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.

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.

Microstructural Gray Matter Integrity Deteriorates After an Ischemic Stroke and Is Associated with Processing Speed.

Microstructural changes after an ischemic stroke (IS) have mainly been described in white matter. Data evaluating microstructural changes in gray matter (GM) remain scarce. The aim of the present study was to evaluate the integrity of GM on longitudinal data using mean diffusivity (MD), and its influence on post-IS cognitive performances. A prospective study was conducted, including supra-tentorial IS patients without pre-stroke disability. A cognitive assessment was performed at baseline and 1 year, including a Montreal Cognitive Assessment, an Isaacs set test, and a Zazzo cancelation task (ZCT): completion time and number of errors. A 3-T brain MRI was performed at the same two time-points, including diffusion tensor imaging for the assessment of GM MD. GM volume was also computed, and changes in GM volume and GM MD were evaluated, followed by the assessment of the relationship between these structural changes and changes in cognitive performances. One hundred and four patients were included (age 68.5 ± 21.5, 38.5% female). While no GM volume loss was observed, GM MD increased between baseline and 1 year. The increase of GM MD in left fronto-temporal regions (dorsolateral prefrontal cortex, superior and medial temporal gyrus, p < 0.05, Threshold-Free Cluster Enhancement, 5000 permutations) was associated with an increase time to complete ZCT, regardless of demographic confounders, IS volume and location, GM, and white matter hyperintensity volume. GM integrity deterioration was thus associated with processing speed slowdown, and appears to be a biomarker of cognitive frailty. This broadens the knowledge of post-IS cognitive impairment mechanisms.

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.

Normal-Appearing White Matter Deteriorates over the Year After an Ischemic Stroke and Is Associated with Global Cognition.

Normal-appearing white matter (NAWM) is a hub of plasticity, but data relating to its influence on post-ischemic stroke (IS) outcome remain scarce. The aim of this study was to evaluate the relationship between NAWM integrity and cognitive outcome after an IS. A longitudinal study was conducted including supra-tentorial IS patients. A 3-Tesla brain MRI was performed at baseline and 1 year, allowing the analyses of mean fractional anisotropy (FA) and mean diffusivity (MD) in NAWM masks, along with the volume of white matter hyperintensities (WMH) and IS. A Montreal Cognitive Assessment (MoCA), an Isaacs set test, and a Zazzo's cancellation task were performed at baseline, 3 months and 1 year. Mixed models were built, followed by Tract-based Spatial Statistics (TBSS) analyses. Ninety-five patients were included in the analyses (38% women, median age 69 ± 20). FA significantly decreased, and MD significantly increased between baseline and 1 year, while cognitive scores improved. Patients who decreased their NAWM FA more over the year had a slower cognitive improvement on MoCA (ß = - 0.11, p = 0.05). The TBSS analyses showed that patients who presented the highest decrease of FA in various tracts of white matter less improved their MoCA performances, regardless of WMH and IS volumes, demographic confounders, and clinical severity. NAWM integrity deteriorates over the year after an IS, and is associated with a cognitive recovery slowdown. The diffusion changes recorded here in patients starting with an early preserved white matter structure could have long term impact on cognition.

The new insights into human brain imaging after stroke.

Over the last two decades, developments of human brain stroke imaging have raised several questions about the place of new MRI biomarkers in the acute management of stroke and the prediction of poststroke outcome. Recent studies have demonstrated the main role of perfusion-weighted imaging in the identification of the best cerebral perfusion profile for a better response after reperfusion therapies in acute ischemic stroke. A major issue remains the early prediction of stroke outcome. While voxel-based lesion-symptom mapping emphasized the influence of stroke location, the analysis of the brain parenchyma underpinning the stroke lesion showed the relevance of prestroke cerebral status, including cortical atrophy, white matter integrity, or presence of chronic cortical cerebral microinfarcts. Moreover, besides the evaluation of the visually abnormal brain tissue, the analysis of normal-appearing brain parenchyma using diffusion tensor imaging and magnetization transfer imaging or spectroscopy offered new biomarkers to improve the prediction of the prognosis and new targets to follow in therapeutic trials. The aim of this review was to depict the main new radiological biomarkers reported in the last two decades that will provide a more thorough prediction of functional, motor, and neuropsychological outcome following the stroke. These new developments in neuroimaging might be a cornerstone in the emerging personalized medicine for stroke patients.

