Writing Committee of Korean clinical practice guidelines for secondary prevention of stroke has reviewed recent randomized controlled trials of cilostazol published after the first edition of Korean clinical practice guidelines that considered evidences published before June 2007. Two clinical trials and 1 meta-analysis which compared cilostazol directly with aspirin in the prevention of stroke in patients with cerebral infarction or transient ischemic attack (TIA) were identified and included for the current guideline update. Review of findings indicates that cilostazol as compared to aspirin achieved a greater reduction of stroke as well as composite vascular events of stroke, myocardial infarction, and vascular death. For safety, cilostazol was associated with fewer major bleeding events than aspirin. Accordingly, new recommendations for cilostazol are made for prevention of stroke in the setting of noncardioembolic stroke or TIA. Changes in the guidelines necessitated by new evidences will be continuously reflected in future guidelines.
Aspirin ; Cerebral Infarction ; Hemorrhage ; Humans ; Ischemic Attack, Transient ; Myocardial Infarction ; Secondary Prevention ; Stroke ; Tetrazoles ; Writing

BackgroundRemote ischemic postconditioning (RIPostC) appears to protect distant organs from ischemia-reperfusion injury (IRI). However, cerebral protection results have remained inconclusive. In the present study, a meta-analysis was performed to compare stroke patients with and without RIPostC.

MethodsCNKI, WanFang, VIP, CBM, PubMed, and Cochrane Library databases were searched up to July 2016. Data were analyzed using both fixed-effects and random-effects models by Review Manager. For each outcome, risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) were calculated.

ResultsA total of 13 randomized controlled trials that enrolled a total of 794 study participants who suffered from or are at risk for brain IRI were selected. Compared with controls, RIPostC significantly reduced the recurrence of stroke or transient ischemic attacks (RR = 0.37; 95% CI: 0.26-0.55; P < 0.00001). Moreover, it can reduce the levels of the National Institutes of Health Stroke Scale score (MD: 1.96; 95% CI: 2.18-1.75; P < 0.00001), modified Rankin Scale score (MD: 0.73; 95% CI: 1.20-0.25; P = 0.00300), and high-sensitivity C-reactive protein (MD: 4.17; 95% CI: 4.71-3.62; P < 0.00001) between the two groups. There was no side effect of RIPostC using tourniquet cuff around the limb on ischemic stroke treating based on different intervention duration.

ConclusionThe present meta-analysis suggests that RIPostC might offer cerebral protection for stroke patients suffering from or are at risk of brain IRI.

Brain Ischemia ; prevention & control ; Humans ; Ischemic Attack, Transient ; prevention & control ; therapy ; Ischemic Postconditioning ; methods ; Randomized Controlled Trials as Topic ; Stroke ; prevention & control

Forty-three patients with aneurysmal subarachnoid hemorrhage entered a nimodipine trial in the Department of Neurosurgery, Yonsei university to determine the efficacy of the drug in preventing vasospasm and to evaluate the tolerability of this calcium channel blocker. Thirty-three patients completed the study. Treatment was started within four days of initial bleeding and continued for two weeks. Delayed neurological deficits developed in seven of the 33 patients-four from vasospasm, two from elevated intracranial pressure, and one from recurrent bleeding. The incidence of symptomatic vasospasm which developed after calcium channel blocker (nimodipine) treatment was 12.1%, which is about one third of the rate experienced at our department during the past five years (33.2%). Twenty-five patients were operated on without surgical mortality and the morbidity rate was 8%. Side effects due to nimodipine treatment were reversible and insignificant. This study suggests that treatment with a calcium channel blocker that has a selective cerebrovascular effect may prevent or reduce the incidence of delayed ischemic deficits in patients with aneurysmal subarachnoid hemorrhage.
Clinical Trials ; Human ; Ischemic Attack, Transient/prevention & control* ; Nimodipine/therapeutic use* ; Prospective Studies ; Subarachnoid Hemorrhage/drug therapy*

