination than a single highly localized brain region (i.e. a “focus”) where seizures start. PMID:26513359

Flexible modulation of network connectivity related to cognition in Alzheimer's disease.

PubMed

McLaren, Donald G; Sperling, Reisa A; Atri, Alireza

2014-10-15

Functional neuroimaging tools, such as fMRI methods, may elucidate the neural correlates of clinical, behavioral, and cognitive performance. Most functional imaging studies focus on regional task-related activity or resting state connectivity rather than how changes in functional connectivity across conditions and tasks are related to cognitive and behavioral performance. To investigate the promise of characterizing context-dependent connectivity-behavior relationships, this study applies the method of generalized psychophysiological interactions (gPPI) to assess the patterns of associative-memory-related fMRI hippocampal functional connectivity in Alzheimer's disease (AD) associated with performance on memory and other cognitively demanding neuropsychological tests and clinical measures. Twenty-four subjects with mild AD dementia (ages 54-82, nine females) participated in a face-name paired-associate encoding memory study. Generalized PPI analysis was used to estimate the connectivity between the hippocampus and the whole brain during encoding. The difference in hippocampal-whole brain connectivity between encoding novel and encoding repeated face-name pairs was used in multiple-regression analyses as an independent predictor for 10 behavioral, neuropsychological and clinical tests. The analysis revealed connectivity-behavior relationships that were distributed, dynamically overlapping, and task-specific within and across intrinsic networks; hippocampal-whole brain connectivity-behavior relationships were not isolated to single networks, but spanned multiple brain networks. Importantly, these spatially distributed performance patterns were unique for each measure. In general, out-of-network behavioral associations with encoding novel greater than repeated face-name pairs hippocampal-connectivity were observed in the default-mode network, while correlations with encoding repeated greater than novel face-name pairs hippocampal-connectivity were observed in the executive control network (p<0.05, cluster corrected). Psychophysiological interactions revealed significantly more extensive and robust associations between paired-associate encoding task-dependent hippocampal-whole brain connectivity and performance on memory and behavioral/clinical measures than previously revealed by standard activity-behavior analysis. Compared to resting state and task-activation methods, gPPI analyses may be more sensitive to reveal additional complementary information regarding subtle within- and between-network relations. The patterns of robust correlations between hippocampal-whole brain connectivity and behavioral measures identified here suggest that there are 'coordinated states' in the brain; that the dynamic range of these states is related to behavior and cognition; and that these states can be observed and quantified, even in individuals with mild AD. Copyright © 2014 Elsevier Inc. All rights reserved.

Congenital brain infections.

PubMed

Arbelaez, Andres; Restrepo, Feliza; Davila, Jorge; Castillo, Mauricio

2014-06-01

Pediatric congenital intracranial infections are a group of different and important entities that constitute a small percentage of all pediatric infections. The causal factors and clinical presentations are different in children compared with adults. They require early recognition because delay diagnosis and initiation of treatment may have catastrophic consequences. Despite improvements in prenatal screening, vaccine safety, and antibiotics, infections of the central nervous system remain an important cause of neurological disabilities worldwide. This article reviews the most common congenital infections and their imaging findings.

Brain Activity in Patients With Adductor Spasmodic Dysphonia Detected by Functional Magnetic Resonance Imaging.

PubMed

Kiyuna, Asanori; Kise, Norimoto; Hiratsuka, Munehisa; Kondo, Shunsuke; Uehara, Takayuki; Maeda, Hiroyuki; Ganaha, Akira; Suzuki, Mikio

2017-05-01

Spasmodic dysphonia (SD) is considered a focal dystonia. However, the detailed pathophysiology of SD remains unclear, despite the detection of abnormal activity in several brain regions. The aim of this study was to clarify the pathophysiological background of SD. This is a case-control study. Both task-related brain activity measured by functional magnetic resonance imaging by reading the five-digit numbers and resting-state functional connectivity (FC) measured by 150 T2-weighted echo planar images acquired without any task were investigated in 12 patients with adductor SD and in 16 healthy controls. The patients with SD showed significantly higher task-related brain activation in the left middle temporal gyrus, left thalamus, bilateral primary motor area, bilateral premotor area, bilateral cerebellum, bilateral somatosensory area, right insula, and right putamen compared with the controls. Region of interest voxel FC analysis revealed many FC changes within the cerebellum-basal ganglia-thalamus-cortex loop in the patients with SD. Of the significant connectivity changes between the patients with SD and the controls, the FC between the left thalamus and the left caudate nucleus was significantly correlated with clinical parameters in SD. The higher task-related brain activity in the insula and cerebellum was consistent with previous neuroimaging studies, suggesting that these areas are one of the unique characteristics of phonation-induced brain activity in SD. Based on FC analysis and their significant correlations with clinical parameters, the basal ganglia network plays an important role in the pathogenesis of SD. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Neural stimulation for Parkinson's disease: current therapies and future directions.

PubMed

Neimat, Joseph S; Hamani, Clement; Lozano, Andres M

2006-01-01

Neural stimulation has rapidly become an integral tool in the treatment of Parkinson's disease and other movement disorders. Today it serves as an important adjunct to medical therapy that continues to gain applicability to patients in whom the disease has progressed significantly. Studies have demonstrated efficacy in several deep-brain targets, with prolonged benefit exceeding 5-year follow-up times. Continuing study is teaching us more about the mechanism of deep-brain stimulation effect. New targets, which may treat the disease more successfully, are being examined. In this review, the history of deep-brain stimulation, the rationale for the known targets of stimulation; the clinical evidence demonstrating their benefit and, finally, future perspectives on new treatments that are being investigated and may have an impact on the field are discussed.

Clinical study and numerical simulation of brain cancer dynamics under radiotherapy

NASA Astrophysics Data System (ADS)

Nawrocki, S.; Zubik-Kowal, B.

2015-05-01

We perform a clinical and numerical study of the progression of brain cancer tumor growth dynamics coupled with the effects of radiotherapy. We obtained clinical data from a sample of brain cancer patients undergoing radiotherapy and compare it to our numerical simulations to a mathematical model of brain tumor cell population growth influenced by radiation treatment. We model how the body biologically receives a physically delivered dose of radiation to the affected tumorous area in the form of a generalized LQ model, modified to account for the conversion process of sublethal lesions into lethal lesions at high radiation doses. We obtain good agreement between our clinical data and our numerical simulations of brain cancer progression given by the mathematical model, which couples tumor growth dynamics and the effect of irradiation. The correlation, spanning a wide dataset, demonstrates the potential of the mathematical model to describe the dynamics of brain tumor growth influenced by radiotherapy.

Neuromonitoring after major neurosurgical procedures.

PubMed

Messerer, M; Daniel, R T; Oddo, M

2012-07-01

Postoperative care of major neurosurgical procedures is aimed at the prevention, detection and treatment of secondary brain injury. This consists of a series of pathological events (i.e. brain edema and intracranial hypertension, cerebral hypoxia/ischemia, brain energy dysfunction, non-convulsive seizures) that occur early after the initial insult and surgical intervention and may add further burden to primary brain injury and thus impact functional recovery. Management of secondary brain injury requires specialized neuroscience intensive care units (ICU) and continuous advanced monitoring of brain physiology. Monitoring of intracranial pressure (ICP) is a mainstay of care and is recommended by international guidelines. However, ICP monitoring alone may be insufficient to detect all episodes of secondary brain insults. Additional invasive (i.e. brain tissue PO2, cerebral microdialysis, regional cerebral blood flow) and non-invasive (i.e. transcranial doppler, near-infrared spectroscopy, EEG) brain monitoring devices might complement ICP monitoring and help clinicians to target therapeutic interventions (e.g. management of cerebral perfusion pressure, blood transfusion, glucose control) to patient-specific pathophysiology. Several independent studies demonstrate such multimodal approach may optimize patient care after major neurosurgical procedures. The aim of this review is to evaluate some of the available monitoring systems and summarize recent important data showing the clinical utility of multimodal neuromonitoring for the management of main acute neurosurgical conditions, including traumatic brain injury, subarachnoid hemorrhage and stroke.

Effect of clinical decision rules, patient cost and malpractice information on clinician brain CT image ordering: a randomized controlled trial.

PubMed

Gimbel, Ronald W; Pirrallo, Ronald G; Lowe, Steven C; Wright, David W; Zhang, Lu; Woo, Min-Jae; Fontelo, Paul; Liu, Fang; Connor, Zachary

2018-03-12

The frequency of head computed tomography (CT) imaging for mild head trauma patients has raised safety and cost concerns. Validated clinical decision rules exist in the published literature and on-line sources to guide medical image ordering but are often not used by emergency department (ED) clinicians. Using simulation, we explored whether the presentation of a clinical decision rule (i.e. Canadian CT Head Rule - CCHR), findings from malpractice cases related to clinicians not ordering CT imaging in mild head trauma cases, and estimated patient out-of-pocket cost might influence clinician brain CT ordering. Understanding what type and how information may influence clinical decision making in the ordering advanced medical imaging is important in shaping the optimal design and implementation of related clinical decision support systems. Multi-center, double-blinded simulation-based randomized controlled trial. Following standardized clinical vignette presentation, clinicians made an initial imaging decision for the patient. This was followed by additional information on decision support rules, malpractice outcome review, and patient cost; each with opportunity to modify their initial order. The malpractice and cost information differed by assigned group to test the any temporal relationship. The simulation closed with a second vignette and an imaging decision. One hundred sixteen of the 167 participants (66.9%) initially ordered a brain CT scan. After CCHR presentation, the number of clinicians ordering a CT dropped to 76 (45.8%), representing a 21.1% reduction in CT ordering (P = 0.002). This reduction in CT ordering was maintained, in comparison to initial imaging orders, when presented with malpractice review information (p = 0.002) and patient cost information (p = 0.002). About 57% of clinicians changed their order during study, while 43% never modified their imaging order. This study suggests that ED clinician brain CT imaging decisions may be influenced by clinical decision support rules, patient out-of-pocket cost information and findings from malpractice case review. NCT03449862 , February 27, 2018, Retrospectively registered.

Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases.

PubMed

Sun, Bao-Liang; Wang, Li-Hua; Yang, Tuo; Sun, Jing-Yi; Mao, Lei-Lei; Yang, Ming-Feng; Yuan, Hui; Colvin, Robert A; Yang, Xiao-Yi

2017-09-10

The belief that the vertebrate brain functions normally without classical lymphatic drainage vessels has been held for many decades. On the contrary, new findings show that functional lymphatic drainage does exist in the brain. The brain lymphatic drainage system is composed of basement membrane-based perivascular pathway, a brain-wide glymphatic pathway, and cerebrospinal fluid (CSF) drainage routes including sinus-associated meningeal lymphatic vessels and olfactory/cervical lymphatic routes. The brain lymphatic systems function physiological as a route of drainage for interstitial fluid (ISF) from brain parenchyma to nearby lymph nodes. Brain lymphatic drainage helps maintain water and ion balance of the ISF, waste clearance, and reabsorption of macromolecular solutes. A second physiological function includes communication with the immune system modulating immune surveillance and responses of the brain. These physiological functions are influenced by aging, genetic phenotypes, sleep-wake cycle, and body posture. The impairment and dysfunction of the brain lymphatic system has crucial roles in age-related changes of brain function and the pathogenesis of neurovascular, neurodegenerative, and neuroinflammatory diseases, as well as brain injury and tumors. In this review, we summarize the key component elements (regions, cells, and water transporters) of the brain lymphatic system and their regulators as potential therapeutic targets in the treatment of neurologic diseases and their resulting complications. Finally, we highlight the clinical importance of ependymal route-based targeted gene therapy and intranasal drug administration in the brain by taking advantage of the unique role played by brain lymphatic pathways in the regulation of CSF flow and ISF/CSF exchange. Copyright © 2017. Published by Elsevier Ltd.

Posterior reversible encephalopathy syndrome in Korean patients with systemic lupus erythematosus: risk factors and clinical outcome.

PubMed

Jung, S M; Moon, S-J; Kwok, S-K; Ju, J H; Park, K-S; Park, S-H; Kim, H-Y

2013-08-01

Posterior reversible encephalopathy syndrome (PRES) is an uncommon neurologic condition associated with systemic lupus erythematosus (SLE). This study aimed to demonstrate the risk factors and clinical outcome of PRES in patients with SLE. Fifteen patients with SLE were diagnosed with PRES by characteristic clinical manifestations and magnetic resonance imaging (MRI) features from 2000 to 2012. Clinical profiles and outcomes were assessed for this study population. Additionally, 48 SLE patients with neurologic symptoms who underwent brain MRI were included for comparative analyses. The median age and duration of SLE in patients with PRES was 27 and 6.1 years, respectively. Comparison between patients with and without PRES revealed significant differences in the presentation of hypertension and seizure, lupus nephritis with renal insufficiency, treatment with high-dose steroid and cyclophosphamide, recent transfusion, and lupus activity measured by SLE disease activity index. Renal failure was the single independent factor with a high odds ratio of 129.250 by multivariate analysis. Of 15 patients, four experienced relapse and two died of sepsis during hospitalization. Our results suggest that lupus nephritis with renal dysfunction and other related clinical conditions can precede the occurrence of PRES in patients with SLE. It is important to perform early brain imaging for a timely diagnosis of PRES when clinically suspected.

Experimental Evidences Supporting the Benefits of Exercise Training in Heart Failure.

PubMed

Ichige, Marcelo H A; Pereira, Marcelo G; Brum, Patrícia C; Michelini, Lisete C

2017-01-01

Heart Failure (HF), a common end point for many cardiovascular diseases, is a syndrome with a very poor prognosis. Although clinical trials in HF have achieved important outcomes in reducing mortality, little is known about functional mechanisms conditioning health improvement in HF patients. In parallel with clinical studies, basic science has been providing important discoveries to understand the mechanisms underlying the pathophysiology of HF, as well as to identify potential targets for the treatment of this syndrome. In spite of being the end-point of cardiovascular derangements caused by different etiologies, autonomic dysfunction, sympathetic hyperactivity, oxidative stress, inflammation and hormonal activation are common factors involved in the progression of this syndrome. Together these causal factors create a closed link between three important organs: brain, heart and the skeletal muscle. In the past few years, we and other groups have studied the beneficial effects of aerobic exercise training as a safe therapy to avoid the progression of HF. As summarized in this chapter, exercise training, a non-pharmacological tool without side effects, corrects most of the HF-induced neurohormonal and local dysfunctions within the brain, heart and skeletal muscles. These adaptive responses reverse oxidative stress, reduce inflammation, ameliorate neurohormonal control and improve both cardiovascular and skeletal muscle function, thus increasing the quality of life and reducing patients' morbimortality.

Avian reflex and electroencephalogram responses in different states of consciousness.

PubMed

Sandercock, Dale A; Auckburally, Adam; Flaherty, Derek; Sandilands, Victoria; McKeegan, Dorothy E F

2014-06-22

Defining states of clinical consciousness in animals is important in veterinary anaesthesia and in studies of euthanasia and welfare assessment at slaughter. The aim of this study was to validate readily observable reflex responses in relation to different conscious states, as confirmed by EEG analysis, in two species of birds under laboratory conditions (35-week-old layer hens (n=12) and 11-week-old turkeys (n=10)). We evaluated clinical reflexes and characterised electroencephalograph (EEG) activity (as a measure of brain function) using spectral analyses in four different clinical states of consciousness: conscious (fully awake), semi-conscious (sedated), unconscious-optimal (general anaesthesia), unconscious-sub optimal (deep hypnotic state), as well as assessment immediately following euthanasia. Jaw or neck muscle tone was the most reliable reflex measure distinguishing between conscious and unconscious states. Pupillary reflex was consistently observed until respiratory arrest. Nictitating membrane reflex persisted for a short time (<1 min) after respiratory arrest and brain death (isoelectric EEG). The results confirm that the nictitating membrane reflex is a conservative measure of death in poultry. Using spectral analyses of the EEG waveforms it was possible to readily distinguish between the different states of clinical consciousness. In all cases, when birds progressed from a conscious to unconscious state; total spectral power (PTOT) significantly increased, whereas median (F50) and spectral edge (F95) frequencies significantly decreased. This study demonstrates that EEG analysis can differentiate between clinical states (and loss of brain function at death) in birds and provides a unique integration of reflex responses and EEG activity. Copyright © 2014 Elsevier Inc. All rights reserved.

Regional brain injury on conventional and diffusion weighted MRI is associated with outcome after pediatric cardiac arrest.

PubMed

Fink, Ericka L; Panigrahy, A; Clark, R S B; Fitz, C R; Landsittel, D; Kochanek, P M; Zuccoli, G

2013-08-01

To assess regional brain injury on magnetic resonance imaging (MRI) after pediatric cardiac arrest (CA) and to associate regional injury with patient outcome and effects of hypothermia therapy for neuroprotection. We performed a retrospective chart review with prospective imaging analysis. Children between 1 week and 17 years of age who had a brain MRI in the first 2 weeks after CA without other acute brain injury between 2002 and 2008 were included. Brain MRI (1.5 T General Electric, Milwaukee, WI, USA) images were analyzed by 2 blinded neuroradiologists with adjudication; images were visually graded. Brain lobes, basal ganglia, thalamus, brain stem, and cerebellum were analyzed using T1, T2, and diffusion-weighted images (DWI). We examined 28 subjects with median age 1.9 years (IQR 0.4-13.0) and 19 (68 %) males. Increased intensity on T2 in the basal ganglia and restricted diffusion in the brain lobes were associated with unfavorable outcome (all P < 0.05). Therapeutic hypothermia had no effect on regional brain injury. Repeat brain MRI was infrequently performed but demonstrated evolution of lesions. Children with lesions in the basal ganglia on conventional MRI and brain lobes on DWI within the first 2 weeks after CA represent a group with increased risk of poor outcome. These findings may be important for developing neuroprotective strategies based on regional brain injury and for evaluating response to therapy in interventional clinical trials.

Adult hippocampal neurogenesis: an important target associated with antidepressant effects of exercise.

PubMed

Sun, Lina; Sun, Qingshan; Qi, Jinshun

2017-10-26

Depression is a prevalent devastating mental disorder that affects the normal life of patients and brings a heavy burden to whole society. Although many efforts have been made to attenuate depressive/anxiety symptoms, the current clinic antidepressants have limited effects. Scientists have long been making attempts to find some new strategies that can be applied as the alternative antidepressant therapy. Exercise, a widely recognized healthy lifestyle, has been suggested as a therapy that can relieve psychiatric stress. However, how exercise improves the brain functions and reaches the antidepressant target needs systematic summarization due to the complexity and heterogeneous feature of depression. Brain plasticity, especially adult neurogenesis in the hippocampus, is an important neurophysiology to facilitate animals for neurogenesis can occur in not only humans. Many studies indicated that an appropriate level of exercise can promote neurogenesis in the adult brains. In this article, we provide information about the antidepressant effects of exercise and its implications in adult neurogenesis. From the neurogenesis perspective, we summarize evidence about the effects of exercise in enhancing neurogenesis in the hippocampus through regulating growth factors, neurotrophins, neurotransmitters and metabolism as well as inflammations. Taken together, a large number of published works indicate the multiple benefits of exercise in the brain functions of animals, particularly brain plasticity like neurogenesis and synaptogenesis. Therefore, a new treatment method for depression therapy can be developed by regulating the exercise activity.

The role of "mixed" orexigenic and anorexigenic signals and autoantibodies reacting with appetite-regulating neuropeptides and peptides of the adipose tissue-gut-brain axis: relevance to food intake and nutritional status in patients with anorexia nervosa and bulimia nervosa.

PubMed

Smitka, Kvido; Papezova, Hana; Vondra, Karel; Hill, Martin; Hainer, Vojtech; Nedvidkova, Jara

2013-01-01

Eating disorders such as anorexia (AN) and bulimia nervosa (BN) are characterized by abnormal eating behavior. The essential aspect of AN is that the individual refuses to maintain a minimal normal body weight. The main features of BN are binge eating and inappropriate compensatory methods to prevent weight gain. The gut-brain-adipose tissue (AT) peptides and neutralizing autoantibodies play an important role in the regulation of eating behavior and growth hormone release. The mechanisms for controlling food intake involve an interplay between gut, brain, and AT. Parasympathetic, sympathetic, and serotoninergic systems are required for communication between brain satiety centre, gut, and AT. These neuronal circuits include neuropeptides ghrelin, neuropeptide Y (NPY), peptide YY (PYY), cholecystokinin (CCK), leptin, putative anorexigen obestatin, monoamines dopamine, norepinephrine (NE), serotonin, and neutralizing autoantibodies. This extensive and detailed report reviews data that demonstrate that hunger-satiety signals play an important role in the pathogenesis of eating disorders. Neuroendocrine dysregulations of the AT-gut-brain axis peptides and neutralizing autoantibodies may result in AN and BN. The circulating autoantibodies can be purified and used as pharmacological tools in AN and BN. Further research is required to investigate the orexigenic/anorexigenic synthetic analogs and monoclonal antibodies for potential treatment of eating disorders in clinical practice.

Aging Effects on Whole-Brain Functional Connectivity in Adults Free of Cognitive and Psychiatric Disorders.

PubMed

Ferreira, Luiz Kobuti; Regina, Ana Carolina Brocanello; Kovacevic, Natasa; Martin, Maria da Graça Morais; Santos, Pedro Paim; Carneiro, Camila de Godoi; Kerr, Daniel Shikanai; Amaro, Edson; McIntosh, Anthony Randal; Busatto, Geraldo F

2016-09-01

Aging is associated with decreased resting-state functional connectivity (RSFC) within the default mode network (DMN), but most functional imaging studies have restricted the analysis to specific brain regions or networks, a strategy not appropriate to describe system-wide changes. Moreover, few investigations have employed operational psychiatric interviewing procedures to select participants; this is an important limitation since mental disorders are prevalent and underdiagnosed and can be associated with RSFC abnormalities. In this study, resting-state fMRI was acquired from 59 adults free of cognitive and psychiatric disorders according to standardized criteria and based on extensive neuropsychological and clinical assessments. We tested for associations between age and whole-brain RSFC using Partial Least Squares, a multivariate technique. We found that normal aging is not only characterized by decreased RSFC within the DMN but also by ubiquitous increases in internetwork positive correlations and focal internetwork losses of anticorrelations (involving mainly connections between the DMN and the attentional networks). Our results reinforce the notion that the aging brain undergoes a dedifferentiation processes with loss of functional diversity. These findings advance the characterization of healthy aging effects on RSFC and highlight the importance of adopting a broad, system-wide perspective to analyze brain connectivity. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Invasion of Peripheral Immune Cells into Brain Parenchyma after Cardiac Arrest and Resuscitation.

PubMed

Zhang, Can; Brandon, Nicole R; Koper, Kerryann; Tang, Pei; Xu, Yan; Dou, Huanyu

2018-06-01

Although a direct link has long been suspected between systemic immune responses and neuronal injuries after stroke, it is unclear which immune cells play an important role. A question remains as to whether the blood brain barrier (BBB) is transiently disrupted after circulatory arrest to allow peripheral immune cells to enter brain parenchyma. Here, we developed a clinically relevant cardiac arrest and resuscitation model in mice to investigate the BBB integrity using noninvasive magnetic resonance imaging. Changes in immune signals in the brain and periphery were assayed by immunohistochemistry and flow cytometry. Quantitative variance maps from T1-weighted difference images before and after blood-pool contrast clearance revealed BBB disruptions immediately after resuscitation and one day after reperfusion. Time profiles of hippocampal CA1 neuronal injuries correlated with the morphological changes of microglia activation. Cytotoxic T cells, CD11b + CD11c + dendritic cells, and CD11b + CD45 +hi monocytes and macrophages were significantly increased in the brain three days after cardiac arrest and resuscitation, suggesting direct infiltration of these cells following the BBB disruption. Importantly, these immune cell changes were coupled with a parallel increase in the same subset of immune cell populations in the bone marrow and blood. We conclude that neurovascular breakdown during the initial reperfusion phase contributes to the systemic immune cell invasion and subsequent neuropathogenesis affecting the long-term outcome after cardiac arrest and resuscitation.

[Clinical predictors correlated to outcome of war missile penetrating brain injury].

PubMed

Splavski, Bruno; Vranković, Duro; Saftić, Robert; Muzević, Dario; Kosuta, Maja; Gmajnić, Rudika

2006-09-01

The purpose of this retrospective study was to review and discuss the outcome of surgical management and other clinical predictors influencing the prognosis of war missile penetrating brain injuries. To determine clinical predictors that influence the prognosis of war missile penetrating brain injury, 126 surgically treated patients who had sustained such an injury during the two-year period of war in Croatia (1991-1993) were retrospectively analyzed. Investigated clinical features were: Glasgow Coma Scale (GCS) score on admission; extent of brain injury; time between injury and hospital admission; presence of intracranially retained foreign bodies or bone fragments; development of postinjury and posttraumatic complications; and Glasgow Outcome Score (GOS) at six-month follow up. The data were statistically analyzed. Sixty-seven patients survived penetrating missile brain injury, in most of them with GCS score above 8 on admission. The mean time interval to hospital admission in this group of patients was less than two hours. Twelve of 67 patients developed different complications. All patients recovered well according to GOS (GOS 5 and 4) at six-month follow up. Fifty-nine patients died. The wounded who were in moribund state on the hospital admission (n = 11), and those who died during surgery (n = 8) were excluded from the analysis. The remaining 40 patients who did not survive were analyzed. The majority of them had GCS score 3-8 on admission. They mostly sustained bilateral hemispheric lesion, and/or ventricular lesion, and developed brain edema. The mean time interval between injury and hospital admission was over two hours in this group of patients. Postoperative complication developed in 9 of 40 patients. The patients with GCS score exceeding 8 had by far more favorable outcome in comparison to those with GCS score less than 8. Considering the extent of injury, patients suffering unihemispheric brain wounds had a more favorable outcome than those with lesions of both hemispheres, and particularly those with transventricular lesions. The time between injury and hospital admission proved to be another important prognostic factor. The majority of patients admitted up to one hour of injury survived, while two thirds of those admitted between one and three hours of injury succumbed. The presence of intracranially retained foreign bodies and bone fragments, and postinjury and postoperative complications implied worse outcome in comparison with their absence. The state of consciousness on admission was the most sensitive criterion as far as the prognosis is concerned. The outcome also depended on the extent of brain damage since the wounds associated with a high mortality rate were predominantly bihemispheric. Concerning survival, the time between injury and hospital admission also appeared to be important, as well as intracranially retained foreign bodies and bone fragments, and development of complications. There was no relationship between the presence of retained fragments and development of infection, suggesting that it is not necessary to reoperate for retained fragments. We assume that early surgery is essential for treatment outcome, although it is not necessary to reoperate for retained fragments.

Implications of sodium hydrogen exchangers in various brain diseases.

PubMed

Verma, Vivek; Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar Singh

2015-09-01

Na+/H+ exchangers (NHEs) are the transporter proteins that play an important role in intracellular pH (pHi) regulation, cell differentiation and cell volume and that mediate transepithelial Na+ and HCO3- absorption on the basis of chemical gradients across the plasma membrane. Its activation causes an increase in intracellular Na+, which further leads to Ca+ overload and cell death. The pharmacological inhibition of these transporter proteins prevents myocardial infarction and other heart diseases like congestive heart failure in experimental animal models as well as in clinical situations. The more recent studies have implicated the role of these exchangers in the pathophysiology of brain diseases. Out of nine NHE isoforms, NHE-1 is the major isoform present in the brain and regulates the trans-cellular ion transport through blood-brain barrier membrane, and alteration in their function leads to severe brain abnormalities. NHEs were shown to be involved in pathophysiologies of many brain diseases like epilepsy, Alzheimer's disease, neuropathic pain and ischemia/reperfusion-induced cerebral injury. Na+/H+-exchanger inhibitors (e.g., amiloride and cariporide) produce protective effects on ischemia/reperfusion-induced brain injury (e.g., stroke), exhibit good antiepileptic potential and attenuate neuropathic pain in various animal models. The present review focuses on the pathophysiological role of these ion exchangers in different brain diseases with possible mechanisms.

