Alex Abou-Chebl

BACKGROUND: Hypothermia reduces ischemic injury in preclinical stroke models, yet translation into the clinical setting remains challenging. We aimed to assess the feasibility of inducing adjuvant systemic hypothermia among patients with large-vessel occlusion stroke during mechanical thrombectomy. METHODS: This was a phase II randomized feasibility-controlled trial involving 10 sites in the United States, conducted between May 2019 and May 2024. All eligible patients had confirmed proximal middle cerebral artery or internal carotid artery occlusions, an Alberta Stroke Program Early Computed Tomography Score of 6 to 10, and symptom onset within 24 hours. Patients underwent mechanical thrombectomy and were randomly assigned to either treatment with adjuvant hypothermia using a novel intravascular cooling catheter or standard of care. The primary feasibility end points were the ability to achieve a target temperature of P =0.70). Final infarct volumes were numerically lower in the hypothermia treatment arm (hypothermia: 11 cm ³ [IQR, 5–42] versus control: 30 cm ³ [IQR, 6–80]; P =0.13), with no significant differences in the rates of hemorrhagic conversion or pneumonia. There was a higher number of serious adverse events in the hypothermia arm (45.5% versus 24.2%; P =0.12), although the trial was not powered for differences in serious adverse events or clinical efficacy. CONCLUSIONS: This is the first clinical trial to demonstrate the feasibility of early and rapid systemic hypothermia as an adjunct therapy during mechanical thrombectomy without delaying time to reperfusion. The potential impact on infarct volumes and serious adverse events, however, warrants further investigation. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03804060.

BACKGROUND: The impact of internal carotid artery tortuosity on achieving first-pass effect in mechanical thrombectomy has been described; however, middle cerebral artery (MCA) tortuosity remains understudied. We investigated the association of MCA tortuosity with radiographic and functional outcome using quantitative and qualitative measures. METHODS: The ARISE II study (Analysis of Revascularization in Ischemic Stroke With EmboTrap) was used to identify patients with anterior circulation stroke. MCA tortuosity was calculated using the Inflection Count Metric by 2 readers blinded to the angiographic/clinical outcomes. The total cohort was trichotomized into 3 groups (A, B, and C) based on M1 tortuosity tertiles, with group A representing the lowest tertile and group C representing the highest tertile. The primary efficacy end point was the achievement of first-pass expanded Thrombolysis in Cerebral Ischemia reperfusion ≥2c. A good functional outcome was defined as a 90-day modified Rankin Scale score of 0 to 2. Baseline and procedural data were compared between groups. RESULTS: A total of 168 patients with M1 or M2 occlusion and measurable MCA tortuosity were identified. Patients in group C were more likely to have renal disease and hyperlipidemia, whereas patients in group A were more likely to have hypertension ( P P =0.024). The rate of final expanded Thrombolysis in Cerebral Ischemia reperfusion ≥2c was higher in group A (87.5%) versus in groups B and C (77.8% and 66%, respectively; P =0.026); achieving modified Rankin Scale score of 0 to 2 was more likely in group A (77.8%) versus in groups B and C (74.5% and 52.7%, respectively; P =0.008). There were no differences in distal emboli or symptomatic intracranial hemorrhage. First-pass effect and angiographic outcomes were consistent with standard angle of curvature tortuosity. CONCLUSIONS: Patients with higher MCA tortuosity were less likely to achieve first-pass effect, successful reperfusion, and good functional outcome at 90 days postmechanical thrombectomy for acute ischemic stroke. REGISTRATION: URL: http://clinicaltrials.gov ; Unique identifier: NCT02488915.

Background: Endovascular treatment (EVT) is the standard of care for selected patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO).Objective: To systematically review the available data on: (1) incidence, predictors, and outcomes of patients with reocclusion after successful EVT for AIS and, (2) the characteristics, complications, and outcomes of patients with reocclusion treated with repeated EVT (rEVT) within 30 days of the first procedure.Methods: PubMed was searched (between January 2012 and April 2021) to identify studies reporting reocclusion following successful EVT (Thrombolysis in Cerebral Infarction ≥2b) in patients with AIS due to LVO. Pooled incidence of reocclusion per 100 patients with successful recanalization following EVT was calculated using a random-effects model with Freeman-Tukey double arcsine transformation. Extracted incidences of reocclusion according to etiology and use of intravenous thrombolysis were pooled using random-effects meta-analytic models.Results: A total of 840 studies was identified and seven studies qualified for the quantitative analysis, which described 91 same-vessel reocclusions occurring within the first 7 days after treatment among 2067 patients (4.9%; 95% CI 3% to 7%, I²=70.2%). Large vessel atherosclerosis was associated with an increased risk of reocclusion (OR=3.44, 95% CI 1.12 to 10.61, I²=50%). We identified 90 patients treated with rEVT for recurrent LVO, described in five studies. The rates of procedural complications, mortality, and unfavorable functional outcome at 3 months were 18.0%, 18.9%, and 60.3%, respectively.Conclusion: In cohorts of patients with AIS due to LVO, 5% of patients experienced reocclusion within 7 days after successful EVT. Repeated EVT can be a safe and effective treatment for selected patients with reocclusion.

