Relevance of Brain Regions' Eloquence Assessment in Patients With a Large Ischemic Core Treated With Mechanical Thrombectomy.

OBJECTIVE: Individualized patient selection for mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) and large ischemic core (LIC) at baseline is an unmet need. We tested the hypothesis that assessing the functional relevance of both infarcted and hypoperfused brain tissue would improve the selection framework of patients with LIC for MT. METHODS: We performed a multicenter, retrospective study of adults with LIC (ischemic core volume >70 mL on MRI diffusion-weighted imaging) with MRI perfusion treated with MT or best medical management (BMM). Primary outcome was 3-month modified Rankin Scale (mRS), favorable if 0-3. Global and regional eloquence-based core perfusion mismatch ratios were derived. The predictive accuracy for clinical outcome of eloquent regions involvement was compared in multivariable and bootstrap random forest models. RESULTS: A total of 138 patients with baseline LIC were included (MT n = 96 or BMM n = 42; mean age ± SD, 72.4 ± 14.4 years; 34.1% female; mRS 0-3: 45.1%). Mean core and critically hypoperfused volume were 100.4 mL ± 36.3 mL and 157.6 ± 56.2 mL, respectively, and did not differ between groups. Models considering the functional relevance of the infarct location showed a better accuracy for the prediction of mRS 0-3 with a c statistic of 0.76 and 0.83 for logistic regression model and bootstrap random forest testing sets, respectively. In these models, the interaction between treatment effect of MT and the mismatch was significant (p = 0.04). In comparison, in the logistic regression model disregarding functional eloquence, the c statistic was 0.67 and the interaction between MT and the mismatch was insignificant. CONCLUSIONS: Considering functional eloquence of hypoperfused tissue in patients with a large infarct core at baseline allows for a more precise estimation of treatment expected benefit. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, in patients with AIS and LIC, considering the functional eloquence of the infarct location improves prediction of disability status at 3 months.

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.

Perfusion Imaging to Select Patients with Large Ischemic Core for Mechanical Thrombectomy.

BACKGROUND AND PURPOSE: Patients with acute ischemic stroke, proximal vessel occlusion and a large ischemic core at presentation are commonly not considered for mechanical thrombectomy (MT). We tested the hypothesis that in patients with baseline large infarct cores, identification of remaining penumbral tissue using perfusion imaging would translate to better outcomes after MT. METHODS: This was a multicenter, retrospective, core lab adjudicated, cohort study of adult patients with proximal vessel occlusion, a large ischemic core volume (diffusion weighted imaging volume ≥70 mL), with pre-treatment magnetic resonance imaging perfusion, treated with MT (2015 to 2018) or medical care alone (controls; before 2015). Primary outcome measure was 3-month favorable outcome (defined as a modified Rankin Scale of 0-3). Core perfusion mismatch ratio (CPMR) was defined as the volume of critically hypo-perfused tissue (Tmax >6 seconds) divided by the core volume. Multivariable logistic regression models were used to determine factors that were independently associated with clinical outcomes. Outputs are displayed as adjusted odds ratio (aOR) and 95% confidence interval (CI). RESULTS: A total of 172 patients were included (MT n=130; Control n=42; mean age 69.0±15.4 years; 36% females). Mean core-volume and CPMR were 102.3±36.7 and 1.8±0.7 mL, respectively. As hypothesized, receiving MT was associated with increased probability of favorable outcome and functional independence, as CPMR increased, a difference becoming statistically significant above a mismatch-ratio of 1.72. Similarly, receiving MT was also associated with favorable outcome in the subgroup of 74 patients with CPMR >1.7 (aOR, 8.12; 95% CI, 1.24 to 53.11; P=0.028). Overall (prior to stratification by CPMR) 73 (42.4%) patients had a favorable outcome at 3 months, with no difference amongst groups. CONCLUSION: s In patients currently deemed ineligible for MT due to large infarct ischemic cores at baseline, CPMR identifies a subgroup strongly benefiting from MT. Prospective studies are warranted.

Effect of hyperglycemia on stroke outcome is not homogeneous to all patients treated with mechanical thrombectomy.

OBJECTIVES: Admission hyperglycemia is a penumbra-modifying factor that is associated with poor functional outcome in acute ischemic stroke (AIS) patients treated with intravenous rt-PA and/or mechanical thrombectomy (MT). Insulin therapy has failed to demonstrate a clinical benefit and the question of the patient selection remains under debate. We assessed the relationship between admission glycemia (AG) and functional outcome in AIS patients treated by MT according to both penumbra characteristics and reperfusion status. PATIENTS AND METHODS: We performed a retrospective analysis of a multi-center registry of consecutive AIS (NIHSS ≥ 10) due to middle cerebral artery occlusion treated by MT (± tissue Plasminogen Activator (tPA)). To evaluate the association between AG and the 3-month functional outcome (modified Rankin Scale (mRS) ≤2), univariable and multivariable analyses were used. Subgroup analyses were performed according to both clinical-ASPECTS Mismatch (CAM2) and the complete recanalization (CR) status defined by a mTICI scale (modified Thrombolysis in Cerebral Infarction) 2b/3. RESULTS: 216 AIS patients were included (Median Age: 68.43[58.12-77.95], median NIHSS: 18[15-21]). 104/216 (48.15%) patients had mRS≤2 at 3 months. AG was an independent predictor of functional outcome (/1 g/L OR: 0.10[0.03-0.37]) after adjusting for potential cofounders. Among subgroups formed by combining CAM2 and CR, AG was found to be predictor of functional outcome only in CAM2+/CR+ and specifically when recanalization was early. CONCLUSION: This study highlights the fact that the relationship between AG and prognosis is not homogeneous for all patients and indicates that AG has a deleterious effect on the ischemic penumbra, thus explaining its statistical association with functional outcome. Stroke neuroprotection by targeting hyperglycemia should be considered in acute stroke patients with mismatch and early complete recanalization. More prospective randomized trials are needed to generalize the conclusions.

The different patterns of seizure-induced aphasia in temporal lobe epilepsies.

OBJECTIVES: Ictal language disturbances may occur in dominant hemisphere temporal lobe epilepsy (TLE), but little is known about the precise anatomoelectroclinical correlations. This study investigated the different facets of ictal aphasia in intracerebrally recorded TLE. METHODS: Video-stereoelectroencephalography (SEEG) recordings of 37 seizures in 17 right-handed patients with drug-resistant TLE were analyzed; SEEG electroclinical correlations between language disturbance and involvement of temporal lobe structures were assessed. In the clinical analysis, we separated speech disturbance from loss of consciousness. RESULTS: According to the region involved, different patterns of ictal aphasia in TLE were identified. Impaired speech comprehension was associated with posterior lateral involvement, anomia and reduced verbal fluency with anterior mediobasal structures, and jargonaphasia with basal temporal involvement. The language production deficits, such as anomia and low fluency, cannot be simply explained by an involvement of Broca's area, since this region was not affected by seizure discharge. SIGNIFICANCE: Assessment of language function in the early ictal state can be successfully performed and provides valuable information on seizure localization within the temporal lobe as well as potentially useful information for guiding surgery.