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Background and Purpose— Many ischemic strokes or transient ischemic attacks are labeled cryptogenic but may have undetected atrial fibrillation (AF). We sought to identify those most likely to have subclinical AF. Methods— We prospectively studied patients with cryptogenic stroke or transient ischemic attack aged ≥55 years in sinus rhythm, without known AF, enrolled in the intervention arm of the 30 Day Event Monitoring Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event (EMBRACE) trial. Participants underwent baseline 24-hour Holter ECG poststroke; if AF was not detected, they were randomly assigned to 30-day ECG monitoring with an AF auto-detect external loop recorder. Multivariable logistic regression assessed the association between baseline variables (Holter-detected atrial premature beats [APBs], runs of atrial tachycardia, age, and left atrial enlargement) and subsequent AF detection. Results— Among 237 participants, the median baseline Holter APB count/24 h was 629 (interquartile range, 142–1973) among those who subsequently had AF detected versus 45 (interquartile range, 14–250) in those without AF ( P <0.001). APB count was the only significant predictor of AF detection by 30-day ECG ( P <0.0001), and at 90 days ( P =0.0017) and 2 years ( P =0.0027). Compared with the 16% overall 90-day AF detection rate, the probability of AF increased from <9% among patients with <100 APBs/24 h to 9% to 24% in those with 100 to 499 APBs/24 h, 25% to 37% with 500 to 999 APBs/24 h, 37% to 40% with 1000 to 1499 APBs/24 h, and 40% beyond 1500 APBs/24 h. Conclusions— Among older cryptogenic stroke or transient ischemic attack patients, the number of APBs on a routine 24-hour Holter ECG was a strong dose-dependent independent predictor of prevalent subclinical AF. Those with frequent APBs have a high probability of AF and represent ideal candidates for prolonged ECG monitoring for AF detection. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00846924.

BACKGROUND AND PURPOSE:The pathophysiology of IIH remains unknown. TS stenoses have been observed in a high proportion of these patients. Stent placement to remove this potential obstruction to venous outflow has been proposed as a treatment option for patients with IIH refractory to medical treatment.

Membrane lipids and proteins required for axonal growth and regeneration are generally believed to be synthesized in the cell bodies of neurons and transported into the axons. However, we have demonstrated recently that, in cultured rat sympathetic neurons, axons themselves have the capacity to synthesize phosphatidylcholine, sphingomyelin, and phosphatidylethanolamine. In these experiments, we employed a compartment model of neuron culture in which pure axons grow in a fluid environment separate from that containing the cell bodies. In the present study, we again used compartmented cultures to confirm and extend the previous results. We have shown that three enzymes of phosphatidylcholine biosynthesis via the CDP-choline pathway are present in axons. We have also shown that the rate-limiting step in the biosynthesis of phosphatidylcholine by this route in neurons, and locally in axons, is catalyzed by the enzyme CTP:phosphocholine cytidylyltransferase. The biosynthesis of other membrane lipids, such as phosphatidylserine, phosphatidylethanolamine derived by decarboxylation of phosphatidylserine, phosphatidylinositol, and fatty acids, also occurs in axons. However, the methylation pathway for the conversion of phosphatidylethanolamine into phosphatidylcholine appears to be a quantitatively insignificant route for phosphatidylcholine synthesis in neurons. Moreover, our data provided no evidence for the biosynthesis of another important membrane lipid, cholesterol, in axons.

Sphingolipids are abundant constituents of neuronal membranes and have been implicated in intracellular signaling. We show that two analogs of glycosphingolipid biosynthetic intermediates, fumonisin B 1 (which inhibits dihydroceramide synthesis) and DL-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) (which inhibits glucosylceramide synthesis) decrease glycosphingolipid synthesis in rat sympathetic neurons. Although both fumonisin and PPMP inhibit glycosphingolipid synthesis, these inhibitors have differential effects on ceramide metabolism in axons. threo-PPMP, but not erythro-PPMP or fumonisin, induces an accumulation of [ 3 H]palmitate-labeled ceramide and impairs axonal growth. Moreover, exogenously added, cell-permeable C 6 -ceramide, but not C 6 -dihydroceramide, mimicks the effect of PPMP. Our studies suggest that the lipid second messenger ceramide acts in distal axons, but not cell bodies, as a negative regulator of neurite growth. Glycosphingolipids (GSLs)1 are major components of eukaryotic cell membranes and are particularly enriched in neuronal membranes. Lipids of this class contain one or more sugar residues attached to a sphingoid base backbone. GSLs are present in the outer leaflet of the plasma membrane (1, 2) where they have been postulated to play a role in a number of important cellular processes including cell-cell and cell-substratum recognition, adhesion, differentiation, proliferation, and oncogenic transformation. The pattern of GSLs differs among cell types and changes during development, cellular differentiation, and oncogenic transformation suggesting an important role for GSLs in cell growth and proliferation (3-5).In addition, intermediates in the biosynthesis and catabolism of sphingolipids and GSLs may function as lipid second messengers mediating the effects of extracellular agents and agonists (6 -8). One approach used extensively to examine the function of GSLs is the exogenous addition of GSLs to cells, since the amphipathic nature of GSLs permits their incorporation into cellular membranes. The enrichment of gangliosides (sialic acid containing GSLs) in neuronal membranes induces neuritogenesis (3, 9 -12), modulates growth factor receptor activity (reviewed in Refs. 3,13,14), potentiates responses to neurotrophic factors (13, 15), and protects against apoptotic death caused by withdrawal of trophic support (16). Moreover, antibodies raised against gangliosides inhibit neurite outgrowth from neural cells and tissues slices in vitro (17, 18). Tettamanti and Riboni (19) have summarized the role of gangliosides in neurodifferentiation, neuritogenesis, and synaptogenesis.Only recently has the effect of the reduction of cellular GSL levels on neurons, through the inhibition of endogenous GSL synthesis, been examined. Inhibition of dihydroceramide synthesis, an early step in the synthesis of all GSLs (see Fig. 1), in cultured hippocampal neurons disrupts axonal growth (20) and the formation and maintenance of axonal branches (21). Similar studies have found that sphingolipi...