Non-vitamin-K oral anticoagulants (NOACs) represent a major advance in the prevention of stroke in patients with atrial fibrillation (AF), offering a similar, if not superior, efficacy and safety profile and several practical advantages over oral vitamin K antagonists (VKAs). The rapid onset of action of the NOACs, their relatively short half-live, and the availability of specific reversal agents may be advantageous when managing acute ischemic strokes, and in the post-stroke, post-transient ischemic attack, and post-intracranial hemorrhage settings. In this review article, we offer practical guidance on the use of NOACs in these settings, focusing on managing the acute event and on initiating or resuming anticoagulation for secondary prevention. We also assess the use of NOACs to prevent stroke and bleeding in patients with AF who have chronic kidney disease, are elderly, or cognitively impaired, and we offer guidance on optimizing the use of NOACs and VKAs in these patient groups in the absence of evidence-based guidelines.
Aged ; Anticoagulants* ; Atrial Fibrillation ; Hemorrhage ; Humans ; Ischemic Attack, Transient ; Renal Insufficiency, Chronic ; Secondary Prevention ; Stroke* ; Vitamin K

OBJECTIVE: The early management of patients with acute symptoms due to carotid stenosis remains a subject of debate. Carotid endarterectomy (CEA) has been shown to reduce the risk of stroke in patients with symptomatic extracranial carotid artery stenosis. Carotid artery stenting (CAS) has recently emerged as an alternative to CEA for the primary and secondary prevention of stroke in patients who are at a high risk for complications from surgery. The aim of this study is to evaluate and analyze the clinical outcome of symptomatic high-risk patients with carotid stenosis that was treated with early CAS in a single stroke center. METHODS: From January 2008 to October 2009, we retrospectively analyzed 75 symptomatic high-risk carotid stenosis patients who had been admitted to the stroke center of our neurosurgical department and who were treated with early CAS. Twenty-five patients had transient ischemic attack (TIA) and 50 patients had minor or major stroke and all of them were at a high medical and surgical risk for carotid endarterectomy. They were treated with early CAS as soon as possible (treatment was done within 2 weeks from the onset of symptoms). RESULTS: At three months, 15 patients (20%) in the TIA and stroke group experienced an improvement in their initial neurologic deficit (a decreased modified Rankin scale greater than 2), while in 59 patients (78.4%) the deficit remained stable, and only one patient had a neurological impairment. CONCLUSION: Our data indicates that urgent assessment and early initiation of a combination of existing preventive treatments can reduce the risk of early recurrent stroke after TIA and minor or major stroke in the symptomatic high-risk patients with carotid stenosis.
Carotid Arteries ; Carotid Stenosis ; Endarterectomy, Carotid ; Humans ; Ischemic Attack, Transient ; Neurologic Manifestations ; Retrospective Studies ; Secondary Prevention ; Stents ; Stroke

BACKGROUND: Endothelial dysfunction, the initial pathogenic factor in atherosclerosis, can be alleviated via transient limb ischemia. We observed the effects of regular transient limb ischemia (RTLI) on atherosclerosis in hypercholesterolemic rabbits. METHODS: Twenty-eight rabbits were randomized to control, cholesterol, sham, ischemia groups (n = 7 each) between October 2010 and March 2011. They were fed a normal diet in the control group and hypercholesterolemic diet in other groups for 12 weeks. Six cycles of RTLI were performed once per day on the ischemia group. Serum samples were prepared to measure the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) before the experiment (W0), at the end of weeks 4, 8, 12 (W4, W8, W12). The whole aorta was harvested at W12 and stained using Sudan IV to identify the plaque. The plaque area was measured using Image J. Results were analyzed by analysis of variance or rank sum test. RESULTS: Concentrations of TC in the cholesterol group were higher than those in the control group at W4 (29.60 [23.75, 39.30] vs. 1.00 [0.80, 1.55], Z = -2.745, P = 0.006), W8 (41.78 [28.08, 47.37] vs. 0.35 [0.10, 0.68], Z = -2.739, P = 0.006), W12 (48.32 [40.04, 48.95] vs. 0.61 [0.50, 0.86], Z = -2.739, P = 0.006). Similar results were obtained for HDL-C and LDL-C. Serum concentrations of TC, HDL-C, and LDL-C in the hypercholesterolemic groups had no differences (all P > 0.05). The percentage of plaque area in the cholesterol group was higher than that in the control group (47.22 ± 23.89% vs. 0, Z = -2.986, P = 0.003). Square root of the percentage of plaque area was smaller in the ischemia group than that in the cholesterol (0.44 ± 0.13 vs. 0.67 ± 0.18, P = 0.014) or sham groups (0.44 ± 0.13 vs. 0.61 ± 0.12, P = 0.049). CONCLUSION In hypercholesterolemic rabbits, RTLI might prevent atherosclerosis progression by reducing the percentage of plaque area.
Animals ; Atherosclerosis ; blood ; prevention & control ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Extremities ; pathology ; Hypercholesterolemia ; blood ; Ischemic Attack, Transient ; blood ; Ischemic Postconditioning ; methods ; Male ; Rabbits ; Triglycerides ; blood

