Perfusion Abnormalities on 24-Hour Perfusion Imaging in Patients With Complete Endovascular Reperfusion.

BACKGROUND: Perfusion abnormalities in the infarct and salvaged penumbra have been proposed as a potential reason for poor clinical outcome (modified Rankin Scale score >2) despite complete angiographic reperfusion (Thrombolysis in Cerebral Infarction [TICI3]). In this study, we aimed to identify different microvascular perfusion patterns and their association with clinical outcomes among TICI3 patients. METHODS: University Hospital Bern's stroke registry of all patients between February 2015 and December 2021. Macrovascular reperfusion was graded using the TICI scale. Microvascular reperfusion status was evaluated within the infarct area on cerebral blood volume and cerebral blood flow perfusion maps obtained 24-hour postintervention. Primary outcome was functional independence (90-day modified Rankin Scale score 0-2) evaluated with the logistic regression analysis adjusted for age, sex, and 24-hour infarct volume from follow-up imaging. RESULTS: Based on microvascular perfusion findings, the entire cohort (N=248) was stratified into one of the 4 clusters: (1) normoperfusion (no perfusion abnormalities; n=143/248); (2) hyperperfusion (hyperperfusion on both cerebral blood volume and cerebral blood flow; n=54/248); (3) hypoperfusion (hypoperfusion on both cerebral blood volume and cerebral blood flow; n=14/248); and (4) mixed (discrepant findings, eg, cerebral blood volume hypoperfusion and cerebral blood flow hyperperfusion; n=37/248). Compared with the normoperfusion cluster, patients in the hypoperfusion cluster were less likely to achieve functional independence (adjusted odds ratio, 0.3 [95% CI, 0.1-0.9]), while patients in the hyperperfusion cluster tended to have better outcomes (adjusted odds ratio, 3.3 [95% CI, 1.3-8.8]). CONCLUSIONS: In around half of TICI3 patients, perfusion abnormalities on the microvascular level can be observed. Microvascular hypoperfusion, despite complete macrovascular reperfusion, is rare but may explain the poor clinical course among some TICI3 patients, while a detrimental effect of hyperperfusion after reperfusion could not be confirmed.

Early Versus Late Initiation of Endovascular Therapy in Patients with Severe Cerebral Venous Sinus Thrombosis.

BACKGROUND: Endovascular therapy (EVT) for severe cerebral venous sinus thrombosis (CVST) is controversial in terms of indication and clinical benefit. The impact of delay of EVT on functional recovery is unclear. This study aimed to investigate the effect of early versus late initiation of EVT in severe CVST. METHODS: From prospective EVT and CVST registries, patients with CVST diagnosed between January 2010 and December 2022 were retrospectively identified for this multicenter collaboration. EVT was considered in severe CVST with features prone to a poor prognosis. We compared early (< 24 h) with late (> 24 h) initiation of EVT after the presentation in the emergency department and subsequent CVST diagnosis. Outcome parameters included functional independence (modified Rankin Scale [mRS] score 0-2) at 90 days, mRS score at discharge, in-hospital mortality, and mortality at 3 months. RESULTS: Of 363 patients with CVST, 45 (12.4%; 31 [early EVT] vs. 14 [late EVT]) were included in this study. We found a higher proportion of patients with functional independence at 3 months among early versus late EVT (66.7% vs. 27.3%; odds ratio [OR] 5.3; 95% confidence interval 1.02-25; p = 0.036). In multivariate logistic regression, late EVT was inversely correlated with functional independence (OR 0.17 [0.04-0.83]; p = 0.011). The mortality rate was 16.7% versus 36.4% (mRS 6 at 3 months, OR 0.34, 95% confidence interval 0.07-1.75; p = 0.217) at 90 days for early versus late EVT. CONCLUSIONS: We observed a higher rate of functional independence in patients with early EVT. These preliminary findings must be confirmed in subsequent randomized controlled trials evaluating a "time-is-brain" paradigm for EVT in CVST.

Factors impacting D-dimer levels in patients with acute ischemic cerebrovascular events.

