Cubic root total infarct volume by AF status (no, new and known AF).

<p>Cubic root total infarct volume by AF status (no, new and known AF).</p

Association of stroke size and voxelwise ischemic involvement across 582 patients.

<p>Larger strokes were associated with more frequent ischemic lesions in the MCA territory of both hemispheres and parts of the posterior circulation while smaller strokes were not associated with more frequent ischemic insults of any brain area. (Red-to-yellow: areas significantly associated with higher crIV, blue-to-lightblue: areas significantly associated with lower crIV across all n = 582 patients; thresholded at FDR-corrected q = 0.01; age and gender included as covariates of no interest, AF status unmodeled).</p

Composition of the analyzed cohort of patients.

<p>(AF: atrial fibrillation, MRI: magnetic resonance imaging, N: number).</p

Clinical characteristics of included patients.

<p>(AF: atrial fibrillation; NIHSSS: National Institute of Health Stroke Scale Score; IQR: Interquartile range; n: number; SD: standard deviation).</p

Voxelwise stroke lesion counts for the whole cohort and the diagnostic subgroups of different AF status.

<p>(A): Voxelwise stroke lesion counts and the margins of 1% and 4% total empirical stroke probability for the entire cohort of 582 acute ischemic stroke patients. Note the accumulation of ischemic lesions in the right insula, as illustrated by the 4% stroke probability margin. (Red-to-yellow: stroke lesion counts scaled between 1 to 20 lesions per voxel; green: margin of 1% total empirical stroke probability; blue: margin of 4% total empirical stroke probability). (B): Voxelwise empirical stroke probabilities for patients with new (top), known (middle) and without (bottom) AF. Smaller infarct volumes in patients without AF (cf. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0177474#pone.0177474.g003" target="_blank">Fig 3</a>) lead to less overlap of the ischemic lesions across subjects and thus much fewer voxels above the 4% empirical stroke probability threshold (set to display for illustration) while for the larger strokes of new and known AF ischemic lesions accumulate in both middle cerebral artery territories and centrally around the insula, in particular. (C): Voxelwise empirical stroke probabilities (thresholded at 10%) reveal that AF (new and known combined) leads to an accumulation of stroke lesions in the right MCA territory and insula, in particular. (AF: atrial fibrillation; MCA: middle cerebral artery).</p

Differences of infarct locations: New AF versus no AF.

<p>(A): New AF was, compared to patients without AF, associated with ischemic lesions in a) the right (peri-) insular cortex and the caput of the right caudate nucleus and b) in the left PCA territory. Patients without AF had significantly more often strokes in the left parietal lobe than patients with new AF. (Red-to-yellow: areas significantly more often associated with strokes in patients with new AF vs. without AF, blue-to-lightblue: vice versa and green: overlap projections; thresholded at FDR-corrected q = 0.01; age and gender were included as covariates of no interest, with infarct volume unaccounted for in this analysis). (B): Including infarct volume into the analysis revealed that no specific brain region was associated with significantly more stroke lesions in patients with new AF compared to patients without AF. Vice versa, patients without AF still had more often left parietal involvement compared to patients with new AF. (Red-to-yellow: areas significantly more often associated with strokes in patients with new AF vs. without AF [none], blue-to-lightblue: vice versa; FDR-corrected q = 0.01; with removal of the confounding effect of cubic root infarct volume normalized for brain size, age and gender).</p

Cubic root total infarct volume by AF status (no, new and known AF).

<p>Cubic root total infarct volume by AF status (no, new and known AF).</p

Stress Mediators and Immune Dysfunction in Patients with Acute Cerebrovascular Diseases

<div><p>Background</p><p>Post-stroke immune depression contributes to the development of infections which are major complications after stroke. Previous experimental and clinical studies suggested that humoral stress mediators induce immune dysfunction. However, prospective clinical studies testing this concept are missing and no data exists for other cerebrovascular diseases including intracerebral hemorrhage (ICH) and TIA.</p><p>Methods</p><p>We performed a prospective clinical study investigating 166 patients with TIA, ischemic and hemorrhagic stroke. We measured a broad panel of stress mediators, leukocyte subpopulations, cytokines and infection markers from hospital admission to day 7 and on follow-up after 2–3 months. Multivariate regression analyses detected independent predictors of immune dysfunction and bacterial infections. ROC curves were used to test the diagnostic value of these parameters.</p><p>Results</p><p>Only severe ischemic strokes and ICH increased some catecholamine metabolites, ACTH and cortisol levels. Immunodysfunction was eminent already on hospital admission after large brain lesions with lymphocytopenia as a key feature. None of the stress mediators was an independent predictor of lymphocytopenia or infections. However, lymphocytopenia on hospital admission was detected as an independent explanatory variable of later infections. NIHSSS and lymphocytopenia on admission were excellent predictors of infection.</p><p>Conclusions</p><p>Our results question the present pathophysiological concept of stress-hormone mediated immunodysfunction after stroke. Early lymphocytopenia was identified as an early independent predictor of post-stroke infections. Absence of lymphocytopenia may serve as a negative predictive marker for stratification for early antibiotic treatment.</p></div

FTY720 changes serum cytokine levels.

<p>Serum cytokine concentrations of the pro-inflammatory cytokines IL-6, IFN-γ and TNF-α (<b>A–C</b>) and anti-inflammatory cytokines TGF-β and IL-10 (<b>D,E</b>) were measured in naïve mice and at 24 h and 5d after FTY720 or control treatment. Each assay was performed in duplicate (n = 5, serum sampling as 2–3 individual experiments, assays as one experiment). * P<0.05 between treatment groups at the respective time point.</p

FTY720 decreases cerebral lymphocyte invasion.

<p>(<b>A</b>) Brain sections were stained 5d after MCAO for T cells (CD3), B cells (B220), granulocytes (MPO) and activated microglia/macrophages (IBA1). (<b>B</b>) Analysis of absolute cell counts of T cells, B cells, granulocytes and microglia/macrophages per total hemisphere in PBS and FTY720 treated animals at 5d after MCAO (n = 6–10 per group, 2–3 individual experiments).</p