Histone Deacetylase Inhibitor MS-275 Exhibits Poor Brain Penetration: Pharmacokinetic Studies of [11C]MS-275 using Positron Emission Tomography

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

Hooker, J.M.; Hooker, J.M.; Kim, S.W.

2009-10-01

MS-275 (entinostat) is a histone deacetylase (HDAC) inhibitor currently in clinical trials for the treatment of several types of cancer. Recent reports have noted that MS-275 can cross the blood-brain barrier (BBB) and cause region-specific changes in rodent brain histone acetylation. To characterize the pharmacokinetics and distribution of MS-275 in the brain using positron emission tomography (PET), we labeled the carbamate carbon of MS-275 with carbon-11. Using PET, we determined that [{sup 11}C]MS-275 has low uptake in brain tissue when administered intravenously to nonhuman primates. In rodent studies, we observed that pharmacokinetics and brain accumulation of [{sup 11}C]MS-275 were notmore » changed by the coadministration of large doses of unlabeled MS-275. These results, which both highlight the poor brain penetration of MS-275, clearly suggest its limitation as a therapeutic agent for the central nervous system (CNS). Moreover, our study demonstrates the effectiveness of PET at providing brain pharmacokinetic data for HDAC inhibitors. These data are important not only for the development of new compounds for peripheral cancer treatment (where CNS exclusion is often advantageous) but also for the treatment of neurological disorders (where CNS penetration is critical).« less

Blood-brain barrier shuttle peptides enhance AAV transduction in the brain after systemic administration.

PubMed

Zhang, Xintao; He, Ting; Chai, Zheng; Samulski, R Jude; Li, Chengwen

2018-09-01

The adeno-associated virus (AAV) vector has been used in preclinical and clinical trials of gene therapy for central nervous system (CNS) diseases. One of the biggest challenges of effectively delivering AAV to the brain is to surmount the blood-brain barrier (BBB). Herein, we identified several potential BBB shuttle peptides that significantly enhanced AAV8 transduction in the brain after a systemic administration, the best of which was the THR peptide. The enhancement of AAV8 brain transduction by THR is dose-dependent, and neurons are the primary THR targets. Mechanism studies revealed that THR directly bound to the AAV8 virion, increasing its ability to cross the endothelial cell barrier. Further experiments showed that binding of THR to the AAV virion did not interfere with AAV8 infection biology, and that THR competitively blocked transferrin from binding to AAV8. Taken together, our results demonstrate, for the first time, that BBB shuttle peptides are able to directly interact with AAV and increase the ability of the AAV vectors to cross the BBB for transduction enhancement in the brain. These results will shed important light on the potential applications of BBB shuttle peptides for enhancing brain transduction with systemic administration of AAV vectors. Copyright © 2018 Elsevier Ltd. All rights reserved.

Public education and misinformation on brain death in mainstream media.

PubMed

Lewis, Ariane; Lord, Aaron S; Czeisler, Barry M; Caplan, Arthur

2016-09-01

We sought to evaluate the caliber of education mainstream media provides the public about brain death. We reviewed articles published prior to July 31, 2015, on the most shared/heavily trafficked mainstream media websites of 2014 using the names of patients from two highly publicized brain death cases, "Jahi McMath" and "Marlise Muñoz." We reviewed 208 unique articles. The subject was referred to as being "alive" or on "life support" in 72% (149) of the articles, 97% (144) of which also described the subject as being brain dead. A definition of brain death was provided in 4% (9) of the articles. Only 7% (14) of the articles noted that organ support should be discontinued after brain death declaration unless a family has agreed to organ donation. Reference was made to well-known cases of patients in persistent vegetative states in 16% (34) of articles and 47% (16) of these implied both patients were in the same clinical state. Mainstream media provides poor education to the public on brain death. Because public understanding of brain death impacts organ and tissue donation, it is important for physicians, organ procurement organizations, and transplant coordinators to improve public education on this topic. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neurocognitive status in patients with newly-diagnosed brain tumors in good neurological condition: The impact of tumor type, volume, and location.

PubMed

Hendrix, Philipp; Hans, Elisa; Griessenauer, Christoph J; Simgen, Andreas; Oertel, Joachim; Karbach, Julia

2017-05-01

Neurocognitive function is of great importance in patients with brain tumors. Even patients in good neurological condition may suffer from neurocognitive dysfunction that affects their daily living. The purpose of the present study was to identify risk factors for neurocognitive dysfunction in patients suffering from common supratentorial brain tumors with minor neurological deficits. A prospective study evaluating neurocognitive dysfunction in patients with a newly-diagnosed brain tumor in good neurological condition was performed at a major German academic institution. Patients underwent extensive neurocognitive testing assessing perceptual speed, executive function, visual-spatial and verbal working memory, short- and long-term memory, verbal fluency, fluid intelligence, anxiety, and depression. For each patient, a healthy control was pair-matched based on age, sex, handedness, and profession. A total of 46 patients and 46 healthy controls underwent neurocognitive testing. Patients suffered from glioblastoma multiforme (10), cerebral metastasis (10), pituitary adenoma (13), or meningioma (13). There was neither any difference in age, educational level, fluid intelligence, neurological deficits, and anxiety nor in any depression scores between tumor subgroups. Overall, neurocognitive performance was significantly worse in patients compared to healthy controls. Larger tumor volume, frontal location, and left/dominant hemisphere were associated with worse executive functioning and verbal fluency. Additionally, larger tumors and left/dominant location correlated with impairments on perceptual speed tasks. Frontal tumor location was related to worse performance in visual-spatial and short- and long-term memory. Tumor type, clinical presentation, and patient self-awareness were not associated with specific neurocognitive impairments. Patients suffering from newly-diagnosed brain tumors presenting in good neurological condition display neurocognitive impairments in various domains. Larger tumor volumes, frontal location, and left/dominant hemisphere are important predictors for potential neurocognitive deficits. Tumor type, clinical presentation, or self-awareness are less significant at the time of diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Central nervous system abnormalities in Fanconi anaemia: patterns and frequency on magnetic resonance imaging

PubMed Central

Alston, Robert; Wright, Neville B; Chandler, Kate; Bonney, Denise; Wynn, Robert F; Will, Andrew M; Punekar, Maqsood; Loughran, Sean; Kilday, John-Paul; Schindler, Detlev; Patel, Leena; Meyer, Stefan

2015-01-01

Objective: Fanconi anaemia (FA) is an inherited disease associated with congenital and developmental abnormalities resulting from the disruption of a multigenic DNA damage response pathway. This study aimed to define the MRI appearances of the brain in patients with FA in correlation with their genetic and clinical features. Methods: A review of the brain MRI in 20 patients with FA was performed. Pituitary size and frequencies of the radiological findings of individuals with FA and age-matched controls were determined. Results: Abnormalities were identified in 18 (90%) patients with FA, the commonest being a small pituitary (68%, p < 0.01 females and p < 0.001 males). In five cases (25%, p = 0.02), the pituitary morphology was also abnormal. Posterior fossa abnormalities were seen in six cases (30%, p = 0.01) including Chiari I malformation (n = 3), Dandy–Walker variant (n = 2) and cerebellar atrophy (n = 2). Six patients (30%, p = 0.01) had morphological structural variation of the corpus callosum (CC). Conclusion: The incidence of central nervous system (CNS) abnormalities in FA is higher than previously reported, with a midline predominance that points to impact in the early stages of CNS development. MRI brain imaging is important for endocrine assessment and pre-transplant evaluation and can make an important contribution to clinical decision-making. Advances in knowledge: The incidence of brain structural abnormalities in FA is higher than previously reported, with abnormalities of the posterior fossa, CC and pituitary being common. There is an association with gender and reduction in pituitary size which does not strongly correlate with biochemically evident endocrine abnormality. PMID:26369989

Longitudinal Regional Brain Development and Clinical Risk Factors in Extremely Preterm Infants.

PubMed

Kersbergen, Karina J; Makropoulos, Antonios; Aljabar, Paul; Groenendaal, Floris; de Vries, Linda S; Counsell, Serena J; Benders, Manon J N L

2016-11-01

To investigate third-trimester extrauterine brain growth and correlate this with clinical risk factors in the neonatal period, using serially acquired brain tissue volumes in a large, unselected cohort of extremely preterm born infants. Preterm infants (gestational age <28 weeks) underwent brain magnetic resonance imaging (MRI) at around 30 weeks postmenstrual age and again around term equivalent age. MRIs were segmented in 50 different regions covering the entire brain. Multivariable regression analysis was used to determine the influence of clinical variables on volumes at both scans, as well as on volumetric growth. MRIs at term equivalent age were available for 210 infants and serial data were available for 131 infants. Growth over these 10 weeks was greatest for the cerebellum, with an increase of 258%. Sex, birth weight z-score, and prolonged mechanical ventilation showed global effects on brain volumes on both scans. The effect of brain injury on ventricular size was already visible at 30 weeks, whereas growth data and volumes at term-equivalent age revealed the effect of brain injury on the cerebellum. This study provides data about third-trimester extrauterine volumetric brain growth in preterm infants. Both global and local effects of several common clinical risk factors were found to influence serial volumetric measurements, highlighting the vulnerability of the human brain, especially in the presence of brain injury, during this period. Copyright © 2016 Elsevier Inc. All rights reserved.

Improving Emotional Face Perception in Autism with Diuretic Bumetanide: A Proof-of-Concept Behavioral and Functional Brain Imaging Pilot Study

ERIC Educational Resources Information Center

Hadjikhani, Nouchine; Zürcher, Nicole R; Rogier, Ophelie; Ruest, Torsten; Hippolyte, Loyse; Ben-Ari, Yehezkel; Lemonnier, Eric

2015-01-01

Clinical observations have shown that GABA-acting benzodiazepines exert paradoxical excitatory effects in autism, suggesting elevated intracellular chloride (Cl-)[subscript i] and excitatory action of GABA. In a previous double-blind randomized study, we have shown that the diuretic NKCC1 chloride importer antagonist bumetanide, that decreases…

Putting the Mind in the Brain: Promoting an Appreciation of the Biological Basis to Understanding Human Behavior

ERIC Educational Resources Information Center

Neumann, David L.

2010-01-01

A surprising number of students in psychology, behavioral science, and related social science classes fail to appreciate the importance of biological mechanisms to understanding behavior. To help teachers promote this understanding, this paper outlines six sources of evidence. These are (a) phylogenetic, (b) genetic/developmental, (c) clinical,…

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

Cryptococcoma mimicking a brain tumor in an immunocompetent patient: case report of an extremely rare presentation.

PubMed

Paiva, Aline Lariessy Campos; Aguiar, Guilherme Brasileiro de; Lovato, Renan Maximilian; Zanetti, Arthus Vilar Deolindo; Panagopoulos, Alexandros Theodoros; Veiga, José Carlos Esteves

2017-11-06

Central nervous system (CNS) infectious diseases have high prevalence in developing countries and their proper diagnosis and treatment are very important for public health planning. Cryptococcus neoformans is a fungus that may cause several CNS manifestations, especially in immunocompromised patients. Cryptococcal meningitis is the most common type of involvement. Mass-effect lesions are uncommon: they are described as cryptococcomas and their prevalence is even lower among immunocompetent patients. The aim here was to report an extremely rare case of cryptococcoma causing a mass effect and mimicking a brain tumor in an immunocompetent patient. The literature on CNS cryptococcal infections was reviewed with emphasis on cryptococcomas. Clinical, surgical and radiological data on a female patient with this rare presentation of cryptococcoma mimicking a brain tumor are described. A 54-year-old female patient presented to the emergency department with a rapid-onset progressive history of confusion and completely dependency for basic activities. Neuroimaging showed a left occipital lesion and neurosurgical treatment was proposed. From histopathological evaluation, a diagnosis of cryptococcoma was established. She received clinical support with antifungals, but despite optimal clinical treatment, her condition evolved to death. Cryptococcal infections have several forms of presentation and, in immunocompetent patients, their manifestation may be even more different. Cryptococcoma is an extremely rare presentation in which proper surgical and clinical treatment should be instituted as quickly as possible, but even so, there is a high mortality rate.

Persistent Sleep Disturbances Independently Predict Poorer Functional and Social Outcomes 1 Year After Mild Traumatic Brain Injury.

PubMed

Chan, Lai Gwen; Feinstein, Anthony

2015-01-01

To investigate the effect of sleep disturbances on functional and social outcomes after mild traumatic brain injury. Outpatient traumatic brain injury clinic in a tertiary trauma center. A total of 374 mild traumatic brain injury patients were assessed within 3 months of injury and followed up every 3 months for 1 year. Analysis of a historical cohort in a naturalistic clinical setting. At each visit, symptoms of concussion and psychological distress and indices of functional and social outcomes were measured with the Rivermead Postconcussion Questionnaire, 28-item General Health Questionnaire, and Rivermead Head Injury Follow-up Questionnaire, respectively. Changes in outcome scores over time were explored using repeated measures analysis of variance and compared between subjects with persistent (SD) and recovered (SR) sleep disturbances. Predictors of functional/social outcome were determined using linear regression. The percentages of subjects reporting sleep disturbances at each time point were 71.9%, 57.2%, 55.1%, and 53.7%, respectively. For functional and social outcomes, significant effects of time (F3,315 = 9.54; P < .001), group (SD vs SR) F1,317 = 5.32; P = .022, and time X group interaction F3,315 = 4.14; P = .007 were found. Persistent sleep disturbance (P = 0.011) and higher symptom burden at 6 months postinjury (P < .0001) were independent predictors of poorer outcome. Sleep disturbance, independent of psychological distress, is an important prognostic factor of functional and social outcomes after mild traumatic brain injury.

Society for Neuro-Oncology 2014 annual meeting updates on central nervous system metastases.

PubMed

Lukas, Rimas V; Mehta, Minesh P; Lesniak, Maciej S

2015-06-01

The 19th Annual Meeting of the Society for Neuro-Oncology (SNO) took place in November of 2014. The focus of many abstracts, as well as the Education Day, was on recent advances in the study of central nervous system (CNS) metastases. Key studies evaluating the factors in tumors and their microenvironment associated with the development and growth of brain metastases are reviewed. Studies investigating the factors that independently influence survival in participants with brain metastases are presented. The Response Assessment for Neuro-Oncology criteria for brain metastases (RANO-BM) and the Neurological Assessment in Neuro-Oncology (NANO) criteria, which were both presented, are recapped. Studies are reviewed evaluating factors that influence survival outcomes in participants with brain metastases who were treated with radiotherapy. Studies investigating the potential risk of radiation necrosis with the combination of radiotherapy and immunotherapies are presented. Brain metastases-focused subset analyses from the ASCEND-1 trial for ALK-translocated non-small cell lung cancer are presented. Preclinical and clinical work on solid tumor leptomeningeal carcinomatosis is also covered. An overview is provided of treatment- related toxicities as well as important concepts that may influence strategies to protect against these toxicities. Key concepts regarding tumor biology, prognostication, response assessment, therapeutic management, and sequelae of treatment for CNS metastases are summarized. Advances in our understanding of the basic and clinical science of CNS metastases have the potential to improve outcomes for patients.

Frontotemporal lobar degeneration: current perspectives

PubMed Central

Riedl, Lina; Mackenzie, Ian R; Förstl, Hans; Kurz, Alexander; Diehl-Schmid, Janine

2014-01-01

The term frontotemporal lobar degeneration (FTLD) refers to a group of progressive brain diseases, which preferentially involve the frontal and temporal lobes. Depending on the primary site of atrophy, the clinical manifestation is dominated by behavior alterations or impairment of language. The onset of symptoms usually occurs before the age of 60 years, and the mean survival from diagnosis varies between 3 and 10 years. The prevalence is estimated at 15 per 100,000 in the population aged between 45 and 65 years, which is similar to the prevalence of Alzheimer’s disease in this age group. There are two major clinical subtypes, behavioral-variant frontotemporal dementia and primary progressive aphasia. The neuropathology underlying the clinical syndromes is also heterogeneous. A common feature is the accumulation of certain neuronal proteins. Of these, the microtubule-associated protein tau (MAPT), the transactive response DNA-binding protein, and the fused in sarcoma protein are most important. Approximately 10% to 30% of FTLD shows an autosomal dominant pattern of inheritance, with mutations in the genes for MAPT, progranulin (GRN), and in the chromosome 9 open reading frame 72 (C9orf72) accounting for more than 80% of familial cases. Although significant advances have been made in recent years regarding diagnostic criteria, clinical assessment instruments, neuropsychological tests, cerebrospinal fluid biomarkers, and brain imaging techniques, the clinical diagnosis remains a challenge. To date, there is no specific pharmacological treatment for FTLD. Some evidence has been provided for serotonin reuptake inhibitors to reduce behavioral disturbances. No large-scale or high-quality studies have been conducted to determine the efficacy of non-pharmacological treatment approaches in FTLD. In view of the limited treatment options, caregiver education and support is currently the most important component of the clinical management. PMID:24600223

Parkinson's Disease Gene Therapy: Success by Design Meets Failure by Efficacy

PubMed Central

Bartus, Raymond T; Weinberg, Marc S; Samulski, R. Jude

2014-01-01

Over the past decade, nine gene therapy clinical trials for Parkinson's disease (PD) have been initiated and completed. Starting with considerable optimism at the initiation of each trial, none of the programs has yet borne sufficiently robust clinical efficacy or found a clear path toward regulatory approval. Despite the immediately disappointing nature of the efficacy outcomes in these trials, the clinical data garnered from the individual studies nonetheless represent tangible and significant progress for the gene therapy field. Collectively, the clinical trials demonstrate that we have overcome the major safety hurdles previously suppressing central nervous system (CNS) gene therapy, for none produced any evidence of untoward risk or harm after administration of various vector-delivery systems. More importantly, these studies also demonstrated controlled, highly persistent generation of biologically active proteins targeted to structures deep in the human brain. Therefore, a renewed, focused emphasis must be placed on advancing clinical efficacy by improving clinical trial design, patient selection and outcome measures, developing more predictive animal models to support clinical testing, carefully performing retrospective analyses, and most importantly moving forward—beyond our past limits. PMID:24356252

Egas Moniz: 90 Years (1927-2017) from Cerebral Angiography.

PubMed

Artico, Marco; Spoletini, Marialuisa; Fumagalli, Lorenzo; Biagioni, Francesca; Ryskalin, Larisa; Fornai, Francesco; Salvati, Maurizio; Frati, Alessandro; Pastore, Francesco Saverio; Taurone, Samanta

2017-01-01

In June 2017 we celebrate the 90th anniversary of the pioneer discovery of cerebral angiography, the seminal imaging technique used for visualizing cerebral blood vessels and vascular alterations as well as other intracranial disorders. Egas Moniz (1874-1955) was the first to describe the use of this revolutionary technique which, until 1975 (when computed tomography, CT, scan was introduced in the clinical practice), was the sole diagnostic tool to provide an imaging of cerebral vessels and therefore alterations due to intracranial pathology. Moniz introduced in the clinical practice this fundamental and important diagnostic tool. The present contribution wishes to pay a tribute to the Portuguese neurosurgeon, who was also a distinguished neurologist and statesman. Despite his tremendous contribution in modern brain imaging, Egas Moniz was awarded the Nobel Prize in Physiology or Medicine in 1949 for prefrontal leucotomy, the neurosurgical intervention nowadays unacceptable, but should rather be remembered for his key contribution to modern brain imaging.

Clinical utility of EEG in diagnosing and monitoring epilepsy in adults.

PubMed

Tatum, W O; Rubboli, G; Kaplan, P W; Mirsatari, S M; Radhakrishnan, K; Gloss, D; Caboclo, L O; Drislane, F W; Koutroumanidis, M; Schomer, D L; Kasteleijn-Nolst Trenite, D; Cook, Mark; Beniczky, S

2018-05-01

Electroencephalography (EEG) remains an essential diagnostic tool for people with epilepsy (PWE). The International Federation of Clinical Neurophysiology produces new guidelines as an educational service for clinicians to address gaps in knowledge in clinical neurophysiology. The current guideline was prepared in response to gaps present in epilepsy-related neurophysiological assessment and is not intended to replace sound clinical judgement in the care of PWE. Furthermore, addressing specific pathophysiological conditions of the brain that produce epilepsy is of primary importance though is beyond the scope of this guideline. Instead, our goal is to summarize the scientific evidence for the utility of EEG when diagnosing and monitoring PWE. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

The impacts of acute carbon monoxide poisoning on the brain: Longitudinal clinical and 99mTc ethyl cysteinate brain SPECT characterization of patients with persistent and delayed neurological sequelae.

PubMed

Tsai, Chung-Fen; Yip, Ping-Keung; Chen, Shao-Yuan; Lin, Jen-Cheng; Yeh, Zai-Ting; Kung, Lan-Yu; Wang, Cheng-Yi; Fan, Yu-Ming

2014-04-01

Acute carbon monoxide (CO) poisoning poses a significant threat to the central nervous system. It can cause brain injury and diverse neurological deficits including persistent neurological sequelae (PNS) and delayed neurological sequelae (DNS). The study aimed to investigate the long-term impacts of acute CO poisoning on brain perfusion and neurological function, and to explore potential differences between PNS and DNS patients. We evaluated brain perfusion using (99m)Tc ethyl cysteinate (ECD) brain single photon emission computed tomography (SPECT) and assessed clinical neurological symptoms and signs one month following acute poisoning. For DNS patients, ECD SPECT and clinical evaluation were performed when their delayed symptoms appeared. All patients had follow-up SPECT imaging, along with clinical assessments six months following poisoning. 12 PNS and 12 DNS patients were recruited between 2007 and 2010. Clinically, the main characteristic presentations were cognitive decline, emotional instability, and gait disturbance. SPECT imaging demonstrated consistent frontal hypoperfusion of varying severities in all patients, which decreased in severity at follow-up imaging. DNS patients usually had more severe symptoms and perfusion defects, along with worse clinical outcomes than the PNS group. These results suggest that acute CO poisoning might lead to long term brain injuries and neurological sequelae, particularly in DNS patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Gut-Brain Axis and Behavior.

PubMed

Martin, Clair R; Mayer, Emeran A

2017-01-01

In the last 5 years, interest in the interactions among the gut microbiome, brain, and behavior has exploded. Preclinical evidence supports a role of the gut microbiome in behavioral responses associated with pain, emotion, social interactions, and food intake. Limited, but growing, clinical evidence comes primarily from associations of gut microbial composition and function to behavioral and clinical features and brain structure and function. Converging evidence suggests that the brain and the gut microbiota are in bidirectional communication. Observed dysbiotic states in depression, chronic stress, and autism may reflect altered brain signaling to the gut, while altered gut microbial signaling to the brain may play a role in reinforcing brain alterations. On the other hand, primary dysbiotic states due to Western diets may signal to the brain, altering ingestive behavior. While studies performed in patients with depression and rodent models generated by fecal microbial transfer from such patients suggest causation, evidence for an influence of acute gut microbial alterations on human behavioral and clinical parameters is lacking. Only recently has an open-label microbial transfer therapy in children with autism tentatively validated the gut microbiota as a therapeutic target. The translational potential of preclinical findings remains unclear without further clinical investigation. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial: A TITE-CRM Phase I/II Clinical Trial.

PubMed

Kim, Michelle M; Parmar, Hemant; Cao, Yue; Pramanik, Priyanka; Schipper, Matthew; Hayman, James; Junck, Larry; Mammoser, Aaron; Heth, Jason; Carter, Corey A; Oronsky, Arnold; Knox, Susan J; Caroen, Scott; Oronsky, Bryan; Scicinski, Jan; Lawrence, Theodore S; Lao, Christopher D

2016-04-01

Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases. Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial. Published by Elsevier Inc.

High-resolution whole-brain DCE-MRI using constrained reconstruction: Prospective clinical evaluation in brain tumor patients.

PubMed

Guo, Yi; Lebel, R Marc; Zhu, Yinghua; Lingala, Sajan Goud; Shiroishi, Mark S; Law, Meng; Nayak, Krishna

2016-05-01

To clinically evaluate a highly accelerated T1-weighted dynamic contrast-enhanced (DCE) MRI technique that provides high spatial resolution and whole-brain coverage via undersampling and constrained reconstruction with multiple sparsity constraints. Conventional (rate-2 SENSE) and experimental DCE-MRI (rate-30) scans were performed 20 minutes apart in 15 brain tumor patients. The conventional clinical DCE-MRI had voxel dimensions 0.9 × 1.3 × 7.0 mm(3), FOV 22 × 22 × 4.2 cm(3), and the experimental DCE-MRI had voxel dimensions 0.9 × 0.9 × 1.9 mm(3), and broader coverage 22 × 22 × 19 cm(3). Temporal resolution was 5 s for both protocols. Time-resolved images and blood-brain barrier permeability maps were qualitatively evaluated by two radiologists. The experimental DCE-MRI scans showed no loss of qualitative information in any of the cases, while achieving substantially higher spatial resolution and whole-brain spatial coverage. Average qualitative scores (from 0 to 3) were 2.1 for the experimental scans and 1.1 for the conventional clinical scans. The proposed DCE-MRI approach provides clinically superior image quality with higher spatial resolution and coverage than currently available approaches. These advantages may allow comprehensive permeability mapping in the brain, which is especially valuable in the setting of large lesions or multiple lesions spread throughout the brain.

Clinical efficacy of positron emission tomography

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

Heiss, W.D.; Pawlick, G.; Herholz, K.

1987-01-01

The contents of this book are: Brain: Cerebral Vascular Disease; Brain: Movement Disorders; Brain: Epilepsy and Pediatric Neurology; Brain: Dementias; Brain: Schizophrenia; Heart: Angina Pectoris; Heart: Infarction; Lungs; Soft Tissue Tumors; and Brain Tumors.

BrainNetCNN: Convolutional neural networks for brain networks; towards predicting neurodevelopment.

PubMed

Kawahara, Jeremy; Brown, Colin J; Miller, Steven P; Booth, Brian G; Chau, Vann; Grunau, Ruth E; Zwicker, Jill G; Hamarneh, Ghassan

2017-02-01

We propose BrainNetCNN, a convolutional neural network (CNN) framework to predict clinical neurodevelopmental outcomes from brain networks. In contrast to the spatially local convolutions done in traditional image-based CNNs, our BrainNetCNN is composed of novel edge-to-edge, edge-to-node and node-to-graph convolutional filters that leverage the topological locality of structural brain networks. We apply the BrainNetCNN framework to predict cognitive and motor developmental outcome scores from structural brain networks of infants born preterm. Diffusion tensor images (DTI) of preterm infants, acquired between 27 and 46 weeks gestational age, were used to construct a dataset of structural brain connectivity networks. We first demonstrate the predictive capabilities of BrainNetCNN on synthetic phantom networks with simulated injury patterns and added noise. BrainNetCNN outperforms a fully connected neural-network with the same number of model parameters on both phantoms with focal and diffuse injury patterns. We then apply our method to the task of joint prediction of Bayley-III cognitive and motor scores, assessed at 18 months of age, adjusted for prematurity. We show that our BrainNetCNN framework outperforms a variety of other methods on the same data. Furthermore, BrainNetCNN is able to identify an infant's postmenstrual age to within about 2 weeks. Finally, we explore the high-level features learned by BrainNetCNN by visualizing the importance of each connection in the brain with respect to predicting the outcome scores. These findings are then discussed in the context of the anatomy and function of the developing preterm infant brain. Copyright © 2016 Elsevier Inc. All rights reserved.