BACKGROUND AND OBJECTIVES: A better understanding of the factors influencing D-dimer levels in code stroke patients is needed to guide further investigations of concomitant thrombotic conditions. This study aimed to investigate the impact of time from symptom onset and other factors on D-dimer levels in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). METHODS: Data on consecutive AIS and TIA patients treated at our tertiary-care stroke center between January 2015 and December 2020 were retrospectively assessed. Patients with available D-dimer levels were evaluated for eligibility. Multivariable non-linear regression analyses were performed. RESULTS: In total, 2467 AIS patients and 708 TIA patients were included. The median D-dimer levels differed between the AIS and TIA groups (746 µg/L [interquartile range 381-1468] versus 442 µg/L [interquartile range 244-800], p<0.001). In AIS patients, an early increase in D-dimer levels was demonstrated within the first 6 h (standardized beta coefficient [ß] 0.728; 95% confidence interval [CI] 0.324-1.121). This was followed by an immediate decrease (ß -13.022; 95% CI -20.401 to -5.643) and then by a second, late increase after 35 h (ß 11.750; 95% CI 4.71-18.791). No time-dependent fluctuation in D-dimer levels was observed in TIA patients. CONCLUSION: The time from symptom onset may affect D-dimer levels in patients with AIS but not those with TIA. Further studies confirming these findings and validating time-specific variations are needed to enable D-dimer levels to be used efficiently as an acute stroke and thrombotic risk biomarker.

External Validation of a Model for Persistent Perfusion Deficit in Patients With Incomplete Reperfusion After Thrombectomy: EXTEND-PROCEED.

BACKGROUND AND OBJECTIVES: We recently developed a model (PROCEED) that predicts the occurrence of persistent perfusion deficit (PPD) at 24 hours in patients with incomplete angiographic reperfusion after thrombectomy. This study aims to externally validate the PROCEED model using prospectively acquired multicenter data. METHODS: Individual patient data for external validation were obtained from the Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection, Tenecteplase versus Alteplase Before Endovascular Therapy for Ischemic Stroke part 1 and 2 trials, and a prospective cohort of the Medical University of Graz. The model's primary outcome was the occurrence of PPD, defined as a focal, wedge-shaped perfusion delay on 24-hour follow-up perfusion imaging that corresponds to the capillary phase deficit on last angiographic series in patients with

Prevalence of right-to-left shunt in stroke patients with cancer.

BACKGROUND AND OBJECTIVES: Cancer is associated with an increased risk of acute ischemic stroke (AIS) and venous thromboembolism. The role of a cardiac right-to-left shunt (RLS) as a surrogate parameter for paradoxical embolism in cancer-related strokes is uncertain. We sought to investigate the relationship between the presence of an RLS and cancer in AIS patients. METHODS: We included consecutive AIS patients hospitalized at our tertiary stroke center between January 2015 and December 2020 with available RLS status as detected on transesophageal echocardiography (TEE). Active cancers were retrospectively identified and the association with RLS was assessed with multivariable logistic regression and inverse probability of treatment weighting to minimize the ascertainment bias of having a TEE obtained. RESULTS: Of the 2236 AIS patients included, 103 (4.6%) had active cancer, of whom 24 (23%) were diagnosed with RLS. An RLS was present in 774 out of the 2133 AIS patients without active cancer (36%). After adjustment and weighting, the absence of RLS was associated with active cancer (adjusted odds ratio (aOR) 2.29; 95% confidence interval (CI), 1.14-4.58). When analysis was restricted to patients younger than 60 years of age or those with a high-risk RLS (Risk of Paradoxical Embolism Score ⩾ 6), there was no association between RLS and cancer (aOR, 3.07; 95% CI, 0.79-11.88 and aOR, 0.56; 95% CI, 0.10-3.10, respectively). CONCLUSION: RLS was diagnosed less frequently in AIS patients with cancer than in cancer-free patients, suggesting that arterial sources may play a larger role in cancer-related strokes than paradoxical venous embolization. Future studies are needed to validate these findings and evaluate potential therapeutic implications, such as the general indication, or lack thereof, for patent foramen ovale (PFO) closure in this patient population.

Intravenous thrombolysis in patients with recent intake of direct oral anticoagulants: A target trial analysis after the liberalization of institutional guidelines.

