Persistent perfusion abnormalities at day 1 correspond to different clinical trajectories after stroke.

BACKGROUND: Perfusion abnormalities after thrombolysis are frequent within and surrounding ischemic lesions, but their relative frequency is not well known. OBJECTIVE: To describe the different patterns of perfusion abnormalities observed at 24 hours and compare the characteristics of the patients according to their perfusion pattern. METHODS: From our thrombolysis registry, we included 226 consecutive patients with an available arterial spin labeling (ASL) perfusion sequence at day 1. We performed a blinded assessment of the perfusion status (hypoperfusion-h, hyperperfusion-H, or normal-N) in the ischemic lesion and in the surrounding tissue. We compared the time course of clinical recovery, the rate of arterial recanalization, and hemorrhagic transformations in the different perfusion profiles. RESULTS: We identified seven different perfusion profiles at day 1. Four of these (h/h, h/H, H/H, and H/N) represented the majority of the population (84.1%). The H/H profile was the most frequent (34.5%) and associated with 3-month good outcome (modified Rankin Scale (mRS): 63.5%). Patients with persistent hypoperfusion within and outside the lesion (h/h, 12.4%) exhibited worse outcomes after treatment (mRS score 0-2: 23.8%) than other patients, were less frequently recanalized (40.7%), and had more parenchymal hematoma (17.8%). The h/H profile had an intermediate clinical trajectory between the h/h profile and the hyperperfused profiles. CONCLUSION: ASL hypoperfusion within the infarct and the surrounding tissue was associated with poor outcome. A more comprehensive view of the mechanisms in the hypoperfused surrounding tissue could help to design new therapeutic approaches during and after reperfusion therapies.

Safety and effectiveness of mechanical thrombectomy for primary isolated distal vessel occlusions: A monocentric retrospective comparative study.

BACKGROUND: Distal vessel occlusions represent about 25-40% of acute ischemic stroke (AIS), either as primary occlusion or secondary occlusion complicating mechanical thrombectomy (MT) for large vessel occlusion. OBJECTIVE: Our aim was to evaluate safety and effectiveness of MT associated with the best medical treatment (BMT) in the management of AIS patients with distal vessel occlusion in comparison with the BMT alone. METHODS: Retrospective analysis was conducted on AIS patients treated by MT+BMT for primary distal vessel occlusion between 2015 and 2020, and were compared with a historic cohort managed by BMT alone between 2006 and 2015 selected based on the same inclusion criteria. A secondary analysis was conducted using propensity score matching (PSM) including the following: NIHSS, age and treatment with intravenous thrombolysis (IVT) as covariates. RESULTS: Of 650 patients screened, 44 patients with distal vessel occlusions treated by MT+BMT were selected and compared with 36 patients who received BMT alone. After PSM, 28 patients in each group were matched without significant difference. Good clinical outcome defined as mRS≤2 was achieved by 53.6% of the MT+BMT group and 57% of the BMT group (OR, 0.87; 95%CI, 0.3-2.4; p = 1.00). The mortality rate was comparable in both groups (7% vs. 10.7% in MT+BMT and BMT patients, respectively; OR=0.64; 95%CI, 0.1-4; p = 1.00). Symptomatic intracranial hemorrhage (ICH) was seen in only one patient treated by MT+BMT (3.6%). CONCLUSION: Mechanical thrombectomy seems to be comparable with the best medical treatment regarding the effectiveness and safety in the management of patients with distal vessel occlusions.

Cognitive Status Predicts Return to Functional Independence After Minor Stroke: A Decision Tree Analysis.

About two-thirds of patients with minor strokes are discharged home. However, these patients may have difficulties returning to their usual living activities. To investigate the factors associated with successful home discharge, our aim was to provide a decision tree (based on clinical data) that could identify if a patient discharged home could return to pre-stroke activities and to perform an external validation of this decision tree on an independent cohort. Two cohorts of patients with minor strokes gathered from stroke registries at the Hôpital Pitié-Salpêtrière and University Hospital Bern were included in this study (n = 105 for the construction cohort coming from France; n = 100 for the second cohort coming from Switzerland). The decision tree was built using the classification and regression tree (CART) analysis on the construction cohort. It was then applied to the validation cohort. Accuracy, sensitivity, specificity, false positive, and false-negative rates were reported for both cohorts. In the construction cohort, 60 patients (57%) returned to their usual, pre-stroke level of independence. The CART analysis produced a decision tree with the Montreal Cognitive Assessment (MoCA) as the first decision point, followed by discharge NIHSS score or age, and then by the occupational status. The overall prediction accuracy to the favorable outcome was 80% in the construction cohort and reached 72% accuracy in the validation cohort. This decision tree highlighted the role of cognitive function as a crucial factor for patients to return to their usual activities after a minor stroke. The algorithm may help clinicians to tailor planning of patients' discharge.

