Valeria Caso

Guidelines for Management of Ischaemic Stroke and Transient Ischaemic Attack 2008

This article represents the update of the European Stroke Initiative Recommendations for Stroke Management. These guidelines cover both ischaemic stroke and transient ischaemic attacks, which are now considered to be a single entity. The article covers referral and emergency management, Stroke Unit service, diagnostics, primary and secondary prevention, general stroke treatment, specific treatment including acute management, management of complications, and rehabilitation.

Effect of a Novel Free Radical Scavenger, Edaravone (MCI-186), on Acute Brain Infarction

Edaravone, a novel free radical scavenger, demonstrates neuroprotective effects by inhibiting vascular endothelial cell injury and ameliorating neuronal damage in ischemic brain models. The present study was undertaken to verify its therapeutic efficacy following acute ischemic stroke. We performed a multicenter, randomized, placebo-controlled, double-blind study on acute ischemic stroke patients commencing within 72 h of onset. Edaravone was infused at a dose of 30 mg, twice a day, for 14 days. At discharge within 3 months or at 3 months after onset, the functional outcome was evaluated using the modified Rankin Scale. Two hundred and fifty-two patients were initially enrolled. Of these, 125 were allocated to the edaravone group and 125 to the placebo group for analysis. Two patients were excluded because of subarachnoid hemorrhage and disseminated intravascular coagulation. A significant improvement in functional outcome was observed in the edaravone group as evaluated by the modified Rankin Scale (p = 0.0382). Edaravone represents a neuroprotective agent which is potentially useful for treating acute ischemic stroke, since it can exert significant effects on functional outcome as compared with placebo.

Early Hemorrhagic Transformation of Brain Infarction: Rate, Predictive Factors, and Influence on Clinical Outcome Results of a Prospective Multicenter Study

Background and Purpose— Early hemorrhagic transformation (HT) is a complication of ischemic stroke but its effect on patient outcome is unclear. The aims of this study were to assess: (1) the rate of early HT in patients admitted for ischemic stroke, (2) the correlation between early HT and functional outcome at 3 months, and (3) the risk factors for early HT. Methods— Consecutive patients with ischemic stroke were included in this prospective study in 4 study centers. Early HT was assessed by CT examination performed at day 5±2 after stroke onset. Study outcomes were 3-month mortality or disability. Disability was assessed using a modified Rankin score (≥3 indicating disabling stroke) by neurologists unaware of the occurrence of HT in the individual cases. Outcomes in patients with and without early HT were compared by &khgr;2 test. Multiple logistic regression analysis was used to identify predictors for HT. Results— Among 1125 consecutive patients (median age 76.00 years), 98 (8.7%) had HT, 62 (5.5%) had hemorrhagic infarction, and 36 (3.2%) parenchymal hematoma. At 3 months, 455 patients (40.7%) were disabled or died. Death or disability was seen in 33 patients with parenchymal hematoma (91.7%), in 35 patients with hemorrhagic infarction (57.4%) as compared with 387 of the 1021 patients without HT (37.9%). At logistic regression analysis, parenchymal hematoma, but not hemorrhagic infarction, was independently associated with an increased risk for death or disability (OR 15.29; 95% CI 2.35 to 99.35). At logistic regression analysis, parenchymal hematoma was predicted by large lesions (OR 12.20, 95% CI 5.58 to 26.67), stroke attributable to cardioembolism (OR 5.25; 95% CI 2.27 to 12.14) or to other causes (OR 6.77; 95% CI 1.75 to 26.18), high levels of blood glucose (OR 1.01; 95% CI 1.00 to 1.01), and thrombolytic treatment (OR 3.54, 95% CI 1.04 to 11.95). Conclusions— Early HT occurs in about 9% of patients. Parenchymal hematoma, seen in about 3% of patients, is associated with an adverse outcome. Parenchymal hematoma was predicted by large lesions attributable to cardioembolism or other causes, high blood glucose, and treatment with thrombolysis.

Efficacy and Safety of Anticoagulant Treatment in Acute Cardioembolic Stroke A Meta-Analysis of Randomized Controlled Trials

Background and Purpose— The role of anticoagulant treatment for acute cardioembolic stroke is uncertain. We performed an updated meta-analysis of all randomized trials to obtain the best estimates of the efficacy and safety of anticoagulants for the initial treatment of acute cardioembolic stroke. Methods— Using electronic and manual searches of the literature, we identified randomized trials comparing anticoagulants (unfractionated heparin or low-molecular-weight heparin or heparinoids), started within 48 hours, with other treatments (aspirin or placebo) in patients with acute ischemic cardioembolic stroke. Two reviewers independently selected studies and extracted data on study design, quality, and clinical outcomes, including death or disability, all strokes, recurrent ischemic stroke, and cerebral symptomatic bleeding. Odds ratios for individual outcomes were calculated for each trial and data from all the trials were pooled using the Mantel-Haenszel method. Results— Seven trials, involving 4624 patients with acute cardioembolic stroke, met the criteria for inclusion. Compared with other treatments, anticoagulants were associated with a nonsignificant reduction in recurrent ischemic stroke within 7 to 14 days (3.0% versus 4.9%, odds ratio 0.68, 95% CI: 0.44 to 1.06, P=0.09, number needed to treat=53), a significant increase in symptomatic intracranial bleeding (2.5% versus 0.7%, odds ratio 2.89; 95% CI: 1.19 to 7.01, P=0.02, number needed to harm=55), and a similar rate of death or disability at final follow up (73.5% versus 73.8%, odds ratio 1.01; 95% CI: 0.82 to 1.24, P=0.9). Conclusions— Our findings indicate that in patients with acute cardioembolic stroke, early anticoagulation is associated with a nonsignificant reduction in recurrence of ischemic stroke, no substantial reduction in death and disability, and an increased intracranial bleeding.

