Early change in apparent diffusion coefficient as a predictor of response to neoadjuvant androgen deprivation and external beam radiation therapy for intermediate- to high-risk prostate cancer.

AIM: To determine the role of serial apparent diffusion coefficient (ADC) as a biomarker for response to neoadjuvant androgen deprivation therapy (nADT) followed by external beam radiation therapy (EBRT) in intermediate- to high-risk prostate cancer (PCa) patients. METHODS: This Health Insurance Portability and Accountability Act (HIPAA)-compliant, institutional review board (IRB)-approved prospective study included 12 patients with intermediate- to high-risk PCa patients prior to nADT and EBRT, who underwent serial serum prostate-specific antigen (PSA) and multiparametric prostate magnetic resonance imaging (mpMRI) at baseline (BL), 8-weeks after nADT initiation (time point [TP]1), 6-weeks into EBRT delivery (TP2), and 6-months after nADT initiation (TP3). Tumour volume (tVOL) and tumour and normal tissue ADC (tADC and nlADC) were determined at all TPs. tADC and nlADC dynamics were correlated with post-treatment PSA using Pearson's correlation coefficient. Paired t-tests compared pre/post-treatment ADC. RESULTS: There was a sequential decrease in PSA at all TPs, reaching their lowest values at TP3 post-treatment completion. Mean tADC increased significantly from baseline to TP1 (917.8 ± 107.7 × 10-6 versus 1033.8 ± 139.3 × 10-6 mm2/s; p<0.01), with no subsequent change at TP2 or TP3. Both percentage and absolute change in tADC from BL to TP1 correlated with post-treatment PSA (r=-0.666, r=-0.674; p=0.02). Post-treatment PSA in good responders (<0.1 ng/ml) versus poor responders (≥ 0.1 ng/ml) was associated with a greater increase in tADC from BL to TP1 (169.2 ± 122.4 × 10-6 versus 22.9 ± 75.5 × 10-6 mm2/s, p=0.03). CONCLUSION: This pilot study demonstrates the potential for early ADC metrics as a biomarker of response to nADT and EBRT in intermediate to high-risk PCA.

The organization of frontostriatal brain wiring in non-affective early psychosis compared with healthy subjects using a novel diffusion imaging fiber cluster analysis.

BACKGROUND: Alterations in brain connectivity may underlie neuropsychiatric conditions such as schizophrenia. We here assessed the degree of convergence of frontostriatal fiber projections in 56 young adult healthy controls (HCs) and 108 matched Early Psychosis-Non-Affective patients (EP-NAs) using our novel fiber cluster analysis of whole brain diffusion magnetic resonance imaging tractography. METHODS: Using whole brain tractography and our fiber clustering methodology on harmonized diffusion magnetic resonance imaging data from the Human Connectome Project for Early Psychosis we identified 17 white matter fiber clusters that connect frontal cortex (FCtx) and caudate (Cd) per hemisphere in each group. To quantify the degree of convergence and, hence, topographical relationship of these fiber clusters, we measured the inter-cluster mean distances between the endpoints of the fiber clusters at the level of the FCtx and of the Cd, respectively. RESULTS: We found (1) in both groups, bilaterally, a non-linear relationship, yielding convex curves, between FCtx and Cd distances for FCtx-Cd connecting fiber clusters, driven by a cluster projecting from inferior frontal gyrus; however, in the right hemisphere, the convex curve was more flattened in EP-NAs; (2) that cluster pairs in the right (p = 0.03), but not left (p = 0.13), hemisphere were significantly more convergent in HCs vs EP-NAs; (3) in both groups, bilaterally, similar clusters projected significantly convergently to the Cd; and, (4) a significant group by fiber cluster pair interaction for 2 right hemisphere fiber clusters (numbers 5, 11; p = .00023; p = .00023) originating in selective PFC subregions. CONCLUSIONS: In both groups, we found the FCtx-Cd wiring pattern deviated from a strictly topographic relationship and that similar clusters projected significantly more convergently to the Cd. Interestingly, we also found a significantly more convergent pattern of connectivity in HCs in the right hemisphere and that 2 clusters from PFC subregions in the right hemisphere significantly differed in their pattern of connectivity between groups.

Infection, learning, and memory: Focus on immune activation and aversive conditioning.

