Deep Learning-Based Automatic Classification of Ischemic Stroke Subtype Using Diffusion-Weighted Images.

BACKGROUND AND PURPOSE: Accurate classification of ischemic stroke subtype is important for effective secondary prevention of stroke. We used diffusion-weighted image (DWI) and atrial fibrillation (AF) data to train a deep learning algorithm to classify stroke subtype. METHODS: Model development was done in 2,988 patients with ischemic stroke from three centers by using U-net for infarct segmentation and EfficientNetV2 for subtype classification. Experienced neurologists (n=5) determined subtypes for external test datasets, while establishing a consensus for clinical trial datasets. Automatically segmented infarcts were fed into the model (DWI-only algorithm). Subsequently, another model was trained, with AF included as a categorical variable (DWI+AF algorithm). These models were tested: (1) internally against the opinion of the labeling experts, (2) against fresh external DWI data, and (3) against clinical trial dataset. RESULTS: In the training-and-validation datasets, the mean (±standard deviation) age was 68.0±12.5 (61.1% male). In internal testing, compared with the experts, the DWI-only and the DWI+AF algorithms respectively achieved moderate (65.3%) and near-strong (79.1%) agreement. In external testing, both algorithms again showed good agreements (59.3%-60.7% and 73.7%-74.0%, respectively). In the clinical trial dataset, compared with the expert consensus, percentage agreements and Cohen's kappa were respectively 58.1% and 0.34 for the DWI-only vs. 72.9% and 0.57 for the DWI+AF algorithms. The corresponding values between experts were comparable (76.0% and 0.61) to the DWI+AF algorithm. CONCLUSION: Our model trained on a large dataset of DWI (both with or without AF information) was able to classify ischemic stroke subtypes comparable to a consensus of stroke experts.

Assessing Regional Disparities and Vulnerability in Stroke Care across Gyeonggi Province: A Focus on Hospital Service Areas.

BACKGROUND: This study aims to illuminate regional disparities and identify vulnerable areas in stroke care across Gyeonggi Province's hospital service areas. METHODS: Using data from the Korea National Cardio-cerebrovascular Disease Management Commission, we included 4,427 acute stroke patients admitted in 2018 to hospitals within Gyeonggi Province. Our evaluation focused on: 1) stroke care quality indicators, including rates of defect-free care, intravenous thrombolysis (IVT), endovascular thrombectomy (EVT), and acute reperfusion therapy (either IVT or EVT); 2) intra-regional treatment rates; and 3) one-year mortality across the province and its 12 hospital service areas. These were compared both with national averages and inter-regionally. Vulnerable areas were pinpointed by evaluating the number of quality indicators falling below the national average and through visual distribution mapping, categorizing each indicator into higher (ranks 1-4), middle (ranks 5-8), and lower (ranks 9-12) tiers. RESULTS: Despite fewer qualified stroke centers and specialists, Gyeonggi Province exhibited higher defect-free care rates (84.6% vs. 80.7%), intra-regional treatment rates (57.8% vs. 51.0%), and marginally lower one-year mortality (16.2% vs. 17.3%) compared to national averages. Notable regional disparities were observed; the highest-performing areas for defect-free care and acute reperfusion therapy exceeded the lowest by 1.4 and 3.3 times, respectively. Nine out of twelve areas fell below the national average for EVT rates, seven for IVT and reperfusion therapy rates, and five for intra-regional treatment rates. Pyeongtaek, with all stroke care quality indicators below the national average coupled with the highest one-year mortality, emerges as a critical area needing improvement in acute stroke care. CONCLUSION: This study not only exposes the regional disparities in stroke care within Gyeonggi Province's hospital service areas but also identifies areas most vulnerable. Consequently, a customized support strategy for these areas is imperative.

Regional Disparities in Prehospital Delay of Acute Ischemic Stroke: The Korean Stroke Registry.

BACKGROUND: Late hospital arrival keeps patients with stroke from receiving recanalization therapy and is associated with poor outcomes. This study used a nationwide acute stroke registry to investigate the trends and regional disparities in prehospital delay and analyze the significant factors associated with late arrivals. METHODS: Patients with acute ischemic stroke or transient ischemic attack between January 2012 and December 2021 were included. The prehospital delay was identified, and its regional disparity was evaluated using the Gini coefficient for nine administrative regions. Multivariate models were used to identify factors significantly associated with prehospital delays of >4.5 h. RESULTS: A total of 144,014 patients from 61 hospitals were included. The median prehospital delay was 460 min (interquartile range, 116-1912), and only 36.8% of patients arrived at hospitals within 4.5 h. Long prehospital delays and high regional inequality (Gini coefficient > 0.3) persisted throughout the observation period. After adjusting for confounders, age > 65 years old (adjusted odds ratio [aOR] = 1.23; 95% confidence interval [CI], 1.19-1.27), female sex (aOR = 1.09; 95% CI, 1.05-1.13), hypertension (aOR = 1.12; 95% CI, 1.08-1.16), diabetes mellitus (aOR = 1.38; 95% CI, 1.33-1.43), smoking (aOR = 1.15, 95% CI, 1.11-1.20), premorbid disability (aOR = 1.44; 95% CI, 1.37-1.52), and mild stroke severity (aOR = 1.55; 95% CI, 1.50-1.61) were found to independently predict prehospital delays of >4.5 h. CONCLUSION: Prehospital delays were lengthy and had not improved in Korea, and there was a high regional disparity. To overcome these inequalities, a deeper understanding of regional characteristics and further research is warranted to address the vulnerabilities identified.

Bayesian modelling disentangles language versus executive control disruption in stroke.

Stroke is the leading cause of long-term disability worldwide. Incurred brain damage can disrupt cognition, often with persisting deficits in language and executive capacities. Yet, despite their clinical relevance, the commonalities and differences between language versus executive control impairments remain under-specified. To fill this gap, we tailored a Bayesian hierarchical modelling solution in a largest-of-its-kind cohort (1080 patients with stroke) to deconvolve language and executive control with respect to the stroke topology. Cognitive function was assessed with a rich neuropsychological test battery including global cognitive function (tested with the Mini-Mental State Exam), language (assessed with a picture naming task), executive speech function (tested with verbal fluency tasks), executive control functions (Trail Making Test and Digit Symbol Coding Task), visuospatial functioning (Rey Complex Figure), as well as verbal learning and memory function (Soul Verbal Learning). Bayesian modelling predicted interindividual differences in eight cognitive outcome scores three months after stroke based on specific tissue lesion topologies. A multivariate factor analysis extracted four distinct cognitive factors that distinguish left- and right-hemispheric contributions to ischaemic tissue lesions. These factors were labelled according to the neuropsychological tests that had the strongest factor loadings: One factor delineated language and general cognitive performance and was mainly associated with damage to left-hemispheric brain regions in the frontal and temporal cortex. A factor for executive control summarized mental flexibility, task switching and visual-constructional abilities. This factor was strongly related to right-hemispheric brain damage of posterior regions in the occipital cortex. The interplay of language and executive control was reflected in two distinct factors that were labelled as executive speech functions and verbal memory. Impairments on both factors were mainly linked to left-hemispheric lesions. These findings shed light onto the causal implications of hemispheric specialization for cognition; and make steps towards subgroup-specific treatment protocols after stroke.

Trends in Dual Antiplatelet Therapy of Aspirin and Clopidogrel and Outcomes in Ischemic Stroke Patients Noneligible for POINT/CHANCE Trial Treatment.

BACKGROUND: Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT-AC) in early-presenting patients with minor ischemic stroke. However, the impact of these trials over time on the use and outcomes of DAPT-AC among the patients with nonminor or late-presenting stroke who do not meet the eligibility criteria of these trials has not been delineated. METHODS AND RESULTS: In a multicenter stroke registry, this study examined yearly changes from April 2008 to August 2022 in DAPT-AC use for stroke patients ineligible for CHANCE/POINT (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events/Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) clinical trials due to National Institutes of Health Stroke Scale >4 or late arrival beyond 24 hours of onset. A total of 32 118 patients (age, 68.1±13.1 years; male, 58.5%) with National Institutes of Health Stroke Scale of 4 (interquartile range, 1-7) were analyzed. In 2008, DAPT-AC was used in 33.0%, other antiplatelets in 62.7%, and no antiplatelet in 4.3%. The frequency of DAPT-AC was relatively unchanged through 2013, when the CHANCE trial was published, and then increased steadily, reaching 78% in 2022, while other antiplatelets decreased to 17.8% in 2022 (Ptrend<0.001). From 2011 to 2022, clinical outcomes nonsignificantly improved, with an average relative risk reduction of 2%/y for the composite of stroke, myocardial infarction, and all-cause mortality, both among patients treated with DAPT-AC and patients treated with other antiplatelets. CONCLUSIONS: Use of DAPT-AC in stroke patients with stroke ineligible for recent DAPT clinical trials increased markedly and steadily after CHANCE publication in 2013, reaching deployment in nearly 4 of every 5 patients by 2022. The secondary prevention in patients with ischemic stroke seems to be gradually improving, possibly due to the enhancement of risk factor control.

Strategic white matter hyperintensity locations associated with post-stroke cognitive impairment: A multicenter study in 1568 stroke patients.

BACKGROUND: Post-stroke cognitive impairment (PSCI) occurs in up to 50% of stroke survivors. Presence of pre-existing vascular brain injury, in particular the extent of white matter hyperintensities (WMH), is associated with worse cognitive outcome after stroke, but the role of WMH location in this association is unclear. AIMS: We determined if WMH in strategic white matter tracts explain cognitive performance after stroke. METHODS: Individual patient data from nine ischemic stroke cohorts with magnetic resonance imaging (MRI) were harmonized through the Meta VCI Map consortium. The association between WMH volumes in strategic tracts and domain-specific cognitive functioning (attention and executive functioning, information processing speed, language and verbal memory) was assessed using linear mixed models and lasso regression. We used a hypothesis-driven design, primarily addressing four white matter tracts known to be strategic in memory clinic patients: the left and right anterior thalamic radiation, forceps major, and left inferior fronto-occipital fasciculus. RESULTS: The total study sample consisted of 1568 patients (39.9% female, mean age = 67.3 years). Total WMH volume was strongly related to cognitive performance on all four cognitive domains. WMH volume in the left anterior thalamic radiation was significantly associated with cognitive performance on attention and executive functioning and information processing speed and WMH volume in the forceps major with information processing speed. The multivariable lasso regression showed that these associations were independent of age, sex, education, and total infarct volume and had larger coefficients than total WMH volume. CONCLUSION: These results show tract-specific relations between WMH volume and cognitive performance after ischemic stroke, independent of total WMH volume. This implies that the concept of strategic lesions in PSCI extends beyond acute infarcts and also involves pre-existing WMH. DATA ACCESS STATEMENT: The Meta VCI Map consortium is dedicated to data sharing, following our guidelines.

Network analysis of stroke systems of care in Korea.

Background: The landscape of stroke care has shifted from stand-alone hospitals to cooperative networks among hospitals. Despite the importance of these networks, limited information exists on their characteristics and functional attributes. Methods: We extracted patient-level data on acute stroke care and hospital connectivity by integrating national stroke audit data with reimbursement claims data. We then used this information to transform interhospital transfers into a network framework, where hospitals were designated as nodes and transfers as edges. Using the Louvain algorithm, we grouped densely connected hospitals into distinct stroke care communities. The quality and characteristics in given stroke communities were analysed, and their distinct types were derived using network parameters. The clinical implications of this network model were also explored. Results: Over 6 months, 19 113 patients with acute ischaemic stroke initially presented to 1009 hospitals, with 3114 (16.3%) transferred to 246 stroke care hospitals. These connected hospitals formed 93 communities, with a median of 9 hospitals treating a median of 201 patients. Derived communities demonstrated a modularity of 0.904, indicating a strong community structure, highly centralised around one or two hubs. Three distinct types of structures were identified: single-hub (n=60), double-hub (n=22) and hubless systems (n=11). The endovascular treatment rate was highest in double-hub systems, followed by single-hub systems, and was almost zero in hubless systems. The hubless communities were characterised by lower patient volumes, fewer hospitals, no hub hospital and no stroke unit. Conclusions: This network analysis could quantify the national stroke care system and point out areas where the organisation and functionality of acute stroke care could be improved.

Developing a national surveillance system for stroke and acute myocardial infarction using claims data in the Republic of Korea: a retrospective study.

BACKGROUND: Limited information is available concerning the epidemiology of stroke and acute myocardial infarction (AMI) in the Republic of Korea. This study aimed to develop a national surveillance system to monitor the incidence of stroke and AMI using national claims data. METHODS: We developed and validated identification algorithms for stroke and AMI using claims data. This validation involved a 2-stage stratified sampling method with a review of medical records for sampled cases. The weighted positive predictive value (PPV) and negative predictive value (NPV) were calculated based on the sampling structure and the corresponding sampling rates. Incident cases and the incidence rates of stroke and AMI in the Republic of Korea were estimated by applying the algorithms and weighted PPV and NPV to the 2018 National Health Insurance Service claims data. RESULTS: In total, 2,200 cases (1,086 stroke cases and 1,114 AMI cases) were sampled from the 2018 claims database. The sensitivity and specificity of the algorithms were 94.3% and 88.6% for stroke and 97.9% and 90.1% for AMI, respectively. The estimated number of cases, including recurrent events, was 150,837 for stroke and 40,529 for AMI in 2018. The age- and sex-standardized incidence rate for stroke and AMI was 180.2 and 46.1 cases per 100,000 person-years, respectively, in 2018. CONCLUSION: This study demonstrates the feasibility of developing a national surveillance system based on claims data and identification algorithms for stroke and AMI to monitor their incidence rates.

Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.

BACKGROUND AND OBJECTIVES: The association between statin use and the risk of intracranial hemorrhage (ICrH) following ischemic stroke (IS) or transient ischemic attack (TIA) in patients with cerebral microbleeds (CMBs) remains uncertain. This study investigated the risk of recurrent IS and ICrH in patients receiving statins based on the presence of CMBs. METHODS: We conducted a pooled analysis of individual patient data from the Microbleeds International Collaborative Network, comprising 32 hospital-based prospective studies fulfilling the following criteria: adult patients with IS or TIA, availability of appropriate baseline MRI for CMB quantification and distribution, registration of statin use after the index stroke, and collection of stroke event data during a follow-up period of ≥3 months. The primary endpoint was the occurrence of recurrent symptomatic stroke (IS or ICrH), while secondary endpoints included IS alone or ICrH alone. We calculated incidence rates and performed Cox regression analyses adjusting for age, sex, hypertension, atrial fibrillation, previous stroke, and use of antiplatelet or anticoagulant drugs to explore the association between statin use and stroke events during follow-up in patients with CMBs. RESULTS: In total, 16,373 patients were included (mean age 70.5 ± 12.8 years; 42.5% female). Among them, 10,812 received statins at discharge, and 4,668 had 1 or more CMBs. The median follow-up duration was 1.34 years (interquartile range: 0.32-2.44). In patients with CMBs, statin users were compared with nonusers. Compared with nonusers, statin therapy was associated with a reduced risk of any stroke (incidence rate [IR] 53 vs 79 per 1,000 patient-years, adjusted hazard ratio [aHR] 0.68 [95% CI 0.56-0.84]), a reduced risk of IS (IR 39 vs 65 per 1,000 patient-years, aHR 0.65 [95% CI 0.51-0.82]), and no association with the risk of ICrH (IR 11 vs 16 per 1,000 patient-years, aHR 0.73 [95% CI 0.46-1.15]). The results in aHR remained consistent when considering anatomical distribution and high burden (≥5) of CMBs. DISCUSSION: These observational data suggest that secondary stroke prevention with statins in patients with IS or TIA and CMBs is associated with a lower risk of any stroke or IS without an increased risk of ICrH. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with IS or TIA and CMBs, statins lower the risk of any stroke or IS without increasing the risk of ICrH.

Effect of Statin Therapy on Cardiovascular Outcome in Stroke Patients with Low Baseline Low-Density Lipoprotein Cholesterol.

OBJECTIVES: To investigate whether post-stroke statin therapy reduces subsequent major vascular events in statin-naïve patients with pretreatment low-density lipoprotein cholesterol (LDL-C) below the recommended target (≤70 mg/dL for atherosclerotic stroke and ≤100 mg/dL for non-atherosclerotic stroke) at stroke onset. METHODS: Patients from an ongoing stroke registry who had an ischemic stroke between 2011 and 2020 were screened. Statin naïve patients with baseline LDL-C below the target were assessed. The effect of post-stroke statin therapy on major vascular events (composite of recurrent stroke, myocardial infarction, and death) was investigated using weighted Cox regression analyses using stabilized inverse probability treatment weighting. RESULTS: The baseline LDL-C level of the 1,858 patients (mean age 67.9 ± 15.3 years, 61.4% men, 13.2% atherosclerotic stroke) included in the study was 75.7 ± 17.0 mg/dL. Statins were prescribed to 1,256 (67.7%) patients (low-to-moderate intensity, 23.5%; high intensity, 44.1%). Post-stroke statin therapy was associated with a lower risk of major vascular events during 1-year follow-up (weighted hazard ratio 0.55, 95% confidence interval 0.42-0.71). In a subgroup of patients who were at very high risk of atherosclerotic cardiovascular disease with LDL-C <55 mg/dL or patients who were not at very high risk of atherosclerotic cardiovascular disease with LDL-C <70 mg/dL, post-stroke statin therapy was also associated with a reduction in major vascular events (weighted hazard ratio 0.45, 95% confidence interval 0.29-0.70). The intensity of the most beneficial statin varied by subtype of stroke. INTERPRETATION: Statin therapy may improve vascular outcomes after ischemic stroke, even in cases of LDL-C below the target without pre-stroke lipid-lowering therapy. ANN NEUROL 2024;95:876-885.

Emerging Concept of Intracranial Arterial Diseases: The Role of High Resolution Vessel Wall MRI.

Intracranial arterial disease (ICAD) is a heterogeneous condition characterized by distinct pathologies, including atherosclerosis. Advances in magnetic resonance technology have enabled the visualization of intracranial arteries using high-resolution vessel wall imaging (HR-VWI). This review summarizes the anatomical, embryological, and histological differences between the intracranial and extracranial arteries. Next, we review the heterogeneous pathophysiology of ICAD, including atherosclerosis, moyamoya or RNF213 spectrum disease, intracranial dissection, and vasculitis. We also discuss how advances in HR-VWI can be used to differentiate ICAD etiologies. We emphasize that one should consider clinical presentation and timing of imaging in the absence of pathology-radiology correlation data. Future research should focus on understanding the temporal profile of HR-VWI findings and developing quantitative interpretative approaches to improve the decision-making and management of ICAD.

Efficacy of Endovascular Thrombectomy in Acute Basilar Artery Occlusion with Low PC-ASPECTS: A Nationwide Prospective Registry-Based Study.

OBJECTIVE: We evaluated the efficacy of endovascular thrombectomy (EVT) on the functional outcome of patients with acute basilar artery occlusion and low posterior circulation acute stroke prognosis early computed tomography score (PC-ASPECTS). METHODS: We identified patients with acute ischemic stroke due to basilar artery occlusion and PC-ASPECTS of 6 or less, presenting within 24 h between August 2008 and April 2022. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-3 at 90 days. The secondary outcomes included an mRS score of 0-2, a favorable shift in the ordinal mRS scale, the occurrence of symptomatic intracranial hemorrhage (sICH), and mortality at 90 days. We compared the outcome of patients treated with EVT and those without EVT, using the inverse probability of treatment weighting methods. RESULTS: Out of 566 patients, 55.5% received EVT. In the EVT group, 106 (33.8%) achieved favorable outcomes, compared to 56 patients (22.2%) in the conservative group. EVT significantly increased the likelihood of achieving a favorable outcome compared to conservative treatment (relative risk [RR] 1.39, 95% confidence interval [CI], 1.11-1.74, p = 0.004). EVT was associated with a favorable shift in the mRS (RR 1.85, 95% CI, 1.49-2.29, p < 0.001) and reduced mortality without an increase in the risk of sICH. It did not have an impact on achieving an mRS score of 0-2. INTERPRETATION: Patients with acute basilar artery occlusion and a PC-ASPECTS of 6 or less might benefit from EVT without an increasing sICH. ANN NEUROL 2024;95:788-799.

Cutting Balloon Angioplasty for Severe In-Stent Restenosis after Carotid Artery Stenting: Long-Term Outcomes and Review of Literature.

PURPOSE: Cutting balloon-percutaneous transluminal angioplasty (CB-PTA) is a feasible treatment option for in-stent restenosis (ISR) after carotid artery stenting (CAS). However, the longterm durability and safety of CB-PTA for ISR after CAS have not been well established. MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with ISR after CAS who had been treated with CB-PTA from 2012 to 2021 in our center. Detailed information of baseline characteristics, periprocedural and long-term outcomes, and follow-up imaging was collected. RESULTS: During 2012-2021, a total of 301 patients underwent CAS. Of which, CB-PTA was performed on 20 lesions exhibiting severe ISR in 18 patients following CAS. No patient had any history of receiving carotid endarterectomy or radiation therapy. These lesions were located at the cervical segment of the internal carotid artery (n=16), proximal external carotid artery (n=1), and distal common carotid artery (n=1). The median time interval between initial CAS and detection of ISR was 390 days (interquartile range 324-666 days). The follow-up period ranged from 9 months to 9 years with a median value of 21 months. Four patients (22.2%) were symptomatic. The average of stenotic degree before and after the procedure was 79.2% and 34.7%, respectively. Out of the 18 patients receiving CB-PTA, 16 (88.9%) did not require additional stenting, and 16 (88.9%) did not experience recurrent ISR during the follow-up period. Two patients who experienced recurrent ISR were successfully treated with CB-PTA and additional stenting. No periprocedural complication was observed in any case. CONCLUSION: Regarding favorable periprocedural and long-term outcomes in our single-center experience, CB-PTA was a feasible and safe option for the treatment of severe ISR after CAS.

Secular Trends in Outcomes and Impact of Novel Oral Anticoagulants in Atrial Fibrillation-Related Acute Ischemic Stroke.

BACKGROUND: Novel oral anticoagulants (NOACs) are currently recommended for the secondary prevention of stroke in patients with acute ischemic stroke (AIS) accompanied by atrial fibrillation (AF). However, the impact of NOACs on clinical outcomes in real-world practice remains ambiguous. This study analyzes the trend of clinical events in patients with AF-related AIS and determines how much the introduction of NOACs has mediated this trend. METHODS: We identified patients with AIS and AF between January 2011 and December 2019 using a multicenter stroke registry. Annual rates of NOAC prescriptions and clinical events within 1 year were evaluated. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. To assess the mediation effect of NOACs on the relationship between the calendar year and these outcomes, we used natural effect models and conducted exposure-mediator, exposure-outcome, and mediator-outcome analyses using multivariable regression models or accelerated failure time models, adjusting for potential confounders. RESULTS: Among the 12 977 patients with AF-related AIS, 12 500 (average age: 74.4 years; 51.3% male) were analyzed after excluding cases of valvular AF. Between 2011 and 2019, there was a significant decrease in the 1-year incidence of the primary composite outcome from 28.3% to 21.7%, while the NOAC prescription rate increased from 0% to 75.6%. A 1-year increase in the calendar year was independently associated with delayed occurrence of the primary outcome (adjusted time ratio, 1.10 [95% CI, 1.07-1.14]) and increased NOAC prescription (adjusted odds ratio, 2.20 [95% CI, 2.14-2.27]). Increased NOAC prescription was associated with delayed occurrence of the primary outcome (adjusted time ratio, 3.82 [95% CI, 3.17 to 4.61]). Upon controlling for NOAC prescription (mediator), the calendar year no longer influenced the primary outcome (adjusted time ratio, 0.97 [95% CI, 0.94-1.00]). This suggests that NOAC prescription mediates the association between the calendar year and the primary outcome. CONCLUSIONS: Our study highlights a temporal reduction in major clinical events or death in Korean patients with AF-related AIS, mediated by increased NOAC prescription, emphasizing NOAC use in this population.

What have clinical trials taught us about brain health?

The Global Burden of Disease Study projects an almost tripling of dementia cases worldwide in the next 30 years making it important to recognize and understand modifiable risks and preventatives for cognitive impairment. Recent studies suggest that prevention or treatment of cardiovascular risks may be an important strategy to prevent or slow the progression of cognitive impairment. In 2017, the American Heart Association and American Stroke Association introduced metrics for "optimal brain health". These metrics defined brain health in terms of ideal health behaviors and factors. Since then and leading up to 2017, a number of clinical trials have been conducted to investigate the potential of modification of cardiovascular risks on prevention of dementia or cognitive impairment and thus, enhancement of brain health. This discussion is a review of findings from clinical trials focusing on interventions, including antihypertensive agents, glycemic control and lipid-lowering therapies, multidomain approaches, and antithrombotic medications. Notably, the results highlight the promise of intensive blood pressure lowering strategies and multidomain approaches, as evidenced by the FINGER trial. The review also discusses the potential of treatment or prevention of cerebral small vessel disease (cSVD) and the application of Mendelian randomization as a strategy to preserve brain structure and function.

Clinical Associations and Prognostic Value of MRI-Visible Perivascular Spaces in Patients With Ischemic Stroke or TIA: A Pooled Analysis

BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; p = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH.

Brain Frailty and Outcomes of Acute Minor Ischemic Stroke With Large-Vessel Occlusion.

BACKGROUND AND PURPOSE: The influence of imaging features of brain frailty on outcomes were investigated in acute ischemic stroke patients with minor symptoms and large-vessel occlusion (LVO). METHODS: This was a retrospective analysis of a prospective, multicenter, nationwide registry of consecutive patients with acute (within 24 h) minor (National Institutes of Health Stroke Scale score=0-5) ischemic stroke with anterior circulation LVO (acute minor LVO). Brain frailty was stratified according to the presence of an advanced white-matter hyperintensity (WMH) (Fazekas grade 2 or 3), silent/old brain infarct, or cerebral microbleeds. The primary outcome was a composite of stroke, myocardial infarction, and all-cause mortality within 1 year. RESULTS: In total, 1,067 patients (age=67.2±13.1 years [mean±SD], 61.3% males) were analyzed. The proportions of patients according to the numbers of brain frailty burdens were as follows: no burden in 49.2%, one burden in 30.0%, two burdens in 17.3%, and three burdens in 3.5%. In the Cox proportional-hazards analysis, the presence of more brain frailty burdens was associated with a higher risk of 1-year primary outcomes, but after adjusting for clinically relevant variables there were no significant associations between burdens of brain frailty and 1-year vascular outcomes. For individual components of brain frailty, an advanced WMH was independently associated with an increased risk of 1-year primary outcomes (adjusted hazard ratio [aHR]=1.33, 95% confidence interval [CI]=1.03-1.71) and stroke (aHR=1.32, 95% CI=1.00-1.75). CONCLUSIONS: The baseline imaging markers of brain frailty were common in acute minor ischemic stroke patients with LVO. An advanced WMH was the only frailty marker associated with an increased risk of vascular events. Further research is needed into the association between brain frailty and prognosis in patients with acute minor LVO.

Differential impacts of admission LDL-cholesterol on early vascular outcomes by ischemic stroke subtypes.

BACKGROUND: Because ischemic stroke is heterogeneous, the associations between low-density lipoprotein (LDL)-cholesterol levels and early vascular outcomes might be different according to the stroke subtype in acute ischemic stroke patients. METHODS: This study was an analysis of a prospective, multicenter, stroke registry. Acute ischemic stroke patients previously not treated with statins were included. Admission LDL-cholesterol levels were divided into 7 groups at 20 mg/dl intervals for comparison. The primary early vascular outcome was a composite of stroke, myocardial infarction (MI) and all-cause mortality within 3 months. RESULTS: A total of 38,531 patients (age, 68.5 ± 12.8 yrs; male, 59.6%) were analyzed for this study. The 3-month cumulative incidences of the composite of stroke, MI, and all-cause mortality significantly differed among the LDL-cholesterol level groups, with the highest event rate (11.11%) in the lowest LDL-cholesterol group (<70 mg/dl). After adjustment, the U-shaped associations of LDL-cholesterol levels with primary outcome and all-cause mortality were observed. For the stroke subtypes, there were substantial interactions between the LDL-cholesterol groups and stroke subtype and all-cause mortality (Pinteraction=0.07). Different patterns, with higher risks of all-cause mortality in the lower LDL-cholesterol in the large artery atherosclerosis subtype (adjusted hazard ratio [aHR] 1.29, 95% confidence interval [CI] 0.98-1.69), but in the higher LDL-cholesterol in the cardioembolism subtype (aHR 1.71 95% CI [1.28-2.29]), were observed among stroke subtypes. CONCLUSION: We found that there were differential associations of admission LDL-cholesterol levels with all-cause mortality within 3 months among stroke subtypes. These results suggest that admission LDL-cholesterol and early vascular outcomes had complex relationships in patients with ischemic stroke according to the stroke subtypes.

