Systemic markers of inflammation are independently associated with S100B concentration: results of an observational study in subjects with acute ischaemic stroke

<p>Abstract</p> <p>Background</p> <p>Vascular dysfunction and brain inflammation are thought to contribute to the pathophysiology of cerebral injury in acute stroke. However acute inflammation and vascular dysfunction may simply be markers of an acute phase response to cerebral injury, reflecting the size of the cerebral lesion. We aimed to determine if systemic markers of vascular dysfunction and inflammation are independently associated with concentrations of the astroglial protein S100B, a marker of brain injury, in participants with acute ischaemic stroke.</p> <p>Methods</p> <p>Fifty-seven men and women recruited within 96 hours of acute ischaemic stroke at two tertiary hospitals participated in this cross sectional observational study. Clinical, imaging (stroke lesions area measured with perfusion CT) and laboratory data were the independent variables and co-variates. The outcome variable was serum S100B concentration, analysed by multivariate regression.</p> <p>Results</p> <p>High sensitivity-CRP (<it>B </it>= 0.41) and lesion area (<it>B </it>= 0.69) were independently associated with S100B concentration (R²= 0.75, p < 0.01). Other variables with significant univariate associations with S100B concentration were not independently associated with S100B concentration in the final multivariate model.</p> <p>Conclusion</p> <p>The degree of systemic inflammation is associated with S100B concentration in acute ischaemic stroke, independent of the size of the ischaemic lesion.</p

Reduced relative volume in motor and attention regions in developmental coordination disorder: a voxel-based morphometry study.

Background and Objectives: Developmental coordination disorder (DCD) is a prevalent childhood movement disorder, impacting the ability to perform movement skills at an age appropriate level. Although differences in grey matter (GM) volumes have been found in related developmental disorders, no such evidence has been linked with DCD to date. This cross-sectional study assessed structural brain differences in children with and without DCD. Methods: High-resolution structural images were acquired from 44 children aged 7.8–12 years, including 22 children with DCD (≤16th percentile on MABC-2; no ADHD/ASD), and 22 typically developing controls (≥20th percentile on MABC-2). Structural voxel-based morphology analysis was performed to determine group differences in focal GM volumes. Results: Children with DCD were found to have significant, large, right lateralised reductions in grey matter volume in the medial and middle frontal, and superior frontal gyri compared to controls. The addition of motor proficiency as a covariate explained the between-group GM volume differences, suggesting that GM volumes in motor regions are reflective of the level of motor proficiency. A positive correlation between motor proficiency and relative GM volume was also identified in the left posterior cingulate and precuneus. Conclusions: GM volume reductions in premotor frontal regions may underlie the motor difficulties characteristic of DCD. It is possible that intervention approaches targeting motor planning, attention, and executive functioning processes associated with the regions of reduced GM volume may result in functional improvements in children with DCD

Efficacy of probucol on cognitive function in Alzheimer's disease: study protocol for a double-blind, placebo-controlled, randomised phase II trial (PIA study).

INTRODUCTION: Preclinical, clinical and epidemiological studies support the hypothesis that aberrant systemic metabolism of amyloid beta (Aβ) in the peripheral circulation is causally related to the development of Alzheimer's disease (AD). Specifically, recent studies suggest that increased plasma concentrations of lipoprotein-Aβ compromise the brain microvasculature, resulting in extravasation and retention of the lipoprotein-Aβ moiety. The latter results in an inflammatory response and neurodegeneration ensues. Probucol, a historic cholesterol-lowering drug, has been shown in murine models to suppress lipoprotein-Aβ secretion, concomitant with maintaining blood-brain-barrier function, suppressing neurovascular inflammation and supporting cognitive function. This protocol details the probucol in Alzheimer's study, a drug intervention trial investigating if probucol has potential to attenuate cognitive decline, delay brain atrophy and reduce cerebral amyloid burden in patients with mild-to-moderate AD. METHODS AND ANALYSIS: The study is a phase II, randomised, placebo-controlled, double-blind single-site clinical trial held in Perth, Australia. The target sample is 314 participants with mild-to-moderate AD. Participants will be recruited and randomised (1:1) to a 104-week intervention consisting of placebo induction for 2 weeks followed by 102 weeks of probucol (Lorelco) or placebo. The primary outcome is changed in cognitive performance determined via the Alzheimer's Disease Assessment Scales-Cognitive Subscale test between baseline and 104 weeks. Secondary outcomes measures will be the change in brain structure and function, cerebral amyloid load, quality of life, and the safety and tolerability of Lorelco, after a 104week intervention. ETHICS AND DISSEMINATION: The study has been approved by the Bellberry Limited Human Research Ethics Committee (approval number: HREC2019-11-1063; Version 4, 6 October 2021). Informed consent will be obtained from participants prior to any study procedures being performed. The investigator group will disseminate study findings through peer-reviewed publications, key conferences and local stakeholder events. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12621000726853)

Cortical functioning in children with developmental coordination disorder:a motor overflow study

This study examined brain activation in children with developmental coordination disorder (DCD) to reveal areas that may contribute to poor movement execution and/or abundant motor overflow. Using functional magnetic resonance imaging, 13 boys with DCD (mean age = 9.6 years ±0.8) and 13 typically developing controls (mean age = 9.3 years ±0.6) were scanned performing two tasks (finger sequencing and hand clenching) with their dominant hand, while a four-finger motion sensor recorded contralateral motor overflow on their non-dominant hand. Despite displaying increased motor overflow on both functional tasks during scanning, there were no obvious activation deficits in the DCD group to explain the abundant motor overflow seen. However, children with DCD were found to display decreased activation in the left superior frontal gyrus on the finger-sequencing task, an area which plays an integral role in executive and spatially oriented processing. Decreased activation was also seen in the left inferior frontal gyrus, an area typically active during the observation and imitation of hand movements. Finally, increased activation in the right postcentral gyrus was seen in children with DCD, which may reflect increased reliance on somatosensory information during the execution of complex fine motor tasks

Gliolan induced fluorescence in an isolated cerebral cryptococcoma

Background: Cerebral cryptococcomas can mimic high grade gliomas on magnetic resonance imaging (MRI). Under the impression of cerebral malignancy, Gliolan can be administered to facilitate fluorescence guided surgical resection of the lesion. Intraoperative fluorescence has however, been confounded by a variety of non-glioma pathologies, including one report of fluorescence in a cryptococcoma. Case description: A 39 year-old immunocompetent male with no significant medical history, presented with two weeks of headache and left homonymous hemianopia. He was constitutionally well with no symptoms of infection. Brain MRI identified an irregular peripherally enhancing necrotic mass located at the right parieto-occipital region, with facilitated diffusion on diffusion weighted imaging. He proceeded to a craniotomy and resection of the lesion. Gliolan-induced fluorescence was visualised intraoperatively within and beyond the lesion. Histopathological analysis demonstrated Cryptococcus gattii infection despite imaging and intraoperative fluorescence being suggestive of a high-grade glial series tumour. Conclusion: This is the second report of Gliolan-induced fluorescence of a cerebral cryptococcoma, but the first to describe fluorescence beyond the lesion itself. It is important to be aware of this appearance and thus, the risk of neurological compromise due to extensive surgical resection

Diffusion and perfusion magnetic resonance imaging in childhood stroke

Two magnetic resonance imaging techniques, diffusion and perfusion imaging, are being used increasingly for evaluation of pathophysiology of stroke. This article introduces these techniques and reports some initial studies using these approaches, together with conventional T2-weighted magnetic resonance imaging, for investigation of childhood stroke. It is shown that the combination of T2-weighted and diffusion images can provide information about the timing of stroke events in childhood, and perfusion imaging can detect abnormalities not visible by other magnetic resonance imaging techniques. These magnetic resonance methods therefore should play an important role in investigation of children with stroke and could be of particular value in studies of at-risk populations of children such as those with sickle cell disease.</p