Is Intracranial Atherosclerosis an Independent Risk Factor for Cerebral Atrophy? A Retrospective Evaluation

<p>Abstract</p> <p>Background</p> <p>Our purpose was to study the association between the intracranial atherosclerosis as measured by cavernous carotid artery calcification (ICAC) observed on head CT and atrophic changes of supra-tentorial brain demonstrated by MRI.</p> <p>Methods</p> <p>Institutional review board approval was obtained for this retrospective study incorporating 65 consecutive patients presenting acutely who had both head CT and MRI. Arterial calcifications of the intracranial cavernous carotids (ICAC) were assigned a number (1 to 4) in the bone window images from CT scans. These 4 groups were then combined into high (grades 3 and 4) and low calcium (grades 1 and 2) subgroups. Brain MRI was independently evaluated to identify cortical and central atrophy. Demographics and cardiovascular risk factors were evaluated in subjects with high and low ICAC. Relationship between CT demonstrated ICAC and brain atrophy patterns were evaluated both without and with adjustment for cerebral ischemic scores and cardiovascular risk factors.</p> <p>Results</p> <p>Forty-six of the 65 (71%) patients had high ICAC on head CT. Subjects with high ICAC were older, and had higher prevalence of hypertension, diabetes, coronary artery disease (CAD), atrial fibrillation and history of previous stroke (CVA) compared to those with low ICAC. Age demonstrated strong correlation with both supratentorial atrophy patterns. There was no correlation between ICAC and cortical atrophy. There was correlation however between central atrophy and ICAC. This persisted even after adjustment for age.</p> <p>Conclusion</p> <p>Age is the most important determinant of atrophic cerebral changes. However, high ICAC demonstrated age independent association with central atrophy.</p

The role of rapid diagnostics in managing Ebola epidemics

Ebola emerged in West Africa around December 2013 and swept through Guinea, Sierra Leone and Liberia, giving rise to 27,748 confirmed, probable and suspected cases reported by 29 July 2015. Case diagnoses during the epidemic have relied on polymerase chain reaction-based tests. Owing to limited laboratory capacity and local transport infrastructure, the delays from sample collection to test results being available have often been 2 days or more. Point-of-care rapid diagnostic tests offer the potential to substantially reduce these delays. We review Ebola rapid diagnostic tests approved by the World Health Organization and those currently in development. Such rapid diagnostic tests could allow early triaging of patients, thereby reducing the potential for nosocomial transmission. In addition, despite the lower test accuracy, rapid diagnostic test-based diagnosis may be beneficial in some contexts because of the reduced time spent by uninfected individuals in health-care settings where they may be at increased risk of infection; this also frees up hospital beds. We use mathematical modelling to explore the potential benefits of diagnostic testing strategies involving rapid diagnostic tests alone and in combination with polymerase chain reaction testing. Our analysis indicates that the use of rapid diagnostic tests with sensitivity and specificity comparable with those currently under development always enhances control, whether evaluated at a health-care-unit or population level. If such tests had been available throughout the recent epidemic, we estimate, for Sierra Leone, that their use in combination with confirmatory polymerase chain-reaction testing might have reduced the scale of the epidemic by over a third

Ascending central canal dilation and progressive ependymal disruption in a contusion model of rodent chronic spinal cord injury

<p>Abstract</p> <p>Background</p> <p>Chronic spinal cord injury (SCI) can lead to an insidious decline in motor and sensory function in individuals even years after the initial injury and is accompanied by a slow and progressive cytoarchitectural destruction. At present, no pathological mechanisms satisfactorily explain the ongoing degeneration.</p> <p>Methods</p> <p>Adult female Sprague-Dawley rats were anesthetized laminectomized at T10 and received spinal cord contusion injuries with a force of 250 kilodynes using an Infinite Horizon Impactor. Animals were randomly distributed into 5 groups and killed 1 (n = 4), 28 (n = 4), 120 (n = 4), 450 (n = 5), or 540 (n = 5) days after injury. Morphometric and immunohistochemical studies were then performed on 1 mm block sections, 6 mm cranial and 6 mm caudal to the lesion epicenter. The SPSS 11.5 t test was used to determine differences between quantitative measures.</p> <p>Results</p> <p>Here, we document the first report of an ascending central canal dilation and progressive ependymal disruption cranial to the epicenter of injury in a contusion model of chronic SCI, which was characterized by extensive dural fibrosis and intraparenchymal cystic cavitation. Expansion of the central canal lumen beyond a critical diameter corresponded with ependymal cell ciliary loss, an empirically predictable thinning of the ependymal region, and a decrease in cell proliferation in the ependymal region. Large, aneurysmal dilations of the central canal were accompanied by disruptions in the ependymal layer, periependymal edema and gliosis, and destruction of the adjacent neuropil.</p> <p>Conclusion</p> <p>Cells of the ependymal region play an important role in CSF homeostasis, cellular signaling and wound repair in the spinal cord. The possible effects of this ascending pathology on ependymal function are discussed. Our studies suggest central canal dilation and ependymal region disruption as steps in the pathogenesis of chronic SCI, identify central canal dilation as a marker of chronic SCI and provide novel targets for therapeutic intervention.</p

