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Background and objectivesTaking a detailed history of symptoms is important for differentiating incipient ischemic stroke and migraine aura. The aim of our study is to describe in detail symptom type and temporal pattern of symptom evolution (i.e., symptom succession and the time lapse between symptoms) and to identify differentiating clinical features in patients with ischemic stroke and migraine with aura.MethodsConsecutive patients with ischemic stroke and migraine with aura were interviewed using a structured questionnaire. Stroke diagnosis was confirmed by imaging and migraine with aura was diagnosed according to the current criteria of the International Headache Society. Wake-up strokes and patients with severe cognitive deficits were excluded.ResultsIn stroke patients and migraine patients, respectively, 50/78 (64%) vs. 123/326 (37%) had one, 18 (23%) vs. 127 (38%) had two, 5 (6%) vs. 69 (21%) had three, 2 (2%) vs. 4 (1%) had four, and 3 (3%) vs. 3 (1%) had five visual symptoms. In respect of sensory symptoms, 76/145 (52.4%) vs. 116/175 (66%) reported paresthesia and 92/145 (63.4%) vs. 132 (75%) numbness. Looking at the beginning, visual symptoms were the first symptom more often in migraine aura than in ischemic stroke (72.1 vs 18.8%, P < 0.001; PPV 86.8%). Sensory (29 vs 13.9%, P = 0.001; PPV 54.8%) and motor symptoms (20.5 vs 1.4%, P < 0.001; PPV 88.9%) were the first symptom more frequently in ischemic stroke. Of patients with consecutive symptoms, 39 of 201 (19%) compared to 34 of 117 (29%) (P = 0.02; PPV 46.6%) reported at least two simultaneous symptoms. A time lapse between symptoms of < 1 min (18.6 vs 6.3%, P < 0.001; PPV 57.1%) and > 360 min (15.8 vs 0%, χ2 = 39.61, P < 0.001; PPV 100%) was more frequent in stroke whereas a time lapse between 5 and 60 min was more frequent in migraine aura (41.1 vs 68.7%, χ2 = 23.52, P < 0.001; PPV 78.7%).ConclusionThere is a significant overlap in the clinical presentation of stroke and migraine aura. In particular, a substantial proportion of patients in one group had symptoms that are traditionally attributed to the other group. This study highlights the similarities and differences between symptoms of ischemic stroke and migraine aura and challenges our reasoning in daily clinical practice.

In general, suddenly occurring neurological deficits, i.e., negative neurological symptoms, are considered symptoms of focal cerebral ischemia, while positive irritative symptoms with gradual onset are viewed as the characteristics of migraine aura. Nevertheless, cortical spreading depolarization, the pathophysiological basis of migraine aura, has also been observed in acute ischemic stroke. The aim of our study was to determine the frequency of migraine aura-like symptoms at ischemic stroke onset and stroke-like symptoms in migraine with aura.We interviewed 350 consecutive patients with ischemic stroke and 343 with migraine with aura using a structured questionnaire. Stroke diagnosis was confirmed by imaging, and migraine with aura was diagnosed according to the current criteria of the International Headache Society. Patients with wake-up strokes or severe cognitive deficits that precluded a useful interview were excluded from the study.Seventy-eight patients with stroke (22.3%) reported visual symptoms, 145 (41.4%) sensory symptoms, 197 (56.3%) a paresis, and 201 patients (57.4%) more than one symptom, compared to 326 migraine patients with aura (95%) with visual symptoms (Many patients with stroke experience migraine-like symptoms at stroke onset, and many migraine with aura patients have stroke-like symptoms. Though overall the symptom frequencies of the two groups are significantly different, clarifying the differential diagnosis in an individual patient requires additional history elements, physical findings, or results of ancillary investigations.

Introduction: Patent foramen ovale (PFO) closure is effective for secondary stroke prevention in well selected patients. After device implantation some patients have residual shunting. There was no impact of incomplete closure on recurrent stroke risk in any of the trials but outcome rates are low with little power to detect an effect. Hypothesis: Patients with residual shunts after PFO closure have more recurrent strokes than those with complete elimination of shunting. Methods: We pooled individual patient data from 5 of 6 randomized clinical trials comparing medical therapy to PFO closure + medical therapy. Residual shunt data were not available for 1 trial. This analysis only includes PFO closure subjects. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated with Cox proportional hazards regression, adjusted for age, sex, coronary disease, diabetes, hypertension, hyperlipidemia, prior stroke/TIA, smoking, index event (stroke vs TIA), hypermobile septum, shunt size (large vs small) and infarct location (superficial vs deep). Multiple imputation of missing values for adjusted variables was used. Results: Among 1475 patients treated with PFO closure and with non-missing residual shunt data, 149 (10%) had incomplete closure. The median time from procedure to shunt measurement was 204 days (25 th -75 th percentile, 181-722). In the complete closure group the primary endpoint of recurrent ischemic stroke occurred in 30 patients (2.3%; 95% CI 1.5-3.2%) compared to 4 (2.7%; 95% CI 0.7-6.7%) with incomplete closure. Unadjusted and adjusted HRs comparing incomplete vs complete closure were 1.37 (0.48, 3.92) and 1.69 (0.37, 4.95) respectively. The secondary endpoint of recurrent ischemic stroke, TIA, or vascular death occurred in 66 (5.0%; 95% CI 3.9-6.3%) patients with complete closure compared to 9 (6.0%; 95% CI 2.8-11.2%) without. Unadjusted and adjusted HRs were 1.26 (0.63, 2.54) and 1.39 (0.68, 2.83) respectively. Conclusions: Our pooled analysis of individual subjects after PFO closure from 5 of 6 relevant randomized clinical trials, showed no association between residual shunt and recurrent stroke events. This analysis was limited by low rates of residual shunt and recurrent events even in this large, combined dataset.

