Location-weighted versus Volume-weighted Mismatch at MRI for Response to Mechanical Thrombectomy in Acute Stroke.

Background A target mismatch profile can identify good clinical response to recanalization after acute ischemic stroke, but does not consider region specificities. Purpose To test whether location-weighted infarction core and mismatch, determined from diffusion and perfusion MRI performed in patients with acute stroke, could improve prediction of good clinical response to mechanical thrombectomy compared with a target mismatch profile. Materials and Methods In this secondary analysis, two prospectively collected independent stroke data sets (2012-2015 and 2017-2019) were analyzed. From the brain before stroke (BBS) study data (data set 1), an eloquent map was computed through voxel-wise associations between the infarction core (based on diffusion MRI on days 1-3 following stroke) and National Institutes of Health Stroke Scale (NIHSS) score. The French acute multimodal imaging to select patients for mechanical thrombectomy (FRAME) data (data set 2) consisted of large vessel occlusion-related acute ischemic stroke successfully recanalized. From acute MRI studies (performed on arrival, prior to thrombectomy) in data set 2, target mismatch and eloquent (vs noneloquent) infarction core and mismatch were computed from the intersection of diffusion- and perfusion-detected lesions with the coregistered eloquent map. Associations of these imaging metrics with early neurologic improvement were tested in multivariable regression models, and areas under the receiver operating characteristic curve (AUCs) were compared. Results Data sets 1 and 2 included 321 (median age, 69 years [IQR, 58-80 years]; 207 men) and 173 (median age, 74 years [IQR, 65-82 years]; 90 women) patients, respectively. Eloquent mismatch was positively and independently associated with good clinical response (odds ratio [OR], 1.14; 95% CI: 1.02, 1.27; P = .02) and eloquent infarction core was negatively associated with good response (OR, 0.85; 95% CI: 0.77, 0.95; P = .004), while noneloquent mismatch was not associated with good response (OR, 1.03; 95% CI: 0.98, 1.07; P = .20). Moreover, adding eloquent metrics improved the prediction accuracy (AUC, 0.73; 95% CI: 0.65, 0.81) compared with clinical variables alone (AUC, 0.65; 95% CI: 0.56, 0.73; P = .01) or a target mismatch profile (AUC, 0.67; 95% CI: 0.59, 0.76; P = .03). Conclusion Location-weighted infarction core and mismatch on diffusion and perfusion MRI scans improved the identification of patients with acute stroke who would benefit from mechanical thrombectomy compared with the volume-based target mismatch profile. Clinical trial registration no. NCT03045146 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Nael in this issue.

Etiologic and prognostic value of external carotid artery thrombus detection during endovascular therapy for anterior circulation proximal occlusions.

BACKGROUND AND PURPOSE: An early understanding of stroke mechanism may improve treatment and outcome in patients presenting with large vessel occlusion stroke (LVOS) treated with mechanical thrombectomy (MT). We aimed to investigate whether spontaneous external carotid artery (ECA) embolism detection during MT is associated with stroke etiology and clinical outcome. METHODS: We retrospectively reviewed our prospectively maintained institutional database including consecutive patients with anterior circulation LVOS treated with MT between January 2015 and August 2020. RESULTS: An ECA embolus was detected in 68 of 1298 patients (5.2%). The kappa coefficient for interobserver agreement was 0.89 (95% confidence interval [CI] 0.82-0.95). ECA embolism was significantly associated with intracranial internal carotid artery (ICA) occlusion (p < 0.001), cardioembolic etiology (p < 0.001) and a lower clot burden score (p < 0.001). Day-1 variation of National Institutes of Health Stroke Scale score (adjusted odds ratio [OR] -2.7, 95% CI -4.9 to 0.3; p = 0.021) and delta Alberta Stroke Program Early Computed Tomography Score (adjusted OR 0.9, 95% CI 0.2 to 1.5; p = 0.004) were worse among patients with ECA emboli. There was no significant difference in 90-day functional outcome between groups (adjusted OR 0.8, 95% CI 0.42 to 1.52; p = 0.50). CONCLUSION: In patients with anterior circulation LVOS treated with MT, ECA embolism was significantly associated with cardioembolic etiology, high thrombus burden and proximal intracranial ICA occlusions. This underexplored angiographic pattern might provide a valuable etiologic clue to the underlying cause of anterior circulation LVOS and may also help determine the appropriate revascularization strategy.

Early multidisciplinary prevention program of post-stroke shoulder pain: A randomized clinical trial.