Background and Purpose: Mechanical thrombectomy (MT) is now the standard of care for large vessel occlusion (LVO) stroke. However, little is known about the frequency and outcomes of repeat MT (rMT) for patients with recurrent LVO. Methods: This is a retrospective multicenter cohort of patients who underwent rMT at 6 tertiary institutions in the United States between March 2016 and March 2020. Procedural, imaging, and outcome data were evaluated. Outcome at discharge was evaluated using the modified Rankin Scale. Results: Of 3059 patients treated with MT during the study period, 56 (1.8%) underwent at least 1 rMT. Fifty-four (96%) patients were analyzed; median age was 64 years. The median time interval between index MT and rMT was 2 days; 35 of 54 patients (65%) experienced recurrent LVO during the index hospitalization. The mechanism of stroke was cardioembolism in 30 patients (56%), intracranial atherosclerosis in 4 patients (7%), extracranial atherosclerosis in 2 patients (4%), and other causes in 18 patients (33%). A final TICI recanalization score of 2b or 3 was achieved in all 54 patients during index MT (100%) and in 51 of 54 patients (94%) during rMT. Thirty-two of 54 patients (59%) experienced recurrent LVO of a previously treated artery, mostly the pretreated left MCA (23 patients, 73%). Fifty of the 54 patients (93%) had a documented discharge modified Rankin Scale after rMT: 15 (30%) had minimal or no disability (modified Rankin Scale score ≤2), 25 (50%) had moderate to severe disability (modified Rankin Scale score 3–5), and 10 (20%) died. Conclusions: Almost 2% of patients treated with MT experience recurrent LVO, usually of a previously treated artery during the same hospitalization. Repeat MT seems to be safe and effective for attaining vessel recanalization, and good outcome can be expected in 30% of patients.

Treatment of patients with cerebral large vessel occlusion with thrombectomy and tissue plasminogen activator (tPA) leads to incomplete reperfusion. Using rat models of embolic and transient middle cerebral artery occlusion (eMCAO and tMCAO), we investigated the effect on stroke outcomes of small extracellular vesicles (sEVs) derived from rat cerebral endothelial cells (CEC-sEVs) in combination with tPA (CEC-sEVs/tPA) as a treatment of eMCAO and tMCAO in rat. The effect of sEVs derived from clots acquired from patients who had undergone mechanical thrombectomy on healthy human CEC permeability was also evaluated. CEC-sEVs/tPA administered 4 h after eMCAO reduced infarct volume by ∼36%, increased recanalization of the occluded MCA, enhanced cerebral blood flow (CBF), and reduced blood-brain barrier (BBB) leakage. Treatment with CEC-sEVs given upon reperfusion after 2 h tMCAO significantly reduced infarct volume by ∼43%, and neurological outcomes were improved in both CEC-sEVs treated models. CEC-sEVs/tPA reduced a network of microRNAs (miRs) and proteins that mediate thrombosis, coagulation, and inflammation. Patient-clot derived sEVs increased CEC permeability, which was reduced by CEC-sEVs. CEC-sEV mediated suppression of a network of pro-thrombotic, -coagulant, and -inflammatory miRs and proteins likely contribute to therapeutic effects. Thus, CEC-sEVs have a therapeutic effect on acute ischemic stroke by reducing neurovascular damage.