Pros and Cons While Looking Through an Asian Window on the Rome IV Criteria for Irritable Bowel Syndrome: Pros.

PubMed

Ghoshal, Uday C

2017-07-30

A decade after Rome III, in 2016, Rome IV criteria were published. There are major differences between Rome IV and the earlier iteration, some of which are in line with Asian viewpoints. The clinical applicability of the Rome IV criteria of irritable bowel syndrome (IBS) in Asian perspective is reviewed here. Instead of considering functional gastrointestinal disorders (FGIDs) to be largely psychogenic, Rome IV suggested the importance of the gut over brain ("disorders of gut-brain interaction" not "brain-gut interaction"). The word "functional" is underplayed. Multi-dimensional clinical profile attempts to recognize micro-organic nature, like slow colon transit and fecal evacuation disorders in constipation and dietary intolerance including that of lactose and fructose, bile acid malabsorption, non-celiac wheat sensitivity, small intestinal bacterial overgrowth, and gastrointestinal infection in diarrhea. Overlap between different FGIDs has been recognized as Rome IV suggests these to be a spectrum rather than discrete disorders. Bloating, common in Asia, received attention, though less. Sub-typing of IBS may be more clinician-friendly now as the patient-reported stool form may be used than a diary. However, a few issues, peculiar to Asia, need consideration; Rome IV, like Rome III, suggests that Bristol type I-II stool to denote constipation though Asian experts include type III as well. Work-up for physiological factors should be given greater importance. Language issue is important. Bloating, common in IBS, should be listed in the criteria. Threshold values for symptoms in Rome IV criteria are based on Western data. Post-infectious malabsorption (tropical sprue) should be excluded to diagnose post-infectious IBS, particularly in Asia.

Alterations of Intrinsic Brain Connectivity Patterns in Depression and Bipolar Disorders: A Critical Assessment of Magnetoencephalography-Based Evidence

PubMed Central

Alamian, Golnoush; Hincapié, Ana-Sofía; Combrisson, Etienne; Thiery, Thomas; Martel, Véronique; Althukov, Dmitrii; Jerbi, Karim

2017-01-01

Despite being the object of a thriving field of clinical research, the investigation of intrinsic brain network alterations in psychiatric illnesses is still in its early days. Because the pathological alterations are predominantly probed using functional magnetic resonance imaging (fMRI), many questions about the electrophysiological bases of resting-state alterations in psychiatric disorders, particularly among mood disorder patients, remain unanswered. Alongside important research using electroencephalography (EEG), the specific recent contributions and future promise of magnetoencephalography (MEG) in this field are not fully recognized and valued. Here, we provide a critical review of recent findings from MEG resting-state connectivity within major depressive disorder (MDD) and bipolar disorder (BD). The clinical MEG resting-state results are compared with those previously reported with fMRI and EEG. Taken together, MEG appears to be a promising but still critically underexploited technique to unravel the neurophysiological mechanisms that mediate abnormal (both hyper- and hypo-) connectivity patterns involved in MDD and BD. In particular, a major strength of MEG is its ability to provide source-space estimations of neuromagnetic long-range rhythmic synchronization at various frequencies (i.e., oscillatory coupling). The reviewed literature highlights the relevance of probing local and interregional rhythmic synchronization to explore the pathophysiological underpinnings of each disorder. However, before we can fully take advantage of MEG connectivity analyses in psychiatry, several limitations inherent to MEG connectivity analyses need to be understood and taken into account. Thus, we also discuss current methodological challenges and outline paths for future research. MEG resting-state studies provide an important window onto perturbed spontaneous oscillatory brain networks and hence supply an important complement to fMRI-based resting-state measurements in psychiatric populations. PMID:28367127

Barriers to investigator-initiated deep brain stimulation and device research

PubMed Central

Malone, Donald; Okun, Michael S.; Booth, Joan; Machado, Andre G.

2014-01-01

The success of device-based research in the clinical neurosciences has overshadowed a critical and emerging problem in the biomedical research environment in the United States. Neuroprosthetic devices, such as deep brain stimulation (DBS), have been shown in humans to be promising technologies for scientific exploration of neural pathways and as powerful treatments. Large device companies have, over the past several decades, funded and developed major research programs. However, both the structure of clinical trial funding and the current regulation of device research threaten investigator-initiated efforts in neurologic disorders. The current atmosphere dissuades clinical investigators from pursuing formal and prospective research with novel devices or novel indications. We review our experience in conducting a federally funded, investigator-initiated, device-based clinical trial that utilized DBS for thalamic pain syndrome. We also explore barriers that clinical investigators face in conducting device-based clinical trials, particularly in early-stage studies or small disease populations. We discuss 5 specific areas for potential reform and integration: (1) alternative pathways for device approval; (2) eliminating right of reference requirements; (3) combining federal grant awards with regulatory approval; (4) consolidation of oversight for human subjects research; and (5) private insurance coverage for clinical trials. Careful reformulation of regulatory policy and funding mechanisms is critical for expanding investigator-initiated device research, which has great potential to benefit science, industry, and, most importantly, patients. PMID:24670888

Noninvasive brain stimulation to suppress craving in substance use disorders: review of human evidence and methodological considerations for future work

PubMed Central

Hone-Blanchet, Antoine; Ciraulo, Domenic A; Pascual-Leone, Alvaro; Fecteau, Shirley

2016-01-01

Substance use disorders (SUDs) can be viewed as a pathology of neuroadaptation. The pharmacological overstimulation of neural mechanisms of reward, motivated learning and memory leads to drug-seeking behavior. A critical characteristic of SUDs is the appearance of craving, the motivated desire and urge to use, which is a main focus of current pharmacological and behavioral therapies. Recent proof-of-concept studies have tested the effects of non-invasive brain stimulation on craving. Although its mechanisms of action are not fully understood, this approach shows interesting potential in tuning down craving and possibly consumption of diverse substances. This article reviews available results on the use of repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES) in SUDs, specifically tobacco, alcohol and psychostimulant use disorders. We discuss several important factors that need to be addressed in future works to improve clinical assessment and effects of non-invasive brain stimulation in SUDs. Factors discussed include brain stimulation devices and parameters, study designs, brain states and subjects’ characteristics. PMID:26449761

Comparison of laterality index of upper and lower limb movement using brain activated fMRI

NASA Astrophysics Data System (ADS)

Harirchian, Mohammad Hossein; Oghabian, Mohammad Ali; Rezvanizadeh, Alireza; Bolandzadeh, Niousha

2008-03-01

Asymmetry of bilateral cerebral function, i.e. laterality, is an important phenomenon in many brain actions such as motor functions. This asymmetry maybe altered in some clinical conditions such as Multiple Sclerosis (MS). The aim of this study was to delineate the laterality differences for upper and lower limbs in healthy subjects to compare this pattern with subjects suffering from MS in advance. Hence 9 Male healthy subjects underwent fMRI assessment, while they were asked to move their limbs in a predetermined pattern. The results showed that hands movement activates the brain with a significant lateralization in pre-motor cortex in comparison with lower limb. Also, dominant hands activate brain more lateralized than the non-dominant hand. In addition, Left basal ganglia were observed to be activated regardless of the hand used, While, These patterns of Brain activation was not detected in lower limbs. We hypothesize that this difference might be attributed to this point that hand is usually responsible for precise and fine voluntary movements, whereas lower limb joints are mainly responsible for locomotion, a function integrating voluntary and automatic bilateral movements.

Noninvasive brain stimulation to suppress craving in substance use disorders: Review of human evidence and methodological considerations for future work.

PubMed

Hone-Blanchet, Antoine; Ciraulo, Domenic A; Pascual-Leone, Alvaro; Fecteau, Shirley

2015-12-01

Substance use disorders (SUDs) can be viewed as a pathology of neuroadaptation. The pharmacological overstimulation of neural mechanisms of reward, motivated learning and memory leads to drug-seeking behavior. A critical characteristic of SUDs is the appearance of craving, the motivated desire and urge to use, which is a main focus of current pharmacological and behavioral therapies. Recent proof-of-concept studies have tested the effects of noninvasive brain stimulation on craving. Although its mechanisms of action are not fully understood, this approach shows interesting potential in tuning down craving and possibly consumption of diverse substances. This article reviews available results on the use of repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES) in SUDs, specifically tobacco, alcohol and psychostimulant use disorders. We discuss several important factors that need to be addressed in future works to improve clinical assessment and effects of noninvasive brain stimulation in SUDs. Factors discussed include brain stimulation devices and parameters, study designs, brain states and subjects' characteristics. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Is it still the "royal way"? The dream as a junction of neurobiology and psychoanalysis].

PubMed

Simon, Mária

2011-01-01

Some decades ago the dream seemed to be randomly generated by brain stem mechanisms in the cortical and subcortical neuronal networks. However, most recent empirical data, studies on brain lesions and functional neuroimaging results have refuted this theory. Several data support that motivation pathways, memory systems, especially implicit, emotional memory play an important role in dream formation. This essay reviews how the results of neurobiology and cognitive psychology can be fitted into the theoretical frameworks and clinical practice of the psychoanalysis. The main aim is to demonstrate that results of neurobiology and empirical observations of psychoanalysis are complementary rather than contradictory.

Intracranial aneurysm and arachnoid cyst: just a coincidence? A case report.

PubMed

Aguiar, Guilherme Brasileiro de; Santos, Rafael Gomes Dos; Paiva, Aline Lariessy Campos; Silva, João Miguel de Almeida; Silva, Rafael Carlos da; Veiga, José Carlos Esteves

2017-12-18

Presence of an arachnoid cyst and a non-ruptured intracystic brain aneurysm is extremely rare. The aim of this paper was to describe a case of a patient with an arachnoid cyst and a non-ruptured aneurysm inside it. Clinical, surgical and radiological data were analyzed and the literature was reviewed. A patient complained of chronic headache. She was diagnosed as having a temporal arachnoid cyst and a non-ruptured middle cerebral artery aneurysm inside it. Surgery was performed to clip the aneurysm and fenestrate the cyst. This report raises awareness about the importance of intracranial vascular investigation in patients with arachnoid cysts and brain hemorrhage.

Gender differences in brain activity and the relationship between brain activity and differences in prevalence rates between male and female major depressive disorder patients: a resting-state fMRI study.

PubMed

Yao, Zhijian; Yan, Rui; Wei, Maobin; Tang, Hao; Qin, Jiaolong; Lu, Qing

2014-11-01

We examined the gender-difference effect on abnormal spontaneous neuronal activity of male and female major depressive disorder (MDD) patients using the amplitude of low-frequency fluctuation (ALFF) and the further clarified the relationship between the abnormal ALFF and differences in MDD prevalence rates between male and female patients. Fourteen male MDD patients, 13 female MDD patients and 15 male and 15 female well matched healthy controls (HCs) completed this study. The ALFF approach was used, and Pearson correlation was conducted to observe a possible clinical relevance. There were widespread differences in ALFF values between female and male MDD patients, including some important parts of the frontoparietal network, auditory network, attention network and cerebellum network. In female MDD patients, there was a positive correlation between average ALFF values of the left postcentral gyrus and the severity of weight loss symptom. The gender-difference effect leading to abnormal brain activity is an important underlying pathomechanism for different somatic symptoms in MDD patients of different genders and is likely suggestive of higher MDD prevalence rates in females. The abnormal ALFF resulting from the gender-difference effect might improve our understanding of the differences in prevalence rates between male and female MDD patients from another perspective. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Monoamine oxidase: isoforms and inhibitors in Parkinson's disease and depressive illness

PubMed Central

Youdim, Moussa B H; Bakhle, Y S

2006-01-01

A few years after the foundation of the British Pharmacological Society, monoamine oxidase (MAO) was recognized as an enzyme of crucial interest to pharmacologists because it catalyzed the major inactivation pathway for the catecholamine neurotransmitters, noradrenaline, adrenaline and dopamine (and, later, 5-hydroxytryptamine, as well). Within the next decade, the therapeutic value of inhibitors of MAO in the treatment of depressive illness was established. Although this first clinical use exposed serious side effects, pharmacological interest in, and investigation of, MAO continued, resulting in the characterization of two isoforms, MAO-A and -B, and isoform-selective inhibitors. Selective inhibitors of MAO-B have found a therapeutic role in the treatment of Parkinson's disease and further developments have provided reversible inhibitors of MAO-A, which offer antidepressant activity without the serious side effects of the earlier inhibitors. Clinical observation and subsequent pharmacological analysis have also generated the concept of neuroprotection, reflecting the possibility of slowing, halting and maybe reversing, neurodegeneration in Parkinson's or Alzheimer's diseases. Increased levels of oxidative stress in the brain may be critical for the initiation and progress of neurodegeneration and selective inhibition of brain MAO could contribute importantly to lowering such stress. There are complex interactions between free iron levels in brain and MAO, which may have practical outcomes for depressive disorders. These aspects of MAO and its inhibition and some indication of how this important area of pharmacology and therapeutics might develop in the future are summarized in this review. PMID:16402116

Relationships between the resting-state network and the P3: Evidence from a scalp EEG study

NASA Astrophysics Data System (ADS)

Li, Fali; Liu, Tiejun; Wang, Fei; Li, He; Gong, Diankun; Zhang, Rui; Jiang, Yi; Tian, Yin; Guo, Daqing; Yao, Dezhong; Xu, Peng

2015-10-01

The P3 is an important event-related potential that can be used to identify neural activity related to the cognitive processes of the human brain. However, the relationships, especially the functional correlations, between resting-state brain activity and the P3 have not been well established. In this study, we investigated the relationships between P3 properties (i.e., amplitude and latency) and resting-state brain networks. The results indicated that P3 amplitude was significantly correlated with resting-state network topology, and in general, larger P3 amplitudes could be evoked when the resting-state brain network was more efficient. However, no significant relationships were found for the corresponding P3 latency. Additionally, the long-range connections between the prefrontal/frontal and parietal/occipital brain regions, which represent the synchronous activity of these areas, were functionally related to the P3 parameters, especially P3 amplitude. The findings of the current study may help us better understand inter-subject variation in the P3, which may be instructive for clinical diagnosis, cognitive neuroscience studies, and potential subject selection for brain-computer interface applications.

Functional Plasticity in Childhood Brain Disorders: When, What, How, and Whom to Assess

PubMed Central

Dennis, Maureen; Spiegler, Brenda J.; Simic, Nevena; Sinopoli, Katia J.; Wilkinson, Amy; Yeates, Keith Owen; Taylor, H. Gerry; Bigler, Erin D.; Fletcher, Jack M.

2014-01-01

At every point in the lifespan, the brain balances malleable processes representing neural plasticity that promote change with homeostatic processes that promote stability. Whether a child develops typically or with brain injury, his or her neural and behavioral outcome is constructed through transactions between plastic and homeostatic processes and the environment. In clinical research with children in whom the developing brain has been malformed or injured, behavioral outcomes provide an index of the result of plasticity, homeostasis, and environmental transactions. When should we assess outcome in relation to age at brain insult, time since brain insult, and age of the child at testing? What should we measure? Functions involving reacting to the past and predicting the future, as well as social-affective skills, are important. How should we assess outcome? Information from performance variability, direct measures and informants, overt and covert measures, and laboratory and ecological measures should be considered. In whom are we assessing outcome? Assessment should be cognizant of individual differences in gene, socio-economic status (SES), parenting, nutrition, and interpersonal supports, which are moderators that interact with other factors influencing functional outcome. PMID:24821533

Creatine in the central nervous system: From magnetic resonance spectroscopy to creatine deficiencies.

PubMed

Rackayova, Veronika; Cudalbu, Cristina; Pouwels, Petra J W; Braissant, Olivier

2017-07-15

Creatine (Cr) is an important organic compound acting as intracellular high-energy phosphate shuttle and in energy storage. While located in most cells where it plays its main roles in energy metabolism and cytoprotection, Cr is highly concentrated in muscle and brain tissues, in which Cr also appears to act in osmoregulation and neurotransmission. This review discusses the basis of Cr metabolism, synthesis and transport within brain cells. The importance of Cr in brain function and the consequences of its impaired metabolism in primary and secondary Cr deficiencies are also discussed. Cr and phosphocreatine (PCr) in living systems can be well characterized using in vivo magnetic resonance spectroscopy (MRS). This review describes how 1 H MRS allows the measurement of Cr and PCr, and how 31 P MRS makes it possible to estimate the creatine kinase (CK) rate constant and so detect dynamic changes in the Cr/PCr/CK system. Absolute quantification by MRS using creatine as internal reference is also debated. The use of in vivo MRS to study brain Cr in a non-invasive way is presented, as well as its use in clinical and preclinical studies, including diagnosis and treatment follow-up in patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer's Disease Pathogenesis.

PubMed

Kyrtsos, Christina Rose; Baras, John S

2015-01-01

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting over 10% population over the age of 65 years. Clinically, AD is described by the symptom set of short term memory loss and cognitive decline, changes in mentation and behavior, and eventually long-term memory deficit as the disease progresses. On imaging studies, significant atrophy with subsequent increase in ventricular volume have been observed. Pathology on post-mortem brain specimens demonstrates the classic findings of increased beta amyloid (Aβ) deposition and the presence of neurofibrillary tangles (NFTs) within affected neurons. Neuroinflammation, dysregulation of blood-brain barrier transport and clearance, deposition of Aβ in cerebral blood vessels, vascular risk factors such as atherosclerosis and diabetes, and the presence of the apolipoprotein E4 allele have all been identified as playing possible roles in AD pathogenesis. Recent research has demonstrated the importance of the glymphatic system in the clearance of Aβ from the brain via the perivascular space surrounding cerebral blood vessels. Given the variety of hypotheses that have been proposed for AD pathogenesis, an interconnected, multilayer model offers a unique opportunity to combine these ideas into a single unifying model. Results of this model demonstrate the importance of vessel stiffness and heart rate in maintaining adequate clearance of Aβ from the brain.

Neuroimaging study of sex differences in the neuropathology of cocaine abuse.

PubMed

Li, Chiang-shan Ray; Kemp, Kathleen; Milivojevic, Verica; Sinha, Rajita

2005-09-01

Female and male substance abusers differ in their disease patterns and clinical outcomes. An important question in addiction neuroscience thus concerns the neural substrates underlying these sex differences. This article aims to examine what is known of the neural mechanisms involved in the sex differences between substance abusers. We reviewed neuroimaging studies that addressed sex differences in cerebral perfusion deficits after chronic cocaine use and in regional brain activation during pharmacologic challenge and cue-induced craving. We also present results from a preliminary study in which cocaine-dependent men and women participated in script-guided imagery of stress- and drug cue-related situations while blood oxygenation level-dependent signals of their brain were acquired in a 1.5T scanner. Spatial pre-processing and statistical analysis of brain images were performed. Regional brain activation was compared between stress and drug cue trials in men versus women. The results of our study showed greater activation in the left uncus and right claustrum (both, statistical threshold of P = 0.01, uncorrected; extent = 10 voxels) in men (n = 5) during drug cue trials compared with stress trials. No brain regions showed greater activation during stress trials compared with drug cue trials. In contrast, women (n = 6) showed greater activation in the right medial and superior frontal gyri during stress trials compared with drug cue trials at the same statistical threshold. No brain regions showed more activation during drug cue trials than during stress trials. The studies reviewed underscore the need to consider sex-related factors in examining the neuropathology of cocaine addiction. Our preliminary results also suggest important sex differences in the effect of stress- and drug cue-associated brain activation in individuals with cocaine use disorder.

The effect of coaching on the simulated malingering of memory impairment.

PubMed

Rüsseler, Jascha; Brett, Alexandra; Klaue, Ulrike; Sailer, Michael; Münte, Thomas F

2008-10-07

Detecting malingering or exaggeration of impairments in brain function after traumatic brain injury is of increasing importance in neuropsychological assessment. Lawyers involved in brain injury litigation cases routinely coach their clients how to approach neuropsychological testing to their advantage. Thus, it is important to know how robust assessment methods are with respect to symptom malingering or exaggeration. The influence of different coaching methods on the simulated malingering of memory impairments is investigated in neurologically healthy participants using the Short-Term-Memory Test from the Bremer Symptom-Validierung (STM-BSV). Cut-offs were derived from patients with mild to severe traumatic brain injury. For comparison purposes, the German adaptation of the Rey Auditory Verbal Learning Test (AVLT), and the Rey 15 Items Test (FIT) were additionally administered. Four groups of neurologically healthy subjects were instructed to (1) perform as best as they can, (2) simulate brain injury, (3) simulate brain injury and received additional information about the sequelae of head trauma, (4) simulate brain injury and received additional information on how to avoid detection. Furthermore, a group of patients with mild to severe closed head injury performed the tests with best effort. The naïve simulator and the symptom coached groups were the easiest to detect, whereas the symptom plus test coached group was the hardest to detect. The AVLT and the FIT were not suited to detect simulators (sensitivities from 0% to 50.8% at 75% specificity) whereas the STM-BSV detected simulators with 67% - 88% sensitivity at a specificity of 73%. However, the STM-BSV was not robust to coaching. The present investigation shows that symptom validity testing as implemented in the BSV-STM is one clinically useful element in the detection of memory malingering. However, clinicians have to be aware that coaching influences performance in the test.

Regional Delivery of Chimeric Antigen Receptor-Engineered T Cells Effectively Targets HER2+ Breast Cancer Metastasis to the Brain.

PubMed

Priceman, Saul J; Tilakawardane, Dileshni; Jeang, Brook; Aguilar, Brenda; Murad, John P; Park, Anthony K; Chang, Wen-Chung; Ostberg, Julie R; Neman, Josh; Jandial, Rahul; Portnow, Jana; Forman, Stephen J; Brown, Christine E

2018-01-01

Purpose: Metastasis to the brain from breast cancer remains a significant clinical challenge, and may be targeted with CAR-based immunotherapy. CAR design optimization for solid tumors is crucial due to the absence of truly restricted antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we have optimized HER2-CAR T cells for the treatment of breast to brain metastases, and determined optimal second-generation CAR design and route of administration for xenograft mouse models of breast metastatic brain tumors, including multifocal and leptomeningeal disease. Experimental Design: HER2-CAR constructs containing either CD28 or 4-1BB intracellular costimulatory signaling domains were compared for functional activity in vitro by measuring cytokine production, T-cell proliferation, and tumor killing capacity. We also evaluated HER2-CAR T cells delivered by intravenous, local intratumoral, or regional intraventricular routes of administration using in vivo human xenograft models of breast cancer that have metastasized to the brain. Results: Here, we have shown that HER2-CARs containing the 4-1BB costimulatory domain confer improved tumor targeting with reduced T-cell exhaustion phenotype and enhanced proliferative capacity compared with HER2-CARs containing the CD28 costimulatory domain. Local intracranial delivery of HER2-CARs showed potent in vivo antitumor activity in orthotopic xenograft models. Importantly, we demonstrated robust antitumor efficacy following regional intraventricular delivery of HER2-CAR T cells for the treatment of multifocal brain metastases and leptomeningeal disease. Conclusions: Our study shows the importance of CAR design in defining an optimized CAR T cell, and highlights intraventricular delivery of HER2-CAR T cells for treating multifocal brain metastases. Clin Cancer Res; 24(1); 95-105. ©2017 AACR . ©2017 American Association for Cancer Research.

A system architecture for sharing de-identified, research-ready brain scans and health information across clinical imaging centers.

PubMed

Chervenak, Ann L; van Erp, Theo G M; Kesselman, Carl; D'Arcy, Mike; Sobell, Janet; Keator, David; Dahm, Lisa; Murry, Jim; Law, Meng; Hasso, Anton; Ames, Joseph; Macciardi, Fabio; Potkin, Steven G

2012-01-01

Progress in our understanding of brain disorders increasingly relies on the costly collection of large standardized brain magnetic resonance imaging (MRI) data sets. Moreover, the clinical interpretation of brain scans benefits from compare and contrast analyses of scans from patients with similar, and sometimes rare, demographic, diagnostic, and treatment status. A solution to both needs is to acquire standardized, research-ready clinical brain scans and to build the information technology infrastructure to share such scans, along with other pertinent information, across hospitals. This paper describes the design, deployment, and operation of a federated imaging system that captures and shares standardized, de-identified clinical brain images in a federation across multiple institutions. In addition to describing innovative aspects of the system architecture and our initial testing of the deployed infrastructure, we also describe the Standardized Imaging Protocol (SIP) developed for the project and our interactions with the Institutional Review Board (IRB) regarding handling patient data in the federated environment.

A System Architecture for Sharing De-Identified, Research-Ready Brain Scans and Health Information Across Clinical Imaging Centers

PubMed Central

Chervenak, Ann L.; van Erp, Theo G.M.; Kesselman, Carl; D’Arcy, Mike; Sobell, Janet; Keator, David; Dahm, Lisa; Murry, Jim; Law, Meng; Hasso, Anton; Ames, Joseph; Macciardi, Fabio; Potkin, Steven G.

2015-01-01

Progress in our understanding of brain disorders increasingly relies on the costly collection of large standardized brain magnetic resonance imaging (MRI) data sets. Moreover, the clinical interpretation of brain scans benefits from compare and contrast analyses of scans from patients with similar, and sometimes rare, demographic, diagnostic, and treatment status. A solution to both needs is to acquire standardized, research-ready clinical brain scans and to build the information technology infrastructure to share such scans, along with other pertinent information, across hospitals. This paper describes the design, deployment, and operation of a federated imaging system that captures and shares standardized, de-identified clinical brain images in a federation across multiple institutions. In addition to describing innovative aspects of the system architecture and our initial testing of the deployed infrastructure, we also describe the Standardized Imaging Protocol (SIP) developed for the project and our interactions with the Institutional Review Board (IRB) regarding handling patient data in the federated environment. PMID:22941984

The Peptide Oxytocin Antagonist F-792, When Given Systemically, Does Not Act Centrally in Lactating Rats.

PubMed

Leng, G; Russell, J A

2016-04-01

Oxytocin secreted by nerve terminals in the posterior pituitary has important actions for ensuring a successful outcome of pregnancy: it stimulates uterine contractions that lead to birth and it is essential in the milk-ejection reflex, enabling milk to be expelled from the mammary glands into the mouths of suckling young. Oxytocin also has important actions in the brain: released from dendrites of neurones that innervate the posterior pituitary, oxytocin auto-excites the neurones to fire action potentials in co-ordinated bursts, causing secretion of pulses of oxytocin. Central oxytocin actions are blocked by an oxytocin antagonist given into the brain and, consequently, milk transfer stops. Systemic peptide oxytocin antagonist (atosiban) treatment is used clinically in management of pre-term labour, a major obstetric problem. Hence, it is important to know whether an oxytocin antagonist given peripherally can enter the brain and interfere with central oxytocin actions. In the present study, we tested F792, a peptide oxytocin antagonist. In urethane-anaesthetised suckled rats, we show that the mammary gland responsiveness to oxytocin is blocked by i.v. injections of 7 μg/kg of F792, and the milk-ejection reflex is blocked when F792 is given directly into the brain at a dose of 0.2 μg. To critically test whether F792 given systemically can enter the brain, we recorded the suckling- and oxytocin-induced burst-firing of individual antidromically identified oxytocin neurones in the paraventricular nucleus. Given systemically at 100 μg/kg i.v., F792 acted only peripherally, blocking the milk-ejecting actions of oxytocin, but not the burst-firing of oxytocin neurones during suckling (n = 5 neurones in five rats). Hence, this peptide oxytocin antagonist does not enter the brain from the circulation to interfere with an essential oxytocin function in the brain. Furthermore, the functions of oxytocin in the brain evidently cannot be explored with a systemic peptide antagonist. © 2015 British Society for Neuroendocrinology.