OBJECTIVE: To evaluate if positioning the upper-limb promoting abduction, external rotation and flexion of the shoulder reduces the intensity of post-stroke shoulder pain at day-7 compared to usual clinical practice. DESIGN & SETTING: Prospective single-center randomized clinical trial using a superiority design comparing two preventive strategies of post-stroke shoulder pain in a stroke unit. SUBJECTS: Patients were included within 2 days from a first symptomatic ischemic stroke affecting shoulder motor function. INTERVENTIONS: Intervention group included specific positioning of the shoulder in abduction, external rotation and flexion in bed, chair and during mobilization. Control group referred to usual practice i.e. positioning using a standard support scarf. MAIN MEASURES: Primary outcome was the intensity of shoulder pain assessed by the visual analog scale (VAS) (0-100) at day-7 post-stroke. Other outcomes measured at day-7 and 2 months post-stroke were the VAS, motor function, spasticity, depression, functional independence and rates of complex regional Pain syndrome (CRPS). RESULTS: 76 patients (49 males; mean age = 68.3) were randomized. The shoulder pain at day-7 was not different between the control group (16.1, SD = 27.4) and the intervention group (10.3, SD = 21.5, p = 0.18) as well as at 2 months (p = 0.12). A lower rate of depression was observed in the intervention group at 2 months 36.7% (CI95% 19.9;56.1) vs 52.9% (CI95% 35.1;70.2). No between-group difference in other outcomes was observed at 2 months. CONCLUSIONS: This study failed to demonstrate the benefit of a specific positioning tool in reducing the intensity of post-stroke shoulder pain which was lower than previously reported in the literature.

Severity of Small Vessel Disease Biomarkers Reduces the Magnitude of Cognitive Recovery after Ischemic Stroke.

OBJECTIVE: The objective of this study was to evaluate the impact of radiological biomarkers suggestive of cerebral small vessel disease (SVD) on the evolution of cognitive performances after an ischemic stroke (IS). METHODS: We studied patients with a supratentorial IS recruited consecutively to a prospective monocentric longitudinal study. A cognitive assessment was performed at baseline, 3 months, and 1 year and was based on a Montreal Cognitive Assessment, an Isaacs set test of verbal fluency (IST), and a Zazzo's cancellation task (ZCT) for the evaluation of attentional functions and processing speed. The following cerebral SVD biomarkers were detected on a 3-T brain MRI performed at baseline: white matter hyperintensities (WMHs), deep and lobar microbleeds, enlarged perivascular spaces in basal ganglia and centrum semiovale, previous small deep infarcts, and cortical superficial siderosis (cSS). Generalized linear mixed models were used to evaluate the relationship between these biomarkers and changes in cognitive performances. RESULTS: A total of 199 patients (65 ± 13 years, 68% male) were analyzed. Overall, the cognitive performances improved, more significantly in the first 3 months. Severe WMH was identified in 34% of the patients, and focal cSS in 3.5%. Patients with severe WMH and focal cSS had overall worse cognitive performances. Those with severe WMH had less improvement over time for IST (ß = -0.16, p = 0.02) and the number of errors to ZCT (ß = 0.19, p = 0.02), while those with focal cSS had less improvement over time for ZCT completion time (ß = 0.14, p = 0.01) and number of errors (ß = 0.17, p = 0.008), regardless of IS volume and location, gray matter volume, demographic confounders, and clinical and cardiovascular risk factors. CONCLUSION: The severity of SVD biomarkers, encompassing WMH and cSS, seems to reduce the magnitude of cognitive recovery after an IS. The detection of such SVD biomarkers early after stroke might help to identify patients with a cognitive vulnerability and a higher risk of poststroke cognitive impairment.

Antiplatelet therapy increases symptomatic ICH risk after thrombolysis and thrombectomy.

