Small Vessel Occlusion Subtype Research Articles

Effectiveness of statin treatment for recurrent stroke according to stroke subtypes

Understanding the effectiveness of statin treatment is essential for developing tailored stroke prevention strategies. We aimed to evaluate the efficacy of statin treatment in preventing recurrent stroke among patients with various ischemic stroke subtypes. Using data from the Clinical Research Collaboration for Stroke-Korea-National Institute for Health (CRCS-K-NIH) registry, we included patients with acute ischemic stroke admitted between January 2011 and July 2020. To evaluate the differential effects of statin treatment based on the ischemic stroke subtype, we analyzed patients with large artery atherosclerosis (LAA), cardio-embolism (CE), and small vessel occlusion (SVO). The primary outcomes were recurrent ischemic stroke and recurrent stroke events. The hazard ratio for outcomes between statin users and nonusers was compared using a Cox proportional hazards model adjusted for covariates. A total of 46,630 patients who met the inclusion criteria were analyzed. Statins were prescribed to 92%, 93%, and 78% of patients with LAA, SVO, and CE subtypes, respectively. The hazards of recurrent ischemic stroke and recurrent stroke in statin users were reduced to 0.79 (95% confidence interval [CI], 0.63-0.99) and 0.77 (95% CI, 0.62-0.95) in the LAA subtype and 0.63 (95% CI, 0.52-0.76) and 0.63 (95% CI, 0.53-0.75) in CE subtype compared to nonusers. However, the hazards of these outcomes did not significantly decrease in the SVO subtype. The effectiveness of statin treatment in reducing the risk of recurrent stroke in patients with LAA and CE subtypes has been suggested. Nonetheless, no significant effect was observed in the SVO subtype, suggesting a differential effect of statins on different stroke subtypes.

The Untargeted Metabolomics Reveals Differences in Energy Metabolism in Patients with Different Subtypes of Ischemic Stroke.

Ischemic stroke (IS) is the most common subtype of stroke. The risk factors and pathogenesis of IS are complex and varied due to different subtypes. Therefore, we used metabolomics technology to investigate the biomarkers and potential pathophysiological mechanisms of different subtypes of IS. We included 126 IS patients and divided them into two groups based on the TOAST classification: large-artery atherosclerosis (LAA) group (n = 87) and small-vessel occlusion (SVO) group (n = 39). Plasma metabolomics analysis was performed using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) to identify metabolic profiles in LAA and SVO subtype IS patients and to determine metabolic differences between patients with the two subtypes of IS. We identified 26 differential metabolites between LAA and SVO subtype IS. A multiple prediction model based on the plasm metabolites had good predictive ability for IS subtyping (AUC = 0.822, accuracy = 77.8%), with 12,13-DHOME being the most important differential metabolite in the model. The differential metabolic pathways between the two subtypes of IS patients included tricarboxylic acid (TCA) cycle, alanine, aspartate and glutamate metabolism, and pyruvate metabolism, mainly focused on energy metabolism. 12,13-DHOME emerged as the primary discriminatory metabolite between LAA and SVO subtypes of IS. In LAA subtype IS patients, energy metabolism, encompassing pyruvate metabolism and the TCA cycle, exhibited lower activity levels when compared to patients with the SVO subtype IS. The utilization of targeted metabolomics holds the potential to improve diagnostic accuracy for distinguishing stroke subtypes.

Association of HbA1c with functional outcome by ischemic stroke subtypes and age.