Background and PurposeClots rich in platelets and fibrin retrieved from patients with acute ischemic stroke (AIS) have been shown to be independently associated with the absence of the susceptibility vessel sign (SVS) on MRI and active malignancy. This study analyzed the association of SVS and the presence of active malignancy in patients with AIS who underwent mechanical thrombectomy (MT).MethodsThis single-center, retrospective, and cross-sectional study included consecutive patients with AIS with admission MRI treated with MT between January 2010 and December 2018. SVS status was evaluated on susceptibility-weighted imaging. Adjusted odds ratios (aORs) were calculated to determine the association between absent SVS and the presence of active or occult malignancy. The performance of predictive models incorporating and excluding SVS status was compared using areas under the receiver operating characteristics curve (auROC).ResultsOf 577 patients with AIS with assessable SVS status, 40 (6.9%) had a documented active malignancy and 72 (12.5%) showed no SVS. The absence of SVS was associated with active malignancy (aOR 4.85, 95% CI 1.94–12.11) or occult malignancy (aOR 11.42, 95% CI 2.36–55.20). The auROC of predictive models, including demographics and common malignancy biomarkers, was higher but not significant (0.85 vs. 0.81, p = 0.07) when SVS status was included.ConclusionAbsence of SVS on admission MRI of patients with AIS undergoing MT is associated with malignancy, regardless of whether known or occult. Therefore, the SVS might be helpful in detecting paraneoplastic coagulation disorders and occult malignancy in patients with AIS.

ImportanceThe Patent Foramen Ovale (PFO)–Associated Stroke Causal Likelihood classification system combines information regarding noncardiac patient features (vascular risk factors, infarct topography) and PFO features (shunt size and presence of atrial septal aneurysm [ASA]) to classify patients into 3 validated categories of responsiveness to treatment with PFO closure. However, the distinctive associations of shunt size and ASA, alone and in combination, have not been completely delineated.ObjectiveTo evaluate the association of PFO closure with stroke recurrence according to shunt size and/or the presence of an ASA.Design, Setting, and ParticipantsPooled individual patient data from 6 randomized clinical trials conducted from February 2000 to October 2017 that compared PFO closure with medical therapy. Patients in North America, Europe, Australia, Brazil, and South Korea with PFO-associated stroke were included. Analysis was completed in January 2022.ExposuresTranscatheter PFO closure plus antithrombotic therapy vs antithrombotic therapy alone, stratified into 4 groups based on the combination of 2 features: small vs large PFO shunt size and the presence or absence of an ASA.Main Outcomes and MeasuresRecurrent ischemic stroke.ResultsA total of 121 recurrent ischemic strokes occurred in the pooled 3740 patients (mean [SD] age, 45 [10] years; 1682 [45%] female) during a median (IQR) follow-up of 57 (23.7-63.8) months. Treatment with PFO closure was associated with reduced risk for recurrent ischemic stroke (adjusted hazard ratio [aHR], 0.41 [95% CI, 0.28-0.60]; P P = .02). At 2 years, the absolute risk reduction of recurrent stroke was greater (5.5% [95% CI, 2.7-8.3]) in patients with large shunt and ASA than for patients in the other 3 categories (1.0% for all).Conclusions and RelevancePatients with both a large shunt and an ASA showed a substantially greater beneficial association with PFO closure than patients with large shunt alone, patients with small shunt and ASA, and patients with neither large shunt nor ASA. These findings, combined with other patient features, may inform shared patient-clinician decision-making.

Background and Purpose: To identify factors associated with prior stroke at presentation in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO). Methods: We studied cross-sectional data from the International PFO Consortium Study (NCT00859885). Patients with first-ever stroke and those with prior stroke at baseline were analyzed for an association with PFO-related (right-to-left shunt at rest, atrial septal aneurysm, deep venous thrombosis, pulmonary embolism, and Valsalva maneuver) and PFO-unrelated factors (age, gender, BMI, hypertension, diabetes mellitus, hypercholesterolemia, smoking, migraine, coronary artery disease, aortic plaque). A multivariable analysis was used to adjust effect estimation for confounding, e.g., owing to the age-dependent definition of study groups in this cross-sectional study design. Results: We identified 635 patients with first-ever and 53 patients with prior stroke. Age, BMI, hypertension, diabetes mellitus, hypercholesterolemia, coronary artery disease, and right-to-left shunt (RLS) at rest were significantly associated with prior stroke. Using a pre-specified multivariable logistic regression model, age (Odds Ratio 1.06), BMI (OR 1.06), hypercholesterolemia (OR 1.90) and RLS at rest (OR 1.88) were strongly associated with prior stroke.Based on these factors, we developed a nomogram to illustrate the strength of the relation of individual factors to prior stroke. Conclusion: In patients with CS and PFO, the likelihood of prior stroke is associated with both, PFO-related and PFO-unrelated factors. CA extern

Background CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome.Methods In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1,2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 mu m(2)/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered.Findings We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0.47 [95% CI 0.30-0.72], p=0.0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0.77 [0.69-0.86] per 10 mL, p(interaction)=0.29; diffusion MRI OR 0.87 [0.81-0.94] per 10 mL, p(interaction)=0.94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low.Interpretation Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imagingto-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions. Copyright (C) 2018 Elsevier Ltd. All rights reserved.