BACKGROUND AND PURPOSE: The influence of chronic treatment by antiplatelet drug (APD) at stroke onset on the outcomes of patients with acute ischemic stroke (AIS) treated with combined intravenous thrombolysis (IVT) and endovascular therapy (EVT) is unclear. We investigated whether prior APD use influences the risk of symptomatic intracranial hemorrhage (sICH) and functional outcome in AIS patients treated with combined reperfusion therapy. METHODS: A single-center retrospective analysis of AIS patients with proximal intracranial occlusion who underwent IVT and EVT between January 2015 and May 2017. The main outcomes were the incidence of sICH using the Heidelberg Bleeding Classification and patients' functional status at 90 days, as defined by the modified Rankin scale (mRS). Outcomes were evaluated according to daily exposure to APD, and associations were assessed using multivariate logistic regression analysis. RESULTS: This study included 204 patients: 71 (34.8%) were taking APD before AIS. Patients with chronic treatment by APD at stroke onset had a higher rate of sICH (26.7% vs. 3.7%; p< .001) and worse functional outcome (mRS >2) at 90 days (69% vs. 36.8%; p < .001). Prior APD use was associated with an increased likelihood of sICH (OR 9.8; 95%CI [3.6-31.3], p < .05) and of functional dependence at 90 days (OR 5.72; 95%CI [2.09-1.72], p < .001), independent of confounders on multivariate analysis. CONCLUSIONS: Chronic treatment by APD at stroke onset in AIS patients with proximal intracranial occlusion treated using IVT and EVT increases the risk of sICH and worsens the functional prognosis. Further investigation to refine acute revascularization strategies in this population might be required.

Normal-Appearing White Matter Integrity Is a Predictor of Outcome After Ischemic Stroke.

Background and Purpose- The aim of the present study was to evaluate the relationship between normal-appearing white matter (NAWM) integrity and postischemic stroke recovery in 4 main domains including cognition, mood, gait, and dependency. Methods- A prospective study was conducted, including patients diagnosed for an ischemic supratentorial stroke on a 3T brain MRI performed 24 to 72 hours after symptom onset. Clinical assessment 1 year after stroke included a Montreal Cognitive Assessment, an Isaacs set test, a Zazzo cancelation task, a Hospital Anxiety and Depression scale, a 10-meter walking test, and a modified Rankin Scale (mRS). Diffusion tensor imaging parameters in the NAWM were computed using FMRIB (Functional Magnetic Resonance Imaging of the Brain) Diffusion Toolbox. The relationships between mean NAWM diffusion tensor imaging parameters and the clinical scores were assessed using linear and ordinal regression analyses, including the volumes of white matter hyperintensities, gray matter, and ischemic stroke as radiological covariates. Results- Two hundred seven subjects were included (66±13 years old; 67% men; median National Institutes of Health Stroke Scale score, 3; interquartile range, 2-6). In the models including only radiological variables, NAWM fractional anisotropy was associated with the mRS and the cognitive scores. After adjusting for demographic confounders, NAWM fractional anisotropy remained a significant predictor of mRS (ß=-0.24; P=0.04). Additional path analysis showed that NAWM fractional anisotropy had a direct effect on mRS (ß=-0.241; P=0.001) and a less important indirect effect mediating white matter hyperintensity burden. Similar results were found with mean diffusivity, axial diffusivity, and radial diffusivity. In further subgroup analyses, a relationship between NAWM integrity in widespread white matter tracts, mRS, and Isaacs set test was found in right hemispheric strokes. Conclusions- NAWM diffusion tensor imaging parameters measured early after an ischemic stroke are independent predictors of functional outcome and may be additional markers to include in studies evaluating poststroke recovery.

Chronic Cortical Cerebral Microinfarcts Slow Down Cognitive Recovery After Acute Ischemic Stroke.

Background and Purpose- Cortical cerebral microinfarcts (CMIs) have been associated with vascular dementia and Alzheimer disease. The aim of the present study was to evaluate the role of cortical CMI detected on 3T magnetic resonance imaging, on the evolution of cognition during the year following an acute ischemic stroke. Methods- We conducted a prospective and monocentric study, including patients diagnosed for a supratentorial ischemic stroke with a National Institutes of Health Stroke Scale score ≥1, without prestroke dementia or neurological disability. Cortical CMIs were assessed on a brain 3T magnetic resonance imaging realized at baseline, as well as markers of small vessel disease, stroke characteristics, and hippocampal atrophy. Cognitive assessment was performed at 3 time points (baseline, 3 months, and 1 year) using the Montreal Cognitive Assessment, the Isaacs set test, and the Zazzo's cancellation task. Generalized linear mixed models were performed to evaluate the relationships between the number of cortical CMI and changes in cognitive scores over 1 year. Results- Among 199 patients (65±13 years old, 68% men), 88 (44%) had at least one cortical CMI. Hypertension was the main predictor of a higher cortical CMI load (B=0.58, P=0.005). The number of cortical CMI was associated with an increase time at the Zazzo's cancellation task over 1 year (B=3.84, P=0.01), regardless of the other magnetic resonance imaging markers, stroke severity, and demographic factors. Conclusions- Cortical CMIs are additional magnetic resonance imaging markers of poorer processing speed after ischemic stroke. These results indicate that a high load of cortical CMI in patients with stroke can be considered as a cerebral frailty condition which counteracts to the recovery process, suggesting a reduced brain plasticity among these patients.

