Haemorrhagic stroke and brain vascular malformations in women: risk factors and clinical features.

Haemorrhagic stroke is a severe condition with poor prognosis. Biological sex influences the risk factors, presentations, treatment, and patient outcomes of intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and vascular malformations. Women are usually older at onset of intracerebral haemorrhage compared with men but have an increased risk of aneurysmal subarachnoid haemorrhage as they age. Female-specific factors such as pregnancy, eclampsia or pre-eclampsia, postmenopausal status, and hormone therapy influence a woman's long-term risk of haemorrhagic stroke. The presence of intracranial aneurysms, arteriovenous malformations, or cavernous malformations poses unique clinical dilemmas during pregnancy and delivery. In the absence of evidence-based guidelines for managing the low yet uncertain risk of haemorrhagic stroke during pregnancy and delivery in women with vascular malformations, multidisciplinary teams should carefully assess the risks and benefits of delivery methods for these patients. Health-care providers should recognise and address the challenges that women might have to confront when recovering from haemorrhagic stroke.

Clinical relevance of intracranial hemorrhage after thrombectomy versus medical management for large core infarct: a secondary analysis of the SELECT2 randomized trial.

BACKGROUND: The incidence of intracerebral hemorrhage (ICH) and its effect on the outcomes after endovascular thrombectomy (EVT) for patients with large core infarcts have not been well-characterized. METHODS: SELECT2 trial follow-up imaging was evaluated using the Heidelberg Bleeding Classification (HBC) to define hemorrhage grade. The association of ICH with clinical outcomes and treatment effect was examined. RESULTS: Of 351 included patients, 194 (55%) and 189 (54%) demonstrated intracranial and intracerebral hemorrhage, respectively, with a higher incidence in EVT (134 (75%) and 130 (73%)) versus medical management (MM) (60 (35%) and 59 (34%), both P<0.001). Hemorrhagic infarction type 1 (HBC=1a) and type 2 (HBC=1b) accounted for 93% of all hemorrhages. Parenchymal hematoma (PH) type 1 (HBC=1c) and type 2 (HBC=2) were observed in 1 (0.6%) EVT-treated and 4 (2.2%) MM patients. Symptomatic ICH (sICH) (SITS-MOST definition) was seen in 0.6% EVT patients and 1.2% MM patients. No trend for ICH with core volumes (P=0.10) or Alberta Stroke Program Early CT Score (ASPECTS) (P=0.74) was observed. Among EVT patients, the presence of any ICH did not worsen clinical outcome (modified Rankin Scale (mRS) at 90 days: 4 (3-6) vs 4 (3-6); adjusted generalized OR 1.00, 95% CI 0.68 to 1.47, P>0.99) or modify EVT treatment effect (Pinteraction=0.77). CONCLUSIONS: ICH was present in 75% of the EVT population, but PH or sICH were infrequent. The presence of any ICH did not worsen functional outcomes or modify EVT treatment effect at 90-day follow-up. The high rate of hemorrhages overall still represents an opportunity for adjunctive therapies in EVT patients with a large ischemic core.

Endovascular Thrombectomy Treatment Effect in Direct vs Transferred Patients With Large Ischemic Strokes: A Prespecified Analysis of the SELECT2 Trial.

