Search

Approximately one-quarter of strokes occur in individuals with prior stroke. Despite the advancement in secondary stroke prevention, the long-term risk of recurrent stroke has remained unchanged. The objective of this study was to identify metabolite risk markers that are associated with recurrent stroke. We performed targeted metabolomic profiling of 162 metabolites by liquid chromatography-tandem mass spectrometry in baseline plasma in a stroke case-cohort study nested within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, an observational cohort study of 30,239 individuals aged 45 and older enrolled in 2003-2007. Weighted Cox proportional hazard models were used to identify metabolites that had a differential effect on first-time versus recurrent stroke using an interaction term between metabolite and prior stroke at baseline (yes or no). The study included 1391 incident stroke cases identified during 7.1 ± 4.5 years of follow-up and 1050 participants in the random cohort sample. Among 162 metabolites, 13 candidates had a metabolite-by-prior stroke interaction at a p-value <0.05, with one metabolite, acetylglutamine, surpassing the Bonferroni adjusted p-value threshold (p for interaction = 5.78 × 10 -5 ). In an adjusted model that included traditional stroke risk factors, acetylglutamine was associated with recurrent stroke (HR = 2.27 per SD increment, 95% CI = 1.60-3.20, p = 3.52 × 10 -6 ) but not with first-time stroke (HR = 0.96 per SD increment, 95% CI = 0.87-1.06, p = 0.44). Acetylglutamine was associated with recurrent stroke but not first-time stroke, independent of traditional stroke risk factors. Future studies are warranted to elucidate the pathogenesis of acetylglutamine and recurrent stroke risk., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives: Ultra-processed foods (UPFs) are linked to cardiometabolic diseases and neurologic outcomes, such as cognitive decline and stroke. However, it is unclear whether food processing confers neurologic risk independent of dietary pattern information. We aimed to (1) investigate associations between UPFs and incident cognitive impairment and stroke and (2) compare these associations with other commonly recommended dietary patterns in the REasons for Geographic and Racial Differences in Stroke study. This prospective, observational cohort study enrolled Black and White adults in the United States from 2003 to 2007., Methods: The NOVA system was used to categorize items from a baseline food frequency questionnaire according to the level of processing. Participants with incomplete or implausible self-reported dietary data were excluded. Consumption for each category (grams) was normalized to total grams consumed. Scores quantifying adherence to a Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet were also calculated. Incident cognitive impairment was defined using performance relative to a normative sample on memory and fluency assessments. Incident stroke was identified through adjudicated review of medical records., Results: The cognitive impairment cohort (n = 14,175) included participants without evidence of impairment at baseline who underwent follow-up testing. The stroke cohort (n = 20,243) included participants without a history of stroke. In multivariable Cox proportional hazards models, a 10% increase in relative intake of UPFs was associated with higher risk of cognitive impairment (hazard ratio [HR] = 1.16, 95% CI 1.09-1.24, p = 1.01 × 10 -5 ) and intake of unprocessed or minimally processed foods with lower risk of cognitive impairment (HR = 0.88, 95% CI 0.83-0.94, p = 1.83 × 10 -4 ). Greater intake of UPFs (HR = 1.08, 95% CI 1.02-1.14, p = 1.12 × 10 -2 ) and unprocessed or minimally processed foods (HR = 0.91, 95% CI 0.86-0.95, p = 2.13 × 10 -4 ) were also associated with risk of stroke in multivariable Cox models. The effect of UPFs on stroke risk was greater among Black than White participants (UPF-by-race interaction HR = 1.15, 95% CI 1.03-1.29, p = 1.50 × 10 -2 ). Associations between UPFs and both cognitive impairment and stroke were independent of adherence to the Mediterranean, DASH, and MIND diets., Discussion: Food processing may be important to brain health in older adults independent of known risk factors and adherence to recommended dietary patterns.