INTRODUCTION: This study aimed to report the safety and efficacy of off-label intravenous thrombolysis (IVT) with alteplase after sequentially liberalizing our institutional guidelines allowing IVT for patients under direct oral anticoagulants (DOACs) regardless of plasma levels, time of last intake, and without prior anticoagulation reversal therapy. PATIENTS AND METHODS: We utilized the target-trial methodology to emulate hypothetical criteria of a randomized controlled trial in our prospective stroke registry. Consecutive DOAC patients (06/2021-11/2023) otherwise qualifying for IVT were included. Safety and efficacy outcomes (symptomatic intracranial hemorrhage [ICH], any radiological ICH, major bleeding, 90-day mortality, 90-day good functional outcome [mRS 0-2 or return to baseline]) were assessed using inverse-probability-weighted regression-adjustment comparing patients with versus without IVT. RESULTS: Ninety eight patients fulfilled the target-trial criteria. IVT was given in 49/98 (50%) patients at a median of 178 (interquartile range 134-285) min after symptom onset with median DOAC plasma level of 77 ng/ml (15 patients had plasma levels > 100 ng/ml; 25/49 [51%] were treated within 12 h after last DOAC ingestion). Endovascular therapy was more frequent in patients without IVT (73% vs 33%). Symptomatic ICH occurred in 0/49 patients receiving IVT and 2/49 patients without IVT (adjusted difference -2.5%; 95% CI -5.9 to 0.8). The rates of any radiological ICH were comparable. Patients receiving IVT were more likely to have good functional outcomes. DISCUSSION AND CONCLUSION: After liberalizing our approach for IVT regardless of recent DOAC intake, we did not experience any safety concerns. The association of IVT with better functional outcomes warrants prospective randomized controlled trials.

Time to Treatment With Intravenous Thrombolysis Before Thrombectomy and Functional Outcomes in Acute Ischemic Stroke: A Meta-Analysis.

Importance: The benefit of intravenous thrombolysis (IVT) for acute ischemic stroke declines with longer time from symptom onset, but it is not known whether a similar time dependency exists for IVT followed by thrombectomy. Objective: To determine whether the benefit associated with IVT plus thrombectomy vs thrombectomy alone decreases with treatment time from symptom onset. Design, Setting, and Participants: Individual participant data meta-analysis from 6 randomized clinical trials comparing IVT plus thrombectomy vs thrombectomy alone. Enrollment was between January 2017 and July 2021 at 190 sites in 15 countries. All participants were eligible for IVT and thrombectomy and presented directly at thrombectomy-capable stroke centers (n = 2334). For this meta-analysis, only patients with an anterior circulation large-vessel occlusion were included (n = 2313). Exposure: Interval from stroke symptom onset to expected administration of IVT and treatment with IVT plus thrombectomy vs thrombectomy alone. Main Outcomes and Measures: The primary outcome analysis tested whether the association between the allocated treatment (IVT plus thrombectomy vs thrombectomy alone) and disability at 90 days (7-level modified Rankin Scale [mRS] score range, 0 [no symptoms] to 6 [death]; minimal clinically important difference for the rates of mRS scores of 0-2: 1.3%) varied with times from symptom onset to expected administration of IVT. Results: In 2313 participants (1160 in IVT plus thrombectomy group vs 1153 in thrombectomy alone group; median age, 71 [IQR, 62 to 78] years; 44.3% were female), the median time from symptom onset to expected administration of IVT was 2 hours 28 minutes (IQR, 1 hour 46 minutes to 3 hours 17 minutes). There was a statistically significant interaction between the time from symptom onset to expected administration of IVT and the association of allocated treatment with functional outcomes (ratio of adjusted common odds ratio [OR] per 1-hour delay, 0.84 [95% CI, 0.72 to 0.97], P = .02 for interaction). The benefit of IVT plus thrombectomy decreased with longer times from symptom onset to expected administration of IVT (adjusted common OR for a 1-step mRS score shift toward improvement, 1.49 [95% CI, 1.13 to 1.96] at 1 hour, 1.25 [95% CI, 1.04 to 1.49] at 2 hours, and 1.04 [95% CI, 0.88 to 1.23] at 3 hours). For a mRS score of 0, 1, or 2, the predicted absolute risk difference was 9% (95% CI, 3% to 16%) at 1 hour, 5% (95% CI, 1% to 9%) at 2 hours, and 1% (95% CI, -3% to 5%) at 3 hours. After 2 hours 20 minutes, the benefit associated with IVT plus thrombectomy was not statistically significant and the point estimate crossed the null association at 3 hours 14 minutes. Conclusions and Relevance: In patients presenting at thrombectomy-capable stroke centers, the benefit associated with IVT plus thrombectomy vs thrombectomy alone was time dependent and statistically significant only if the time from symptom onset to expected administration of IVT was short.

