Prevention Of Ischemic Stroke Research Articles

A Comparative Study on the Neuroprotective Effect of Geopung-Chunghyuldan on In Vitro Oxygen-Glucose Deprivation and In Vivo Permanent Middle Cerebral Artery Occlusion Models.

Geopung-Chunghyuldan (GCD), which is a mixture of Chunghyuldan (CD), Radix Salviae Miltiorrhizae, Radix Notoginseng, and Borneolum Syntheticum, is used to treat ischemic stroke in traditional Korean medicine. This study aimed to investigate the effects of GCD and CD on ischemic brain damage using in vitro and in vivo stroke models, as well as to elucidate the synergistic effects of GCD against ischemic insult. To study the effect of GCD in an in vitro ischemia model, SH-SY5Y cells were exposed to oxygen-glucose deprivation (OGD). Cell death after 16 h of OGD exposure was measured using the MTT assay and live/dead cell counting methods. An in vivo ischemia mice model was established through permanent middle cerebral artery occlusion (pMCAO). To determine the neuroprotective effect of GCD, it was orally administered immediately and 2 h after pMCAO. The infarct volume was measured through 2,3,5-triphenyltetrazolium chloride staining at 24 h after pMCAO. Compared with the control group, GCD treatment significantly reduced OGD-induced cell death in SH-SY5Y cells; however, CD treatment did not show a significant protective effect. In the pMCAO model, compared with the control group, treatment with GCD and CD significantly and mildly reduced the infarct volume, respectively. Our findings indicate that compared with CD, GCD may allow a more enhanced neuroprotective effect in acute ischemic stroke, indicating a potential synergistic neuroprotective effect. The possibility of GCD as a novel alternative choice for the prevention and treatment of ischemic stroke is suggested.

Contemporary Antiplatelet and Anticoagulant Therapies for Secondary Stroke Prevention: A Narrative Review of Current Literature and Guidelines.

Stroke is a leading cause of death and disability worldwide. The annual incidence of new or recurrent stroke is approximately 795,000 cases per year in the United States, of which 87% are ischemic in nature. In addition to the management of modifiable high-risk factors to reduce the risk of recurrent stroke, antithrombotic agents (antiplatelets and anticoagulants) play an important role in secondary stroke prevention. This review will discuss the published literature on the use of antiplatelets and anticoagulants in secondary prevention of acute ischemic stroke and transient ischemic attack (TIA), including their pharmacology, efficacy, and adverse effects. We will also highlight the role of dual antiplatelet therapy (DAPT) in secondary stroke prevention, along with supporting literature. Single antiplatelet therapy (SAPT) with aspirin or clopidogrel reduces the risk of recurrent ischemic stroke in patients with non-cardioembolic ischemic stroke or TIA. However, as shown in recent trials, short-term DAPT with aspirin and clopidogrel or ticagrelor for 21-30days is more effective than SAPT in patients with minor acute non-cardioembolic stroke or high-risk TIA. Although short-term DAPT is highly effective in preventing recurrent stroke, a more prolonged course can increase bleeding risks without additional benefit. DAPT for 90days, followed by aspirin monotherapy for patients with large vessel intracranial atherosclerotic disease, is suitable for secondary stroke prevention. However, patients need to be monitored for both minor (e.g., bruising) and major (e.g., intracranial) bleeding complications. Conversely, oral warfarin and newer direct oral anticoagulant (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban are the agents of choice for secondary stroke prevention in patients with non-valvular cardioembolic strokes. DOACs may be preferred over warfarin due to decreased bleeding risks, including ICH, lack of need for international normalized ratio monitoring, no dietary restrictions, and limited drug-drug interactions. The choice between different antiplatelets and anticoagulants for prevention of ischemic stroke depends on the underlying stroke mechanism, cytochrome P450 2C19 polymorphisms, bleeding risk profile, compliance, drug tolerance, and drug resistance. Physicians must carefully weigh each patient's relative benefits and bleeding risks before initiating an antiplatelet/anticoagulant treatment regimen. Further studies are warranted to study the optimal duration of DAPT in symptomatic intracranial atherosclerosis since the benefit is most pronounced in the short term while the bleeding risk remains high during the extended duration of therapy.

