Small Vessel Occlusion Stroke Research Articles

Cerebral blood flow and cognition after 3 months tadalafil treatment in small vessel disease (ETLAS-2): study protocol for a randomized controlled trial

BackgroundTargeted treatment is highly warranted for cerebral small vessel disease, a causal factor of one in four strokes and a major contributor to vascular dementia. Patients with cerebral small vessel disease have impaired cerebral blood flow and vessel reactivity. Tadalafil is a specific phosphodiesterase 5 inhibitor shown to improve vascular reactivity in the brain.MethodsThe ETLAS-2 trial is a phase 2 double-blind, randomized placebo-controlled, parallel trial with the feasibility of tadalafil as the primary outcome. The trial aims to include 100 patients with small vessel occlusion stroke or transitory ischemic attacks and signs of cerebral small vessel disease more than 6 months before administration of study medication. Patients are treated for 3 months with tadalafil 20 mg or placebo daily and undergo magnetic resonance imaging (MRI) to evaluate changes in small vessel disease according to the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE) criteria as well as cerebral blood flow, cerebrovascular reactivity, and neurovascular coupling in a functional MRI sub-study. The investigation includes comprehensive cognitive testing using paper–pencil tests and Cambridge Neuropsychological Test Automated Battery (CANTAB) tests in a cognitive sub-study.DiscussionThe ETLAS-2 trial tests the feasibility of long-term treatment with tadalafil and explores vascular and cognitive effects in cerebral small vessel disease in trial sub-studies. The study aims to propose a new treatment target and improve the understanding of small vessel disease. Currently, 64 patients have been included and the trial is estimated to be completed in the year 2024.Trial registrationClinicaltrials.gov, NCT05173896. Registered on 30 December 2021.

Lipid Profiles and Atrial Fibrillation in Ischemic Stroke Patients Treated with Thrombectomy: Experience from a Tertiary Italian Stroke Hospital.

To assess acute lipid profiles, atrial fibrillation and other cardiovascular risk factors in patients undergoing treatments by thrombectomy (EVT) with acute ischemic stroke (AIS). We performed a retrospective analysis of the lipid profile and vascular risk factor in 1639 consecutive patients with acute ischemic stroke between January 2016 and December 2021. To assess lipid profiles, laboratory tests, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were obtained the day after admission. We also examined the association between lipid profile, AF and EVT in multivariate logistic regression analysis. Median age of patients was 74 years, 54.9% were males (95% CI 52.5-57.4%), and 26.8% (95% CI, 24.7-29.0%) had AF. EVT patients (n = 370; 22.57 %; 95% CI, 20.6-24.7) showed no difference in age (median 73 years (IQR; 63-80) versus 74 years (IQR; 63-82)), HbA1c levels (median 5.8 (IQR; 5.4-6.2) versus 5.9 (IQR; 5.4-6.4)), TG/HDL ratio (median 2.40 (IQR; 1.65-3.48) versus 2.51 (IQR; 1.73-3.64)), diabetes (OR 0.82; 95% CI 0.61 to 1.08), hypertension (OR 0.87; 95% CI 0.68 to 1.12) and obesity (OR 1.06; 95% CI 0.78 to 1.42) compared to non-EVT patients. Conversely, EVT patients showed lower levels of TC (160 mg/dl (IQR; 139- 187) versus 173 mg/dl (IQR; 148-202); p <0.001), LDL-C (105 mg/dl (IQR; 80-133) versus 113 mg/dl (IQR; 88-142); p <0.01), TG (98 mg/dl (IQR; 76-126) versus 107 mg/dl (IQR; 85-139); p <0.001), non-HDL-C (117 mg/dl (IQR; 94-145) versus 127 mg/dl (IQR; 103-154); p <0.001), HC (8.3 mmol/l (IQR; 6-11) versus 10 mmol/l (IQR; 7.3-13.5); p <0.001) than non-EVT patients. Multivariate logistic regression analysis showed an independent association of EVT with TC (OR 0.99, 95% CI 0.98-0.99), AF (OR 1.79, 95% CI 1.34-2.38), age (OR 0.98, 95% CI 0.96-0.99), and NIHSS (OR 1.17, 95% CI 0.14-1.19). Total cholesterol and all cholesterol-related measures were significantly lower in patients undergoing thrombectomy than in other stroke patients. Conversely, we found that AF was significantly high in patients with EVT, suggesting that hypercholesterolemia could be mainly linked to small-vessel occlusion stroke while large vessel occlusion (LVO) stroke could show different causes. AIS patients may have different pathogenesis and their understanding may improve the discovery of specific and tailored preventive treatments.

Stroke recurrence and osteoporotic conditions in postmenopausal patients with atherosclerotic ischemic stroke

Recurrence after stroke is common, and associated with a high mortality rate. Degradation of the elastic tissue in the arterial wall has been shown to aggravate atherosclerosis in blood vessels. Considering that type 1 collagen is present in both bone and vascular smooth muscle cells, we explored whether osteoporotic conditions affect the likelihood of stroke recurrence in postmenopausal women following atherosclerotic ischemic stroke. To determine actual bone mineral density (BMD), the Hounsfield unit values in the frontal skull were evaluated using brain computed tomography (CT) scans taken at admission. A multivariate Cox regression analysis was also performed to examine if osteoporosis could independently predict stroke recurrence in postmenopausal patients with large artery atherosclerosis (LAA) or small vessel occlusion (SVO) stroke. This study included 2130 consecutive patients (both males and females aged 50 and older) with acute LAA or SVO strokes. After adjusting for all covariates, hypothetical osteoporosis was identified as an independent predictor of stroke recurrence in female patients ≥50 years with acute LAA or SVO stroke (hazard ratio, 1.84; 95 % confidence interval, 1.05 to 3.24; p = 0.034). Our findings showed that osteoporosis could potentially affect the recurrence of ischemic stroke in postmenopausal patients with LAA or SVO stroke.

Clinical characteristics of stroke in SARS-CoV-2 infected patients in Japan: A prospective nationwide study

IntroductionWe investigated the clinical characteristics and outcomes of stroke in SARS-CoV-2 infected patients in Japan. MethodsThis prospective, multicenter observational study of stroke in patients with SARS-CoV-2 infection involving 563 primary stroke centers across Japan was conducted between July 2020, and May 2022. We included 159 stroke cases (131 ischemic stroke, 2 transient ischemic attack (TIA), 21 intracranial hemorrhage, and 5 subarachnoid hemorrhage) and collected their clinical characteristics. Ischemic stroke and TIA (n = 133) were analyzed separately. ResultsThe mean age of the 159 patients was 70.6 years, with 66% being men. Poor outcomes (modified Rankin Scale score 5–6) occurred in 40% (63/159) at discharge. Among patients with ischemic stroke and TIA, 30%, 18%, 10%, and 42% had cardioembolism, large-artery atherosclerosis, small-vessel occlusion, and cryptogenic stroke or embolic stroke of undetermined source, respectively. One-third (34%) presented with large vessel occlusion (LVO) of the internal carotid, middle cerebral M1, or basilar arteries. Poor outcomes included age (adjusted odds ratio (aOR): 1.06, 95%CI: 1.01–1.12), ischemic heart disease (IHD) history (aOR: 13.00, 95%CI: 1.51–111.70), moderate to severe pneumonia (aOR: 7.78, 95%CI: 1.18–51.42), an National Institutes of Health Stroke Scale score at baseline (aOR: 1.10, 95%CI: 1.03–1.17), LVO (aOR: 14.88, 95%CI: 2.33–94.97), and log10 D-dimer (aOR: 3.38, 95%CI: 1.01–11.26). ConclusionUpon discharge, 40% of SARS-CoV-2 infected patients with ischemic stroke and TIA had poor outcomes. Poor outcomes were associated with older age, IHD history, moderate to severe pneumonia, higher NIHSS scores, LVO, and higher log10 D-dimer.Registration: UMIN Clinical Trials Registry: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000041226.

Impact of white matter hyperintensity volumes estimated by automated methods using deep learning on stroke outcomes in small vessel occlusion stroke.

Although white matter hyperintensity (WMH) shares similar vascular risk and pathology with small vessel occlusion (SVO) stroke, there were few studies to evaluate the impact of the burden of WMH volume on early and delayed stroke outcomes in SVO stroke. Using a multicenter registry database, we enrolled SVO stroke patients between August 2013 and November 2022. The WMH volume was estimated by automated methods using deep learning (VUNO Med-DeepBrain, Seoul, South Korea), which was a commercially available segmentation model. After propensity score matching (PSM), we evaluated the impact of WMH volume on early neurological deterioration (END) and poor functional outcomes at 3-month modified Ranking Scale (mRS), defined as mRS score >2 at 3 months, after an SVO stroke. Among 1,718 SVO stroke cases, the prevalence of subjects with severe WMH (Fazekas score ≥ 3) was 68.9%. After PSM, END and poor functional outcomes at 3-month mRS (mRS > 2) were higher in the severe WMH group (END: 6.9 vs. 13.5%, p < 0.001; 3-month mRS > 2: 11.4 vs. 24.7%, p < 0.001). The logistic regression analysis using the PSM cohort showed that total WMH volume increased the risk of END [odd ratio [OR], 95% confidence interval [CI]; 1.01, 1.00-1.02, p = 0.048] and 3-month mRS > 2 (OR, 95% CI; 1.02, 1.01-1.03, p < 0.001). Deep WMH was associated with both END and 3-month mRS > 2, but periventricular WMH was associated with 3-month mRS > 2 only. This study used automated methods using a deep learning segmentation model to assess the impact of WMH burden on outcomes in SVO stroke. Our findings emphasize the significance of WMH burden in SVO stroke prognosis, encouraging tailored interventions for better patient care.

Effect of pre-stroke antiplatelet use on stroke outcomes in acute small vessel occlusion stroke with moderate to severe white matter burden

BackgroundCerebral small vessel disease is characterized by white matter hyperintensities (WMH) and acute small vessel occlusion (SVO) stroke. We investigated the effect of prior antiplatelet use (APU) on stroke outcome in 1151 patients with acute SVO stroke patients and moderate to severe WMH. MethodsUsing a multicenter database, this retrospective study used quantitative WMH volume measurements and propensity score matching (PSM) for comparisons between patients with prior APU and without APU. Primary outcomes were stroke progression and poor functional outcome (modified Rankin Scale>2) at 3 months. Logistic regression analyses assessed associations between prior APU, WMH burden, and stroke outcomes. ResultsStroke progression was lower in the prior APU group in both the total cohort (14.8% vs. 6.9%, p < 0.001) and the PSM cohort (16.3% vs. 6.9%, p < 0.001). The proportion of poor functional outcomes at 3 months was not significantly different in the total cohort, but the PSM cohort showed a lower proportion in the prior APU group (30.8% vs. 20.2%, p = 0.002). Logistic regression analysis confirmed that prior APU was associated with a reduced risk of stroke progression (OR, 0.39; 95% CI, 0.22–0.70; p = 0.001) and poor functional outcome at 3 months (OR, 0.37; 95% CI, 0.23–0.59; p < 0.001). ConclusionPrior APU is associated with reduced stroke progression and improved functional outcome at 3 months in acute SVO stroke patients with moderate to severe WMH. Early treatment of WMH and acute SVO stroke may have potential benefits in improving stroke outcomes.

Time Window for Induced Hypertension in Acute Small Vessel Occlusive Stroke With Early Neurological Deterioration.

Therapeutic-induced hypertension treatment (iHTN) is helpful for alleviating early neurological deterioration (END) in acute small vessel occlusive stroke. We examined the time parameters related to iHTN effectiveness in these patients. We retrospectively reviewed patients with acute small vessel occlusive stroke who underwent iHTN for END, defined as an increase of ≥2 points in total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 point in motor items of NIHSS. The primary outcome was an early neurological improvement (ENI; a decrease of ≥2 points in total NIHSS score or ≥1 point in motor items of NIHSS), and the secondary outcome was any neurological improvement (a decrease of ≥1 point in the total NIHSS score). We conducted a multivariable logistic regression analysis, adjusting for demographics, risk factors, baseline clinical status, and intervention-related variables. We also generated a restricted cubic spline curve for the END-to-iHTN time cutoff. Among the 1062 patients with small vessel occlusive stroke screened between 2017 and 2021, 136 patients who received iHTN within 24 hours from END were included. The mean age was 65.1 (±12.0) years, and 61.0% were male. Sixty-five (47.8%) patients showed ENI and 77 (56.6%) patients showed any neurological improvement. END-to-iHTN time was significantly shorter in patients with ENI (150 [49-322] versus 290 [97-545] minutes; P=0.018) or any neurological improvement (150 [50-315] versus 300 [130-573] minutes; P=0.002). A 10-minute increase in the time between END and iHTN decreased the odds of achieving ENI (odds ratio, 0.984 [95% CI, 0.970-0.997]; P=0.019) or any neurological improvement (odds ratio, 0.978 [95% CI, 0.964-0.992]; P=0.002). The restricted cubic spline curve showed that the odds ratio of ENI reached its minimum at ≈3 hours. Among patients with small vessel occlusive stroke with END, a shorter interval between END and the initiation of iHTN was associated with increased odds of achieving neurological improvement. The efficacy of iHTN may be limited to induction within the first 3 hours of END.

The diagnostic tests and functional outcomes of acute ischemic stroke or transient ischemic attack in young adults: A 4-year hospital-based observational study.

Ischemic strokes in young adults have been a significant concern due to various potential etiologies and had substantial clinical and public health impacts. We aimed to study the diagnostic tests, etiologies, and functional outcomes of acute ischemic stroke (AIS) and transient ischemic attack (TIA) in young adult patients. The data were retrieved from the Chiang Mai University Hospital Stroke Registry between January 2018 and December 2021. Consecutive AIS or TIA patients were included if they were 18-50 years and had no stroke mimics. Study outcomes were proportions of positive diagnostic tests, and 90-day modified Rankin Scale (mRS). Of 244 enrolled patients, 59.0% (n = 144) were male, and 38.1% (n = 93) were aged 18-40, classified as the younger age group. There was a high incidence of diabetes (24.5%) and dyslipidemia (54.3%) among patients aged 41-50, associated with small-vessel occlusion and large-artery atherosclerosis stroke classification in this age group. Patients aged 18-40 years had more other determined etiologies (39.8%), with hypercoagulability (8.2%), arterial dissection (7.8%), and cardiac sources (6.6%) being the first three causes, which were associated with higher anticoagulant treatment. The cerebrovascular study, cardiac evaluation using echocardiography, and antiphospholipid syndrome testing were commonly performed, of which computed tomography angiography provided a high proportion of positive results (80.3%). 76.3% of young adult patients had excellent functional outcomes (mRS 0-1) with a median mRS of 0 (interquartile range 0-1) at 90-day follow-up. Stroke of other determined etiology remained the common cause of stroke in young adults, and most affected individuals had excellent clinical outcomes. Blood tests for arterial hypercoagulability and noninvasive vascular and cardiac evaluations are encouraged in selected patients to determine the stroke etiology and guide for appropriate preventive strategies.

Ischemic Stroke and Cerebral Microbleeds: A Two-Sample Bidirectional Mendelian Randomization Study.

Recent observational studies have reported the association between ischemic stroke (IS) and cerebral microbleeds (CMBs). Whether this reflects a causal association remains to be established. Herein, we adopted a two-sample bidirectional Mendelian randomization (MR) analysis to comprehensively evaluate the causal association of IS and CMBs. The summary-level genome-wide association studies (GWASs) data of IS were obtained from the GIGASTROKE consortium (62,100 European ancestry cases and 1,234,808 European ancestry controls). All IS cases could be further divided into large-vessel atherosclerosis stroke (LVS, n = 6399), cardio-embolic stroke (CES, n = 10,804) and small-vessel occlusion stroke (SVS, n = 6811). Meanwhile, we used publicly available summary statistics from published GWASs of CMBs (3556 of the 25,862 European participants across 2 large initiatives). A bidirectional MR analysis was conducted using inverse-variance weighting (IVW) as the major outcome, whereas MR-Egger and weighted median (WM) were used to complement the IVW estimates as they can provide more robust estimates in a broader set of scenarios but are less efficient (wider CIs). A Bonferroni-corrected threshold of p < 0.0125 was considered significant, and p values between 0.0125 and 0.05 were considered suggestive of evidence for a potential association. We detected that higher risk of IS [IVW odds ratio (OR) 1.47, 95% confidence interval (CI) 1.04-2.07, p = 0.03] and SVS (IVW OR 1.62, 95% CI 1.07-2.47, p = 0.02) were significantly associated with CMBs. Reverse MR analyses found no significant evidence for a causal effect of CMBs on IS and its subtypes. Our study provides potential evidence that IS and SVS are causally linked to increased risk of CMBs. Further research is needed to determine the mechanisms of association between IS and CMBs.

Myasthenia Gravis and Ischemic Stroke: A Bidirectional Mendelian Randomization Study.

Autoimmune diseases are associated with cardiovascular and cerebrovascular diseases. However, whether myasthenia gravis (MG) and ischemic stroke (IS) are causally related remains unclear. This study aimed to evaluate potential causal links between MG and IS using bidirectional Mendelian randomization (MR). We conducted a two-sample MR analysis to assess the potential associations between MG and IS. Genetic variants associated with MG and IS as well as their subtypes were extracted from genome-wide association studies by meta-analysis. The inverse-variance weighted method was used for the main MR analysis. Sensitivity analyses, including the MREgger, simple mode, simple median, weighted mode, and weighted median approaches were applied to test the robustness of the results. The MR analyses indicated no causal effects of general MG on IS of all causes (odds ratio [OR] = 0.990, 95% confidence interval [CI]: 0.953-1.029, P = 0.615), large vessel atherosclerosis stroke (OR = 0.943, 95% CI: 0.856-1.039, P = 0.233), cardioembolic stroke (OR = 0.975, 95% CI: 0.867-1.096, P = 0.670), and small vessel occlusion stroke (OR = 1.059, 95% CI 0.974-1.150, P = 0.178). Subgroup analyses indicated no causal effects of early- or late-onset MG on IS and its subtypes (all P > 0.05). The reverse MR analysis showed no significant causal associations of IS on MG (all P > 0.05). Bidirectional MR analysis did not provide evidence to support a causal relationship between genetically predicted MG and IS, although observational studies have found such a potential link.

Utility Of Transesophageal Echocardiogram In Acute Ischemic Stroke For Cardioembolic Sources Diagnosis: A Retrospective Cohort Study In A Third Level Hospital In Buenos Aires, Argentina. (P6-5.008)

<h3>Objective:</h3> To describe and analyze the proportion, characteristics, and predictors for changes in therapeutic management in adults with acute ischemic stroke (AIS) who underwent a transesophageal echocardiogram (TEE). <h3>Background:</h3> Cerebrovascular disease is a major cause of acquired disability and up to 30% of strokes have a cardioembolic source. Echocardiography plays an important role in its early identification and is a routine study during stroke workup. However, it is still unclear which patients might benefit from TEE. <h3>Design/Methods:</h3> A retrospective cohort study was conducted between October 1st, 2015, and September 30th, 2022, which included adults with AIS who underwent TEE. Patients with small vessel occlusion or large artery atherosclerotic stroke were excluded. A change in therapeutic management was defined as the indication of anticoagulation or antibiotics, or when cardiac surgery was performed related to TEE findings. Major and minor cardioembolic sources were defined according to the ACE guidelines classification. <h3>Results:</h3> 624 observations were included. The median age was 76 years (IQR 17) and 45.3% were male. A major cardioembolic source was found in 6.7 % of the patients, and a minor source in 29,6%. Changes in therapeutic management occurred in 103 patients (16%). In multivariable logistic regression, age and history of myocardial infarction were independently associated with changes in therapeutic management, OR 0.98 (CI95%, 0.97–0.99, p=0.03) and OR 2.33 (CI95%, 1.03–5.01, p=0.03) respectively. No association with this outcome was found in bivariate analysis. In the group of patients with changes in therapeutic management, 70.9% had only minor cardioembolic sources, 24.3% only major sources, and 16.5% had both. <h3>Conclusions:</h3> 16% of TEE findings were associated with changes in therapeutic management and minor cardioembolic sources were the main cause. Also, age and history of myocardial infarction were independently associated with changes in therapeutic management. <b>Disclosure:</b> Alejandra Heriz has nothing to disclose. Dr. Marquez has nothing to disclose. Mr. Ayerbe has nothing to disclose. Juan Pablo Rodriguez has nothing to disclose. Dr. Sanjinez has nothing to disclose. Dr. Escandon has nothing to disclose. Dr. VEGA VEGA has nothing to disclose. Dr. Stupenengo has nothing to disclose. Natalia Balian has nothing to disclose. Marcelo Rugiero Rodriguez has nothing to disclose.

Acute ischemic stroke thrombolysis- experience from a rural hospital in Kerala, India

Outcome assessment of thrombolysis with intravenous rt-PA in acute ischemic stroke.All patients with acute ischemic stroke patients who underwent IV thrombolysis with rt-PA from January 2019 to December 2021 were studied retrospectively. Clinical efficacy outcome was the favourable outcome on modified Rankin scale at 90 days defined as a score of ≤2. During our study period, a total of 50 patients with ischemic stroke thrombolysis underwent intravenous recombinant tissue plasminogen activator (rt‑PA). The study consisted of 33 males and 17 females with a mean age of 64.82 ( 12.21 standard deviation) years. The median time from onset of symptoms to IV rt-PA administration was 120 minutes (interquartile range 90 - 160). The mean door to needle time was 50.1 ( 21.32 SD) minutes. Favourable outcome (mRS score ≤2) was observed in 38 patients (76%) at three months’ follow-up. Poor outcome (mRS score &amp;#62;2) was seen in the remaining 12 patients (24%).Large artery atherosclerosis had the most favourable outcome followed by small vessel occlusive stroke. Factors predicting favourable outcome in our study were age &amp;#60;60 years (p = 0.03), female gender (p &amp;#60; 0.001) and large vessel occlusion (p &amp;#60; 0.001). Factors predicting poor outcome were hypertension (p &amp;#60; 0.001), dyslipidemia (p = 0.01), prior stroke (p &amp;#60; 0.001) and symptomatic haemorrhage (p = 0.02). Ischemic stroke patients can be thrombolysed in a safe and effective even in rural settings if proper institutional protocol is formulated and its implementation is ensured.

Circulating N-Terminal Probrain Natriuretic Peptide Levels in Relation to Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study.

Mendelian randomization was used to evaluate the potential causal association between N-terminal probrain natriuretic peptide (NT-proBNP) and ischemic stroke based on summary statistics data from large-scale genome-wide association studies. Three single-nucleotide polymorphisms (SNPs) rs198389, rs13107325, and rs11105306 associated with NT-proBNP levels found in large general populations and in patients with acute heart disease were used as instrumental variables. The results of genetic association analysis of each single SNP show that there is no significant association between NT-proBNP levels and ischemic stroke or its subtypes, whereas rs198389 alone has a suggestive association with large-artery atherosclerosis stroke. The MR analysis of three SNPs shows that NT-proBNP levels may reduce the risk of small-vessel occlusion stroke suggestively. This genetic analysis provides insights into the pathophysiology and treatment of ischemic stroke.

Differential value of intima thickness in ischaemic stroke due to large-artery atherosclerosis and small-vessel occlusion.

No study has examined the differential value of arterial intima thickness in the subtypes of acute ischaemic stroke. This study aimed to assess whether intima thickness of carotid artery (CIT), radial artery (RIT) and dorsalis pedis artery (PIT) have an independent and additive value in differentiating ischaemic stroke subtypes due to large‐artery atherosclerosis (LAA) or small‐vessel occlusion (SVO). One hundred and sixty‐one patients with LAA and 79 patients with SVO were recruited. CIT, RIT and PIT were measured with a 24‐MHz ultrasound transducer. Binary logistic regression analysis was used to evaluate the differential values of the different parameters in the two subtypes. ROC curve analyses were plotted to compare the differential performance of different parameters and the combination model. Both RIT and PIT were substantially thicker in LAA than in SVO stroke patients. RIT and carotid intima‐media thickness had similar performances in differentiating stroke subtypes. Introduction of RIT to traditional atherosclerotic associated risk factors had a marginal satisfactory differential performance for LAA and SVO stroke patients (AUC 0.775). RIT is a promising parameter for LAA and SVO subgroup classification. The combination of RIT and traditional risk factors might be a promising tool for differentiating ischaemic stroke subgroups.

Bacterial lipopolysaccharide is associated with stroke

We aimed to determine if plasma levels of bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA) are associated with different causes of stroke and correlate with C-reactive protein (CRP), LPS-binding protein (LBP), and the NIH stroke scale (NIHSS). Ischemic stroke (cardioembolic (CE), large artery atherosclerosis (LAA), small vessel occlusion (SVO)), intracerebral hemorrhage (ICH), transient ischemic attack (TIA) and control subjects were compared (n = 205). Plasma LPS, LTA, CRP, and LBP levels were quantified by ELISA. LPS and CRP levels were elevated in ischemic strokes (CE, LAA, SVO) and ICH compared to controls. LBP levels were elevated in ischemic strokes (CE, LAA) and ICH. LTA levels were increased in SVO stroke compared to TIA but not controls. LPS levels correlated with CRP and LBP levels in stroke and TIA. LPS, LBP and CRP levels positively correlated with the NIHSS and WBC count but negatively correlated with total cholesterol. Plasma LPS and LBP associate with major causes of ischemic stroke and with ICH, whereas LPS/LBP do not associate with TIAs. LTA only associated with SVO stroke. LPS positively correlated with CRP, LBP, and WBC but negatively correlated with cholesterol. Higher LPS levels were associated with worse stroke outcomes.

Adherence to Antithrombotic Treatment and Ischemic Stroke Recurrence in Egypt and Germany: A Comparative Analysis

Background: The burden of stroke weighs heavily in developing countries where recurrence rates clearly exceed that of developed countries. The impact of nonadherence to antithrombotic treatment within this context has been poorly investigated. Objective: The objective of this study was to evaluate patients with recurrent ischemic stroke in Egypt and Germany with focus on stroke subtype distribution and adherence to antithrombotic therapy. Methods: We conducted a comparative cross-sectional retrospective cohort study enrolling consecutive patients hospitalized for recurrent ischemic stroke in 2017 in 2 academic centers. Data were collected on demographics, risk factors, stroke subtypes, and medication adherence. Nonadherence to antithrombotic agents was analyzed at the time point of index stroke (recurrent stroke). Predictors of nonadherence were analyzed using logistic regression. Results: A total of 373 Egyptian and 468 German patients with ischemic stroke were included. The proportion of recurrent ischemic stroke among all patients was higher in the Egyptian cohort compared to the German cohort (33 vs. 10%, p < 0.05). Small-vessel occlusion stroke was the most frequent subtype in Egyptians, with a significantly greater proportion than in Germans (45 vs. 26%, p < 0.05). Nonadherence to antiplatelets at the time point of the recurrent stroke was higher in Egyptians than in Germans (82 vs. 19%, p < 0.001). Low educational attainment among Egyptians (OR 0.14, 95% CI [0.00–0.19], p < 0.01) and high comorbidity scores among Germans (OR 2.45, 95% CI [1.06–5.66], p < 0.05) were found to be predictors of nonadherence to antithrombotic treatment. Conclusions: The large stroke recurrence burden in Egypt may be partly explained by differing adherence to secondary preventative antithrombotic pharmacotherapy. Predictors of medication nonadherence have to be addressed to reduce stroke recurrence disparities.

Serum Homocysteine Is Associated With HDL Only in Stroke Patients With Small Vessel Occlusion.

Background: Although controversial, homocysteine (Hcy) and lipid parameters have been associated with particular stroke subtypes. However, there are limited studies concerning the relationship between Hcy and lipid levels in acute ischemic stroke (AIS). We evaluated the impact of Hcy levels on lipid profiles in terms of specific stroke subtypes.Methods: A total of 2,324 patients with first-ever AIS were recruited from two hospitals in South Korea. The exclusion criteria were as follows: (a) pre-stroke modified Rankin scale (mRS) ≥ 1, (b) undetermined or other stroke etiology, and (c) absence of Hcy data. Among the 1,580 eligible patients, the Hcy level was divided into tertile groups. Logistic regression was used to assess association of Hcy levels with lipid levels by stroke subtypes.Results: Significant downward trends in total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were only observed in patients with small vessel occlusion (SVO) as Hcy increased. In logistic regression analysis, while in patients with SVO subtype, the highest level of Hcy tertiles (OR = 1.648, 95% CI = 1.047–2.594) was associated with the lower HDL level (≤40 mg/dL), the significance disappeared in patients with LAA and CE subtypes.Conclusion: Although our study does not demonstrate causal relationship, we suggest that Hcy might play a mediating role between HDL and SVO stroke development. To clarify the role of Hcy on AIS, this study will provide academic support for designing future research.

Effects of liraglutide and semaglutide on stroke subtypes in patients with type 2 diabetes: a post hoc analysis of the LEADER, SUSTAIN 6 and PIONEER 6 trials

Abstract Introduction Diabetes is an independent risk factor for stroke, with approximately a two-fold excess risk in people with versus those without diabetes. Accumulating evidence suggests glucagon-like peptide-1 (GLP-1) analogues (including liraglutide and semaglutide) may reduce the risk of stroke in patients with type 2 diabetes (T2D). Purpose We examined the effect of liraglutide and semaglutide on stroke and its subtypes based on pooled data from LEADER, SUSTAIN 6 and PIONEER 6. Methods LEADER (NCT01179048), SUSTAIN 6 (NCT01720446) and PIONEER 6 (NCT02692716) were global randomised cardiovascular (CV) outcomes trials of liraglutide, subcutaneous semaglutide and oral semaglutide, respectively, in patients with T2D at high CV risk. In this post hoc analysis, we evaluated the effect of these GLP-1 analogue treatments (pooled) on time to first occurrence of all strokes and subtypes of stroke. Ischaemic stroke was subcategorised according to the TOAST classification, based on aetiology by an external blinded reviewer. A Cox proportional hazards model stratified by trial with pooled treatment as a factor was used to examine treatment effects. Results Across the three trials, 216/7907 (2.7%) patients in the GLP-1 analogue group and 262/7913 (3.3%) in the placebo group had a stroke. The risk of first occurrence of all strokes was significantly reduced in the GLP-1 analogue versus placebo group (HR 0.82, 95% CI 0.68–0.98; p=0.030). Treatment effects were consistent across stroke subtypes: ischaemic (HR 0.84, 95% CI 0.69–1.02; p=0.08), haemorrhagic (HR 0.72, 95% CI 0.42–1.22; p=0.22) and undetermined (HR 0.71, 95% CI 0.32–1.60; p=0.41; Figure 1). Across TOAST subcategories, there was a trend that GLP-1 analogue treatment had the greatest benefit versus placebo in small vessel occlusion strokes compared with large artery disease or cardioembolic strokes; however, no statistically significant effects were found in any subcategory. Conclusion In this post hoc analysis of the LEADER, SUSTAIN 6 and PIONEER 6 trials, GLP-1 analogue treatment reduced the risk of stroke in patients with T2D and high CV risk, with an indication using TOAST criteria of the strongest effect on stroke caused by small vessel occlusion. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novo Nordisk A/S. WDS is supported by the NIHR Exeter Clinical Research Facility. MAJ is supported by the NIHR SW Peninsula Applied Research Collaboration. This abstract does not necessarily reflect the views of the NIHR, the Exeter Clinical Research Facility, the NHS or the UK Department of Health.

Association of Coronavirus Disease (COVID-19) With Large Vessel Occlusion Strokes: A Case-Control Study.

BACKGROUND. An increase in frequency of acute ischemic strokes has been observed among patients presenting with acute neurologic symptoms during the coronavirus disease (COVID-19) pandemic. OBJECTIVE. The purpose of this study was to investigate the association between COVID-19 and stroke subtypes in patients presenting with acute neurologic symptoms. METHODS. This retrospective case-control study included patients for whom a code for stroke was activated from March 16 to April 30, 2020, at any of six New York City hospitals that are part of a single health system. Demographic data (age, sex, and race or ethnicity), COVID-19 status, stroke-related risk factors, and clinical and imaging findings pertaining to stroke were collected. Univariate and multivariate analyses were conducted to evaluate the association between COVID-19 and stroke subtypes. RESULTS. The study sample consisted of 329 patients for whom a code for stroke was activated (175 [53.2%] men, 154 [46.8%] women; mean age, 66.9 ± 14.9 [SD] years). Among the 329 patients, 35.3% (116) had acute ischemic stroke confirmed with imaging; 21.6% (71) had large vessel occlusion (LVO) stroke; and 14.6% (48) had small vessel occlusion (SVO) stroke. Among LVO strokes, the most common location was middle cerebral artery segments M1 and M2 (62.0% [44/71]). Multifocal LVOs were present in 9.9% (7/71) of LVO strokes. COVID-19 was present in 38.3% (126/329) of the patients. The 61.7% (203/329) of patients without COVID-19 formed the negative control group. Among individual stroke-related risk factors, only Hispanic ethnicity was significantly associated with COVID-19 (38.1% of patients with COVID-19 vs 20.7% of patients without COVID-19; p = 0.001). LVO was present in 31.7% of patients with COVID-19 compared with 15.3% of patients without COVID-19 (p = 0.001). SVO was present in 15.9% of patients with COVID-19 and 13.8% of patients without COVID-19 (p = 0.632). In multivariate analysis controlled for race and ethnicity, presence of COVID-19 had a significant independent association with LVO stroke (odds ratio, 2.4) compared with absence of COVID-19 (p = 0.011). CONCLUSION. COVID-19 is associated with LVO strokes but not with SVO strokes. CLINICAL IMPACT. Patients with COVID-19 presenting with acute neurologic symptoms warrant a lower threshold for suspicion of large vessel stroke, and prompt workup for large vessel stroke is recommended.

Risk and Secondary Prevention of Stroke Recurrence: A Population-Base Cohort Study.

With recent advances in secondary prevention management, stroke recurrence rates may have changed substantially. We aim to estimate risks and trends of stroke recurrence over the past 2 decades in a population-based cohort of patients with stroke. Patients with a first-ever stroke between 1995 and 2018 in South London, United Kingdom (n=6052) were collected and analyzed. Rates of recurrent stroke with 95% CIs were stratified by 5-year period of index stroke and etiologic TOAST (Trial of ORG 10172 in Acute Stroke Treatment) subtype. Cumulative incidences were estimated and multivariate Cox models applied to examine associations of recurrence and recurrence-free survival. The rate of stroke recurrence at 5 years reduced from 18% (95% CI, 15%-21%) in those who had their stroke in 1995 to 1999 to 12% (10%-15%) in 2000 to 2005, and no improvement since. Recurrence-free survival has improved (35%, 1995-1999; 67%, 2010-2015). Risk of recurrence or death is lowest for small-vessel occlusion strokes and other ischemic causes (36% and 27% at 5 years, respectively). For cardioembolic and hemorrhagic index strokes around half of first recurrences are of the same type (54% and 51%, respectively). Over the whole study period a 54% increased risk of recurrence was observed among those who had atrial fibrillation before the index stroke (hazard ratio, 1.54 [1.09-2.17]). The rate of recurrence reduced until mid-2000s but has not changed over the last decade. The majority of cardioembolic or hemorrhagic strokes that have a recurrence are stroke of the same type indicating that the implementation of effective preventive strategies is still suboptimal in these stroke subtypes.