Value of intravenous alteplase before thrombectomy among patients with tandem lesions and emergent carotid artery stenting: A subgroup analysis of the SWIFT DIRECT trial.

BACKGROUND AND PURPOSE: The value of intravenous thrombolysis (IVT) in eligible tandem lesion patients undergoing endovascular treatment (EVT) is unknown. We investigated treatment effect heterogeneity of EVT + IVT versus EVT-only in tandem lesion patients. Additional analyses were performed for patients undergoing emergent internal carotid artery (ICA) stenting. METHODS: SWIFT DIRECT randomized IVT-eligible patients to either EVT + IVT or EVT-only. Primary outcome was 90-day functional independence (modified Rankin Scale score 0-2) after the index event. Secondary endpoints were reperfusion success, 24 h intracranial hemorrhage rate, and 90-day all-cause mortality. Interaction models were fitted for all predefined outcomes. RESULTS: Among 408 included patients, 63 (15.4%) had a tandem lesion and 33 (52.4%) received IVT. In patients with tandem lesions, 20 had undergone emergent ICA stenting (EVT + IVT: 9/33, 27.3%; EVT: 11/30, 36.7%). Tandem lesion did not show treatment effect modification of IVT on rates of functional independence (tandem lesion EVT + IVT vs. EVT: 63.6% vs. 46.7%, non-tandem lesion EVT + IVT vs. EVT: 65.6% vs. 58.2%; p for interaction = 0.77). IVT also did not increase the risk of intracranial hemorrhage  among tandem lesion patients (tandem lesion EVT + IVT vs. EVT: 34.4% vs. 46.7%, non-tandem lesion EVT + IVT vs. EVT: 33.5% vs. 26.3%; p for interaction = 0.15). No heterogeneity was noted for other endpoints (p for interaction > 0.05). CONCLUSIONS: No treatment effect heterogeneity of EVT + IVT versus EVT-only was observed among tandem lesion patients. Administering IVT in patients with anticipated emergent ICA stenting seems safe, and the latter should not be a factor to consider when deciding to administer IVT before EVT.

Intracerebral haemorrhage in patients taking different types of oral anticoagulants: a pooled individual patient data analysis from two national stroke registries.

BACKGROUND: We investigated outcomes in patients with intracerebral haemorrhage (ICH) according to prior anticoagulation treatment with Vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or no anticoagulation. METHODS: This is an individual patient data study combining two prospective national stroke registries from Switzerland and Norway (2013-2019). We included all consecutive patients with ICH from both registries. The main outcomes were favourable functional outcome (modified Rankin Scale 0-2) and mortality at 3 months. RESULTS: Among 11 349 patients with ICH (mean age 73.6 years; 47.6% women), 1491 (13.1%) were taking VKAs and 1205 (10.6%) DOACs (95.2% factor Xa inhibitors). The median percentage of patients on prior anticoagulation was 23.7 (IQR 22.6-25.1) with VKAs decreasing (from 18.3% to 7.6%) and DOACs increasing (from 3.0% to 18.0%) over time. Prior VKA therapy (n=209 (22.3%); adjusted ORs (aOR), 0.64; 95% CI, 0.49 to 0.84) and prior DOAC therapy (n=184 (25.7%); aOR, 0.64; 95% CI, 0.47 to 0.87) were independently associated with lower odds of favourable outcome compared with patients without anticoagulation (n=2037 (38.8%)). Prior VKA therapy (n=720 (49.4%); aOR, 1.71; 95% CI, 1.41 to 2.08) and prior DOAC therapy (n=460 (39.7%); aOR, 1.28; 95% CI, 1.02 to 1.60) were independently associated with higher odds of mortality compared with patients without anticoagulation (n=2512 (30.2%)). CONCLUSIONS: The spectrum of anticoagulation-associated ICH changed over time. Compared with patients without prior anticoagulation, prior VKA treatment and prior DOAC treatment were independently associated with lower odds of favourable outcome and higher odds of mortality at 3 months. Specific reversal agents unavailable during the study period might improve outcomes of DOAC-associated ICH in the future.