Background and Purpose— EmboTrap is a novel stent retriever designed to achieve rapid and substantial flow restoration in acute ischemic stroke secondary to large-vessel occlusions. Here, we evaluated EmboTrap’s safety and efficacy compared with established stent retrievers. Methods— ARISE II (Analysis of Revascularization in Ischemic Stroke With EmboTrap) was a single-arm, prospective, multicenter study, comparing the EmboTrap device to a composite performance goal criterion derived using a Bayesian meta-analysis from the pivotal SWIFT (Solitaire device) and TREVO 2 (Trevo device) trials. Patients at 11 US and 8 European sites were eligible for inclusion if they had large-vessel occlusions and moderate-to-severe neurological deficits within 8 hours of symptom onset. The primary efficacy end point was achievement of modified Thrombolysis in Cerebral Ischemia (mTICI) reperfusion scores of ≥2b within 3 EmboTrap passes as adjudicated by the core laboratory. The primary safety end point was a composite of symptomatic intracerebral hemorrhage and serious adverse device effects. Secondary end points included functional independence (modified Rankin Scale, 0–2) and all-cause mortality at 90 days. Results— Between October 2015 and February 2017, 227 patients were enrolled and treated with the EmboTrap device. The primary efficacy end point (mTICI ≥2b within 3 passes) was achieved in 80.2% (95% confidence interval, 74%–85% versus 56% performance goal criterion; P value, Conclusions— The EmboTrap stent-retriever mechanical thrombectomy device demonstrated high rates of substantial reperfusion and functional independence in patients with acute ischemic stroke secondary to large-vessel occlusions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02488915.

BACKGROUND: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care.METHODS: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered.FINDINGS: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09-2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75-3·10, pINTERPRETATION: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons.FUNDING: Medtronic.

BACKGROUND Behavioral changes are common in patients with multiple sclerosis (MS), however not as readily recognized as cognitive impairments. OBJECTIVE The aim of this study was to analyze behavioral changes and its relation to disease characteristics, disability, and cognitive impairments in patients with MS. METHOD This is a single-center cross-sectional study. A detailed neuropsychological examination, including the Frontal Systems Behavior Scale (FrSBe), the Beck depression inventory (BDI), and the Wuerzburg Fatigue Inventory for Multiple Sclerosis (WEIMuS) test, was performed. FrSBe results were correlated with disease characteristics, disability, and cognitive assessments. RESULTS 66 patients were enrolled (mean age: 43.4 years; disease duration: 9.3 years; Expanded Disability Status Scale: 3.0). Up to one third of patients showed behavioral changes in at least one domain or the total score of the FrSBe. Patients were mildly affected with regard to cognitive functioning. Consistent correlation was found between behavioral changes and fatigue (WEIMuS) and depressive symptoms (BDI), but not with disease characteristics, disability, or cognitive functions. There was an increase of behavioral changes on all FrSBe scales in the current status compared to the retrospectively rated status before disease onset. Self- and family ratings with regard to current behavioral changes were similar. CONCLUSION Behavioral changes are common in otherwise mildly affected MS patients with up to one third being affected. In this patient cohort, behavioral changes occur largely independent of disease characteristics, physical disability, and cognitive functioning but correlate with both fatigue and depressive symptoms. Therefore, they should be tested specifically.

Background and Purpose- We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome. Methods- We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2-4, ≥5, and10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3- to 6-month functional outcome (modified Rankin score2). Results- In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09-2.07; P=0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73-5.35; P0.001) but not symptomatic ICH. Both cerebral amyloid angiopathy and noncerebral amyloid angiopathy patterns of CMBs were associated with PH and PHr. Increasing CMB burden category was associated with the risk of symptomatic ICH ( P=0.014), PH ( P=0.013), and PHr ( P0.00001). Five or more and10 CMBs independently predicted poor 3- to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10-3.12; P=0.020; and odds ratio: 3.99; 95% confidence interval: 1.55-10.22; P=0.004, respectively). Conclusions- Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3- to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke.

Percutaneous patent foramen ovale (PFO) closure has become a routine procedure and was proven to be safe and feasible. In a recently published pooled analysis of randomized trials, percutaneous PFO closure was shown to more effectively reduce recurrent stroke when compared with medical therapy in patients with cryptogenic strokes. However, procedural safety and closure rate are device dependent.We performed a propensity-score matched comparison of 28 patients undergoing percutaneous PFO closure using the Cera PFO occluder (CPO) with 28 patients who received the Amplatzer PFO occluder (APO). The main endpoints were procedural complications and closure rate at 6 months verified by transesophageal echocardiography.The implantation procedure using the CPO was successful and without complications in all cases. After propensity-score matching, there was no significant difference between groups for the primary endpoint of residual shunt at 6 months (7% in the CPO group vs 4% in the APO group; log-rank test P=.15).With regard to procedural safety and closure rate at 6 months, the performance of the CPO is comparable with the APO in this small patient cohort.