Importance: Patients with large ischemic core stroke have poor clinical outcomes and are frequently not considered for interfacility transfer for endovascular thrombectomy (EVT). Objective: To assess EVT treatment effects in transferred vs directly presenting patients and to evaluate the association between transfer times and neuroimaging changes with EVT clinical outcomes. Design, Setting, and Participants: This prespecified secondary analysis of the SELECT2 trial, which evaluated EVT vs medical management (MM) in patients with large ischemic stroke, evaluated adults aged 18 to 85 years with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) as well as an Alberta Stroke Program Early CT Score (ASPECTS) of 3 to 5, core of 50 mL or greater on imaging, or both. Patients were enrolled between October 2019 and September 2022 from 31 EVT-capable centers in the US, Canada, Europe, Australia, and New Zealand. Data were analyzed from August 2023 to January 2024. Interventions: EVT vs MM. Main Outcomes and Measures: Functional outcome, defined as modified Rankin Scale (mRS) score at 90 days with blinded adjudication. Results: A total of 958 patients were screened and 606 patients were excluded. Of 352 enrolled patients, 145 (41.2%) were female, and the median (IQR) age was 66.5 (58-75) years. A total of 211 patients (59.9%) were transfers, while 141 (40.1%) presented directly. The median (IQR) transfer time was 178 (136-230) minutes. The median (IQR) ASPECTS decreased from the referring hospital (5 [4-7]) to an EVT-capable center (4 [3-5]). Thrombectomy treatment effect was observed in both directly presenting patients (adjusted generalized odds ratio [OR], 2.01; 95% CI, 1.42-2.86) and transferred patients (adjusted generalized OR, 1.50; 95% CI, 1.11-2.03) without heterogeneity (P for interaction = .14). Treatment effect point estimates favored EVT among 82 transferred patients with a referral hospital ASPECTS of 5 or less (44 received EVT; adjusted generalized OR, 1.52; 95% CI, 0.89-2.58). ASPECTS loss was associated with numerically worse EVT outcomes (adjusted generalized OR per 1-ASPECTS point loss, 0.89; 95% CI, 0.77-1.02). EVT treatment effect estimates were lower in patients with transfer times of 3 hours or more (adjusted generalized OR, 1.15; 95% CI, 0.73-1.80). Conclusions and Relevance: Both directly presenting and transferred patients with large ischemic stroke in the SELECT2 trial benefited from EVT, including those with low ASPECTS at referring hospitals. However, the association of EVT with better functional outcomes was numerically better in patients presenting directly to EVT-capable centers. Prolonged transfer times and evolution of ischemic change were associated with worse EVT outcomes. These findings emphasize the need for rapid identification of patients suitable for transfer and expedited transport. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

Endovascular thrombectomy plus medical care versus medical care alone for large ischaemic stroke: 1-year outcomes of the SELECT2 trial.

BACKGROUND: Multiple randomised trials have shown efficacy and safety of endovascular thrombectomy in patients with large ischaemic stroke. The aim of this study was to evaluate long-term (ie, at 1 year) evidence of benefit of thrombectomy for these patients. METHODS: SELECT2 was a phase 3, open-label, international, randomised controlled trial with blinded endpoint assessment, conducted at 31 hospitals in the USA, Canada, Spain, Switzerland, Australia, and New Zealand. Patients aged 18-85 years with ischaemic stroke due to proximal occlusion of the internal carotid artery or of the first segment of the middle cerebral artery, showing large ischaemic core on non-contrast CT (Alberta Stroke Program Early Computed Tomographic Score of 3-5 [range 0-10, with lower values indicating larger infarctions]) or measuring 50 mL or more on CT perfusion and MRI, were randomly assigned, within 24 h of ischaemic stroke onset, to thrombectomy plus medical care or to medical care alone. The primary outcome for this analysis was the ordinal modified Rankin Scale (range 0-6, with higher scores indicating greater disability) at 1-year follow-up in an intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT03876457) and is completed. FINDINGS: The trial was terminated early for efficacy at the 90-day follow-up after 352 patients had been randomly assigned (178 to thrombectomy and 174 to medical care only) between Oct 11, 2019, and Sept 9, 2022. Thrombectomy significantly improved the 1-year modified Rankin Scale score distribution versus medical care alone (Wilcoxon-Mann-Whitney probability of superiority 0·59 [95% CI 0·53-0·64]; p=0·0019; generalised odds ratio 1·43 [95% CI 1·14-1·78]). At the 1-year follow-up, 77 (45%) of 170 patients receiving thrombectomy had died, compared with 83 (52%) of 159 patients receiving medical care only (1-year mortality relative risk 0·89 [95% CI 0·71-1·11]). INTERPRETATION: In patients with ischaemic stroke due to a proximal occlusion and large core, thrombectomy plus medical care provided a significant functional outcome benefit compared with medical care alone at 1-year follow-up. FUNDING: Stryker Neurovascular.