Is Incidentally Discovered Covert Cerebrovascular Disease Ignorable?

This Viewpoint discusses the clinical implications of incidentally discovered covert cerebrovascular disease.

Characteristics of acute ischemic stroke and unusual aura in patients with migraine with aura.

BACKGROUND: Sometimes migraine aura changes from attack to attack, raising the question of whether the change is heralding an ischemic stroke or an unusual aura. Differentiating unusual migraine aura from the onset of an acute ischemic stroke in patients with migraine with aura (MwA) can be challenging. OBJECTIVE: The aim of this cohort study was to assess clinical characteristics that help distinguish between MwA and minor stroke in patients with a previous history of MwA who presented with suspicion of stroke. METHODS: We interviewed patients with MwA and ischemic stroke (MwA + IS) and patients with MwA and unusual aura, but without ischemic stroke (MwA - IS) from a tertiary hospital using a structured questionnaire. We assessed how symptoms of ischemic stroke or unusual aura differed from usual, that is, the typical aura in each patient. Stroke or exclusion of stroke was verified by multimodal magnetic resonance imaging. RESULTS: Seventeen patients with MwA + IS and twelve patients with MwA - IS were included. New focal neurological symptoms (13/17 [76%] vs. 3/12 [25%]), change of the first symptom (10/17 [59%] vs. 1/12 [8%]), and absence of headache (6/15 [40%] vs. 2/10 [20%]) were more often reported during ischemic stroke. The physical examination was normal in 8/17 (47%) MwA + IS and in 6/12 (50%) MwA - IS patients. In 5/17 (29%) patients with MwA + IS, there were unequivocal physical signs suggestive of stroke such as persistent visual loss, ataxia, or paresis. CONCLUSION: There are clues from the history that might help identify stroke in patients with MwA with changed aura symptoms. These might be particularly useful in patients presenting without physical findings suggestive of stroke.

Value of Immediate Flat Panel Perfusion Imaging after Endovascular Therapy (AFTERMATH): A Proof of Concept Study.

BACKGROUND AND PURPOSE: Potential utility of flat panel CT perfusion imaging (FPCT-PI) performed immediately after mechanical thrombectomy (MT) is unknown. We aimed to assess whether FPCT-PI obtained directly post-MT could provide additional potentially relevant information on tissue reperfusion status. MATERIALS AND METHODS: This was a single-center analysis of all patients with consecutive acute stroke admitted between June 2019 and March 2021 who underwent MT and postinterventional FPCT-PI (n = 26). A core lab blinded to technical details and clinical data performed TICI grading on postinterventional DSA images and qualitatively assessed reperfusion on time-sensitive FPCT-PI maps. According to agreement between DSA and FPCT-PI, all patients were classified into 4 groups: hypoperfusion findings perfectly matched by location (group 1), hypoperfusion findings mismatched by location (group 2), complete reperfusion on DSA with hypoperfusion on FPCT-PI (group 3), and hypoperfusion on DSA with complete reperfusion on FPCT-PI (group 4). RESULTS: Detection of hypoperfusion (present/absent) concurred in 21/26 patients. Of these, reperfusion findings showed perfect agreement on location and size in 16 patients (group 1), while in 5 patients there was a mismatch by location (group 2). Of the remaining 5 patients with disagreement regarding the presence or absence of hypoperfusion, 3 were classified into group 3 and 2 into group 4. FPCT-PI findings could have avoided TICI overestimation in all false-positive operator-rated TICI 3 cases (10/26). CONCLUSIONS: FPCT-PI may provide additional clinically relevant information in a considerable proportion of patients undergoing MT. Hence, FPCT-PI may complement the evaluation of reperfusion efficacy and potentially inform decision-making in the angiography suite.