The Role of Clinical Proteomics, Lipidomics, and Genomics in the Diagnosis of Alzheimer's Disease.

PubMed

Martins, Ian James

2016-03-31

The early diagnosis of Alzheimer's disease (AD) has become important to the reversal and treatment of neurodegeneration, which may be relevant to premature brain aging that is associated with chronic disease progression. Clinical proteomics allows the detection of various proteins in fluids such as the urine, plasma, and cerebrospinal fluid for the diagnosis of AD. Interest in lipidomics has accelerated with plasma testing for various lipid biomarkers that may with clinical proteomics provide a more reproducible diagnosis for early brain aging that is connected to other chronic diseases. The combination of proteomics with lipidomics may decrease the biological variability between studies and provide reproducible results that detect a community's susceptibility to AD. The diagnosis of chronic disease associated with AD that now involves genomics may provide increased sensitivity to avoid inadvertent errors related to plasma versus cerebrospinal fluid testing by proteomics and lipidomics that identify new disease biomarkers in body fluids, cells, and tissues. The diagnosis of AD by various plasma biomarkers with clinical proteomics may now require the involvement of lipidomics and genomics to provide interpretation of proteomic results from various laboratories around the world.

Symptom validity testing in memory clinics: Hippocampal-memory associations and relevance for diagnosing mild cognitive impairment.

PubMed

Rienstra, Anne; Groot, Paul F C; Spaan, Pauline E J; Majoie, Charles B L M; Nederveen, Aart J; Walstra, Gerard J M; de Jonghe, Jos F M; van Gool, Willem A; Olabarriaga, Silvia D; Korkhov, Vladimir V; Schmand, Ben

2013-01-01

Patients with mild cognitive impairment (MCI) do not always convert to dementia. In such cases, abnormal neuropsychological test results may not validly reflect cognitive symptoms due to brain disease, and the usual brain-behavior relationships may be absent. This study examined symptom validity in a memory clinic sample and its effect on the associations between hippocampal volume and memory performance. Eleven of 170 consecutive patients (6.5%; 13% of patients younger than 65 years) referred to memory clinics showed noncredible performance on symptom validity tests (SVTs, viz. Word Memory Test and Test of Memory Malingering). They were compared to a demographically matched group (n = 57) selected from the remaining patients. Hippocampal volume, measured by an automated volumetric method (Freesurfer), was correlated with scores on six verbal memory tests. The median correlation was r = .49 in the matched group. However, the relation was absent (median r = -.11) in patients who failed SVTs. Memory clinic samples may include patients who show noncredible performance, which invalidates their MCI diagnosis. This underscores the importance of applying SVTs in evaluating patients with cognitive complaints that may signify a predementia stage, especially when these patients are relatively young.

Can nutraceuticals prevent Alzheimer's disease? Potential therapeutic role of a formulation containing shilajit and complex B vitamins.

PubMed

Carrasco-Gallardo, Carlos; Farías, Gonzalo A; Fuentes, Patricio; Crespo, Fernando; Maccioni, Ricardo B

2012-11-01

Alzheimer's disease (AD) is a brain disorder displaying a prevalence and impact in constant expansion. This expansive and epidemic behavior is concerning medical and public opinion while focusing efforts on its prevention and treatment. One important strategy to prevent this brain impairment is based on dietary changes and nutritional supplements, functional foods and nutraceuticals. In this review we discuss the potential contributions of shilajit and complex B vitamins to AD prevention. We analyze the status of biological studies and present data of a clinical trial developed in patients with mild AD. Studies suggest that shilajit and its active principle fulvic acid, as well as a formula of shilajit with B complex vitamins, emerge as novel nutraceutical with potential uses against this brain disorder. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

Postischemic dementia with Alzheimer phenotype: selectively vulnerable versus resistant areas of the brain and neurodegeneration versus β-amyloid peptide.

PubMed

Pluta, Ryszard; Jabłoński, Mirosław; Czuczwar, Stanisław J

2012-01-01

The road to clarity for postischemic dementia mechanisms has been one fraught with a wide range of complications and numerous revisions with a lack of a final solution. Importantly, brain ischemia is a leading cause of death and cognitive impairment worldwide. However, the mechanisms of progressive cognitive decline following brain ischemia are not yet certain. Data from animal models and clinical pioneering studies of brain ischemia have demonstrated an increase in expression and processing of amyloid precursor protein to a neurotoxin oligomeric β-amyloid peptide. Functional and memory brain restoration after ischemic brain injury is delayed and incomplete due to a lesion related increase in the amount of the neurotoxin amyloid protein. Moreover, ischemic injury is strongly accelerated by aging, too. In this review, we will present our current thinking about biogenesis of amyloid from the amyloid precursor protein in ischemic brain injury, and how this factor presents etiological, therapeutic and diagnostic targets that are now under consideration. Progressive injury of the ischemic brain parenchyma may be caused not only by degeneration of selectively vulnerable neurons destroyed during ischemia but also by acute and chronic damage of resistant areas of the brain and progressive damage in the blood-brain barrier. We propose that in postischemic dementia an initial ischemic injury precedes the cerebrovascular and brain parenchyma accumulation of Alzheimer disease related neurotoxin β-amyloid peptide, which in turn amplifies the neurovascular dysfunction triggering focal ischemic episodes as a vicious cycle preceding final neurodegenerative pathology. Persistent ischemic blood-brain barrier insufficiency with accumulation of neurotoxin β-amyloid protein in the brain tissue, especially in extracellular perivascular space and blood-brain barrier microvessels, may gradually, over a lifetime, progress to brain atrophy and to full-blown ischemic dementia with Alzheimer phenotype.

Controversies about the enhanced vulnerability of the adolescent brain to develop addiction.

PubMed

Bernheim, Aurélien; Halfon, Olivier; Boutrel, Benjamin

2013-11-28

Adolescence, defined as a transition phase toward autonomy and independence, is a natural time of learning and adjustment, particularly in the setting of long-term goals and personal aspirations. It also is a period of heightened sensation seeking, including risk taking and reckless behaviors, which is a major cause of morbidity and mortality among teenagers. Recent observations suggest that a relative immaturity in frontal cortical neural systems may underlie the adolescent propensity for uninhibited risk taking and hazardous behaviors. However, converging preclinical and clinical studies do not support a simple model of frontal cortical immaturity, and there is substantial evidence that adolescents engage in dangerous activities, including drug abuse, despite knowing and understanding the risks involved. Therefore, a current consensus considers that much brain development during adolescence occurs in brain regions and systems that are critically involved in the perception and evaluation of risk and reward, leading to important changes in social and affective processing. Hence, rather than naive, immature and vulnerable, the adolescent brain, particularly the prefrontal cortex, should be considered as prewired for expecting novel experiences. In this perspective, thrill seeking may not represent a danger but rather a window of opportunities permitting the development of cognitive control through multiple experiences. However, if the maturation of brain systems implicated in self-regulation is contextually dependent, it is important to understand which experiences matter most. In particular, it is essential to unveil the underpinning mechanisms by which recurrent adverse episodes of stress or unrestricted access to drugs can shape the adolescent brain and potentially trigger life-long maladaptive responses.

Gelsolin as therapeutic target in Alzheimer's disease.

PubMed

Carro, Eva

2010-06-01

Fibrillar amyloid beta-protein (Abeta) is a major component of amyloid plaques in the brains of individuals with Alzheimer's disease (AD). However, a comprehensive explanation of the mechanisms leading to brain amyloidosis is still pending. Previous studies have identified the anti-amyloidogenic role of gelsolin in AD. Gelsolin can reduce amyloid burden by acting as an inhibitor of Abeta fibrillization, and as an antioxidant and anti-apoptotic protein. Recent evidence indicates reduced brain gelsolin levels in AD. Therefore, a better understanding of the roles of gelsolin in AD pathology, particularly those related with cognition, is required. Most of the information reviewed here relates to experimental studies. However, gelsolin may progress from the present evidence to preclinical and clinical applications. In addition, a greater insight into the environmental factors contributing to abnormally reduced gelsolin function in AD brains may become crucial for the development of much needed disease-modifying strategies. Because, the efficacy of available medicines is still poor, there is an urgent need for novel AD treatments. In this sense, gelsolin could play an important role.

Tuberculous brain abscess and subdural empyema in an immunocompetent child: Significance of AFB staining in aspirated pus

PubMed Central

Vijayakumar, B.; Sarin, K.; Mohan, Girija

2012-01-01

Tuberculous brain abscess and subdural empyema are extremely rare manifestations of central nervous system tuberculosis. Here, we report a case of an 11-year-old immunocompetent child who developed temporal lobe abscess and subdural empyema following chronic otitis media. A right temporal craniotomy was performed and the abscess was excised. The Ziehl Nielsen staining of the aspirated pus from the temporal lobe abscess yielded acid fast bacilli. Prompt administration of antituberculous treatment resulted in complete recovery of the child. Even though the subdural abscess was not drained, we presume that to be of tubercular aetiology. Ours is probably the first case of brain abscess and subdural empyema due to Mycobacterium tuberculosis reported in the same child. This case is being reported because of its rarity and to stress the importance of routine staining for tubercle bacilli in all cases of brain abscess, especially in endemic areas, as it is difficult to differentiate tuberculous from pyogenic abscess clinically as well as histopathologically. PMID:22566728

Tuberculous brain abscess and subdural empyema in an immunocompetent child: Significance of AFB staining in aspirated pus.

PubMed

Vijayakumar, B; Sarin, K; Mohan, Girija

2012-04-01

Tuberculous brain abscess and subdural empyema are extremely rare manifestations of central nervous system tuberculosis. Here, we report a case of an 11-year-old immunocompetent child who developed temporal lobe abscess and subdural empyema following chronic otitis media. A right temporal craniotomy was performed and the abscess was excised. The Ziehl Nielsen staining of the aspirated pus from the temporal lobe abscess yielded acid fast bacilli. Prompt administration of antituberculous treatment resulted in complete recovery of the child. Even though the subdural abscess was not drained, we presume that to be of tubercular aetiology. Ours is probably the first case of brain abscess and subdural empyema due to Mycobacterium tuberculosis reported in the same child. This case is being reported because of its rarity and to stress the importance of routine staining for tubercle bacilli in all cases of brain abscess, especially in endemic areas, as it is difficult to differentiate tuberculous from pyogenic abscess clinically as well as histopathologically.

Emerging MRI and metabolic neuroimaging techniques in mild traumatic brain injury.

PubMed

Lu, Liyan; Wei, Xiaoer; Li, Minghua; Li, Yuehua; Li, Wenbin

2014-01-01

Traumatic brain injury (TBI) is one of the leading causes of death worldwide, and mild traumatic brain injury (mTBI) is the most common traumatic injury. It is difficult to detect mTBI using a routine neuroimaging. Advanced techniques with greater sensitivity and specificity for the diagnosis and treatment of mTBI are required. The aim of this review is to offer an overview of various emerging neuroimaging methodologies that can solve the clinical health problems associated with mTBI. Important findings and improvements in neuroimaging that hold value for better detection, characterization and monitoring of objective brain injuries in patients with mTBI are presented. Conventional computed tomography (CT) and magnetic resonance imaging (MRI) are not very efficient for visualizing mTBI. Moreover, techniques such as diffusion tensor imaging, magnetization transfer imaging, susceptibility-weighted imaging, functional MRI, single photon emission computed tomography, positron emission tomography and magnetic resonance spectroscopy imaging were found to be useful for mTBI imaging.

Molecular genetics in fetal neurology.

PubMed

Huang, Jin; Wah, Isabella Y M; Pooh, Ritsuko K; Choy, Kwong Wai

2012-12-01

Brain malformations, particularly related to early brain development, are a clinically and genetically heterogeneous group of fetal neurological disorders. Fetal cerebral malformation, predominantly of impaired prosencephalic development namely agenesis of the corpus callosum and septo-optic dysplasia, is the main pathological feature in fetus, and causes prominent neurodevelopmental retardation, and associated with congenital facial anomalies and visual disorders. Differential diagnosis of brain malformations can be extremely difficult even through magnetic resonance imaging. Advances in genomic and molecular genetics technologies have led to the identification of the sonic hedgehog pathways and genes critical to the normal brain development. Molecular cytogenetic and genetic studies have identified numeric and structural chromosomal abnormalities as well as mutations in genes important for the etiology of fetal neurological disorders. In this review, we update the molecular genetics findings of three common fetal neurological abnormalities, holoprosencephaly, lissencephaly and agenesis of the corpus callosum, in an attempt to assist in perinatal and prenatal diagnosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Skull removal in MR images using a modified artificial bee colony optimization algorithm.

PubMed

Taherdangkoo, Mohammad

2014-01-01

Removal of the skull from brain Magnetic Resonance (MR) images is an important preprocessing step required for other image analysis techniques such as brain tissue segmentation. In this paper, we propose a new algorithm based on the Artificial Bee Colony (ABC) optimization algorithm to remove the skull region from brain MR images. We modify the ABC algorithm using a different strategy for initializing the coordinates of scout bees and their direction of search. Moreover, we impose an additional constraint to the ABC algorithm to avoid the creation of discontinuous regions. We found that our algorithm successfully removed all bony skull from a sample of de-identified MR brain images acquired from different model scanners. The obtained results of the proposed algorithm compared with those of previously introduced well known optimization algorithms such as Particle Swarm Optimization (PSO) and Ant Colony Optimization (ACO) demonstrate the superior results and computational performance of our algorithm, suggesting its potential for clinical applications.

Future Directions for Examination of Brain Networks in Neurodevelopmental Disorders.

PubMed

Uddin, Lucina Q; Karlsgodt, Katherine H

2018-01-01

Neurodevelopmental disorders are associated with atypical development and maturation of brain networks. A recent focus on human connectomics research and the growing popularity of open science initiatives has created the ideal climate in which to make real progress toward understanding the neurobiology of disorders affecting youth. Here we outline future directions for neuroscience researchers examining brain networks in neurodevelopmental disorders, highlighting gaps in the current literature. We emphasize the importance of leveraging large neuroimaging and phenotypic data sets recently made available to the research community, and we suggest specific novel methodological approaches, including analysis of brain dynamics and structural connectivity, that have the potential to produce the greatest clinical insight. Transdiagnostic approaches will also become increasingly necessary as the Research Domain Criteria framework put forth by the National Institute of Mental Health permeates scientific discourse. During this exciting era of big data and increased computational sophistication of analytic tools, the possibilities for significant advancement in understanding neurodevelopmental disorders are limitless.

The promises and pitfalls of applying computational models to neurological and psychiatric disorders.

PubMed

Teufel, Christoph; Fletcher, Paul C

2016-10-01

Computational models have become an integral part of basic neuroscience and have facilitated some of the major advances in the field. More recently, such models have also been applied to the understanding of disruptions in brain function. In this review, using examples and a simple analogy, we discuss the potential for computational models to inform our understanding of brain function and dysfunction. We argue that they may provide, in unprecedented detail, an understanding of the neurobiological and mental basis of brain disorders and that such insights will be key to progress in diagnosis and treatment. However, there are also potential problems attending this approach. We highlight these and identify simple principles that should always govern the use of computational models in clinical neuroscience, noting especially the importance of a clear specification of a model's purpose and of the mapping between mathematical concepts and reality. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Clinician perspectives on decision-making capacity after acquired brain injury.

PubMed

Mukherjee, Debjani; McDonough, Carol

2006-01-01

Acquired brain injury frequently alters an individual's ability to make health care decisions based on a clear understanding of the situation and options. This exploratory study investigated the ways health care providers address issues of decisionmaking capacity (DMC) on a daily, functional basis. 33 clinicians providing rehabilitation services to persons with acquired brain injury participated in 1 of 5 semi-structured focus groups. All 33 participants, representing 8 different occupations, agreed that DMC determinations affected their practice every day. Participants underscored a multidimensional rather than a unitary definition of DMC, with an emphasis on fluctuating capacities due to the injury. Important concerns were for the safety of the person with brain injury, the health care provider, and community members. Other themes included rehabilitation team involvement, family context, and professional socialization. Clinical determinations of DMC are context dependent and are affected by the abilities of the individual and the substance and consequences of the decision being made and include the concepts of regaining trust and reclaiming capacity.

Consciousness Regained: Disentangling Mechanisms, Brain Systems, and Behavioral Responses

PubMed Central

2017-01-01

How consciousness (experience) arises from and relates to material brain processes (the “mind-body problem”) has been pondered by thinkers for centuries, and is regarded as among the deepest unsolved problems in science, with wide-ranging theoretical, clinical, and ethical implications. Until the last few decades, this was largely seen as a philosophical topic, but not widely accepted in mainstream neuroscience. Since the 1980s, however, novel methods and theoretical advances have yielded remarkable results, opening up the field for scientific and clinical progress. Since a seminal paper by Crick and Koch (1998) claimed that a science of consciousness should first search for its neural correlates (NCC), a variety of correlates have been suggested, including both content-specific NCCs, determining particular phenomenal components within an experience, and the full NCC, the neural substrates supporting entire conscious experiences. In this review, we present recent progress on theoretical, experimental, and clinical issues. Specifically, we (1) review methodological advances that are important for dissociating conscious experience from related enabling and executive functions, (2) suggest how critically reconsidering the role of the frontal cortex may further delineate NCCs, (3) advocate the need for general, objective, brain-based measures of the capacity for consciousness that are independent of sensory processing and executive functions, and (4) show how animal studies can reveal population and network phenomena of relevance for understanding mechanisms of consciousness. PMID:29118218

Traumatic brain injury produced by exposure to blasts, a critical problem in current wars: biomarkers, clinical studies, and animal models

NASA Astrophysics Data System (ADS)

Dixon, C. Edward

2011-06-01

Traumatic brain injury (TBI) resulting from exposure to blast energy released by Improvised Explosive Devices (IEDs) has been recognized as the "signature injury" of Operation Iraqi Freedom and Operation Enduring Freedom. Repeated exposure to mild blasts may produce subtle deficits that are difficult to detect and quantify. Several techniques have been used to detect subtle brain dysfunction including neuropsychological assessments, computerized function testing and neuroimaging. Another approach is based on measurement of biologic substances (e.g. proteins) that are released into the body after a TBI. Recent studies measuring biomarkers in CSF and serum from patients with severe TBI have demonstrated the diagnostic, prognostic, and monitoring potential. Advancement of the field will require 1) biochemical mining for new biomarker candidates, 2) clinical validation of utility, 3) technical advances for more sensitive, portable detectors, 4) novel statistical approach to evaluate multiple biomarkers, and 5) commercialization. Animal models have been developed to simulate elements of blast-relevant TBI including gas-driven shock tubes to generate pressure waves similar to those produced by explosives. These models can reproduce hallmark clinical neuropathological responses such as neuronal degeneration and inflammation, as well as behavioral impairments. An important application of these models is to screen novel therapies and conduct proteomic, genomic, and lipodomic studies to mine for new biomarker candidates specific to blast relevant TBI.

Review article: the endocannabinoid system in liver disease, a potential therapeutic target.

PubMed

Basu, P P; Aloysius, M M; Shah, N J; Brown, R S

2014-04-01

Endocannabinoids are a family of potent lipid-soluble molecules, acting on the cannabinoid (CB) receptors that mediate the effects of marijuana. The CB receptors, endocannabinoids and the enzymes involved in their synthesis and degradation are located in the brain and peripheral tissues, including the liver. To review the current understanding of the role of the endocannabinoid system in liver disease-associated pathophysiological conditions, and drugs targeting the endocannabinoid system as therapy for liver disease. Original articles and reviews were used to summarise the relevant pre-clinical and clinical research findings relating to this topic. The endocannabinoid system as a whole plays an important role in liver diseases (i.e. non-alcoholic liver disease, alcoholic liver disease, hepatic encephalopathy and autoimmune hepatitis) and related pathophysiological conditions (i.e. altered hepatic haemodynamics, cirrhotic cardiomyopathy, metabolic syndrome and ischaemia/reperfusion disease). Pharmacological targeting of the endocannabinoid system has had success as treatment for patients with liver disease, but adverse events led to withdrawal of marketing approval. However, there is optimism over novel therapeutics targeting the endocannabinoid system currently in the pre-clinical stage of development. The endocannabinoid system plays an important role in the pathophysiology of liver disease and its associated conditions. While some drugs targeting the endocannabinoid system have deleterious neurological adverse events, there is promise for a newer generation of therapies that do not cross the blood-brain barrier. © 2014 John Wiley & Sons Ltd.

Brain age and other bodily 'ages': implications for neuropsychiatry.

PubMed

Cole, James H; Marioni, Riccardo E; Harris, Sarah E; Deary, Ian J

2018-06-11

As our brains age, we tend to experience cognitive decline and are at greater risk of neurodegenerative disease and dementia. Symptoms of chronic neuropsychiatric diseases are also exacerbated during ageing. However, the ageing process does not affect people uniformly; nor, in fact, does the ageing process appear to be uniform even within an individual. Here, we outline recent neuroimaging research into brain ageing and the use of other bodily ageing biomarkers, including telomere length, the epigenetic clock, and grip strength. Some of these techniques, using statistical approaches, have the ability to predict chronological age in healthy people. Moreover, they are now being applied to neurological and psychiatric disease groups to provide insights into how these diseases interact with the ageing process and to deliver individualised predictions about future brain and body health. We discuss the importance of integrating different types of biological measurements, from both the brain and the rest of the body, to build more comprehensive models of the biological ageing process. Finally, we propose seven steps for the field of brain-ageing research to take in coming years. This will help us reach the long-term goal of developing clinically applicable statistical models of biological processes to measure, track and predict brain and body health in ageing and disease.

Characterizing Focused-Ultrasound Mediated Drug Delivery to the Heterogeneous Primate Brain In Vivo with Acoustic Monitoring

NASA Astrophysics Data System (ADS)

Wu, Shih-Ying; Sanchez, Carlos Sierra; Samiotaki, Gesthimani; Buch, Amanda; Ferrera, Vincent P.; Konofagou, Elisa E.

2016-11-01

Focused ultrasound with microbubbles has been used to noninvasively and selectively deliver pharmacological agents across the blood-brain barrier (BBB) for treating brain diseases. Acoustic cavitation monitoring could serve as an on-line tool to assess and control the treatment. While it demonstrated a strong correlation in small animals, its translation to primates remains in question due to the anatomically different and highly heterogeneous brain structures with gray and white matteras well as dense vasculature. In addition, the drug delivery efficiency and the BBB opening volume have never been shown to be predictable through cavitation monitoring in primates. This study aimed at determining how cavitation activity is correlated with the amount and concentration of gadolinium delivered through the BBB and its associated delivery efficiency as well as the BBB opening volume in non-human primates. Another important finding entails the effect of heterogeneous brain anatomy and vasculature of a primate brain, i.e., presence of large cerebral vessels, gray and white matter that will also affect the cavitation activity associated with variation of BBB opening in different tissue types, which is not typically observed in small animals. Both these new findings are critical in the primate brain and provide essential information for clinical applications.

Loss of T cells influences sex differences in behavior and brain structure.

PubMed

Rilett, Kelly C; Friedel, Miriam; Ellegood, Jacob; MacKenzie, Robyn N; Lerch, Jason P; Foster, Jane A

2015-05-01

Clinical and animal studies demonstrate that immune-brain communication influences behavior and brain function. Mice lacking T cell receptor β and δ chains were tested in the elevated plus maze, open field, and light-dark test and showed reduced anxiety-like behavior compared to wild type. Interestingly sex differences were observed in the behavioural phenotype of TCRβ-/-δ- mice. Specifically, female TCRβ-/-δ- mice spent more time in the light chamber compared to wild type females, whereas male TCRβ-/-δ- spent more time in the center of the open field compared to wild type males. In addition, TCRβ-/-δ- mice did not show sex differences in activity-related behaviors observed in WT mice. Ex vivo brain imaging (7 Tesla MRI) revealed volume changes in hippocampus, hypothalamus, amygdala, periaqueductal gray, and dorsal raphe and other brain regions between wild type and T cell receptor knockout mice. There was also a loss of sexual dimorphism in brain volume in the bed nucleus of the stria terminalis, normally the most sexually dimorphic region in the brain, in immune compromised mice. These data demonstrate the presence of T cells is important in the development of sex differences in CNS circuitry and behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterizing Focused-Ultrasound Mediated Drug Delivery to the Heterogeneous Primate Brain In Vivo with Acoustic Monitoring

PubMed Central

Wu, Shih-Ying; Sanchez, Carlos Sierra; Samiotaki, Gesthimani; Buch, Amanda; Ferrera, Vincent P.; Konofagou, Elisa E.

2016-01-01

Focused ultrasound with microbubbles has been used to noninvasively and selectively deliver pharmacological agents across the blood-brain barrier (BBB) for treating brain diseases. Acoustic cavitation monitoring could serve as an on-line tool to assess and control the treatment. While it demonstrated a strong correlation in small animals, its translation to primates remains in question due to the anatomically different and highly heterogeneous brain structures with gray and white matteras well as dense vasculature. In addition, the drug delivery efficiency and the BBB opening volume have never been shown to be predictable through cavitation monitoring in primates. This study aimed at determining how cavitation activity is correlated with the amount and concentration of gadolinium delivered through the BBB and its associated delivery efficiency as well as the BBB opening volume in non-human primates. Another important finding entails the effect of heterogeneous brain anatomy and vasculature of a primate brain, i.e., presence of large cerebral vessels, gray and white matter that will also affect the cavitation activity associated with variation of BBB opening in different tissue types, which is not typically observed in small animals. Both these new findings are critical in the primate brain and provide essential information for clinical applications. PMID:27853267

Intestinal microbiome-gut-brain axis and irritable bowel syndrome.

PubMed

Moser, Gabriele; Fournier, Camille; Peter, Johannes

2018-03-01

Psychological comorbidity is highly present in irritable bowel syndrome (IBS). Recent research points to a role of intestinal microbiota in visceral hypersensitivity, anxiety, and depression. Increased disease reactivity to psychological stress has been described too. A few clinical studies have attempted to identify features of dysbiosis in IBS. While animal studies revealed strong associations between stress and gut microbiota, studies in humans are rare. This review covers the most important studies on intestinal microbial correlates of psychological and clinical features in IBS, including stress, anxiety, and depression.

Neurological Disease in Lupus: Toward a Personalized Medicine Approach.

PubMed

McGlasson, Sarah; Wiseman, Stewart; Wardlaw, Joanna; Dhaun, Neeraj; Hunt, David P J

2018-01-01

The brain and nervous system are important targets for immune-mediated damage in systemic lupus erythematosus (SLE), resulting in a complex spectrum of neurological syndromes. Defining nervous system disease in lupus poses significant challenges. Among the difficulties to be addressed are a diversity of clinical manifestations and a lack of understanding of their mechanistic basis. However, despite these challenges, progress has been made in the identification of pathways which contribute to neurological disease in SLE. Understanding the molecular pathogenesis of neurological disease in lupus will inform both classification and approaches to clinical trials.

Semiautomated Workflow for Clinically Streamlined Glioma Parametric Response Mapping

PubMed Central

Keith, Lauren; Ross, Brian D.; Galbán, Craig J.; Luker, Gary D.; Galbán, Stefanie; Zhao, Binsheng; Guo, Xiaotao; Chenevert, Thomas L.; Hoff, Benjamin A.