Neurodegeneration of the Substantia Nigra after Ipsilateral Infarct: MRI R2* Mapping and Relationship to Clinical Outcome.

Background The substantia nigra (SN) is suspected to be affected after remote infarction, in view of its large array of connections with the supratentorial brain. Whether secondary involvement of SN worsens overall clinical outcome after a supratentorial stroke has not previously been studied. Purpose To assess longitudinal changes in SN R2* by using MRI in the setting of ipsilesional supratentorial infarct and the relationship of SN signal change to clinical outcome. Materials and Methods Participants prospectively included from 2012 to 2015 were evaluated at 24-72 hours (baseline visit) and at 1 year with MRI to quantify R2*. The SN was segmented bilaterally to calculate an R2* asymmetry index (SN-AI); greater SN-AI indicated greater relative R2* in the ipsilateral compared with contralateral SN. The 95th percentile of R2* (hereafter, SN-AI95) was compared according to infarct location with mixed linear regression models. We also conducted voxel-based comparisons of R2* and identified individual infarcted voxels associated with high SN-AI95 through voxel-based lesion-symptom mapping. Multivariable regression models tested the association between SN-AI95 and clinical scores. Results A total of 181 participants were evaluated (127 men, 54 women; mean age ± standard deviation, 64.2 years ± 13.1; 75 striatum infarcts, 106 other locations). Visual inspection, SN-AI95, and average maps consistently showed higher SN R2* at 1 year if ipsilateral striatum was infarcted than if it was not (SN-AI95, 4.25 vs -0.88; P < .001), but this was not observed at baseline. The striatal location of the infarct was associated with higher SN-AI95 at 1 year independently from infarct volume, SN-AI95 at baseline, microbleeds, age, and sex (ß = 4.99; P < .001). Voxel-based lesion-symptom mapping confirmed that striatum but also insula, internal capsule, and external capsule were associated with higher SN-AI95 at 1 year. SN-AI95 was an independent contributor of poor motor outcome (Box and Block Test, ß = -.62 points; P = .01). Conclusion In patients with stroke, greater substantia nigra R2*, likely reflective of greater iron content, can be observed at 1 year ipsilateral from remote infarcts of specific location, which is associated with worse motor function. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Vernooij in this issue.

The Influence of Stroke Location on Cognitive and Mood Impairment. A Voxel-Based Lesion-Symptom Mapping Study.

BACKGROUND AND PURPOSE: The role of stroke location as a determinant of mood and cognitive symptoms is still a matter of debate. The aim of this study was to identify the predictive value of ischemic stroke location, on a voxel basis, for mood and cognitive outcome. MATERIALS AND METHODS: A prospective monocentric study including patients with a supratentorial ischemic stroke was conducted. A 3 Tesla brain MRI was performed at baseline. Mood and cognition were assessed using Hospital Anxiety and Depression scale (HAD), apathy inventory (AI), and Montreal Cognitive Assessment scale subscores, performed at 3 months poststroke. Statistical maps of ischemic stroke location associated with 3 months mood and cognitive scores were obtained using a voxel-based lesion-symptom mapping approach (Brunner and Munzel test). Significant voxels (false discovery rate [FDR] corrected-P < .01) were identified using the standard Montreal Neurological Institute-152 space template. RESULTS: Two hundred and sixty-five nonsevere stroke patients were included (64% men, mean age 66 ± 14, median National Institute of Health Stroke Score 3, interquartile range 2-6). Ischemic stroke location was not associated with HAD or AI scores. Language, abstraction, and delayed recall performances were mainly associated with left-side hemispheric lesions. Lesions in both hemispheres were associated with lower performances in visuospatial and executive functions, naming, attention, and orientation. CONCLUSION: Ischemic stroke location does not predict mood outcome at 3 months but is a determinant of cognitive outcome in specific domains.

Trendelenburg Positioning in Large Vessel Ischaemic Stroke: A Pre-Post Observational Study Using Propensity Score Matching.