Endovascular Thrombectomy for Large Ischemic Stroke Across Ischemic Injury and Penumbra Profiles.

Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain. Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect. Design, Setting, and Participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022. Intervention: EVT vs MM. Main Outcomes and Measures: Primary outcome was functional outcome-90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI. Results: Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled. Conclusion and Relevance: In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

Impact of the COVID-19 Pandemic on Stroke Subtype Presentation in Patients Without COVID-19 Infection.

BACKGROUND & AIMS: It is unknown if the COVID-19 pandemic and public health measures had an immediate impact on stroke subtypes and etiologies in patients not infected with COVID-19. We aimed to evaluate if the proportion of non-COVID-19-related stroke subtypes (ischemic vs. hemorrhagic) and etiologies (cardioembolic, atherosclerosis, small vessel disease, and others) during the pandemic's first wave were different from prepandemic. METHODS: For this retrospective cohort study, we included patients without COVID-19 with ischemic or hemorrhagic stroke at two large Canadian stroke centers between March-May 2019 (prepandemic cohort) and March-May 2020 (pandemic cohort). Proportions of stroke subtypes and etiologies were compared between cohorts using chi-square tests. RESULTS: The prepandemic cohort consisted of 234 stroke patients and the pandemic cohort of 207 stroke patients. There were no major differences in baseline characteristics. The proportions of ischemic versus hemorrhagic stroke were similar (ischemic stroke: 77% prepandemic vs. 75% pandemic; hemorrhagic stroke:12% prepandemic vs. 14% pandemic; p > 0.05). There were no differences in etiologies, except for a decreased proportion of ischemic stroke due to atherosclerosis in the pandemic cohort (26% prepandemic vs. 15% pandemic; difference: 10.6%, 95%CI: 1.4-19.7; p = 0.03). Notably, during the pandemic, the cause of ischemic stroke was more often unknown because of incomplete work-up (13.3% prepandemic vs. 28.2% pandemic, difference: 14.9%, 95%-CI: 5.7-24.2; p = <0.01). CONCLUSIONS: In this study, the pandemic had no clear effect on stroke subtypes and etiologies suggesting a limited impact of the pandemic on stroke triggers. However, the shift from atherosclerosis toward other causes warrants further exploration.

Use of the neuroform atlas for stenting of intracranial atherosclerotic disease: Clinical and angiographic outcomes.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is a potential cause of ischemic stroke. Treatment of ICAD can include intracranial stenting. There are specifically designed stents for this use-case; however, less is known about the off-label use of the Neuroform Atlas stent. In this study, we describe the outcomes of the Neuroform Atlas stent for treatment of ICAD. METHODS: Adult patients with symptomatic ICAD failing best medical treatment undergoing elective intracranial stenting using the Neuroform Atlas stent between November 2018 and March 2021 were included. Patient demographics, procedure-related details and clinical and imaging outcomes were analyzed. RESULTS: Eighteen patients met the inclusion criteria, with a mean follow-up duration of 9.6 ± 6.8 (standard deviation) months. There were two procedure-related mortalities (one massive intracranial hemorrhage and one groin site complication with sepsis). Fifteen patients were alive at the 6-month follow-up, all with satisfactory stent patency on follow-up imaging without any new ischemic events. Modified Rankin Scale at latest follow-up was 1.9 (interquartile range 5). CONCLUSION: In this single-center consecutive series, intracranial stenting with the Neuroform Atlas stent was a safe and effective treatment for symptomatic ICAD patients failing best medical management.

A dual-center validation of the PIRAMD scoring system for assessing the severity of ischemic Moyamoya disease.

