Significant Mortality Associated With COVID-19 and Comorbid Cerebrovascular Disease: A Quantitative Systematic Review.

We report the first quantitative systematic review of cerebrovascular disease in coronavirus disease 2019 (COVID-19) to provide occurrence rates and associated mortality. Through a comprehensive search of PubMed we identified 8 cohort studies, 5 case series, and 2 case reports of acute cerebrovascular disease in patients with confirmed COVID-19 diagnosis. Our first meta-analysis utilizing the identified publications focused on comorbid cerebrovascular disease in recovered and deceased patients with COVID-19. We performed 3 additional meta-analyses of proportions to produce point estimates of the mortality and incidence of acute cerebrovascular disease in COVID-19 patients. Patient's with COVID-19 who died were 12.6 times more likely to have a history of cerebrovascular disease. We estimated an occurrence rate of 2.6% (95% confidence interval, 1.2-5.4%) for acute cerebrovascular disease among consecutively admitted patients with COVID-19. While for those with severe COVID-19' we estimated an occurrence rate of 6.5% (95% confidence interval, 4.4-9.6%). Our analysis estimated a rate of 35.5% for in-hospital mortality among COVID-19 patients with concomitant acute cerebrovascular disease. This was consistent with a mortality rate of 34.0% which we obtained through an individual patient analysis of 47 patients derived from all available case reports and case series. COVID-19 patients with either acute or chronic cerebrovascular disease have a high mortality rate with higher occurrence of cerebrovascular disease in patients with severe COVID-19.

Endovascular Thrombectomy for Treatment of Acute Ischemic Stroke During Pregnancy and the Early Postpartum Period.

BACKGROUND AND PURPOSE: Acute ischemic stroke (AIS) is a rare occurrence during pregnancy and the postpartum period. Existing literature evaluating endovascular mechanical thrombectomy (MT) for this patient population is limited. METHODS: The National Inpatient Sample was queried from 2012 to 2018 to identify and characterize pregnant and postpartum patients (up to 6 weeks following childbirth) with AIS treated with MT. Complications and outcomes were compared with nonpregnant female patients treated with MT and to other pregnant and postpartum patients managed medically. Complex samples regression models and propensity score matching were implemented to assess adjusted associations and to address confounding by indication, respectively. RESULTS: Among 4590 pregnant and postpartum patients with AIS, 180 (3.9%) were treated with MT, and rates of utilization increased following the MT clinical trial era (2015-2018; 1.9% versus 5.3%, P=0.011). Compared with nonpregnant patients with AIS treated with MT, they experienced lower rates of intracranial hemorrhage (11% versus 24%, P=0.069) and poor functional outcome (50% versus 72%, P=0.003) at discharge. Pregnant/postpartum status was independently associated with a lower likelihood of development of intracranial hemorrhage (adjusted odds ratio, 0.26 [95% CI, 0.09-0.70]; P=0.008) following multivariable analysis adjusting for age, illness severity, and stroke severity. Following propensity score matching, pregnant and postpartum patients treated with MT and those medically managed differed in frequency of venous thromboembolism (17% versus 0%, P=0.001) and complications related to pregnancy (44% versus 64%, P=0.034), but not in functional outcome at discharge or hospital length of stay. Pregnant and postpartum women treated with MT did not experience mortality or miscarriage during hospitalization. CONCLUSIONS: This large-scale analysis utilizing national claims data suggests that MT is a safe and efficacious therapy for AIS during pregnancy and the postpartum period. In the absence of prospective clinical trials, population-based cross-sectional analyses such as the present study provide valuable clinical insight.

Multifocal Atraumatic Convexity Subarachnoid Hemorrhage.