Background and Purpose— Preclinical studies showed that thrombi can be permeable and may, therefore, allow for residual blood flow in occluded arteries of patients having acute ischemic stroke. This perviousness may increase tissue oxygenation, improve thrombus dissolution, and augment intra-arterial treatment success. We hypothesize that the combination of computed tomographic angiography and noncontrast computed tomography imaging allows measurement of contrast agent penetrating a permeable thrombus, and it is associated with improved outcome. Methods— Thrombus and contralateral artery attenuations in noncontrast computed tomography and computed tomographic angiography images were measured in 184 Multicenter Randomized Clinical trial of Endovascular treatment of acute ischemic stroke in the Netherlands (MR CLEAN) patients with thin-slice images. Two quantitative estimators of the thrombus permeability were introduced: computed tomographic angiography attenuation increase (Δ) and thrombus void fraction (ε). Patients were dichotomized as having a pervious or impervious thrombus and associated with outcome, recanalization, and final infarct volume. Results— Patients with Δ≥10.9 HU (n=81 [44%]) and ε≥6.5% (n=77 [42%]) were classified as having a pervious thrombus. These patients were 3.2 (95% confidence interval, 1.7–6.4) times more likely to have a favorable outcome, and 2.5 (95% confidence interval, 1.3–4.8) times more likely to recanalyze, for Δ based classification, and similarly for ε. These odds ratios were independent from intravenous or intra-arterial treatment. Final infarct volume was negatively correlated with both perviousness estimates (correlation coefficient, −0.39 for Δ and −0.40 for ε). Conclusions— This study shows that simultaneous measurement of thrombus attenuation in noncontrast computed tomography and computed tomographic angiography allows for quantification of thrombus perviousness. Thrombus perviousness is strongly associated with improved functional outcome, smaller final infarct volume, and higher recanalization rate.

Background and Purpose— Randomized trials suggested a different benefit of intravenous thrombolysis (IVT) and intra-arterial thrombolysis (IAT) between men and women with anterior circulation stroke because of a worse outcome of women in the control group. Methods— We compared outcome and recanalization in men and women with basilar artery occlusion treated with antithrombotic treatment alone, IVT or combined IVT–IAT, or IAT in the Basilar Artery International Cooperation Study. Results— Overall, 389 male and 226 female patients were analyzed. In the antithrombotic treatment group, 68 of 111 (61%) men and 47 of 70 (67%) women had a poor outcome defined as a modified Rankin Scale score of 4 to 6 (adjusted risk ratio [aRR], 0.96; 95% CI, 0.75 to 1.24), in the IVT/combined IVT–IAT group, 47 of 77 (61%) men and 24 of 43 (56%) women (aRR, 1.19; 95% CI, 0.89 to 1.60), and in the IAT group, 142 of 185 (77%) men and 71 of 102 (70%) women (aRR, 1.01; 95% CI, 0.88 to 1.17). Mortality was not different between men and women in the antithrombotic treatment group (aRR, 0.80; 95% CI, 0.55 to 1.16), the IVT/combined IVT–IAT group (aRR, 1.11; 95% CI, 0.72 to 1.73), or in the IAT group (aRR, 1.01; 95% CI, 0.75 to 1.36). Insufficient recanalization after combined IVT–IAT or IAT was similar in men and women (23% versus 22%; aRR, 0.92; 95% CI, 0.58 to 1.46). Conclusions— In patients with acute basilar artery occlusion, no significant gender differences for outcome and recanalization were observed, regardless of treatment modality.

Background and purpose: Recurrent ischemic stroke in patients with CS and PFO has been proposed as a marker of increased risk for paradoxical embolism. It is unclear, whether the excess risk is driven by specific features of the PFO (right-to-left shunt (RLS) size, RLS at rest, associated atrial septum aneurysm (ASA)) or the presence of vascular risk factors (vRF). We compare the prevalence of vRF, TEE features, and baseline medications in PFO patients with first-ever versus multiple CS. Methods: From September 2008 to March 2013, the International PFO Consortium enrolled 993 patients with ischemic stroke or transient ischemic attack (TIA) and newly diagnosed PFO. In this analysis of baseline data, we included 386 patients with first-ever CS and no radiological evidence of prior cerebral ischemia (first-ever CS group, mean age, 52y) as well as 71 patients with recurrent CS and multiple ischemic lesions on CT and/or MRI (multiple CS group, mean age, 59y). Patients with TIA as index event, those with first-ever CS but additional “silent” ischemic lesions on imaging as well as those with recurrent CS without radiological findings of prior cerebral ischemia were excluded. We used nonparametric tests for independent samples and the Bonferroni correction for multiple comparisons. Results: Age > 55y (63% vs. 44%, P=0.001), hypertension (52% vs. 30%, P=0.001), hyperlipidemia (64% vs. 44%, P=0.003), and coronary artery disease (15% vs. 3%, P=0.001) were significantly more frequent in the multiple CS than in the first-ever CS group. The frequencies of male gender, current smoking, diabetes, migraine with or without aura, associated ASA, RLS size, and RLS at rest did not differ between groups. At baseline, patients with multiple CS were more likely to be on antiplatelets (50% vs. 18%), antihypertensive (51% vs. 22%) or lipid lowering drugs (44% vs. 10%, P=0.001 for each comparison) than patients with first-ever CS. The frequency of anticoagulant treatment did not differ between groups. Conclusions: In patients with CS, vRF but not specific PFO features were associated with recurrent cerebral ischemic events. The ongoing prospective part of the International PFO Consortium will likely shed light upon the role of vRF control for secondary stroke prevention in patients with PFO.

