We investigated whether admission LDL-C levels are associated with clinical profile and outcomes after acute ischaemic stroke by comparing patients stratified into five LDL-C groups. We retrospectively analyzed consecutively included patients ≥18 years admitted to the Bernese Stroke Centre (02/2015–03/2023). Patients were stratified into five LDL-C groups: >3.0 mmol/L (n=493), 2.6–3.0 mmol/L (n=225), 1.8–2.6 mmol/L (n=490), 1.4–1.8 mmol/L (n=254) and <1.4 mmol/L (n=172). LDL-C was measured within 24 h of admission. Outcomes included successful reperfusion, symptomatic intracranial haemorrhage, favourable and excellent functional outcomes at 3 months, and 3-month mortality. Separate complete-case multivariable logistic regression models evaluated LDL-C as a continuous and five-level categorical exposure, adjusting for prespecified clinical covariates. Among 1634 patients, those with LDL-C <1.4 mmol/L were older (median 78 vs. 73 years; p<0.001), more often male (59

Background and Objectives More than half of the endovascularly treated ischemic stroke patients with incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction [eTICI] <3) show delayed reperfusion (DR) on 24-hour perfusion imaging, which is associated with favorable clinical outcome. The effect of intravenous thrombolysis (IVT) on the rates of DR remains unclear. This study aimed to assess the treatment effect of IVT on the occurrence of DR. Methods Pooled data from 3 randomized controlled trials (EXTEND-IA and EXTEND-IA TNK parts 1 and 2) and 2 comprehensive stroke centers (University Hospitals Graz and Bern) were analyzed. Only patients with a final reperfusion score of eTICI 2a-2c and available perfusion imaging at follow-up of 24 +/- 12 hours were included. The primary outcome was the presence of DR on 24-hour follow-up CT/MRI perfusion imaging, defined as the absence of any focal perfusion deficit on perfusion imaging, despite incomplete reperfusion on the final angiography series during thrombectomy. For the secondary analysis, we explored the association between the primary outcome (DR) and the time elapsed between start of IVT and the end of an intervention. To address confounding in observational data, we performed a target trial emulation. Results Of 832 included patients with eTICI 2a-2c (median age 74 years, 49% female), 511 (61%) had DR. There was an independent treatment effect of IVT on DR (standardized risk ratio [sRR] 1.1, 95% CI 1.0-1.3; standardized risk difference [sRD] 8.2%, 95% CI 0.2%-16.1%), after adjusting for age, sex, atrial fibrillation, number of device passes, collateral score, and eTICI. Among those patients who have received IVT (n = 524/832, 63%), when adjusting for the aforementioned covariates, there was a causal effect of shorter time between administration of thrombolytics and end of the intervention on DR (sRR 0.93%, 95% CI 0.87-0.98; sRD -5.2%; 95% CI -9.1% to -1.3%, per hour increase). Discussion Exposure to thrombolytics showed independent treatment effect on the occurrence of DR among patients with incomplete reperfusion after thrombectomy who undergo perfusion imaging at the 24-hour follow-up. The effect of thrombolytics on DR was observed if there was a high chance of therapeutic concentrations of thrombolytics at the time point when the proximal vessel was recanalized, but distal occlusions persisted and/or occurred. Classification of Evidence This study is rated Class III because it is a nonrandomized study and there are substantial differences in baseline characteristics of the treatment groups.

BACKGROUND:Selection of acute stroke patients for endovascular thrombectomy (EVT) within 6 h from symptom onset can be done using MRI or CT. However, association of either imaging modality with better clinical outcomes or shorter workflow times is still not fully understood. METHODS:We searched Medline and Ovid-Embase for studies comparing outcomes and workflow metrics between patients selected for EVT using CT or MRI from inception to November 30, 2024. The primary outcome was the association of imaging modality with functional independence (modified Rankin Scale score, 0-2) at 90-days and workflow metrics. Pooled odds ratios with 95% CIs were calculated using a random-effects model. RESULTS:Nine studies with 11,202 patients (3018 with MRI vs 8184 with CT) were analysed. Patients selected with MRI had similar odds of 90-day mRS 0-2 (adjusted odds ratio [aOR] 1.1195% CI 0.84-1.47) and lower mortality (aOR 0.6695% CI 0.57-0.76) compared to those selected with CT. Door-to-imaging time (mean difference [MD] 11.2 min 95% CI 4.8 to 18.4) and door-to-intravenous thrombolysis initiation time (MD 10.1 min 95% CI 4.9 to 15.2) were longer in patients selected with MRI. However, door-to-arterial puncture time was similar between both groups (MD 6.8 min 95% CI -4.6 to 18.1). CONCLUSION:In stroke patients undergoing EVT within 6 h from symptom onset, MRI before EVT could be a feasible alternative to CT without significant delays from door to puncture time. Randomized trials are needed before these findings can be generalized.