Time for "code ICH"? - Workflow metrics of hyperacute treatments and outcome in patients with intracerebral haemorrhage.

INTRODUCTION: Knowledge about uptake and workflow metrics of hyperacute treatments in patients with non-traumatic intracerebral haemorrhage (ICH) in the emergency department are 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 73years, IQR 63-81 and GCS 14 points, IQR 11-15, onset-to-admission-time 284 minutes, IQR 111-708minutes) 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 >150mmHG received IV antihypertensive 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 hours of admission. Median treatment times from admission to first IV-antihypertensive treatment was 38 minutes (IQR 18-72minutes) and 59 minutes (IQR 37-111 minutes) for PCC, with significant differences according to mode of referral (p<0.001) but not early arrival (≤6hours of onset, p=0.92). The median time in the emergency department was 139 minutes (IQR 85-220 minutes) and among patients with elevated blood pressure, only 44% achieved a successful control (<140mmHG) during ED stay. In multivariate analysis, code ICH concordant treatment was associated with significantly lower odds for in-hopsital mortality (aOR 0.30, 95%CI 0.12-0.73, p=0.008) and a 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 advocating for a "code ICH" to streamline acute treatments.

Transient perivascular inflammation of the carotid artery-A transient but potentially recurrent disease.

Transient perivascular inflammation of the carotid artery (TIPIC syndrome) is a rare, unclassified vascular syndrome that usually affects the distal part of the common carotid artery and has a favorable prognosis. The disease is often misdiagnosed even by neurologists due to the moderate intensity of clinical symptoms and their transient character. We present a case of a 52-year-old man who experienced two episodes of transient neck pain and moderate local tenderness one and a half years apart. Different imaging modalities, such as ultrasound, CT angiography, and high-resolution 3T MR, were applied to better visualize the perivascular inflammation of the common carotid arteries. Based on the clinical-radiological characteristics of our case and applying the diagnostic criteria, we established the diagnosis of TIPIC syndrome. The patient was treated with nonsteroidal anti-inflammatory drugs for few weeks, and reduction in perivascular changes was observed in both episodes. The case raises questions about the phases of the disease, its duration and the intervals between follow-ups. Our article also increases the awareness of this rare clinical-radiological entity and presents recent data from the literature.

Connecting the DOTs: a novel imaging sign on flat-panel detector CT indicating distal vessel occlusions after thrombectomy.

BACKGROUND: Immediate non-contrast post-interventional flat-panel detector CT (FPDCT) has been suggested as an imaging tool to assess complications after endovascular therapy (EVT). We systematically investigated a new imaging finding of focal hyperdensities correlating with remaining distal vessel occlusion after EVT. METHODS: A single-center retrospective analysis was conducted for all acute ischemic stroke patients admitted between July 2020 and December 2022 who underwent EVT and immediate post-interventional FPDCT. A blinded core lab performed reperfusion grading on post-interventional digital subtraction angiography (DSA) images and evaluated focal hyperdensities on FPDCT (here called the distal occlusion tracker (DOT) sign). DOT sign was defined as a tubular or punctiform, vessel confined, hyperdense signal within the initial occlusion target territory. We assessed sensitivity and specificity of the DOT sign when compared with DSA findings. RESULTS: The median age of the cohort (n=215) was 74 years (IQR 63-82) and 58.6% were male. The DOT sign was positive in half of the cohort (51%, 110/215). The DOT sign had high specificity (85%, 95% CI 72% to 93%), but only moderate sensitivity (63%, 95% CI 55% to 70%) for detection of residual vessel occlusions. In comparison to the core lab, operators overestimated complete reperfusion in a quarter of the entire cohort (25%, 53/215). In more than half of these cases (53%, 28/53) there was a positive DOT sign, which could have mitigated this overestimation. CONCLUSION: The DOT sign appears to be a frequent finding on immediate post-interventional FPDCT. It correlates strongly with incomplete reperfusion and indicates residual distal vessel occlusions. In the future, it may be used to complement grading of reperfusion success and may help mitigating overestimation of reperfusion in the acute setting.

