Early recurrent ischemic stroke complicating intravenous thrombolysis for stroke: incidence and association with atrial fibrillation

<p><b>Background and Purpose:</b> Mechanisms of early neurologic deterioration after treatment with intravenous, recombinant, tissue-type plasminogen activator (IV rt-PA) include symptomatic intracerebral hemorrhage (SICH) and early recurrent ischemic stroke. We observed a number of cases of acute deterioration due to recurrent ischemic events.</p> <p><b>Methods:</b> We undertook a single-center, retrospective analysis of consecutive acute stroke patients treated with IV rt-PA between January 2006 and December 2008 to define the incidence of early neurologic deterioration (>= 4-point drop on the National Institutes of Health Stroke Scale within 72 hours) and its mechanism. Deterioration was attributed to SICH when associated with a PH1 or PH2 hemorrhage on postdeterioration computed tomography scans, to recurrent ischemic stroke when there was clinical and radiologic evidence of a new territorial infarction or new vessel occlusion, and otherwise to evolution of the incident stroke.</p> <p><b>Results:</b> Of 228 consecutive IV rt-PA-treated patients, 34 (15%) developed early neurologic deterioration, 18 (8%) secondary to incident strokes 10 (4.4%) due to SICH, and 6 (2.6%) due to early recurrent ischemic events, which were significantly associated with atrial fibrillation (present in 5 of 6 patients; 4 paroxysmal, 1 permanent). In 4 patients, sudden clinical deterioration developed during or shortly after IV rt-PA infusion, and in 2, deterioration developed 3 days later. All died 2 days to 2 weeks later. The single case without atrial fibrillation had a recurrent, contralateral, middle cerebral artery stroke during IV rt-PA infusion and multiple high-signal emboli detected by transcranial Doppler. Early recurrent ischemic stroke accounted for 5 of 12 (42%) cases of early neurologic deterioration in patients with atrial fibrillation.</p> <p><b>Conclusion:</b> In this single-center series, the incidence of early recurrent ischemic stroke after IV rt-PA was 2.6% and was associated with previous atrial fibrillation.</p&gt

Effects of magnesium treatment in a model of internal capsule lesion in spontaneously hypertensive rats

<p><b>Background and Purpose:</b> The study aim was to assess the effects of magnesium sulfate (MgSO4) administration on white matter damage in vivo in spontaneously hypertensive rats.</p> <p><b>Methods:</b> The left internal capsule was lesioned by a local injection of endothelin-1 (ET-1; 200 pmol) in adult spontaneously hypertensive rats. MgSO4 was administered (300 mg/kg SC) 30 minutes before injection of ET-1, plus 200 mg/kg every hour thereafter for 4 hours. Infarct size was measured by T2-weighted magnetic resonance imaging (day 2) and histology (day 11), and functional recovery was assessed on days 3 and 10 by the cylinder and walking-ladder tests.</p> <p><b>Results:</b> ET-1 application induced a small, localized lesion within the internal capsule. Despite reducing blood pressure, MgSO4 did not significantly influence infarct volume (by magnetic resonance imaging: median, 2.1 mm3; interquartile range, 1.3 to 3.8, vs 1.6 mm3 and 1.2 to 2.1, for the vehicle-treated group; by histology: 0.3 mm3 and 0.2 to 0.9 vs 0.3 mm3 and 0.2 to 0.5, respectively). Significant forelimb and hindlimb motor deficits were evident in the vehicle-treated group as late as day 10. These impairments were significantly ameliorated by MgSO4 in both cylinder (left forelimb use, P<0.01 and both-forelimb use, P<0.03 vs vehicle) and walking-ladder (right hindlimb score, P<0.02 vs vehicle) tests.</p> <p><b>Conclusions:</b> ET-1–induced internal capsule ischemia in spontaneously hypertensive rats represents a good model of lacunar infarct with small lesion size, minimal adverse effects, and a measurable motor deficit. Despite inducing mild hypotension, MgSO4 did not significantly influence infarct size but reduced motor deficits, supporting its potential utility for the treatment of lacunar infarct.</p&gt

Allopurinol use yields potentially beneficial effects on inflammatory indices in those with recent ischemic stroke: a randomized, double-blind, placebo-controlled trial

<p><b>Background and Purpose</b>: Elevated serum uric acid level is associated with poor outcome and increased risk of recurrent events after stroke. The xanthine oxidase inhibitor allopurinol lowers uric acid but also attenuates expression of inflammatory adhesion molecules in murine models, reduces oxidative stress in the vasculature, and improves endothelial function. We sought to investigate whether allopurinol alters expression of inflammatory markers after acute ischemic stroke.</p> <p><b>Methods</b>: We performed a randomized, double-blind, placebo-controlled trial to investigate the safety, tolerability, and effect of 6 weeks’ treatment with high- (300 mg once a day) or low- (100 mg once a day) dose allopurinol on levels of uric acid and circulating inflammatory markers after ischemic stroke.</p> <p><b>Results</b>: We enrolled 50 patients with acute ischemic stroke (17, 17, and 16 in the high, low, and placebo groups, respectively). Mean (±SD) age was 70 (±13) years. Groups had similar characteristics at baseline. There were no serious adverse events. Uric acid levels were significantly reduced at both 7 days and 6 weeks in the high-dose group (by 0.14 mmol/L at 6 weeks, P=0.002). Intercellular adhesion molecule-1 concentration (ng/mL) rose by 51.2 in the placebo group, rose slightly (by 10.6) in the low-dose allopurinol group, but fell in the high-dose group (by 2.6; difference between groups P=0.012, Kruskal-Wallis test).</p> <p><b>Conclusion</b>: Allopurinol treatment is well tolerated and attenuates the rise in intercellular adhesion molecule-1 levels seen after stroke. Uric acid levels were lowered with high doses. These findings support further evaluation of allopurinol as a preventive measure after stroke.</p&gt