BACKGROUND:Intravenous thrombolysis (IVT) in patients with recent ingestion of direct oral anticoagulants (DOACs) is a frequent challenge and remains controversial. The benefit of DOAC reversal before IVT is uncertain. METHODS:Using target trial methodology, we analyzed data from 28 comprehensive stroke centers. Patients on DOACs were included if they met IVT criteria, had a National Institutes of Health Stroke Scale score of ≥2, and last DOAC intake within 48 hours or was undeterminable. Safety and efficacy outcomes (symptomatic intracerebral hemorrhage, any intracerebral hemorrhage, major bleeding, 90-day mortality, and good functional outcome [modified Rankin Scale score of 0-2 or return to baseline]) were compared between those receiving IVT versus no IVT and IVT with versus without reversal. In addition, a comparison was made with patients from the New Zealand stroke registry, all of whom underwent reversal with idarucizumab. We adjusted for covariates known to be associated with safety and efficacy outcomes, including age, stroke severity, intended thrombectomy, blood glucose, blood pressure, DOAC reversal, and time from last intake. RESULTS:Overall, 1342 patients fulfilled the target trial criteria. The median age was 80 (interquartile range, 73-86) years, median National Institutes of Health Stroke Scale score was 11, 50% were female, and 52% of patients received endovascular therapy. IVT was given in 342 of 1342 (25%) patients. Of these, 141 (41.2%) had verified DOAC intake <12 hours before admission, and 92 (26.9%) within 12 to 24 hours. Symptomatic intracerebral hemorrhage occurred in 10 of 328 (3.0%) of patients receiving IVT and 54 of 921 (5.9%) patients not receiving IVT (adjusted difference, -2.1% [95% CI, -5.3% to +1.2]). Patients receiving IVT were more likely to have good functional outcomes (adjusted difference, +14.4% [95% CI, +7.1% to +21.8%]). Comparing 289 patients with reversal (from the additional New Zealand registry) and 283 patients without reversal before IVT (from the target trial population), there was no significant difference in symptomatic intracerebral hemorrhage, major bleeding, or efficacy outcomes. CONCLUSIONS:This target trial confirms previous observational data regarding the safety of off-label IVT in patients with recent DOAC intake. More data and dedicated trials are needed for patients with confirmed high DOAC plasma levels and regarding the efficacy and safety of DOAC reversal before IVT.

More than half of the endovascularly treated ischemic stroke patients with incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction [eTICI] <3) show delayed reperfusion (DR) on 24-hour perfusion imaging, which is associated with favorable clinical outcome. The effect of intravenous thrombolysis (IVT) on the rates of DR remains unclear. This study aimed to assess the treatment effect of IVT on the occurrence of DR. Pooled data from 3 randomized controlled trials (EXTEND-IA and EXTEND-IA TNK parts 1 and 2) and 2 comprehensive stroke centers (University Hospitals Graz and Bern) were analyzed. Only patients with a final reperfusion score of eTICI 2a-2c and available perfusion imaging at follow-up of 24 ± 12 hours were included. The primary outcome was the presence of DR on 24-hour follow-up CT/MRI perfusion imaging, defined as the absence of any focal perfusion deficit on perfusion imaging, despite incomplete reperfusion on the final angiography series during thrombectomy. For the secondary analysis, we explored the association between the primary outcome (DR) and the time elapsed between start of IVT and the end of an intervention. To address confounding in observational data, we performed a target trial emulation. Of 832 included patients with eTICI 2a-2c (median age 74 years, 49% female), 511 (61%) had DR. There was an independent treatment effect of IVT on DR (standardized risk ratio [sRR] 1.1, 95% CI 1.0-1.3; standardized risk difference [sRD] 8.2%, 95% CI 0.2%-16.1%), after adjusting for age, sex, atrial fibrillation, number of device passes, collateral score, and eTICI. Among those patients who have received IVT (n = 524/832, 63%), when adjusting for the aforementioned covariates, there was a causal effect of shorter time between administration of thrombolytics and end of the intervention on DR (sRR 0.93%, 95% CI 0.87-0.98; sRD -5.2%; 95% CI -9.1% to -1.3%, per hour increase). Exposure to thrombolytics showed independent treatment effect on the occurrence of DR among patients with incomplete reperfusion after thrombectomy who undergo perfusion imaging at the 24-hour follow-up. The effect of thrombolytics on DR was observed if there was a high chance of therapeutic concentrations of thrombolytics at the time point when the proximal vessel was recanalized, but distal occlusions persisted and/or occurred. This study is rated Class III because it is a nonrandomized study and there are substantial differences in baseline characteristics of the treatment groups.