2017-01-01

Management of glioblastoma multiforme remains a challenging problem despite recent advances in targeted therapies. Timely assessment of therapeutic agents is hindered by the lack of standard quantitative imaging protocols for determining targeted response. Clinical response assessment for brain tumors is determined by volumetric changes assessed at 10 weeks post-treatment initiation. Further, current clinical criteria fail to use advanced quantitative imaging approaches, such as diffusion and perfusion magnetic resonance imaging. Development of the parametric response mapping (PRM) applied to diffusion-weighted magnetic resonance imaging has provided a sensitive and early biomarker of successful cytotoxic therapy in brain tumors while maintaining a spatial context within the tumor. Although PRM provides an earlier readout than volumetry and sometimes greater sensitivity compared with traditional whole-tumor diffusion statistics, it is not routinely used for patient management; an automated and standardized software for performing the analysis and for the generation of a clinical report document is required for this. We present a semiautomated and seamless workflow for image coregistration, segmentation, and PRM classification of glioblastoma multiforme diffusion-weighted magnetic resonance imaging scans. The software solution can be integrated using local hardware or performed remotely in the cloud while providing connectivity to existing picture archive and communication systems. This is an important step toward implementing PRM analysis of solid tumors in routine clinical practice. PMID:28286871

Neuroimaging and Neuromodulation: Complementary Approaches for Identifying the Neuronal Correlates of Tinnitus

PubMed Central

Langguth, Berthold; Schecklmann, Martin; Lehner, Astrid; Landgrebe, Michael; Poeppl, Timm Benjamin; Kreuzer, Peter Michal; Schlee, Winfried; Weisz, Nathan; Vanneste, Sven; De Ridder, Dirk

2012-01-01

An inherent limitation of functional imaging studies is their correlational approach. More information about critical contributions of specific brain regions can be gained by focal transient perturbation of neural activity in specific regions with non-invasive focal brain stimulation methods. Functional imaging studies have revealed that tinnitus is related to alterations in neuronal activity of central auditory pathways. Modulation of neuronal activity in auditory cortical areas by repetitive transcranial magnetic stimulation (rTMS) can reduce tinnitus loudness and, if applied repeatedly, exerts therapeutic effects, confirming the relevance of auditory cortex activation for tinnitus generation and persistence. Measurements of oscillatory brain activity before and after rTMS demonstrate that the same stimulation protocol has different effects on brain activity in different patients, presumably related to interindividual differences in baseline activity in the clinically heterogeneous study cohort. In addition to alterations in auditory pathways, imaging techniques also indicate the involvement of non-auditory brain areas, such as the fronto-parietal “awareness” network and the non-tinnitus-specific distress network consisting of the anterior cingulate cortex, anterior insula, and amygdale. Involvement of the hippocampus and the parahippocampal region putatively reflects the relevance of memory mechanisms in the persistence of the phantom percept and the associated distress. Preliminary studies targeting the dorsolateral prefrontal cortex, the dorsal anterior cingulate cortex, and the parietal cortex with rTMS and with transcranial direct current stimulation confirm the relevance of the mentioned non-auditory networks. Available data indicate the important value added by brain stimulation as a complementary approach to neuroimaging for identifying the neuronal correlates of the various clinical aspects of tinnitus. PMID:22509155

Preterm EEG: a multimodal neurophysiological protocol.

PubMed

Stjerna, Susanna; Voipio, Juha; Metsäranta, Marjo; Kaila, Kai; Vanhatalo, Sampsa

2012-02-18

Since its introduction in early 1950s, electroencephalography (EEG) has been widely used in the neonatal intensive care units (NICU) for assessment and monitoring of brain function in preterm and term babies. Most common indications are the diagnosis of epileptic seizures, assessment of brain maturity, and recovery from hypoxic-ischemic events. EEG recording techniques and the understanding of neonatal EEG signals have dramatically improved, but these advances have been slow to penetrate through the clinical traditions. The aim of this presentation is to bring theory and practice of advanced EEG recording available for neonatal units. In the theoretical part, we will present animations to illustrate how a preterm brain gives rise to spontaneous and evoked EEG activities, both of which are unique to this developmental phase, as well as crucial for a proper brain maturation. Recent animal work has shown that the structural brain development is clearly reflected in early EEG activity. Most important structures in this regard are the growing long range connections and the transient cortical structure, subplate. Sensory stimuli in a preterm baby will generate responses that are seen at a single trial level, and they have underpinnings in the subplate-cortex interaction. This brings neonatal EEG readily into a multimodal study, where EEG is not only recording cortical function, but it also tests subplate function via different sensory modalities. Finally, introduction of clinically suitable dense array EEG caps, as well as amplifiers capable of recording low frequencies, have disclosed multitude of brain activities that have as yet been overlooked. In the practical part of this video, we show how a multimodal, dense array EEG study is performed in neonatal intensive care unit from a preterm baby in the incubator. The video demonstrates preparation of the baby and incubator, application of the EEG cap, and performance of the sensory stimulations.

An investigation of fMRI time series stationarity during motor sequence learning foot tapping tasks.

PubMed

Muhei-aldin, Othman; VanSwearingen, Jessie; Karim, Helmet; Huppert, Theodore; Sparto, Patrick J; Erickson, Kirk I; Sejdić, Ervin

2014-04-30

Understanding complex brain networks using functional magnetic resonance imaging (fMRI) is of great interest to clinical and scientific communities. To utilize advanced analysis methods such as graph theory for these investigations, the stationarity of fMRI time series needs to be understood as it has important implications on the choice of appropriate approaches for the analysis of complex brain networks. In this paper, we investigated the stationarity of fMRI time series acquired from twelve healthy participants while they performed a motor (foot tapping sequence) learning task. Since prior studies have documented that learning is associated with systematic changes in brain activation, a sequence learning task is an optimal paradigm to assess the degree of non-stationarity in fMRI time-series in clinically relevant brain areas. We predicted that brain regions involved in a "learning network" would demonstrate non-stationarity and may violate assumptions associated with some advanced analysis approaches. Six blocks of learning, and six control blocks of a foot tapping sequence were performed in a fixed order. The reverse arrangement test was utilized to investigate the time series stationarity. Our analysis showed some non-stationary signals with a time varying first moment as a major source of non-stationarity. We also demonstrated a decreased number of non-stationarities in the third block as a result of priming and repetition. Most of the current literature does not examine stationarity prior to processing. The implication of our findings is that future investigations analyzing complex brain networks should utilize approaches robust to non-stationarities, as graph-theoretical approaches can be sensitive to non-stationarities present in data. Copyright © 2014 Elsevier B.V. All rights reserved.

Discovering the Importance of Play through Personal Histories and Brain Images: An Interview with Stuart L. Brown

ERIC Educational Resources Information Center

American Journal of Play, 2009

2009-01-01

Stuart L. Brown is founder of the National Institute for Play, a California-based, not-for-profit organization dedicated to the notion that play can help transform the lives of individuals, families, schools, and organizations. Trained in general and internal medicine, psychiatry, and clinical research, Brown was a physician in the United States…

The trouble with sex differences.

PubMed

Eliot, Lise

2011-12-22

Sex differences in the brain are real and clinically important but often grossly distorted in popular discourse. Considering the public's deep fascination with sex difference research and its impact on issues from mental health to education and workplace equity, neuroscientists should pay greater heed to its misappropriation and to studying how gender enculturation shapes neural function. Copyright © 2011 Elsevier Inc. All rights reserved.

A framework for correcting brain retraction based on an eXtended Finite Element Method using a laser range scanner.

PubMed

Li, Ping; Wang, Weiwei; Song, Zhijian; An, Yong; Zhang, Chenxi

2014-07-01

Brain retraction causes great distortion that limits the accuracy of an image-guided neurosurgery system that uses preoperative images. Therefore, brain retraction correction is an important intraoperative clinical application. We used a linear elastic biomechanical model, which deforms based on the eXtended Finite Element Method (XFEM) within a framework for brain retraction correction. In particular, a laser range scanner was introduced to obtain a surface point cloud of the exposed surgical field including retractors inserted into the brain. A brain retraction surface tracking algorithm converted these point clouds into boundary conditions applied to XFEM modeling that drive brain deformation. To test the framework, we performed a brain phantom experiment involving the retraction of tissue. Pairs of the modified Hausdorff distance between Canny edges extracted from model-updated images, pre-retraction, and post-retraction CT images were compared to evaluate the morphological alignment of our framework. Furthermore, the measured displacements of beads embedded in the brain phantom and the predicted ones were compared to evaluate numerical performance. The modified Hausdorff distance of 19 pairs of images decreased from 1.10 to 0.76 mm. The forecast error of 23 stainless steel beads in the phantom was between 0 and 1.73 mm (mean 1.19 mm). The correction accuracy varied between 52.8 and 100 % (mean 81.4 %). The results demonstrate that the brain retraction compensation can be incorporated intraoperatively into the model-updating process in image-guided neurosurgery systems.

Clinical Applications for EPs in the ICU.

PubMed

Koenig, Matthew A; Kaplan, Peter W

2015-12-01

In critically ill patients, evoked potential (EP) testing is an important tool for measuring neurologic function, signal transmission, and secondary processing of sensory information in real time. Evoked potential measures conduction along the peripheral and central sensory pathways with longer-latency potentials representing more complex thalamocortical and intracortical processing. In critically ill patients with limited neurologic exams, EP provides a window into brain function and the potential for recovery of consciousness. The most common EP modalities in clinical use in the intensive care unit include somatosensory evoked potentials, brainstem auditory EPs, and cortical event-related potentials. The primary indications for EP in critically ill patients are prognostication in anoxic-ischemic or traumatic coma, monitoring for neurologic improvement or decline, and confirmation of brain death. Somatosensory evoked potentials had become an important prognostic tool for coma recovery, especially in comatose survivors of cardiac arrest. In this population, the bilateral absence of cortical somatosensory evoked potentials has nearly 100% specificity for death or persistent vegetative state. Historically, EP has been regarded as a negative prognostic test, that is, the absence of cortical potentials is associated with poor outcomes while the presence cortical potentials are prognostically indeterminate. In recent studies, the presence of middle-latency and long-latency potentials as well as the amplitude of cortical potentials is more specific for good outcomes. Event-related potentials, particularly mismatch negativity of complex auditory patterns, is emerging as an important positive prognostic test in patients under comatose. Multimodality predictive algorithms that combine somatosensory evoked potentials, event-related potentials, and clinical and radiographic factors are gaining favor for coma prognostication.

Brain atrophy and lesion load measures over 1 year relate to clinical status after 6 years in patients with clinically isolated syndromes.

PubMed

Di Filippo, M; Anderson, V M; Altmann, D R; Swanton, J K; Plant, G T; Thompson, A J; Miller, D H

2010-02-01

Conventional MRI lesion measures modestly predict long term disability in some clinically isolated syndrome (CIS) studies. Brain atrophy suggests neuroaxonal loss in multiple sclerosis (MS) with the potential to reflect disease progression to a greater extent than lesion measures. To investigate whether brain atrophy and lesion load, during the first year in patients presenting with CIS, independently predict clinical outcome (development of MS and disability at 6 years). 99 patients presenting with CIS were included in the study. T1 gadolinium enhanced and T2 weighted brain MRI was acquired at baseline and approximately 1 year later. Percentage brain atrophy rate between baseline and follow-up scans was analysed using SIENA. Mean annual brain atrophy rates were -0.38% for all patients, -0.50% in patients who had developed MS at 6 years and -0.26% in those who had not. Brain atrophy rate (p = 0.005) and baseline T2 lesion load (p<0.001) were independent predictors of clinically definite MS. While brain atrophy rate was a predictor of Expanded Disability Status Scale (EDSS) score in a univariate analysis, only 1 year T2 lesion load change (p = 0.007) and baseline gadolinium enhancing lesion number (p = 0.03) were independent predictors of EDSS score at the 6 year follow-up. T1 lesion load was the only MRI parameter which predicted Multiple Sclerosis Functional Composite score at the 6 year follow-up. The findings confirm that brain atrophy occurs during the earliest phases of MS and suggest that 1 year longitudinal measures of MRI change, if considered together with baseline MRI variables, might help to predict clinical status 6 years after the first demyelinating event in CIS patients, better than measurements such as lesion or brain volumes on baseline MRI alone.

Label-free imaging of brain and brain tumor specimens with combined two-photon excited fluorescence and second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Jiang, Liwei; Wang, Xingfu; Wu, Zanyi; Du, Huiping; Wang, Shu; Li, Lianhuang; Fang, Na; Lin, Peihua; Chen, Jianxin; Kang, Dezhi; Zhuo, Shuangmu

2017-10-01

Label-free imaging techniques are gaining acceptance within the medical imaging field, including brain imaging, because they have the potential to be applied to intraoperative in situ identifications of pathological conditions. In this paper, we describe the use of two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) microscopy in combination for the label-free detection of brain and brain tumor specimens; gliomas. Two independently detecting channels were chosen to subsequently collect TPEF/SHG signals from the specimen to increase TPEF/SHG image contrasts. Our results indicate that the combined TPEF/SHG microscopic techniques can provide similar rat brain structural information and produce a similar resolution like conventional H&E staining in neuropathology; including meninges, cerebral cortex, white-matter structure corpus callosum, choroid plexus, hippocampus, striatum, and cerebellar cortex. It can simultaneously detect infiltrating human brain tumor cells, the extracellular matrix collagen fiber of connective stroma within brain vessels and collagen depostion in tumor microenvironments. The nuclear-to-cytoplasmic ratio and collagen content can be extracted as quantitative indicators for differentiating brain gliomas from healthy brain tissues. With the development of two-photon fiberscopes and microendoscope probes and their clinical applications, the combined TPEF and SHG microcopy may become an important multimodal, nonlinear optical imaging approach for real-time intraoperative histological diagnostics of residual brain tumors. These occur in various brain regions during ongoing surgeries through the method of simultaneously identifying tumor cells, and the change of tumor microenvironments, without the need for the removal biopsies and without the need for tissue labelling or fluorescent markers.

Concussion: the history of clinical and pathophysiological concepts and misconceptions.

PubMed

McCrory, P R; Berkovic, S F

2001-12-26

Concussion is a well-recognized clinical entity; however, its pathophysiologic basis remains a mystery. One unresolved issue is whether concussion is associated with lesser degrees of diffuse structural change seen in severe traumatic brain injury, or is the mechanism entirely caused by reversible functional changes. This issue is clouded not only by the lack of critical data, but also by confusion in terminology, even in contemporary literature. This confusion began in ancient times when no distinction was made between the transient effects of concussion and severe traumatic brain injury. The first clear separate recognition of concussion was made by the Persian physician, Rhazes, in the 10th century. Lanfrancus subsequently expanded this concept as brain "commotion" in the 13th century, although other Renaissance physicians continued to obscure this concept. By the 18th century, a variety of hypotheses for concussion had emerged. The 19th century discovery of petechial hemorrhagic lesions in severe traumatic brain injury led to these being posited as the basis of concussion, and a similar logic was used later to suggest diffuse axonal injury was responsible. The neuropathology and pathophysiology of concussion has important implications in neurology, sports medicine, medicolegal medicine, and in the understanding of consciousness. Fresh approaches to these questions are needed and modern research tools, including functional imaging and experimental studies of ion-channel function, could help elucidate this puzzle that has evolved over the past 3,000 years.

Finding regional models of the Alzheimer disease by fusing information from neuropsychological tests and structural MR images

NASA Astrophysics Data System (ADS)

Giraldo, Diana L.; García-Arteaga, Juan D.; Romero, Eduardo

2016-03-01

Initial diagnosis of Alzheimer's disease (AD) is based on the patient's clinical history and a battery of neuropsy-chological tests. This work presents an automatic strategy that uses Structural Magnetic Resonance Imaging (MRI) to learn brain models for different stages of the disease using information from clinical assessments. Then, a comparison of the discriminant power of the models in different anatomical areas is made by using the brain region of the models as a reference frame for the classification problem, by using the projection into the AD model a Receiver Operating Characteristic (ROC) curve is constructed. Validation was performed using a leave- one-out scheme with 86 subjects (20 AD and 60 NC) from the Open Access Series of Imaging Studies (OASIS) database. The region with the best classification performance was the left amygdala where it is possible to achieve a sensibility and specificity of 85% at the same time. The regions with the best performance, in terms of the AUC, are in strong agreement with those described as important for the diagnosis of AD in clinical practice.

Imaging outcome measures for progressive multiple sclerosis trials

PubMed Central

Moccia, Marcello; de Stefano, Nicola; Barkhof, Frederik

2017-01-01

Imaging markers that are reliable, reproducible and sensitive to neurodegenerative changes in progressive multiple sclerosis (MS) can enhance the development of new medications with a neuroprotective mode-of-action. Accordingly, in recent years, a considerable number of imaging biomarkers have been included in phase 2 and 3 clinical trials in primary and secondary progressive MS. Brain lesion count and volume are markers of inflammation and demyelination and are important outcomes even in progressive MS trials. Brain and, more recently, spinal cord atrophy are gaining relevance, considering their strong association with disability accrual; ongoing improvements in analysis methods will enhance their applicability in clinical trials, especially for cord atrophy. Advanced magnetic resonance imaging (MRI) techniques (e.g. magnetization transfer ratio (MTR), diffusion tensor imaging (DTI), spectroscopy) have been included in few trials so far and hold promise for the future, as they can reflect specific pathological changes targeted by neuroprotective treatments. Position emission tomography (PET) and optical coherence tomography have yet to be included. Applications, limitations and future perspectives of these techniques in clinical trials in progressive MS are discussed, with emphasis on measurement sensitivity, reliability and sample size calculation. PMID:29041865

Comprehensive evaluation of the child with intellectual disability or global developmental delays.

PubMed

Moeschler, John B; Shevell, Michael

2014-09-01

Global developmental delay and intellectual disability are relatively common pediatric conditions. This report describes the recommended clinical genetics diagnostic approach. The report is based on a review of published reports, most consisting of medium to large case series of diagnostic tests used, and the proportion of those that led to a diagnosis in such patients. Chromosome microarray is designated as a first-line test and replaces the standard karyotype and fluorescent in situ hybridization subtelomere tests for the child with intellectual disability of unknown etiology. Fragile X testing remains an important first-line test. The importance of considering testing for inborn errors of metabolism in this population is supported by a recent systematic review of the literature and several case series recently published. The role of brain MRI remains important in certain patients. There is also a discussion of the emerging literature on the use of whole-exome sequencing as a diagnostic test in this population. Finally, the importance of intentional comanagement among families, the medical home, and the clinical genetics specialty clinic is discussed. Copyright © 2014 by the American Academy of Pediatrics.

The brain network reflecting bodily self-consciousness: a functional connectivity study

PubMed Central

Ionta, Silvio; Martuzzi, Roberto; Salomon, Roy

2014-01-01

Several brain regions are important for processing self-location and first-person perspective, two important aspects of bodily self-consciousness. However, the interplay between these regions has not been clarified. In addition, while self-location and first-person perspective in healthy subjects are associated with bilateral activity in temporoparietal junction (TPJ), disturbed self-location and first-person perspective result from damage of only the right TPJ. Identifying the involved brain network and understanding the role of hemispheric specializations in encoding self-location and first-person perspective, will provide important information on system-level interactions neurally mediating bodily self-consciousness. Here, we used functional connectivity and showed that right and left TPJ are bilaterally connected to supplementary motor area, ventral premotor cortex, insula, intraparietal sulcus and occipitotemporal cortex. Furthermore, the functional connectivity between right TPJ and right insula had the highest selectivity for changes in self-location and first-person perspective. Finally, functional connectivity revealed hemispheric differences showing that self-location and first-person perspective modulated the connectivity between right TPJ, right posterior insula, and right supplementary motor area, and between left TPJ and right anterior insula. The present data extend previous evidence on healthy populations and clinical observations in neurological deficits, supporting a bilateral, but right-hemispheric dominant, network for bodily self-consciousness. PMID:24396007

Neural hijacking: action of high-frequency electrical stimulation on cortical circuits.

PubMed

Cheney, P D; Griffin, D M; Van Acker, G M

2013-10-01

Electrical stimulation of the brain was one of the first experimental methods applied to understanding brain organization and function and it continues as a highly useful method both in research and clinical applications. Intracortical microstimulation (ICMS) involves applying electrical stimuli through a microelectrode suitable for recording the action potentials of single neurons. ICMS can be categorized into single-pulse stimulation; high-frequency, short-duration stimulation; and high-frequency, long-duration stimulation. For clinical and experimental reasons, considerable interest focuses on the mechanism of neural activation by electrical stimuli. In this article, we discuss recent results suggesting that action potentials evoked in cortical neurons by high-frequency electrical stimulation do not sum with the natural, behaviorally related background activity; rather, high-frequency stimulation eliminates and replaces natural activity. We refer to this as neural hijacking. We propose that a major component of the mechanism underlying neural hijacking is excitation of axons by ICMS and elimination of natural spikes by antidromic collision with stimulus-driven spikes evoked at high frequency. Evidence also supports neural hijacking as an important mechanism underlying the action of deep brain stimulation in the subthalamic nucleus and its therapeutic effect in treating Parkinson's disease.

Current understanding of neuroinflammation after traumatic brain injury and cell-based therapeutic opportunities.

PubMed

Xiong, Ye; Mahmood, Asim; Chopp, Michael

2018-06-01

Traumatic brain injury (TBI) remains a major cause of death and disability worldwide. Increasing evidence indicates that TBI is an important risk factor for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and chronic traumatic encephalopathy. Despite improved supportive and rehabilitative care of TBI patients, unfortunately, all late phase clinical trials in TBI have yet to yield a safe and effective neuroprotective treatment. The disappointing clinical trials may be attributed to variability in treatment approaches and heterogeneity of the population of TBI patients as well as a race against time to prevent or reduce inexorable cell death. TBI is not just an acute event but a chronic disease. Among many mechanisms involved in secondary injury after TBI, emerging preclinical studies indicate that posttraumatic prolonged and progressive neuroinflammation is associated with neurodegeneration which may be treatable long after the initiating brain injury. This review provides an overview of recent understanding of neuroinflammation in TBI and preclinical cell-based therapies that target neuroinflammation and promote functional recovery after TBI. Copyright © 2018 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

The Aging Brain and Cognition

PubMed Central

Marchant, Natalie L.; Reed, Bruce R.; Sanossian, Nerses; Madison, Cindee M.; Kriger, Stephen; Dhada, Roxana; Mack, Wendy J.; DeCarli, Charles; Weiner, Michael W.; Mungas, Dan M.; Chui, Helena C.; Jagust, William J.

2013-01-01

Importance β-Amyloid (Aβ) deposition and vascular brain injury (VBI) frequently co-occur and are both associated with cognitive decline in aging. Determining whether a direct relationship exists between them has been challenging. We sought to understand VBI’s influence on cognition and clinical impairment, separate from and in conjunction with pathologic changes associated with Alzheimer disease (AD). Objective To examine the relationship between neuroimaging measures of VBI and brain Aβ deposition and their associations with cognition. Design and Setting A cross-sectional study in a community- and clinic-based sample recruited for elevated vascular disease risk factors. Participants Clinically normal (mean age, 77.1 years [N=30]), cognitively impaired (mean age, 78.0 years [N=24]), and mildly demented (mean age, 79.8 years [N=7]) participants. Interventions Magnetic resonance imaging, Aβ (Pitts-burgh Compound B–positron emission tomographic [PiB-PET]) imaging, and cognitive testing. Main Outcome Measures Magnetic resonance images were rated for the presence and location of infarct (34 infarct-positive participants, 27 infarct-negative participants) and were used to quantify white matter lesion volume. The PiB-PET uptake ratios were used to create a PiB index by averaging uptake across regions vulnerable to early Aβ deposition; PiB positivity (29 PiB-positive participants, 32 PiB-negative participants) was determined from a data-derived threshold. Standardized composite cognitive measures included executive function and verbal and nonverbal memory. Results Vascular brain injury and Aβ were independent in both cognitively normal and impaired participants. Infarction, particularly in cortical and subcortical gray matter, was associated with lower cognitive performance in all domains (P<.05 for all comparisons). Pittsburgh Compound B positivity was neither a significant predictor of cognition nor interacted with VBI. Conclusions and Relevance In this elderly sample with normal cognition to mild dementia, enriched for vascular disease, VBI was more influential than Aβ in contemporaneous cognitive function and remained predictive after including the possible influence of Aβ. There was no evidence that VBI increases the likelihood of Aβ deposition. This finding highlights the importance of VBI in mild cognitive impairment and suggests that the impact of cerebrovascular disease should be considered with respect to defining the etiology of mild cognitive impairment. PMID:23400560

High-resolution whole-brain DCE-MRI using constrained reconstruction: Prospective clinical evaluation in brain tumor patients

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

Guo, Yi, E-mail: yiguo@usc.edu; Zhu, Yinghua; Lingala, Sajan Goud

Purpose: To clinically evaluate a highly accelerated T1-weighted dynamic contrast-enhanced (DCE) MRI technique that provides high spatial resolution and whole-brain coverage via undersampling and constrained reconstruction with multiple sparsity constraints. Methods: Conventional (rate-2 SENSE) and experimental DCE-MRI (rate-30) scans were performed 20 minutes apart in 15 brain tumor patients. The conventional clinical DCE-MRI had voxel dimensions 0.9 × 1.3 × 7.0 mm{sup 3}, FOV 22 × 22 × 4.2 cm{sup 3}, and the experimental DCE-MRI had voxel dimensions 0.9 × 0.9 × 1.9 mm{sup 3}, and broader coverage 22 × 22 × 19 cm{sup 3}. Temporal resolution was 5 smore » for both protocols. Time-resolved images and blood–brain barrier permeability maps were qualitatively evaluated by two radiologists. Results: The experimental DCE-MRI scans showed no loss of qualitative information in any of the cases, while achieving substantially higher spatial resolution and whole-brain spatial coverage. Average qualitative scores (from 0 to 3) were 2.1 for the experimental scans and 1.1 for the conventional clinical scans. Conclusions: The proposed DCE-MRI approach provides clinically superior image quality with higher spatial resolution and coverage than currently available approaches. These advantages may allow comprehensive permeability mapping in the brain, which is especially valuable in the setting of large lesions or multiple lesions spread throughout the brain.« less

Use of 64-channel electroencephalography to study neural otolith-evoked responses.

PubMed

McNerney, Kathleen M; Lockwood, Alan H; Coad, Mary Lou; Wack, David S; Burkard, Robert F

2011-03-01

The vestibular evoked myogenic potential (VEMP) is a myogenic response that can be used clinically to evaluate the function of the saccule. However, to date, little is known about the thalamo-cortical representation of saccular activation. It is important to understand all aspects of the VEMP, as this test is currently used clinically in the evaluation of saccular function. To identify the areas of the brain that are activated in response to stimuli used clinically to evoke the VEMP. Electroencephalography (EEG) recordings combined with current density analyses were used to identify the areas of the brain that are activated in response to stimuli presented above VEMP threshold (500 Hz, 120 dB peak SPL [pSPL] tone bursts), as compared to stimuli presented below VEMP threshold (90 dB pSPL, 500 Hz tone bursts). Ten subjects without any history of balance or hearing impairment participated in the study. The neural otolith-evoked responses (NOERs) recorded in response to stimuli presented below VEMP threshold were absent or smaller than NOERs that were recorded in response to stimuli presented above VEMP threshold. Subsequent analyses with source localization techniques, followed by statistical analysis with SPM5 (Statistical Parametric Mapping), revealed several areas that were activated in response to the 120 dB pSPL tone bursts. These areas included the primary visual cortex, the precuneus, the precentral gyrus, the medial temporal gyrus, and the superior temporal gyrus. The present study found a number of specific brain areas that may be activated by otolith stimulation. Given the findings and source localization techniques (which required limited input from the investigator as to where the sources are believed to be located in the brain) used in the present study as well as the similarity in findings between studies employing galvanic stimuli, fMRI (functional magnetic resonance imaging), and scalp-recorded potentials in response to VEMP-eliciting stimuli, our study provides additional evidence that these brain regions are activated in response to stimuli that can be used clinically to evoke the VEMP. American Academy of Audiology.