To determine whether high HbA1c levels are related to short-and long-term functional outcomes in patients with ischemic stroke (IS) and whether this association differs according to the IS subtype and the patient's age. The data of 7,380 IS patients admitted to 16 hospitals or regional stroke centers in South-Korea, between May 2017 and December 2019, were obtained from the Clinical Research Collaboration for Stroke-Korea-National Institute of Health database and retrospectively analyzed. Among these patients, 4,598 were followed-up for one-year. The HbA1c levels were classified into three groups (<5.7, 5.7 to <6.5%, ≥6.5%). Short-and long-term poor functional outcomes were defined using the modified Rankin Scale score of 2 to 6 at three-months and one-year, respectively. IS subtypes were categorized according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. There was an association between higher HbA1c (≥6.5%) and poor functional outcomes at three-months in all patients (three-months; OR, 1.299, 95% CI 1.098, 1.535, one-year; OR, 1.181, 95% CI 0.952, 1.465). When grouped by age, the associations after both 3 months and 1 year observed in younger adult group (<65 years), but not in group aged 65 years and older (three-months; <65 years OR, 1.467, 95% CI 1.112, 1.936, ≥65 years OR, 1.220, 95% CI 0.987, 1.507, p for interaction = 0.038, one-year; <65 years OR, 1.622, 95% CI 1.101, 2.388, ≥65 years OR, 1.010, 95% CI 0.778, 1.312, p for interaction = 0.018). Among younger adult group, the higher HbA1c level was related to short-and long-term functional loss in patients with the small vessel occlusion subtype (three-months; OR, 2.337, 95%CI 1.334, 4.095, one-year; OR, 3.004, 95% CI 1.301, 6.938). However, in patients with other TOAST subtypes, a high HbA1c level did not increase the risk of poor outcomes, regardless of the age of onset. High HbA1c levels increase the risk of short-and long-term poor functional outcomes after IS onset. However, this association differs according to stroke subtype and age. Thus, pre-stroke hyperglycemia, reflected by HbA1c, may be a significant predictor for a poor prognosis after ischemic stroke, particular in young- and middle-aged adults.

Admission hyperglycemia, stroke subtypes, outcomes in acute ischemic stroke

AimsWhether admission hyperglycemia is differentially associated with early vascular outcomes in acute ischemic stroke (AIS) depending on stroke subtype has been incompletely delineated. MethodsIn a multicenter, prospective stroke registry, patients with AIS were categorized based on admission glucose levels into normoglycemia, moderate hyperglycemia, and severe hyperglycemia (<140mg/dl, 140–179mg/dl, and ≥180mg/dl, respectively) groups. Multivariate analysis assessed the interaction between the hyperglycemia and ischemic stroke subtypes of large artery atherothrombosis (LAA), cardioembolism (CE), and small vessel occlusion (SVO) and early vascular outcomes (3-month stroke, all-cause mortality, and composite of stroke, MI, and all-cause mortality). ResultsAmong the 32,772 patients (age:69.0±12.6yrs, male:58.4%) meeting eligibility criteria, 61.9% were in the normoglycemia group, 19.5% were in the moderate hyperglycemia group, and 18.7% were in the severe hyperglycemia group. Substantial interactions between hyperglycemia groups and stroke subtypes were observed for 3-month stroke (Pinteraction = 0.003) and composite of stroke, MI, and all-cause mortality (Pinteraction = 0.001), with differential recurrence strongest among CE, intermediate among LAA, and least among SVO. ConclusionsHyperglycemia was differently associated with the risk of 3-month stroke by ischemic stroke subtype. The associations of hyperglycemia with 3-month stroke were greatest in CE subtype but not in SVO subtype. These results suggest that the effect of glucose-lowering treatment after AIS may differ according to stroke subtype.

Association of Prestroke Glycemic Control With Vascular Events During 1-Year Follow-up

