Background-Thromboembolic disease secondary to complicated carotid atherosclerotic plaque is a major cause of cerebral ischemia. Clinical management relies on the detection of significant (Ͼ70%) carotid stenosis. A large proportion of patients suffer irreversible cerebral ischemia as a result of lesser degrees of stenosis. Diagnostic techniques that can identify nonstenotic high-risk plaque would therefore be beneficial. High-risk plaque is defined histologically if it contains hemorrhage/thrombus. Magnetic resonance direct thrombus imaging (MRDTI) is capable of detecting methemoglobin within intraplaque hemorrhage. We assessed this as a marker of complicated plaque and compared its accuracy with histological examination of surgical endarterectomy specimens. Methods and Results-Sixty-three patients underwent successful MRDTI and endarterectomy with histological examination. Of these, 44 were histologically defined as complicated (type VI plaque). MRDTI demonstrated 3 false-positive and 7 false-negative results, giving a sensitivity and specificity of 84%, negative predictive value of 70%, and positive predictive value of 93%. The interobserver (ϭ0.75) and intraobserver (ϭ0.9) agreement for reading MRDTI scans was good. Conclusions-MRDTI of the carotid vessels in patients with cerebral ischemia is an accurate means of identifying histologically confirmed complicated plaque. The high contrast generated by short T 1 species within the plaque allows for ease of interpretation, making this technique highly applicable in the research and clinical setting for the investigation of carotid atherosclerotic disease. Key Words: thrombus Ⅲ plaque Ⅲ carotid arteries Ⅲ imaging Ⅲ cerebral ischemia A therothrombotic carotid disease is a major cause of cerebral ischemia. Embolization from the surface of an atherosclerotic plaque to cerebral vessels can result in occlusion, which, if sufficiently prolonged, will result in cerebral infarction. More transient vascular occlusion may result in temporary ischemia, producing a neurological deficit that recovers with little or no residual brain damage. Clinically, transient ischemic attacks (TIAs) provide a warning of further cerebral ischemic events; Ϸ10% of patients who sustain a TIA, left untreated, will suffer a definitive stroke in the following year, 1 followed by a rate of 5% per annum. A warning TIA therefore offers the chance to intervene to prevent future permanent cerebral damage. The North American 2 and European 3 endarterectomy trials have both shown the positive benefit of surgery in patients with significant stenosis. The trials also indicate that lesser degrees of carotid disease are responsible for a significant number of strokes, but the risks of surgery matched or outweighed the benefits. Techniques have been sought to further define those among the group with moderate stenosis who are at high risk.In 1995, Stary et al, 4 for the American Heart Association, defined different atherosclerotic subtypes, the purpose being to pathologically identify plaque more likely to ...

SummaryBackgroundResults of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.MethodsFOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.FindingsBetween Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months.InterpretationFluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.FundingUK Stroke Association and NIHR Health Technology Assessment Programme.

Background-It is recognized that complicated plaque largely accounts for the morbidity and mortality from atherosclerosis. Ideally, investigation of symptomatic and asymptomatic patients would identify atheromatous plaques independently of stenosis. We have previously shown that a magnetic resonance direct thrombus imaging (MRDTI) technique demonstrates complicated atheroma as high signal within the carotid arterial wall. We used this technique to examine the prevalence of complicated carotid plaque in vivo in the ipsilateral arteries of recently symptomatic patients with suspected carotid artery stenosis and to compare this with their contralateral arteries and with those of healthy age-and sex-matched controls. Methods and Results-The carotid arteries of 120 patients with suspected severe carotid artery stenosis and previous acute cerebral ischemia were imaged using MRDTI, as were 28 control arteries. High signal was not seen in any control artery. However, there was a 60% prevalence of high signal, suggestive of complicated plaque in the patients' ipsilateral arteries. The prevalence of high signal was significantly greater in the patients' ipsilateral vessels compared with the contralateral, asymptomatic side (60% versus 36%, 2 PϽ0.001), particularly for vessels of only moderate stenosis. Conclusions-MRDTI high signal suggestive of complicated plaque is prevalent in the ipsilateral carotid arteries of patients with carotid stenosis and recent cerebral ischemic events. MRDTI has a potential role in identifying "at risk" plaque, studying atherogenesis and the effects of plaque-modifying strategies. (Circulation. 2003;107:3053-3058.)

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