Association between neurological outcome and poststroke comorbid mood and anxiety disorders: A real-life experience.

INTRODUCTION: Poststroke depression (PSD) and anxiety (PSA) are prevalent and have a strong impact on functional outcome. Beside stroke severity, little is known on their clinical determinants. This study investigated the association between stroke mechanism, neurological poststroke complications and remaining vascular risk factors and the presence of comorbid PSD and PSA, termed poststroke emotional distress (PSED). METHODS: This was a retrospective analysis of a prospectively compiled medical records database of consecutive patients evaluated during a follow-up visit 3- to 4-month poststroke. HAD scale was used to define PSED category (PSD+PSA vs. NoPSD+NoPSA). Stroke mechanism and poststroke complications were identified clinically or using appropriate scales. Their association with PSED was tested using a multivariate logistic regression model. RESULTS: The sample included 2,300 patients (male: 64.8%); 19% had a PSED and 56.39% were free of any depression or anxiety. The most frequent poststroke complications were fatigue/fatigability (58.4%), sleep problems (26.7%), and pain (20.4%). While no association was observed between PSED and stroke mechanism, higher functional disability (OR:1.572), lower cognitive abilities (OR:0.953), sleep problems (OR:2.334), pain (OR:1.478), fatigue/fatigability (OR:2.331), and abnormal movements (OR:2.380) were all independent risk factors. Persisting tobacco consumption (OR:1.360) was the only vascular significant risk factor. CONCLUSIONS: The frequency of comorbid PSED remains high (1/5 patient) despite improved awareness of these conditions. The association between poststroke complications and the presence of PSED emphasizes the need for standardized neurological and psychological evaluations at follow-up. These results foster the need to improve the management of addictive behaviors to reduce the burden of PSED.

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.

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.

Delayed Gadolinium Leakage in Ocular Structures: A Potential Marker for Age- and Vascular Risk Factor-Related Small Vessel Disease?

BACKGROUND: Gadolinium leakage in ocular structures (GLOS) was recently observed in fluid-attenuated inversion recovery (FLAIR) images obtained the day after an initial gadolinium injection in stroke patients. The specificity of GLOS to stroke and its mechanisms remain unclear. OBJECTIVE: We investigated the factors associated with GLOS in a cohort of patients presenting with acute neurological deficits. MATERIALS AND METHODS: This retrospective study included consecutive patients admitted to our stroke unit for acute neurological deficit between July 2017 and August 2018 who underwent baseline brain magnetic resonance imaging with the injection of a macrocyclic gadolinium agent and another scan without injection within 72 hours. The patients were separated into a stroke group and a stroke mimic group based on diffusion-weighted images. Gadolinium leakage in ocular structures was defined as a bright signal in the vitreous in follow-up FLAIR compared with baseline FLAIR (pregadolinium). Clinical data were collected together with imaging features from the baseline scans, including the volume of the infarct and of hypoperfusion if applicable, white matter hyperintensities, the number of lacunes, and the number of microbleeds, which were combined to yield a small vessel disease (SVD) score. We compared the prevalence of GLOS in both groups using the χ2 test. In the entire cohort, univariate and multivariate regression models were used to test the associations between GLOS and the collected data. RESULTS: Among the 467 patients included in the study, GLOS was observed in similar proportions in the stroke group (32.2%, 136/422) and the stroke mimic group (28.9%, 13/45; mean difference, 3.3%; 95% confidence interval, -10.9 to 17.6; P = 0.65). In univariate analysis, GLOS was associated with older age, increased prevalence of vascular risk factors, brain imaging features of SVD (white matter hyperintensities, lacunes, microbleeds), as well as with impairment of renal function and increased dose of gadolinium. No associations were found with factors related to stroke, such as its volume, acute treatment, or rate of recanalization. Multivariate analyses showed that aging (P < 0.001), diabetes (P = 0.010), severe renal failure (P = 0.004), and increased dose of gadolinium (P < 0.001) were independent contributors to GLOS. CONCLUSIONS: Gadolinium leakage in ocular structures, which occurs more commonly at higher concentrations of gadolinium, is not specific to stroke and may represent increased permeability of the blood-retinal barrier associated with age- and vascular risk factor-related SVD.