BACKGROUND AND OBJECTIVES:Covert brain infarcts (CBIs) in patients with first-ever ischemic stroke (IS) and atrial fibrillation (AF) are associated with an increased risk of stroke recurrence. We aimed to assess whether CBIs modify the treatment effect of early vs late initiation of direct oral anticoagulants (DOACs) in patients with IS and AF. METHODS:We conducted a post hoc analysis of the international, multicenter, randomized-controlled ELAN trial, which compared early (<48 hours after ischemic stroke for minor and moderate stroke, 6-7 days for major stroke) vs late (>48 hours for minor, 3-4 days for moderate, 12-14 days for major stroke) initiation of DOACs in patients with IS and AF. The primary outcome was a composite of recurrent IS, symptomatic intracranial hemorrhage (sICH), major extracranial bleeding, systemic embolism, or vascular death within 30 days after stroke; secondary outcomes were the individual components. We estimated outcomes based on the presence of CBIs (any CBI vs no CBI) on prerandomization imaging (core-lab rating) using adjusted risk differences (aRDs) between treatment arms. Point estimates and 95% CIs are presented without reporting p values. RESULTS:Of the 1,694 participants with first-ever IS included (median age: 77 years, 45.9% female), 678 (40.0%) had CBI. The imaging core-lab interrater reliability for the presence of CBI was 0.87 (0.81-0.94). The primary outcome occurred in 8 (2.3%; recurrent IS: 3/342) of 342 participants with CBI assigned to the early treatment arm vs 20 (6.0%; recurrent IS: 12/336) of 336 assigned to the late treatment arm (aRD: -3.6%, 95% CI -6.6 to -0.6) (p for interaction: 0.063). With early DOAC treatment, IS recurrence risk was lower in participants with CBI (aRD: -2.7%, 95% CI -5.0 to -0.4), but not in participants without CBI (aRD: -0.4, 95% CI -2.1 to 1.2). No sICH was observed in the early treatment group. DISCUSSION:The presence of CBI may indicate a subgroup of patients with first-ever IS and AF who particularly benefits from early DOAC initiation to prevent ischemic event recurrence, without increasing harm. Our findings should be considered in clinical decision making regarding timely DOAC treatment in patients with stroke and AF. CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that in patients with covert brain infarcts, atrial fibrillation, and first-ever ischemic stroke, early (vs late) initiation of DOACs is associated with lower risk of recurrent stroke with no increase in harm. TRIAL REGISTRATION INFORMATION:URL: clinicaltrials.gov/study/NCT03148457; Unique identifier: NCT03148457; submitted: April 7, 2017; first patient enrolled: November 6, 2017.