Background Multifocal convexity subarachnoid hemorrhage (cSAH) has generally been described in the setting of traumatic brain injury, however, it has also been reported in the absence of trauma in conditions such as with reversible cerebral vasoconstriction syndrome. We describe the clinical and radiographic characteristics of multifocal cSAH in an academic center. Methods We analyzed our single-center retrospective database of nontraumatic convexity subarachnoid hemorrhage from January 2015-January 2018. Convexity subarachnoid hemorrhage was defined as blood in one or more cortical sulci in the absence of trauma; patients with blood in the cisterns or Sylvian fissure were excluded. Multifocal location was defined as at least two distinct foci of hemorrhage occurring in two or more lobes. Clinical and neuroimaging data were collected. Results Out of 70 total patients with convexity subarachnoid hemorrhage, 13 cases were of multifocal convexity subarachnoid hemorrhage, occurring in 18.6% of all cases. The mean age was 58 years (SD = 14.7). Eleven patients were female. Seven patients had reversible cerebral vasoconstriction syndrome (RCVS)/posterior reversible encephalopathy syndrome (PRES), two had cerebral amyloid angiopathy (CAA), three had intrinsic coagulopathy, and one patient had endocarditis as the etiology of multifocal cSAH. Headache was the most common complaint, in eight (61.5%) patients. Conclusion Multifocal cSAH occurs in approximately 18.6% of all cSAH and can occur in the absence of trauma. In our larger cohort of all cSAH, CAA was the most common cause; however, multifocal cSAH is more commonly caused by RCVS/PRES spectrum. Clinicians should be aware that multifocal cSAH can occur in the absence of trauma, and may be a harbinger of RCVS/PRES, particularly in young patients with thunderclap headaches.

Short- and long-term opioid use in survivors of subarachnoid hemorrhage.

OBJECTIVES: Opioids are frequently used for analgesia in patients with acute subarachnoid hemorrhage (SAH) due to a high prevalence of headache and neck pain. However, it is unclear if this practice may pose a risk for opioid dependence, as long-term opioid use in this population remains unknown. We sought to determine the prevalence of opioid use in SAH survivors, and to identify potential risk factors for opioid utilization. METHODS: We analyzed a cohort of consecutive patients admitted with non-traumatic and suspected aneurysmal SAH to an academic referral center. We included patients who survived hospitalization and excluded those who were not opioid-naïve. Potential risk factors for opioid prescription at discharge, 3 and 12 months post-discharge were assessed. RESULTS: Of 240 SAH patients who met our inclusion criteria (mean age 58.4 years [SD 14.8], 58% women), 233 (97%) received opioids during hospitalization and 152 (63%) received opioid prescription at discharge. Twenty-eight patients (12%) still continued to use opioids at 3 months post-discharge, and 13 patients (6%) at 12-month follow up. Although patients with poor Hunt and Hess grades (odds ratio 0.19, 95% CI 0.06-0.57) and those with intraventricular hemorrhage (odds ratio 0.38, 95% CI 0.18-0.87) were less likely to receive opioid prescriptions at discharge, we did not find significant differences between patients who had long-term opioid use and those who did not. CONCLUSION: Opioids are regularly used in both the acute SAH setting and immediately after discharge. A considerable number of patients also continue to use opioids in the long-term. Opioid-sparing pain control strategies should be explored in the future.

Association of Early White Blood Cell Trend with Outcomes in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: An increasing white blood cell (WBC) count in early course of aneurysmal subarachnoid hemorrhage (SAH) can indicate a systemic inflammatory state triggered by the initial insult. We sought to determine the significance of the early WBC trend as a potential predictor of outcomes. METHODS: We analyzed a cohort of consecutive patients with aneurysmal SAH. The WBC values in first 5 days of admission, plus relevant clinical and imaging data, and modified Rankin Scale (mRS) at 3 months after hospital discharge were retrieved and analyzed. Favorable outcome was defined as mRS 0-3. The association between WBC counts and outcomes including mRS and delayed cerebral ischemia (DCI) was determined using binary logistic regression models. We used receiver operating characteristic curve analysis to assess accuracy of WBC in predicting outcomes. RESULTS: We included 167 patients in final analysis. Mean age was 56.4 (standard deviation [SD] 14.8) years, and 65% (109) of patients were female. Peak WBC was greater in patients with poor functional outcome (mean 17 × 109 cells/L, SD 6.4 vs. 13.5 × 109 cells/L SD 4.7). Combining peak WBC with modified Fisher scale slightly increased accuracy in predicting DCI (area under the curve 0.670, 95% confidence interval 0.586-0.755) compared with each component alone. CONCLUSIONS: WBC count in the early course of SAH may have prognostic values in predicting DCI and functional outcome. WBC count monitoring may be used in conjunction with other clinical and radiographic tools to stratify patients with SAH into high- and low-risk groups to tailor neuromonitoring and treatment strategies.