CADMUS: A Novel MRI-Based Classification of Spontaneous Intracerebral Hemorrhage Associated With Cerebral Small Vessel Disease

BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (SVD) is the major cause of intracerebral hemorrhage (ICH). There is no comprehensive, easily applicable classification of ICH subtypes according to the presumed underlying SVD using MRI. We developed an MRI-based classification for SVD-related ICH. METHODS: We performed a retrospective study in the prospectively collected Swiss Stroke Registry (SSR, 2013-2019) and the Stroke InvestiGation in North And central London (SIGNAL) cohort. Patients with nontraumatic, SVD-related ICH and available MRI within 3 months were classified as Cerebral Amyloid angiopathy (CAA), Deep perforator arteriopathy (DPA), Mixed CAA-DPA, or Undetermined SVD using hemorrhagic and nonhemorrhagic MRI markers (CADMUS classification). The primary outcome was inter-rater reliability using Gwet's AC1. Secondary outcomes were recurrent ICH/ischemic stroke at 3 months according to the CADMUS phenotype. We performed Firth penalized logistic regressions and competing risk analyses. RESULTS: The SSR cohort included 1,180 patients (median age [interquartile range] 73 [62-80] years, baseline NIH Stroke Scale 6 [2-12], 45.6% lobar hematoma, systolic blood pressure on admission 166 [145-185] mm Hg). The CADMUS phenotypes were as follows: mixed CAA-DPA (n = 751 patients, 63.6%), undetermined SVD (n = 203, 17.2%), CAA (n = 154, 13.1%), and DPA (n = 72, 6.3%), with a similar distribution in the SIGNAL cohort (n = 313). Inter-rater reliability was good (Gwet's AC1 for SSR/SIGNAL 0.69/0.74). During follow-up, 56 patients had 57 events (28 ICH, 29 ischemic strokes). Three-month event rates were comparable between the CADMUS phenotypes. DISCUSSION: CADMUS, a novel MRI-based classification for SVD-associated ICH, is feasible and reproducible and may improve the classification of ICH subtypes in clinical practice and research.

Thrombolysis for ischaemic stroke despite direct oral anticoagulation.

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.

MRI vs CT for Baseline Imaging Evaluation in Acute Large Artery Ischemic Stroke: A Subanalysis of the SWIFT-DIRECT Trial

BACKGROUND AND OBJECTIVES: Whether MRI or CT is preferable for the evaluation of patients with suspected stroke remains a matter of debate, given that the imaging modality acquired at baseline may be a relevant determinant of workflow delays and outcomes with it, in patients with stroke undergoing acute reperfusion therapies. METHODS: In this post hoc analysis of the SWIFT-DIRECT trial that investigated noninferiority of thrombectomy alone vs IV thrombolysis (IVT) + thrombectomy in patients with an acute ischemic anterior circulation large vessel occlusive stroke eligible to receive IVT within 4.5 hours after last seen well, we tested for a potential interaction between baseline imaging modality (MRI/MR-angiography [MRA] vs CT/CT-angiography [CTA]) and the effect of acute treatment (thrombectomy vs IVT + thrombectomy) on clinical and safety outcomes and procedural metrics (primary analysis). Moreover, we examined the association between baseline imaging modality and these outcomes using regression models adjusted for age, sex, baseline NIH Stroke Scale (NIHSS), occlusion location, and Alberta Stroke Program Early CT Score (ASPECTS) (secondary analysis). Endpoints included workflow times, the modified Rankin scale (mRS) score at 90 days, the rate of successful reperfusion, the odds for early neurologic deterioration within 24 hours, and the risk of symptomatic intracranial hemorrhage. The imaging modality acquired was chosen at the discretion of the treating physicians and commonly reflects center-specific standard procedures. RESULTS: Four hundred five of 408 patients enrolled in the SWIFT-DIRECT trial were included in this substudy. Two hundred (49.4%) patients underwent MRI/MRA, and 205 (50.6%) underwent CT/CTA. Patients with MRI/MRA had lower NIHSS scores (16 [interquartile range (IQR) 12-20] vs 18 [IQR 14-20], p = 0.012) and lower ASPECTS (8 [IQR 6-9] vs 8 [IQR 7-9], p = 0.021) compared with those with CT/CTA. In terms of the primary analysis, we found no evidence for an interaction between baseline imaging modality and the effect of IVT + thrombectomy vs thrombectomy alone. Regarding the secondary analysis, MRI/MRA acquisition was associated with workflow delays of approximately 20 minutes, higher odds of functional independence at 90 days (adjusted odds ratio [aOR] 1.65, 95% CI 1.07-2.56), and similar mortality rates (aOR 0.73, 95% CI 0.36-1.47) compared with CT/CTA. DISCUSSION: This post hoc analysis does not suggest treatment effect heterogeneity of IVT + thrombectomy vs thrombectomy alone in large artery stroke patients with different imaging modalities. There was no evidence that functional outcome at 90 days was less favorable following MRI/MRA at baseline compared with CT/CTA, despite significant workflow delays. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03192332.