We evaluated the association between admission glycated hemoglobin (HbA1c) and subsequent risk of composite vascular events, including stroke, myocardial infarction (MI), and vascular death, in patients with acute ischemic stroke and diabetes. Patients who had a TIA or an acute ischemic stroke within 7 days of symptom onset and diabetes were included in a retrospective cohort design using the stroke registry of the Clinical Research Center for Stroke in Korea. The association between admission HbA1c and composite vascular events, including stroke, MI, and vascular death, during 1-year follow-up was estimated using the Fine-Gray model. The risk of composite vascular events according to the ischemic stroke subtype was explored using fractional polynomial and linear-quadratic models. Of the 18,567 patients, 1,437 developed composite vascular events during follow-up. In multivariable analysis using HbA1c as a categorical variable, the risk significantly increased at a threshold of 6.8%-7.0%. The influence of admission HbA1c level on the risk of composite vascular events was pronounced particularly among those in whom fasting glucose at admission was ≤130 mg/dL. The optimal ranges of HbA1c associated with minimal risks for composite vascular events were lowest for the small vessel occlusion subtype (6.6 [95% confidence internal [CI], 6.3-6.9]) compared to the large artery atherosclerosis (7.3 [95% CI, 6.8-7.9]) or the cardioembolic subtype (7.4 [95% CI, 6.3-8.5]). In patients with ischemic stroke and diabetes, the risks of composite vascular events were significantly associated with admission HbA1c. The optimal range of admission HbA1c was below 6.8%-7.0% and differed according to the ischemic stroke subtype.

Cerebral amyloid angiopathy, comorbid atrial fibrillation

Cerebral amyloid angiopathy (CAA) is caused by the deposition of β-amyloid in small vessels in the cerebral cortex and leptomeninges. Nowadays, CAA is recognized more often due to the development of neuroimaging technologies. The frequency of CAA increases in old age that explains its frequent association with cardiovascular diseases. Combination of CAA with atrial fibrillation (AF) causes particular difficulties in managing of the patients, since antithrombotic drugs prescribed to patients with AF mostly contraindicated in CAA because of increased risk of intracerebral hemorrhages. The article presents a case report of the patient with AF who was admitted to the stroke center with acute ischemic stroke. According to MRI, the focus of acute ischemia was small and localized in the cerebellum. This stroke was regarded as having an undetermined etiology according TOAST classification. Small-vessel occlusion subtype was not diagnosed because the TOAST criteria do not attribute an ischemic focus in the cerebellum to a lacunar stroke, while cardioembolic subtype was rejected due to a small (less than 1.5 cm in diameter) size of the focus. Probable CAA in the patient was diagnosed on the basis of the following MRI data: multiple cortical-subcortical micro-hemorrhages (T2*GRE); a single cortical focus with features of the hemorrhage at the stage of intracellular methemoglobin deposition (T1- weighted MR images); bilateral enlargement of perivascular spaces in semioval centers (FLAIR); a negative fronto-occipital gradient (T2-weighted MR images). A diagnosis of CAA was made in accordance with the 2010 Boston criteria and 2019 recommendations of the International CAA Association. The article discusses the hemorrhagic and non-hemorrhagic MRI features of CAA. Frequency of occurrence of cortical microinfarcts in CAA is discussed as well as their differences from small cardioembolic infarcts in AF. Algorithms for antithrombotic therapy for secondary prevention of ischemic stroke in patients with CAA and AF are considered.

Carotid Intima-Media Thickness, Genetic Risk, and Ischemic Stroke: A Family-Based Study in Rural China.

Background: Carotid intima-media thickness (cIMT) has been associated with an elevated risk of ischemic stroke (IS) in several studies, but the results are inconsistent. We investigated whether the association between cIMT and IS varied across different IS subtypes, and further assessed gene–cIMT interactions’ association with IS risk. Methods: A total of 1048 IS cases (795 large-artery atherosclerosis (LAA) cases, 103 small-vessel occlusion (SVO) cases, and 150 other subtypes) and 2696 IS-free controls across 2179 families were included in the analysis. Self-reported IS cases were confirmed through medical records’ review and head imaging by computed tomography and/or magnetic resonance imaging. The mean values of the common cIMT obtained in bilateral distal and proximal carotid artery segments were used. The genotype information of rs2910164 polymorphism in microRNA-146a (miR-146a) was also collected. Results: We found that cIMT was significantly associated with a higher risk of IS and LAA subtype but not SVO subtype in the multivariate-adjusted models. The odds ratio (OR) and 95% confidence interval (CI) in the highest quartile versus the lowest quartile of cIMT was 2.48 (1.92–3.20) for IS and 2.75 (2.08–3.64) for LAA (both p trend <0.001). The results also showed that there was a significant interaction between cIMT and rs2910164 genotype with the risk of IS (p interaction = 0.03) and LAA (p interaction = 0.02). The associations of cIMT with IS and LAA were strengthened among participants carried rs2910164_GG genotype compared with those with rs2910164_CC genotype. Conclusions: Our results indicate that higher cIMT levels were significantly associated with IS and LAA subtype but not SVO subtype, and the relations were modified by rs2910164 polymorphism in miR-146a.

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.

Inconsistent centralised versus non-centralised ischaemic stroke aetiology

Background and purposeThe Trial of Org 10 172 in Acute Stroke Treatment (TOAST) system is the most widely used aetiological categorisation system in clinical practice and research. Limited studies have...

Imaging-based pregenetic screening for NOTCH3 p.R544C mutation in ischemic stroke in Taiwan.

ObjectiveTo develop an easily applicable screening score to guide NOTCH3 p.R544C genetic testing for patients who presented with acute ischemic cerebrovascular events in Taiwan.Methods1734 patients who presented with ischemic cerebrovascular events were enrolled from the Formosa Stroke Genetic Consortium stroke registry and were screened for the NOTCH3 p.R544C mutation. Clinical and MRI characteristics of NOTCH3 p.R544C mutation carriers (n = 36) and a subset of noncarriers (n = 673) were tested in a logistic regression model to identify key features associated with the NOTCH3 p.R544C carrier status. Variables and their odds ratios in the regression model were used to develop the R544C screening score to predict positive NOTCH3 p.R544C test results.ResultsWe constructed the R544C screening score using five clinical and imaging characteristics, including stroke onset before 50 years of age, the small vessel occlusion subtype, a family history of stroke/TIA in siblings, external capsule involvement, and advanced deep white matter hyperintensity. The area under the ROC curve of the screening score was 0.867 (95% CI = 0.810‐0.924). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 0.75, 0.88, 0.13, 0.99, and 0.88, respectively, for a cutoff score of 5 points. In addition, the R544C screening score was validated in another cohort composed of 235 stroke patients with comparable performance (area under the ROC curve = 0.957, 95% CI = 0.916‐0.997).InterpretationsFor Taiwanese patients presenting with acute ischemic cerebrovascular events, the R544C screening score is easily applicable and can efficiently select high‐risk patients for NOTCH3 p.R544C mutation test.

Bosnian Study on Markers of Ischaemic Stroke in Adults 20–50 Years Old (SMISAO): Preliminary Report

Previous research suggested that several genetic polymorphisms are associated with increased risk of ischaemic stroke (IS) in young adults. However, the predictive biomarkers of IS in young adults are still unclear. Our aim was to assess the contribution of modifiable and genetic factors in IS in young adults. In total, 40 stroke patients and 40 healthy controls aged 20 to 50 years were recruited. Data on modifiable factors were collected, then participants were genotyped for seven SNPs linked to thrombophilia: ACE rs1799752, PAI-1 rs1799889, APOE rs1412 and rs429358, FV rs6025 and rs1800595, and FII rs62623459. Significantly increased risk factors: hypertension and dyslipidaemia in stroke patients compared with the controls: 50.0 % vs 27.5 % and 75.0 % vs 40.0% (P = 0.039 and P = 0.002, respectively) were observed. Stroke patients compared with controls did not differ in distribution of ACE, APOE, FV, and FII variants. The 4G4G homozygotes of the PAI-1 gene were significantly more prevalent in stroke patients compared to the controls: 42.5 % vs 17.5 %, (P = 0.033). In the group with the small vessel occlusion subtype of stroke, statistically significant overrepresentation of 4G4G homozygotes and frequency of the 4G allele compared with controls: 57.1 % vs 17.5 % and 0.7 vs 0.45 (P = 0.026 and P = 0.03, respectively) were observed. Independent predictors of stroke incident were: dyslipidaemia (OR (95% CI) = 4.2 (1.4–12.4)) and 4G4G genotype (OR (95% CI) = 3.9 (1.1–13.7)). These results confirm the contribution of dyslipidaemia and 4G4G genotype in the increased risk of IS in young Bosnian adults.

Five-year readmission and mortality differ by ischemic stroke subtype

BackgroundIschemic stroke subtype may influence the risk of readmission and mortality after ischemic stroke (IS) and transient ischemic attack (TIA) due to differences in comorbidity, risk factors, and stroke severity. We aimed to study the five-year incidence and risk of all-cause readmission, cause-specific readmission and mortality after IS or TIA by stroke subtype. MethodsThe medical records of 1453 patients admitted with IS or TIA to the stroke unit at Haukeland University Hospital, Norway, between 2007 and 2012 were reviewed for identification of unplanned readmissions within five years after discharge. Stroke etiology was classified as large-artery atherosclerosis (LAA), cardioembolism (CE), small vessel occlusion (SVO), stroke of other determined etiology (SOE), multiple etiologies (ME), or cryptogenic stroke (CS). Kaplan-Meier estimates and Cox regression analyses were used to determine incidences and risk of readmission and death. ResultsThe five-year incidence of all-cause readmission was 72.6% (74% LAA, 81% CE, 65% SVO, 55% SOE, 71% ME, and 67% CS), with infections, cardiac disease, stroke-related events and fractures as the most frequent causes. Compared to patients with other subtypes, SVO subtype had a 21% lower risk of all-cause readmission and a 48% lower risk of death, whereas CE had a 25% higher risk of all cause readmission and a 34% higher risk of death. CE subtype also had a 75% higher risk of readmission due to cardiac disease, whereas CS subtype had a 44% lower risk of readmission with cardiac disease. ConclusionThe five-year incidence of readmission and mortality varied among the stroke subtypes. The risk of readmission and death are especially high in patients with CE subtype, and lowest for patients with SVO subtype.

Comparative Effectiveness of Aspirin and Clopidogrel Versus Aspirin in Acute Minor Stroke or Transient Ischemic Attack.

Background and Purpose- This study aimed to compare the effectiveness of dual antiplatelet therapy with clopidogrel-aspirin to that of aspirin monotherapy in patients with acute minor cerebral ischemia using a prospective, nationwide, multicenter, stroke registry database in South Korea. Methods- CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events)-like patients who met eligibility criteria modeled on the CHANCE trial eligibility criteria, including (1) acute minor ischemic stroke defined as National Institutes of Health Stroke Scale score ≤3 or lesion positive transient ischemic attack within 24 hours of onset and (2) noncardioembolic stroke mechanism. Propensity scores using the inverse probability of treatment weighting was used to adjust for baseline imbalances. The primary outcome was the composite of all stroke (ischemic and hemorrhagic), myocardial infarction, and vascular death by 3 months. Results- Among 5590 patients meeting the eligibility criteria, age was 64±13 year and 62.6% were male. Aspirin and combination of clopidogrel-aspirin were administered in 66.1% and 33.9% of patients, respectively. In unadjusted analysis, rates of the 3-month primary vascular event outcome were lower with clopidogrel-aspirin versus aspirin, 9.9% versus 12.2% (hazard ratio, 0.79 [0.67-0.95]). In propensity-weighted Cox proportional hazards regression with robust estimation, clopidogrel-aspirin was associated with a lower risk of the primary vascular event outcome (hazard ratio, 0.76 [0.63-0.92]) and all stroke events (hazard ratio, 0.74 [0.61-0.90]). Among 6 predefined subgroup analyses, 3 showed potential modification of treatment effect, with lesser benefit associated with the absence of prior antiplatelet use (Pinteraction=0.01) and younger age (<75 years, Pinteraction=0.07), and absence of benefit associated with small vessel occlusion subtype (Pinteraction=0.08). Conclusions- Dual antiplatelet therapy with aspirin and clopidogrel was associated with reduced stroke, myocardial infarction, and vascular death in the 3 months following a presenting minor, noncardioembolic ischemic stroke. Benefits may be particularly magnified in patients with a history of prior antiplatelet therapy, older age, and nonsmall vessel disease stroke mechanism.

