The progressive course of neurological symptoms in anterior choroidal artery infarcts.

BACKGROUND: Infarctions of the anterior choroidal artery affect multiple anatomical structures, leading to a wide spectrum of neurological deficits with frequent symptom fluctuation or progression. AIMS: To assess etiological mechanisms, frequency, and predictors of symptom progression, as well as its impact on prognosis. METHODS: Anterior choroidal artery infarct patients were prospectively identified via predefined infarct locations with ischemic lesions ≥1·5 cm vertical diameter in cerebral imaging. Definition of neurological progression was ≥2 National Institutes of Health Stroke Scale points in motor function or ≥4 in total National Institutes of Health Stroke Scale. Stroke etiology was determined according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. We assessed demographical data, risk factors, and acute phase parameters in order to find predictors of neurological progression. RESULTS: Thirty patients fulfilled the inclusion criteria. Eighteen patients (60%) had neurological progression during days 1-3. Despite similar stroke severity at admission (median National Institutes of Health Stroke Scale in progressive infarcts 4·5 versus 4; P = 0·72), patients with progression had more severe deficits at day 3 (median National Institutes of Health Stroke Scale 9 vs. 3·5; P = 0·04) and worse three-month outcome. Only 31% of patients with progression scored <2 in the modified Rankin Scale compared with 89% without progression (P = 0·01) after three-months. No statistically significant differences regarding possible predictors of progression were found. Magnetic resonance imaging findings and etiological assessment suggest overlapping mechanisms of small and large vessel disease. CONCLUSIONS: Neurological deterioration is frequent in anterior choroidal artery infarcts and is associated with worse outcome. While mechanisms of small and large vessel disease seem to overlap in anterior choroidal artery infarction, we were not able to identify predictors of neurological progression.

Grey-matter atrophy in Alzheimer's disease is asymmetric but not lateralized.

In Alzheimer's disease (AD), brain atrophy has been proposed to be left lateralized. Here, we reinvestigated the asymmetry and lateralization (i.e., asymmetry directed toward one hemisphere) of grey-matter (GM) distribution in 35 patients with AD, 24 patients with amnestic mild cognitive impairment (aMCI, a state of increased risk for AD), and 30 age-matched healthy controls (HC). We analyzed GM distribution by applying voxel-based morphometry (VBM) including analyses for asymmetry and lateralization. When comparing MCI with AD patients, VBM revealed GM loss in the entorhinal, temporoparietal, dorsofrontal, and occipital cortices as well as in the precuneus; when comparing HCs with MCI patients, we found similar differences, which were less pronounced especially within the temporoparietal cortex and precuneus. Analyses of regional asymmetry and regional lateralization as well as global lateralization did not yield significant results. However, lobar asymmetry of the temporal, parietal, and occipital lobes increased from HC to AD. Moreover, in aMCI and AD patients, performance of language-based neuropsychological tests correlated with lateralization of GM loss to the left hemisphere. We conclude that, in principle, brain atrophy in AD is asymmetric rather than lateralized. At the individual level however, asymmetry contributes to cognitive deficits.

Mycophenolate acid inhibits endothelial NAD(P)H oxidase activity and superoxide formation by a Rac1-dependent mechanism.

Endothelial dysfunction precedes hypertension and atherosclerosis and predicts cardiac allograft vasculopathy and death in heart transplant recipients. Endothelial overproduction of reactive oxygen species, such as superoxide anions produced by NAD(P)H oxidase, induces endothelial dysfunction. Because immunosuppressive drugs have been associated with increased reactive oxygen species production and endothelial dysfunction, we sought to elucidate the underlying mechanisms. Reactive oxygen species, release of superoxide anions, and NAD(P)H oxidase activity were studied in human umbilical vein endothelial cells and in polymorphonuclear neutrophils. Gp91ds-tat was used to specifically block NAD(P)H oxidase. Transcriptional activation of different subunits of NAD(P)H oxidase was assessed by real-time RT-PCR. Rac1 subunit translocation and activation were studied by membrane fractionation and pull-down assays. Calcineurin inhibitors significantly increased endothelial superoxide anions production because of NAD(P)H oxidase, whereas mycophenolate acid (MPA) blocked it. MPA also attenuated the respiratory burst induced by neutrophil NAD(P)H oxidase. Because transcriptional activation of NAD(P)H oxidase was not affected, but addition of guanosine restored endothelial superoxide anions formation after MPA treatment, we speculate that the inhibitory effect of MPA was mediated by depletion of cellular guanosine triphosphate content. This prevented activation of Rac1 and, thus, of endothelial NAD(P)H oxidase. Because all heart transplant recipients are at risk for cardiac allograft vasculopathy development, these differential effects of immunosuppressants on endothelial oxidative stress should be considered in the choice of immunosuppressive drugs.