Application of acute stroke imaging: selecting patients for revascularization therapy

Due to the dynamic and versatile characteristics of ischemic penumbra, selecting the right acute ischemic stroke (AIS) patients for revascularization therapy (RT) based on initial available imaging can be challenging. The main patient selection criterion for RT is the size of the mismatch between the potentially salvageable tissue (penumbra) and the irreversibly damaged tissue (core). The goal of revascularization RT is to "freeze" the core and prevent it from extending to the penumbral tissue. Penumbral imaging selection of AIS patients for RT, using magnetic resonance or CT-based studies, may provide more clinical benefit to the appropriate patients, although direct evidence is pending. Not all penumbra-core mismatches beyond 3 hours are equal and need treatment, and defining which mismatches to target for RT is the current goal of ongoing clinical trials. In addition to "penumbral"-based imaging, large vessel occlusion and clot length estimation based on CT angiography and noncontrasted ultrathin CT scan has been used to identify patients who are refractory to systemic thrombolysis and may be eligible for endovascular therapy. The application of various imaging modalities in selecting and triaging AIS patients for RT is discussed in this review. Larger prospective randomized trials are needed to better understand the role of various imaging modalities in selecting AIS patients for RT and to understand its influence on clinical outcome

Acute Stroke Evaluation and Management

Stroke is the fourth leading cause of death and the leading cause of ­disability in the United States. Several new therapeutic strategies such as institution of recanalization therapies in the first few hours after ischemic stroke are now available to reduce death and stroke-related disability. Understanding the stroke epidemiology and pathophysiology, and knowledge of evidence-based guidelines are the cornerstones of high-quality emergent acute stroke management. Stroke is typically characterized by sudden onset of focal neurological deficits. Advanced neuroimaging (CT and MRI) can help ­confirm the clinical diagnosis and guide treatment. Ischemic stroke is by far the most common form of stroke resulting from sudden arterial occlusion in a vascular territory. Common etiologies include cardiogenic embolism, extracranial and intracranial large artery atherosclerosis, lacunar stroke, and cryptogenic stroke. In acute ischemic stroke, intravenous tPA should be given with 4.5 h after symptom onset in patients without contraindications. Endovascular therapy shows benefit in selected patients within certain time window. Most strokes after transient ischemic attack occur within 90 days, and majority within 48 h. Urgent evaluation and treatment of patient with TIA especially in high-risk patients are important. Intracerebral hemorrhage and subarachnoid hemorrhage are devastating diseases. Hypertension and smoking are common risk factors. The clinical symptoms are characterized by focal neurological deficits associated with headache and other signs of high intracranial pressure. Blood pressure management is critical in managing intracerebral hemorrhage. Recently clinical trials suggested that aggressive blood pressure reduction does not worse the outcome. In subarachnoid hemorrhage, emergent aneurysm occlusion with coiling or clipping to prevent rebleed is crucial in acute phase. Delayed cerebral vasospasm should be monitored closely. Cerebral venous thrombosis (CVT) is uncommon. Headache and seizures are the common symptoms. Anticoagulation is the primary therapy for CVT

1-Methyl-4-phenylpyridinium (MPP+)-induced apoptosis and mitochondrial oxidant generation: role of transferrin-receptor-dependent iron and hydrogen peroxide.

1-Methyl-4-phenylpyridinium (MPP(+)) is a neurotoxin used in cellular models of Parkinson's Disease. Although intracellular iron plays a crucial role in MPP(+)-induced apoptosis, the molecular signalling mechanisms linking iron, reactive oxygen species (ROS) and apoptosis are still unknown. We investigated these aspects using cerebellar granule neurons (CGNs) and human SH-SY5Y neuroblastoma cells. MPP(+) enhanced caspase 3 activity after 24 h with significant increases as early as 12 h after treatment of cells. Pre-treatment of CGNs and neuroblastoma cells with the metalloporphyrin antioxidant enzyme mimic, Fe(III)tetrakis(4-benzoic acid)porphyrin (FeTBAP), completely prevented the MPP(+)-induced caspase 3 activity as did overexpression of glutathione peroxidase (GPx1) and pre-treatment with a lipophilic, cell-permeable iron chelator [N, N '-bis-(2-hydroxybenzyl)ethylenediamine-N, N '-diacetic acid, HBED]. MPP(+) treatment increased the number of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labelling)-positive cells which was completely blocked by pre-treatment with FeTBAP. MPP(+) treatment significantly decreased the aconitase and mitochondrial complex I activities; pre-treatment with FeTBAP, HBED and GPx1 overexpression reversed this effect. MPP(+) treatment increased the intracellular oxidative stress by 2-3-fold, as determined by oxidation of dichlorodihydrofluorescein and dihydroethidium (hydroethidine). These effects were reversed by pre-treatment of cells with FeTBAP and HBED and by GPx1 overexpression. MPP(+)-treatment enhanced the cell-surface transferrin receptor (TfR) expression, suggesting a role for TfR-induced iron uptake in MPP(+) toxicity. Treatment of cells with anti-TfR antibody (IgA class) inhibited MPP(+)-induced caspase activation. Inhibition of nitric oxide synthase activity did not affect caspase 3 activity, apoptotic cell death or ROS generation by MPP(+). Overall, these results suggest that MPP(+)-induced cell death in CGNs and neuroblastoma cells proceeds via apoptosis and involves mitochondrial release of ROS and TfR-dependent iron

FLAIR distal hyperintense vessels as a marker of perfusion-diffusion mismatch in acute stroke

Distal hyperintense vessels (DHV) on MRI FLAIR sequences in acute brain ischemia are thought to represent leptomeningeal collateral flow. We hypothesized that DHV are more common in acute stroke patients with perfusion-diffusion weighted mismatch (PDM) than in those without. We performed a retrospective study of consecutive anterior circulation stroke patients who underwent multimodal MRI within 8 hours of onset. We correlated DHV occurrence with the presence or absence of PDM, and analyzed DHV correlates when angiography was available. Twenty-one patients with PDM and 28 without were included. On univariate analysis, there was no significant difference regarding demographic variables between the two groups, with the exception of a higher frequency of atrial fibrillation (33% vs. 7%; P = .02) and intravenous tissue plasminogen activator use (57% vs 25%; P = .03) in the PDM patients. The PDM group more commonly had DHV (85% vs 25%; P < .001). On multivariate analysis, DHV presence (odds ratio, 6.01; 95% confidence-interval, 1.08-33.29; P = .04) and vessel occlusion site (odds ratio, 3.17; 95% confidence-interval, 1.21-8.31; P = .01) were the only variables independently associated with PDM. Conventional angiography was useful correlating DHV presence and collateral flow in a subset of patients. DHV may be a surrogate marker for PDM in patients with hyperacute ischemic stroke