Guillaume Turc

Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke

BACKGROUND Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy. METHODS In a multicenter, randomized, open‐label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long‐term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet‐only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3. RESULTS A total of 663 patients underwent randomization and were followed for a mean (±SD) of 5.3±2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet‐only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet‐only group (4.6% vs. 0.9%, P=0.02). The number of serious adverse events did not differ significantly between the treatment groups (P=0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone. CONCLUSIONS Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation. (Funded by the French Ministry of Health; CLOSE ClinicalTrials.gov number, NCT00562289.)

DWI Lesions and TIA Etiology Improve the Prediction of Stroke After TIA

Background and Purpose— The ABCD2 score has been shown to predict the early risk of stroke after transient ischemic attack (TIA). The additional predictive value of diffusion-weighted imaging (DWI) and TIA etiology is not well known. Methods— From January 2003 to June 2007, 343 consecutive patients (mean±SD age, 62.4±15.4 years) with TIA were admitted to our stroke unit. Most (339) patients underwent DWI and all had an etiologic work-up and were followed up for 3 months. The predictive value of the ABCD2 score, positive DWI findings, large-artery atherosclerosis (LAA), and atrial fibrillation (AF) with respect to occurrence of ischemic stroke at 1 week and 3 months was assessed. Results— DWI was positive in 136 (40%) patients. Sixty (17%) patients had LAA and 27 (8%) had AF. Patients with positive DWI findings were more likely to have unilateral weakness (odds ratio [OR]=2.2; 95% CI, 1.3 to 3.7), TIA duration ≥60 minutes (OR=2.6; 95% CI, 1.3 to 5.2), ABCD2 >5 (OR=4.7; 95% CI, 2.0 to 11.0), LAA (OR=1.8; 95% CI, 1.0 to 3.1), and AF (OR=3.5; 95% CI, 1.5 to 8.0). During follow-up, 5 patients had a stroke within 7 days (absolute risk=1.5%, 95% CI, 0.3% to 2.7%), and 10 had a stroke within 3 months (absolute risk=2.9%; 95% CI, 1.1% to 4.7%). All early strokes but 1 occurred in patients with positive DWI findings. ABCD2 score and positive DWI findings were associated with an increased 7-day and 3-month risk of stroke. At 3 months, ABCD2 score >5 (hazard ratio=10.1; 95% CI, 1.1 to 93.4), positive DWI result (hazard ratio=8.7; 95% CI, 1.1 to 71.0), and LAA (hazard ratio=3.4; 95% CI, 1.0 to 11.8) were independently associated with an increased risk of stroke. There was no association with AF. Conclusions— Taking DWI and TIA etiology into account in addition to the ABCD2 score improves the prediction of the early risk of stroke after TIA.

Diffusion Lesion Reversal After Thrombolysis: A MR Correlate of Early Neurological Improvement

Background and Purpose— In acute stroke, diffusion-weighted imaging (DWI) lesions are commonly considered markers of irreversible ischemia yet can occasionally reverse. However, the extent and clinical correlates of DWI reversal in thrombolyzed patients remain unclear. We assessed the extent of reversible acute DWI lesions (RADs) and their relationships with clinical outcome in patients thrombolyzed ⩽4.5 hours from onset. Methods— Data were retrospectively analyzed. RAD was defined as an acute DWI lesion not part of a 24-hour DWI lesion as determined voxelwise. Associations with an early neurological improvement (early neurological improvement=&Dgr;National Institutes of Health Stroke Scale ≥8 or National Institutes of Health Stroke Scale ⩽2 at 24 hours) or an excellent outcome (modified Rankin Scale ⩽1) were assessed in multivariate analyses. Results— One hundred seventy-six patients were included. The median (interquartile range) time to treatment from onset was 150 minutes (120–194). Eighty-nine patients (50%) exhibited visually-detectable RAD irrespective of its extent. Over the whole population, the median percentage and volume of RAD were 11% (4–36) and 2.4mL (0.5–8). Subtracting RAD from initial DWI altered perfusion-weighted imaging–DWI classification in 5 of 100 patients (shift from “no mismatch” to “mismatch” profile in all). Percent RAD was significantly greater in patients treated ⩽3 hours (P=0.049), without proximal occlusion (P=0.003), and in 24-hour recanalizers (P<0.001). Early neurological improvement was independently associated with percent RAD. This association increased with percent RAD split in quartiles in a “dose-dependent” manner (P for trend=0.01). Excellent outcome was independently associated with percent RAD (P for trend <0.001). Conclusion— DWI reversal was often sizeable in patients treated ⩽4.5 hours. It was strongly associated with, albeit not necessarily causal for, early neurological improvement.