BACKGROUND: Along with pharmacological and mechanical recanalization, improving cerebral perfusion through the recruitment of collateral vessels during the acute phase of ischaemic stroke (IS) is a clinical challenge. Our objective was to assess the effectiveness and safety of Trendelenburg positioning (TP), a procedure intended to increase cerebral blood flow, on the outcome of IS. METHODS: Two cohorts of patients with an acute supratentorial IS related to a large artery occlusion were compared. In the first cohort (n = 119), we used standard positioning (0 to +30°); in the second cohort (n = 90), we used TP (0 to -15°). The primary outcome measure was the improvement of National Institutes of Health Stroke Scale (NIHSS) score between admission and day 2. Factors associated with an improvement ≥4 points of NIHSS score were assessed using multiple logistic regression and propensity score (PS) matching analyses. RESULTS: TP was significantly associated with a greater improvement of NIHSS score within 48 h following stroke onset (4.0 ± 5.7 vs. 1.8 ± 5.9, p = 0.011) but also at discharge (p = 0.005). Multiple logistic regression analysis suggested that TP was an independent predictor of early neurological improvement (adjusted OR 1.81, 95% CI 1.00-3.27) in a model controlling recanalization and haemoglobin level. In addition, PS matching analysis confirmed the possible effectiveness of TP (unadjusted OR 1.99, 95% CI 1.04-3.82), especially in male subjects. The effect of TP was more pronounced in patients with admission mean arterial blood pressure ≥100 mm Hg, those exhibiting a good collateral vessel network on admission CT-angiography or experiencing an effective recanalization. Furthermore, TP was not associated with life-threatening complications. CONCLUSION: TP could be an effective and safe strategy in patients with large IS resulting from the proximal occlusion of a large vessel.

Thalamic alterations remote to infarct appear as focal iron accumulation and impact clinical outcome.

See Duering and Schmidt (doi:10.1093/awx135) for a scientific commentary on this article.Thalamic alterations have been observed in infarcts initially sparing the thalamus but interrupting thalamo-cortical or cortico-thalamic projections. We aimed at extending this knowledge by demonstrating with in vivo imaging sensitive to iron accumulation, one marker of neurodegeneration, that (i) secondary thalamic alterations are focally located in specific thalamic nuclei depending on the initial infarct location; and (ii) such secondary alterations can contribute independently to the long-term outcome. To tackle this issue, 172 patients with an infarct initially sparing the thalamus were prospectively evaluated clinically and with magnetic resonance imaging to quantify iron through R2* map at 24-72 h and at 1-year follow-up. An asymmetry index was used to compare R2* within the thalamus ipsilateral versus contralateral to infarct and we focused on the 95th percentile of R2* as a metric of high iron content. Spatial distribution within the thalamus was analysed on an average R2* map from the entire cohort. The asymmetry index of the 95th percentile within individual nuclei (medio-dorsal, pulvinar, lateral group) were compared according to the initial infarct location in simple and multiple regression analyses and using voxel-based lesion-symptom mapping. Associations between the asymmetry index of the 95th percentile and functional, cognitive and emotional outcome were calculated in multiple regression models. We showed that R2* was not modified at 24-72 h but showed heterogeneous increase at 1 year mainly within the medio-dorsal and pulvinar nuclei. The asymmetry index of the 95th percentile within the medio-dorsal nucleus was significantly associated with infarcts involving anterior areas (frontal P = 0.05, temporal P = 0.02, lenticular P = 0.01) while the asymmetry index of the 95th percentile within the pulvinar nucleus was significantly associated with infarcts involving posterior areas (parietal P = 0.046, temporal P < 0.001) independently of age, gender and infarct volume, which was confirmed by voxel-based lesion-symptom mapping. The asymmetry index of the 95th percentile within the entire thalamus at 1 year was independently associated with poor functional outcome (P = 0.04), poor cognitive outcome (P = 0.03), post-stroke anxiety (P = 0.04) and post-stroke depression (P = 0.02). We have therefore identified that iron accumulates within the thalamus ipsilateral to infarct after a delay with a focal distribution that is strongly linked to the initial infarct location (in relation with the pattern of connectivity between thalamic nuclei and cortical areas or deep nuclei), which independently contributes to functional, cognitive and emotional outcome.

Immune-Thrombotic Thrombocytopenic Purpura is a Rare Cause of Ischemic Stroke in Young Adults: Case Reports and Literature Review.