Background In people with suspected stroke the first assessment occurs under time pressure in the emergency department and is based solely on clinical information. Working hypotheses include mechanism and localization of the clinical deficit on imaging. To assess the performance of neurologists in such situation, we investigated the accuracy with which board‐certified neurologists make the correct diagnosis based solely on clinical information. Methods In this prospective diagnostic accuracy study done at an emergency department of a university hospital, neurologists had to commit themselves to a diagnosis in people with suspected acute stroke. The main analysis was the accuracy with which they distinguished vascular from nonvascular causes using the discharge diagnosis as a reference. Secondary analyses included the distinction of ischemic from hemorrhagic strokes, and the accuracy with which the lesion location and site of vessel occlusion were identified. The performance of neurologists was also compared to residents and medical students. Results Of 800 people with suspected stroke, 567 (71%) had a vascular (508 ischemic stroke or transient ischemic attack and 59 hemorrhagic stroke) and 233 (29%) had a nonvascular disorder (72 seizures, 33 migraine auras, 12 functional neurological disorders, and 116 other diseases). Vessel occlusion was found in 227 of 410 people with ischemic stroke. Neurologists identified vascular origin with an accuracy of 0.86 (95% CI: 0.83–0.89), a sensitivity of 0.93 (0.90–0.95), and a specificity of 0.66 (0.58–0.73). The accuracy to identify ischemia compared with hemorrhage was 0.91 (0.87–0.93). Neurologists’ accuracy to predict the presence of vessel occlusion was 0.66 (0.61–0.71), of exact lesion location was 42%, and of the affected blood vessel 57%. Conclusion In people with acute neurological deficits, the accuracy with which neurologists identify vascular origin is high and depends on neurological education. Experienced physicians should be involved early in the management of people with “code stroke.”

BACKGROUND: A third of endovascularly treated patients with stroke experience incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction [eTICI] <3), and the natural evolution of this incomplete reperfusion remains unknown. We systematically reviewed the literature and performed a meta-analysis on the natural evolution of incomplete reperfusion after endovascular therapy. METHODS:A systematic review of MEDLINE, Embase, and PubMed up until March 1, 2024, using a predefined strategy. Only full-text English-written articles reporting rates of either favorable (ie, delayed reperfusion (DR) or no new infarct) or unfavorable progression (ie, persistent perfusion deficit or new infarct) of incompletely reperfused tissue were included. The primary outcome was the rate of DR and its association with functional independence (modified Rankin Scale score, 0-2) at 90 days postintervention. Pooled odds ratios with 95% CIs were calculated using a random-effects model. RESULTS: Six studies involving 950 patients (50.7% female; median age, 71 years; interquartile range, 60-79) were included. Four studies assessed the evolution of incomplete reperfusion on magnetic resonance imaging perfusion imaging, while 2 studies used diffusion-weighted imaging and noncontrast computed tomography imaging, where new infarct was used to denote unfavorable progression. Five studies defined incomplete reperfusion as eTICI 2b50 or 2c. DR occurred in 41% (interquartile range, 33%-51%) of cases 24 hours postintervention. Achieving DR was associated with a higher likelihood of functional independence at 90 days (odds ratio, 2.5 [95% CI, 1.9-3.4]). CONCLUSIONS: Nearly half of eTICI <3 patients achieve DR, leading to favorable clinical outcomes. This subgroup may derive limited or potentially harmful effects from pursuing additional reperfusion strategies (eg, intra-arterial lytics or secondary thrombectomy). Accurately predicting the evolution of incomplete reperfusion could optimize patient selection for adjunctive reperfusion strategies at the end of an intervention.

BACKGROUND AND OBJECTIVES:Diffusion-weighted imaging (DWI) lesions in patients with intracerebral hemorrhage (ICH) are associated with poor outcomes. Knowledge about the underlying pathophysiology is scarce, and it is hypothesized that they are related to either the ICH itself, adverse effects of treatment, or the activity of the underlying small vessel disease (SVD) causing the ICH. We investigated their association with time point of MRI acquisition and underlying SVD type and burden. METHODS:In this Swiss multicenter ICH cohort, we enrolled patients who underwent MRI within 15 days after SVD-associated ICH. The primary outcome was presence of DWI lesions. Time point of MRI was investigated as a continuous (days) and dichotomized (hyperacute = MRI on admission vs subacute = MRI during follow-up) variable. We measured cerebral amyloid angiopathy (CAA) and SVD severity using MRI burden scores and defined the type of SVD using CADMUS classification and Boston 2.0 criteria. At 3 months, we assessed functional outcome using the modified Rankin Scale score, recurrent ICH, and ischemic stroke. RESULTS:We included 644 patients (median age 73 years, interquartile range [IQR] 64-79, median SVD burden 1 IQR 1-2; median CAA burden 2 IQR 1-3; 208 patients/32.3% with Boston 2.0 CAA, 431 patients/66.9% with mixed CAA-DPA phenotype according to CADMUS). Among enrolled patients, 16.0% underwent hyperacute MRI and 84.0% underwent subacute MRI (median on day 2 IQR 1-5), and 166 patients (25.8%) had DWI lesions (18.4% with hyperacute MRI vs 27.2% with subacute MRI). We observed no association of presence of DWI lesions with hyperacute MRI (adjusted odds ratio [aOR] 0.61, 95% CI 0.36-1.00, p = 0.073) but with time to MRI in days (aOR 1.07, 95% CI 1.00-1.13, p = 0.007). Higher SVD (aOR 1.33, 95% CI 1.12-1.59, p = 0.001) and CAA (aOR 1.29, 95% CI 1.15-1.44, p < 0.001) burdens were associated with presence of DWI lesions. There was no association between type of SVD (CADMUS) or CAA (Boston criteria) and DWI lesions. There was no association between DWI lesions and functional outcome, recurrent ICH or ischemic stroke at 3 months. DISCUSSION:DWI lesions in patients with ICH are already common at baseline. Their prevalence is higher with a longer time since symptom onset and with higher SVD burden. Overall, these findings suggest a relation with the underlying condition resulting in ICH. The significant number of DWI lesions visible on admission MRI might diminish their use as surrogate outcome in future trials in ICH.