Clinical Scales Do Not Reliably Identify Acute Ischemic Stroke Patients With Large-Artery Occlusion

Background and Purpose— It remains debated whether clinical scores can help identify acute ischemic stroke patients with large-artery occlusion and hence improve triage in the era of thrombectomy. We aimed to determine the accuracy of published clinical scores to predict large-artery occlusion. Methods— We assessed the performance of 13 clinical scores to predict large-artery occlusion in consecutive patients with acute ischemic stroke undergoing clinical examination and magnetic resonance or computed tomographic angiography ⩽6 hours of symptom onset. When no cutoff was published, we used the cutoff maximizing the sum of sensitivity and specificity in our cohort. We also determined, for each score, the cutoff associated with a false-negative rate ⩽10%. Results— Of 1004 patients (median National Institute of Health Stroke Scale score, 7; range, 0–40), 328 (32.7%) had an occlusion of the internal carotid artery, M1 segment of the middle cerebral artery, or basilar artery. The highest accuracy (79%; 95% confidence interval, 77–82) was observed for National Institute of Health Stroke Scale score ≥11 and Rapid Arterial Occlusion Evaluation Scale score ≥5. However, these cutoffs were associated with false-negative rates >25%. Cutoffs associated with an false-negative rate ⩽10% were 5, 1, and 0 for National Institute of Health Stroke Scale, Rapid Arterial Occlusion Evaluation Scale, and Cincinnati Prehospital Stroke Severity Scale, respectively. Conclusions— Using published cutoffs for triage would result in a loss of opportunity for ≥20% of patients with large-artery occlusion who would be inappropriately sent to a center lacking neurointerventional facilities. Conversely, using cutoffs reducing the false-negative rate to 10% would result in sending almost every patient to a comprehensive stroke center. Our findings, therefore, suggest that intracranial arterial imaging should be performed in all patients with acute ischemic stroke presenting within 6 hours of symptom onset.

Risk of Symptomatic Intracerebral Hemorrhage After Intravenous Thrombolysis in Patients With Acute Ischemic Stroke and High Cerebral Microbleed Burden: A Meta-analysis.

IMPORTANCE Cerebral microbleeds (CMBs) have been established as an independent predictor of cerebral bleeding. There are contradictory data regarding the potential association of CMB burden with the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT). OBJECTIVE To investigate the association of high CMB burden (>10 CMBs on a pre-IVT magnetic image resonance [MRI] scan) with the risk of sICH following IVT for AIS. DATA SOURCES Eligible studies were identified by searching Medline and Scopus databases. No language or other restrictions were imposed. The literature search was conducted on October 7, 2015. This meta-analysis has adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal. STUDY SELECTION Eligible prospective study protocols that reported sICH rates in patients with AIS who underwent MRI for CMB screening prior to IVT. DATA EXTRACTION AND SYNTHESIS The reported rates of sICH complicating IVT in patients with AIS with pretreatment MRI were extracted independently for groups of patients with 0 CMBs (CMB absence), 1 or more CMBs (CMB presence), 1 to 10 CMBs (low to moderate CMB burden), and more than 10 CMBs (high CMB burden). An individual-patient data meta-analysis was also performed in the included studies that provided complete patient data sets. MAIN OUTCOMES AND MEASURES Symptomatic intracerebral hemorrhage based on the European Cooperative Acute Stroke Study-II definition (any intracranial bleed with ≥4 points worsening on the National Institutes of Health Stroke Scale score). RESULTS We included 9 studies comprising 2479 patients with AIS. The risk of sICH after IVT was found to be higher in patients with evidence of CMB presence, compared with patients without CMBs (risk ratio [RR], 2.36; 95% CI, 1.21-4.61; P = .01). A higher risk for sICH after IVT was detected in patients with high CMB burden (>10 CMBs) when compared with patients with 0 to 10 CMBs (RR, 12.10; 95% CI, 4.36-33.57; P < .001) or 1 to 10 CMBs (RR, 7.01; 95% CI, 3.20-15.38; P < .001) on pretreatment MRI. In the individual-patient data meta-analysis, high CMB burden was associated with increased likelihood of sICH before (unadjusted odds ratio, 31.06; 95% CI, 7.12-135.44; P < .001) and after (adjusted odds ratio, 18.17; 95% CI, 2.39-138.22; P = .005) adjusting for potential confounders. CONCLUSIONS AND RELEVANCE Presence of CMB and high CMB burdens on pretreatment MRI were independently associated with sICH in patients with AIS treated with IVT. High CMB burden may be included in individual risk stratification scores predicting sICH risk following IVT for AIS.