Balloons may not be required to treat all patients with carotid stenosis. A stent alone was feasible in 79% of patients, and 79% of patients were alive and free from ipsilateral stroke or restenosis at 1 year. Restenosis rates with this approach are higher than with conventional angioplasty and stent insertion. Carotid arteries with very severe stenoses (> 90%) and circumferential calcification may be more successfully treated with angioplasty combined with stent placement.

Background and Purpose-Early anticoagulation after cardioembolic stroke remains controversial because of the potential for hemorrhagic transformation (HT). We tested the safety and feasibility of initiating rivaroxaban ≤14 days after cardioembolic stroke/transient ischemic attack. Methods-A prospective, open-label study of patients with atrial fibrillation treated with rivaroxaban ≤14 days of transient ischemic attack or ischemic stroke (National Institute of Health Stroke Scale <9). All patients underwent magnetic resonance imaging <24 hours of rivaroxaban initiation and day 7. The primary end point was symptomatic HT at day 7. Results-Sixty patients (mean±SD age 71±19 years, 82% stroke/18% transient ischemic attack) were enrolled. Median (interquartile range) time from onset to rivaroxaban was 3 (5) days. At treatment initiation, median National Institute of Health Stroke Scale was 2 (4), and median diffusion-weighted imaging volume was 7.9 (13.7) mL. At baseline, HT was present in 25 (42%) patients (hemorrhagic infarct [HI]1=19, HI2=6). On follow-up magnetic resonance imaging, no patients developed symptomatic HT. New asymptomatic HI1 developed in 3 patients, and asymptomatic progression from HI1 to HI2 occurred in 5 patients; otherwise, HT remained unchanged at day 7. Conclusions-These data support the safety of rivaroxaban initiation ≤14 days of mild-moderate cardioembolic stroke/ transient ischemic attack. Magnetic resonance imaging evidence of petechial HT, which is common, does not appear to increase the risk of symptomatic HT.

Background and Purpose-The hyperdense middle cerebral artery sign (HMCAS) is a well-established marker of early ischemia on noncontrast computed tomography of the brain (NCCT). Recently the MCA dot sign has been described and proposed to indicate thrombosis of the M2 or M3 middle cerebral artery branches. The purpose of this study was to define the hyperdense ICA sign (HICAS) and determine its prevalence, diagnostic and prognostic value, and its reliability as a marker for ischemia. Methods-Noncontrast computed tomography scans of 71 patients with acute ischemic stroke were analyzed for the presence of a HICAS, HMCAS, or MCA dot sign. For the validation of HICA and HMCA signs on NCCT, 32 of 71 patients who underwent gold standard CT angiography (CTA) before thrombolytic therapy were included in the analysis. The presence of a HICAS was correlated with initial neurological severity and the short and long-term outcomes. Results-A HICAS was found in 24% of patients on NCCT. In patients with a HICAS, mean age was 63Ϯ17.4 and mean time from symptom onset to CT was 103 minutes. Interobserver agreement was excellent for the HICAS. The HICAS has high specificity (100%) and positive predictive value (100%) in predicting the presence of distal internal carotid artery thrombus on CTA. Patients with a HICAS had a more severe initial neurological deficit and worse prognosis than patients without a HICAS. Conclusion-The HICAS is a reliable and a highly specific marker of thromboembolic occlusion of the distal ICA and is associated with severe initial neurological deficit and worse outcome despite thrombolytic therapy.