The Role of Imaging in Clinical Stroke Scales That Predict Functional Outcome: A Systematic Review.

BACKGROUND AND PURPOSE: Numerous stroke scales have been developed to predict functional outcomes following acute ischemic stroke. The goal of this study was to summarize functional outcome scores in stroke that incorporate neuroimaging with those that don't incorporate neuroimaging. METHODS: Searches were conducted in Ovid MEDLINE, Ovid Embase, and the Cochrane Library Database from inception to January 23, 2015. Additional records were identified by employing the "Cited by" and "View References" features in Scopus. We included studies that described stroke prognosis models or scoring systems that predict functional outcome based on clinical and/or imaging data available on presentation. Score performance was evaluated based on area under the receiver operating characteristic curve (AUC). RESULTS: A total of 3300 articles were screened, yielding 14 scores that met inclusion criteria. Half (7) of the scores included neuroimaging as a predictor variable. Neuroimaging parameters included infarct size on magnetic resonance diffusion-weighted imaging, infarct size defined by computed tomography hypodensity, and hemodynamic abnormality on perfusion imaging. The modified Rankin Scale at 3 months poststroke was the most common functional outcome reported (13 of 14 scores). The AUCs ranged from 0.64 to 0.84 for scores that included neuroimaging as a predictor and 0.64 to 0.94 for scores that did not include neuroimaging. External validation has been performed for 7 scores. CONCLUSIONS: Due to the marked heterogeneity in the scores and populations in which they were applied, it is unclear whether current imaging-based scores offer advantages over simpler approaches for predicting poststroke function.

Infiltrative pattern of carcinomatosis in extremity muscles on MRI.

Carcinomas can cause an unusual, infiltrative pattern of metastatic carcinoma in extremity muscles on MRI. To assess this pattern, reports of MRI exams of 907 consecutive patients with a diagnosis of carcinoma were reviewed retrospectively to identify those that mentioned muscle metastasis or myositis in an extremity. Thirty-six (4%) of those reports described muscle metastasis (n=18) or myositis (n=18); based on medical record review and imaging follow-up, 17 cases represented metastases. Metastases manifested as an infiltrative carcinomatosis pattern in five patients, resulted from primary esophageal or gastric adenocarcinomas, and often were misdiagnosed as myositis.

The use of 18F-FDG PET ratios in the differential diagnosis of common malignant brain tumors.

OBJECTIVE: This study examined the use of positron emission tomography (PET) ratios to improve the diagnostic ability of 18F-FDG PET/computed tomography (CT) in the differentiation of enhancing brain metastases, central nervous system lymphomas, and gliomas. MATERIALS AND METHODS: Seventy-six patients with malignant brain tumors and available magnetic resonance imaging and PET/CT examinations were included. RESULTS: Among standardized uptake value (SUV)-related parameters tested, tumor maximum SUV to ipsilateral cortex maximum SUV ratio (Tmax:WMimax) and maximum SUV (SUVmax) proved to be the two most valuable parameters for differential diagnosis. CONCLUSION: In addition to SUVmax, Tmax:WMimax also seems to provide helpful information for the differential diagnosis of lymphomas from other malignant brain tumors.

Altered fear learning across development in both mouse and human.

The only evidence-based behavioral treatment for anxiety and stress-related disorders involves desensitization techniques that rely on principles of extinction learning. However, 40% of patients do not respond to this treatment. Efforts have focused on individual differences in treatment response, but have not examined when, during development, such treatments may be most effective. We examined fear-extinction learning across development in mice and humans. Parallel behavioral studies revealed attenuated extinction learning during adolescence. Probing neural circuitry in mice revealed altered synaptic plasticity of prefrontal cortical regions implicated in suppression of fear responses across development. The results suggest a lack of synaptic plasticity in the prefrontal regions, during adolescence, is associated with blunted regulation of fear extinction. These findings provide insight into optimizing treatment outcomes for when, during development, exposure therapies may be most effective.

Structure of Escherichia coli aspartate α-decarboxylase Asn72Ala: probing the role of Asn72 in pyruvoyl cofactor formation.

The crystal structure of the Asn72Ala site-directed mutant of Escherichia coli aspartate α-decarboxylase (ADC) has been determined at 1.7 Å resolution. The refined structure is consistent with the presence of a hydrolysis product serine in the active site in place of the pyruvoyl group required for catalysis, which suggests that the role of Asn72 is to protect the ester formed during ADC activation from hydrolysis. In previously determined structures of activated ADC, including the wild type and other site-directed mutants, the C-terminal region of the protein is disordered, but in the Asn72Ala mutant these residues are ordered owing to an interaction with the active site of the neighbouring symmetry-related multimer.

Transitional and translational studies of risk for anxiety.