Cerebral Small Vessel Disease MRI Features Do Not Improve the Prediction of Stroke Outcome.

OBJECTIVE: To determine whether the total small vessel disease (SVD) score adds information to the prediction of stroke outcome compared to validated predictors, we tested different predictive models of outcome in patients with stroke. METHODS: White matter hyperintensity, lacunes, perivascular spaces, microbleeds, and atrophy were quantified in 2 prospective datasets of 428 and 197 patients with first-ever stroke, using MRI collected 24 to 72 hours after stroke onset. Functional, cognitive, and psychological status were assessed at the 3- to 6-month follow-up. The predictive accuracy (in terms of calibration and discrimination) of age, baseline NIH Stroke Scale score (NIHSS), and infarct volume was quantified (model 1) on dataset 1, the total SVD score was added (model 2), and the improvement in predictive accuracy was evaluated. These 2 models were also developed in dataset 2 for replication. Finally, in model 3, the MRI features of cerebral SVD were included rather than the total SVD score. RESULTS: Model 1 showed excellent performance for discriminating poor vs good functional outcomes (area under the curve [AUC] 0.915), and fair performance for identifying cognitively impaired and depressed patients (AUCs 0.750 and 0.688, respectively). A higher SVD score was associated with a poorer outcome (odds ratio 1.30 [1.07-1.58], p = 0.0090 at best for functional outcome). However, adding the total SVD score (model 2) or individual MRI features (model 3) did not improve the prediction over model 1. Results for dataset 2 were similar. CONCLUSIONS: Cerebral SVD was independently associated with functional, cognitive, and psychological outcomes, but had no clinically relevant added value to predict the individual outcomes of patients when compared to the usual predictors, such as age and baseline NIHSS.

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.

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.

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.

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.

Gait Change Is Associated with Cognitive Outcome after an Acute Ischemic Stroke.

Background: Cognition and gait have often been studied separately after stroke whereas it has been suggested that these two domains could interact through a cognitive-motor interference. Objective: To evaluate the influence of gait changes on cognitive outcome after an ischemic stroke (IS). Methods: We conducted a prospective and monocentric study including patients admitted for an acute supratentorial IS with a National Institute of Health Stroke Score ≤ 15. Cognition, gait and motor disability were evaluated at baseline, 3 months and 1 year post-stroke, using the Montreal Cognitive Assessment (MoCA), the 10-m walking test (10-MWT) and the Fugl-Meyer motor assessment (FMMA). The effect of changes in 10-MWT over the year of follow-up on MoCA changes was estimated using a generalized linear mixed model with FMMA, age and gender as covariates. Results: Two hundred and Twelve patients were included (71% male, age 64 ± 13 years old). 10-MWT improved from baseline to 1 year (p < 0.001), as did MoCA (p < 0.001) and FMMA (p < 0.001) scores. Ninety-nine patients (47%) had a MoCA <26 at 1 year. Changes in 10-MWT were independently associated with changes in MoCA (ß = -0.2, 95% CI -0.24 to -0.07, Bonferroni-corrected p-value = 0.002). Analyses of MoCA sub-scores suggested that changes in gait performance was associated with changes in executive functions and recall. Conclusion: Gait performance is associated with cognitive outcome after a mild to moderate IS, suggesting that they should be managed together to improve post-stroke independence.