Incidence of Neo-Intimal Hyperplasia in Anterior Circulation Aneurysms Following Pipeline Flow Diversion.

INTRODUCTION: Flow diversion of the distal anterior circulation cerebral vasculature may be used for management of wide necked aneurysms not amenable to other endovascular approaches. Follow-up angiography sometimes demonstrates neo-intimal hyperplasia within or adjacent to the stent, however there is limited evidence in the literature examining the incidence in MCA and ACA aneurysms. We present our experience with flow diversion of the distal vasculature and evaluate the incidence of neo-intimal hyperplasia. MATERIALS AND METHODS: Retrospective review of patients who underwent Pipeline embolization device (PED) treatment for ruptured and unruptured anterior circulation aneurysms. RESULTS: A total of 251 anterior circulation aneurysms were treated by pipeline flow diversion, of which 175 were ICA aneurysms, 14 were ACA aneurysms and 18 were MCA aneurysms. 6-month follow-up angiography was available in 207 patients. The incidence of neo-intimal hyperplasia was 15.9%, 21.4%, and 61.1% in ICA, ACA, and MCA aneurysms, respectively. MCA-territory aneurysms developed neo-intimal hyperplasia at a significantly higher rate than aneurysms in other vessel territories. Rates of aneurysmal occlusion did not significantly differ from those patients who did not exhibit intimal hyperplasia on follow-up angiography. CONCLUSION: In our experience, flow diversion of distal wide-necked MCA and ACA aneurysms is a safe and effective treatment strategy. The presence of neo-intimal hyperplasia at 6-month angiography is typically clinically asymptomatic. Given the statistically higher rate of neo-intimal hyperplasia in MCA aneurysms at 6-month angiography, we propose delaying initial follow-up angiography to 12-months and maintaining dual antiplatelet therapy during that time.

Cerebral Venous Sinus Thrombosis in COVID-19 Infection: A Case Series and Review of The Literature.

SARS-CoV-2, the virus responsible for novel Coronavirus (COVID-19) infection, has recently been associated with a myriad of hematologic derangements; in particular, an unusually high incidence of venous thromboembolism has been reported in patients with COVID-19 infection. It is postulated that either the cytokine storm induced by the viral infection or endothelial damage caused by viral binding to the ACE-2 receptor may activate a cascade leading to a hypercoaguable state. Although pulmonary embolism and deep venous thrombosis have been well described in patients with COVID-19 infection, there is a paucity of literature on cerebral venous sinus thrombosis (cVST) associated with COVID-19 infection. cVST is an uncommon etiology of stroke and has a higher occurrence in women and young people. We report a series of three patients at our institution with confirmed COVID-19 infection and venous sinus thrombosis, two of whom were male and one female. These cases fall outside the typical demographic of patients with cVST, potentially attributable to COVID-19 induced hypercoaguability. This illustrates the importance of maintaining a high index of suspicion for cVST in patients with COVID-19 infection, particularly those with unexplained cerebral hemorrhage, or infarcts with an atypical pattern for arterial occlusive disease.

Acute subdural hematomas secondary to aneurysmal subarachnoid hemorrhage confer poor prognosis: a national perspective.