Adolescence reflects a period of increased rates of anxiety, depression, and suicide. Yet most teens emerge from this period with a healthy, positive outcome. In this article, we identify biological factors that may increase risk for some individuals during this developmental period by: (1) examining changes in neural circuitry underlying core phenotypic features of anxiety as healthy individuals transition into and out of adolescence; (2) examining genetic factors that may enhance the risk for psychopathology in one individual over another using translation from mouse models to human neuroimaging and behavior; and (3) examining the effects of early experiences on core phenotypic features of anxiety using human neuroimaging and behavioral approaches. Each of these approaches alone provides only limited information on genetic and environmental influences on complex human behavior across development. Together, they reflect an emerging field of translational developmental neuroscience in forming important bridges between animal models of neurodevelopmental and neuropsychiatric disorders.

Variant brain-derived neurotrophic factor Val66Met endophenotypes: implications for posttraumatic stress disorder.

Recently, a common single nucleotide polymorphism (SNP) has been identified in the gene encoding brain-derived neurotrophic factor (BDNF). The variant BDNF(Met) has been shown to have decreased activity-dependent BDNF secretion from neurons and to lead to impairments in specific forms of learning and altered susceptibility to stress. A mouse model containing BDNF(Met) has also been linked to increased anxiety-like behavior. In a translational study, mice and human carriers of the BDNF(Met) allele were compared in their ability to extinguish a learned fear memory. Both showed slower suppression of the learned fear response. In humans, the neural correlates of this behavior were validated using fMRI. As anxiety and fear extinction lie at the core of symptoms and therapeutic approaches to posttraumatic stress disorder (PTSD), we propose that BDNF genotype and neuroimaging may be useful as biomarkers to provide guidance for more customized therapeutic directions. The aim of this paper is to review the available knowledge on the BDNF Val66Met SNP, with emphasis on anxiety- and fear-related endophenotypes and its potential implications for PTSD.

Imaging genetics and development: challenges and promises.

Excitement with the publication of the human genome has served as catalyst for scientists to uncover the functions of specific genes. The main avenues for understanding gene function have been in behavioral genetics on one end and on the other end, molecular mouse models. Attempts to bridge these approaches have used brain imaging to conveniently link anatomical abnormalities seen in knockout/transgenic mouse models and abnormal patterns of brain activity seen in humans. Although a convenient approach, this article provides examples of challenges for imaging genetics, its application to developmental questions, and promises for future directions. Attempts to link genes, brain, and behavior using behavioral genetics, imaging genetics, and mouse models of behavior are described. Each of these approaches alone, provide limited information on gene function in complex human behavior, but together, they are forming bridges between animal models and human psychiatric disorders.

The storm and stress of adolescence: insights from human imaging and mouse genetics.

The characterization of adolescence as a time of "storm and stress" remains an open debate. Intense and frequent negative affect during this period has been hypothesized to explain the increased rates of affective disorders, suicide, and accidental death during this time of life. Yet some teens emerge from adolescence with minimal turmoil. We provide a neurobiological model of adolescence that proposes an imbalance in the development of subcortical limbic (e.g., amygdala) relative to prefrontal cortical regions as a potential mechanism for heightened emotionality during this period. Empirical support for this model is provided from recent behavioral and human imaging studies on the development of emotion regulation. We then provide examples of environmental factors that may exacerbate imbalances in amygdala-ventrofrontal function increasing risk for anxiety related behaviors. Finally we present data from human and mouse studies to illustrate how genetic factors may enhance or diminish this risk. Together, these studies provide a converging methods approach for understanding the highly variable stress and turmoil experienced in adolescence.

A genetic variant BDNF polymorphism alters extinction learning in both mouse and human.

Mouse models are useful for studying genes involved in behavior, but whether they are relevant to human behavior is unclear. Here, we identified parallel phenotypes in mice and humans resulting from a common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, which is involved in anxiety-related behavior. An inbred genetic knock-in mouse strain expressing the variant BDNF recapitulated the phenotypic effects of the human polymorphism. Both were impaired in extinguishing a conditioned fear response, which was paralleled by atypical frontoamygdala activity in humans. Thus, this variant BDNF allele may play a role in anxiety disorders showing impaired learning of cues that signal safety versus threat and in the efficacy of treatments that rely on extinction mechanisms, such as exposure therapy.

Ecological nuances in functional magnetic resonance imaging (fMRI): psychological stressors, posture, and hydrostatics.

Brain imaging techniques such as functional magnetic resonance imaging (fMRI) have forged an impressive link between psychology and neuroscience. Whereas most experiments in cognitive psychology require participants to perform while sitting upright in front of display devices, fMRI obliges participants to perform cognitive tasks while lying supine and motionless inside a narrow bore. In addition to introducing psychological and physical stressors, such as loud thumps and head restraints, fMRI procedures also alter brain hydrostatics. The ecological factors associated with current fMRI technology, such as supine posture, may skew cognitive processing and influence hemodynamic and electrophysiological measurements, especially in extreme age groups and pathological populations. Recognizing the central role of fMRI in unraveling the neural mechanisms of cognition, we outline ways to address these limitations.