BACKGROUND:Chronic cerebellar lesions of presumed ischemic origin are frequently found in patients with ischemic stroke and as incidental findings. However, the differentiation of embolic lesions from lesions caused by cerebral small vessel disease (SVD) is unclear. We aimed to investigate whether the location of chronic cerebellar ischemic lesions (deep versus cortical) indicates the underlying cause (embolic versus SVD). METHODS:This study was a post hoc data analysis from the multinational ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Patients With Postischemic Stroke With Atrial Fibrillation), which included patients with acute ischemic stroke and atrial fibrillation cohort between 2017 and 2022. For comparison, data from 2 cohorts (DiViNAS [Disease Variability in NOTCH3-Associated SVD] and VASCAMY [Vascular and Amyloid Predictors of Neurodegeneration and Cognitive Decline in Nondemented Subjects]) consisting of participants with hereditary cerebral SVD (ie, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) were analyzed (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy cohort). Brain magnetic resonance imaging scans were evaluated for presence and location of chronic cerebellar ischemic lesions. The association between these lesions and the severity of supratentorial SVD was analyzed using univariable and multivariable models, adjusting for key covariables. RESULTS:In the atrial fibrillation cohort (N=790), 278 (35%) patients had chronic cerebellar ischemic lesions (cortical: n=242; deep: n=36). In multivariable analyses, features of cerebral SVD were associated with deep cerebellar ischemic lesions (summary SVD score; odds ratio per point, 2.5 [95% CI, 1.5-3.5]; P<0.001), while there was no association of SVD markers and cortical cerebellar ischemic lesions (summary SVD score; odds ratio per point, 1.1 [95% CI, 0.9-1.3]; P=0.107). In the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy cohort (N=257), chronic cerebellar ischemic lesions (n=108 [42%]) were almost exclusively identified in deep cerebellar regions (n=101, 94%). CONCLUSIONS:Chronic cerebellar ischemic lesions in deep but not cortical regions were associated with supratentorial cerebral SVD. Therefore, cerebral SVD is likely the primary cause of chronic ischemic lesions in deep cerebellar regions, while cortical cerebellar lesions are more likely attributable to embolic etiologies. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03148457.