Background: Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD) is a recently proposed imaging-based scoring system that incorporates the severity of disease and its impact on parenchymal hemodynamics in order to better support clinical management and evaluate response to intervention. In particular, PIRAMD may have merit in identifying symptomatic patients that may benefit most from revascularization. Our aim was to validate the PIRAMD scoring system. Methods: Patients with ischemic Moyamoya disease, who underwent catheter angiographic [modified Suzuki Score (mSS) and collateralization status], morphological MRI and a parenchymal hemodynamic evaluation with blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) at two transatlantic centers, were retrospectively included. The primary outcome was the presence of neurological symptoms. The diagnostic capacity of each PIRAMD feature alone was evaluated, as well as combined and the inter-institutional differences of each parameter were evaluated. Results: Seventy-two hemispheres of 38 patients were considered for analysis, of which 39 (54%) were classified as symptomatic. The presence of a prior infarct had the highest odds ratio [odds ratio (OR) =24; 95% CI: 6.7-87.2] for having neurological symptoms, followed by impaired CVR (OR =17; 95% CI: 5-62). No inter-institutional differences in the odds ratios or area under the curve (AUC) were found for any study parameter. The PIRAMD score had an AUC of 0.88 (95% CI: 0.80-0.96) with a similar AUC for the PIRAMD grading score. Conclusions: Our multicentric validation of the recently published PIRAMD scoring system was highly effective in rating the severity of ischemic Moyamoya disease with excellent inter-institutional agreement. Future studies should investigate the prognostic value of this novel imaging-based score in symptomatic patients with Moyamoya disease.

Trial of Endovascular Thrombectomy for Large Ischemic Strokes.

BACKGROUND: Trials of the efficacy and safety of endovascular thrombectomy in patients with large ischemic strokes have been carried out in limited populations. METHODS: We performed a prospective, randomized, open-label, adaptive, international trial involving patients with stroke due to occlusion of the internal carotid artery or the first segment of the middle cerebral artery to assess endovascular thrombectomy within 24 hours after onset. Patients had a large ischemic-core volume, defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower scores indicating larger infarction) or a core volume of at least 50 ml on computed tomography perfusion or diffusion-weighted magnetic resonance imaging. Patients were assigned in a 1:1 ratio to endovascular thrombectomy plus medical care or to medical care alone. The primary outcome was the modified Rankin scale score at 90 days (range, 0 to 6, with higher scores indicating greater disability). Functional independence was a secondary outcome. RESULTS: The trial was stopped early for efficacy; 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group. The generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (95% confidence interval [CI], 1.20 to 1.89; P<0.001). A total of 20% of the patients in the thrombectomy group and 7% in the medical-care group had functional independence (relative risk, 2.97; 95% CI, 1.60 to 5.51). Mortality was similar in the two groups. In the thrombectomy group, arterial access-site complications occurred in 5 patients, dissection in 10, cerebral-vessel perforation in 7, and transient vasospasm in 11. Symptomatic intracranial hemorrhage occurred in 1 patient in the thrombectomy group and in 2 in the medical-care group. CONCLUSIONS: Among patients with large ischemic strokes, endovascular thrombectomy resulted in better functional outcomes than medical care but was associated with vascular complications. Cerebral hemorrhages were infrequent in both groups. (Funded by Stryker Neurovascular; SELECT2 ClinicalTrials.gov number, NCT03876457.).

Thoracolumbar spinal dural arteriovenous fistulae present with longer arteriovenous transit compared to cranial and cervical dural fistulae.

BACKGROUND: Thoraco-lumbar spinal dural arteriovenous fistulae represent a rare subset of central nervous system vascular malformations. One of the unique features of spinal dural arteriovenous fistulae is their extremely low propensity to cause hemorrhage (either parenchymal or subarachnoid), with a distinct clinical presentation of myelopathy secondary to spinal venous congestion. The exact mechanism for this unique presentation is still unclear. METHODS: Following institutional review board approval, we retrospectively analyzed our prospectively maintained database of spinal dural arteriovenous fistulae and cranial (cr) DAVF cases presenting between 2008 and 2021. For all cases, angiograms were reviewed and arteriovenous transit times were calculated. Patient demographics, angiographic features, and clinical and radiological outcomes were assessed. RESULTS: In total, 66 patients presenting with confirmed thoracolumbar spinal dural arteriovenous fistulaes were identified and compared to patients presenting with cervical spinal dural arteriovenous fistulaes (n = 10), ruptured crDAVFs (n = 32) and unruptured crDAVFs (n = 20). Mean age in the target group was 66 ± 13 versus 57-62 in the other groups, p < 0.05 on one-way analysis of variance; with 80% males versus 50%-65% in other groups. Mean arteriovenous transit time in the thoracolumbar group measured 1.98 s ± 0.96 versus 0.25-0.5 s range in other groups (p < 0.0001 on one-way analysis of variance). CONCLUSION: Prolonged arteriovenous transit times may represent a distinct feature of thoracolumbar spinal dural arteriovenous fistulaes. This may, amongst other factors, play a role in the observed lesser likelihood of hemorrhagic complications compared to other dural arteriovenous shunts.