BACKGROUND: Aneurysmal ruptures typically cause subarachnoid bleeding with intraparenchymal and intraventricular extension. However, rare instances of acute aneurysmal ruptures present with concomitant, non-traumatic subdural hemorrhage (SDH). We explored the incidence and difference in outcomes of SDH with aneurysmal subarachnoid hemorrhage (aSAH) as compared with aSAH alone. METHODS: Retrospective cohort study from 2012 to 2015 from the National (Nationwide) Inpatient Sample (NIS) (20% stratified sample of all hospitals in the United States). NIS database (2012 to September 2015) queried to identify all patients presenting with aSAH. From this population, the patients with concomitant SDH were identified. RESULTS: A total of 10 075 patients with both cerebral aneurysms and aSAH were included. Of these, 335 cases of concomitant SDH and aSAH were identified. There was no significant change in the rate of SDH in aSAH over time. SDH with aSAH patients had a mortality of 24% compared with 12% (p=0.003) in the SAH only group, and only 16% were discharged home vs 37% (p=0.003) in the SAH group. CONCLUSIONS: There is a 3.5% incidence of acute SDH in patients presenting with non-traumatic aSAH. Patients with SDH and aSAH have nearly double the mortality, higher rate of discharge to nursing home and rehabilitation, and a significantly lower rate of discharge to home and return to routine functioning. This information is useful in counseling and prognostication of patients with concomitant SDH and aSAH.

Association of Dexamethasone with Shunt Requirement, Early Disability, and Medical Complications in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Current guidelines do not support the routine use of corticosteroids in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, corticosteroids use in aSAH has been practiced at some centers by convention. The aim of the study was to determine the incidence of hydrocephalus requiring ventriculoperitoneal shunt (VPS) placement as well as functional outcome on discharge and adverse events attributed to corticosteroids in patients with aSAH treated with different dexamethasone (DXM) treatment schemes. METHODS: We retrospectively analyzed 206 patients with aSAH stratified to three groups based on the DXM treatment scheme: no corticosteroids, short course of DXM (S-DXM; 4 mg every 6 h for 1 day followed by a daily total dose reduction by 25% and then by 50% on last day), and long course of DXM (L-DXM; 4 mg every 6 h for 5-7 days followed by reduction by 50% every other day). The primary outcome measure was the placement of a VPS, and the secondary outcome was a good functional outcome [modified Rankin Scale (mRS) 0-3] at hospital discharge. Safety measures were the incidence of infection (pneumonia, urinary tract infection, ventriculitis, meningitis), presence of delirium, and hyperglycemia. RESULTS: There was no difference in the rate of external ventricular drain (EVD) (p = 0.164) and VPS placement (p = 0.792), nor in the rate of good outcome (p = 0.928) among three defined treatment regimens. Moreover, the median duration of treatment with EVD did not differ between subjects treated with no corticosteroids, S-DXM, and L-DXM (p = 0.905), and the probability of EVD removal was similar when stratified according to treatment regimens (log-rank; p = 0.256). Patients who received L-DXM had significantly more complications as compared to patients, who received no corticosteroids or S-DXM (78.4% vs. 58.6%; p = 0.005). After adjustment, L-DXM remained independently associated with increased risk of combined adverse events (OR = 2.72; 95%CI, 1.30-5.72; p = 0.008), infection (OR = 3.45; 95%CI, 1.63-7.30; p = 0.001) and hyperglycemia (OR = 2.05; 95%CI, 1.04-4.04; p = 0.039). CONCLUSIONS: DXM use among patients with aSAH did not relate to the rate of EVD and VPS placement, duration of EVD treatment, and functional disability at discharge but increased the risk of medical complications.

Flow diversion in anterior cerebral artery aneurysms.