Background: Sex disparities exist in cardiometabolic diseases. Metabolomic profiling offers insight into disease mechanisms, as the metabolome is influenced by environmental and genetic factors. We identified metabolites associated with sex and determined if sex-associated metabolites are associated with incident stoke, incident coronary heart disease, prevalent hypertension, and prevalent chronic kidney disease., Methods and Results: Targeted metabolomics was conducted for 357 metabolites in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) case-cohort substudy for incident stroke. Weighted logistic regression models were used to identify metabolites associated with sex in REGARDS. Sex-associated metabolites were replicated in the HyperGEN (Hypertension Genetic Epidemiology Network) and using the literature. Weighted Cox proportional hazard models were used to evaluate associations between metabolites and incident stroke. Cox proportional hazard models were used to evaluate associations between metabolites and incident coronary heart disease. Weighted logistic regression models were used to evaluate associations between metabolites and hypertension and chronic kidney disease. Fifty-one replicated metabolites were associated with sex. Higher levels of 6 phosphatidylethanolamines were associated with incident stroke. No metabolites were associated with incident coronary heart disease. Higher levels of uric acid and leucine and lower levels of a lysophosphatidylcholine were associated with hypertension. Higher levels of indole-3-lactic acid, 7 phosphatidylethanolamines, and uric acid, and lower levels of betaine and bilirubin were associated with chronic kidney disease., Conclusions: These findings suggest that the sexual dimorphism of the metabolome may contribute to sex differences in stroke, hypertension, and chronic kidney disease.

Importance: Although increasing evidence suggests that trimethylamine N-oxide (TMAO) is associated with atherosclerosis, little is known about whether TMAO and its related metabolites (ie, choline, betaine, and carnitine) are associated with small vessel disease., Objective: To evaluate the association between TMAO and its related metabolites with features of cerebral small vessel disease, including white matter hyperintensity volume (WMHV) and acute lacunar infarction., Design, Setting, and Participants: This cross-sectional study included patients enrolled in the Specialized Programs of Translational Research in Acute Stroke biorepository. The registry included 522 patients with acute ischemic stroke who were 18 years or older who presented at the Massachusetts General Hospital or Brigham and Women's Hospital within 9 hours after onset between January 2007 and April 2010. The analyses in this study were conducted between November 2022 and April 2023., Exposures: Plasma TMAO, choline, betaine, and carnitine were measured by liquid chromatography-tandem mass spectrometry., Main Outcomes and Measures: WMHV was quantified by a semiautomated approach using signal intensity threshold with subsequent manual editing. Ischemic stroke subtype was classified using the Causative Classification System., Results: Among 351 patients included in this study, the mean (SD) age was 69 (15) years; 209 patients (59.5%) were male and had a median (IQR) admission National Institute of Health Stroke Scale of 6 (3-13). The magnetic resonance imaging subgroup consisted of 291 patients with a mean (SD) age of 67 (15) years. Among these, the median (IQR) WMHV was 3.2 (1.31-8.4) cm3. TMAO was associated with WMHV after adjustment for age and sex (β, 0.15; 95% CI, 0.01-0.29; P < .001). TMAO remained significant in a multivariate analysis adjusted for age, sex, hypertension, diabetes, and smoking (β, 0.14; 95% CI, 0-0.29; P = .05). TMAO was associated with lacunar stroke but not other ischemic stroke subtypes in a model adjusted for age, sex, hypertension, diabetes, and smoking (OR, 1.67; 95% CI, 1.05-2.66; P = .03)., Conclusions and Relevance: In this observational study, TMAO was associated with cerebral small vessel disease determined by WMHV and acute lacunar infarction. The association was independent of traditional vascular risk factors.

Several metabolite markers are independently associated with incident ischemic stroke. However, prior studies have not accounted for intercorrelated metabolite networks. We used exploratory factor analysis (EFA) to determine if metabolite factors were associated with incident ischemic stroke. Metabolites (n = 162) were measured in a case-control cohort nested in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, which included 1,075 ischemic stroke cases and 968 random cohort participants. Cox models were adjusted for age, gender, race, and age-race interaction (base model) and further adjusted for the Framingham stroke risk factors (fully adjusted model). EFA identified fifteen metabolite factors, each representing a well-defined metabolic pathway. Of these, factor 3, a gut microbiome metabolism factor, was associated with an increased risk of stroke in the base (hazard ratio per one-unit standard deviation, HR = 1.23; 95%CI = 1.15-1.31; P = 1.98 × 10 -10 ) and fully adjusted models (HR = 1.13; 95%CI = 1.06-1.21; P = 4.49 × 10 -4 ). The highest tertile had a 45% increased risk relative to the lowest (HR = 1.45; 95%CI = 1.25-1.70; P = 2.24 × 10 -6 ). Factor 3 was also associated with the Southern diet pattern, a dietary pattern previously linked to increased stroke risk in REGARDS (β = 0.11; 95%CI = 0.03-0.18; P = 8.75 × 10 -3 ). These findings highlight the role of diet and gut microbial metabolism in relation to incident ischemic stroke.