Benefit of mechanical thrombectomy in acute ischemic stroke related to calcified cerebral embolus.

PURPOSE: Mechanical thrombectomies (MT) in patients with large vessel occlusion (LVO) related to calcified cerebral embolus (CCE) have been reported, through small case series, being associated with low reperfusion rate and worse outcome, compared to regular MT. The purpose of the MASC (Mechanical Thrombectomy in Acute Ischemic Stroke Related to Calcified Cerebral Embolus) study was to evaluate the incidence of CCEs treated by MT and the effectiveness of MT in this indication. METHODS: The MASC study is a retrospective multicentric (n = 37) national study gathering the cases of adult patients who underwent MT for acute ischemic stroke with LVO related to a CCE in France from January 2015 to November 2019. Reperfusion rate (mTICI ≥ 2B), complication rate and 90-day mRS were systematically collected. We then conducted a systematic review by searching for articles in PubMed, Cochrane Library, Embase and Google Scholar from January 2015 to March 2020. A meta-analysis was performed to estimate clinical outcome at 90 days, reperfusion rate and complications. RESULTS: We gathered data from 35 patients. Reperfusion was obtained in 57% of the cases. Good clinical outcome was observed in 28% of the patients. The meta-analysis retrieved 136 patients. Reperfusion and good clinical outcome were obtained in 50% and 29% of the cases, respectively. CONCLUSION: The MASC study found worse angiographic and clinical outcomes compared to regular thrombectomies. Individual patient-based meta-analysis including the MASC findings shows a 50% reperfusion rate and a 29% of good clinical outcome.

Effect of emergent carotid stenting during endovascular therapy for acute anterior circulation stroke patients with tandem occlusion: A multicenter, randomized, clinical trial (TITAN) protocol.

BACKGROUND AND HYPOTHESIS: There is no consensus on the optimal endovascular management of the extracranial internal carotid artery steno-occlusive lesion in patients with acute ischemic stroke due to tandem occlusion. We hypothesized that intracranial mechanical thrombectomy plus emergent internal carotid artery stenting (and at least one antiplatelet therapy) is superior to intracranial mechanical thrombectomy alone in patients with acute tandem occlusion. STUDY DESIGN: TITAN is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) study. Eligibility requires a diagnosis of acute ischemic stroke, pre-stroke modified Rankin Scale (mRS)≤2 (no upper age limit), National Institutes of Health Stroke Scale (NIHSS)≥6, Alberta Stroke Program Early Computed Tomography Score (ASPECTS)≥6, and tandem occlusion on the initial catheter angiogram. Tandem occlusion is defined as large vessel occlusion (intracranial internal carotid artery , M1 and/or M2 segment) and extracranial severe internal carotid artery stenosis ≥90% (NASCET) or complete occlusion. Patients are randomized in two balanced parallel groups (1:1) to receive either intracranial mechanical thrombectomy plus internal carotid artery stenting (and at least one antiplatelet therapy) or intracranial mechanical thrombectomy alone within 8 h of stroke onset. Up to 432 patients are randomized after tandem occlusion confirmation on angiogram. STUDY OUTCOMES: The primary outcome measure is complete reperfusion rate at the end of endovascular procedure, assessed as a modified Thrombolysis in Cerebral Infarction (mTICI) 3, and ≥4 point decrease in NIHSS at 24 h. Secondary outcomes include infarct growth, recurrent clinical ischemic event in the ipsilateral carotid territory, type and dose of antiplatelet therapy used, mRS at 90 (±15) days and 12 (±1) months. Safety outcomes are procedural complications, stent patency, intracerebral hemorrhage, and death. Economics analysis includes health-related quality of life, and costs utility comparison, especially with the need or not of endarterectomy. DISCUSSION: TITAN is the first randomized trial directly comparing two types of treatment in patients with acute ischemic stroke due to anterior circulation tandem occlusion, and especially assessing the safety and efficacy of emergent internal carotid artery stenting associated with at least one antiplatelet therapy in the acute phase of stroke reperfusion. TRIAL REGISTRATION: ClinicalTrials.gov NCT03978988.