INTRODUCTION: Anterior cerebral artery (ACA) aneurysms are commonly encountered in clinical practice but can be challenging to treat. Flow diversion is a viable treatment in this population. METHODS: We retrospectively evaluated patients treated at our center from May 2017 to December 2020 who underwent flow diversion for an ACA aneurysm at or distal to the anterior communicating artery (ACOM). We defined ACA aneurysms as any aneurysm involving the ACOM itself, at the junction of the ACA with the ACOM (A1/A2), or in distal A2/A3 branches; both ruptured and unruptured aneurysms were included. Baseline and follow-up clinical and angiographic data were collected; the primary measure was elimination of the aneurysm on follow-up angiogram. Patients underwent flow diversion with a Pipeline stent. A single flow diverting stent was placed in the dominant ACA spanning from the A2 segment extending into the A1 segment; two patients required H-pipe technique. Distal aneurysms were treated with a single Pipeline device deployed across the parent vessel, covering the aneurysm. RESULTS: Two-seven patients underwent a total of 28 flow diversion procedures; median age was 57 and 16 (59.3%) were male. Thirteen (48.2%) patients presented with subarachnoid hemorrhage; of these, four were treated within 6 weeks of the index hemorrhage. Most patients (22; 81.5%) had significant ACA asymmetry. There was one postoperative intracerebral hemorrhage and one groin complication. Follow-up data were available for 19 patients, 15 (78.9%) of which showed no residual aneurysm and 17 (89.5%) had protection of the dome. CONCLUSION: Flow diversion of ACA aneurysms can be a primary treatment modality in an unruptured aneurysm or a complement to initial coil protection of a ruptured aneurysm. Further studies are needed to confirm these results.

Acute Cerebrovascular Disorders and Vasculopathies Associated with Significant Mortality in SARS-CoV-2 Patients Admitted to The Intensive Care Unit in The New York Epicenter.

The current Coronavirus pandemic due to the novel SARS-Cov-2 virus has proven to have systemic and multi-organ involvement with high acuity neurological conditions including acute ischemic strokes. We present a case series of consecutive COVID-19 patients with cerebrovascular disease treated at our institution including 3 cases of cerebral artery dissection including subarachnoid hemorrhage. Knowledge of the varied presentations including dissections will help treating clinicians at the bedside monitor and manage these complications preemptively.

Management of Small Unruptured Intracranial Aneurysms: To Treat or Not to Treat?

Unruptured intracranial aneurysms measuring <7 mm in diameter have become increasingly prevalent due to advances in diagnostic imaging. The most feared complication is aneurysm rupture leading to a subarachnoid hemorrhage. Based on the current literature, the 3 main treatments for an unruptured intracranial aneurysm are conservative management with follow-up imaging, endovascular coiling, or surgical clipping. However, there remains no consensus on the best treatment approach. The natural history of the aneurysm and risk factors for aneurysm rupture must be considered to individualize treatment. Models including population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage from a prior aneurysm, site of aneurysm score, Unruptured Intracranial Aneurysm Treatment Score, and advanced neuroimaging can assist physicians in assessing the risk of aneurysm rupture. Macrophages and other inflammatory modulators have been elucidated as playing a role in intracranial aneurysm progression and eventual rupture. Further studies need to be conducted to explore the effects of therapeutic drugs targeting inflammatory modulators.

Cerebral Herniation Secondary to Stroke-Associated Hemorrhagic Transformation, Fulminant Cerebral Edema in Setting of COVID-19 Associated ARDS and Active Malignancy.

SARS-CoV-2 infection has been associated with ischemic stroke as well as systemic complications such as acute respiratory failure; cytotoxic edema is a well-known sequelae of acute ischemic stroke and can be worsened by the presence of hypercarbia induced by respiratory failure. We present the case of a very rapid neurologic and radiographic decline of a patient with an acute ischemic stroke who developed rapid fulminant cerebral edema leading to herniation in the setting of hypercarbic respiratory failure attributed to SARS-CoV-2 infection. Given the elevated incidence of cerebrovascular complications in patients with COVID-19, it is imperative for clinicians to be aware of the risk of rapidly progressive cerebral edema in patients who develop COVID-19 associated acute respiratory distress syndrome.