No-reflow phenomenon in stroke patients: A systematic literature review and meta-analysis of clinical data.

BACKGROUND: The no-reflow phenomenon refers to the absence of microvascular reperfusion despite macrovascular reperfusion. AIM: The aim of this analysis was to summarize the available clinical evidence on no-reflow in patients with acute ischemic stroke. METHODS: A systematic literature review and a meta-analysis of clinical data on definition, rates, and impact of the no-reflow phenomenon after reperfusion therapy was carried out. A predefined research strategy was formulated according to the Population, Intervention, Comparison, and Outcome (PICO) model and was used to screen for articles in PubMed, MEDLINE, and Embase up to 8 September 2022. Whenever possible, quantitative data were summarized using a random-effects model. RESULTS: Thirteen studies with a total of 719 patients were included in the final analysis. Most studies (n = 10/13) used variations of the Thrombolysis in Cerebral Infarction scale to evaluate macrovascular reperfusion, whereas microvascular reperfusion and no-reflow were mostly assessed on perfusion maps (n = 9/13). In one-third of stroke patients with successful macrovascular reperfusion (29%, 95% confidence interval (CI), 21-37%), the no-reflow phenomenon was observed. Pooled analysis showed that no-reflow was consistently associated with reduced rates of functional independence (odds ratio (OR), 0.21, 95% CI, 0.15-0.31). CONCLUSION: The definition of no-reflow varied substantially across studies, but it appears to be a common phenomenon. Some of the no-reflow cases may simply represent remaining vessel occlusions, and it remains unclear whether no-reflow is an epiphenomenon of the infarcted parenchyma or causes infarction. Future studies should focus on standardizing the definition of no-reflow with more consistent definitions of successful macrovascular reperfusion and experimental set-ups that could detect the causality of the observed findings.

Susceptibility vessel sign, a predictor of long-term outcome in patients with stroke treated with mechanical thrombectomy.

BACKGROUND: The absence of the susceptibility vessel sign (SVS) in patients treated with mechanical thrombectomy (MT) is associated with poor radiological and clinical outcomes after 3 months. Underlying conditions, such as cancer, are assumed to influence SVS status and could potentially impact the long-term outcome. We aimed to assess SVS status as an independent predictor of long-term outcomes in MT-treated patients. METHODS: SVS status was retrospectively determined in consecutive MT-treated patients at a comprehensive stroke center between 2010 and 2018. Predictors of long-term mortality and poor functional outcome (modified Rankin Scale (mRS) ≥3) up to 8 years were identified using multivariable Cox and logistic regression, respectively. RESULTS: Of the 558 patients included, SVS was absent in 13% (n=71) and present in 87% (n=487) on baseline imaging. Patients without SVS were more likely to have active cancer (P=0.003) and diabetes mellitus (P<0.001) at the time of stroke. The median long-term follow-up time was 1058 days (IQR 533-1671 days). After adjustment for active cancer and diabetes mellitus, among others, the absence of SVS was associated with long-term mortality (adjusted HR (aHR) 2.11, 95% CI 1.35 to 3.29) and poor functional outcome in the long term (adjusted OR (aOR) 2.90, 95% CI 1.29 to 6.55). CONCLUSION: MT-treated patients without SVS have higher long-term mortality rates and poorer long-term functional outcome. It appears that this association cannot be explained by comorbidities alone, and further studies are warranted.