Implantable cardiac monitors (ICM) are increasingly being utilized for atrial fibrillation (AF) screening after ischemic stroke, but its yield depends on patient selection and prior testing. This prospective registry study included consecutive patients with a cryptogenic ischemic stroke and at least one of the following predictors of incident AF: age >65 years, NT-proBNP >400 pg/mL, left atrial diameter >44 mm, frequent atrial ectopy, or involvement of multiple cerebrovascular territories compatible with an embolic source. Prior to ICM implantation, all patients underwent in-hospital telemetry monitoring (within the first 24–72 hours post-stroke) and a 7-day Holter ECG at discharge. Patients diagnosed with AF during these tests were excluded. The primary endpoint of the study was any AF episode lasting >2 minutes detected by remote monitoring of the ICM. Of the 308 patients who received an ICM since January 2020, 212 (69%) were male, with a mean age at implantation of 64±12 years (Table). After a median follow-up of 17.8±13.7 months, AF was detected in 66 patients (21%) overall. Twelve months after implantation, AF was diagnosed in 19% of patients (Figure). Longest AF episodes recorded by the ICM until the end of follow-up exceeded 2 minutes in 65 patients (21.1%), 6 minutes in 59 (19.2%), one hour in 49 (15.9%), 6 hours in 27 (8.8%) and 24 hours in 8 (2.6%). In one patient, we could not retrieve any information on AF episode duration. Among patients with AF diagnosis, oral anticoagulation therapy was started in 60 patients and two patients had left atrial appendage occlusion. Oral anticoagulation was recommended in the remaining four patients. Device-related complications included vasovagal reaction during the implantation procedure in one patient and premature explantation due to infection or discomfort in seven patients. Using sequential prior testing and a pragmatic selection approach of patients with cryptogenic ischemic stroke, AF was detected by an ICM in 19% of patients after 12 months. However, only a minority of patients had AF episodes lasting longer than 24 hours.

Background:Approximately 5-10% of patients with acute ischemic stroke (AIS) have known active cancer. These patients are at high risk for both recurrent AIS and major bleeding. The optimal antithrombotic strategy for cancer-related stroke is uncertain. This study compared clinical outcomes among patients with cancer-related stroke treated with anticoagulant versus antiplatelet therapy for secondary prevention. Methods:We identified consecutive patients with AIS and active cancer hospitalized at our comprehensive stroke center from 2015 through 2020. Patients with cardioembolic mechanisms were excluded. We used Cox regression and inverse probability of treatment weighting (IPTW) analyses to evaluate the associations between type of antithrombotic therapy at discharge (anticoagulant versus antiplatelet therapy) and the main outcomes of 1-year mortality and long-term recurrent AIS. Results:Among 5,012 AIS patients, 306 had active cancer. After applying study eligibility criteria, we analyzed 135 patients (median age 72 years; 44% women), of whom 58 (43%) were treated with anticoagulant and 77 (57%) with antiplatelet therapy. The median follow-up time was 495 days (IQR, 57-1,029). Patients treated with anticoagulants, compared to patients treated with antiplatelet therapy, were younger (median 69 versus 75 years), had more metastatic disease (72% versus 41%), and higher median baseline D-dimer levels (median 8,536 μg/L versus 1,010 μg/L). Anticoagulant versus antiplatelet therapy was associated with similar risks of 1-year mortality (adjusted hazard ratio [aHR], 0.76; 95% confidence interval [CI], 0.36-1.63) and long-term recurrent AIS (aHR 0.49; 95% CI 0.08-2.83). The IPTW analyses for 1-year mortality confirmed the results of the main analyses (HR 0.82; 95%CI: 0.39-1.72, p = 0.61). Conclusion:Factors associated with anticoagulant use in patients with cancer-related stroke include younger age, more advanced cancer, and elevated D-dimer. Similar outcomes were seen with anticoagulant versus antiplatelet therapy in these patients highlighting the need for future randomized trials to determine the preferred antithrombotic strategy.

BACKGROUND AND OBJECTIVES:While MRI is known to be crucial for TIA workup, the benefit of perfusion-weighted imaging (PWI) is underexplored. We aimed to assess the association between focal hypoperfusion on baseline PWI MRI and the long-term incidence of subsequent acute ischemic stroke (AIS) after TIA. METHODS:Consecutive patients with TIA who underwent baseline PWI MRI as part of their emergency consultation between January 2015 and December 2019 were retrospectively identified. For study inclusion, both a time-based (symptom duration <24 hours) and an imaging-based (no signs of ischemia on diffusion-weighted imaging) TIA definition were applied. Long-term incidences of AIS after TIA were identified based on follow-up reports. Associations between focal hypoperfusion and subsequent AIS were assessed using Cox regression models adjusted for predefined predictors of stroke occurrence including symptomatic extracranial or intracranial stenosis. In subgroup analyses, we aimed to determine effects of focal hypoperfusion within vs outside the expected TIA territory, defined as a brain region potentially correlating with TIA symptoms. RESULTS:Of 1,359 eligible patients with TIA, 1,075 with PWI MRI (79%) were included (median age 70 years, 46% female). Focal hypoperfusion was identified in 211 patients (20%); in 116 of 211 (55%), hypoperfusion occurred within the expected TIA territory. The median time from symptom onset to imaging was 233 minutes (interquartile range [IQR] 131-632) for patients with focal hypoperfusion vs 229 minutes [IQR 140-441] for patients without (p = 0.42). Focal hypoperfusion was associated with a higher incidence of AIS (adjusted hazard ratio [aHR] 2.13; 95% CI 1.19-3.80). While this was observed for focal hypoperfusion within the expected TIA territory (aHR 3.95; 95% CI 2.05-7.60), there was no such association in case of focal hypoperfusion outside the expected TIA territory (aHR 0.72; 95% CI 0.25-2.03). DISCUSSION:Focal hypoperfusion on acute PWI MRI was found in 1 in 5 patients with TIA. It was associated with a higher incidence of AIS during long-term follow-up, especially when within the expected TIA territory. Further research is needed to clarify the predictive value of focal hypoperfusion in relation to the incidence of AIS after TIA and to explore potential therapeutic implications.