Reversible cerebral vasoconstriction syndrome and dissection in the setting of COVID-19 infection.

The current COVID-19 pandemic has recently brought to attention the myriad of neuro- logic sequelae associated with Coronavirus infection including the predilection for stroke, particularly in young patients. Reversible cerebral vasoconstriction syndrome (RCVS) is a well-described clinical syndrome leading to vasoconstriction in the intracra- nial vessels, and has been associated with convexity subarachnoid hemorrhage and oc- casionally cervical artery dissection. It is usually reported in the context of a trigger such as medications, recreational drugs, or the postpartum state; however, it has not been described in COVID-19 infection. We report a case of both cervical vertebral ar- tery dissection as well as convexity subarachnoid hemorrhage due to RCVS, in a pa- tient with COVID-19 infection and no other triggers.

Mechanical Thrombectomy in Ischemic Stroke Patients with Severe Pre-Stroke Disability.

Frequency and outcomes of mechanical thrombectomy (MT) in clinical practice for patients with severe pre-stroke disability are largely unknown. In this case series, we aim to describe the disability make-up and outcomes of 33 patients with severe pre-stroke disability undergoing MT. Patients with a permanent, severe, pre-stroke disability (modified Rankin Score, mRS, 4-5) were identified from a prospectively-maintained database of consecutive, MT-treated, anterior circulation acute ischemic stroke patients at two comprehensive stroke centers in the United States. We present details on the cause of disability and socio-demographic status as well as procedural and functional outcomes. This study, despite the lack of inferential testing due to limited sample size, provides insight into demographics and outcomes of MT-treated patients with severe pre-stroke disability. Rate of return to functional baseline as well as rates of procedural success and complications were comparable to that reported in the literature for patients without any pre-existing disability.

Mechanical Thrombectomy in Patients With Ischemic Stroke With Prestroke Disability.

Background and Purpose- We aimed to compare functional and procedural outcomes of patients with acute ischemic stroke with none-to-minimal (modified Rankin Scale [mRS] score, 0-1) and moderate (mRS score, 2-3) prestroke disability treated with mechanical thrombectomy. Methods- Consecutive adult patients undergoing mechanical thrombectomy for an anterior circulation stroke were prospectively identified at 2 comprehensive stroke centers from 2012 to 2018. Procedural and 90-day functional outcomes were compared among patients with prestroke mRS scores 0 to 1 and 2 to 3 using χ2, logistic, and linear regression tests. Primary outcome and significant differences in secondary outcomes were adjusted for prespecified covariates. Results- Of 919 patients treated with mechanical thrombectomy, 761 were included and 259 (34%) patients had moderate prestroke disability. Ninety-day mRS score 0 to 1 or no worsening of prestroke mRS was observed in 36.7% and 26.7% of patients with no-to-minimal and moderate prestroke disability, respectively (odds ratio, 0.63 [0.45-0.88], P=0.008; adjusted odds ratio, 0.90 [0.60-1.35], P=0.6). No increase in the disability at 90 days was observed in 22.4% and 26.7%, respectively. Rate of symptomatic intracerebral hemorrhage (7.3% versus 6.2%, P=0.65), successful recanalization (86.7% versus 83.8%, P=0.33), and median length of hospital stay (5 versus 5 days, P=0.06) were not significantly different. Death by 90 days was higher in patients with moderate prestroke disability (14.3% versus 40.3%; odds ratio, 4.06 [2.82-5.86], P<0.001; adjusted odds ratio, 2.83 [1.84, 4.37], P<0.001). Conclusions- One-third of patients undergoing mechanical thrombectomy had a moderate prestroke disability. There was insufficient evidence that functional and procedural outcomes were different between patients with no-to-minimal and moderate prestroke disability. Patients with prestroke disability were more likely to die by 90 days.