Cangrelor and Stenting in Acute Ischemic Stroke : Monocentric Case Series.

PURPOSE: Cangrelor is an intravenous P2Y12 receptor inhibitor with a rapid onset/offset of action and a short half-life (3-6 min). The objective was to present a preliminary experience regarding the safety and effectiveness using cangrelor, in combination with aspirin, in acute ischemic stroke patients requiring acute stenting. MATERIAL AND METHODS: Retrospective analysis for patients who underwent stenting (intracranial and/or extracranial) in the setting of acute ischemic stroke with cangrelor and aspirin as antiplatelet therapy. RESULTS: Cangrelor was used in 12 patients, 4 (33%) with extracranial stenting, 6 (50%) with intracranial stenting and 2 (17%) with combined extracranial and intracranial stenting. The mean age was 67 years (44-88) and 9 patients (75%) were female. The median National Institutes of Health Stroke Score at admission was 15 (IQR: 8-22). Of the patients, six (50%) received intravenous thrombolysis. All patients (100%) obtained modified thrombolysis in cerebral infarction score ≥2b. Good clinical outcome, defined as modified Rankin scale score ≤2 at 3­months follow-up, was observed in 7 patients (58%). None of the patients experienced intraprocedural thromboembolic complications. Postprocedural stent thrombosis after cessation of cangrelor infusion due to emergency craniotomy surgery to manage malignant cerebral infarction occurred in one patient (8%). Of the patients, two (17%) experienced asymptomatic intracranial hemorrhage (ICH), one patient (8%) experienced symptomatic ICH and one (8%) retroperitoneal hematoma was observed, which was managed conservatively. CONCLUSION: Cangrelor might be a safe and effective antiplatelet medication owing to its on/off activity for acute stenting in the setting of acute ischemic stroke. Further investigations through randomized studies with larger samples are necessary.

Outcome and recanalization rate of tandem basilar artery occlusion treated by mechanical thrombectomy.

BACKGROUND: Tandem basilar artery occlusions (tBAO) are defined as concomitant basilar artery and extracranial dominant vertebral artery occlusions. The prognosis of such tBAO treated by mechanical thrombectomy (MT) has been scantly reported. The purpose of our study was to compare the safety and effectiveness of MT for patients with tBAO compared to those with non-tandem basilar artery occlusions (ntBAO). PATIENTS AND METHODS: Retrospective analysis of a database of patients who underwent MT at two academic centres. All patients treated for BAO were retrieved. Patients with tBAO, defined as a concomitant BAO and extracranial vertebral artery (VA) occlusion or severe stenosis ≥70% (V1 or proximal V2 segment) were compared with patients with ntBAO. RESULTS: A total of 15 patients with tBAO and 74 patients with ntBAO were enrolled. Successful reperfusion (modified thrombolysis in cerebral infarction score ≥2b) was obtained in 73.3% versus 90.5% (OR = 0.29, 95%CI: 0.07-1.15), good clinical outcome (3-months modified Rankin scale ≤2) was reached by 26.7% versus 32.4% (OR = 0.76; 95% CI: 0.24-2.63) and mortality at 3-months was 46.7% versus 31% (OR = 1.94; 95%CI: 0.63-6) of patients with tBAO versus ntBAO, respectively. Two patients (13.3%) with tBAO and three (4%) with ntBAO had symptomatic intracranial haemorrhage (OR = 3.64; 95% CI: 0.55-24). CONCLUSION: Mechanical thrombectomy for patients with tandem basilar artery occlusion tends to be associated with lower rates of successful reperfusion and good clinical outcome, and higher rate of mortality. Larger multicentre studies are warranted to better precise the proper selection and management of such patients.