Using Functional or Structural Magnetic Resonance Images and Personal Characteristic Data to Identify ADHD and Autism

PubMed Central

Ghiassian, Sina; Greiner, Russell; Jin, Ping; Brown, Matthew R. G.

2016-01-01

A clinical tool that can diagnose psychiatric illness using functional or structural magnetic resonance (MR) brain images has the potential to greatly assist physicians and improve treatment efficacy. Working toward the goal of automated diagnosis, we propose an approach for automated classification of ADHD and autism based on histogram of oriented gradients (HOG) features extracted from MR brain images, as well as personal characteristic data features. We describe a learning algorithm that can produce effective classifiers for ADHD and autism when run on two large public datasets. The algorithm is able to distinguish ADHD from control with hold-out accuracy of 69.6% (over baseline 55.0%) using personal characteristics and structural brain scan features when trained on the ADHD-200 dataset (769 participants in training set, 171 in test set). It is able to distinguish autism from control with hold-out accuracy of 65.0% (over baseline 51.6%) using functional images with personal characteristic data when trained on the Autism Brain Imaging Data Exchange (ABIDE) dataset (889 participants in training set, 222 in test set). These results outperform all previously presented methods on both datasets. To our knowledge, this is the first demonstration of a single automated learning process that can produce classifiers for distinguishing patients vs. controls from brain imaging data with above-chance accuracy on large datasets for two different psychiatric illnesses (ADHD and autism). Working toward clinical applications requires robustness against real-world conditions, including the substantial variability that often exists among data collected at different institutions. It is therefore important that our algorithm was successful with the large ADHD-200 and ABIDE datasets, which include data from hundreds of participants collected at multiple institutions. While the resulting classifiers are not yet clinically relevant, this work shows that there is a signal in the (f)MRI data that a learning algorithm is able to find. We anticipate this will lead to yet more accurate classifiers, over these and other psychiatric disorders, working toward the goal of a clinical tool for high accuracy differential diagnosis. PMID:28030565

Potential and problems in ultrasound-responsive drug delivery systems

PubMed Central

Zhao, Ying-Zheng; Du, Li-Na; Lu, Cui-Tao; Jin, Yi-Guang; Ge, Shu-Ping

2013-01-01

Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS) have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington’s disease, thrombolysis, and disruption of the blood–brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future. PMID:23637531

MR imaging of adult acute infectious encephalitis.

PubMed

Bertrand, A; Leclercq, D; Martinez-Almoyna, L; Girard, N; Stahl, J-P; De-Broucker, T

2017-05-01

Imaging is a key tool for the diagnosis of acute encephalitis. Brain CT scan must be urgently performed to rule out a brain lesion with mass effect that would contraindicate lumbar puncture. Brain MRI is less accessible than CT scan, but can provide crucial information with patients presenting with acute encephalitis. We performed a literature review on PubMed on April 1, 2015 with the search terms "MRI" and "encephalitis". We first described the various brain MRI abnormalities associated with each pathogen of acute encephalitis (HSV, VZV, other viral agents targeting immunocompromised patients or travelers; tuberculosis, listeriosis, other less frequent bacterial agents). Then, we identified specific patterns of brain MRI abnomalies that may suggest a particular pathogen. Limbic encephalitis is highly suggestive of HSV; it also occurs less frequently in encephalitis due to HHV6, syphillis, Whipple's disease and HIV primary infection. Rhombencephalitis is suggestive of tuberculosis and listeriosis. Acute ischemic lesions can occur in patients presenting with severe bacterial encephalitis, tuberculosis, VZV encephalitis, syphilis, and fungal infections. Brain MRI plays a crucial role in the diagnosis of acute encephalitis. It detects brain signal changes that reinforce the clinical suspicion of encephalitis, especially when the causative agent is not identified by lumbar puncture; it can suggest a particular pathogen based on the pattern of brain abnormalities and it rules out important differential diagnosis (vascular, tumoral or inflammatory causes). Copyright © 2017 Elsevier Masson SAS. All rights reserved.

S100 B: A new concept in neurocritical care

PubMed Central

Rezaei, Omidvar; Pakdaman, Hossein; Gharehgozli, Kurosh; Simani, Leila; Vahedian-Azimi, Amir; Asaadi, Sina; Sahraei, Zahra; Hajiesmaeili, Mohammadreza

2017-01-01

After brain injuries, concentrations of some brain markers such as S100B protein in serum and cerebrospinal fluid (CSF) are correlated with the severity and outcome of brain damage. To perform an updated review of S100B roles in human neurocritical care domain, an electronic literature search was carried among articles published in English prior to March 2017. They were retrieved from PubMed, Scopus, EMBSCO, CINAHL, ISC and the Cochrane Library using keywords including “brain”, “neurobiochemical marker”, “neurocritical care”, and “S100B protein”. The integrative review included 48 studies until March 2017. S100B protein can be considered as a marker for blood brain barrier damage. The marker has an important role in the development and recovery of normal central nervous system (CNS) after injury. In addition to extra cerebral sources of S100B, the marker is principally built in the astroglial and Schwann cells. The neurobiochemical marker, S100B, has a pathognomonic role in the diagnosis of a broad spectrum of brain damage including traumatic brain injury (TBI), brain tumor, and stroke. Moreover, a potential predicting role for the neurobiochemical marker has been presumed in the efficiency of brain damage treatment and prognosis. However further animal and human studies are required before widespread routine clinical introduction of S100 protein. PMID:28761630

A combined solenoid-surface RF coil for high-resolution whole-brain rat imaging on a 3.0 Tesla clinical MR scanner.

PubMed

Underhill, Hunter R; Yuan, Chun; Hayes, Cecil E

2010-09-01

Rat brain models effectively simulate a multitude of human neurological disorders. Improvements in coil design have facilitated the wider utilization of rat brain models by enabling the utilization of clinical MR scanners for image acquisition. In this study, a novel coil design, subsequently referred to as the rat brain coil, is described that exploits and combines the strengths of both solenoids and surface coils into a simple, multichannel, receive-only coil dedicated to whole-brain rat imaging on a 3.0 T clinical MR scanner. Compared with a multiturn solenoid mouse body coil, a 3-cm surface coil, a modified Helmholtz coil, and a phased-array surface coil, the rat brain coil improved signal-to-noise ratio by approximately 72, 61, 78, and 242%, respectively. Effects of the rat brain coil on amplitudes of static field and radiofrequency field uniformity were similar to each of the other coils. In vivo, whole-brain images of an adult male rat were acquired with a T(2)-weighted spin-echo sequence using an isotropic acquisition resolution of 0.25 x 0.25 x 0.25 mm(3) in 60.6 min. Multiplanar images of the in vivo rat brain with identification of anatomic structures are presented. Improvement in signal-to-noise ratio afforded by the rat brain coil may broaden experiments that utilize clinical MR scanners for in vivo image acquisition. 2010 Wiley-Liss, Inc.

[Description of functional outcome in pediatric traumatic brain injury after a comprehensive rehabilitation programme].

PubMed

Laxe, Sara; León, Daniel; Salgado, Dalila; Zabaleta, Mikel

2015-01-01

Traumatic brain injury is the leading cause of mortality and disability in children in the developed countries. Despite the plasticity of an infant's brain, injury at this early stage can lead to important sequelae that will affect functioning later in life. The understanding of the functional profile after a traumatic brain injury is important for planning interventions and treatment resources once the preventive phase has failed. This was a retrospective study of the patients admitted in a neurorehabilitation unit with the aim of describing their functioning after an intensive rehabilitation programme. A total of 65 records of children with a mean age of 10.38 years that had been admitted to a rehabilitation programme were reviewed. Of the traumatic brain injuries, 89.2% were severe and 78.4% were secondary to traffic accidents. The mean length of stay was 79.35 days. At discharge, 72% were able to walk, but 76.9% showed some cognitive impairment. Despite good physical recovery, only 29.2% of the children were able to return to school. Permanence of deficits made 21.5% of the children unable to return to any type of education. The population under study was characterised by a good clinical outcome as well as good physical improvement. Nevertheless, cognitive problems were notable and were the main factor responsible for the changes in school attendance and return to normal life. Copyright © 2014 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Brain Mechanisms Supporting Violated Expectations of Pain

PubMed Central

Zeidan, Fadel; Lobanov, Oleg V.; Kraft, Robert A.; Coghill, Robert C.

2015-01-01

The subjective experience of pain is influenced by interactions between prior experiences, future predictions and incoming afferent information. Expectations of high pain can exacerbate pain while expectations of low pain during a consistently noxious stimulus can produce significant reductions in pain. However, the brain mechanisms associated with processing mismatches between expected and experienced pain are poorly understood, but are important for imparting salience to a sensory event in order to override erroneous top-down expectancy-mediated information. The present investigation examined pain-related brain activation when expectations of pain were abruptly violated. After conditioning participants to cues predicting low or high pain, ten incorrectly cued stimuli were administered across 56 stimulus trials to determine if expectations would be less influential on pain when there is a high discordance between pre-stimulus cues and corresponding thermal stimulation. Incorrectly cued stimuli produced pain ratings and pain-related brain activation consistent with placebo analgesia, nocebo hyperalgesia, and violated expectations. Violated expectations of pain were associated with activation in distinct regions of the inferior parietal lobe, including the supramarginal and angular gyrus, and intraparietal sulcus, the superior parietal lobe, cerebellum and occipital lobe. Thus, violated expectations of pain engage mechanisms supporting salience-driven sensory discrimination, working memory, and associative learning processes. By overriding the influence of expectations on pain, these brain mechanisms are likely engaged in clinical situations where patients’ unrealistic expectations for pain relief diminish the efficacy of pain treatments. Accordingly, these findings underscore the importance of maintaining realistic expectations to augment the effectiveness of pain management. PMID:26083664

The Role of “Mixed” Orexigenic and Anorexigenic Signals and Autoantibodies Reacting with Appetite-Regulating Neuropeptides and Peptides of the Adipose Tissue-Gut-Brain Axis: Relevance to Food Intake and Nutritional Status in Patients with Anorexia Nervosa and Bulimia Nervosa

PubMed Central

Papezova, Hana; Vondra, Karel; Hill, Martin; Hainer, Vojtech; Nedvidkova, Jara

2013-01-01

Eating disorders such as anorexia (AN) and bulimia nervosa (BN) are characterized by abnormal eating behavior. The essential aspect of AN is that the individual refuses to maintain a minimal normal body weight. The main features of BN are binge eating and inappropriate compensatory methods to prevent weight gain. The gut-brain-adipose tissue (AT) peptides and neutralizing autoantibodies play an important role in the regulation of eating behavior and growth hormone release. The mechanisms for controlling food intake involve an interplay between gut, brain, and AT. Parasympathetic, sympathetic, and serotoninergic systems are required for communication between brain satiety centre, gut, and AT. These neuronal circuits include neuropeptides ghrelin, neuropeptide Y (NPY), peptide YY (PYY), cholecystokinin (CCK), leptin, putative anorexigen obestatin, monoamines dopamine, norepinephrine (NE), serotonin, and neutralizing autoantibodies. This extensive and detailed report reviews data that demonstrate that hunger-satiety signals play an important role in the pathogenesis of eating disorders. Neuroendocrine dysregulations of the AT-gut-brain axis peptides and neutralizing autoantibodies may result in AN and BN. The circulating autoantibodies can be purified and used as pharmacological tools in AN and BN. Further research is required to investigate the orexigenic/anorexigenic synthetic analogs and monoclonal antibodies for potential treatment of eating disorders in clinical practice. PMID:24106499

Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis.

PubMed

Stillman, Chelsea M; Cohen, Jamie; Lehman, Morgan E; Erickson, Kirk I

2016-01-01

Physical activity (PA) is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models. While information about basic cellular and molecular mechanisms is an important foundation from which to build our understanding of how PA promotes cognitive health in humans, there are other pathways that could play a role in this relationship. For example, PA-induced changes to cellular and molecular pathways likely initiate changes to macroscopic properties of the brain and/or to behavior that in turn influence cognition. The present review uses a more macroscopic lens to identify potential brain and behavioral/socioemotional mediators of the association between PA and cognitive function. We first summarize what is known regarding cellular and molecular mechanisms, and then devote the remainder of the review to discussing evidence for brain systems and behavioral/socioemotional pathways by which PA influences cognition. It is our hope that discussing mechanisms at multiple levels of analysis will stimulate the field to examine both brain and behavioral mediators. Doing so is important, as it could lead to a more complete characterization of the processes by which PA influences neurocognitive function, as well as a greater variety of targets for modifying neurocognitive function in clinical contexts.

Fingolimod inhibits brain atrophy and promotes brain-derived neurotrophic factor in an animal model of multiple sclerosis.

PubMed

Smith, Paul A; Schmid, Cindy; Zurbruegg, Stefan; Jivkov, Magali; Doelemeyer, Arno; Theil, Diethilde; Dubost, Valérie; Beckmann, Nicolau

2018-05-15

Longitudinal brain atrophy quantification is a critical efficacy measurement in multiple sclerosis (MS) clinical trials and the determination of No Evidence of Disease Activity (NEDA). Utilising fingolimod as a clinically validated therapy we evaluated the use of repeated brain tissue volume measures during chronic experimental autoimmune encephalomyelitis (EAE) as a new preclinical efficacy measure. Brain volume changes were quantified using magnetic resonance imaging (MRI) at 7 Tesla and correlated to treatment-induced brain derived neurotrophic factor (BDNF) measured in blood, cerebrospinal fluid, spinal cord and brain. Serial brain MRI measurements revealed slow progressive brain volume loss in vehicle treated EAE mice despite a stable clinical score. Fingolimod (1 mg/kg) significantly ameliorated brain tissue atrophy in the cerebellum and striatum when administered from established EAE disease onwards. Fingolimod-dependent tissue preservation was associated with induction of BDNF specifically within the brain and co-localized with neuronal soma. In contrast, therapeutic teriflunomide (3 mg/kg) treatment failed to inhibit CNS autoimmune mediated brain degeneration. Finally, weekly anti-IL-17A antibody (15 mg/kg) treatment was highly efficacious and preserved whole brain, cerebellum and striatum volume. Fingolimod-mediated BDNF increases within the CNS may contribute to limiting progressive tissue loss during chronic neuroinflammation. Copyright © 2018 Elsevier B.V. All rights reserved.

Targeted Therapies for Brain Metastases from Breast Cancer.

PubMed

Venur, Vyshak Alva; Leone, José Pablo

2016-09-13

The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor, mechanistic target of rapamycin (mTOR) pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6) pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%-30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways.

Identification of brain metastasis genes and therapeutic evaluation of histone deacetylase inhibitors in a clinically relevant model of breast cancer brain metastasis.

PubMed

Kim, Soo-Hyun; Redvers, Richard P; Chi, Lap Hing; Ling, Xiawei; Lucke, Andrew J; Reid, Robert C; Fairlie, David P; Baptista Moreno Martin, Ana Carolina; Anderson, Robin L; Denoyer, Delphine; Pouliot, Normand

2018-05-21

Breast cancer brain metastasis remains largely incurable. While several mouse models have been developed to investigate the genes and mechanisms regulating breast cancer brain metastasis, these models often lack clinical relevance since they require the use of immune-compromised mice and/or are poorly metastatic to brain from the mammary gland. We describe the development and characterisation of an aggressive brain metastatic variant of the 4T1 syngeneic model (4T1Br4) that spontaneously metastasises to multiple organs, but is selectively more metastatic to the brain from the mammary gland than parental 4T1 tumours. By immunohistochemistry, 4T1Br4 tumours and brain metastases display a triple negative phenotype, consistent with the high propensity of this breast cancer subtype to spread to brain. In vitro assays indicate that 4T1Br4 cells have an enhanced ability to adhere to or migrate across a brain-derived endothelial monolayer and greater invasive response to brain-derived soluble factors compared to 4T1 cells. These properties are likely to contribute to the brain-selectivity of 4T1Br4 tumours. Expression profiling and gene set enrichment analyses demonstrate the clinical relevance of the 4T1Br4 model at the transcriptomic level. Pathway analyses implicate tumour-intrinsic immune regulation and vascular interactions in successful brain colonisation, revealing potential therapeutic targets. Evaluation of two histone deacetylase inhibitors, SB939 and 1179.4b, shows partial efficacy against 4T1Br4 metastasis to brain and other sites in vivo and potent radio-sensitising properties in vitro The 4T1Br4 model provides a clinically relevant tool for mechanistic studies and to evaluate novel therapies against brain metastasis. © 2018. Published by The Company of Biologists Ltd.

Clinical evidence of inflammation driving secondary brain injury: A systematic review

PubMed Central

Hinson, Holly E.; Rowell, Susan; Schreiber, Martin

2015-01-01

Background Despite advances in both prevention and treatment, traumatic brain injury (TBI) remains one of the most burdensome diseases; 2% of the US population currently lives with disabilities resulting from TBI. Recent advances in the understanding of inflammation and its impact on the pathophysiology of trauma have increased the interest in inflammation as a possible mediator in TBI outcome. Objectives The goal of this systematic review is to address the question: “What is the evidence in humans that inflammation is linked to secondary brain injury?” As the experimental evidence has been well described elsewhere, this review will focus on the clinical evidence for inflammation as a mechanism of secondary brain injury. Data Sources Medline database (1996-Week 1 June 2014), Pubmed and Google Scholar databases were queried for relevant studies. Study Eligibility Criteria Studies were eligible if participants were adults and/or children who sustained moderate or severe TBI in the acute phase of injury, published in English. Studies published in the last decade (since 2004) were preferentially included. Trials could be observational or interventional in nature. Appraisal and Synthesis Methods To address the quality of the studies retrieved, we applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria to assess the limitations of the included studies. Results Trauma initiates local central nervous system as well as systemic immune activation. Numerous observational studies describe elevation of pro-inflammatory cytokines that are associated with important clinical variables including neurologic outcome and mortality. A small number of clinical trials have included immunomodulating strategies, but no intervention to date has proven effective in improving outcomes after TBI. Limitations Inclusion of studies not initially retrieved by the search terms may have biased our results. Additionally, some reports may have been inadvertently excluded due to use of non-search term key words. Conclusions and Implications of Key Findings Clinical evidence of inflammation causing secondary brain injury in humans is gaining momentum. While inflammation is certainly present, it is not clear from the literature at what juncture inflammation becomes maladaptive, promoting secondary injury rather than facilitating repairand identifying patients with maladaptive inflammation (neuro-inflammation, systemic, or both) after TBI remains elusive. Direct agonism/antagonism represents an exciting target for future study. Level of Evidence Systematic review, level III. PMID:25539220

High grade glioma mimicking voltage gated potassium channel complex associated antibody limbic encephalitis.

PubMed

Athauda, Dilan; Delamont, R S; Pablo-Fernandez, E De

2014-01-01

Though raised titres of voltage gated potassium channel (VGKC) complex antibodies have been occasionally associated with extracranial tumours, mainly presenting as Morvan's Syndrome or neuromyotonia, they have not yet been reported to be associated with an intracranial malignancy. This is especially important as misdiagnosis of these conditions and delay of the appropriate treatment can have important prognostic implications. We describe a patient with a high grade glioma presenting with clinical, radiological, and serological features consistent with the diagnosis of VGKC antibody associated limbic encephalitis (LE). This is the first association between a primary brain tumour and high titre of VGKC complex antibodies. Clinicoradiological progression despite effective immunosuppressive treatment should prompt clinicians to look for alternative diagnoses. Further studies to elucidate a possible association between VGKC complex and other surface antigen antibodies with primary brain tumours should be carried out.

Persistent cognitive dysfunction after traumatic brain injury: A dopamine hypothesis

PubMed Central

Bales, James W.; Wagner, Amy K.; Kline, Anthony E.; Dixon, C. Edward

2010-01-01

Traumatic brain injury (TBI) represents a significant cause of death and disability in industrialized countries. Of particular importance to patients the chronic effect that TBI has on cognitive function. Therapeutic strategies have been difficult to evaluate because of the complexity of injuries and variety of patient presentations within a TBI population. However, pharmacotherapies targeting dopamine (DA) have consistently shown benefits in attention, behavioral outcome, executive function, and memory. Still it remains unclear what aspect of TBI pathology is targeted by DA therapies and what time-course of treatment is most beneficial for patient outcomes. Fortunately, ongoing research in animal models has begun to elucidate the pathophysiology of DA alterations after TBI. The purpose of this review is to discuss clinical and experimental research examining DAergic therapies after TBI, which will in turn elucidate the importance of DA for cognitive function/dysfunction after TBI as well as highlight the areas that require further study. PMID:19580914

Future directions in treatment of brain metastases

PubMed Central

Barani, Igor J.; Larson, David A.; Berger, Mitchel S.

2013-01-01

Background: Brain metastases affect up to 30% of patients with cancer. Management of brain metastases continues to evolve with ever increasing focus on cognitive preservation and quality of life. This manuscript reviews current state of brain metastases management and discusses various treatment controversies with focus on future clinical trials. Stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are discussed in context of multiple (4+ brain metastases) as well as new approaches combining radiation and targeted agents. A brief discussion of modified WBRT approaches, including hippocampal-avoidance WBRT (HA-WBRT) is included as well as a section on recently presented results of Radiation Therapy Oncology Group (RTOG) 0614, a randomized, double-blind, placebo-controlled trial of menantine for prevention of neurocognitive injury after WBRT. Methods: A search of selected studies relevant to management of brain metastases was performed in PubMed as well as in various published meeting abstracts. This data was collated and analyzed in context of contemporary management and future clinical trial plans. This data is presented in tabular form and discussed extensively in the text. Results: The published data demonstrate continued evolution of clinical trials and management strategies designed to minimize and/or prevent cognitive decline following radiation therapy management of brain metastases. Hippocampal avoidance whole-brain radiation therapy (HA-WBRT) and radiosurgery treatments for multiple brain metastases are discussed along with preliminary results of RTOG 0614, a trial of memantine therapy to prevent cognitive decline following WBRT. Trial results appear to support the use of memantine for prevention of cognitive decline. Conclusions: Different management strategies for multiple brain metastases (>4 brain metastases) are currently being evaluated in prospective clinical trials to minimize the likelihood of cognitive decline following WBRT. PMID:23717793

Future directions in treatment of brain metastases.

PubMed

Barani, Igor J; Larson, David A; Berger, Mitchel S

2013-01-01

Brain metastases affect up to 30% of patients with cancer. Management of brain metastases continues to evolve with ever increasing focus on cognitive preservation and quality of life. This manuscript reviews current state of brain metastases management and discusses various treatment controversies with focus on future clinical trials. Stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are discussed in context of multiple (4+ brain metastases) as well as new approaches combining radiation and targeted agents. A brief discussion of modified WBRT approaches, including hippocampal-avoidance WBRT (HA-WBRT) is included as well as a section on recently presented results of Radiation Therapy Oncology Group (RTOG) 0614, a randomized, double-blind, placebo-controlled trial of menantine for prevention of neurocognitive injury after WBRT. A search of selected studies relevant to management of brain metastases was performed in PubMed as well as in various published meeting abstracts. This data was collated and analyzed in context of contemporary management and future clinical trial plans. This data is presented in tabular form and discussed extensively in the text. The published data demonstrate continued evolution of clinical trials and management strategies designed to minimize and/or prevent cognitive decline following radiation therapy management of brain metastases. Hippocampal avoidance whole-brain radiation therapy (HA-WBRT) and radiosurgery treatments for multiple brain metastases are discussed along with preliminary results of RTOG 0614, a trial of memantine therapy to prevent cognitive decline following WBRT. Trial results appear to support the use of memantine for prevention of cognitive decline. Different management strategies for multiple brain metastases (>4 brain metastases) are currently being evaluated in prospective clinical trials to minimize the likelihood of cognitive decline following WBRT.

An audit of clinical practice, referral patterns, and appropriateness of clinical indications for brain MRI examinations: A single-centre study in Ghana.

PubMed

Piersson, A D; Nunoo, G; Gorleku, P N

2018-05-01

The aim of this study was to investigate current brain MRI practice, pattern of brain MRI requests, and their appropriateness using the American College of Radiology (ACR) Appropriateness Criteria. We used direct observation and questionnaires to obtain data concerning routine brain MRI practice. We then retrospectively analyzed (i) demographic characteristics, (ii) clinical history, and (iii) appropriateness of brain MRI requests against published criteria. All patients were administered the screening questionnaire; however, no reviews were undertaken directly with patients, and no signature of the radiographer was recorded. Apart from routine brain protocol, there were dedicated protocols for epilepsy and stroke. Brain MRI images from 161 patients (85 Males; 76 Females) were analyzed. The age group with most brain MRI requests were from 26 to 45 year olds. The commonest four clinical indications for imaging were brain tumour, headache, seizure, and stroke. Using the ACR Appropriateness Criteria, almost 43% of the brain MRI scans analyzed were found to be "usually appropriate", 38% were "maybe appropriate" and 19% were categorized as "usually not appropriate". There was knowledge gap with regards to MRI safety in local practice, thus there is the utmost need for MRI safety training. Data on the commonest indications for performing brain MRI in this study should be used to inform local neuroradiological practice. Dedicated stroke and epilepsy MRI protocols require additional sequences i.e. MRA and 3D T1 volume acquisition, respectively. The ACR Appropriateness Criteria is recommended for use by the referring practitioners to improve appropriateness of brain MRI requests. Copyright © 2017 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.

The Minimal Clinically Important Difference for the Mayo-Portland Adaptability Inventory.

PubMed

Malec, James F; Kean, Jacob; Monahan, Patrick O

To determine the Minimal Clinically Important Difference (MCID) and Robust Clinically Important Difference (RCID) of the Mayo-Portland Adaptability Inventory-4 (MPAI-4) as measures of response to intervention. Retrospective analysis of existing data. Both distribution- and anchor-based methods were used to triangulate on the MCID and to identify a moderate, that is, more robust, level of change (RCID) for the MPAI-4. These were further evaluated with respect to clinical provider ratings. Data for individuals with acquired brain injury in rehabilitation programs throughout the United States in the OutcomeInfo Database (n = 3087) with 2 MPAI-4 ratings. MPAI-4, Supervision Rating Scale, Clinician Rating of Global Clinical Improvement. Initial analyses suggested 5 T-score points (5T) as the MCID and 9T as the RCID. Eighty-one percent to 87% of clinical raters considered a 5T change and 99% considered a 9T change to indicate meaningful improvement. 5T represents the MCID for the MPAI-4 and 9T, the RCID. Both values are notably less than the Reliable Change Index (RCI). While the RCI indicates change with a high level of statistical confidence, it may be insensitive to change that is considered meaningful by providers and participants as indicated by the MCID.

Automated detection and quantification of residual brain tumor using an interactive computer-aided detection scheme

NASA Astrophysics Data System (ADS)

Gaffney, Kevin P.; Aghaei, Faranak; Battiste, James; Zheng, Bin

2017-03-01

Detection of residual brain tumor is important to evaluate efficacy of brain cancer surgery, determine optimal strategy of further radiation therapy if needed, and assess ultimate prognosis of the patients. Brain MR is a commonly used imaging modality for this task. In order to distinguish between residual tumor and surgery induced scar tissues, two sets of MRI scans are conducted pre- and post-gadolinium contrast injection. The residual tumors are only enhanced in the post-contrast injection images. However, subjective reading and quantifying this type of brain MR images faces difficulty in detecting real residual tumor regions and measuring total volume of the residual tumor. In order to help solve this clinical difficulty, we developed and tested a new interactive computer-aided detection scheme, which consists of three consecutive image processing steps namely, 1) segmentation of the intracranial region, 2) image registration and subtraction, 3) tumor segmentation and refinement. The scheme also includes a specially designed and implemented graphical user interface (GUI) platform. When using this scheme, two sets of pre- and post-contrast injection images are first automatically processed to detect and quantify residual tumor volume. Then, a user can visually examine segmentation results and conveniently guide the scheme to correct any detection or segmentation errors if needed. The scheme has been repeatedly tested using five cases. Due to the observed high performance and robustness of the testing results, the scheme is currently ready for conducting clinical studies and helping clinicians investigate the association between this quantitative image marker and outcome of patients.