Sex Differences in Functional Outcomes Following Endovascular Treatment for Acute Ischemic Stroke.

BACKGROUND: Sex disparities have been reported across many aspects of acute ischemic stroke (AIS) care; however, there is a relative paucity of research examining sex differences in outcomes following endovascular treatment (EVT). Some studies report worse functional independence for females following EVT. Few, if any of these studies account for differences in age, baseline function, and comorbidity burden. This retrospective cohort study aimed to assess for sex differences in functional outcomes following EVT by comparing 90-day modified Rankin Scale (mRS) of males and females while controlling for baseline function and comorbidity burden. METHODS: Baseline demographic and clinical data, and stroke severity were compared for 230 consecutive patients undergoing EVT for AIS between October 2014 and July 2019 at a tertiary stroke centre in Toronto, Canada. Effect of sex on likelihood of functional independence post-EVT was assessed using regression analysis with and without correction for age, baseline mRS, and Charlson Comorbidity Index (CCI). RESULTS: Females undergoing EVT for AIS were older (75 ± 13 vs. 66 ± 15, p < 0.0001), with worse clinical and functional baselines. Unadjusted, males were more functionally independent (90-day mRS < 3) [OR = 1.831, 95%CI 1.082-3.098]. After controlling for age, baseline mRS and CCI, there was no difference between groups [OR 1.21, 95%CI 0.61-2.37]. CONCLUSIONS: This study provides evidence that prior findings of sex disparities in function after EVT may be accounted for by differences in age, baseline clinical status and functional independence between males and females when a comprehensive measure of comorbidity burden is utilized.

Sex differences in endovascular thrombectomy outcomes in large vessel occlusion: a propensity-matched analysis from the SELECT study.

BACKGROUND: Sex disparities in acute ischemic stroke outcomes are well reported with IV thrombolysis. Despite several studies, there is still a lack of consensus on whether endovascular thrombectomy (EVT) outcomes differ between men and women. OBJECTIVE: To compare sex differences in EVT outcomes at 90-day follow-up and assess whether progression in functional status from discharge to 90-day follow-up differs between men and women. METHODS: From the Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) prospective cohort study (2016-2018), adult men and women (≥18 years) with anterior circulation large vessel occlusion (internal carotid artery, middle cerebral artery M1/M2) treated with EVT up to 24 hours from last known well were matched using propensity scores. Discharge and 90-day modified Rankin Scale (mRS) scores were compared between men and women. Furthermore, we evaluated the improvement in mRS scores from discharge to 90 days in men and women using a repeated-measures, mixed-effects regression model. RESULTS: Of 285 patients, 139 (48.8%) were women. Women were older with median (IQR) age 69 (57-81) years vs 64.5 (56-75), p=0.044, had smaller median perfusion deficits (Tmax >6 s) 109 vs 154 mL (p<0.001), and had better collaterals on CT angiography and CT perfusion but similar ischemic core size (relative cerebral blood flow <30%: 7.6 (0-25.2) vs 11.4 (0-38) mL, p=0.22). In 65 propensity-matched pairs, despite similar discharge functional independence rates (women: 42% vs men: 48%, aOR=0.55, 95% CI 0.18 to 1.69, p=0.30), women exhibited worse 90-day functional independence rates (women: 46% vs men: 60%, aOR=0.41, 95% CI 0.16 to 1.00, p=0.05). The reduction in mRS scores from discharge to 90 days also demonstrated a significantly larger improvement in men (discharge 2.49 and 90 days 1.88, improvement 0.61) than in women (discharge 2.52 and 90 days 2.44, improvement 0.08, p=0.036). CONCLUSION: In a propensity-matched cohort from the SELECT study, women had similar discharge outcomes as men following EVT, but the improvement from discharge to 90 days was significantly worse in women, suggesting the influence of post-discharge factors. Further exploration of this phenomenon to identify target interventions is warranted. TRIAL REGISTRATION NUMBER: NCT02446587.

