Vasospasm is one of the leading causes of morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). Radiographic vasospasm usually develops between 5 and 15 days after the initial hemorrhage, and is associated with clinically apparent delayed ischemic neurological deficits (DID) in one-third of patients. The pathophysiology of this reversible vasculopathy is not fully understood but appears to involve structural changes and biochemical alterations at the levels of the vascular endothelium and smooth muscle cells. Blood in the subarachnoid space is believed to trigger these changes. In addition, cerebral perfusion may be concurrently impaired by hypovolemia and impaired cerebral autoregulatory function. The combined effects of these processes can lead to reduction in cerebral blood flow so severe as to cause ischemia leading to infarction. Diagnosis is made by some combination of clinical, cerebral angiographic, and transcranial doppler ultrasonographic factors. Nimodipine, a calcium channel antagonist, is so far the only available therapy with proven benefit for reducing the impact of DID. Aggressive therapy combining hemodynamic augmentation, transluminal balloon angioplasty, and intra-arterial infusion of vasodilator drugs is, to varying degrees, usually implemented. A panoply of drugs, with different mechanisms of action, has been studied in SAH related vasospasm. Currently, the most promising are magnesium sulfate, 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, nitric oxide donors and endothelin-1 antagonists. This paper reviews established and emerging therapies for vasospasm. IntroductionVasospasm is a common complication that follows aneurysmal subarachnoid hemorrhage (SAH). Ecker was first to point out the occurrence of arterial spasm following SAH [1]. Before him, Robertson had attributed ischemic brain lesions found on autopsy of patients with SAH to probable 'spasm of arteries ' [2]. Despite growing literature, skepticism regarding the association between angiographic vasospasm and clinical findings persisted [3], until CM Fisher and colleagues published a synopsis on the matter in 1977 [4]. This seminal publication comprehensively described the deficits accompanying vasospasm and, most importantly, made the association between vasospasm and neurological deficits, also known as delayed ischemic deficits (DID).The term vasospasm implies a reduction in the caliber of a vessel; however, in SAH it has multiple meanings. SAHinduced vasospasm is a complex entity due in part to a delayed and reversible vasculopathy, impaired autoregulatory function, and hypovolemia causing a regional reduction of cerebral perfusion to the point of causing ischemia [5,6].Radiographic evidence of vasospasm develops in 50% to 70% of patients with SAH, but only half of those experience symptoms of DID [7][8][9][10][11][12]. Proximal vessels, situated at the base of the brain, are preferentially affected; however, more distal arteries could also develop impaired vascular reactivity (autoregulation...

Objective: Elevated systolic blood pressure (SBP) after successful revascularization (SR) via endovascular therapy (EVT) is a known predictor of poor outcome. However, the optimal SBP goal following EVT is still unknown. Our objective was to compare functional and safety outcomes between different SBP goals after EVT with SR. Methods: This international multicenter study included 8 comprehensive stroke centers and patients with anterior circulation large vessel occlusion who were treated with EVT and achieved SR. SR was defined as modified thrombolysis in cerebral ischemia 2b to 3. Patients were divided into 3 groups based on SBP goal in the first 24 hours after EVT. Inverse probability of treatment weighting (IPTW) propensity analysis was used to assess the effect of different SBP goals on clinical outcomes. Results: A total of 1,019 patients were included. On IPTW analysis, the SBP goal of <140mmHg was associated with a higher likelihood of good functional outcome and lower odds of hemicraniectomy compared to SBP goal of <180mmHg. Similarly, SBP goal of <160mmHg was associated with lower odds of mortality compared to SBP goal of <180mmHg. In subgroup analysis including only patients with pre-EVT SBP of ≥140mmHg, an SBP of <140mmHg was associated with a higher likelihood of good functional outcome, lower odds of symptomatic intracranial hemorrhage, and lower odds of requirement for hemicraniectomy compared to SBP goal of <180mmHg.View this article online at wileyonlinelibrary.com.