Non-implementation of Rational Expectations as a Perfect Bayesian Equilibrium

We show that a rational expectations equilibrium need not be incentive compatible, need not be implementable as a perfect Bayesian equilibrium and may not be fully Pareto optimal, unless the utility functions are state independent. A comparison of rational expectations equilibria with core concepts is also provided.Differential information economy, Rational expectations equilibrium, Implementation, Game trees, Private core

Results of the MRI substudy of the intravenous magnesium efficacy in stroke trial

<p><b>Background and Purpose:</b>Although magnesium is neuroprotective in animal stroke models, no clinical benefit was confirmed in the Intravenous Magnesium Efficacy in Stroke (IMAGES) trial of acute stroke patients. The Magnetic Resonance in IMAGES (MR IMAGES) substudy investigated the effects of magnesium on the imaging surrogate outcome of infarct growth.</p> <p><b>Methods:</b> IMAGES trial patients in participating centers were randomized to receive either intravenous magnesium or placebo within 12 hours of stroke onset. Infarct growth was defined as volume difference between baseline diffusion-weighted imaging and day 90 fluid-attenuated inversion recovery image lesions. Patients who died were imputed the largest infarct growth observed.</p> <p><b>Results:</b> Among the 90 patients included in the primary analysis, there was no difference in infarct growth (median absolute growth, P=0.639; median percentage growth, P=0.616; proportion with any growth, P=0.212) between the 46 treated with magnesium and 44 with placebo. Infarct growth correlated with NIHSS score change from baseline to day 90. There was a trend showing baseline serum glucose correlated with infarct growth with magnesium treatment, but not in the placebo group. The mismatch frequency was reduced from 73% to 47% by increasing the mismatch threshold from >20% to >100% of core volume.</p> <p><b>Conclusions:</b> Infarct growth, confirmed here as a surrogate for clinical progression, was similar between magnesium and placebo treatment, paralleling the main IMAGES trial clinical outcomes. Glucose was a covariate for infarct growth with magnesium treatment. A more stringent mismatch threshold to define penumbra more appropriately would have excluded half of the patients in this 12-hour time window stroke study.</p&gt

Resting state connectivity and cognitive performance in adults with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Cognitive impairment is an inevitable feature of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), affecting executive function, attention and processing speed from an early stage. Impairment is associated with structural markers such as lacunes, but associations with functional connectivity have not yet been reported. Twenty-two adults with genetically-confirmed CADASIL (11 male; aged 49.8 ± 11.2 years) underwent functional magnetic resonance imaging at rest. Intrinsic attentional/executive networks were identified using group independent components analysis. A linear regression model tested voxel-wise associations between cognitive measures and component spatial maps, and Pearson correlations were performed with mean intra-component connectivity z-scores. Two frontoparietal components were associated with cognitive performance. Voxel-wise analyses showed an association between one component cluster and processing speed (left middle temporal gyrus; peak −48, −18, −14; ZE = 5.65, pFWEcorr = 0.001). Mean connectivity in both components correlated with processing speed (r = 0.45, p = 0.043; r = 0.56, p = 0.008). Mean connectivity in one component correlated with faster Trailmaking B minus A time (r = −0.77, p < 0.001) and better executive performance (r = 0.56, p = 0.011). This preliminary study provides evidence for associations between cognitive performance and attentional network connectivity in CADASIL. Functional connectivity may be a useful biomarker of cognitive performance in this population

¹⁴C AMS at SUERC: improving QA data from the 5 MV tandem AMS and 250 kV SSAMS

In 2003, a National Electrostatics Corporation (NEC) 5MV tandem accelerator mass spectrometer was installed at SUERC, providing the radiocarbon laboratory with 14C measurements to 4–5‰ repeatability. In 2007, a 250kV single-stage accelerator mass spectrometer (SSAMS) was added to provide additional 14C capability and is now the preferred system for 14C analysis. Changes to the technology and to our operations are evident in our copious quality assurance data: typically, we now use the 134-position MC-SNICS source, which is filled to capacity. Measurement of standards shows that spectrometer running without the complication of on-line δ13C evaluation is a good operational compromise. Currently, 3‰ 14C/13C measurements are routinely achieved for samples up to nearly 3 half-lives old by consistent sample preparation and an automated data acquisition algorithm with sample random access for measurement repeats. Background and known-age standard data are presented for the period 2003–2008 for the 5MV system and 2007–2008 for the SSAMS, to demonstrate the improvements in data quality