Serum alpha-1 antitrypsin in acute ischemic stroke: A prospective pilot study.

BACKGROUND: Alpha-1 antitrypsin (AAT) is a potent anti-protease enzyme which may play a role in arterial wall stability. A variant of its encoding gene has been recently linked to ischemic stroke due to large artery atherosclerosis (LAA). We sought to explore potential relationships between ischemic stroke mechanisms, atherosclerosis burden and serum AAT levels. METHODS: We performed a prospective observational study of consecutive patients with acute ischemic stroke who were admitted to an academic comprehensive stroke center over a three-month period. Blood samples were collected within 24 h of hospital admission, and stroke subtype classification was determined based on modified TOAST criteria. Modified Woodcock scoring system was used to quantify calcification of major cervico-cranial arteries as a surrogate for atherosclerosis burden. Linear regression analysis was used to assess the association between serum AAT levels and calcification scores, both as continuous variables. RESULTS: Among eighteen patients met our inclusion criteria and were enrolled in our study, 10 patients (56%) were men; mean age was 66 (SD 12.5); median NIH stroke scale was 4 (IQR 9.5); 8 patients (44%) had stroke due to LAA. The median serum level of AAT was 140 mg/dl (IQR 41.7) for patients with LAA-related stroke, and 148.5 mg/dl (IQR 37.7) for patients with other stroke mechanisms (p = 0.26). Higher serum AAT levels was associated with lower modified Woodcock calcification scores. (p-value = 0.038) CONCLUSIONS: Measurement of AAT levels in patients with acute stroke is feasible, and there may be associations between AAT levels and stroke mechanism that warrant further study in larger samples.

Thrombectomy in DAWN- and DEFUSE-3-Ineligible Patients: A Subgroup Analysis From the BEST Prospective Cohort Study.

BACKGROUND: Because of the overwhelming benefit of thrombectomy for highly selected trial patients with large vessel occlusion (LVO), some trial-ineligible patients are being treated in practice. OBJECTIVE: To determine the safety and efficacy of thrombectomy in DAWN/DEFUSE-3-ineligible patients. METHODS: Using a multicenter prospective observational study of consecutive patients with anterior circulation LVO who underwent late thrombectomy, we compared symptomatic intracerebral hemorrhage (sICH) and good outcome (90-d mRS 0-2) among DAWN/DEFUSE-3-ineligible patients to trial-eligible patients and to untreated DAWN/DEFUSE-3 controls. RESULTS: Ninety-eight patients had perfusion imaging and underwent thrombectomy >6 h; 46 (47%) were trial ineligible (41% M2 occlusions, 39% mild deficits, 28% ASPECTS <6). In multivariable regression, the odds of a good outcome (aOR 0.76, 95% CI 0.49-1.19) and sICH (aOR 3.33, 95% CI 0.42-26.12) were not different among trial-ineligible vs eligible patients. Patients with mild deficits were more likely to achieve a good outcome (aOR 3.62, 95% CI 1.48-8.86) and less sICH (0% vs 10%, P = .16), whereas patients with ASPECTS <6 had poorer outcomes (aOR 0.14, 95% CI 0.05-0.44) and more sICH (aOR 24, 95% CI 5.7-103). Compared to untreated DAWN/DEFUSE-3 controls, trial-ineligible patients had more sICH (13%BEST vs 3%DAWN [P = .02] vs 4%DEFUSE [P = .05]), but were more likely to achieve a good outcome at 90 d (36%BEST vs 13%DAWN [P < .01] vs 17%DEFUSE [P = .01]). CONCLUSION: Thrombectomy is used in practice for some patients ineligible for the DAWN/DEFUSE-3 trials with potentially favorable outcomes. Additional trials are needed to confirm the safety and efficacy of thrombectomy in broader populations, such as large core infarction and M2 occlusions.