Background and Objectives: In the United States, the risk of stroke is greater among Black compared with that among White individuals. However, the reasons for the difference in stroke incidence are not fully elucidated. We aimed to identify metabolites that account for higher prevalent hypertension and incident ischemic stroke among Black adults., Methods: We used a stroke case cohort nested within the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Targeted metabolomic profiling of 162 plasma metabolites was performed by liquid chromatography-tandem mass spectrometry. We identified metabolites that were associated with prevalent hypertension and incident ischemic stroke and mediated the relationship between hypertension and ischemic stroke by weighted logistic regression, Cox proportional hazard model, and inverse odds ratio weighting mediation analysis., Results: Incident ischemic stroke cases adjudicated through April 1, 2019 (n = 1,075) were included in the study. The random cohort sample was derived from the full cohort using stratified sampling (n = 968). Among 162 metabolites, gluconic acid was associated with prevalent hypertension in Black adults (odds ratio [OR] 1.86, 95% CI 1.39-2.47, p = 2.58 × 10 -5 ) but not in White adults (OR 1.00, 95% CI 0.80-1.24, p = 0.97; p for interaction = 4.57 × 10 -4 ). Gluconic acid also demonstrated an association with incident ischemic stroke among Black participants (hazard ratio [HR] 1.53, 95% CI 1.28-1.81, p = 1.76 × 10 -6 ) but not White participants (HR 1.16, 95% CI 1.00-1.34, p = 0.057; p for interaction = 0.019). In mediation analysis, gluconic acid mediated 25.4% (95% CI 4.1%-46.8%, p = 0.02) of the association between prevalent hypertension and incident ischemic stroke among Black individuals. Specific socioeconomic factors were linked to elevated gluconic acid level among Black adults in multivariable analysis, including a Southern dietary pattern (β = 0.18, 95% CI 0.08-0.28, p < 0.001), lower educational attainment (β = 0.45, 95% CI 0.19-0.72, p = 0.001), and a lack of exercise (β = 0.26, 95% CI 0.01-0.51, p = 0.045)., Discussion: Gluconic acid is associated with prevalent hypertension and incident ischemic stroke and mediates the relationship between hypertension and ischemic stroke in Black but not White adults. Gluconic acid is a biomarker that is associated with social determinants of health including a Southern diet, low educational attainment, and low physical activity., (© 2023 American Academy of Neurology.)

Objective: While dietary intake is linked to stroke risk, surrogate markers that could inform personalized dietary interventions are lacking. We identified metabolites associated with diet patterns and incident stroke in a nested cohort from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study., Methods: Levels of 162 metabolites were measured in baseline plasma from stroke cases (n = 1,198) and random controls (n = 904). We examined associations between metabolites and a plant-based diet pattern previously linked to reduced stroke risk in REGARDS. Secondary analyses included 3 additional stroke-associated diet patterns: a Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Southern diet. Metabolites were tested using Cox proportional hazards models with incident stroke as the outcome. Replication was performed in the Jackson Heart Study (JHS). Inverse odds ratio-weighted mediation was used to determine whether metabolites mediated the association between a plant-based diet and stroke risk., Results: Metabolites associated with a plant-based diet included the gut metabolite indole-3-propionic acid (β = 0.23, 95% confidence interval [CI] [0.14, 0.33], p = 1.14 × 10 -6 ), guanosine (β = -0.13, 95% CI [-0.19, -0.07], p = 6.48 × 10 -5 ), gluconic acid (β = -0.11, 95% CI [-0.18, -0.04], p = 2.06 × 10 -3 ), and C7 carnitine (β = -0.16, 95% CI [-0.24, -0.09], p = 4.14 × 10 -5 ). All of these metabolites were associated with both additional diet patterns and altered stroke risk. Mediation analyses identified guanosine (32.6% mediation, p = 1.51 × 10 -3 ), gluconic acid (35.7%, p = 2.28 × 10 -3 ), and C7 carnitine (26.2%, p = 1.88 × 10 -2 ) as mediators linking a plant-based diet to reduced stroke risk., Interpretation: A subset of diet-related metabolites are associated with risk of stroke. These metabolites could serve as surrogate markers that inform dietary interventions. ANN NEUROL 2023;93:500-510., (© 2022 American Neurological Association.)

Stroke-like symptoms after COVID-19 vaccination was thought to be functional if there was no anatomical image abnormality. We aimed to analyze brain perfusion changes in these patients. A case-control study of brain perfusion single photon emission computed tomography (SPECT) of 12 vaccinated patients with left-sided stroke-like symptoms were compared with 12 age- and gender-matched normal interictal brain SPECTs using voxel-based analysis. Significant hyperperfusion was seen on the right side in postcentral, inferior parietal, mid temporal, parahippocampal, and caudate regions, and on the left side in the thalamus, hippocampus, and mid temporal areas. In addition, there were hypoperfused bilateral superior frontal gyri and right mid/posterior cingulate cortex (Family-wise-error corrected p-values  < .05). Both hypoperfusion and hyperperfusion in the brain are demonstrated. We hypothesize that these findings might be the result of the functional neurological disorder. However, based on other previous studies, circulating spike protein in the patients' plasma early after vaccination might also be the cause., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: After the initiation of the COVID-19 vaccination program in Thailand, thousands of patients have experienced unusual focal neurological symptoms. We report 8 patients with focal neurological symptoms after receiving inactivated virus vaccine, CoronaVac., Case Series: Patients were aged 24-48 years and 75% were female. Acute onset of focal neurological symptoms occurred within the first 24 h after vaccination in 75% and between 1-7d in 25%. All presented with lateralized sensory deficits, motor deficits, or both, of 2-14 day duration. Migraine headache occurred in half of the patients. Magnetic resonance imaging of the brain during and after the attacks did not demonstrate any abnormalities suggesting ischemic stroke. All patients showed moderately large regions of hypoperfusion and concurrent smaller regions of hyperperfusion on SPECT imaging while symptomatic. None developed permanent deficits or structural brain injury., Discussions: Here, we present a case series of transient focal neurological syndrome following Coronavac vaccination. The characteristic sensory symptoms, history of migraine, female predominant, and abnormal functional brain imaging without structural changes suggest migraine aura as pathophysiology. We propose that pain related to vaccine injection, component of vaccine, such as aluminum, or inflammation related to vaccination might trigger migraine aura in susceptible patients., (© 2022. The Author(s).)

Background: Acute vertigo is a common presentation of inner ear disease. However, it can also be caused by more serious conditions, especially posterior circulation stroke. Differentiating between these two conditions by clinical presentations and imaging studies during the acute phase can be challenging. This study aimed to identify serum microRNA (miRNA) candidates that could differentiate between posterior circulation stroke and peripheral vertigo, among patients presenting with acute vertigo., Methods: Serum levels of six miRNAs including miR-125a-5p, miR-125b-5p, miR-143-3p, miR-342-3p, miR-376a-3p, and miR-433-5p were evaluated. Using quantitative reverse-transcription polymerase chain reaction (RT-qPCR), the serum miRNAs were assessed in the acute phase and at a 90 day follow-up visit., Results: A total of 58 patients with posterior circulation stroke (n = 23) and peripheral vertigo (n = 35) were included in the study. Serum miR-125a-5p (P = 0.001), miR-125b-5p (P <  0.001), miR-143-3p (P = 0.014) and miR-433-5p (P = 0.0056) were present at significantly higher levels in the acute phase, in the patients with posterior circulation infarction. Based on the area under the receiver operating characteristic curve (AUROC) only miR-125a-5p (0.75), miR-125b-5p(0.77), and miR-433-5p (0.71) had an acceptable discriminative ability to differentiate between the central and peripheral vertigo. A combination of miRNAs revealed no significant improvement of AUROC when compared to single miRNAs., Conclusion: This study demonstrated the potential of serum miR-125a-5p, miR-125b-5p, and miR-433-5p as biomarkers to assist in the diagnosis of posterior circulation infarction among patients presenting with acute vertigo.

Background: Chulalongkorn Stroke Center is a comprehensive stroke center (CSC) located in Bangkok, Thailand. Our stroke network consists of different levels of spoke hospitals, ranging from community hospitals where thrombolytic treatment is not available, to those capable of onsite thrombolytic therapy. This study aimed to assess the time to treatment and outcomes among acute ischemic stroke patients who received thrombolytic treatment in the Chulalongkorn Stroke Network by 1.) Direct arrival at the CSC (mothership) 2.) Telestroke-assisted thrombolytic treatment with secondary transfer to the CSC (drip-and-ship) 3.) Referral from community hospital to the CSC for thrombolytic treatment (ship-and-drip)., Methods: Acute ischemic stroke patients who received thrombolytic treatment during January 2016-December 2017 in the Chulalongkorn Stroke Network were studied. Time to treatment and clinical outcomes were compared among treatment groups., Results: There were 273 patients in the study including 147, 87, and 39 patients in mothership, drip-and-ship, and ship-and-drip paradigms, respectively. The door-to-needle-time (DTN) and onset-to-needle-time (OTN) times were significantly longest in ship-and-drip group (146.5 ± 62/205.03 ± 44.88 mins) compared to mothership (38 ± 23/155.2 ± 60.54 mins) and drip-and-ship (63.0 ± 44/166.09 ± 87 mins), P < 0.05. There was no significant difference regarding functional independence defined by modified Rankin Scale (mRS) ≤ 2 at 3 months (P = 0.12), in-hospital mortality (P = 0.37), mortality at 3 months (P = 0.73), and symptomatic intracerebral hemorrhage (P = 0.24) among groups., Conclusion: Thrombolytic treatment with drip and ship method under teleconsultation is feasible in Thailand. There was no difference of clinical outcome among the 3 treatment paradigms. However, DTN time and OTN time were longest in the ship-and-drip paradigm.

Background: Acute ischemic stroke patients in Lao People's Democratic Republic (Lao PDR) are unable to access the intravenous thrombolytic therapy using recombinant tissue plasminogen activator (rtPA) due to various reasons., Aims: This study aimed to evaluate the feasibility and safety of thrombolytic therapy administration at Mittaphab Hospital, Lao PDR under the international telestroke consultation system from King Chulalongkorn Memorial Hospital, Thailand., Methods: Acute ischemic stroke patients who presented at Mittaphab Hospital within 4.5 hours after the onset and received thrombolytic therapy between December 2016 and June 2017 were studied. An immediate real time teleconsultation with 24 hours availability between neurologists at Mittaphab hospital and the Chulalongkorn stroke team was performed in all cases for patient evaluation and decision for thrombolytic treatment., Results: There were 205 patients with acute stroke, 28 patients (14%) arrived at the hospital within 4.5 hours after the onset. Ten patients (5%) were eligible for intravenous rtPA. The mean duration from onset to hospital arrival was 122.50 minutes and the mean door to needle time was 108 minutes. The mean National Institute of Health stroke scale (NIHSS) before thrombolysis was 10. At 90 days, the mean NIHSS was 3 and the mean mRS was 2. Seventy percent of patients had good outcome (mRS ≤2). Only one patient developed massive cerebral infarction. None of the patient developed symptomatic intracerebral hemorrhage or major bleedings., Conclusions: Telestroke consultation from Thailand can facilitate the thrombolytic therapy for acute ischemic stroke patients in Lao PDR., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Concurrent acute ischemic stroke and acute myocardial infarction is an uncommon medical emergency condition. The challenge for the physicians regarding the management of this situation is paramount since early management of one condition will inevitably delay the other. We present two illustrative cases of "hyperacute simultaneous cardiocerebral infarction" who presented with simultaneous cardiocerebral infarction and arrived at the hospital within the thrombolytic therapeutic window for acute ischemic stroke of 4.5 h. We propose an algorithm for managing the patient with hyperacute simultaneous cardiocerebral infarction based on hemodynamic status and suggest close cardiac monitoring based on the site of cerebral infarction. [ABSTRACT FROM AUTHOR]