Clot Burden Score on Admission T2*-MRI Predicts Recanalization in Acute Stroke

Background and Purpose— To propose a T2*-MR adaptation of the computed tomography angiography-clot burden score (CBS), and assess its value as predictor of 24-hour recanalization and clinical outcome in anterior circulation stroke treated by intravenous thrombolysis ⩽4.5 hours from onset. Methods— Two independent observers retrospectively analyzed pretreatment T2* images for evaluation of clot burden, using a 10-point scale T2*-CBS. Three points are subtracted for susceptibility vessel sign in the supraclinoid internal carotid artery, 2 points each for susceptibility vessel sign in the proximal and distal part of middle cerebral artery, and 1 point each for susceptibility vessel sign in middle cerebral artery branches (with a maximum of 2 points) and for susceptibility vessel sign in anterior cerebral artery. Associations with 24-hour recanalization and favorable outcome (3-month modified Rankin Scale score, ⩽2) were assessed in multivariate analyses. Results— We analyzed 184 consecutive patients (mean age, 67 years) with median (interquartile range) admission National Institutes of Health Stroke Scale score and onset-to-treatment time of 15 (9–19) and 151 (120–185) minutes, respectively. The intraclass correlation for T2*-CBS between observers was 0.97 (95% confidence interval, 0.97–0.98). In multivariate analyses, T2*-CBS >6 was significantly associated with 24-hour recanalization (adjusted odds ratio, 5.1 [1.9–13.5]; P=0.001) or with favorable outcome (adjusted odds ratio, 4.2 [1.7–10.8]; P=0.003). Conclusions— T2*-CBS, a new reproducible semiquantitative score adapted from the computed tomography angiography-CBS, is associated with 24-hour recanalization and 3-month outcome after intravenous thrombolysis. This score needs external validation and could be useful to identify poor responders to intravenous thrombolysis.

Three-tesla functional MR language mapping: Comparison with direct cortical stimulation in gliomas

Objective: To evaluate the accuracy of functional MRI (fMRI) at 3T, as currently used in the preoperative mapping of language areas, compared with direct cortical stimulation (DCS) during awake surgery, in patients with supratentorial gliomas; and to identify clinical, histopathologic, and radiologic factors associated with fMRI/DCS discrepancies. Methods: Language mapping with fMRI and DCS of 40 consecutive patients with gliomas (24 low-grade, 16 high-grade) in functional areas were retrospectively analyzed. Three block-designed tasks were performed during fMRI (letter word generation, category word generation, semantic association). During awake surgery, eloquent areas were mapped using DCS, blinded to fMRI. A site-by-site comparison of the 2 techniques was performed using a cortical grid. fMRI sensitivity and specificity were calculated using DCS as the reference. Associations of clinical, histopathologic, and radiologic features (including relative cerebral blood volume [rCBV] measured with dynamic susceptibility contrast MRI) with fMRI false-positive and false-negative occurrence were assessed using hierarchical logistic regressions. Results: Of 2,114 stimulated cortical sites, 103 were positive for language during DCS. Sensitivity and specificity of language fMRI combining the 3 tasks reached 37.1% (95% confidence interval [CI] 20.7–57.2) and 83.4% (95% CI 77.1–88.3), respectively. Astrocytoma subtype (odds ratio [OR] 2.50 [1.32–4.76]; p = 0.007), tumor rCBV <1.5 (OR 2.17 [1.08–4.35]; p = 0.03), higher cortical rCBV (OR 2.22 [1.15–4.17]; p = 0.02), and distance to tumor >1 cm (OR 2.46 [1.82–3.32]; p ≤ 0.001) were independently associated with fMRI false-positive occurrence. Conclusions: There are pitfalls in preoperative fMRI as currently used in preoperative language mapping in glioma patients, made more complicated when high-grade and hyperperfused tumors are evaluated.