SUMMARY: Coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Inflammation affects atherosclerotic plaque vulnerability and promotes a thrombogenic environment. We report a series of 6 patients with COVID-19 with acute ischemic stroke due to intraluminal carotid artery thrombus presenting during an 8-day period. Six patients were included (5 men) with a mean age of 65.8 years (range, 55–78 years). COVID-19 was diagnosed by detection of Severe Acute Respiratory Syndrome coronavirus 2 in 5 patients and was presumed due to typical clinical and imaging findings in 1 patient. All patients had vascular risk factors including diabetes (83%), hyperlipidemia (100%), and smoking (17%). Four patients presented with large infarcts with initial NIHSS scores of 24–30. During their hospitalization, all patients had elevated D-dimer and C-reactive protein levels, 5 patients had elevated lactate dehydrogenase and ferritin levels, 3 had elevated interleukin-6 levels, and 2 had elevated troponin levels. Inflammation related to COVID-19 may result in rupture of vulnerable atherosclerotic plaques, resulting in thrombosis and acute ischemic stroke.

Background and Purpose—: General anesthesia (GA) for endovascular therapy (EVT) of acute ischemic stroke may be associated with worse outcomes. Methods—: The Interventional Management of Stroke III trial randomized patients within 3 hours of acute ischemic stroke onset to intravenous tissue-type plasminogen activator±EVT. GA use within 7 hours of stroke onset was recorded per protocol. Good outcome was defined as 90-day modified Rankin Scale ≤2. A multivariable analysis adjusting for dichotomized National Institutes of Health Stroke Scale (NIHSS; 8–19 versus ≥20), age, and time from onset to groin puncture was performed. Results—: Four hundred thirty-four patients were randomized to EVT, 269 (62%) were treated under local anesthesia and 147 (33.9%) under GA; 18 (4%) were undetermined. The 2 groups were comparable except for median baseline NIHSS (16 local anesthesia versus 18 GA; P P =0.0056) and had increased in-hospital mortality (adjusted relative risk, 2.84; confidence interval, 1.65–4.91; P =0.0002). Those with medically indicated GA had worse outcomes (adjusted relative risk, 0.49; confidence interval, 0.30–0.81; P =0.005) and increased mortality (relative risk, 3.93; confidence interval, 2.18–7.10; P P =0.32) or symptomatic intracerebral hemorrhage ( P =0.37). Conclusions—: GA was associated with worse neurological outcomes and increased mortality in the EVT arm; this was primarily true among patients with medical indications for GA. Relative risk estimates, though not statistically significant, suggest reduced risk for subarachnoid hemorrhage and symptomatic intracerebral hemorrhage under local anesthesia. Although the reasons for these associations are not clear, these data support the use of local anesthesia when possible during EVT. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00359424.

Background and Purpose—: Previous work that predated the availability of the safer stent-retriever devices has suggested that general anesthesia (GA) may have a negative impact on outcomes in patients with acute ischemic stroke undergoing endovascular therapy. Methods—: We reviewed demographic, clinical, procedural (GA versus local anesthesia [LA], etc), and site-adjudicated angiographic and clinical outcomes data from consecutive patients treated with the Solitaire FR device in the investigator-initiated North American SOLITAIRE Stent-Retriever Acute Stroke (NASA) Registry. The primary outcomes were 90-day modified Rankin Scale, mortality, and symptomatic intracranial hemorrhage. Results—: A total of 281 patients from 18 centers were enrolled. GA was used in 69.8% (196/281) of patients. Baseline demographic and procedural factors were comparable between the LA and GA groups, except the former demonstrated longer time-to-groin puncture (395.4±254 versus 337.4±208 min; P =0.04), lower National Institutes of Health Stroke Scale (NIHSS; 16.2±5.8 versus 18.8±6.9; P =0.002), lower balloon-guide catheter usage (22.4% versus 49.2%; P =0.0001), and longer fluoroscopy times (39.5±33 versus 28±22.8 min; P =0.008). Recanalization (thrombolysis in cerebral infarction ≥2b; 72.94% versus 73.6%; P =0.9) and rate of symptomatic intracranial hemorrhage (7.1% versus 11.2%; P =0.4) were similar but modified Rankin Scale ≤2 was achieved in more LA patients, 52.6% versus 35.6% (odds ratio, 1.4 [1.1–1.8]; P =0.01). In multivariate analysis, hypertension, NIHSS, unsuccessful revascularization, and GA use (odds ratio, 3.3 [1.6–7.1]; P =0.001) were associated with death. When only anterior circulation and elective GA patients were included, there was a persistent difference in good outcomes in favor of LA patients (50.7% versus 35.5%; odds ratio, 1.3 [1.01–1.6]; P =0.04). Conclusions—: The NASA Registry has demonstrated that clinical outcomes and survival are significantly better in patients treated with LA, without increased symptomatic intracranial hemorrhage risk. Future trials should prospectively evaluate the effect of GA on outcomes.