Effect of In-Hospital Remote Ischemic Perconditioning on Brain Infarction Growth and Clinical Outcomes in Patients With Acute Ischemic Stroke: The RESCUE BRAIN Randomized Clinical Trial.

Importance: Treatment with remote ischemic perconditioning has been reported to reduce brain infarction volume in animal models of stroke. Whether this neuroprotective effect was observed in patients with acute ischemic stroke remains unknown. Objective: To determine whether treatment with remote ischemic perconditioning administered to the leg of patients with acute ischemic stroke can reduce brain infarction volume growth. Design, Setting, and Participants: This proof-of-concept multicenter prospective randomized open-label with blinded end point clinical trial was performed from January 12, 2015, to May 2, 2018. Patients were recruited from 11 stroke centers in France. Of the 188 patients who received magnetic resonance imaging within 6 hours of symptom onset and were confirmed to have carotid ischemic stroke, 93 were randomized to receive treatment with lower-limb remote ischemic perconditioning in addition to standard care (the intervention group), and 95 were randomized to receive standard care alone (the control group). Interventions: Randomization on a 1:1 ratio to receive treatment with remote ischemic perconditioning (4 cycles of 5-minute inflations and 5-minute deflations to the thigh to 110 mm Hg above systolic blood pressure) in addition to standard care or standard care alone. Main Outcomes and Measures: The change in brain infarction volume growth between baseline and 24 hours, measured by a diffusion-weighted sequence of magnetic resonance imaging scans of the brain. Results: A total of 188 patients (mean [SD] age, 67.2 [15.7] years; 98 men [52.1%]) were included in this intention-to-treat analysis. At hospital admission, the median National Institutes of Health Stroke Scale score was 10 (interquartile range [IQR], 6-16) and the median brain infarction volume was 11.4 cm3 (IQR, 3.6-35.8 cm3); 164 patients (87.2%) received intravenous thrombolysis, and 64 patients (34.0%) underwent mechanical thrombectomy. The median increase in brain infarction growth was 0.30 cm3 (IQR, 0.11-0.48 cm3) in the intervention group and 0.37 cm3 (IQR, 0.19-0.55 cm3) in the control group (mean between-group difference on loge-transformed change, -0.07; 95% CI, -0.33 to 0.18; P = .57). An excellent outcome (defined as a score of 0-1 on the 90-day modified Rankin Scale or a score equal to the prestroke modified Rankin Scale score) was observed in 46 of 90 patients (51.1%) in the intervention group and 37 of 91 patients (40.7%) in the control group (P = .12). No significant differences in 90-day mortality were observed between the intervention and control groups (14 of 90 patients; Kaplan-Meier estimate, 15.8% vs 10 of 91 patients; Kaplan-Meier estimate, 10.4%, respectively; P = .45) or with symptomatic intracerebral hemorrhage (4 of 88 patients [4.5%] in both groups; P = .97). Conclusions and Relevance: In this study, treatment with remote ischemic perconditioning, during or after reperfusion therapies, had no significant effect on brain infarction volume growth at 24 hours after symptom onset. Trial Registration: ClinicalTrials.gov Identifier: NCT02189928.

Rescue stenting versus medical care alone in refractory large vessel occlusions: a systematic review and meta-analysis.

PURPOSE: Mechanical thrombectomy (MT) failure is associated with very poor prognosis. Permanent intracranial stenting (PIS) may be useful in such refractory occlusions. However, this strategy requires an aggressive antithrombotic regimen that may be harmful in extended strokes. The aim of this study was to compare clinical outcomes between patients with refractory acute large vessel occlusions (LVOs) treated by PIS versus patients for whom the procedure was stopped without recanalization. METHODS: We conducted a systematic review by searching for articles in PubMed, the Cochrane Library, and ClinicalTrials.gov from January 2015 to September 2019. Two reviewers independently selected studies comparing PIS after failed MT in addition to usual care versus usual care only. A comparative meta-analysis was performed using random-effects models to estimate odds ratios of favorable clinical outcome at 90 days, defined as a modified Rankin scale 0-2, mortality and symptomatic intracranial hemorrhage (SICH). RESULTS: Four comparative studies were included for a total of 352 patients: 149 in the PIS group versus 203 in the control group. PIS was associated with significantly higher rates of 90-day favorable clinical outcome (odds ratio [OR], 2.87 [95% confidence interval (95% CI), 1.77-4.66]; p < 0.001; I2, 0%) and lower mortality (OR, 0.39 [0.16-0.93]; p = 0.03; I2, 43%), whereas SICH rates did not significantly differ (OR, 0.68 [0.37-1.27]; p = 0.23; I2, 0%). CONCLUSION: From observational study results, attempting PIS after failed MT seems to improve clinical outcomes without increasing the risk of intracranial bleeding. Randomized trials are needed to confirm these results.