Incidence, causes and predictors of neurological deterioration occurring within 24 h following acute ischaemic stroke: a systematic review with pathophysiological implications

Early neurological deterioration (END) following ischaemic stroke is a serious event with manageable causes in only a fraction of patients. The incidence, causes and predictors of END occurring within 24 h of acute ischaemic stroke (END24) have not been systematically reviewed. We systematically reviewed Medline and Embase from January 1990 to April 2013 for all studies on END24 following acute ischaemic stroke (<8 h from onset). We recorded the incidence and presumed causes of and factors associated with END24. Thirty-six studies were included. Depending on the definition used, the incidence of END24 markedly varied among studies. Using the most widely used change in National Institutes of Health Stroke Scale ≥4 definition, the pooled incidence was 13.8% following thrombolysis, ascribed to intracranial haemorrhage and malignant oedema each in ∼20% of these. As other mechanisms were rarely reported, in the majority no clear cause was identified. Few data on END24 occurring in non-thrombolysed patients were available. Across thrombolysed and non-thrombolysed samples, the strongest and most consistent admission predictors were hyperglycaemia, no prior aspirin use, prior transient ischaemic attacks, proximal arterial occlusion and presence of early CT changes, and the most consistent 24 h follow-up associated factors were no recanalisation/reocclusion, large infarcts and intracranial haemorrhage. Finally, END24 was strongly predictive of poor outcome. The above findings are discussed with emphasis on END without a clear mechanism. Data on incidence and predictors of the latter subtype is scarce, and future studies using systematic imaging protocols should address its underlying pathophysiology. This may in turn lead to rational preventative and therapeutic measures for this ominous event.

Relationships Between Recent Intraplaque Hemorrhage and Stroke Risk Factors in Patients With Carotid Stenosis The HIRISC Study

Objective—Intraplaque hemorrhage (IPH) is an emerging marker of plaque instability. However, little is known about the relationships between IPH and traditional risk factors and whether these relationships differ between symptomatic and asymptomatic disease. Methods and Results—Two hundred thirty-four patients with symptomatic (n=114) or asymptomatic (n=120) carotid stenosis underwent high-resolution plaque magnetic resonance imaging. Seventy-five patients had recent IPH (symptomatic, 33%; asymptomatic, 31%). In symptomatic stenosis, recent IPH was independently associated with degree of stenosis (odds ratio [OR]=4.21, 1.61–10.98 for North American Symptomatic Carotid Endarterectomy Trial >35%; OR=2.92, 1.18–7.24 for European Carotid Surgery Trial >60%), qualifying event (OR=4.13; 1.11–15.32 for stroke or hemispheric transient ischemic attack ≥1 hour versus transient ischemic attack <1 hour or ocular symptoms), time from ischemic event (OR=6.65, 1.56–28.35 for ⩽2 weeks; OR=2.24, 0.87–5.81 for 2–12 weeks versus >12 weeks; P for trend=0.03). In asymptomatic stenosis, IPH was only associated with stenosis severity >70% by ECST (OR=6.65; 1.95–22.73) but not by the NASCET method. Conclusion—Our findings support the potential link between recent IPH and risk of ipsilateral stroke in symptomatic disease but also imply that prognostic studies should adjust for known stroke risk factors in multivariate analyses. In asymptomatic stenosis, the potential predictive value of recent IPH is less likely to be confounded by stroke risk factors.

Recanalization therapies in acute ischemic stroke patients: impact of prior treatment with novel oral anticoagulants on bleeding complications and outcome

Background— We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC). Methods and Results— This is a multicenter cohort pilot study. Primary outcome measures were (1) occurrence of intracranial hemorrhage (ICH) in 3 categories: any ICH (ICHany), symptomatic ICH according to the criteria of the European Cooperative Acute Stroke Study II (ECASS-II) (sICHECASS-II) and the National Institute of Neurological Disorders and Stroke (NINDS) thrombolysis trial (sICHNINDS); and (2) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range, 8–22 hours). In VKA patients, median pre-IVT/IAT international normalized ratio was 1.3 (interquartile range, 1.1–1.6). ICHany was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICHECASS-II and sICHNINDS occurred in 2.6%/3.9% NOAC patients, in comparison with 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients in comparison with 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistically significant differences. Conclusions— IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both IVT/IAT in patients on subtherapeutic VKA treatment or in those without previous anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests.