Revolutionizing Stroke Recovery: Unveiling the Promise of Stem Cell Therapy.

Stem cells, renowned for their unique regenerative capabilities, present significant hope in treating stroke, a major cause of disability globally. This review offers a detailed analysis of stem cell applications in stroke (ischemic and hemorrhagic) recovery. It examines therapies based on autologous (patient-derived), allogeneic (donor-derived), and Granulocyte-Colony Stimulating Factor (G-CSF) based stem cells, focusing on cell types such as Mesenchymal Stem/Stromal Cells (MSCs), Bone Marrow Mononuclear Stem Cells (BMMSCs), and Neural Stem/Progenitor Cells (NSCs). The paper compiles clinical trial data to evaluate their effectiveness and safety and addresses the ethical concerns of these innovative treatments. By explaining the mechanisms of stem cell-induced neurological repair, this review underscores stem cells' potential in revolutionizing stroke rehabilitation and suggests avenues for future research.

Characteristics and outcomes of cerebral venous thrombosis associated with COVID-19.

INTRODUCTION: Previous reports and meta-analyses derived from small case series reported a mortality rate of up to 40% in patients with coronavirus disease 2019 associated cerebral venous thrombosis (COVID-CVT). We assessed the clinical characteristics and outcomes in an international cohort of patients with COVID-CVT. PATIENTS AND METHODS: This was a registry study of consecutive COVID-CVT patients diagnosed between March 2020 and March 2023. Data collected by the International Cerebral Venous Thrombosis Consortium from patients with CVT diagnosed between 2017 and 2018 served as a comparison. Outcome analyses were adjusted for age and sex. RESULTS: We included 70 patients with COVID-CVT from 23 hospitals in 15 countries and 206 controls from 14 hospitals in 13 countries. The proportion of women was smaller in the COVID-CVT group (50% vs 68%, p < 0.01). A higher proportion of COVID-CVT patients presented with altered mental state (44% vs 25%, p < 0.01), the median thrombus load was higher in COVID-CVT patients (3 [IQR 2-4] vs 2 [1-3], p < 0.01) and the length of hospital stay was longer compared to controls (11 days [IQR 7-20] vs 8 [4-15], p = 0.02). In-hospital mortality did not differ (5/67 [7%, 95% CI 3-16] vs 7/206 [3%, 2-7], aOR 2.6 [95% CI 0.7-9]), nor did the frequency of functional independence after 6 months (modified Rankin Scale 0-2; 45/58 [78%, 95% CI 65-86] vs 161/185 [87%, 81-91], aOR 0.5 [95% CI 0.2-1.02]). CONCLUSION: In contrast to previous studies, the in-hospital mortality rate and functional outcomes during follow-up did not differ between COVID-CVT patients and the pre-COVID-19 controls.

The surface chemistry of colloidal lead halide perovskite nanowires.

This study explored the interplay between the ligand-surface chemistry of colloidal CsPbBr3 nanowires (NWs) and their optical properties. The ligand equilibrium was probed using nuclear magnetic resonance spectroscopy, and by perturbing the equilibrium via dilution, the gradual removal of ligands from the CsPbBr3 surface was observed. This removal was correlated with an increase in the surface defect density, as suggested by a broadening of the photoluminescence (PL) spectrum, a decrease in the PL quantum yield (PLQY), and quenching of the PL decay. These results highlight similar surface binding between the traditional CsPbBr3 quantum dots and our NWs, thereby expanding the scope of well-established ligand chemistry to a relatively unexplored nanocrystal morphology. By controlling the dilution factor, it was revealed that CsPbBr3 NWs achieve a PLQY of 72% ± 2% and a relatively long average PL lifetime of 400 ± 10 ns, without relying on additional surface passivation techniques, such as ligand exchange.

Lipoprotein(a) as a blood marker for large artery atherosclerosis stroke etiology: validation in a prospective cohort from a swiss stroke center.

BACKGROUND: Lipoprotein (a) [Lp(a)] serum levels are highly genetically determined and promote atherogenesis. High Lp(a) levels are associated with increased cardiovascular morbidity. Serum Lp(a) levels have recently been associated with large artery atherosclerosis (LAA) stroke. We aimed to externally validate this association in an independent cohort. METHODS: This study stems from the prospective multicentre CoRisk study (CoPeptin for Risk Stratification in Acute Stroke patients [NCT00878813]), conducted at the University Hospital Bern, Switzerland, between 2009 and 2011, in which Lp(a) plasma levels were measured within the first 24 hours after stroke onset. We assessed the association of Lp(a) with LAA stroke using multivariable logistic regression and performed interaction analyses to identify potential effect modifiers. RESULTS: Of 743 patients with ischaemic stroke, 105 (14%) had LAA stroke aetiology. Lp(a) levels were higher for LAA stroke than non-LAA stroke patients (23.0 nmol/l vs 16.3 nmol/l, p = 0.01). Multivariable regression revealed an independent association of log10and#xA0;Lp(a) with LAA stroke aetiology (aOR 1.47 [95% CI 1.03and#x2013;2.09], p = 0.03). The interaction analyses showed that Lp(a) was not associated with LAA stroke aetiology among patients with diabetes. CONCLUSIONS: In a well-characterised cohort of patients with ischaemic stroke, we validated the association of higher Lp(a) levels with LAA stroke aetiology, independent of traditional cardiovascular risk factors. These findings may inform randomised clinical trials investigating the effect of Lp(a) lowering agents on cardiovascular outcomes. The CoRisk (CoPeptin for Risk Stratification in Acute Patients) study is registered on ClinicalTrials.gov. REGISTRATION NUMBER: NCT00878813.

Reducing the global burden of cerebral venous thrombosis: An international research agenda.

BACKGROUND: Due to the rarity of cerebral venous thrombosis (CVT), performing high-quality scientific research in this field is challenging. Providing answers to unresolved research questions will improve prevention, diagnosis, and treatment, and ultimately translate to a better outcome of patients with CVT. We present an international research agenda, in which the most important research questions in the field of CVT are prioritized. AIMS: This research agenda has three distinct goals: (1) to provide inspiration and focus to research on CVT for the coming years, (2) to reinforce international collaboration, and (3) to facilitate the acquisition of research funding. SUMMARY OF REVIEW: This international research agenda is the result of a research summit organized by the International Cerebral Venous Thrombosis Consortium in Amsterdam, the Netherlands, in June 2023. The summit brought together 45 participants from 15 countries including clinical researchers from various disciplines, patients who previously suffered from CVT, and delegates from industry and non-profit funding organizations. The research agenda is categorized into six pre-specified themes: (1) epidemiology and clinical features, (2) life after CVT, (3) neuroimaging and diagnosis, (4) pathophysiology, (5) medical treatment, and (6) endovascular treatment. For each theme, we present two to four research questions, followed by a brief substantiation per question. The research questions were prioritized by the participants of the summit through consensus discussion. CONCLUSIONS: This international research agenda provides an overview of the most burning research questions on CVT. Answering these questions will advance our understanding and management of CVT, which will ultimately lead to improved outcomes for CVT patients worldwide.

Post-stroke cognitive impairment remains highly prevalent and disabling despite state-of-the-art stroke treatment.

BACKGROUND: State-of-the-art stroke treatment significantly reduces lesion size and stroke severity, but it remains unclear whether these therapeutic advances have diminished the burden of post-stroke cognitive impairment (PSCI). AIMS: In a cohort of patients receiving modern state-of-the-art stroke care including endovascular therapy, we assessed the frequency of PSCI and the pattern of domain-specific cognitive deficits, identified risk factors for PSCI, and determined the impact of acute PSCI on stroke outcome. METHODS: In this prospective monocentric cohort study, we examined patients with first-ever anterior circulation ischemic stroke without pre-stroke cognitive decline, using a comprehensive neuropsychological assessment ⩽10 days after symptom onset. Normative data were stratified by demographic variables. We defined PSCI as at least moderate (<1.5 standard deviation) deficits in ⩾2 cognitive domains. Multivariable regression analysis was applied to define risk factors for PSCI. RESULTS: We analyzed 329 non-aphasic patients admitted from December 2020 to July 2023 (67.2 ± 14.4 years old, 41.3% female, 13.1 ± 2.7 years of education). Although most patients had mild stroke (median National Institutes of Health Stroke Scale (NIHSS) 24 h = 1.00 (0.00; 3.00); 87.5% with NIHSS ⩽ 5), 69.3% of them presented with PSCI 2.7 ± 2.0 days post-stroke. The most severely and often affected cognitive domains were verbal learning, episodic memory, executive functions, selective attention, and constructive abilities (39.1%-51.2% of patients), whereas spatial neglect was less frequent (18.5%). The risk of PSCI was reduced with more years of education (odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.23-0.99) and right hemisphere lesions (OR = 0.47, 95% CI = 0.26-0.84), and increased with stroke severity (NIHSS 24 h, OR = 4.19, 95% CI = 2.72-6.45), presence of hyperlipidemia (OR = 1.93, 95% CI = 1.01-3.68), but was not influenced by age. After adjusting for stroke severity and depressive symptoms, acute PSCI was associated with poor functional outcome (modified Rankin Scale > 2, F = 13.695, p < 0.001) and worse global cognition (Montreal Cognitive Assessment (MoCA) score, F = 20.069, p < 0.001) at 3 months post-stroke. CONCLUSION: Despite modern stroke therapy and many strokes having mild severity, PSCI in the acute stroke phase remains frequent and associated with worse outcome. The most prevalent were learning and memory deficits. Cognitive reserve operationalized as years of education independently protects post-stroke cognition.

The analysis of association between single features of small vessel disease and stroke outcome shows the independent impact of the number of microbleeds and presence of lacunes.

The impact of small vessel disease (SVD) on stroke outcome was investigated either separately for its single features in isolation or for SVD sum score measuring a qualitative (binary) assessment of SVD-lesions. We aimed to investigate which SVD feature independently impacts the most on stroke outcome and to compare the continuous versus binary SVD assessment that reflects pronouncement and presence correspondingly. Patients with a first-ever anterior circulation ischemic stroke were retrospectively investigated. We performed an ordered logistic regression analysis to predict stroke outcome (mRS 3 months, 0-6) using age, stroke severity, and pre-stroke disability as baseline input variables and adding SVD-features (lacunes, microbleeds, enlarged perivascular spaces, white matter hyperintensities) assessed either continuously (model 1) or binary (model 2). The data of 873 patients (age 67.9 ± 15.4, NIHSS 24 h 4.1 ± 4.8) was analyzed. In model 1 with continuous SVD-features, the number of microbleeds was the only independent predictor of stroke outcome in addition to clinical parameters (OR 1.21; 95% CI 1.07-1.37). In model 2 with the binary SVD assessment, only the presence of lacunes independently improved the prediction of stroke outcome (OR 1.48, 1.1-1.99). In a post hoc analysis, both the continuous number of microbleeds and the presence of lacunes were independent significant predictors. Thus, the number of microbleeds evaluated continuously and the presence of lacunes are associated with stroke outcome independent from age, stroke severity, pre-stroke disability and other SVD-features. Whereas the presence of lacunes is adequately represented in SVD sum score, the microbleeds assessment might require another cutoff and/or gradual scoring, when prediction of stroke outcome is needed.

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.

Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P=0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P=0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; Pinteraction=0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Toward Individual Treatment in Cervical Artery Dissection: Subgroup Analysis of the TREAT-CAD Randomized Trial.

OBJECTIVE: Uncertainty remains regarding antithrombotic treatment in cervical artery dissection. This analysis aimed to explore whether certain patient profiles influence the effects of different types of antithrombotic treatment. METHODS: This was a post hoc exploratory analysis based on the per-protocol dataset from TREAT-CAD (NCT02046460), a randomized controlled trial comparing aspirin to anticoagulation in patients with cervical artery dissection. We explored the potential effects of distinct patient profiles on outcomes in participants treated with either aspirin or anticoagulation. Profiles included (1) presenting with ischemia (no/yes), (2) occlusion of the dissected artery (no/yes), (3) early versus delayed treatment start (median), and (4) intracranial extension of the dissection (no/yes). Outcomes included clinical (stroke, major hemorrhage, death) and magnetic resonance imaging outcomes (new ischemic or hemorrhagic brain lesions) and were assessed for each subgroup in separate logistic models without adjustment for multiple testing. RESULTS: All 173 (100%) per-protocol participants were eligible for the analyses. Participants without occlusion had decreased odds of events when treated with anticoagulation (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.07-0.86). This effect was more pronounced in participants presenting with cerebral ischemia (n = 118; OR = 0.16, 95% CI = 0.04-0.55). In the latter, those with early treatment (OR = 0.26, 95% CI = 0.07-0.85) or without intracranial extension of the dissection (OR = 0.34, 95% CI = 0.11-0.97) had decreased odds of events when treated with anticoagulation. INTERPRETATION: Anticoagulation might be preferable in patients with cervical artery dissection presenting with ischemia and no occlusion or no intracranial extension of the dissection. These findings need confirmation. ANN NEUROL 2024.

Swiss trial of decompressive craniectomy versus best medical treatment of spontaneous supratentorial intracerebral haemorrhage (SWITCH): an international, multicentre, randomised-controlled, two-arm, assessor-blinded trial.

RATIONALE: Decompressive craniectomy (DC) is beneficial in people with malignant middle cerebral artery infarction. Whether DC improves outcome in spontaneous intracerebral haemorrhage (ICH) is unknown. AIM: To determine whether DC without haematoma evacuation plus best medical treatment (BMT) in people with ICH decreases the risk of death or dependence at 6 months compared to BMT alone. METHODS AND DESIGN: SWITCH is an international, multicentre, randomised (1:1), two-arm, open-label, assessor-blinded trial. Key inclusion criteria are age ⩽75 years, stroke due to basal ganglia or thalamic ICH that may extend into cerebral lobes, ventricles or subarachnoid space, Glasgow coma scale of 8-13, NIHSS score of 10-30 and ICH volume of 30-100 mL. Randomisation must be performed <66 h after onset and DC <6 h after randomisation. Both groups will receive BMT. Participants randomised to the treatment group will receive DC of at least 12 cm in diameter according to institutional standards. SAMPLE SIZE: A sample of 300 participants randomised 1:1 to DC plus BMT versus BMT alone provides over 85% power at a two-sided alpha-level of 0.05 to detect a relative risk reduction of 33% using a chi-squared test. OUTCOMES: The primary outcome is the composite of death or dependence, defined as modified Rankin scale score 5-6 at 6 months. Secondary outcomes include death, functional status, quality of life and complications at 180 days and 12 months. DISCUSSION: SWITCH will inform physicians about the outcomes of DC plus BMT in people with spontaneous deep ICH, compared to BMT alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02258919.

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.

Andexanet alfa versus non-specific treatments for intracerebral hemorrhage in patients taking factor Xa inhibitors - Individual patient data analysis of ANNEXA-4 and TICH-NOAC.

BACKGROUND: Data comparing the specific reversal agent andexanet alfa with non-specific treatments in patients with non-traumatic intracerebral hemorrhage (ICH) associated with factor-Xa inhibitor (FXaI) use are scarce. AIM: The study aimed to determine the association between the use of andexanet alfa compared with non-specific treatments with the rate of hematoma expansion and thromboembolic complications in patients with FXaI-associated ICH. METHODS: We performed an individual patient data analysis combining two independent, prospective studies: ANNEXA-4 (180 patients receiving andexanet alfa, NCT02329327) and TICH-NOAC (63 patients receiving tranexamic acid or placebo ± prothrombin complex concentrate, NCT02866838). The primary efficacy outcome was hematoma expansion on follow-up imaging. The primary safety outcome was any thromboembolic complication (ischemic stroke, myocardial infarction, pulmonary embolism, or deep vein thrombosis) at 30 days. We used binary logistic regression models adjusted for baseline hematoma volume, age, calibrated anti-Xa activity, times from last intake of FXaI, and symptom onset to treatment, respectively. RESULTS: Among 243 participants included, the median age was 80 (IQR 75-84) years, baseline hematoma volume was 9.1 (IQR 3.4-21) mL and anti-Xa activity 118 (IQR 78-222) ng/mL. Times from last FXaI intake and symptom onset to treatment were 11 (IQR 7-16) and 4.7 (IQR 3.0-7.6) h, respectively. Overall, 50 patients (22%) experienced hematoma expansion (ANNEXA-4: n=24 (14%); TICH-NOAC: n=26 (41%)). After adjusting for pre-specified confounders (baseline hematoma volume, age, calibrated anti-Xa activity, times from last intake of FXaI, and symptom onset to treatment, respectively), treatment with andexanet alfa was independently associated with decreased odds for hematoma expansion (aOR 0.33, 95% CI 0.13-0.80, p = 0.015). Overall, 26 patients (11%) had any thromboembolic complication within 30 days (ANNEXA-4: n=20 (11%); TICH-NOAC: n=6 (10%)). There was no association between any thromboembolic complication and treatment with andexanet alfa (aOR 0.70, 95% CI 0.16-3.12, p = 0.641). CONCLUSION: The use of andexanet alfa compared to any other non-specific treatment strategy was associated with decreased odds for hematoma expansion, without increased odds for thromboembolic complications.

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.

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.

Cerebral small vessel disease and stroke: Linked by stroke aetiology, but not stroke lesion location or size.

BACKGROUND: Cerebral small vessel disease (SVD) has previously been associated with worse stroke outcome, vascular dementia, and specific post-stroke cognitive deficits. The underlying causal mechanisms of these associations are not yet fully understood. We investigated whether a relationship between SVD and certain stroke aetiologies or a specific stroke lesion anatomy provides a potential explanation. METHODS: In a retrospective observational study, we examined 859 patients with first-ever, non-SVD anterior circulation ischemic stroke (age = 69.0±15.2). We evaluated MRI imaging markers to assess an SVD burden score and mapped stroke lesions on diffusion-weighted MRI. We investigated the association of SVD burden with i) stroke aetiology, and ii) lesion anatomy using topographical statistical mapping. RESULTS: With increasing SVD burden, stroke of cardioembolic aetiology was more frequent (ρ = 0.175; 95 %-CI = 0.103;0.244), whereas cervical artery dissection (ρ = -0.143; 95 %-CI = -0.198;-0.087) and a patent foramen ovale (ρ = -0.165; 95 %-CI = -0.220;-0.104) were less frequent stroke etiologies. However, no significant associations between SVD burden and stroke aetiology remained after additionally controlling for age (all p>0.125). Lesion-symptom-mapping and Bayesian statistics showed that SVD burden was not associated with a specific stroke lesion anatomy or size. CONCLUSIONS: In patients with a high burden of SVD, non-SVD stroke is more likely to be caused by cardioembolic aetiology. The common risk factor of advanced age may link both pathologies and explain some of the existing associations between SVD and stroke. The SVD burden is not related to a specific stroke lesion location.

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.

Discordance between LDL-C and apolipoprotein B is associated with large-artery-atherosclerosis ischemic stroke in patients ⩽70 years of age.

BACKGROUND AND AIMS: Low density lipoprotein (LDL-C) and other atherogenic lipoproteins are coated by apolipoprotein B100 (apoB). The correlation between LDL-C and apoB is usually thight, but in some cases LDL-C underestimates apoB levels and residual cardiovascular risk. We aimed to assess if a discordance of LDL-C-levels with apoB levels is associated with LAA stroke. METHODS: We included patients with an acute ischemic stroke from two prospective studies enrolled at the University Hospital Bern, Basel and Zurich, Switzerland. LDL-C and apoB were measured within 24 h of symptom onset. By linear regression, for each LDL-C, we computed the expected apoB level assuming a perfect correlation. Higher-than-expected apoB was defined as apoB level being in the upper residual tertile. RESULTS: Overall, we included 1783 patients, of which 260 had a LAA stroke (15%). In the overall cohort, higher-than-expected apoB values were not associated with LAA. However, a significant interaction with age was present. Among the 738 patients ⩽70 years of age, a higher-than-expected apoB was more frequent in patients with LAA- versus non LAA-stroke (48% vs 36%, p = 0.02). In multivariate analysis, a higher-than-expected apoB was associated with LAA stroke (aOR = aOR 2.48, 95%CI 1.14-5.38). Among those aged ⩽70 years and with LAA, 11.7% had higher than guideline-recommended apoB despite LDL-C ⩽ 1.8 mmol/L (<70 mg/dl), compared to 5.9% among patients with other stroke etiologies (p = 0.04). A triglyceride cut-off of ⩾0.95 mmol/L had, in external validation, a sensitivity of 71% and specificity of 52% for apoB ⩾ 0.65 g/L among patients with LDL-C <1.8 mmol/L. CONCLUSIONS: Among patients aged ⩽70 years, a higher-than-expected apoB was independently associated with LAA stroke. Measuring apoB may help identify younger stroke patients potentially benefiting from intensified lipid-lowering therapy.

Adaptation of the Concept of Brain Reserve for the Prediction of Stroke Outcome: Proxies, Neural Mechanisms, and Significance for Research.

The prediction of stroke outcome is challenging due to the high inter-individual variability in stroke patients. We recently suggested the adaptation of the concept of brain reserve (BR) to improve the prediction of stroke outcome. This concept was initially developed alongside the one for the cognitive reserve for neurodegeneration and forms a valuable theoretical framework to capture high inter-individual variability in stroke patients. In the present work, we suggest and discuss (i) BR-proxies-quantitative brain characteristics at the time stroke occurs (e.g., brain volume, hippocampus volume), and (ii) proxies of brain pathology reducing BR (e.g., brain atrophy, severity of white matter hyperintensities), parameters easily available from a routine MRI examination that might improve the prediction of stroke outcome. Though the influence of these parameters on stroke outcome has been partly reported individually, their independent and combined impact is yet to be determined. Conceptually, BR is a continuous measure determining the amount of brain structure available to mitigate and compensate for stroke damage, thus reflecting individual differences in neural resources and a capacity to maintain performance and recover after stroke. We suggest that stroke outcome might be defined as an interaction between BR at the time stroke occurs and lesion load. BR in stroke can potentially be influenced, e.g., by modifying cardiovascular risk factors. In addition to the potential power of the BR concept in a mechanistic understanding of inter-individual variability in stroke outcome and establishing individualized therapeutic approaches, it might help to strengthen the synergy of preventive measures in stroke, neurodegeneration, and healthy aging.

Association of covert brain infarct phenotype with stroke recurrence in first-ever manifest ischemic stroke according to etiology.

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.