High blood viscosity in acute ischemic stroke.

Background: The changes in blood viscosity can influence the shear stress at the vessel wall, but there is limited evidence regarding the impact on thrombogenesis and acute stroke. We aimed to investigate the effect of blood viscosity on stroke and the clinical utility of blood viscosity measurements obtained immediately upon hospital arrival. Methods: Patients with suspected stroke visiting the hospital within 24 h of the last known well time were enrolled. Point-of-care testing was used to obtain blood viscosity measurements before intravenous fluid infusion. Blood viscosity was measured as the reactive torque generated at three oscillatory frequencies (1, 5, and 10 rad/sec). Blood viscosity results were compared among patients with ischemic stroke, hemorrhagic stroke, and stroke mimics diagnosed as other than stroke. Results: Among 112 enrolled patients, blood viscosity measurements were accomplished within 2.4 ± 1.3 min of vessel puncture. At an oscillatory frequency of 10 rad/sec, blood viscosity differed significantly between the ischemic stroke (24.2 ± 4.9 centipoise, cP) and stroke mimic groups (17.8 ± 6.5 cP, p < 0.001). This finding was consistent at different oscillatory frequencies (134.2 ± 46.3 vs. 102.4 ± 47.2 at 1 rad/sec and 39.2 ± 11.5 vs. 30.4 ± 12.4 at 5 rad/sec, Ps < 0.001), suggesting a relationship between decreases in viscosity and shear rate. The area under the receiver operating curve for differentiating cases of stroke from stroke mimic was 0.79 (95% confidence interval, 0.69-0.88). Conclusion: Patients with ischemic stroke exhibit increases in whole blood viscosity, suggesting that blood viscosity measurements can aid in differentiating ischemic stroke from other diseases.

Improvement in Delivery of Ischemic Stroke Treatments but Stagnation of Clinical Outcomes in Young Adults in South Korea.

BACKGROUND: There is limited information on the delivery of acute stroke therapies and secondary preventive measures and clinical outcomes over time in young adults with acute ischemic stroke. This study investigated whether advances in these treatments improved outcomes in this population. METHODS: Using a prospective multicenter stroke registry in Korea, young adults (aged 18-50 years) with acute ischemic stroke hospitalized between 2008 and 2019 were identified. The observation period was divided into 4 epochs: 2008 to 2010, 2011 to 2013, 2014 to 2016, and 2017 to 2019. Secular trends for patient characteristics, treatments, and outcomes were analyzed. RESULTS: A total of 7050 eligible patients (mean age, 43.1; men, 71.9%) were registered. The mean age decreased from 43.6 to 42.9 years (Ptrend=0.01). Current smoking decreased, whereas obesity increased. Other risk factors remained unchanged. Intravenous thrombolysis and mechanical thrombectomy rates increased over time from 2008 to 2010 to 2017 to 2019 (9.5%-13.8% and 3.2%-9.2%, respectively; Ptrend<0.01). Door-to-needle time improved (Ptrend <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased (Ptrend<0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; Ptrend=0.04), although the difference was not significant after adjusting for sex and age. CONCLUSIONS: Improvements in the delivery of acute stroke treatments did not necessarily lead to better outcomes in young adults with acute ischemic stroke over the past decade, indicating a need for further progress.