Aims: Endovascular treatment (EVT) for acute ischemic stroke (AIS) has the potential to improve clinical outcome in well selected patients with a major intracranial occlusion. This study aimed to identify easily available pre-hospital predictors and to develop a clinical score to detect AIS patients with such occlusions potentially eligible for acute EVT. Methods: Consecutive AIS enrolled in the ASTRAL registry with good quality CT-angiography within 12h after onset were selected (1’645 patients, Lausanne) and categorized according to occlusion site. Easily accessible demographic and clinical information were used in a logistic regression analysis to derive predictors of major intracranial occlusions (intracranial carotid, basilar and M1-artery). A The score was created developed using the beta-logistic regression coefficients of the logistic regression analysis, and was validated internally and externally (848 patients, Bern). Results: Major intracranial occlusions were present in 316 (21%) acute stroke patients in the derivation and 566 (28%) in the internal validation cohort. From all 12 significant predictors of major intracranial occlusions, a 7- item score was developed to obtain the best diagnostic performance; it was termed ASTRAL-O score according to its constituents: Admission NIHSS (A): (NIHSS 0-4: 0 points; 5-9: 4; 10-14: 8; ≥15: 12), absence of pre-STroke handicap (mRS≤2) (ST: 2 points), absence of previous STroke (ST: 1 point), Right-sided stroke (R: 3 points), Atrial fibrillation (A: 1 point), Level of consciousness decreased (L: 1 point) and wOmen (O:2 points). Diagnostic accuracy of the score in both the internal and external validation cohort was good at different cut-off levels (AUC 0.84 and 0.76 respectively). A Wilcoxon signed rank test showed that the ASTRAL-0 score performed better than NIHSS alone in term of predicted probabilities. Conclusions: The ASTRAL-O score accurately predicts the major intracranial occlusions eligible for EVT. It improves predicted probabilities over the NIHSS alone. This tool could help to rapidly triage stroke patients in the hyper-acute phase

The results of Interventional Management of Stroke (IMS) III, Magnetic Resonance and REcanalization of Stroke Clots Using Embolectomy (MR RESCUE), and SYNTHESIS EXPANSION trials are expected to affect the practice of endovascular treatment for acute ischemic stroke. The purpose of this report is to review the components of the designs and methods of these trials and to describe the influence of those components on the interpretation of trial results.A critical review of trial design and conduct of IMS III, MR RESCUE, and SYNTHESIS EXPANSION is performed with emphasis on patient selection, shortcomings in procedural aspects, and methodology of data ascertainment and analysis. The influence of each component is estimated based on published literature including multicenter clinical trials reporting on endovascular treatment for acute ischemic stroke and myocardial infarction.We critically examined the time interval between symptom onset and treatment and rates of angiographic recanalization to differentiate between "endovascular treatment" and "parameter optimized endovascular treatment" as it relates to the IMS III, MR RESCUE, and SYNTHESIS EXPANSION trials. All the three trials failed to effectively test "parameter optimized endovascular treatment" due to the delay between symptom onset and treatment and less than optimal rates of recanalization. In all the three trials, the magnitude of benefit with endovascular treatment required to reject the null hypothesis was larger than could be expected based on previous studies. The IMS III and SYNTHESIS EXPANSION trials demonstrated that rates of symptomatic intracerebral hemorrhages subsequent to treatment are similar between IV thrombolytics and endovascular treatment in matched acute ischemic stroke patients. The trials also indirectly validated the superiority/equivalence of IV thrombolytics (compared with endovascular treatment) in patients with minor neurological deficits and those without large vessel occlusion on computed tomographic/magnetic resonance angiography.The results do not support a large magnitude benefit of endovascular treatment in subjects randomized in all the three trials. The possibility that benefits of a smaller magnitude exist in certain patient populations cannot be excluded. Large magnitude benefits can be expected with implementation of "parameter optimized endovascular treatment" in patients with ischemic stroke who are candidates for IV thrombolytics.