A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke.

BACKGROUND: The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied. METHODS: In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes. RESULTS: A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups. CONCLUSIONS: After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).

Elucidating the Structural and Functional Correlates of Upper-Limb Poststroke Motor Impairment.

Background and Purpose- Many studies have attempted to bring to light the neural correlates of poststroke motor impairment, but few have used multimodal approach to explain it. The aim of this study was to elucidate neural structural and functional correlates of upper limb motor impairment by combining electrophysiological, anatomic, and functional neuroimaging data. Methods- Forty ischemic stroke patients (median [min-max] age: 63 [33-82] years, time poststroke: 3.5 [1.1-58] months) with unilateral upper limb weakness were included. The upper limb motor impairment was defined by a motor composite score. Simple linear analysis followed by multiple linear regression analysis were performed to identify which variables (corticospinal excitability, laterality indices within the primary motor cortex or corticospinal [CST], and corpus callosum tracts integrity) were the best explaining factors of upper limb motor impairment. Results- There was a significant correlation between the resting motor threshold ratio and CST damage (r= -0.50 [95% CI, -0.70 to -0.22]; P<0.001) as well as the motor-evoked potentials amplitude (r= -0.73 [95% CI, -0.85 to -0.54]; P<0.001). Only the resting motor threshold ratio was retained by the multiple regression model and explained half of the variance (49%; P<0.001) of the upper limb motor impairment after stroke. Conclusions- The implementation of quantitative neurophysiological measurements such as the resting motor threshold as a surrogate marker of impairment could be considered in neurorehabilitation trials.

Acute Diffusivity Biomarkers for Prediction of Motor and Language Outcome in Mild-to-Severe Stroke Patients.

Background and Purpose- Early severity of stroke symptoms-especially in mild-to-severe stroke patients-are imperfect predictors of long-term motor and aphasia outcome. Motor function and language processing heavily rely on the preservation of important white matter fasciculi in the brain. Axial diffusivity (AD) from the diffusion tensor imaging model has repeatedly shown to accurately reflect acute axonal damage and is thus optimal to probe the integrity of important white matter bundles and their relationship with long-term outcome. Our aim was to investigate the independent prognostic value of the AD of white matter tracts in the motor and language network evaluated at 24 hours poststroke for motor and aphasia outcome at 3 months poststroke. Methods- Seventeen (motor cohort) and 28 (aphasia cohort) thrombolyzed patients with initial mild-to-severe stroke underwent a diffusion tensor imaging sequence at 24 hours poststroke. Motor and language outcome were evaluated at 3 months poststroke with a composite motor score and the aphasia handicap scale. We first used stepwise regression to determine which classic (age, initial motor or aphasia severity, and lesion volume) and imaging (ratio of affected/unaffected AD of motor and language fasciculi) factors were related to outcome. Second, to determine the specificity of our a priori choices of fasciculi, we performed voxel-based analyses to determine if the same, additional, or altogether new regions were associated with long-term outcome. Results- The ratio of AD in the corticospinal tract was the sole predictor of long-term motor outcome, and the ratio of AD in the arcuate fasciculus-along with age and initial aphasia severity-was an independent predictor of 3-month aphasia outcome. White matter regions overlapping with these fasciculi naturally emerged in the corresponding voxel-based analyses. Conclusions- AD of the corticospinal tract and arcuate fasciculus are effective biomarkers of long-term motor and aphasia outcome, respectively.

The inter-rater reliability of the Italian version of Aphasia Rapid Test (ART) for acute ischemic stroke.