BACKGROUND AND PURPOSE:Flat-panel detector CT immediately after mechanical thrombectomy can detect complications, including early hemorrhagic transformation and subarachnoid hyperdensities. The clinical significance of subarachnoid hyperdensities in patients undergoing mechanical thrombectomy remains unclear. MATERIALS AND METHODS:We studied 223 patients who underwent mechanical thrombectomy for anterior circulation stroke who had flat-panel detector CT performed immediately after the procedure and had follow-up imaging within 24 hours. Subarachnoid hyperdensity severity was categorized into 5 grades (subarachnoid hyperdensities, 0: absent to subarachnoid hyperdensities, IV: extensive). Baseline and procedural characteristics as well as outcome measures were analyzed using group comparisons and multivariable logistic regression analyses. RESULTS:Overall, 100/223 (45%) patients showed subarachnoid hyperdensities on immediate postinterventional flat-panel detector CT. The factors associated with an increased subarachnoid hyperdensity risk were the following: medium-vessel occlusion or distal-vessel occlusion compared with a large-vessel occlusion, a more distal device position, a higher number of device passes, a larger volume of contrast applied, worse final reperfusion expanded TICI, and after receiving IV thrombolysis. The occurrence of subarachnoid hyperdensity grades II-IV was independently associated with worse functional outcomes (adjusted OR for mRS, 3-6: 2.2; 95% CI 1.1-4.3), whereas patients with subarachnoid hyperdensity grade I had outcomes similar to those in patients without subarachnoid hyperdensities. CONCLUSIONS:Our study identified risk factors for subarachnoid hyperdensities, most of which reflect increasingly challenging procedures or more peripheral recanalization attempts. The presence of subarachnoid hyperdensity grades II-IV was associated with poorer outcomes, suggesting the need for personalized strategies to reduce its incidence and severity or potentially improve recovery after subarachnoid hyperdensities.

The administration of intravenous thrombolysis (IVT) for patients with acute ischemic stroke who have recently ingested direct oral anticoagulants (DOACs) presents a clinical challenge due to the perceived increased risk of intracranial hemorrhage (ICH). Traditional guidelines from the US and European authorities advise against IVT within 48 h of last DOAC ingestion, unless specific coagulation tests indicate safety. However, emerging observational studies suggest that IVT might be safe in selected patients. A US stroke registry study and a global multicenter cohort study both reported no significant increase in symptomatic ICH among patients on DOACs compared to those not on anticoagulants. A systematic review of all published observational studies further supported these findings, showing comparable bleeding rates and functional outcomes in DOAC-treated patients. Reversal agents like idarucizumab for dabigatran have demonstrated potential in facilitating safer IVT administration, though logistical and cost-related barriers limit their widespread use. The variability in global guidelines reflects differing approaches to risk assessment and resource availability, highlighting the need for individualized treatment decisions. In India, the increasing prevalence of atrial fibrillation and stroke as well as prescription of DOACs necessitate adapted guidelines that consider local health-care infrastructure. Despite the promising observational data, the lack of randomized controlled trials underscores the need for further research to establish robust evidence for IVT use in this context. Collaborative international efforts and inclusion of diverse patient populations in future studies will be crucial to refine treatment protocols and improve outcomes for stroke patients on DOACs.