Cardioembolic stroke related to nonvalvular atrial fibrillation is associated with a high recurrence rate and high mortality and morbidity. In this population, therefore, optimal anticoagulant therapy is required to prevent the occurrence of second stroke. Oral anticoagulant, warfarin has been traditionally used, but it is greatly limited by its narrow efficacy window, complex pharmacokinetics, and multiple drug interactions, thus requiring frequent blood monitoring. Recently, oral anticoagulants targeted for a specific coagulation component have been newly developed and tested in large clinical trials. Dabigatran, direct thrombin inhibitor, and rivaroxaban, apixaban, and edoxaban, inhibitors of factor Xa harbor great merits of rapid action time, short half-life, stable plasma concentration, and little drug interaction. Recently, large randomized clinical trials and meta-analyses have been published to show the efficacy and safety of the new oral anticoagulants compared with warfarin. Based on the results from recent clinical trials, we revised recommendations to apply optimal anticoagulant therapy in patients with nonvalvular atrial fibrillation and ischemic stroke or transient ischemic attack.
Anticoagulants ; Atrial Fibrillation* ; Drug Interactions ; Factor Xa ; Half-Life ; Humans ; Ischemic Attack, Transient* ; Mortality ; Pharmacokinetics ; Plasma ; Recurrence ; Secondary Prevention ; Stroke* ; Thrombin ; Warfarin ; Dabigatran ; Rivaroxaban

Cardioembolic stroke related to atrial fibrillation is problematic due to high recurrence, mortality, and morbidity rates. The optimal anticoagulant therapy therefore needs to be applied to prevent the occurrence of a second stroke in patients with nonvalvular atrial fibrillation. The oral anticoagulant warfarin has traditionally been used, but it is limited by its narrow efficacy window, complex pharmacokinetics, and multiple drug interactions, thus requiring frequent blood monitoring. New oral anticoagulants have recently been developed that target a specific coagulation component. Dabigatran (a direct thrombin inhibitor) and rivaroxaban, apixaban, and edoxaban (inhibitors of factor Xa) have advantages of rapid action time, short half-life, stable plasma concentration, and few drug interactions. Large randomized clinical trials and meta-analyses have recently been published on the efficacy and safety of these new oral anticoagulants. Based on the results obtained in recent clinical trials, we have revised the recommendations for selecting optimal anticoagulant therapy in patients with nonvalvular atrial fibrillation.
Anticoagulants ; Atrial Fibrillation* ; Dabigatran ; Drug Interactions ; Half-Life ; Humans ; Ischemic Attack, Transient* ; Mortality ; Pharmacokinetics ; Plasma ; Recurrence ; Rivaroxaban ; Secondary Prevention ; Stroke* ; Thrombin ; Warfarin

BACKGROUNDWater dropwort (Oenanthe javanica) as a popular traditional medicine in Asia shows various biological properties including antioxidant activity. In this study, we firstly examined the neuroprotective effect of Oenanthe javanica extract (OJE) in the hippocampal cornus ammonis 1 region (CA1 region) of the gerbil subjected to transient cerebral ischemia.