BACKGROUND: The Aphasia Rapid Test (ART) is a screening questionnaire used for examining language in acute stroke patients. The ART was initially developed and validated in French. The purpose of this study was to assess the inter-rater reliability of Italian ART. METHODS: The original version of the ART was translated into Italian. The inter-rater reliability was assessed by two independent neurologists who were blind to each other's ratings in 52 acute post-stroke patients. RESULTS: The 52 patients (28 men, 24 women; mean age 73.73 ± 28.99 years) were included within 1 week of stroke onset (46 ischemic, 6 hemorrhagic), as assessed by clinical examination and confirmed by CT and/or MRI. The mean (± SD) ART value was 9.38 (± 9.26) for rater 1 and 9 (±9.31) for rater 2. The inter-rater agreement was very good, with a coefficient of concordance of 0.99 (95% CI 0.986-0.995; p < 0.0001) and a weighted kappa of 0.878 and a quadratic weighted kappa of 0.983. CONCLUSIONS: This study showed that the cross-cultural adaptation of the French version of the ART was successful in an Italian-speaking population.

Multivariate prediction of functional outcome using lesion topography characterized by acute diffusion tensor imaging.

The relationship between stroke topography and functional outcome has largely been studied with binary manual lesion segmentations. However, stroke topography may be better characterized by continuous variables capable of reflecting the severity of ischemia, which may be more pertinent for long-term outcome. Diffusion Tensor Imaging (DTI) constitutes a powerful means of quantifying the degree of acute ischemia and its potential relation to functional outcome. Our aim was to investigate whether using more clinically pertinent imaging parameters with powerful machine learning techniques could improve prediction models and thus provide valuable insight on critical brain areas important for long-term outcome. Eighty-seven thrombolyzed patients underwent a DTI sequence at 24 h post-stroke. Functional outcome was evaluated at 3 months post-stroke with the modified Rankin Score and was dichotomized into good (mRS ≤ 2) and poor (mRS > 2) outcome. We used support vector machines (SVM) to classify patients into good vs. poor outcome and evaluate the accuracy of different models built with fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity asymmetry maps, and lesion segmentations in combination with lesion volume, age, recanalization status, and thrombectomy treatment. SVM classifiers built with axial diffusivity maps yielded the best accuracy of all imaging parameters (median [IQR] accuracy = 82.8 [79.3-86.2]%), compared to that of lesion segmentations (76.7 [73.3-82.8]%) when predicting 3-month functional outcome. The analysis revealed a strong contribution of clinical variables, notably - in descending order - lesion volume, thrombectomy treatment, and recanalization status, in addition to the deep white matter at the crossroads of major white matter tracts, represented by brain regions where model weights were highest. Axial diffusivity is a more appropriate imaging marker to characterize stroke topography for predicting long-term outcome than binary lesion segmentations.

Pooled analysis suggests benefit of catheter-based hematoma removal for intracerebral hemorrhage.

OBJECTIVE: To develop models of outcome for intracerebral hemorrhage (ICH) to identify promising and futile interventions based on their early phase results without need for correction for baseline imbalances. METHODS: We developed a pooled outcome model from the control arms of randomized control trials and tested different interventions against the model at comparable baseline conditions. Eligible clinical trials and large case series were identified from multiple library databases. Models based on baseline factors reported in the control arms were tested for the ability to predict functional outcome (modified Rankin Scale score) and mortality. Interventions were grouped into blood pressure control, fibrinolytic-assisted hematoma evacuation, hemostatic medications, and neuroprotective agents. Statistical intervals around the model were generated at the p = 0.1 level to screen how each trial's outcome compared to expected outcome. RESULTS: Fourteen control arms with 3,386 patients were used to develop 7 alternate models for functional outcome. The model incorporating baseline NIH Stroke Scale, age, and hematoma volume yielded the best fit (adjusted R 2 = 0.89). All early phase treatments that eventually resulted in negative late phase trials were identified as negative by this method. Early phase fibrinolytic-assisted hematoma evacuation studies showed the most promise trending toward improved functional outcome with no suggestion of an increase in mortality, supporting its further study. CONCLUSIONS: We successfully developed an outcome model for ICH that identified interventions destined to be negative while identifying a promising one. Such an approach may assist in prioritizing resources prior to multicenter trial.

Aphasia outcome: the interactions between initial severity, lesion size and location.