INTRODUCTION: Immune thrombotic thrombocytopenic purpura (i-TTP), related to acquired ADAMTS-13 dysfunction, can lead to various neurological symptoms including ischemic stroke. To date the clinical, radiological, and biological characteristics of patients having a stroke as the inaugural manifestation of i-TTP are largely unknown. METHODS: Probable immune-TTP was defined by a low ADAMTS-13 activity associated with the presence of ADAMTS-13 inhibitors and/or favorable clinicobiological response under immunological treatments. The clinical, radiological, biological data and outcome under treatment are described in a cohort of 17 patients coming from 3 local cases and a literature review. RESULTS: Fourteen of the 17 patients were female and the mean age was 41 years. None of the patients had the classical pentad of TTP. Only 41% had a combination of thrombocythemia and hemolysis. Stroke was multifocal in 35% and included large artery strokes. No adverse event was observed following intravenous thrombolysis. Refractory and relapsing forms were observed in 47%. DISCUSSION: The clinical, radiological, and biological presentation of patients with stroke as the inaugural presentation of i-TTP is heterogeneous. This diagnosis should be discussed in every young adult with ischemic stroke of undetermined source.

Clinical Predictors of Stroke Mimics in Patients Treated with Recombinant Tissue Plasminogen Activator according to a Normal Multimodal Computed Tomography Imaging.

BACKGROUND: Multimodal computed tomography imaging (MCTI) is increasingly used for rapid assessment of acute stroke. We investigated characteristics and final diagnoses of patients treated with recombinant tissue plasminogen activator (rt-PA) while admission imaging was unremarkable. METHODS: From our prospectively collected stroke database (2013-2016), we identified consecutive patients treated with rt-PA on the basis of an unremarkable brain MCTI and assessed with a 24-hour follow-up brain magnetic resonance imaging (MRI). Demographic data, medical history, score on the 15-item National Institute of Health Stroke Scale, and final diagnosis were considered. Absence of MRI infarction and alternate diagnosis defined stroke mimics (SMs). Univariable and multivariable logistic regression analyses identified factors predictive of SMs. RESULTS: Sixty-eight (47.9%) SMs, 63 (44.4%) strokes, and 11 (7.7%) aborted strokes were found. SMs had more often aphasia (P = .003) and hemianopia (P = .0008), whereas upper limb weakness (ULW) (P = .03) and limb ataxia (P = .002) were more prevalent in strokes. Headache (adjusted odds ratio [Adj. OR], 3.89 [95% confidence interval {CI} 1.44-10.47]), relevant history of epilepsy, migraine, dementia or depression (Adj. OR 3.66 [95% CI 1.31-10.18]), unilateral sensory loss (Adj. OR 2.60 [95% CI 1.05-6.45]), and hemianopia (Adj. OR 4.94 [95% CI 1.46-16.77]) were independent predictors of SMs whereas ULW (Adj. OR 3.16 [95% CI 1.28-7.82]) and ataxia (Adj. OR 3.81 [95% CI 1.43-10.13]) predicted stroke. Sensitivity of hemianopia or aphasia for SMs was 52.9%, with specificity of 84.1%, positive predictive value of 78.3%, and negative predictive value of 62.4%. CONCLUSIONS: Hemianopia and/or aphasia with normal MCTI suggest SMs. Diffusion-weighted MRI might be discussed before rt-PA administration in patients with such a clinical pattern.

Admission Brain Cortical Volume: An Independent Determinant of Poststroke Cognitive Vulnerability.

BACKGROUND AND PURPOSE: Several markers of poststroke cognitive impairment have been reported. The role of brain cortical volume remains uncertain. The aim of this study was to evaluate the influence of brain cortical volume on cognitive outcomes using a voxel-based morphometry approach in subjects without prestroke dementia. METHODS: Ischemic stroke patients were prospectively recruited 24 to 72 hours post stroke (M0). Cognition was evaluated at M0, 3 months, and 1 year (M12) using the Montreal Cognitive Assessment, the Isaacs set test, and the Zazzo's cancellation task. A 3-T brain magnetic resonance imaging was performed at M0. Grey matter (GM) was segmented using Statistical Parametric Mapping 12 software. Association between global GM volume and cognitive score slopes between M0 and M12 was evaluated using a linear mixed model. Correlations between focal GM volumes and changes in cognitive performance were evaluated using Statistical Parametric Mapping 12. RESULTS: Two-hundred forty-eight patients were included (mean age 65±SD 14 years old, 66% men). Global GM volume was significantly associated with changes in Montreal Cognitive Assessment scores (ß=0.01; P=0.04) and in the number of errors on the Zazzo's cancellation task (ß=-0.02; P=0.04) independently of other clinical/radiological confounders. Subjects with lower GM volumes in the left fronto-temporo-insular cortex were more vulnerable to transient Montreal Cognitive Assessment and Isaacs set test impairment. Subjects with lower GM volumes in right temporo-insular cortex, together with basal ganglia, were more vulnerable to transient cognitive impairment on the Zazzo's cancellation task. CONCLUSIONS: Smaller cortical volumes in fronto-temporo-insular areas measured 24 to 72 hours post stroke are associated with cognitive vulnerability in the subacute stroke phase.