Toward a Better Understanding of Sex- and Gender-Related Differences in Endovascular Stroke Treatment: A Scientific Statement From the American Heart Association/American Stroke Association.

There are many unknowns when it comes to the role of sex in the pathophysiology and management of acute ischemic stroke. This is particularly true for endovascular treatment (EVT). It has only recently been established as standard of care; therefore, data are even more scarce and conflicting compared with other areas of acute stroke. Assessing the role of sex and gender as isolated variables is challenging because they are closely intertwined with each other, as well as with patients' cultural, ethnic, and social backgrounds. Nevertheless, a better understanding of sex- and gender-related differences in EVT is important to develop strategies that can ultimately improve individualized outcome for both men and women. Disregarding patient sex and gender and pursuing a one-size-fits-all strategy may lead to suboptimal or even harmful treatment practices. This scientific statement is meant to outline knowledge gaps and unmet needs for future research on the role of sex and gender in EVT for acute ischemic stroke. It also provides a pragmatic road map for researchers who aim to investigate sex- and gender-related differences in EVT and for clinicians who wish to improve clinical care of their patients undergoing EVT by accounting for sex- and gender-specific factors. Although most EVT studies, including those that form the basis of this scientific statement, report patient sex rather than gender, open questions on gender-specific EVT differences are also discussed.

Thrombectomy versus Medical Management in Mild Strokes due to Large Vessel Occlusion: Exploratory Analysis from the EXTEND-IA Trials and a Pooled International Cohort.

OBJECTIVE: This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch. METHODS: The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial,  Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVTpri ) were compared to those who received primary MM (MMpri ), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90-day modified Rankin Scale = 0-2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality). RESULTS: Of 540 patients, 286 (53%) received EVTpri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26-96] ml vs MMpri : 40 [14-76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2-5] vs MMpri : 3 [2-4], p < 0.001). Functional independence was similar (EVTpri : 77.4% vs MMpri : 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82-2.03, p = 0.27). EVT had worse safety regarding sICH (EVTpri : 16.3% vs MMpri : 1.3%, p < 0.001) and neurological worsening (EVTpri : 19.6% vs MMpri : 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVTpri : 77.4% vs MMpri : 72.7%, aOR = 1.68, 95% CI = 1.01-2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVTpri : 77.4% vs MMpri : 83.3%, aOR = 0.39, 95% CI = 0.12-1.34, p = 0.13) without target mismatch (pinteraction  = 0.06). Similar findings were observed in a propensity score-matched subpopulation. INTERPRETATION: Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364-378.

Endovascular Therapy of Acute Ischemic Stroke in Patients with Large-Vessel Occlusion Associated with Active Malignancy.

PURPOSE: There is limited data on the effectiveness of endovascular therapy (EVT) in stroke patients with active malignancy. In this study, we investigated the outcome of EVT for acute ischemic stroke for patients with active malignancy compared to those without malignancy. METHODS: We selected patients who underwent EVT for acute ischemic stroke between January 2015 and July 2019. Patients were divided into two groups, those with active malignancy (oncology group - OG) and those without (non-oncology group, NOG). RESULTS: 300 patients were included in this study. There were 19 EVT procedures (18 patients) in the OG and 285 procedures (282 patients) in the NOG. There was no difference in recanalization success rate (mTICI 2b & 3) between the groups: 94.7% versus 80.9% in OG and NOG respectively (p = 0.13). Success rate using the direct aspiration (ADAPT) technique of EVT was not different between compared groups (42.9% versus 67.7%; p = 0.18). However, when using smaller-caliber aspiration devices, ADAPT was less successful in OG (0.0% versus 64.7%, p < 0.05). There was no difference in recanalization success rate of EVT when using a stent-retriever or combined technique. Patients in the OG had a less favorable functional outcome than in the NOG group (mRS 0-2 at 90-days post event: 22.2% versus 48.2%, p < 0.05) CONCLUSION: The technical success rate of EVT in patients with active malignancy is similar to the general population of stroke patients. Interestingly, the success rate of EVT using the ADAPT technique was lower in the OG when using smaller caliber aspiration devices.