Conventional photothermal (PT) and photoacousic (PA) imaging, spectroscopy, and cytometry are preferentially based on positive PT/PA effects, when signals are above background. Here, we introduce PT/PA technique based on detection of negative signals below background. Among various new applications, we propose label-free in vivo flow cytometry of circulating clots. No method has been developed for the early detection of clots of different compositions as a source of severe thromboembolisms including ischemia at strokes and myocardial dysfunction at heart attack. When a low-absorbing, platelet-rich clot passes a laser-irradiated vessel volume, a transient decrease in local absorption results in an ultrasharp negative PA hole in blood background. Using this phenomenon alone or in combination with positive contrasts, we demonstrated identification of white, red and mixed clots on a mouse model of myocardial infarction and human blood. The concentration and size of clots were measured with threshold down to few clots in the entire circulation with size as low as 20 µm. This multiparameter diagnostic platform using portable personal high-speed flow cytometer with negative dynamic contrast mode has potential to real-time defining risk factors for cardiovascular diseases, and for prognosis and prevention of stroke or use clot count as a marker of therapy efficacy. Possibility for label-free detection of platelets, leukocytes, tumor cells or targeting them by negative PA probes (e.g., nonabsorbing beads or bubbles) is also highlighted.

Background and purposeA subset of ischaemic stroke patients with atrial fibrillation (AF) have ischaemic stroke despite anticoagulation. We sought to determine the association between prestroke anticoagulant therapy and recurrent ischaemic events and symptomatic intracranial haemorrhage (sICH).MethodsWe included consecutive patients with acute ischaemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study from eight comprehensive stroke centres in the USA. We compared recurrent ischaemic events and delayed sICH risk using adjusted Cox regression analyses between patients who were prescribed anticoagulation (ACp) versus patients who were naïve to anticoagulation therapy prior to the ischaemic stroke (anticoagulation naïve).ResultsAmong 2084 patients in IAC, 1518 had prior anticoagulation status recorded and were followed for 90 days. In adjusted Cox hazard models, ACp was associated with some evidence of a higher risk higher risk of 90-day recurrent ischaemic events only in the fully adjusted model (adjusted HR 1.50, 95% CI 0.99 to 2.28, p=0.058) but not increased risk of 90-day sICH (adjusted HR 1.08, 95% CI 0.46 to 2.51, p=0.862). In addition, switching anticoagulation class was not associated with reduced risk of recurrent ischaemic events (adjusted HR 0.41, 95% CI 0.12 to 1.33, p=0.136) nor sICH (adjusted HR 1.47, 95% CI 0.29 to 7.50, p=0.641).ConclusionAF patients with ischaemic stroke despite anticoagulation may have higher recurrent ischaemic event risk compared with anticoagulation-naïve patients. This suggests differing underlying pathomechanisms requiring different stroke prevention measures and identifying these mechanisms may improve secondary prevention strategies.

The decline in stroke incidence and mortality in the U.S. over the past 20 years is reaching a plateau, and the number of strokes may actually start to increase as the population ages. However, recent clinical trials have demonstrated that there are numerous opportunities to improve stroke prevention strategies and also opportunities to effectively intervene in and treat acute strokes. For patients with diabetes and for those with prior strokes or transient ischemic attacks, it has become evident that aggressive low-density lipoprotein lowering with statin medications will decrease the risk for total and fatal strokes. Optimal anticoagulation and antiplatelet therapy for primary and secondary stroke prevention in atrial fibrillation is being carefully defined. With numerous novel factor Xa and direct thrombin inhibitor drugs completing phase III clinical trials, it is likely that additional oral anticoagulant drugs will be clinically available for stroke prevention soon. Additionally, a major clinical trial is nearing completion that may resolve the role of carotid stenting and carotid endarterectomy in primary and secondary stroke prevention. There are recent notable advances in the acute treatment of stroke. It is likely that the time window for thrombolysis for appropriate patients with strokes will be increased from 3 to 4.5 h, permitting the inclusion of more patients in this treatment approach. There is ongoing investigation of intra-arterial thrombolysis and of acute intra-arterial thrombus extraction for treatment of selected patients with strokes. Unlike the progress in treatment of ischemic strokes, treatment of hemorrhagic stroke is progressing more slowly.