Very early social support following mild stroke is associated with emotional and behavioral outcomes three months later.

OBJECTIVE: To investigate whether social contact and support received during hospitalization for acute ischemic stroke predict depression and daily life functioning three months later. DESIGN: Prospective observational study using Ecological Momentary Assessments to evaluate the number of social contacts as well as social support received from family, friends and medical staff within 24 hours following admission for stroke. Patients also monitored depression symptoms and behavior in real-time and in daily life contexts three months later. SETTING: A university hospital acute stroke unit. SUBJECTS: Thirty-four mild ischemic stroke patients. INTERVENTIONS: None. MAIN MEASURES: One-day Ecological Momentary Assessments immediately following stroke collected information concerning perceived social support, number of social contacts and depression symptoms. Ecological Momentary Assessments was repeated three months later and addressed depression levels as well as activities of daily living, such as working, cooking, shopping and housework. RESULTS: The number of social interactions received at hospitalization did not predict three-month outcomes. However, a better quality of moral support from friends and family immediately after stroke was associated with decreases in later depression levels ( p = 0.041) and increases in activities of daily living ( p = 0.011). Material support from friends and family was associated with increases in activities of daily living ( p = 0.012). No effect was observed for support received from medical staff. CONCLUSIONS: Patient perceptions of better support quality, and not quantity, immediately following mild stroke, are associated with better behavioral and emotional outcomes three months later.

Left Atrial Appendage Closure in Patients with Atrial Fibrillation and Previous Intracerebral Hemorrhage.

BACKGROUND: Percutaneous left atrial appendage closure (LAAC) may be considered in patients with atrial fibrillation and contraindication for long-term anticoagulation. This study aimed to assess the safety and efficacy of LAAC followed by single antiplatelet therapy in patients with atrial fibrillation and previous spontaneous intracerebral hemorrhage (ICH). METHODS: In this explorative, prospective, single-center study, consecutive patients who underwent LAAC because of previous spontaneous ICH over a period of 4 years were analyzed. Risks of ischemic strokes and hemorrhagic complications were estimated using the CHA2DS2-VASc and HAS-BLED scores, respectively. Single antiplatelet therapy was given for at least 6 months post implantation. Clinical follow-up included cardiological evaluations at 1, 3, 6, and 12 months, and neurological evaluations at 3 and 12 months. RESULTS: A total of 46 patients underwent LAAC with a mean follow-up of 12 ± 7 months. The observed annual rate of ischemic stroke was 4.35% compared with an expected rate of 7.23% according to the mean risk of the population based on CHA2DS2-VASc score, which translated into a 40% risk reduction. The observed annual rate of major bleeding was 4.35% compared with an expected rate of 8.05% according to the mean risk of the population based on HAS-BLED score, which translated into a 46% risk reduction. CONCLUSIONS: LAAC followed by single antiplatelet therapy is feasible as an alternative to oral anticoagulation in high-risk patients with previous ICH, with an acceptable periprocedural risk. Longer follow-up in a larger number of patients will be needed to establish the effectiveness of LAAC relative to direct oral anticoagulants.

Stroke Location Is an Independent Predictor of Cognitive Outcome.