Endovascular Treatment Versus Best Medical Therapy in Acute Ischemic Stroke Patients with Mild Symptoms.

BACKGROUND: The benefit of endovascular treatment (EVT) for acute ischemic stroke patients with mild deficits is unknown. We sought to evaluate the natural history of patients with a low National Institute of Health Stroke Score (NIHSS) and an intracranial occlusion. METHODS: We included patients with a computed tomography angiogram-proven intracranial arterial occlusion who presented within 24 hours of symptom onset with an NIHSS of ≤6. We compared outcomes of patients who were treated with EVT and those who were not by performing propensity score-matched analysis. Primary outcome was modified Rankin score (mRS) at 90 days. RESULTS: A total of 66 patients were included: 38 were men (57.6%) with a median age of 69 (interquartile range [IQR], 57-79.5) years. Median NIHSS was 3 (IQR, 2-5). Median time from symptom onset to presentation was 2.87 hours (IQR, 1.3-5.9). Forty of the total cohort underwent best medical therapy alone (60.6%), whereas 26 underwent EVT (39.4%). Nineteen of the 26 patients who underwent EVT had a good clinical outcome (mRS ≤2) (73.1%), compared with 29 of 40 best medical therapy patients (72.5%) (odds ratio, 0.833 with 95% confidence interval, 0.263-2.631; P = 0.755). Following propensity score adjustment there was a tendency toward lower mRS following EVT (P = 0.051). CONCLUSIONS: Despite the higher number of proximal occlusions in the EVT group, overall outcomes were similar, with >70% of patients in each cohort having a good outcome at 90 days.

Association of initial imaging modality and futile recanalization after thrombectomy.

OBJECTIVE: To test the hypothesis that selection by initial imaging modality (MRI vs CT) is associated with rate of futile recanalizations (FRs) after mechanical thrombectomy (MT), we assessed this association in a multicenter, retrospective observational registry (BEYOND-SWIFT [Registry for Evaluating Outcome of Acute Ischemic Stroke Patients Treated With Mechanical Thrombectomy], NCT03496064). METHODS: In 2,011 patients (49.7% female, median age 73 years [61-81]) included between 2009 and 2017, we performed univariate and multivariate analyses regarding the occurrence of FR. FRs were defined as 90-day modified Rankin Scale (mRS) score 4-6 despite successful recanalization in patients selected by MRI (n = 690) and CT (n = 1,321) with a sensitivity analysis considering only patients with mRS 5-6 as futile. RESULTS: MRI as compared to CT resulted in similar rates of subsequent MT (adjusted odds ratio [aOR] 1.048, 95% confidence interval [CI] 0.677-1.624). Rates of FR were as follows: 571/1,489 (38%) FR mRS 4-6 including 393/1,489 (26%) FR mRS 5-6. CT-based selection was associated with increased rates of FRs compared to MRI (44% [41%-47%] vs 29% [25%-32%], p < 0.001; aOR 1.77 [95% CI 1.25-2.51]). These findings were robust in sensitivity analysis. MRI-selected patients had a delay of approximately 30 minutes in workflow metrics in real-world university comprehensive stroke centers. However, functional outcome and mortality were more favorable in patients selected by MRI compared to patients selected with CT. CONCLUSIONS: CT selection for MT was associated with an increased risk of FRs as compared to MRI selection. Efforts are needed to shorten workflow delays in MRI patients. Further research is needed to clarify the role of the initial imaging modality on FR occurrence and to develop a reliable FR prediction algorithm.