The risk of recurrence of cerebrovascular events within the first 72 hours of admission in patients hospitalized with symptomatic carotid artery (CA) stenoses and the risks and benefits of emergency CA intervention within the first hours after the onset of symptoms are not well known. Therefore, the authors aimed to assess (1) the ipsilateral recurrence rate within 72 hours of admission, in the period from 72 hours to 7 days, and after 7 days in patients presenting with nondisabling stroke, transient ischemic attack (TIA), or amaurosis fugax (AF), and with an ipsilateral symptomatic CA stenosis of 50% or more, and (2) the risk of stroke in CA interventions within 48 hours of admission versus the risk in interventions performed after 48 hours.Ninety-four patients were included in this study. These patients were admitted to hospital within 48 hours of a nondisabling stroke, TIA, or AF resulting from a symptomatic CA stenosis of 50% or more. The patients underwent carotid endarterectomy (85 patients) or CA stenting (9 patients). At baseline, the cardiovascular risk factors of the patients, the degree of symptomatic CA stenosis, and the type of secondary preventive treatment were assessed. The in-hospital recurrence rate of stroke, TIA, or AF ipsilateral to the symptomatic CA stenosis was determined for the first 72 hours after admission, from 72 hours to 7 days, and after 7 days. Procedure-related cerebrovascular events were also recorded.The median time from symptom onset to CA intervention was 5 days (interquartile range 3.00-9.25 days). Twenty-one patients (22.3%) underwent CA intervention within 48 hours after being admitted. Overall, 15 recurrent cerebrovascular events were observed in 12 patients (12.8%) in the period between admission and CA intervention: 3 strokes (2 strokes in progress and 1 stroke) (3.2%), 5 TIAs (5.3%), and 1 AF (1.1%) occurred within the first 72 hours (total 9.6%) of admission; 1 TIA (1.1%) occurred between 72 hours and 7 days, and 5 TIAs (5.3%) occurred after more than 7 days. The corresponding actuarial cerebrovascular recurrence rates were 11.4% (within 72 hours of admission), 2.4% (between 72 hours and 7 days), and 7.9% (after 7 days). Among baseline characteristics, no predictive factors for cerebrovascular recurrence were identified. Procedure-related cerebrovascular events occurred at a rate of 4.3% (3 strokes and 1 TIA), and procedures performed within the first 48 hours and procedures performed after 48 hours had a similar frequency of these events (4.5% vs. 4.1%, respectively; p = 0.896).The in-hospital recurrence of cerebrovascular events was quite low, but all recurrent strokes occurred within 72 hours. The risk of stroke associated with a CA intervention performed within the first 48 hours was not increased compared with that for later interventions. This raises the question of the optimal timing of CA intervention in symptomatic CA stenosis. To answer this question, more data are needed, preferably from large randomized trials.

Background The “RoPE Score” is a predictive model created to stratify patients by the likelihood that a patent foramen ovale (PFO) is incidental or pathogenic using clinical variables. We hypothesized that the predictors of recurrent stroke differ between patients with pathogenic and incidental PFOs. Methods Patients in the Risk of Paradoxical Embolism (RoPE) database with cryptogenic stroke (CS) and PFO were classified as having a probable pathogenic PFO (RoPE Score of >6, estimated PFO attributable fraction 72-99%, n=646) and others (RoPE Score of Results Follow-up was available for 91%, 80%, and 58% at 1, 2, and 3 years. Overall, a higher recurrence risk was associated with an index TIA, not being on a statin at baseline, and having a prior radiological stroke. For the low RoPE score group, older age, male sex, high cholesterol and antiplatelet (vs warfarin) treatment predicted recurrence. For those with high RoPE scores, predictors were prior (clinical) stroke/TIA and 2 echo features: septal hypermobility and a small shunt ( Conclusions Predictors of recurrence differ when PFO relatedness is classified by the RoPE Score. The hypothesis that patients with CS and PFO form a heterogenous group with different stroke mechanisms is supported. Conventional stroke risk factors were strong predictors among patients with lower RoPE scores. Echocardiographic features - including a counterintuitive association between smaller shunts and increased recurrence risk - were uniquely predictive in the high RoPE score group (likely pathogenic PFO).

Background Stroke databanks have consistently found a high ratio of anterior circulation (AC) to posterior circulation (PC) strokes without significant differences when compared for vascular risk factors, stroke etiology, treatments and outcome. One study suggested that there was a deviation from this consistent observation when comparing men and women with cryptogenic stroke (CS) and patent foramen ovale (PFO). We tested these associations using the RoPE database. Methods The Risk of Paradoxical Embolism (RoPE) Study is an international collaboration of 12 merged cohort studies of patients with CS and known PFO status (n=3674). This analysis was restricted to those subjects in the RoPE database with index strokes in the AC or PC (excluding both or unknown) from the 7 databases that had data for CS with, and without, PFO. We compared the effect of sex on infarct location among patients with versus without PFO. We used generalized linear mixed models to examine whether PFO status modified the gender effect on infarct location adjusting for study cohort as a random effect. Results Among cryptogenic stroke patients both with and without PFO, AC strokes were more common (61%) than PC overall (n=1535). Among patients with PFO, PC stroke was higher in men than in women (50% vs. 33%, OR 2.23, 95% CI: 1.58-3.13). This gender effect was attenuated in those without PFO (38% vs. 31%; OR 1.32, 95% CI: 0.98-1.77). The gender-by-PFO-status interaction was significant (p= 0.0224) and was highly consistent across study cohorts. Conclusions These data confirm that males with CS and PFO contravene the otherwise consistent pattern that AC strokes are more commonly observed than PC strokes in stroke populations. The potential mechanisms underlying this interaction between gender and PFO-status remain to be elucidated.

Background The options for secondary prevention of cryptogenic embolism in patients with pat ent foramen ovale are administration of antithrombotic medications or percutaneous closure of the patent foramen ovale. We investigated whether closure is superior to medical therapy. Methods We performed a multicenter, superiority trial in 29 centers in Europe, Canada, Brazil, and Australia in which the assessors of end points were unaware of the study-group assignments. Patients with a patent foramen ovale and is che mic stroke, transient is che mic attack (TIA), or a peripheral thromboembolic event were randomly as signed to undergo closure of the patent foramen ovale with the Amplatzer PFO Occluder or to receive medical therapy. The primary end point was a composite of death, nonfatal stroke, TIA, or peripheral embolism. Analysis was performed on data for the intention-to-treat population. Results The mean duration of follow-up was 4.1 years in the closure group and 4.0 years in the medical-therapy group. The primary end point occurred in 7 of the 204 patients (3.4%) in the closure group and in 11 of the 210 patients (5.2%) in the medicaltherapy group (hazard ratio for closure vs. medical therapy, 0.63; 95% confidence interval [CI], 0.24 to 1.62; P = 0.34). Nonfatal stroke occurred in 1 patient (0.5%) in the closure group and 5 patients (2.4%) in the medical-therapy group (hazard ratio, 0.20; 95% CI, 0.02 to 1.72; P = 0.14), and TIA occurred in 5 patients (2.5%) and 7 patients (3.3%), respectively (hazard ratio, 0.71; 95% CI, 0.23 to 2.24; P = 0.56). Conclusions Closure of a patent foramen ovale for secondary prevention of cryptogenic embolism did not result in a significant reduction in the risk of recurrent embolic events or death as compared with medical therapy. (Funded by St. Jude Medical; ClinicalTrials .gov number, NCT00166257.)