Introduction: Knowledge about uptake and workflow metrics of hyperacute treatments in patients with non-traumatic intracerebral haemorrhage (ICH) in the emergency department is scarce. Methods: Single-centre retrospective study of consecutive patients with ICH between 01/2018–08/2020. We assessed uptake and workflow metrics of acute therapies overall and according to referral mode (stroke code, transfer from other hospital, or other). Results: We enrolled 332 patients (age 73 years, IQR: 63–81 and GCS 14 points, IQR: 11–15, onset-to-admission time 284 min, IQR: 111–708 min), of whom 101 patients (35%) had lobar haematoma. Mode of referral was stroke code in 129 patients (38%), transfer from other hospital in 143 patients (43%), and arrival by other means in 60 patients (18%). Overall, 143 of 216 (66%) patients with systolic blood pressure >150 mm Hg received IV-antihypertensive treatment, and 67 of 76 (88%) on therapeutic oral anticoagulation received prothrombin complex concentrate treatment (PCC). Forty-six patients (14%) received any neurosurgical intervention within 3 h of admission. Median treatment times from admission to first IV-antihypertensive treatment were 38 min (IQR: 18–72 min) and 59 min (IQR: 37–111 min) for PCC, with significant differences according to mode of referral (p < 0.001) but not early arrival (≤6 h of onset, p = 0.92). The median time in the emergency department was 139 min (IQR: 85–220 min), and among patients with elevated blood pressure, only 44% achieved a successful control (<140 mm Hg) during ED stay. In multivariate analysis, code ICH concordant treatment was associated with significantly lower odds for in-hospital mortality (aOR 0.30, 95% CI: 0.12–0.73, p = 0.008) and non-significant trends towards better functional outcome measured using the modified Rankin scale score at 3 months (aOR for ordinal shift 0.54, 95% CI: 0.26–1.12, p = 0.097). Conclusion: Uptake of hyperacute therapies for ICH treatment in the ED is heterogeneous. Treatment delays are short, but not all patients achieve treatment targets during ED stay. Code ICH-concordant treatment may improve clinical outcomes. Further improvements seem achievable by advocating for a “code ICH” to streamline acute treatments.

Intravenous thrombolysis is not recommended in anticoagulated patients receiving direct oral anticoagulants (DOACs) and a recent intake within the last 48 hours in US and European guidelines. However, three observational studies now suggest safety of thrombolysis in patients with recent intake of DOACs, and thus support previous experimental data. In this perspective, the current evidence and practical consequences are discussed.

INTRODUCTION:Covert brain infarcts (CBI) are frequent incidental findings on MRI and associated with future stroke risk in patients without a history of clinically evident cerebrovascular events. However, the prognostic value of CBI in first-ever ischemic stroke patients is unclear and previous studies did not report on different etiological stroke subtypes. We aimed to test CBI phenotypes and their association with stroke recurrence in first-ever ischemic stroke patients according to stroke etiology. PATIENTS AND METHODS:This study is a pooled data analysis of two prospectively collected cohorts of consecutive first-ever ischemic stroke patients admitted to the comprehensive stroke centers of Bern (Switzerland) and Graz (Austria). CBI phenotypes were identified on brain MRI within 72 h after admission. All patients underwent a routine follow-up (median: 12 months) to identify stroke recurrence. RESULTS:Of 1577 consecutive ischemic stroke patients (median age: 71 years), 691 patients showed CBI on brain MRI (44%) and 88 patients had a recurrent ischemic stroke (6%). Baseline CBI were associated with stroke recurrence in multivariable analysis (HR 1.9, 95% CI 1.1-3.3). CBI phenotypes with the highest risk for stroke recurrence were cavitatory CBI in small vessel disease (SVD)-related stroke (HR 7.1, 95% CI 1.6-12.6) and cortical CBI in patients with atrial fibrillation (HR 3.0, 95% CI 1.1-8.1). DISCUSSION AND CONCLUSION:This study reports a ≈ 2-fold increased risk for stroke recurrence in first-ever ischemic stroke patients with CBI. The risk of recurrent stroke was highest in patients with cavitatory CBI in SVD-related stroke and cortical CBI in patients with atrial fibrillation.Subject terms: Covert brain infarcts, stroke.