METHODSGerbils were established by the occlusion of common carotid arteries for 5 min. The neuroprotective effect of OJE was estimated by cresyl violet staining. In addition, 4 antioxidants (copper, zinc superoxide dismutase [SOD], manganese SOD, catalase, and glutathione peroxidase) immunoreactivities were investigated by immunohistochemistry.

RESULTSPyramidal neurons in the CA1 region showed neuronal death at 5 days postischemia; at this point in time, all antioxidants immunoreactivities disappeared in CA1 pyramidal neurons and showed in many nonpyramidal cells. Treatment with 200 mg/kg, not 100 mg/kg, OJE protected CA1 pyramidal neurons from ischemic damage. In addition, 200 mg/kg OJE treatment increased or maintained antioxidants immunoreactivities. Especially, among the antioxidants, glutathione peroxidase immunoreactivity was effectively increased in the CA1 pyramidal neurons of the OJE-treated sham-operated and ischemia-operated groups.

CONCLUSIONOur present results indicate that treatment with OJE can protect neurons from transient ischemic damage and that the neuroprotective effect may be closely associated with increased or maintained intracellular antioxidant enzymes by OJE.

Animals ; Antioxidants ; metabolism ; therapeutic use ; Gerbillinae ; Glutathione Peroxidase ; metabolism ; Hippocampus ; drug effects ; metabolism ; Ischemic Attack, Transient ; prevention & control ; Male ; Oenanthe ; chemistry ; Plant Extracts ; therapeutic use

OBJECTIVETo investigate the effect of hyperbaric oxygen(HBO)therapy on mitochondrial free radicals after transient focal cerebral ischemia in rats.

METHODSThe male SD rats were randomly assigned into two groups, control and HBO groups. All animals were subjected to 90 min intra-luminal middle cerebral artery occlusion (MCAO) with the regional cerebral blood flow monitored in vivo by laser Doppler flowmetry. HBO treatment was performed in a pressure chamber with 100% O(2)(3 ATM 1 h) 3 h after ischemia. Twenty-four hours after ischemia, mitochondria in the ischemic core and penumbra were isolated and the contents of H(2)O(2), O(2)(*-), MDA, SOD, GSH-PX and GSH in mitochondria were measured respectively.

RESULTAfter cerebral ischemia-reperfusion, contents of mitochondrial H(2)O(2), O(2)(*-), MDA increased, while the SOD, GSH-PX and GSH in the mitochondria decreased significantly both in the ischemic core and the ischemic penumbra, compared with those in the normal controls(P<0.05). In the ischemic penumbra, HBO therapy increased significantly the content of O(2)(*-)(P<0.05), enhanced the activity of SOD, and decreased the level of MDA (P<0.05). However, HBO therapy did not change the level of MDA, though it also increased the content of O(2)(*-) and the activity of SOD in the ischemic core. HBO therapy had no significant effect on the contents of H(2)O(2), GSH-PX and GSH in the ischemic mitochondria.

CONCLUSIONHBO therapy initiated early after acute transient cerebral ischemia in rats can increase the mitochondrial free radicals level, but also increase the activity of the anti-radical enzymes. HBO treatment inhibits the lipid peroxidation damage of mitochondria in the ischemic penumbra, but not in the ischemic core, which indicates that the mitochondrial function plays a role in the reaction of the free radical in the ischemic area after HBO therapy.

Animals ; Free Radicals ; metabolism ; Glutathione Peroxidase ; metabolism ; Hyperbaric Oxygenation ; methods ; Infarction, Middle Cerebral Artery ; metabolism ; therapy ; Ischemic Attack, Transient ; metabolism ; therapy ; Male ; Mitochondria ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Superoxide Dismutase ; metabolism