Predicting parenting stress in caregivers of children with brain tumours.

PubMed

Bennett, Emily; English, Martin William; Rennoldson, Michael; Starza-Smith, Arleta

2013-03-01

The purpose of the study was to identify factors that contribute to parenting stress in caregivers of children diagnosed with brain tumours. The study was cross-sectional and recruited 37 participants from a clinical database at a specialist children's hospital. Parents were sent questionnaires, which were used to measure factors related to stress in caregivers of children diagnosed with a brain tumour. Stress levels were measured using the Parenting Stress Index-Short Form (PSI/SF). Correlation analysis and multiple linear regression were used to examine the associations between parenting stress and coping styles, locus of control, parent-perceived child disability and time since diagnosis. Results revealed that 51% of parents were experiencing clinically significant levels of stress. The mean stress level of parents in the study was significantly higher than the PSI/SF norms (t = 4.7, p < .001). Regression analysis revealed that external locus of control and coping by accepting responsibility accounted for 67% of the variance in parenting stress. Other styles of coping, child behaviour problems and the amount of time since diagnosis were not found to be predictive of levels of parenting stress. There was a high prevalence of parenting stress in caregivers of children with a brain tumour. An external locus of control and coping by accepting responsibility increased the likelihood of elevated levels of stress. Results emphasised the importance of ongoing support for parents of children with brain tumours. Intervention might helpfully be centred on strategies to increase parents' internal locus of control. Copyright © 2012 John Wiley & Sons, Ltd.

Atlas based brain volumetry: How to distinguish regional volume changes due to biological or physiological effects from inherent noise of the methodology.

PubMed

Opfer, Roland; Suppa, Per; Kepp, Timo; Spies, Lothar; Schippling, Sven; Huppertz, Hans-Jürgen

2016-05-01

Fully-automated regional brain volumetry based on structural magnetic resonance imaging (MRI) plays an important role in quantitative neuroimaging. In clinical trials as well as in clinical routine multiple MRIs of individual patients at different time points need to be assessed longitudinally. Measures of inter- and intrascanner variability are crucial to understand the intrinsic variability of the method and to distinguish volume changes due to biological or physiological effects from inherent noise of the methodology. To measure regional brain volumes an atlas based volumetry (ABV) approach was deployed using a highly elastic registration framework and an anatomical atlas in a well-defined template space. We assessed inter- and intrascanner variability of the method in 51 cognitively normal subjects and 27 Alzheimer dementia (AD) patients from the Alzheimer's Disease Neuroimaging Initiative by studying volumetric results of repeated scans for 17 compartments and brain regions. Median percentage volume differences of scan-rescans from the same scanner ranged from 0.24% (whole brain parenchyma in healthy subjects) to 1.73% (occipital lobe white matter in AD), with generally higher differences in AD patients as compared to normal subjects (e.g., 1.01% vs. 0.78% for the hippocampus). Minimum percentage volume differences detectable with an error probability of 5% were in the one-digit percentage range for almost all structures investigated, with most of them being below 5%. Intrascanner variability was independent of magnetic field strength. The median interscanner variability was up to ten times higher than the intrascanner variability. Copyright © 2016 Elsevier Inc. All rights reserved.

Hyperbaric Oxygen Therapy Can Diminish Fibromyalgia Syndrome – Prospective Clinical Trial

PubMed Central

Efrati, Shai; Golan, Haim; Bechor, Yair; Faran, Yifat; Daphna-Tekoah, Shir; Sekler, Gal; Fishlev, Gregori; Ablin, Jacob N.; Bergan, Jacob; Volkov, Olga; Friedman, Mony; Ben-Jacob, Eshel; Buskila, Dan

2015-01-01

Background Fibromyalgia Syndrome (FMS) is a persistent and debilitating disorder estimated to impair the quality of life of 2–4% of the population, with 9:1 female-to-male incidence ratio. FMS is an important representative example of central nervous system sensitization and is associated with abnormal brain activity. Key symptoms include chronic widespread pain, allodynia and diffuse tenderness, along with fatigue and sleep disturbance. The syndrome is still elusive and refractory. The goal of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on symptoms and brain activity in FMS. Methods and Findings A prospective, active control, crossover clinical trial. Patients were randomly assigned to treated and crossover groups: The treated group patients were evaluated at baseline and after HBOT. Patients in the crossover-control group were evaluated three times: baseline, after a control period of no treatment, and after HBOT. Evaluations consisted of physical examination, including tender point count and pain threshold, extensive evaluation of quality of life, and single photon emission computed tomography (SPECT) imaging for evaluation of brain activity. The HBOT protocol comprised 40 sessions, 5 days/week, 90 minutes, 100% oxygen at 2ATA. Sixty female patients were included, aged 21–67 years and diagnosed with FMS at least 2 years earlier. HBOT in both groups led to significant amelioration of all FMS symptoms, with significant improvement in life quality. Analysis of SPECT imaging revealed rectification of the abnormal brain activity: decrease of the hyperactivity mainly in the posterior region and elevation of the reduced activity mainly in frontal areas. No improvement in any of the parameters was observed following the control period. Conclusions The study provides evidence that HBOT can improve the symptoms and life quality of FMS patients. Moreover, it shows that HBOT can induce neuroplasticity and significantly rectify abnormal brain activity in pain related areas of FMS patients. Trial Registration ClinicalTrials.gov NCT01827683 PMID:26010952

Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate

PubMed Central

Bondulich, Marie K.; Guo, Tong; Meehan, Christopher; Manion, John; Rodriguez Martin, Teresa; Mitchell, Jacqueline C.; Hortobagyi, Tibor; Yankova, Natalia; Stygelbout, Virginie; Brion, Jean-Pierre; Noble, Wendy

2016-01-01

Abstract Human neurodegenerative tauopathies exhibit pathological tau aggregates in the brain along with diverse clinical features including cognitive and motor dysfunction. Post-translational modifications including phosphorylation, ubiquitination and truncation, are characteristic features of tau present in the brain in human tauopathy. We have previously reported an N-terminally truncated form of tau in human brain that is associated with the development of tauopathy and is highly phosphorylated. We have generated a new mouse model of tauopathy in which this human brain-derived, 35 kDa tau fragment (Tau35) is expressed in the absence of any mutation and under the control of the human tau promoter. Most existing mouse models of tauopathy overexpress mutant tau at levels that do not occur in human neurodegenerative disease, whereas Tau35 transgene expression is equivalent to less than 10% of that of endogenous mouse tau. Tau35 mice recapitulate key features of human tauopathies, including aggregated and abnormally phosphorylated tau, progressive cognitive and motor deficits, autophagic/lysosomal dysfunction, loss of synaptic protein, and reduced life-span. Importantly, we found that sodium 4-phenylbutyrate (Buphenyl®), a drug used to treat urea cycle disorders and currently in clinical trials for a range of neurodegenerative diseases, reverses the observed abnormalities in tau and autophagy, behavioural deficits, and loss of synapsin 1 in Tau35 mice. Our results show for the first time that, unlike other tau transgenic mouse models, minimal expression of a human disease-associated tau fragment in Tau35 mice causes a profound and progressive tauopathy and cognitive changes, which are rescued by pharmacological intervention using a clinically approved drug. These novel Tau35 mice therefore represent a highly disease-relevant animal model in which to investigate molecular mechanisms and to develop novel treatments for human tauopathies. PMID:27297240

Predictive value of neuron-specific enolase for prognosis in patients with moderate or severe traumatic brain injury: a systematic review and meta-analysis

PubMed Central

Mercier, Eric; Boutin, Amélie; Shemilt, Michèle; Lauzier, François; Zarychanski, Ryan; Fergusson, Dean A.; Moore, Lynne; McIntyre, Lauralyn A.; Archambault, Patrick; Légaré, France; Rousseau, François; Lamontagne, François; Nadeau, Linda; Turgeon, Alexis F.

2016-01-01

Background: Prognosis is difficult to establish early after moderate or severe traumatic brain injury despite representing an important concern for patients, families and medical teams. Biomarkers, such as neuron-specific enolase, have been proposed as potential early prognostic indicators. Our objective was to determine the association between neuron-specific enolase and clinical outcomes, and the prognostic value of neuron-specific enolase after a moderate or severe traumatic brain injury. Methods: We searched MEDLINE, Embase, The Cochrane Library and Biosis Previews, and reviewed reference lists of eligible articles to identify studies. We included cohort studies and randomized controlled trials that evaluated the prognostic value of neuron-specific enolase to predict mortality or Glasgow Outcome Scale score in patients with moderate or severe traumatic brain injury. Two reviewers independently collected data. The pooled mean differences were analyzed using random-effects models. We assessed risk of bias using a customized Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Subgroup and sensitivity analyses were performed based on a priori hypotheses. Results: We screened 5026 citations from which 30 studies (involving 1321 participants) met our eligibility criteria. We found a significant positive association between neuron-specific enolase serum levels and mortality (10 studies, n = 474; mean difference [MD] 18.46 µg/L, 95% confidence interval [CI] 10.81 to 26.11 µg/L; I2 = 83%) and a Glasgow Outcome Scale ≤ 3 (14 studies, n = 603; MD 17.25 µg/L, 95% CI 11.42 to 23.07 µg/L; I2 = 82%). We were unable to determine a clinical threshold value using the available patient data. Interpretation: In patients with moderate or severe traumatic brain injury, increased neuron-specific enolase serum levels are associated with unfavourable outcomes. The optimal neuron-specific enolase threshold value to predict unfavourable prognosis remains unknown and clinical decision-making is currently not recommended until additional studies are made available. PMID:27975043

N-terminal-pro brain natriuretic peptides in dogs and cats: A technical and clinical review

PubMed Central

de Lima, Gabriela Vieira; Ferreira, Felipp da Silveira

2017-01-01

Biomarkers are quantitative indicators of biological processes performed by an organ or system. In recent years, natriuretic peptides (NPs) have emerged as important tools in the diagnosis and therapeutic monitoring of heart diseases. Research has shown that serum and plasma levels of N-terminal pro brain NP (NT-proBNP) in dogs and cats are the only biomarkers that afford to diagnose and monitor congestive processes and, indirectly, the myocardial function of small animals. The present review discusses the peer-reviewed specialized literature about NT-proBNP and presents and compares the potential clinical applications of this NP in veterinary medicine of small animals, considering diagnosis, follow-up, and prognosis of myocardial or systemic diseases. The relevance of NT-proBNP is associated with sample stability, easy determination in laboratory, sensitivity, accuracy, and the possibility to analyze myocardial function. These advantages are specially important when NT-proBNP is compared with other cardiac biomarkers, mostly those that indicate the integrity of the myocardial cell. Fast NT-proBNP assays are marketed today and may be used in association with complementary tests. Together, these methods are an important source of information in differential diagnosis of heart and lung diseases as well in the early diagnosis of cardiopathy in dogs and cats, proving valuable tools in treatment and prognosis. PMID:29062197

Research Nurse | Center for Cancer Research

Cancer.gov

We are looking for a Research Nurse (Accrual Site Coordinator) to join our neuro-oncology clinical team to help us provide administrative and coordination support for the Brain Tumor Trials Collaborative (BTTC). Duties include, but are not limited to, monitoring and overseeing activities pertaining to clinical protocols and administrative operations supporting the BTTC, with limited interaction with study participants.  Be part of our mission to solve the most important, challenging and neglected problems in modern cancer research and patient care. The National Cancer Institute’s Center for Cancer Research is a world-leading cancer research organization working toward scientific breakthroughs at medicine’s cutting edge. Our scientists can’t do it alone. It takes an extraordinary team of researchers, clinical experts and administrators to improve the lives of cancer patients and answer the most important questions in cancer biology and treatment.

Comparison of PECARN, CATCH, and CHALICE Rules for Children with Minor Head Injury: A prospective cohort study

PubMed Central

Easter, Joshua S.; Bakes, Katherine; Dhaliwal, Jasmeet; Miller, Michael; Caruso, Emily; Haukoos, Jason S.

2014-01-01

Objective To evaluate the diagnostic accuracy of clinical decision rules and physician judgment for identifying clinically important traumatic brain injuries (TBIs) in children with minor head injuries presenting to the emergency department (ED). Methods We prospectively enrolled children <18 years of age with minor head injury (Glasgow Coma Scale 13 – 15) presenting within 24 hours of their injuries. We assessed the ability of 3 clinical decision rules (CATCH, CHALICE, PECARN) and 2 measures of physician judgment (estimated of <1% risk of TBI, actual CT ordering practice) to predict clinically important TBI, as defined by death from TBI, need for neurosurgery, intubation >24 hours for TBI, or hospital admission >2 nights for TBI. Results Among the 1,009 children, 21 (2%; 95% CI: 1% to 3%) had clinically important TBIs. Only physician practice and PECARN identified all clinically important TBIs, with ranked sensitivities as follows (95% CI): Physician practice and PECARN each 100% (84% to 100%), physician estimates 95% (76% to 100%), CATCH 91% (70% to 99%), and CHALICE 84% (60% to 97%). Ranked specificities were as follows: CHALICE 85% (82% to 87%), physician estimates 68% (65% to 71%), PECARN 62% (59% to 66%), physician practice 50% (47% to 53%), and CATCH 44% (41% to 47%). Conclusions Of the 5 modalities studied, only physician practice and PECARN identified all clinically important TBIs, with PECARN being slightly more specific. CHALICE was incompletely sensitive but the most specific of all rules. CATCH was incompletely sensitive and had the poorest specificity of all modalities. PMID:24635987

Quantitative Assessment of Normal Fetal Brain Myelination Using Fast Macromolecular Proton Fraction Mapping.

PubMed

Yarnykh, V L; Prihod'ko, I Y; Savelov, A A; Korostyshevskaya, A M

2018-05-10

Fast macromolecular proton fraction mapping is a recently emerged MRI method for quantitative myelin imaging. Our aim was to develop a clinically targeted technique for macromolecular proton fraction mapping of the fetal brain and test its capability to characterize normal prenatal myelination. This prospective study included 41 pregnant women (gestational age range, 18-38 weeks) without abnormal findings on fetal brain MR imaging performed for clinical indications. A fast fetal brain macromolecular proton fraction mapping protocol was implemented on a clinical 1.5T MR imaging scanner without software modifications and was performed after a clinical examination with an additional scan time of <5 minutes. 3D macromolecular proton fraction maps were reconstructed from magnetization transfer-weighted, T1-weighted, and proton density-weighted images by the single-point method. Mean macromolecular proton fraction in the brain stem, cerebellum, and thalamus and frontal, temporal, and occipital WM was compared between structures and pregnancy trimesters using analysis of variance. Gestational age dependence of the macromolecular proton fraction was assessed using the Pearson correlation coefficient ( r ). The mean macromolecular proton fraction in the fetal brain structures varied between 2.3% and 4.3%, being 5-fold lower than macromolecular proton fraction in adult WM. The macromolecular proton fraction in the third trimester was higher compared with the second trimester in the brain stem, cerebellum, and thalamus. The highest macromolecular proton fraction was observed in the brain stem, followed by the thalamus, cerebellum, and cerebral WM. The macromolecular proton fraction in the brain stem, cerebellum, and thalamus strongly correlated with gestational age ( r = 0.88, 0.80, and 0.73; P < .001). No significant correlations were found for cerebral WM regions. Myelin is the main factor determining macromolecular proton fraction in brain tissues. Macromolecular proton fraction mapping is sensitive to the earliest stages of the fetal brain myelination and can be implemented in a clinical setting. © 2018 by American Journal of Neuroradiology.

The need for clinical quantification of combined PET/MRI data in pediatric epilepsy

NASA Astrophysics Data System (ADS)

Muzik, Otto; Pai, Darshan; Juhasz, Csaba; Hua, Jing

2013-02-01

In the past, multimodality integrative analysis of image data has been used to obtain a better understanding of underlying mechanisms of seizure generation and propagation in children with extratemporal lobe epilepsy. However, despite important advances in the combined analysis of PET, MRI, DTI and EEG data, successful surgical outcome is only achieved in about 2/3 of patients undergoing resective surgery. The advent of simultaneous PET/MR data acquisition promises an important advance in neuroimaging through clinical quantification, which will finally translate the strength of PET (which is the ability to absolutely quantify physiological parameters such as metabolic rates and receptor densities) into clinical work. Taking advantage of recently developed integrated PET/MR devices, absolute physiological values will be available in clinical routine, replacing currently used visual assessment of relative tissue tracer uptake. This will allow assessment of global increases/decreases of brain function during critical phases of development and is likely to have a significant impact on patient management in pediatric epilepsy.

Integrating molecular markers into the World Health Organization classification of CNS tumors: a survey of the neuro-oncology community.

PubMed

Aldape, Kenneth; Nejad, Romina; Louis, David N; Zadeh, Gelareh

2017-03-01

Molecular markers provide important biological and clinical information related to the classification of brain tumors, and the integration of relevant molecular parameters into brain tumor classification systems has been a widely discussed topic in neuro-oncology over the past decade. With recent advances in the development of clinically relevant molecular signatures and the 2016 World Health Organization (WHO) update, the views of the neuro-oncology community on such changes would be informative for implementing this process. A survey with 8 questions regarding molecular markers in tumor classification was sent to an email list of Society for Neuro-Oncology members and attendees of prior meetings (n=5065). There were 403 respondents. Analysis was performed using whole group response, based on self-reported subspecialty. The survey results show overall strong support for incorporating molecular knowledge into the classification and clinical management of brain tumors. Across all 7 subspecialty groups, ≥70% of respondents agreed to this integration. Interestingly, some variability is seen among subspecialties, notably with lowest support from neuropathologists, which may reflect their roles in implementing such diagnostic technologies. Based on a survey provided to the neuro-oncology community, we report strong support for the integration of molecular markers into the WHO classification of brain tumors, as well as for using an integrated "layered" diagnostic format. While membership from each specialty showed support, there was variation by specialty in enthusiasm regarding proposed changes. The initial results of this survey influenced the deliberations underlying the 2016 WHO classification of tumors of the central nervous system. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

Psychoradiology: The Frontier of Neuroimaging in Psychiatry

PubMed Central

Lui, Su; Zhou, Xiaohong Joe; Sweeney, John A.

2016-01-01

Unlike neurologic conditions, such as brain tumors, dementia, and stroke, the neural mechanisms for all psychiatric disorders remain unclear. A large body of research obtained with structural and functional magnetic resonance imaging, positron emission tomography/single photon emission computed tomography, and optical imaging has demonstrated regional and illness-specific brain changes at the onset of psychiatric disorders and in individuals at risk for such disorders. Many studies have shown that psychiatric medications induce specific measurable changes in brain anatomy and function that are related to clinical outcomes. As a result, a new field of radiology, termed psychoradiology, seems primed to play a major clinical role in guiding diagnostic and treatment planning decisions in patients with psychiatric disorders. This article will present the state of the art in this area, as well as perspectives regarding preparations in the field of radiology for its evolution. Furthermore, this article will (a) give an overview of the imaging and analysis methods for psychoradiology; (b) review the most robust and important radiologic findings and their potential clinical value from studies of major psychiatric disorders, such as depression and schizophrenia; and (c) describe the main challenges and future directions in this field. An ongoing and iterative process of developing biologically based nomenclatures with which to delineate psychiatric disorders and translational research to predict and track response to different therapeutic drugs is laying the foundation for a shift in diagnostic practice in psychiatry from a psychologic symptom–based approach to an imaging-based approach over the next generation. This shift will require considerable innovations for the acquisition, analysis, and interpretation of brain images, all of which will undoubtedly require the active involvement of radiologists. © RSNA, 2016 Online supplemental material is available for this article. PMID:27755933

Clinical management of tuberous sclerosis complex over the lifetime of a patient.

PubMed

Frost, Michael; Hulbert, John

2015-01-01

Tuberous sclerosis complex (TSC) is a genetic disorder characterized by nonmalignant tumors (hamartomas) that can occur in various organ systems, including the brain, kidneys, lungs, skin, eyes, and heart. Clinical manifestations of TSC can occur at any age, thereby making the diagnosis difficult. No typical disease presentation is known, and the clinical presentation usually differs between pediatric and adult patients. Furthermore, variable penetrance of the genetic mutation causes a range of disease severity from very mild to severe, and affected individuals can go undetected for years because many of the clinical manifestations of TSC lack specificity. Once a diagnosis is made, TSC management strategies should be tailored to address the symptoms and risks most relevant to the age of the patient. Improved understanding of the genetic basis of TSC and of the central issue of mTOR overactivation has led to use of pharmacotherapies such as the mTOR inhibitors everolimus and sirolimus in the treatment of TSC disease. In Phase II and III studies, everolimus has demonstrated efficacy and safety in the treatment of both brain (subependymal giant cell astrocytoma) and renal (angiomyolipoma) manifestations associated with TSC. It is important to bear in mind that TSC is a lifelong condition, and for those diagnosed as children, a continuum of care will be needed as they transition from pediatric to adult health services. Clearly identifying the likely differences among diagnosis, monitoring, and management of pediatric and adult patients with TSC is an important step in enabling efficiencies to be maximized without compromising the care provided to patients.

Clinical management of tuberous sclerosis complex over the lifetime of a patient

PubMed Central

Frost, Michael; Hulbert, John

2015-01-01

Tuberous sclerosis complex (TSC) is a genetic disorder characterized by nonmalignant tumors (hamartomas) that can occur in various organ systems, including the brain, kidneys, lungs, skin, eyes, and heart. Clinical manifestations of TSC can occur at any age, thereby making the diagnosis difficult. No typical disease presentation is known, and the clinical presentation usually differs between pediatric and adult patients. Furthermore, variable penetrance of the genetic mutation causes a range of disease severity from very mild to severe, and affected individuals can go undetected for years because many of the clinical manifestations of TSC lack specificity. Once a diagnosis is made, TSC management strategies should be tailored to address the symptoms and risks most relevant to the age of the patient. Improved understanding of the genetic basis of TSC and of the central issue of mTOR overactivation has led to use of pharmacotherapies such as the mTOR inhibitors everolimus and sirolimus in the treatment of TSC disease. In Phase II and III studies, everolimus has demonstrated efficacy and safety in the treatment of both brain (subependymal giant cell astrocytoma) and renal (angiomyolipoma) manifestations associated with TSC. It is important to bear in mind that TSC is a lifelong condition, and for those diagnosed as children, a continuum of care will be needed as they transition from pediatric to adult health services. Clearly identifying the likely differences among diagnosis, monitoring, and management of pediatric and adult patients with TSC is an important step in enabling efficiencies to be maximized without compromising the care provided to patients. PMID:29388579

No evidence of early head circumference enlargements in children later diagnosed with autism in Israel.

PubMed

Dinstein, Ilan; Haar, Shlomi; Atsmon, Shir; Schtaerman, Hen

2017-01-01

Large controversy exists regarding the potential existence and clinical significance of larger brain volumes in toddlers who later develop autism. Assessing this relationship is important for determining the clinical utility of early head circumference (HC) measures and for assessing the validity of the early overgrowth hypothesis of autism, which suggests that early accelerated brain development may be a hallmark of the disorder. We performed a retrospective comparison of HC, height, and weight measurements between 66 toddlers who were later diagnosed with autism and 66 matched controls. These toddlers represent an unbiased regional sample from a single health service provider in the southern district of Israel. On average, participating toddlers had >8 measurements between birth and the age of two, which enabled us to characterize individual HC, height, and weight development with high precision and fit a negative exponential growth model to the data of each toddler with exceptional accuracy. The analyses revealed that HC sizes and growth rates were not significantly larger in toddlers with autism even when stratifying the autism group based on verbal capabilities at the time of diagnosis. In addition, there were no significant correlations between ADOS scores at the time of diagnosis and HC at any time-point during the first 2 years of life. These negative results add to accumulating evidence, which suggest that brain volume is not necessarily larger in toddlers who develop autism. We believe that conflicting results reported in other studies are due to small sample sizes, use of misleading population norms, changes in the clinical definition of autism over time, and/or inclusion of individuals with syndromic autism. While abnormally large brains may be evident in some individuals with autism and more clearly visible in MRI scans, converging evidence from this and other studies suggests that enlarged HC is not a common etiology of the entire autism population. Early HC measures, therefore, offer very limited clinical utility for assessment of autism risk in the general population.

Quantitative evaluation of brain development using anatomical MRI and diffusion tensor imaging☆

PubMed Central

Oishi, Kenichi; Faria, Andreia V.; Yoshida, Shoko; Chang, Linda; Mori, Susumu

2013-01-01

The development of the brain is structure-specific, and the growth rate of each structure differs depending on the age of the subject. Magnetic resonance imaging (MRI) is often used to evaluate brain development because of the high spatial resolution and contrast that enable the observation of structure-specific developmental status. Currently, most clinical MRIs are evaluated qualitatively to assist in the clinical decision-making and diagnosis. The clinical MRI report usually does not provide quantitative values that can be used to monitor developmental status. Recently, the importance of image quantification to detect and evaluate mild-to-moderate anatomical abnormalities has been emphasized because these alterations are possibly related to several psychiatric disorders and learning disabilities. In the research arena, structural MRI and diffusion tensor imaging (DTI) have been widely applied to quantify brain development of the pediatric population. To interpret the values from these MR modalities, a “growth percentile chart,” which describes the mean and standard deviation of the normal developmental curve for each anatomical structure, is required. Although efforts have been made to create such a growth percentile chart based on MRI and DTI, one of the greatest challenges is to standardize the anatomical boundaries of the measured anatomical structures. To avoid inter- and intra-reader variability about the anatomical boundary definition, and hence, to increase the precision of quantitative measurements, an automated structure parcellation method, customized for the neonatal and pediatric population, has been developed. This method enables quantification of multiple MR modalities using a common analytic framework. In this paper, the attempt to create an MRI- and a DTI-based growth percentile chart, followed by an application to investigate developmental abnormalities related to cerebral palsy, Williams syndrome, and Rett syndrome, have been introduced. Future directions include multimodal image analysis and personalization for clinical application. PMID:23796902

Prediction of clinical depression scores and detection of changes in whole-brain using resting-state functional MRI data with partial least squares regression

PubMed Central

Shimizu, Yu; Yoshimoto, Junichiro; Takamura, Masahiro; Okada, Go; Okamoto, Yasumasa; Yamawaki, Shigeto; Doya, Kenji

2017-01-01

In diagnostic applications of statistical machine learning methods to brain imaging data, common problems include data high-dimensionality and co-linearity, which often cause over-fitting and instability. To overcome these problems, we applied partial least squares (PLS) regression to resting-state functional magnetic resonance imaging (rs-fMRI) data, creating a low-dimensional representation that relates symptoms to brain activity and that predicts clinical measures. Our experimental results, based upon data from clinically depressed patients and healthy controls, demonstrated that PLS and its kernel variants provided significantly better prediction of clinical measures than ordinary linear regression. Subsequent classification using predicted clinical scores distinguished depressed patients from healthy controls with 80% accuracy. Moreover, loading vectors for latent variables enabled us to identify brain regions relevant to depression, including the default mode network, the right superior frontal gyrus, and the superior motor area. PMID:28700672

Nano to micro delivery systems: targeting angiogenesis in brain tumors.

PubMed

Gilert, Ariel; Machluf, Marcelle

2010-10-08

Treating brain tumors using inhibitors of angiogenesis is extensively researched and tested in clinical trials. Although anti-angiogenic treatment holds a great potential for treating primary and secondary brain tumors, no clinical treatment is currently approved for brain tumor patients. One of the main hurdles in treating brain tumors is the blood brain barrier - a protective barrier of the brain, which prevents drugs from entering the brain parenchyma. As most therapeutics are excluded from the brain there is an urgent need to develop delivery platforms which will bypass such hurdles and enable the delivery of anti-angiogenic drugs into the tumor bed. Such delivery systems should be able to control release the drug or a combination of drugs at a therapeutic level for the desired time. In this mini-review we will discuss the latest improvements in nano and micro drug delivery platforms that were designed to deliver inhibitors of angiogenesis to the brain.

Nano to micro delivery systems: targeting angiogenesis in brain tumors

PubMed Central

2010-01-01

Treating brain tumors using inhibitors of angiogenesis is extensively researched and tested in clinical trials. Although anti-angiogenic treatment holds a great potential for treating primary and secondary brain tumors, no clinical treatment is currently approved for brain tumor patients. One of the main hurdles in treating brain tumors is the blood brain barrier - a protective barrier of the brain, which prevents drugs from entering the brain parenchyma. As most therapeutics are excluded from the brain there is an urgent need to develop delivery platforms which will bypass such hurdles and enable the delivery of anti-angiogenic drugs into the tumor bed. Such delivery systems should be able to control release the drug or a combination of drugs at a therapeutic level for the desired time. In this mini-review we will discuss the latest improvements in nano and micro drug delivery platforms that were designed to deliver inhibitors of angiogenesis to the brain. PMID:20932320

[The predictive value of plasma B-type natriuretic peptide levels on outcome in children with pulmonary hypertension undergoing congenital heart surgery].

PubMed

Baysal, Ayse; Saşmazel, Ahmet; Yildirim, Ayse; Ozyaprak, Buket; Gundogus, Narin; Kocak, Tuncer

2014-01-01

In children undergoing congenital heart surgery, plasma brain natriuretic peptide levels may have a role in development of low cardiac output syndrome that is defined as a combination of clinical findings and interventions to augment cardiac output in children with pulmonary hypertension. In a prospective observational study, fifty-one children undergoing congenital heart surgery with preoperative echocardiographic study showing pulmonary hypertension were enrolled. The plasma brain natriuretic peptide levels were collected before operation, 12, 24 and 48h after operation. The patients enrolled into the study were divided into two groups depending on: (1) Development of LCOS which is defined as a combination of clinical findings or interventions to augment cardiac output postoperatively; (2) Determination of preoperative brain natriuretic peptide cut-off value by receiver operating curve analysis for low cardiac output syndrome. The secondary end points were: (1) duration of mechanical ventilation ≥72h, (2) intensive care unit stay >7days, and (3) mortality. The differences in preoperative and postoperative brain natriuretic peptide levels of patients with or without low cardiac output syndrome (n=35, n=16, respectively) showed significant differences in repeated measurement time points (p=0.0001). The preoperative brain natriuretic peptide cut-off value of 125.5pgmL-1 was found to have the highest sensitivity of 88.9% and specificity of 96.9% in predicting low cardiac output syndrome in patients with pulmonary hypertension. A good correlation was found between preoperative plasma brain natriuretic peptide level and duration of mechanical ventilation (r=0.67, p=0.0001). In patients with pulmonary hypertension undergoing congenital heart surgery, 91% of patients with preoperative plasma brain natriuretic peptide levels above 125.5pgmL-1 are at risk of developing low cardiac output syndrome which is an important postoperative outcome. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options.

PubMed

Konturek, Peter C; Brzozowski, T; Konturek, S J

2011-12-01

Stress, which is defined as an acute threat to homeostasis, shows both short- and long-term effects on the functions of the gastrointestinal tract. Exposure to stress results in alterations of the brain-gut interactions ("brain-gut axis") ultimately leading to the development of a broad array of gastrointestinal disorders including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other functional gastrointestinal diseases, food antigen-related adverse responses, peptic ulcer and gastroesophageal reflux disease (GERD). The major effects of stress on gut physiology include: 1) alterations in gastrointestinal motility; 2) increase in visceral perception; 3) changes in gastrointestinal secretion; 4) increase in intestinal permeability; 5) negative effects on regenerative capacity of gastrointestinal mucosa and mucosal blood flow; and 6) negative effects on intestinal microbiota. Mast cells (MC) are important effectors of brain-gut axis that translate the stress signals into the release of a wide range of neurotransmitters and proinflammatory cytokines, which may profoundly affect the gastrointestinal physiology. IBS represents the most important gastrointestinal disorder in humans, and is characterized by chronic or recurrent pain associated with altered bowel motility. The diagnostic testing for IBS patients include routine blood tests, stool tests, celiac disease serology, abdominal sonography, breath testing to rule out carbohydrate (lactose, fructose, etc.) intolerance and small intestinal bacterial overgrowth. Colonoscopy is recommended if alarming symptoms are present or to obtain colonic biopsies especially in patients with diarrhoea predominant IBS. The management of IBS is based on a multifactorial approach and includes pharmacotherapy targeted against the predominant symptom, behavioural and psychological treatment, dietary alterations, education, reassurance and effective patient-physician relationship. When evaluating for the stress-induced condition in the upper GI tract, the diagnostic testing includes mainly blood tests and gastroscopy to rule out GERD and peptic ulcer disease. The therapy for these conditions is mainly based on the inhibition of gastric acid by proton pump inhibitors and eradication of Helicobacter pylori-infection. Additionally, melatonin an important mediator of brain gut axis has been shown to exhibit important protective effects against stress-induced lesions in the gastrointestinal tract. Finally, probiotics may profoundly affect the brain-gut interactions ("microbiome-gut-brain axis") and attenuate the development of stress-induced disorders in both the upper and lower gastrointestinal tract. Further studies on the brain-gut axis are needed to open new therapeutic avenues in the future.

Intra-cerebral schwannoma simulating glioma.

PubMed

Louis, Elie; Cret, Corina; Poirier, Jacques; Cornu, Philippe; Martin-Duverneuil, Nadine; Delattre, Jean-Yves; Sanson, Marc

2003-09-01

An intra-cerebral schwannoma, presenting as a cystic, calcified, enhancing frontal mass, arising in a 52-year-old woman was misdiagnosed as a glioma and treated with radiotherapy. This observation emphasizes the importance of careful histological reexamination of all brain tumors when a discrepancy appears between the initial histological diagnosis and the clinical evolution, in order to recognize rare curable entities and to avoid potentially toxic treatment.

Late recovery in cerebral fat embolism

PubMed Central

Srikanth, KP; Sundararajan, SR; Rajasekaran, S

2014-01-01

Fat embolism syndrome presenting primarily with cerebral manifestations is rarely reported. We report here two such patients who showed complete recovery following initial deterioration. The aim of these reports is to highlight that prolonged intensive care and good rehabilitation can lead to normal neurologic recovery despite poor clinical picture initially. The importance of adequate oxygenation to prevent secondary brain damage is emphasized during prolonged recovery. PMID:24600071

Gut microbiota, metabolism and psychopathology: A critical review and novel perspectives.

PubMed

Groen, Robin N; de Clercq, Nicolien C; Nieuwdorp, Max; Hoenders, H J Rogier; Groen, Albert K

2018-06-01

Psychiatric disorders are often associated with metabolic comorbidities. However, the mechanisms through which metabolic and psychiatric disorders are connected remain unclear. Pre-clinical studies in rodents indicate that the bidirectional signaling between the intestine and the brain, the so-called microbiome-gut-brain axis, plays an important role in the regulation of both metabolism and behavior. The gut microbiome produces a vast number of metabolites that may be transported into the host and play a part in homeostatic control of metabolism as well as brain function. In addition to short chain fatty acids, many of these metabolites have been identified in recent years. To what extent both microbiota and their products control human metabolism and behavior is a subject of intense investigation. In this review, we will discuss the most recent findings concerning alterations in the gut microbiota as a possible pathophysiological factor for the co-occurrence of metabolic comorbidities in psychiatric disorders.

Acne vulgaris, probiotics and the gut-brain-skin axis - back to the future?

PubMed

Bowe, Whitney P; Logan, Alan C

2011-01-31

Over 70 years have passed since dermatologists John H. Stokes and Donald M. Pillsbury first proposed a gastrointestinal mechanism for the overlap between depression, anxiety and skin conditions such as acne. Stokes and Pillsbury hypothesized that emotional states might alter the normal intestinal microflora, increase intestinal permeability and contribute to systemic inflammation. Among the remedies advocated by Stokes and Pillsbury were Lactobacillus acidophilus cultures. Many aspects of this gut-brain-skin unifying theory have recently been validated. The ability of the gut microbiota and oral probiotics to influence systemic inflammation, oxidative stress, glycemic control, tissue lipid content and even mood itself, may have important implications in acne. The intestinal microflora may also provide a twist to the developing diet and acne research. Here we provide a historical perspective to the contemporary investigations and clinical implications of the gut-brain-skin connection in acne.

Acne vulgaris, probiotics and the gut-brain-skin axis - back to the future?

PubMed Central

2011-01-01

Over 70 years have passed since dermatologists John H. Stokes and Donald M. Pillsbury first proposed a gastrointestinal mechanism for the overlap between depression, anxiety and skin conditions such as acne. Stokes and Pillsbury hypothesized that emotional states might alter the normal intestinal microflora, increase intestinal permeability and contribute to systemic inflammation. Among the remedies advocated by Stokes and Pillsbury were Lactobacillus acidophilus cultures. Many aspects of this gut-brain-skin unifying theory have recently been validated. The ability of the gut microbiota and oral probiotics to influence systemic inflammation, oxidative stress, glycemic control, tissue lipid content and even mood itself, may have important implications in acne. The intestinal microflora may also provide a twist to the developing diet and acne research. Here we provide a historical perspective to the contemporary investigations and clinical implications of the gut-brain-skin connection in acne. PMID:21281494

Blast TBI Models, Neuropathology, and Implications for Seizure Risk

PubMed Central

Kovacs, S. Krisztian; Leonessa, Fabio; Ling, Geoffrey S. F.

2014-01-01

Traumatic brain injury (TBI) due to explosive blast exposure is a leading combat casualty. It is also implicated as a key contributor to war related mental health diseases. A clinically important consequence of all types of TBI is a high risk for development of seizures and epilepsy. Seizures have been reported in patients who have suffered blast injuries in the Global War on Terror but the exact prevalence is unknown. The occurrence of seizures supports the contention that explosive blast leads to both cellular and structural brain pathology. Unfortunately, the exact mechanism by which explosions cause brain injury is unclear, which complicates development of meaningful therapies and mitigation strategies. To help improve understanding, detailed neuropathological analysis is needed. For this, histopathological techniques are extremely valuable and indispensable. In the following we will review the pathological results, including those from immunohistochemical and special staining approaches, from recent preclinical explosive blast studies. PMID:24782820

Blaming the brain for obesity: Integration of hedonic and homeostatic mechanisms

PubMed Central

Berthoud, Hans-Rudolf; Münzberg, Heike; Morrison, Christopher D.

2017-01-01

The brain plays a key role in the controls of energy intake and expenditure and many genes associated with obesity are expressed in the central nervous system. Technological and conceptual advances in both basic and clinical neurosciences have expanded the traditional view of homeostatic regulation of body weight by mainly the hypothalamus to include hedonic controls of appetite by cortical and subcortical brain areas processing external sensory information, reward, cognition, and executive functions. Thus, hedonic controls interact with homeostatic controls to regulate body weight in a flexible and adaptive manner that takes environmental conditions into account. This new conceptual framework has several important implications for the treatment of obesity. Because much of this interactive neural processing is outside awareness, cognitive restraint in a world of plenty is made difficult and prevention and treatment of obesity should be more rationally directed to the complex and often redundant mechanisms underlying this interaction. PMID:28192106

Clinical MRS studies of the brain

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

Hubesch, B.; Marinier, D.S.; Hetherington, H.P.

1989-12-01

Image-guided {sup 31}P and 1H magnetic resonance localized spectroscopy was performed on patients with brain tumors, temporal lobe epilepsy, chronic brain stroke, and deep white matter lesions. Absolute molar concentrations of metabolites, peak area ratios, and pH were obtained. The important findings were that {sup 31}P metabolite concentrations were significantly reduced in tumors, infarcts, and deep white matter lesions. Similarly, {sup 1}H metabolite intensities were reduced in chronic stroke. In the seizure foci of epilepsy patients, in tumors, and in chronic stroke, the pH was more alkaline than the normal pH. Peak area ratios were altered in tumors (reduction ofmore » phosphocreatine/inorganic phosphate) and in chronic stroke (large increases in Cr/NAA and Cho/NAA). Finally, the spectroscopic imaging technique offers a versatile alternative to the single point techniques, producing spectra or images of the spatial distribution of individual {sup 31}P metabolites.« less

GABAA Receptors, Anesthetics and Anticonvulsants in Brain Development

PubMed Central

Henschel, Oliver; Gipson, Keith E.; Bordey, Angelique

2008-01-01

GABA, acting via GABAA receptors, is well-accepted as the main inhibitory neurotransmitter of the mature brain, where it dampens neuronal excitability. The receptor's properties have been studied extensively, yielding important information about its structure, pharmacology, and regulation that are summarized in this review. Several GABAergic drugs have been commonly used as anesthetics, sedatives, and anticonvulsants for decades. However, findings that GABA has critical functions in brain development, in particular during the late embryonic and neonatal period, raise worthwhile questions regarding the side effects of GABAergic drugs that may lead to long-term cognitive deficits. Here, we will review some of these drugs in parallel with the control of CNS development that GABA exerts via activation of GABAA receptors. This review aims to provide a basic science and clinical perspective on the function of GABA and related pharmaceuticals acting at GABAA receptors. PMID:18537647

Hemihydranencephaly: living with half brain dysfunction.

PubMed

Pavone, Piero; Nigro, Francesco; Falsaperla, Raffaele; Greco, Filippo; Ruggieri, Martino; Rizzo, Renata; Praticò, Andrea D; Pavone, Lorenzo

2013-01-16

Hemi-hydranencephaly is a very rare condition characterized by complete or almost near-complete unilateral absence of the cortical cortex, which is filled by a sac of cerebrospinal fluid. Prenatal vascular disruption with occlusion of the carotid artery territories ipsilateral to the damaged brain is the presumed pathogenesis.We have selected nine cases that fit the clinical and pathologic characteristics of hemi-hydranencephaly, demonstrating that destruction of one hemisphere may be not always associated with severe neurologic impairment and may allow an almost normal life. This disorder is an example of a possible prenatal re-organization in which the right and left cerebral hemispheres present functional potentiality to make up the damaged brain.The cases reported in the literature are discussed, including a patient previously reported and followed-up for 10 years. A review of the cases is performed with an evaluation of the most important aspect of this rare and mysterious disorder.

In-Vitro Approaches for Studying Blast-Induced Traumatic Brain Injury

PubMed Central

Chen, Yung Chia; Smith, Douglas H.

2009-01-01

Abstract Traumatic brain injury caused by explosive or blast events is currently divided into four phases: primary, secondary, tertiary, and quaternary blast injury. These phases of blast-induced traumatic brain injury (bTBI) are biomechanically distinct, and can be modeled in both in-vivo and in-vitro systems. The purpose of this review is to consider the mechanical phases of bTBI, how these phases are reproduced with in-vitro models, and to review findings from these models to assess how each phase of bTBI can be examined in more detail. Highlighted are some important gaps in the literature that may be addressed in the future to better identify the exact contributing mechanisms for bTBI. These in-vitro models, viewed in combination with in-vivo models and clinical studies, can be used to assess both the mechanisms and possible treatments for this type of trauma. PMID:19397424

The role of microbiota in the pathogenesis of schizophrenia and major depressive disorder and the possibility of targeting microbiota as a treatment option.

PubMed

Lv, Fengli; Chen, Suling; Wang, Lina; Jiang, Ronghuan; Tian, Hongjun; Li, Jie; Yao, Yudong; Zhuo, Chuanjun

2017-11-21

The importance of interactions between the brain and the gastrointestinal tract has been increasingly recognized in recent years. It has been proposed that dysregulation and abnormalities in the brain-gut axis contribute to the etiology of a variety of central nervous system disorders. Particularly, dysbiosis, or impaired microbiota, has been implicated in multiple neurological and psychological disorders. The present paper reviews current evidence and theories concerning the possible mechanisms by which microbiota dysfunction contributes to the pathogenesis of schizophrenia and major depressive disorder. Clinical trials that investigated the possibility of treating both illnesses by correcting and rebalancing microbiota with probiotics are also reviewed. Overall, despite the accumulated knowledge in this field, more studies are warranted and required to further our understanding of the brain-gut axis and the possibility of targeting microbiota as a treatment option for schizophrenia and major depressive disorder.

VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer

PubMed Central

Gerstner, Elizabeth R.; Duda, Dan G.; di Tomaso, Emmanuelle; Ryg, Peter A.; Loeffler, Jay S.; Sorensen, A. Gregory; Ivy, Percy; Jain, Rakesh K.; Batchelor, Tracy T.

2016-01-01

Most brain tumors oversecrete vascular endothelial growth factor (VEGF), which leads to an abnormally permeable tumor vasculature. This hyperpermeability allows fluid to leak from the intravascular space into the brain parenchyma, which causes vasogenic cerebral edema and increased interstitial fluid pressure. Increased interstitial fluid pressure has an important role in treatment resistance by contributing to tumor hypoxia and preventing adequate tumor penetration of chemotherapy agents. In addition, edema and the corticosteroids needed to control cerebral edema cause significant morbidity and mortality. Agents that block the VEGF pathway are able to decrease vascular permeability and, thus, cerebral edema, by restoring the abnormal tumor vasculature to a more normal state. Decreasing cerebral edema minimizes the adverse effects of corticosteroids and could improve clinical outcomes. Anti-VEGF agents might also be useful in other cancer-related conditions that increase vascular permeability, such as malignant pleural effusions or ascites. PMID:19333229

Fluid dynamics vascular theory of brain and inner-ear function in traumatic brain injury: a translational hypothesis for diagnosis and treatment.

PubMed

Shulman, Abraham; Strashun, Arnold M

2009-01-01

It is hypothesized that in all traumatic brain injury (TBI) patients with a clinical history of closed or penetrating head injury, the initial head trauma is associated with a vibratory sensation and noise exposure, with resultant alteration in vascular supply to the structures and contents of the fluid compartments of brain and ear (i.e., the fluid dynamics vascular theory of brain-inner-ear function [FDVTBE]). The primary etiology-head trauma-results in an initial fluctuation, interference, or interaction in the normal fluid dynamics between brain and labyrinth of the inner ear, with a resultant clinical diversity of complaints varying in time of onset and severity. Normal function of the brain and ear is a reflection of a normal state of homeostasis between the fluid compartments in the brain of cerebrospinal fluid and perilymph-endolymph in the labyrinth of the ear. The normal homeostasis in the structures and contents between the two fluid compartment systems--intracerebral and intralabyrinthine--is controlled by mechanisms involved in the maintenance of normal pressures, water and electrolyte content, and neurotransmitter activities. The initial pathophysiology (a reflection of an alteration in the vascular supply to the brain-ear) is hypothesized to be an initial acute inflammatory response, persistence of which results in ischemia and an irreversible alteration in the involved neural substrates of brain-ear. Clinically, a chronic multisymptom complex becomes manifest. The multisymptom complex, individual for each TBI patient regardless of the diagnostic TBI category (i.e., mild, moderate, or severe), initially reflects processes of inflammation and ischemia which, in brain, result in brain volume loss identified as neurodegeneration and hydrocephalus ex vacuo or an alteration in cerebrospinal fluid production (i.e., pseudotumor cerebri) and, in ear, secondary endolymphatic hydrops with associated cochleovestibular complaints of hearing loss, tinnitus, vertigo, ear blockage, and hyperacusis. The FDVTBE integrates and translates a neurovascular hypothesis for Alzheimer's disease to TBI. This study presents an FDVTBE hypothesis of TBI to explain the clinical association of head trauma (TBI) and central nervous system neurodegeneration with multisensory complaints, highlighted by and focusing on cochleovestibular complaints. A clinical case report, previously published for demonstration of the cerebrovascular medical significance of a particular type of tinnitus, and evidence-based basic science and clinical medicine are cited to provide objective evidence in support and demonstration of the FDVTBE.

Neonatal Brain Hemorrhage (NBH) of Prematurity: Translational Mechanisms of the Vascular-Neural Network

PubMed Central

Lekic, Tim; Klebe, Damon; Poblete, Roy; Krafft, Paul R.; Rolland, William B.; Tang, Jiping; Zhang, John H.

2015-01-01

Neonatal brain hemorrhage (NBH) of prematurity is an unfortunate consequence of preterm birth. Complications result in shunt dependence and long-term structural changes such as post-hemorrhagic hydrocephalus, periventricular leukomalacia, gliosis, and neurological dysfunction. Several animal models are available to study this condition, and many basic mechanisms, etiological factors, and outcome consequences, are becoming understood. NBH is an important clinical condition, of which treatment may potentially circumvent shunt complication, and improve functional recovery (cerebral palsy, and cognitive impairments). This review highlights key pathophysiological findings of the neonatal vascular-neural network in the context of molecular mechanisms targeting the post-hemorrhagic hydrocephalus affecting this vulnerable infant population. PMID:25620100

Gender differences in neurological emergencies part II: a consensus summary and research agenda on traumatic brain injury.

PubMed

Wright, David W; Espinoza, Tamara R; Merck, Lisa H; Ratcliff, Jonathan J; Backster, Anika; Stein, Donald G

2014-12-01

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. There is strong evidence that gender and sex play an important role across the spectrum of TBI, from pathophysiology to clinical care. In May 2014, Academic Emergency Medicine held a consensus conference "Gender-Specific Research in Emergency Care: Investigate, Understand, and Translate How Gender Affects Patient Outcomes." A TBI working group was formed to explore what was known about the influence of sex and gender on TBI and to identify gaps for future research. The findings resulted in four major recommendations to guide the TBI research agenda. © 2014 by the Society for Academic Emergency Medicine.

The neurology of mTOR.

PubMed

Lipton, Jonathan O; Sahin, Mustafa

2014-10-22

The mechanistic target of rapamycin (mTOR) signaling pathway is a crucial cellular signaling hub that, like the nervous system itself, integrates internal and external cues to elicit critical outputs including growth control, protein synthesis, gene expression, and metabolic balance. The importance of mTOR signaling to brain function is underscored by the myriad disorders in which mTOR pathway dysfunction is implicated, such as autism, epilepsy, and neurodegenerative disorders. Pharmacological manipulation of mTOR signaling holds therapeutic promise and has entered clinical trials for several disorders. Here, we review the functions of mTOR signaling in the normal and pathological brain, highlighting ongoing efforts to translate our understanding of cellular physiology into direct medical benefit for neurological disorders.

Angiotensins in Alzheimer's disease - friend or foe?

PubMed

Kehoe, Patrick G; Miners, Scott; Love, Seth

2009-12-01

The renin-angiotensin system (RAS) is an important regulator of blood pressure. Observational and experimental studies suggest that alterations in blood pressure and components of the brain RAS contribute to the development and progression of Alzheimer's disease (AD), resulting in changes that can lead or contribute to cognitive decline. The complexity of the RAS and diversity of its interactions with neurological processes have recently become apparent but large gaps in our understanding still remain. Modulation of activity of components of the brain RAS offers substantial opportunities for the treatment and prevention of dementia, including AD. This paper reviews molecular, genetic, experimental and clinical data as well as the therapeutic opportunities that relate to the involvement of the RAS in AD.

Gender Differences in Neurological Emergencies Part II: A Consensus Summary and Research Agenda on Traumatic Brain Injury

PubMed Central

Wright, David W.; Espinoza, Tamara R.; Merck, Lisa H.; Ratcliff, Jonathan J.; Backster, Anika; Stein, Donald G.

2015-01-01

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. There is strong evidence that gender and sex play an important role across the spectrum of TBI, from pathophysiology to clinical care. In May 2014, Academic Emergency Medicine held a consensus conference “Gender-Specific Research in Emergency Care: Investigate, Understand, and Translate How Gender Affects Patient Outcomes.” A TBI working group was formed to explore what was known about the influence of sex and gender on TBI and to identify gaps for future research. The findings resulted in four major recommendations to guide the TBI research agenda. PMID:25420582

INVITED REVIEW – NEUROIMAGING RESPONSE ASSESSMENT CRITERIA FOR BRAIN TUMORS IN VETERINARY PATIENTS

PubMed Central

Rossmeisl, John H.; Garcia, Paulo A.; Daniel, Gregory B.; Bourland, John Daniel; Debinski, Waldemar; Dervisis, Nikolaos; Klahn, Shawna

2013-01-01

The evaluation of therapeutic response using cross-sectional imaging techniques, particularly gadolinium-enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the Response Evaluation Criteria in Solid Tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging-based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and Response Assessment in Neuro-oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment-induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy-induced changes. Finally, although objective endpoints such as MR-imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria. PMID:24219161

THE ADAPTATION FOR GROUP CLASSROOM USE OF CLINICAL TECHNIQUES FOR TEACHING BRAIN-INJURED CHILDREN.

ERIC Educational Resources Information Center

NOVACK, HARRY S.

THIS STUDY SOUGHT TO DEVELOP A PUBLIC SCHOOL PROGRAM FOR BRAIN-INJURED CHILDREN OF AVERAGE OR LOW AVERAGE INTELLECTUAL POTENTIAL. THE OBJECTIVES WERE--(1) TO COLLECT CLINICAL TUTORING TECHNIQUES BEING USED, (2) TO CLASSIFY CLINICAL TUTORIAL METHODS IN A FRAMEWORK USEFUL FOR DEVELOPING TECHNIQUES FOR GROUP TEACHING, (3) TO ADOPT CLINICAL TUTORIAL…

Non-invasive measurement of brain temperature with microwave radiometry: demonstration in a head phantom and clinical case.

PubMed

Stauffer, Paul R; Snow, Brent W; Rodrigues, Dario B; Salahi, Sara; Oliveira, Tiago R; Reudink, Doug; Maccarini, Paolo F

2014-02-01

This study characterizes the sensitivity and accuracy of a non-invasive microwave radiometric thermometer intended for monitoring body core temperature directly in brain to assist rapid recovery from hypothermia such as occurs during surgical procedures. To study this approach, a human head model was constructed with separate brain and scalp regions consisting of tissue equivalent liquids circulating at independent temperatures on either side of intact skull. This test setup provided differential surface/deep tissue temperatures for quantifying sensitivity to change in brain temperature independent of scalp and surrounding environment. A single band radiometer was calibrated and tested in a multilayer model of the human head with differential scalp and brain temperature. Following calibration of a 500MHz bandwidth microwave radiometer in the head model, feasibility of clinical monitoring was assessed in a pediatric patient during a 2-hour surgery. The results of phantom testing showed that calculated radiometric equivalent brain temperature agreed within 0.4°C of measured temperature when the brain phantom was lowered 10°C and returned to original temperature (37°C), while scalp was maintained constant over a 4.6-hour experiment. The intended clinical use of this system was demonstrated by monitoring brain temperature during surgery of a pediatric patient. Over the 2-hour surgery, the radiometrically measured brain temperature tracked within 1-2°C of rectal and nasopharynx temperatures, except during rapid cooldown and heatup periods when brain temperature deviated 2-4°C from slower responding core temperature surrogates. In summary, the radiometer demonstrated long term stability, accuracy and sensitivity sufficient for clinical monitoring of deep brain temperature during surgery.