BACKGROUND AND PURPOSE: On top of functional outcome, accurate prediction of cognitive outcome for stroke patients is an unmet need with major implications for clinical management. We investigated whether stroke location may contribute independent prognostic value to multifactorial predictive models of functional and cognitive outcomes. METHODS: Four hundred twenty-eight consecutive patients with ischemic stroke were prospectively assessed with magnetic resonance imaging at 24 to 72 hours and at 3 months for functional outcome using the modified Rankin Scale and cognitive outcome using the Montreal Cognitive Assessment (MoCA). Statistical maps of functional and cognitive eloquent regions were derived from the first 215 patients (development sample) using voxel-based lesion-symptom mapping. We used multivariate logistic regression models to study the influence of stroke location (number of eloquent voxels from voxel-based lesion-symptom mapping maps), age, initial National Institutes of Health Stroke Scale and stroke volume on modified Rankin Scale and MoCA. The second part of our cohort was used as an independent replication sample. RESULTS: In univariate analyses, stroke location, age, initial National Institutes of Health Stroke Scale, and stroke volume were all predictive of poor modified Rankin Scale and MoCA. In multivariable analyses, stroke location remained the strongest independent predictor of MoCA and significantly improved the prediction compared with using only age, initial National Institutes of Health Stroke Scale, and stroke volume (area under the curve increased from 0.697-0.771; difference=0.073; 95% confidence interval, 0.008-0.155). In contrast, stroke location did not persist as independent predictor of modified Rankin Scale that was mainly driven by initial National Institutes of Health Stroke Scale (area under the curve going from 0.840 to 0.835). Similar results were obtained in the replication sample. CONCLUSIONS: Stroke location is an independent predictor of cognitive outcome (MoCA) at 3 months post stroke.

Early Fiber Number Ratio Is a Surrogate of Corticospinal Tract Integrity and Predicts Motor Recovery After Stroke.

BACKGROUND AND PURPOSE: The contribution of imaging metrics to predict poststroke motor recovery needs to be clarified. We tested the added value of early diffusion tensor imaging (DTI) of the corticospinal tract toward predicting long-term motor recovery. METHODS: One hundred seventeen patients were prospectively assessed at 24 to 72 hours and 1 year after ischemic stroke with diffusion tensor imaging and motor scores (Fugl-Meyer). The initial fiber number ratio (iFNr) and final fiber number ratio were computed as the number of streamlines along the affected corticospinal tract normalized to the unaffected side and were compared with each other. The prediction of motor recovery (ΔFugl-Meyer) was first modeled using initial Fugl-Meyer and iFNr. Multivariate ordinal logistic regression models were also used to study the association of iFNr, initial Fugl-Meyer, age, and stroke volume with Fugl-Meyer at 1 year. RESULTS: The iFNr correlated with the final fiber number ratio at 1 year (r=0.70; P<0.0001). The initial Fugl-Meyer strongly predicted motor recovery (≈73% of initial impairment) for all patients except those with initial severe stroke (Fugl-Meyer<50). For these severe patients (n=26), initial Fugl-Meyer was not correlated with motor recovery (R(2)=0.13; p=ns), whereas iFNr showed strong correlation (R(2)=0.56; P<0.0001). In multivariate analysis, the iFNr was an independent predictor of motor outcome (ß=2.601; 95% confidence interval=0.304-5.110; P=0.031), improving prediction compared with using only initial Fugl-Meyer, age, and stroke volume (P=0.026). CONCLUSIONS: Early measurement of FNr at 24 to 72 hours poststroke is a surrogate marker of corticospinal tract integrity and provides independent prediction of motor outcome at 1 year especially for patients with severe initial impairment.

Interest of Antiplatelet Drug Testing after an Acute Ischemic Stroke.

BACKGROUND: Stroke occurrence despite chronic antiplatelet drug (APD) treatment is frequent. We aimed at evaluating the relevance of platelet aggregation testing in the identification of stroke etiology in this context. METHODS: Patients admitted for a suspected acute ischemic stroke, while under APD (aspirin and/or clopidogrel), were prospectively included. The efficacy of the APD was evaluated using a Multiplate™ assay. Resistance was confirmed using light transmission aggregometry. A standardized diagnostic work-up was performed to identify stroke mechanism according to the TOAST and the ASCO classifications. We evaluated the influence of APD functional status on stroke severity and identified potential determinants of resistance. RESULTS: APD resistance was observed in 53 of the 287 patients (18.5%). No difference in stroke mechanism depending on APD efficacy was observed. Patients sensitive to APD had less severe initial stroke severity (mean National Institutes of Health Stroke Scale 3.9 ± 5.6 vs. 7.2 ± 6.8; p < 0.01). Main determinants for APD resistance were a worse control of the diabetes and higher baseline levels of inflammation (mean CRP 26.4 ± 56.0 vs. 9.3 ± 21.0; p < 0.01). CONCLUSIONS: Platelet function testing does not provide orientation concerning stroke mechanism in patients who were previously on APDs. However, the high frequency of APD resistance and its association with inflammation and stroke severity are confirmed.