Here we review the effects of immune activation primarily via lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, on hippocampal and non-hippocampal-dependent learning and memory. Rodent studies have found that LPS alters both the acquisition and consolidation of aversive learning and memory, such as those evoking evolutionarily adaptive responses like fear and disgust. The inhibitory effects of LPS on the acquisition and consolidation of contextual fear memory are discussed. LPS-induced alterations in the acquisition of taste and place-related conditioned disgust memory within bottle preference tasks and taste reactivity tests (taste-related), in addition to conditioned context avoidance tasks and the anticipatory nausea paradigm (place-related), are highlighted. Further, conditioned disgust memory consolidation may also be influenced by LPS-induced effects. Growing evidence suggests a central role of immune activation, especially pro-inflammatory cytokine activity, in eliciting the effects described here. Understanding how infection-induced immune activation alters learning and memory is increasingly important as bacterial and viral infections are found to present a risk of learning and memory impairment.

The Organization of Frontostriatal Brain Wiring in Healthy Subjects Using a Novel Diffusion Imaging Fiber Cluster Analysis.

To assess normal organization of frontostriatal brain wiring, we analyzed diffusion magnetic resonance imaging (dMRI) scans in 100 young adult healthy subjects (HSs). We identified fiber clusters intersecting the frontal cortex and caudate, a core component of associative striatum, and quantified their degree of deviation from a strictly topographic pattern. Using whole brain dMRI tractography and an automated tract parcellation clustering method, we extracted 17 white matter fiber clusters per hemisphere connecting the frontal cortex and caudate. In a novel approach to quantify the geometric relationship among clusters, we measured intercluster endpoint distances between corresponding cluster pairs in the frontal cortex and caudate. We show first, the overall frontal cortex wiring pattern of the caudate deviates from a strictly topographic organization due to significantly greater convergence in regionally specific clusters; second, these significantly convergent clusters originate in subregions of ventrolateral, dorsolateral, and orbitofrontal prefrontal cortex (PFC); and, third, a similar organization in both hemispheres. Using a novel tractography method, we find PFC-caudate brain wiring in HSs deviates from a strictly topographic organization due to a regionally specific pattern of cluster convergence. We conjecture cortical subregions projecting to the caudate with greater convergence subserve functions that benefit from greater circuit integration.

Complex spatial and temporally defined myelin and axonal degeneration in Huntington disease.

Although much prior work has focused on the basal ganglia and cortical pathology that defines Huntington's disease (HD), recent studies have also begun to characterize cerebral white matter damage (Rosas et al., 2006; Dumas et al., 2012; Poudel et al., 2014). In this study, we investigated differences in the large fascicular bundles of the cerebral white matter of gene-positive HD carriers, including pre-manifest individuals and early symptomatic patients, using recently developed diffusion tractography procedures. We examined eighteen major fiber bundles in 37 patients with early HD (average age 55.2 ±â€¯11.5, 14 male, 23 female), 31 gene-positive, motor negative pre-symptomatic HD (PHD) (average age 48.1 ±â€¯11.5, 13 male, 18 female), and 38 healthy age-matched controls (average age 55.7 ±â€¯8.6, 14 male, 24 female), using the TRActs Constrained by UnderLying Anatomy (TRACULA) procedure available as part of the FreeSurfer image processing software package. We calculated the mean fractional anisotropy (FA) and the mean radial (RD) and axial diffusivities (AD) for each fiber bundle. We also evaluated the relationships between diffusion measures, cognition and regional cortical thinning. We found that early changes in RD of select tracts in PHD subjects were associated with impaired performance on neuropsychological tests, suggesting that early changes in myelin might underlie early cognitive dysfunction. Finally, we found that increases in AD of select tracts were associated with regionally select cortical thinning of areas known to atrophy in HD, including the sensorimotor, supramarginal and fusiform gyrus, suggesting that AD may be reflecting pyramidal cell degeneration in HD. Together, these results suggest that white matter microstructural changes in HD reflect a complex, clinically relevant and dynamic process.

Behavioral inhibition in childhood predicts smaller hippocampal volume in adolescent offspring of parents with panic disorder.

Behavioral inhibition (BI) is a genetically influenced behavioral profile seen in 15-20% of 2-year-old children. Children with BI are timid with people, objects and situations that are novel or unfamiliar, and are more reactive physiologically to these challenges as evidenced by higher heart rate, pupillary dilation, vocal cord tension and higher levels of cortisol. BI predisposes to the later development of anxiety, depression and substance abuse. Reduced hippocampal volumes have been observed in anxiety disorders, depression and posttraumatic stress disorder. Animal models have demonstrated that chronic stress can damage the hippocampal formation and implicated cortisol in these effects. We, therefore, hypothesized that the hippocampi of late adolescents who had been behaviorally inhibited as children would be smaller compared with those who had not been inhibited. Hippocampal volume was measured with high-resolution structural magnetic resonance imaging in 43 females and 40 males at 17 years of age who were determined to be BI+ or BI- based on behaviors observed in the laboratory as young children. BI in childhood predicted reduced hippocampal volumes in the adolescents who were offspring of parents with panic disorder, or panic disorder with comorbid major depression. We discuss genetic and environmental factors emanating from both child and parent that may explain these findings. To the best of our knowledge, this is the first study to demonstrate a relationship between the most extensively studied form of temperamentally based human trait anxiety, BI, and hippocampal structure. The reduction in hippocampal volume, as reported by us, suggests a role for the hippocampus in human trait anxiety and anxiety disorder that warrants further investigation.

Comparison of CE-FDG-PET/CT with CE-FDG-PET/MR in the evaluation of osseous metastases in breast cancer patients.

BACKGROUND: Despite improvements in treatments, metastatic breast cancer remains difficult to cure. Bones constitute the most common site of first-time recurrence, occurring in 40-75% of cases. Therefore, evaluation for possible osseous metastases is crucial. Technetium 99 ((99)Tc) bone scintigraphy and fluorodexossyglucose (FDG) positron emission tomography (PET)-computed tomography (PET-CT) are the most commonly used techniques to assess osseous metastasis. PET magnetic resonance (PET-MR) imaging is an innovative technique still under investigation. We compared the capability of PET-MR to that of same-day PET-CT to assess osseous metastases in patients with breast cancer. METHODS: One hundred and nine patients with breast cancer, who underwent same-day contrast enhanced (CE)-PET-CT and CE-PET-MR, were evaluated. CE-PET-CT and CE-PET-MR studies were interpreted by consensus by a radiologist and a nuclear medicine physician. Correlations with prior imaging and follow-up studies were used as the reference standard. Binomial confidence intervals and a χ(2) test were used for categorical data, and paired t-test was used for the SUVmax data; a non-informative prior Bayesian approach was used to estimate and compare the specificities. RESULTS: Osseous metastases affected 25 out 109 patients. Metastases were demonstrated by CE-PET-CT in 22 out of 25 patients (88%±7%), and by CE-PET-MR in 25 out of 25 patients (100%). CE-PET-CT revealed 90 osseous metastases and CE-PET-MR revealed 141 osseous metastases (P<0.001). The estimated sensitivity of CE-PET-CT and CE-PET-MR were 0.8519 and 0.9630, respectively. The estimated specificity for CE-FDG-PET-MR was 0.9884. The specificity of CE-PET-CT cannot be determined from patient-level data, because CE-PET-CT yielded a false-positive lesion in a patient who also had other, true metastases. CONCLUSIONS: CE-PET-MR detected a higher number of osseous metastases than did same-day CE-PET-CT, and was positive for 12% of the patients deemed osseous metastasis-negative on the basis of CE-PET-CT.

Imaging appearance of the lateral rectus-superior rectus band in 100 consecutive patients without strabismus.

BACKGROUND AND PURPOSE: The lateral rectus-superior rectus band is an orbital connective tissue structure that has been implicated in a form of strabismus termed sagging eye syndrome. Our purpose was to define the normal MR imaging and CT appearance of this band in patients without strabismus. MATERIALS AND METHODS: Orbital MR imaging and CT examinations in 100 consecutive patients without strabismus were evaluated. Readers graded the visibility of the lateral rectus-superior rectus band on coronal T1WI, coronal STIR, and coronal CT images. Readers determined whether the band demonstrated superotemporal bowing or any discontinuities and whether a distinct lateral levator aponeurosis was seen. Reader agreement was assessed by κ coefficients. Association between imaging metrics and patient age/sex was calculated by using the Fisher exact test. RESULTS: The lateral rectus-superior rectus band was visible in 95% of coronal T1WI, 68% of coronal STIR sequences, and 70% of coronal CT scans. Ninety-five percent of these bands were seen as a continuous, arc-like structure extending from the superior rectus/levator palpebrae muscle complex to the lateral rectus muscle; 24% demonstrated superotemporal bowing; and in 82% of orbits, a distinct lateral levator aponeurosis was visible. Increasing patient age was negatively associated with lateral rectus-superior rectus band visibility (P=.03), positively associated with lateral rectus-superior rectus band superotemporal bowing (P=.03), and positively associated with lateral levator aponeurosis visibility (P=.01). CONCLUSIONS: The lateral rectus-superior rectus band is visible in most patients without strabismus on coronal T1WI. The age effect with respect to its visibility and superotemporal bowing could represent age-related connective tissue degeneration.

Brain white matter microstructure is associated with susceptibility to motion-induced nausea.

Nausea is associated with significant morbidity, and there is a wide range in the propensity of individuals to experience nausea. The neural basis of the heterogeneity in nausea susceptibility is poorly understood. Our previous functional magnetic resonance imaging (fMRI) study in healthy adults showed that a visual motion stimulus caused activation in the right MT+/V5 area, and that increased sensation of nausea due to this stimulus was associated with increased activation in the right anterior insula. For the current study, we hypothesized that individual differences in visual motion-induced nausea are due to microstructural differences in the inferior fronto-occipital fasciculus (IFOF), the white matter tract connecting the right visual motion processing area (MT+/V5) and right anterior insula. To test this hypothesis, we acquired diffusion tensor imaging data from 30 healthy adults who were subsequently dichotomized into high and low nausea susceptibility groups based on the Motion Sickness Susceptibility Scale. We quantified diffusion along the IFOF for each subject based on axial diffusivity (AD); radial diffusivity (RD), mean diffusivity (MD) and fractional anisotropy (FA), and evaluated between-group differences in these diffusion metrics. Subjects with high susceptibility to nausea rated significantly (P < 0.001) higher nausea intensity to visual motion stimuli and had significantly (P < 0.05) lower AD and MD along the right IFOF compared to subjects with low susceptibility to nausea. This result suggests that differences in white matter microstructure within tracts connecting visual motion and nausea-processing brain areas may contribute to nausea susceptibility or may have resulted from an increased history of nausea episodes.

Severity of leukoaraiosis determines clinical phenotype after brain infarction.

OBJECTIVE: To determine whether the extent of leukoaraiosis, a composite marker of baseline brain integrity, differed between patients with TIA with diffusion-weighted imaging (DWI) evidence of infarction (transient symptoms with infarction [TSI]) and patients with ischemic stroke. METHODS: Leukoaraiosis volume on MRI was quantified in a consecutive series of 153 TSI and 354 ischemic stroke patients with comparable infarct volumes on DWI. We explored the relationship between leukoaraiosis volume and clinical phenotype (TIA or ischemic stroke) using a logistic regression model. RESULTS: Patients with TSI tended to be younger (median age 66 vs 69 years, p = 0.062) and had smaller median normalized leukoaraiosis volume (1.2 mL, interquartile range [IQR] 0.2-4.7 mL vs 3.5 mL, IQR 1.2-8.6 mL, p < 0.001). In multivariable analysis controlling for age, stroke risk factors, etiologic stroke mechanism, infarct volume, and infarct location, increasing leukoaraiosis volume remained associated with ischemic stroke (odds ratio 1.05 per mL, 95%confidence interval 1.02-1.09, p = 0.004), along with infarct volume and infarct location. CONCLUSION: The probability of ischemic stroke rather than TSI increases with increasing leukoaraiosis volume, independent of infarct size and location. Our findings support the concept that the integrity of white matter tracts connecting different parts of the brain could contribute to whether or not patients develop TSI or ischemic stroke in an event of brain infarction.

Pooled analysis of brain activity in irritable bowel syndrome and controls during rectal balloon distension.

BACKGROUND: Brain-imaging literature of irritable bowel syndrome (IBS) suggests an abnormal brain-gut communication. We analyzed the literature to evaluate and compare the aspects of brain activity in individuals with IBS and control subjects experiencing controlled rectal stimulation. METHODS: PubMed was searched until September 2010. Data from 16 articles reporting brain activity during rectal balloon distensions in IBS compared to control groups was analyzed. Prevalence rates and pairwise activations were assessed using binomial distributions for 11 selected regions of interest. The data were aggregated to adjust for center effect. KEY RESULTS: There was considerable variability in the literature regarding regions and their activity patterns in controls and individuals with IBS. There was no significant difference found in the thalamus, anterior cingulate cortex, posterior cingulate cortex, and prefrontal cortex, however, results show limited evidence of consensus for the anterior insula (AI) (P = 0.22). Pairwise activity results suggest that pairs involving the AI tend to have more consistent activity together than pairs which do not involve the AI (posterior insula and AI, P = 0.08; posterior cingulate cortex and AI, P = 0.16), however, no pairwise evaluation reached significance. CONCLUSIONS & INFERENCES: Our pooled analysis demonstrates that the literature reports are quite heterogeneous but there is some evidence that there may be patterns of higher activity more common in individuals with IBS than in controls. A consensus, though, regarding study designs, analysis approach and reporting could create a clearer understanding of brain involvement in IBS pathophysiology.

