Neural Substrates of Aphasia in Acute Left Hemispheric Stroke Using Voxel-Based Lesion-symptom Brain Mapping

It is unclear how these brain lesions fit into the language processing in acute stroke. In this study, we aimed to investigate the neuroanatomical lesion related to language processing in acute stage of stroke patients using voxel-based lesion-symptom mapping (VLSM). 73 acute first-ever post-stroke patients were enrolled in this retrospective study, who had undertaken brain magnetic resonance imaging (MRI) and Korean version of the Western Aphasia Test within 1 month from onset. Each voxel was compared with aphasia quotient and subtest scores as dependent variables using VLSM. The aphasia group showed significantly much more involvement of extra-nuclear area, insula, inferior frontal gyrus and superior temporal gyrus compared to non-aphasia group. The deficit of spontaneous speech domain was associated with the inferior parietal lobule, inferior and middle frontal gyrus and insula. The insular cortex, inferior parietal lobule, inferior frontal gyrus, middle frontal gyrus and superior temporal gyrus were related to deficit of comprehension. The inferior parietal lobule, insula, precentral gyrus, inferior frontal gyrus were related to the deficit of repetition. The deficit of naming was related to inferior parietal lobule, insula and inferior frontal gyrus. In conclusion, VLSM from early MRI imaging study after stroke may be useful to understand the language process network and establish early rehabilitation strategies after stroke.ope

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Pathophysiologic and Therapeutic Perspectives Based on Thrombus Histology in Stroke

Recent advances in endovascular thrombectomy have enabled the histopathologic analysis of fresh thrombi in patients with acute stroke. Histologic analysis has shown that the thrombus composition is very heterogeneous between patients. However, the distribution pattern of each thrombus component often differs between patients with cardiac thrombi and those with arterial thrombi, and the efficacy of endovascular thrombectomy is different according to the thrombus composition. Furthermore, the thrombus age is related to the efficacy of reperfusion therapy. Recent studies have shown that neutrophils and neutrophil extracellular traps contribute to thrombus formation and resistance to reperfusion therapy. Histologic features of thrombi in patients with stroke may provide some clues to stroke etiology, which is helpful for determining the strategy of stroke prevention. Research on thrombus may also be helpful for improving reperfusion therapy, including the development of new thrombolytic agents.ope

CYP2C19 Polymorphisms and Smoking Status Affects Responsiveness to the Platelet P2Y12 Receptor Antagonist Clopidogrel

Background: The “comparison of triflusal and clopidogrel effects in secondary prevention of stroke based on cytochrome P450 2C19 (CYP2C19) genotyping (MAESTRO)” study was a prospective, multicenter, randomized, open-label, and blind genotype trial. We performed a subgroup analysis of the MAESTRO study to explore the relationship between VerifyNow P2Y12 assay with regard to CYP2C19 polymorphisms and smoking status in patients with non-cardiogenic ischemic stroke who underwent clopidogrel treatment. Methods: For the study, patients treated with clopidogrel and who underwent VerifyNow P2Y12 assay was selected from the MAESTRO study. Results: Of the 393 patients in 18 hospitals, 256 (65%) patients in 12 hospitals were entered for this subgroup analysis. P2Y12 reaction unit (PRU) was significantly lower and percent inhibition (% INH) was higher in the current smoking group than in the nonsmoking group (p<0.001). The same results were also observed in the good genotype group when compared with the poor genotype group (p<0.001). Among the groups, significant lower PRU and higher % INH was demonstrated in current smoking with good genotype group. However, there was no difference in PRU and % INH between current smoking with poor genotype group and nonsmoking with good genotype group, suggesting that clopidogrel activity was concurrently related to CYP2C19 polymorphisms and smoking status. Conclusions: Regarding secondary stroke prevention, patients who were current smokers and had a poor genotype for clopidogrel metabolism may benefit from clopidogrel treatment similar to that in patients who were nonsmokers and had a good genotype.ope

Changes in High-Density Lipoprotein Cholesterol and Risks of Cardiovascular Events: A Post Hoc Analysis from the PICASSO Trial

Background and purpose: Whether pharmacologically altered high-density lipoprotein cholesterol (HDL-C) affects the risk of cardiovascular events is unknown. Recently, we have reported the Prevention of Cardiovascular Events in Asian Patients with Ischaemic Stroke at High Risk of Cerebral Haemorrhage (PICASSO) trial that demonstrated the non-inferiority of cilostazol to aspirin and superiority of probucol to non-probucol for cardiovascular prevention in ischemic stroke patients (clinicaltrials.gov: NCT01013532). We aimed to determine whether on-treatment HDL-C changes by cilostazol and probucol influence the treatment effect of each study medication during the PICASSO study. Methods: Of the 1,534 randomized patients, 1,373 (89.5%) with baseline cholesterol parameters were analyzed. Efficacy endpoint was the composite of stroke, myocardial infarction, and cardiovascular death. Cox proportional hazards regression analysis examined an interaction between the treatment effect and changes in HDL-C levels from randomization to 1 month for each study arm. Results: One-month post-randomization mean HDL-C level was significantly higher in the cilostazol group than in the aspirin group (1.08 mmol/L vs. 1.00 mmol/L, P<0.001). The mean HDL-C level was significantly lower in the probucol group than in the non-probucol group (0.86 mmol/L vs. 1.22 mmol/L, P<0.001). These trends persisted throughout the study. In both study arms, no significant interaction was observed between HDL-C changes and the assigned treatment regarding the risk of the efficacy endpoint. Conclusions: Despite significant HDL-C changes, the effects of cilostazol and probucol treatment on the risk of cardiovascular events were insignificant. Pharmacologically altered HDL-C levels may not be reliable prognostic markers for cardiovascular risk.ope

Analysis of Ischemic Stroke Patterns Using the Diffusion-Weighted Imaging in Patients with Complicated Aortic Plaques

Background: This study aimed at characterizing the lesion patterns in patients with acute ischemic stroke and complicated aortic plaques using the diffusion-weighted magnetic resonance imaging (DWI). Methods: We retrospectively reviewed 403 consecutive patients with acute ischemic stroke between January 2002 and December 2004, and enrolled patients who had received a trans-esophageal echocardiography (TEE). All the patients should have an acute cerebral infarction within 7 days of the onset of symptoms. We analyzed the ischemic lesion patterns on DWI in the patients who had aortic atheroma protruded into the lumen greater than 4 mm in the aortic arch or ascending aorta (complicated aortic plaques; CAP). Ischemic lesions were classified into subcortical, cortical and multiple infarctions. We investigated the accompanying risk factors for atherosclerosis and stenosis of the relevant major brain artery as well. Results: Of the 403 patients, TEE was performed in 210 (52%) and CAP was found in 25 (12%). Among 25 patients, subcortical infarction was observed in 15 (60%), followed by cortical infarction in 7 (28%), and multiple ischemic lesions in 3 (12%). CAP was frequently associated with hypertension and current smoking, and accompanied with stenosis of the relevant major brain artery as well (68%). Conclusions: CAP may be a potential source of embolism. However, the high prevalence of the small subcortical lesion in this study questions the mechanisms of ischemic stroke in patients with aortic atheroma. CAP may be an uncomplicated marker of advanced systemic atherosclerosis including the cerebral arteries.ope

Agreement and Reliability Analysis of Machine Learning Scaling and Wireless Monitoring in the Assessment of Acute Proximal Weakness by Experts and Non-Experts: A Feasibility Study