Antiplatelets Versus Anticoagulation in Cervical Artery Dissection

Background and Purpose— The widespread preference of anticoagulants over antiplatelets in patients with cervical artery dissection (CAD) is empirical rather than evidence-based. Summary of Review— This article summarizes pathophysiological considerations, clinical experiences, and the findings of a systematic metaanalysis about antithrombotic agents in CAD patients. As a result, there are several putative arguments in favor as well as against immediate anticoagulation in CAD patients. Conclusions— A randomized controlled trial comparing antiplatelets with anticoagulation is needed and ethically justified. However, attributable to the large sample size which is required to gather meaningful results, such a trial represents a huge venture. This comprehensive overview may be helpful for the design and the promotion of such a trial. In addition, it could be used to encourage both participation of centers and randomization of CAD patients. Alternatively, antithrombotic treatment decisions can be customized based on clinical and paraclinical characteristics of individual CAD patients. Stroke severity with National Institutes of Health Stroke Scale score ≥15, accompanying intracranial dissection, local compression syndromes without ischemic events, or concomitant diseases with increased bleeding risk are features in which antiplatelets seem preferable. In turn, in CAD patients with (pseudo)occlusion of the dissected artery, high intensity transient signals in transcranial ultrasound studies despite (dual) antiplatelets, multiple ischemic events in the same circulation, or with free-floating thrombus immediate anticoagulation is favored.

Mechanical thrombectomy in acute ischemic stroke: Consensus statement by ESO-Karolinska Stroke Update 2014/2015, supported by ESO, ESMINT, ESNR and EAN

The original version of this consensus statement on mechanical thrombectomy was approved at the European Stroke Organisation (ESO)-Karolinska Stroke Update conference in Stockholm, 16–18 November 2014. The statement has later, during 2015, been updated with new clinical trials data in accordance with a decision made at the conference. Revisions have been made at a face-to-face meeting during the ESO Winter School in Berne in February, through email exchanges and the final version has then been approved by each society. The recommendations are identical to the original version with evidence level upgraded by 20 February 2015 and confirmed by 15 May 2015. The purpose of the ESO-Karolinska Stroke Update meetings is to provide updates on recent stroke therapy research and to discuss how the results may be implemented into clinical routine. Selected topics are discussed at consensus sessions, for which a consensus statement is prepared and discussed by the participants at the meeting. The statements are advisory to the ESO guidelines committee. This consensus statement includes recommendations on mechanical thrombectomy after acute stroke. The statement is supported by ESO, European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), and European Academy of Neurology (EAN).

Dysphagia following Stroke

Background: Dysphagia is common after stroke. We aimed to study the prognosis of dysphagia (assessed clinically) over the first 3 months after acute stroke and to determine whether specific neurovascular-anatomical sites were associated with swallowing dysfunction. Methods: We prospectively examined consecutive patients with acute first-ever stroke. The assessment of dysphagia was made using standardized clinical methods. The arterial territories involved were determined on CT/MRI. All patients were followed up for 3 months. Results: 34.7% of 406 patients had dysphagia. Dysphagia was more frequent in patients with hemorrhagic stroke (31/63 vs. 110/343; p = 0.01). In patients with ischemic stroke, the involvement of the arterial territory of the total middle cerebral artery was more frequently associated with dysphagia (28.2 vs. 2.2%; p < 0.0001). Multivariate analysis revealed that stroke mortality and disability were independently associated with dysphagia (p < 0.0001). Conclusions: The frequency of dysphagia was relatively high. Regarding anatomical-clinical correlation, the most important factor was the size rather than the location of the lesion. Dysphagia assessed clinically was a significant variable predicting death and disability at 90 days.

Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS): a partial-factorial randomised controlled trial.