A score to predict early risk of recurrence after ischemic stroke.

BACKGROUND: There is currently no instrument to stratify patients presenting with ischemic stroke according to early risk of recurrent stroke. We sought to develop a comprehensive prognostic score to predict 90-day risk of recurrent stroke. METHODS: We analyzed data on 1,458 consecutive ischemic stroke patients using a Cox regression model with time to recurrent stroke as the response and clinical and imaging features typically available to physician at admission as covariates. The 90-day risk of recurrent stroke was calculated by summing up the number of independent predictors weighted by their corresponding beta-coefficients. The resultant score was called recurrence risk estimator at 90 days or RRE-90 score (available at: http://www.nmr.mgh.harvard.edu/RRE-90/). RESULTS: Sixty recurrent strokes (54 had baseline imaging) occurred during the follow-up period. The risk adjusted for time to follow-up was 6.0%. Predictors of recurrence included admission etiologic stroke subtype, prior history of TIA/stroke, and topography, age, and distribution of brain infarcts. The RRE-90 score demonstrated adequate calibration and good discrimination (area under the ROC curve [AUC] = 0.70-0.80), which was maintained when applied to a separate cohort of 433 patients (AUC = 0.70-0.76). The model's performance was also maintained for predicting early (14-day) risk of recurrence (AUC = 0.80). CONCLUSIONS: The RRE-90 is a Web-based, easy-to-use prognostic score that integrates clinical and imaging information available in the acute setting to quantify early risk of recurrent stroke. The RRE-90 demonstrates good predictive performance, suggesting that, if validated externally, it has promise for use in creating individualized patient management algorithms and improving clinical practice in acute stroke care.

Cerebellar stroke without motor deficit: clinical evidence for motor and non-motor domains within the human cerebellum.

OBJECTIVE: To determine whether there are non-motor regions of cerebellum in which sizeable infarcts have little or no impact on motor control. EXPERIMENTAL PROCEDURES: We evaluated motor deficits in patients following cerebellar stroke using a modified version of the International Cooperative Ataxia Rating Scale (MICARS). Lesion location was determined using magnetic resonance imaging (MRI) and computerized axial tomography (CT). Patients were grouped by stroke location-Group I, stroke within the anterior lobe (lobules I-V); Group 2, anterior lobe and lobule VI; Group 3, posterior lobe (lobules VI-IX; including flocculonodular lobe, lobule X); Group 4, posterior lobe but excluding lobule VI (i.e. lobules VII-X); Group 5, stroke within anterior lobe plus posterior lobe. RESULTS: Thirty-nine patients were examined 8.0+/-6.0 days following stroke. There were no Group 1 patients. As mean MICARS scores for Groups 2 through 5 differed significantly (one-way analysis of variance, F(3,35)=10.9, P=0.000 03), post hoc Tukey's least significant difference tests were used to compare individual groups. Group 2 MICARS scores (n=6; mean+/-SD, 20.2+/-6.9) differed from Group 3 (n=6; 7.2+/-3.8; P=0.01) and Group 4 (n=13; 2.5+/-2.0; P=0.000 02); Group 5 (n=14; 18.6+/-12.8) also differed from Group 3 (P=0.009) and Group 4 (P=0.000 02). There were no differences between Groups 2 and 5 (P=0.71), or between Group 3 and Group 4 (P=0.273). However, Group 3 differed from Group 4 when analyzed with a two-sample t-test unadjusted for multiple comparisons (P=0.03). Thus, the cerebellar motor syndrome resulted from stroke in the anterior lobe, but not from stroke in lobules VII-X (Groups 2 plus 5, n=20, MICARS 19.1+/-11.2, vs. Group 4; P=0.000 002). Strokes involving lobule VI produced minimal motor impairment. CONCLUSION: These findings demonstrate that cerebellar stroke does not always result in motor impairment, and they provide clinical evidence for topographic organization of motor versus nonmotor functions in the human cerebellum.

ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes.

BACKGROUND: Rapid and easy clinical assessments for volumes of infarction and perfusion mismatch are needed. We tested whether simple geometric models generated accurate estimates of these volumes. METHODS: Acute diffusion-weighted image (DWI) and perfusion (mean transit time [MTT]) in 63 strokes and established infarct volumes in 50 subacute strokes were measured by computerized planimetry. Mismatch was defined as MTT/DWI > or = 1.2. Observers, blinded to planimetric values, measured lesions in three perpendicular axes A, B, and C. Geometric estimates of sphere, ellipsoid, bicone, and cylinder were compared to planimetric volume by least-squares linear regression. RESULTS: The ABC/2 formula (ellipsoid) was superior to other geometries for estimating volume of DWI (slope 1.16, 95% confidence interval [CI] 0.94 to 1.38; R(2) = 0.91, p = 0.001) and MTT (slope 1.11, 95% CI 0.99 to 1.23; R(2) = 0.89, p = 0.001). The intrarater and interrater reliability for ABC/2 was high for both DWI (0.992 and 0.965) and MTT (0.881 and 0.712). For subacute infarct, the ABC/2 formula also best estimated planimetric volume (slope 1.00, 95% CI 0.98 to 1.19; R(2) = 0.74, p = 0.001). In general, sphere and cylinder geometries overestimated all volumes and bicone underestimated all volumes. The positive predictive value for mismatch was 92% and negative predictive value was 33%. CONCLUSIONS: Of the models tested, ABC/2 is reproducible, is accurate, and provides the best simple geometric estimate of infarction and mean transit time volumes. ABC/2 has a high positive predictive value for identifying mismatch greater than 20% and might be a useful tool for rapid determination of acute stroke treatment.

Hypothalamus and amygdala response to acupuncture stimuli in Carpal Tunnel Syndrome.

Brain processing of acupuncture stimuli in chronic neuropathic pain patients may underlie its beneficial effects. We used fMRI to evaluate verum and sham acupuncture stimulation at acupoint LI-4 in Carpal Tunnel Syndrome (CTS) patients and healthy controls (HC). CTS patients were retested after 5 weeks of acupuncture therapy. Thus, we investigated both the short-term brain response to acupuncture stimulation, as well as the influence of longer-term acupuncture therapy effects on this short-term response. CTS patients responded to verum acupuncture with greater activation in the hypothalamus and deactivation in the amygdala as compared to HC, controlling for the non-specific effects of sham acupuncture. A similar difference was found between CTS patients at baseline and after acupuncture therapy. For baseline CTS patients responding to verum acupuncture, functional connectivity was found between the hypothalamus and amygdala--the less deactivation in the amygdala, the greater the activation in the hypothalamus, and vice versa. Furthermore, hypothalamic response correlated positively with the degree of maladaptive cortical plasticity in CTS patients (inter-digit separation distance). This is the first evidence suggesting that chronic pain patients respond to acupuncture differently than HC, through a coordinated limbic network including the hypothalamus and amygdala.

Neuroanatomic correlates of stroke-related myocardial injury.

BACKGROUND: Myocardial injury can occur after ischemic stroke in the absence of primary cardiac causes. The neuroanatomic basis of stroke-related myocardial injury is not well understood. OBJECTIVE: To identify regions of brain infarction associated with myocardial injury using a method free of the bias of an a priori hypothesis as to any specific location. METHODS: Of 738 consecutive patients with acute ischemic stroke, the authors identified 50 patients in whom serum cardiac troponin T (cTnT) elevation occurred in the absence of any apparent cause within 3 days of symptom onset. Fifty randomly selected, age- and sex-matched patients with ischemic stroke without cTnT elevation served as controls. Diffusion-weighted images with outlines of infarction were co-registered to a template, averaged, and then subtracted to find voxels that differed between the two groups. Voxel-wise p values were determined using a nonparametric permutation test to identify specific regions of infarction that were associated with cTnT elevation. RESULTS: The study groups were well balanced with respect to stroke risk factors, history of coronary artery disease, infarction volume, and frequency of right and left middle cerebral artery territory involvement. Brain regions that were a priori associated with cTnT elevation included the right posterior, superior, and medial insula and the right inferior parietal lobule. Among patients with right middle cerebral artery infarction, the insular cluster was involved in 88% of patients with and 33% without cTnT elevation (odds ratio: 15.00; 95% CI: 2.65 to 84.79). CONCLUSIONS: Infarctions in specific brain regions including the right insula are associated with elevated serum cardiac troponin T level indicative of myocardial injury.

Case clustering in infective endocarditis: the role of availability bias.

Limited data exist regarding the impact of variations in clinical practice and physicians' cognitive bias on the diagnosis of infective endocarditis (IE). As an illustration of these effects, unexpected clustering of IE diagnosis was encountered in a prospectively studied cohort. Transoesophageal echocardiography examinations for suspected IE were performed more frequently following a diagnosis of IE, and were associated with a subsequent cluster of IE cases. The cognitive bias of physicians resulting from a recent case of IE can lead to a transient increase in diagnosing additional cases of IE.

fMRI of sensitization to angry faces.

This study examined what is communicated by facial expressions of anger and mapped the neural substrates, evaluating the motivational salience of these stimuli. During functional magnetic resonance imaging, angry and neutral faces were presented to human subjects. Across experimental runs, signal adaptation was observed. Whereas fearful faces have reproducibly evoked response habituation in amygdala and prefrontal cortex, angry faces evoked sensitization in the insula, cingulate, thalamus, basal ganglia, and hippocampus. Complementary offline rating and keypress experiments determined an aversive rank ordering of angry, fearful, neutral, and happy faces and revealed behavioral sensitization to the angry faces. Subjects rated angry faces, in contrast to other face categories such as fear, as significantly more likely to directly inflict harm. Furthermore, they rated angry faces as significantly less likely to produce positive emotional outcomes than the other face categories. Together these data argue that angry faces, a directly aversive stimulus, produce a sensitization response.

Evidence for more widespread cerebral pathology in early HD: an MRI-based morphometric analysis.

BACKGROUND: Most clinical symptoms of Huntington disease (HD) have been attributed to striatal degeneration, but extrastriatal degeneration may play an important role in the clinical symptoms because postmortem studies demonstrate that almost all brain structures atrophy. OBJECTIVE: To fully characterize the morphometric changes that occur in vivo in HD. METHODS: High-resolution 1.5 mm T1-weighted coronal scans were acquired from 18 individuals in early to mid-stages of HD and 18 healthy age-matched controls. Cortical and subcortical gray and white matter were segmented using a semiautomated intensity contour-mapping algorithm. General linear models for correlated data of the volumes of brain regions were used to compare groups, controlling for age, education, handedness, sex, and total brain volumes. RESULTS: Subjects with HD had significant volume reductions in almost all brain structures, including total cerebrum, total white matter, cerebral cortex, caudate, putamen, globus pallidus, amygdala, hippocampus, brainstem, and cerebellum. CONCLUSIONS: Widespread degeneration occurs in early to mid-stages of HD, may explain some of the clinical heterogeneity, and may impact future clinical trials.

The influence of gender on survival and tumor recurrence following adjuvant therapy of completely resected stages II and IIIa non-small cell lung cancer.

This study evaluates the influence of gender on survival and tumor recurrence following adjuvant therapy of completely resected stages II and IIIa non-small cell lung cancer (NSCLC). The Eastern Cooperative Oncology Group conducted a randomized prospective trial of adjuvant therapy in patients with completely resected stages II and IIIa NSCLC. A laboratory correlative study assessed the prevalence and prognostic significance of p53 and K-ras mutations. Patients were randomized to receive either radiotherapy (RT) alone or four cycles of cisplatin and VP-16 administered concurrently with radiotherapy (CRT). Median survival was 35 months for the 285 men and 41 months for the 203 women enrolled in the study (P = 0.12). The relative risk (RR) of death for men vs women was 1.19 (95% confidence interval [CI], 0.95-1.49). Median survival of the 147 men and 95 women randomized to the RT arm was 39 months each (P = 0.35). Median survival of the 138 men and 108 women randomized to the CRT arm was 30 and 42 months, respectively (P = 0.18). Disease recurrence patterns were similar between the genders. Univariate and multivariate analyses demonstrated improved survival for women with tumors of non-squamous histology (P < 0.01). The distribution of p53 and K-ras mutations was similar between the genders and had no influence on survival. Gender does not influence survival following adjuvant RT or CRT administered to patients with completely resected stages II and IIIa NSCLC. However, women with non-squamous histology have increased survival when compared to men.