The study set out to identify clinical, laboratory and radiological predictors of early mortality after an acute ischaemic stroke (AIS) and to analyse medical and neurological complications that caused death.A total of 479 consecutive patients (mean age 63+/-14 years) with AIS underwent stroke examination and treatment. Examination included clinical evaluation, laboratory tests, and brain CT and/or MRI. Follow-up data at 30 days were available for 467 patients (93%) who were included in the present analysis.The median National Institute of Health Stroke Study (NIHSS) score on admission was 6. A total of 62 patients (13%) died within 30 days. The cause of death was the initial event in 43 (69%), pneumonia in 12 (19%), intracerebral haemorrhage in 9 (15%), recurrent stroke in 6 (10%), myocardial infarction in 2 (3%), and cancer in 1 (2%) of the patients. In univariate comparisons, advanced age (p0.001), hypertension (p=0.013), coronary disease (p=0.001), NIHSS score (p0.001), undetermined stroke etiology (p=0.031), relevant co-morbidities (p=0.008), hyperglycemia (p0.001), atrial fibrillation (p0.001), early CT signs of ischemia (p0.001), dense artery sign (p0.001), proximal vessel occlusion (p0.001), and thrombolysis (p=0.008) were associated with early mortality. In multivariate analysis, advanced age (HR=1.12; 95% CI 1.05-1.19; p0.001) and high NIHSS score on admission (HR=1.15, 95% CI 1.05-1.25; p=0.002) were independent predictors of early mortality.We report 13% mortality at 30 days after AIS. More than two thirds of the deaths are related to the initial stroke. Advanced age and high NIHSS score are the only independent predictors of early mortality in this series.

We set out to investigate the predictors and time course for recanalization of spontaneous dissection of the cervical internal carotid artery (SICAD).We prospectively included 249 consecutive patients (mean age, 45+/-11 years) with 268 SICAD. Ultrasound examinations were performed at presentation, during the first month, and then at 3, 6, and 12 months, and clinical follow-ups after 3, 6, and 12 months.Of 268 SICADs, 20 (7.5%) presented withor=50% stenosis, 31 (11.6%) with 51% to 80% stenosis, 92 (34.3%) with 81% to 99% stenosis, and 125 (46.6%) with an occlusion. Antithrombotic treatment included anticoagulation in 174 (67%) patients, aspirin in 64 (24%) patients, and aspirin followed by anticoagulation or vice versa in 22 (8%) patients. Follow-up ultrasound showed normal findings in 160 (60%),or=50% stenosis in 27 (10%), 51% to 80% stenosis in 4 (1%), 81% to 99% stenosis in 26 (10%), and occlusion in 51 (19%) vessels. The rate of complete recanalization was 16% at 1 month, 50% at 3 months, and 60% at 6 and 12 months. Initial occlusion of the dissected vessels reduced the odds of recanalization (OR, 4.0; 95% CI, 2.2-7.3; P0.001), whereas the occurrence of local symptoms and signs only at presentation were independently associated with complete recanalization (OR, 0.4; 95% CI, 0.2-0.8; P=0.048).These results suggest that recanalization of SICAD occurs mainly within the first 6 months after the onset of symptoms. Initial occlusion reduces the likelihood of complete recanalization, whereas presentation with local symptoms and signs only increases it.

Imaging has become increasingly important for diagnosis and treatment of disorders in neurology and neurosurgery. Often, however, physicians are uncertain which imaging modality to chose for diagnosis and which techniques can be used to help for treatment. To answer a specific question clinicians have to rely on history and clinical findings. According to a cardinal clinical symptom or sign the imaging technique with the highest sensitivity and specificity for the given problem is chosen. In this review imaging techniques for the most common cardinal symptoms and signs in neurology and neurosurgery which need imaging for management are discussed.