Summary Background High blood pressure is associated with poor outcome after stroke. Whether blood pressure should be lowered early after stroke, and whether to continue or temporarily withdraw existing antihypertensive drugs, is not known. We assessed outcomes after stroke in patients given drugs to lower their blood pressure. Methods In our multicentre, partial-factorial trial, we randomly assigned patients admitted to hospital with an acute ischaemic or haemorrhagic stroke and raised systolic blood pressure (systolic 140–220 mm Hg) to 7 days of transdermal glyceryl trinitrate (5 mg per day), started within 48 h of stroke onset, or to no glyceryl trinitrate (control group). A subset of patients who were taking antihypertensive drugs before their stroke were also randomly assigned to continue or stop taking these drugs. The primary outcome was function, assessed with the modified Rankin Scale at 90 days by observers masked to treatment assignment. This study is registered, number ISRCTN99414122. Findings Between July 20, 2001, and Oct 14, 2013, we enrolled 4011 patients. Mean blood pressure was 167 (SD 19) mm Hg/90 (13) mm Hg at baseline (median 26 h [16–37] after stroke onset), and was significantly reduced on day 1 in 2000 patients allocated to glyceryl trinitrate compared with 2011 controls (difference −7·0 [95% CI −8·5 to −5·6] mm Hg/–3·5 [–4·4 to −2·6] mm Hg; both p<0·0001), and on day 7 in 1053 patients allocated to continue antihypertensive drugs compared with 1044 patients randomised to stop them (difference −9·5 [95% CI −11·8 to −7·2] mm Hg/–5·0 [–6·4 to −3·7] mm Hg; both p<0·0001). Functional outcome at day 90 did not differ in either treatment comparison—the adjusted common odds ratio (OR) for worse outcome with glyceryl trinitrate versus no glyceryl trinitrate was 1·01 (95% CI 0·91–1·13; p=0·83), and with continue versus stop antihypertensive drugs OR was 1·05 (0·90–1·22; p=0·55). Interpretation In patients with acute stroke and high blood pressure, transdermal glyceryl trinitrate lowered blood pressure and had acceptable safety but did not improve functional outcome. We show no evidence to support continuing prestroke antihypertensive drugs in patients in the first few days after acute stroke. Funding UK Medical Research Council.

The role of carotid artery stenting and carotid endarterectomy in cognitive performance: a systematic review.

Background and Purpose— Change in cognition is being increasingly recognized as an important outcome measure; however, the role of carotid revascularization on this issue remains to be determined. It is still under debate whether carotid artery stenting and carotid endarterectomy have the same influence on neuropsychological functions. Summary of Review— This article systematically reviews recent literature in an attempt to clarify this issue. A total of 32 papers reporting on neurocognition after carotid endarterectomy (n=25), carotid artery stenting (n=4), or carotid artery stenting versus carotid endarterectomy (n=3) were identified. The studies were different for many methodological factors, eg, sample size, type of patients and control group, statistical measure, type of test, timing of assessment, and so on. There was a lack of consensus in defining the improvement or impairment after either carotid artery stenting or carotid endarterectomy. Furthermore, there were nonuneqivocal results regarding the same domain of assessment (memory, visuomotor, attention). Based on available evidence, it is probable that carotid endarterectomy as well as carotid artery stenting do not change neuropsychological function “per se.” Conclusions— Assessment of cognition after carotid revascularization is probably influenced by many confounding factors such as learning effect, type of test, type of patients, and control group, which are often minimized in their importance. The role of carotid revascularization is to prevent stroke in patients with severe carotid stenosis as highlighted by previous large randomized trials. Although an effect of carotid revascularization on cognition could be missed as a consequence of underpowered studies included in this review, at this time, no prediction can be done regarding its repercussions on higher intellectual functions. Larger studies appropriately designed and powered to assess cognition after carotid revascularization might change this view.

Differential features of carotid and vertebral artery dissections The CADISP Study

Objective: To examine whether risk factor profile, baseline features, and outcome of cervical artery dissection (CEAD) differ according to the dissection site. Methods: We analyzed 982 consecutive patients with CEAD included in the Cervical Artery Dissection and Ischemic Stroke Patients observational study (n = 619 with internal carotid artery dissection [ICAD], n = 327 with vertebral artery dissection [VAD], n = 36 with ICAD and VAD). Results: Patients with ICAD were older (p < 0.0001), more often men (p = 0.006), more frequently had a recent infection (odds ratio [OR] = 1.59 [95% confidence interval (CI) 1.09–2.31]), and tended to report less often a minor neck trauma in the previous month (OR = 0.75 [0.56–1.007]) compared to patients with VAD. Clinically, patients with ICAD more often presented with headache at admission (OR = 1.36 [1.01–1.84]) but less frequently complained of cervical pain (OR = 0.36 [0.27–0.48]) or had cerebral ischemia (OR = 0.32 [0.21–0.49]) than patients with VAD. Among patients with CEAD who sustained an ischemic stroke, the NIH Stroke Scale (NIHSS) score at admission was higher in patients with ICAD than patients with VAD (OR = 1.17 [1.12–1.22]). Aneurysmal dilatation was more common (OR = 1.80 [1.13–2.87]) and bilateral dissection less frequent (OR = 0.63 [0.42–0.95]) in patients with ICAD. Multiple concomitant dissections tended to cluster on the same artery type rather than involving both a vertebral and carotid artery. Patients with ICAD had a less favorable 3-month functional outcome (modified Rankin Scale score >2, OR = 3.99 [2.32–6.88]), but this was no longer significant after adjusting for baseline NIHSS score. Conclusion: In the largest published series of patients with CEAD, we observed significant differences between VAD and ICAD in terms of risk factors, baseline features, and functional outcome.