Interactive effect of acute and chronic glycemic indexes for severity in acute ischemic stroke patients

BackgroundDiabetes mellitus is a well-established risk factor for ischemic stroke and is known to increase stroke risk by 2–6 fold. Numerous studies have reported the relationship between parameters for glycemic status and stroke-related outcomes; however, studies focusing on the interaction between acute and chronic glycemic status indexes with stroke phenotype are lacking.MethodsAcute ischemic stroke patients who were admitted to a tertiary hospital stroke center from 2002 to 2015 were consecutively enrolled in this study. Fasting blood sugar (FBS) and serum glycated hemoglobin (HbA1c) levels were recorded as acute and chronic glycemic indexes, respectively. The associations between initial stroke severity and both glycemic indexes were evaluated with consideration of the interaction between the glycemic indexes. Moreover, the distinct effects of stroke subtypes were evaluated.ResultsA total of 2595 patients were included in the final analysis. After adjustment for covariates, FBS was associated with initial stroke severity (P < 0.001), while HbA1c was not (P = 0.16). However, an interaction between FBS and HbA1c in association with initial stroke severity was observed (P < 0.001). The association between FBS and initial stroke severity was stronger, with a relatively normal HbA1c level. Among stroke subtypes, the interactions were significant for the large artery disease and cardioembolism subtypes (all, P < 0.001), but for the small vessel occlusion subtype (P = 0.63).ConclusionsThis study shows that HbA1c is an effect modifier for the association between FBS and initial stroke severity, and the interactive effect differs among stroke subtypes.

Abstract WP227: Association Of Anemia With Stroke Recurrence In Acute Ischemic Stroke: An Analysis From The Clinical Research Center For Stroke-5th Division Registry In Korea

Background: We have evaluated whether anemia at admission is associated with ischemic stroke recurrence and composite outcome events (stroke, myocardial infarction, and vascular death) according to the age, presence of cerebral artery stenosis, stroke subtype, and initial severity of stroke. Methods: All 27145 patients with transient ischemia attack or acute ischemic stroke admitted between April 2008 and November 2014 from the stroke registry of the fifth section of the Clinical Research Center for Stroke (CRCS-5) were selected. The association between anemia and 1-year stroke recurrence, composite outcome events according to age, presence of cerebral artery stenosis, stroke mechanism, and initial severity of stroke were evaluated. Results: The cumulative 1-year stroke recurrence rate, composite outcome events were significantly higher in patients with anemia than without anemia ( 7.2% vs. 4.8%, p&lt;0.01 for stroke recurrence, 11.8% vs.7.3%, p&lt;0.01 for composite event). Anemia was still an independent predictor of 1-year stroke recurrence and composite vascular event after adjustment (adjusted HR 1.35, 95% CI 1.09-1.66, p&lt;0.01 for stroke recurrence, adjusted HR 1.21, 95% CI 1.03-1.43, p=0.03 for composite outcome events). Anemia significantly increase the stroke recurrence risk in patients with mild to moderate neurological deficit (NIHSS &lt;16, p for interaction=0.04), with stroke of other determined etiology (p for interaction=0.06). Anemia substantially increase the risk of composite outcome events in patients with mild to moderate stroke severity (NIHSS &lt;16, HR 1.84, 95% CI 1.53-2.21, p for interaction&lt;0.01), without cerebral artery stenosis ≥50% (HR 2.02, 95% CI 1.57-2.59, p for interaction=0.03), with stroke of small vessel occlusion (HR 2.74, 95% CI 1.34-5.63, p for interaction=0.09), and with stroke of other determined etiology (HR 2.95, 95% CI 1.69-5.14, p for interaction=0.02). Conclusion: Anemia is an independent predictor of 1-year ischemic stroke recurrence, composite outcome events of stroke, myocardial infarction, and vascular death. Our data suggests that more attention should be paid to the anemic patients with mild to moderate neurological deficit, small vessel occlusion subtype, and stroke of other determined etiology.

Elevated Total Homocysteine Levels in Acute Ischemic Stroke Are Associated With Long-Term Mortality.

Background and Purpose—Total homocysteine (tHcy) levels are associated with secondary vascular events and mortality after stroke. The aim of this study was to investigate whether tHcy levels in the acute phase of a stroke contribute to the recurrence of cerebro-cardiovascular events and mortality.Methods—A total of 3799 patients were recruited after hospital admission for acute ischemic stroke. Levels of tHcy were measured within 24 hours after primary admission. Patients were followed for a median of 48 months.Results—During the follow-up period, 233 (6.1%) patients died. After adjustment for age, smoking status, diabetes mellitus, and other cardiovascular risk factors, patients in the highest tHcy quartile (>18.6 μmol/L) had a 1.61-fold increased risk of death (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.03–2.53) compared with patients in the lowest quartile (≤10 μmol/L). Further subgroup analysis showed that this correlation was only significant in the large-artery atherosclerosis stroke subtype (adjusted HR, 1.80; 95% CI, 1.05–3.07); this correlation was not significant in the small-vessel occlusion subtype (adjusted HR, 0.80; 95% CI, 0.30–2.12). The risk of stroke-related mortality was 2.27-fold higher for patients in the third tHcy quartile (adjusted HR, 2.27; 95% CI, 1.06–4.86) and 2.15-fold more likely for patients in the fourth quartile (adjusted HR, 2.15; 95% CI, 1.01–4.63) than for patients in the lowest tHcy quartile. The risk of cardiovascular-related mortality and the risk of recurrent ischemic stroke were not associated with tHcy levels.Conclusions—Our findings suggest that elevated tHcy levels in the acute phase of an ischemic stroke can predict mortality, especially in stroke patients with the large-vessel atherosclerosis subtype.

Glaucoma in the Hallermann-Streiff syndrome.

<h3>Background and purpose</h3> The Trial of Org 10 172 in Acute Stroke Treatment (TOAST) system is the most widely used aetiological categorisation system in clinical practice and research. Limited studies have validated the accuracy of routine aetiological diagnosis of patients with ischaemic stroke according to the TOAST criteria when the reported subtype is assumed to be correct. We investigated the agreement between centralised and non-centralised (site-reported, at discharge) stroke subtypes in the Third China National Stroke Registry (CNSR-III), and analysed the influence of classification consistency on evaluation during hospitalisation and for secondary prevention strategy. <h3>Methods</h3> All patients with ischaemic stroke from the CNSR-III study with complete diffusion-weighted imaging data were included. We used multivariable Cox proportional-hazard regression models to evaluate the factors associated with consistency between centralised and non-centralised stroke subtypes. Sensitivity analyses were conducted of the subgroup of patients with complete information. <h3>Results</h3> This study included 12 180 patients (mean age, 62.3 years; and women, 31.4%). Agreement between centralised and non-centralised subtype was the highest for the large-artery atherosclerosis subtype stroke (77.4% of centralised patients), followed by the small-vessel occlusion subtype (40.6% of centralised patients). Agreements for cardioembolism and stroke of other determined aetiology subtypes were 38.7% and 12.2%, respectively. Patient-level and hospital-level factors were associated with the inconsistency between centralised/non-centralised aetiological subtyping. This inconsistency was related to differences in secondary prevention strategies. Only 15.3% of the newly diagnosed patients with cardioembolism underwent centralised subtyping with indications to receive oral anticoagulants at discharge. In comparison, 51.3% of the consistent cardioembolism group and 42.0% of the centrally reassigned cardioembolism group with anticoagulation indications were prescribed oral anticoagulants. <h3>Conclusions</h3> Substantial inconsistency exists between centralised and non-centralised subtyping in China. Inaccurate aetiological subtyping could lead to inadequate secondary prevention, especially in patients with cardioembolic stroke.