We sought to assess the safety and clinical efficacy of patent foramen ovale (PFO) closure under fluoroscopic guidance only, without intraprocedural echocardiography.Percutaneous PFO closure has been shown to be safe and feasible using several devices. It is generally performed using simultaneously fluoroscopic and transesophageal or intracardiac echocardiographic guidance. Transesophageal echocardiography requires sedation or general anesthesia and intubation to avoid aspiration. Intracardiac echocardiography is costly and has inherent risks. Both lengthen the procedure. The Amplatzer PFO Occluder (AGA Medical Corporation, Golden Valley, Minnesota) can be safely implanted without echocardiographic guidance.A total of 620 patients (51 +/- 12 years; 66% male) underwent PFO closure using the Amplatzer PFO Occluder for secondary prevention of presumed paradoxical embolism. Based on size and mobility of the PFO and the interatrial septum, an 18-mm device was used in 50 patients, a 25-mm device in 492, and a 35-mm device in 78.All procedures were successful, with 5 procedural complications (0.8%): 4 arteriovenous fistulae requiring elective surgical correction, and 1 transient ischemic attack. Contrast transesophageal echocardiography at 6 months showed complete closure in 91% of patients, whereas a minimal, moderate, or large residual shunt persisted in 6%, 2%, and 1%, respectively. During a mean follow-up period of 3.0 +/- 1.9 years (median: 2.6 years; total patient-years: 1,871), 5 ischemic strokes, 8 transient ischemic attacks, and no peripheral emboli were reported. Freedom from recurrent ischemic stroke, transient ischemic attack, or peripheral embolism was 99% at 1 year, 99% at 2 years, and 97% at 5 years.The Amplatzer PFO Occluder affords excellent safety and long-term clinical efficacy of percutaneous PFO closure without intraprocedural echocardiography.

The suspected cause of clinical manifestations of patent foramen ovale (PFO) is a transient or a permanent right-to-left shunt (RLS). Contrast-enhanced transcranial Doppler ultrasound (c-TCD) is a reliable alternative to transesophageal echocardiography (TEE) for diagnosis of PFO, and enables also the detection of extracardiac RLS. The air-containing echo contrast agents are injected intravenously and do not pass the pulmonary circulation. In the presence of RLS, the contrast agents bypass the pulmonary circulation and cause microembolic signals (MES) in the basal cerebral arteries, which are detected by TCD. The two main echo contrast agents in use are agitated saline and D-galactose microparticle solutions. At least one middle cerebral artery (MCA) is insonated, and the ultrasound probe is fixed with a headframe. The monitored Doppler spectra are stored for offline analysis (e.g., videotape) of the time of occurrence and number of MES, which are used to assess the size and functional relevance of the RLS. The examination is more sensitive, if both MCAs are investigated. In the case of negative testing, the examination is repeated using the Valsalva maneuver. Compared to TEE, c-TCD is more comfortable for the patient, enables an easier assessment of the size and functional relevance of the RLS, and allows also the detection of extracardiac RLS. However, c-TCD cannot localize the site of the RLS. Therefore, TEE and TCD are complementary methods and should be applied jointly in order to increase the diagnostic accuracy for detecting PFO and other types of RLS.

ObjectivesThis study sought to investigate the safety and efficacy of transcatheter treatment of atrial septal aneurysm (ASA) associated with patent foramen ovale (PFO).BackgroundPatients with both ASA and PFO are at high risk for recurrent paradoxical embolism.MethodsThe procedural, echocardiographic, and clinical outcomes of 141 patients with ASA + PFO and ≥1 paradoxical embolic event undergoing transcatheter treatment were compared with 220 patients with PFO alone.ResultsDevice success (ASA + PFO, 99.3%; PFO alone, 99.5%; p = 0.75) and procedural complications (ASA + PFO, 0.7%; PFO alone, 3.2%; p = 0.12) were similar in both groups. Maximal atrial septal excursion in patients with ASA + PFO decreased from 16 ± 4 mm before to 4 ± 3 mm after the intervention (p < 0.0001). At 6 months follow-up, right-to-left shunt was abolished in 120 (86%) patients with ASA + PFO, compared to 187 (85%) patients with PFO alone (p = 0.80). Freedom from recurrent transient ischemic attack, stroke, and peripheral embolism at 4 years was 95% (ASA + PFO) and 94% (PFO alone, p = 0.70), respectively. A residual right-to-left shunt after the intervention was the only predictor for recurrence (hazard ratio [HR] 6.9; 95% confidence interval [CI] 1.3 to 36.9, p < 0.03) in patients with ASA + PFO.ConclusionsTranscatheter treatment of ASA + PFO is safe and effective in patients with paradoxical embolism. The procedure effectively abolishes right-to-left shunt and decreases atrial septal mobility. Long-term prevention of recurrent events appears favorable when compared to patients with PFO alone.

Transcranial Doppler sonography (TCD) is an established method for assessing changes in blood flow velocity (BFV) coupled to brain activity. Our objective was to investigate whether walking induces measurable changes in BFV in healthy subjects.Changes in BFV in both middle cerebral arteries (MCAs) of 40 healthy adult subjects during walking on a treadmill were measured using bilateral TCD. In 8 of the 40 subjects, 1 anterior cerebral artery (ACA) was monitored simultaneously with the contralateral MCA. The percentage increase in BFV (BFVI%) compared with the baseline velocity (V(0)), the percentage decrease in BFV (BFVD%) compared with the V(0), and the normalized ACA-MCA ratio were analyzed.The overall mean (+/- standard deviation [SD]) V(0) was 59.9 +/- 11.6 cm/second in the left MCA and 60.1 +/- 12.9 cm/second in the right MCA. Women had higher V(0) values than men had. Walking evoked an initial mean overall BFVI% in both left (8.4 +/- 5.1%) and right MCAs (9.1 +/- 5.1%), followed by a decrease to below baseline values in 38 of 40 subjects. A statistically significant increase of the normalized ACA-MCA ratio was measured, indicating that changes in BFV in the ACA territory were coupled to brain activation during walking.The use of functional TCD showed different changes in BFV in the ACAs and MCAs during walking. This method may be an interesting tool for monitoring progress in patients with motor deficits of the legs, such as paresis.