OBJECTIVES: The outcome of aphasia at 3 months is variable in patients with moderate/severe stroke. The aim was to predict 3-month aphasia outcome using prediction models including initial severity in addition to the interaction between lesion size and location at the acute phase. METHODS: Patients with post-stroke aphasia (assessed by the Aphasia Rapid Test at day 7-ART D7) and MRI performed at day 1 were enrolled (n = 73). Good outcome at 3-months was defined by an Aphasia Handicap Score of 0-2. Each infarct lesion was overlapped with an area of interest in the left temporo-parietal region to compute an intersection index (proportion of the critical region damaged by the infarct). We tested ART D7, age, lesion volume, and intersection index as well as a combined variable lesion volume*intersection in a univariate analysis. Then, we performed a multivariate analysis to investigate which variables were independent predictors of good outcome. RESULTS: ART at D7, infarct volume, and the intersection index were univariate predictors of good outcome. In the multivariate analysis, ART D7 and "volume ≥ 50 ml or intersection index ≥ 20%" correctly classified 89% of the patients (p < 0.0001). When added to the model, the interaction between both variables was significant indicating that the impact of the size or site variable depends on the initial severity of aphasia. CONCLUSION: In patients with initially severe aphasia, large infarct size or critical damage in left temporoparietal junction is associated with poor language outcome at 3 months.

Impact of infarct location on functional outcome following endovascular therapy for stroke.

OBJECTIVES: The relationship between stroke topography (ie, the regions damaged by the infarct) and functional outcome can aid clinicians in their decision-making at the acute and later stages. However, the side (left or right) of the stroke may also influence the identification of clinically relevant regions. We sought to determine which brain regions are associated with good functional outcome at 3 months in patients with left-sided and right-sided stroke treated by endovascular treatment using the diffusion-weighted imaging-Alberta Stroke Program Early CT Score (DWI-ASPECTS). METHODS: Patients with ischaemic stroke (n = 405) were included from the ASTER trial and Pitié-Salpêtrière registry. Blinded readers rated ASPECTS on day 1 DWI. Stepwise logistic regression analyses were performed to identify the regions related to 3-month outcome in left (n = 190) and right (n = 215) sided strokes with the modified Rankin scale (0-2) as a binary independent variable and with the 10 regions-of-interest of the DWI-ASPECTS as independent variables. RESULTS: Median National Institute of Health Stroke Scale (NIHSS) at baseline was 17 (IQR: 12-20), median age was 70 years (IQR: 58-80) and median day-one NIHSS 9 (IQR: 4-18). Not all brain regions have the same weight in predicting good outcome at 3 months; moreover, these regions depend on the affected hemisphere. In left-sided strokes, the multivariate analysis revealed that preservation of the caudate nucleus, the internal capsule and the cortical M5 region were independent predictors of good outcome. In right-sided strokes, the cortical M3 and M6 regions were found to be clinically relevant. CONCLUSION: Cortical non-motors areas related to outcome differed between left-sided and right-sided strokes. This difference might reflect the specialisation of the dominant and non-dominant hemispheres for language and attention, respectively. These results may influence decision-making at the acute and later stages. TRIAL REGISTRATION NUMBER: NCT02523261.

Critical brain regions related to post-stroke aphasia severity identified by early diffusion imaging are not the same when predicting short- and long-term outcome.

OBJECTIVES: To identify the critical brain regions associated with 7-days, 3 and 6-months aphasia severity using diffusion-weighted imaging (DWI) in acute post-stroke patients. MATERIALS AND METHODS: We performed a voxel-based ADC (Apparent Diffusion Coefficient) analysis to identify the critical brain areas correlated with aphasia at the acute (7-days outcome) and chronic stages (3 and 6-months). The location of these areas was compared with the trajectory of the dorsal (the arcuate fasciculus) and the ventral language pathways (the inferior fronto-occipital and the uncinate fasciculi). RESULTS: Disconnections of the language fasciculi, which were correlated with aphasia outcome, were not the same for the 7-days outcome (disconnection of the ventral stream) and the chronic outcome (3 and 6 months) (disconnection of the dorsal and ventral streams). CONCLUSION: Routine clinical images can be merged with atlases of anatomical connectivity to provide new insights about the relationship between the lesion location and aphasia severity.