Heterogeneity in age-related white matter changes

White matter changes occur endemically in routine magnetic resonance imaging (MRI) scans of elderly persons. MRI appearance and histopathological correlates of white matter changes are heterogeneous. Smooth periventricular hyperintensities, including caps around the ventricular horns, periventricular lining and halos are likely to be of non-vascular origin. They relate to a disruption of the ependymal lining with subependymal widening of the extracellular space and have to be differentiated from subcortical and deep white matter abnormalities. For the latter a distinction needs to be made between punctate, early confluent and confluent types. Although punctate white matter lesions often represent widened perivascular spaces without substantial ischemic tissue damage, early confluent and confluent lesions correspond to incomplete ischemic destruction. Punctate abnormalities on MRI show a low tendency for progression, while early confluent and confluent changes progress rapidly. The causative and modifying pathways involved in the occurrence of sporadic age-related white matter changes are still incompletely understood, but recent microarray and genome-wide association approaches increased the notion of pathways that might be considered as targets for therapeutic intervention. The majority of differentially regulated transcripts in white matter lesions encode genes associated with immune function, cell cycle, proteolysis, and ion transport. Genome-wide association studies identified six SNPs mapping to a locus on chromosome 17q25 to be related to white matter lesion load in the general population. We also report first and preliminary data that demonstrate apolipoprotein E (ApoE) immunoreactivity in white matter lesions and support epidemiological findings indicating that ApoE is another factor possibly related to white matter lesion occurrence. Further insights come from modern MRI techniques, such as diffusion tensor and magnetization transfer imaging, as they provide tools for the characterization of normal-appearing brain tissue beyond what can be expected from standard MRI scans. There is a need for additional pre- and postmortem studies in humans, including these new imaging techniques

New filovirus disease classification and nomenclature

Filoviruses, the members of the family Filoviridae, are currently classified into one proposed and five established genera (Supplementary Table 1). Of the twelve described filoviruses, six have been identified as aetiological agents of naturally occurring human disease outbreaks

New filovirus disease classification and nomenclature.

The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision

Differential Contributions of Lateral Prefrontal Cortex Regions to Visual Memory Processes

The prefrontal cortex (PFC) is the seat of higher level control operations, with recognition and working memory processes critical to those operations. While not strictly organized by the principle of localization, certain functions are clearly more associated with one region than another within PFC dynamic systems. We set out to test the hypothesis that active visual memory comparison (making judgments of novelty) was most associated with the ventrolateral prefrontal cortex (VLPFC), while the monitoring and manipulation of visual information was most associated with the mid-dorsolateral prefrontal cortex (mid-DLPFC). The current study used magnetic resonance volumetry to define the VLPFC and mid-DLPFC as regions of interest (ROIs), and analyzed those in relation to types of visual memory processes. We observed a functional dissociation of working memory within the PFC corresponding to comparison versus monitoring processes. One of the blocks of the monitoring and manipulation task showed a significant positive relationship with left, right, and total mid-DLPFC volume, with no significant relationship to the VLPFC. Performance on a memory comparison task bore a significant positive relationship with right and total VLPFC volume, and no relationship with the mid-DLPFC

Increased cochlear fluid-attenuated inversion recovery signal in patients with vestibular schwannoma.

BACKGROUND AND PURPOSE: Elevated protein levels have been reported in perilymph of patients with vestibular schwannoma. Fluid-attenuated inversion recovery (FLAIR) imaging is sensitive to high protein contents in fluids. The purpose of this study was to investigate if in patients with unilateral vestibular schwannoma, cochlear FLAIR signal intensity on the affected side is increased compared with the unaffected side and control subjects. MATERIALS AND METHODS: Fifteen patients with unilateral vestibular schwannoma and 25 age-matched control subjects (without a history of hearing loss) were retrospectively evaluated. All patients and controls had routine 5-mm FLAIR and T1- and T2-weighted imaging of the brain. The signal intensity of both cochleae was evaluated by placing a small region of interest on FLAIR images. The signal intensity of the brain stem was also determined by placing a second region of interest. A ratio of cochlear signal intensity to brain stem signal intensity (CIBI ratio) was determined. A t test was used to compare the CIBI ratios. RESULTS: In patients, the mean CIBI ratio of the affected side was 0.89 +/- 0.18, and that of the unaffected side was 0.57 +/- 0.12. In control subjects, it was 0.51 +/- 0.07. The CIBI ratio of the affected side was significantly higher compared with the unaffected side (P \u3c .001) and compared with control subjects (P \u3c .001). CONCLUSION: Patients with vestibular schwannoma have increased cochlear FLAIR signal intensity on the affected side compared with the unaffected side and healthy subjects

A multivariate approach to aggression and the orbital frontal cortex in psychiatric patients

The association between orbital frontal cortex (OFC) volume and aggression was investigated in an at-risk psychiatric population. Forty-one psychiatric patients were referred for magnetic resonance imaging and a standardized psychometric assessment of aggression (Lifetime History of Aggression-Revised). Nineteen matched controls had lower levels of aggression and greater OFC volume, establishing the appropriateness of the psychiatric group for studying aggression pathophysiology. Consistent with study hypotheses, left OFC gray matter volume predicted 34% of the variance in self-reported aggression ratings. When impulsivity was not controlled for, left OFC gray matter only accounted for 26% of aggression variance, suggesting a complex relationship between impulsivity and OFC-aggression pathophysiology. Contrary to study hypotheses, right OFC gray matter volume did not predict degree of aggressive behavior. Current models do not account for lateralization, yet this may be quite important. Greater consideration should be given to laterality in OFC regulation of social/emotional behavior. Regulatory focus theory, positing two motivational systems, promotion and prevention, lateralized to the left and right hemispheres, respectively, may provide an explanatory framework for these results. Dysregulation of the left hemisphere \u27promotion\u27 motivational system may help to explain the aggressive behavior present in psychiatric populations