Assessing the symptoms of proximal weakness caused by neurological deficits requires the knowledge and experience of neurologists. Recent advances in machine learning and the Internet of Things have resulted in the development of automated systems that emulate physicians' assessments. The application of those systems requires not only accuracy in the classification but also reliability regardless of users' proficiency in the real environment for the clinical point-of-care and the personalized health management. This study provides an agreement and reliability analysis of using a machine learning-based scaling of Medical Research Council (MRC) proximal scores to evaluate proximal weakness by experts and non-experts. The system trains an ensemble learning model using the signals from sensors attached to the limbs of patients in a neurological intensive care unit. For the agreement analysis, we investigated the percent agreement of MRC proximal scores and Bland-Altman plots of kinematic features between the expert- and non-expert scaling. We also analyzed the intra-class correlation coefficients (ICCs) of kinematic features and Krippendorff's alpha of the observers' scaling for the reliability analysis. The mean percent agreement between the expert- and the non-expert scaling was 0.542 for manual scaling and 0.708 for autonomous scaling. The ICCs of kinematic features measured using sensors ranged from 0.742 to 0.850, whereas the Krippendorff's alpha of manual scaling for the three observers was 0.275. The autonomous assessment system can be utilized by the caregivers, paramedics, or other observers during an emergency to evaluate acute stroke patients.ope

Carotid Artery Disease in Duplex Sonography: 3 Cases

Duplex sonography has been used to non-invasively diagnose carotid artery disease and to follow up patients with this disease. In carotid artery disease, carotid mobile thrombus and dissection are rarely detected by duplex sonography in patients with cerebrovascular events. In particular, carotid dissection occurs when a small tear forms in the tunica intima and makes 2 lumens in the carotid artery, including true and false lumens. This study reports 3 rare cases of carotid mobile thrombus, spontaneous carotid dissection, and carotid dissection in Takayasu arteritis. .ope

Quality of Anticoagulation with Warfarin in Korean Patients with Atrial Fibrillation and Prior Stroke: A Multicenter Retrospective Observational Study

Background and purpose: The quality of anticoagulation is critical for ensuring the benefit of warfarin, but this has been less well studied in Korean ischemic stroke patients with atrial fibrillation (AF). Methods: This study retrospectively analyzed the data of patients who had an AF-related ischemic stroke and were treated with long-term warfarin therapy in 16 Korean centers. The quality of warfarin therapy was primarily assessed by the time in therapeutic range [TTR; international normalized ratio (INR), 2.0-3.0] and additionally by the proportion of INR values within the therapeutic range. Results: The long-term warfarin-treated cohort comprised 1,230 patients. They were aged 70.1±9.7 years (mean±SD), 42.5% were female, and their CHA₂DS₂-VASc score was 4.75±1.41. The TTR analysis included 33,941 INR measurements for 27,487 months: per patients, 27.6 (SD, 22.4) INR measurements for 22.4 (SD, 12.9) months. The mean TTR of individual patients was 49.1% (95% confidence interval, 47.9-50.3%), and the TTR quartiles were 64.5%. None of the 16 centers achieved a mean TTR of >60%. Of all INR measurements, 44.6% were within the therapeutic range, 41.7% were 3.0. Conclusions: In Korean ischemic stroke patients who had AF, the quality of warfarin therapy was low and might be inadequate to effectively prevent recurrent stroke or systemic embolism.ope

Gut Microbiota and Ischemic Stroke: The Role of Trimethylamine N-Oxide

Trimethylamine N-oxide (TMAO) is produced when trimethylamine, a waste product of gut microbes, is converted via hepatic flavin monooxygenases. As TMAO is a potential causative factor in various cardiovascular diseases (CVDs) considerable research interest has arisen on its use as a biomarker. Higher TMAO levels are associated with future risk of both incident CVD in the general population and established CVD, including stroke. The addition of TMAO into models with traditional risk factors significantly improved the prediction of future CVD risk. TMAO promotes atherosclerosis and is associated with platelet hyperreactivity and inflammation, which are in turn associated with the development of stroke and its secondary consequences. Additionally, TMAO may play a key mediator role in the relationship between the diet, gut microbiota, and CVD development. Compelling evidence suggesting that TMAO is both a risk factor and prognostic marker of stroke and CVD. Potential therapeutic strategy of diet and drugs in reducing TMAO levels have emerged. Thus, TMAO is a novel biomarker and target in stroke and CVD prevention.ope