Cerebral autoregulation and blood flow distribution in the precerebral arteries for determining indications of extra-intracranial bypass in patients with carotid artery occlusion

Background. Prevention of ischemic stroke in patients with carotid artery occlusion is conventionally associated with performing cerebral revascularization. However, determining the indications for it is still an actual problem. The informative value of noninvasive assessment of cerebral autoregulation and blood flow distribution in the precerebral arteries in patients with carotid artery stenosis is shown. At the same time, in patients with carotid artery occlusion, these indicators have been studied to a lesser extent.Aim. To evaluate the informative value of cerebral autoregulation and blood flow distribution in the precerebral arte ries for determination the indications of extra‑intracranial bypass in patients with carotid occlusion.Materials and methods. 54 patients (aged from 41 to 83 y. o.) with carotid artery occlusion were studied. Blood flow velocity in intracranial arteries was determined with transcranial Doppler (system Multi‑Dop X), whereas flow velocity index in precerebral arteries – with duplex scanning (system Vivid Е). Cerebral autoregulation was assessed based on phase shift between spontaneous oscillations of blood flow velocity in basal cerebral arteries and systemic blood pressure within the range of Mayer’s waves (80–120 mHz).Results. The state of cerebral autoregulation was imparied on both sides in 90 % patients with the symptomatic carotid occlusion (0.3 ± 0.3 rad ipsilateral, 0.7 ± 0.6 rad contralateral). The state of cerebral autoregulation was not impaired in 79 % patients with asymptomatic carotid occlusion (1.0 ± 0.3 rad ipsilateral, 1.1 ± 0.4 rad contralateral). The flow velocity index in the contralateral internal carotid artery (306 ± 109 ml / min) and the ipsilateral vertebral (139 ± 69 ml / min) and external carotid (175 ± 72 ml / min) arteries was increased.Conclusions. Noninvasive preoperative assessment of cerebral autoregulation and blood flow distribution in the precerebral arteries makes to evaluate the state of the cerebrovascular reserve to quantify and can be used to determining indications for cerebral revascularization in patients with carotid occlusion.

Traditional Chinese medicine in treating ischemic stroke by modulating mitochondria: A comprehensive overview of experimental studies.

Ischemic stroke has been a prominent focus of scientific investigation owing to its high prevalence, complex pathogenesis, and difficulties in treatment. Mitochondria play an important role in cellular energy homeostasis and are involved in neuronal death following ischemic stroke. Hence, maintaining mitochondrial function is critical for neuronal survival and neurological improvement in ischemic stroke, and mitochondria are key therapeutic targets in cerebral stroke research. With the benefits of high efficacy, low cost, and high safety, traditional Chinese medicine (TCM) has great advantages in preventing and treating ischemic stroke. Accumulating studies have explored the effect of TCM in preventing and treating ischemic stroke from the perspective of regulating mitochondrial structure and function. In this review, we discuss the molecular mechanisms by which mitochondria are involved in ischemic stroke. Furthermore, we summarized the current advances in TCM in preventing and treating ischemic stroke by modulating mitochondria. We aimed to provide a new perspective and enlightenment for TCM in the prevention and treatment of ischemic stroke by modulating mitochondria.

Prevention of ischemic stroke in patients with pathological tortuosity of the internal carotid artery

No multicenter randomized clinical trial has been conducted worldwide to date on indications, types of surgery and their comparison with conservative treatment in patients with PI BSA.Aims: of the study is to improve the results of surgical treatment in patients with pathological tortuosity of the internal carotid arteryMaterial and methods. Тhe study included 115 patients (38 (33%) men and 77 (67%) women) with PI ICA aged 35 to 72 years (average age 54.2 ± 7.5 years) divided into 2 groups. 61 patients (53%) of group I underwent BSA resection with lower mouth and 54 patients (47%) of group II underwent BSA prosthetics. Depending on the degree of neurological disorders, patients were distributed according to the classifi cation of A.V. Pokrovsky.Results. In patients with СМН1, the clinical eff ect was due to the absence of cerebrospinal and focal neurological symptoms. As a result of surgical treatment of PI BSA in group I, a clinical eff ect was achieved in 54 (89%) patients. In group II, regression of clinical-neurological symptoms was observed in 40 (74%) patients.Conclusions. Resection and prosthetics of BSA PI in order to stop neurological symptoms and prevent ischemic stroke in patients with this pathology is a safe and eff ective method of surgical treatment.

Increased major bleeding incidence in atrial fibrillation patients with apixaban: a review of Japanese post-marketing surveillance studies of direct oral anticoagulants

Large-scaled post-marketing surveillance studies (PMSSs) of 4 direct oral anticoagulants (DOACs) for stroke prevention in non-valvular atrial fibrillation (AF) were conducted since 2011 in Japan, and the results of the last one have recently been published. Each reported a more than acceptable ischemic stroke prevention. The major bleeding rates were also acceptably low and comparable to each other in the PMSSs of dabigatran (J-dabigatran), rivaroxaban (XAPASS), and edoxaban (ETNA-AF-Japan). However, the incidence in PMSS of apixaban (STANDARD) was more than double the others. This finding appeared to contradict the globally accepted theory that apixaban is less likely than other DOACs to cause bleeding events. Possible responsible mechanisms included (1) the age and kidney function, (2) concomitant antiplatelet therapy, (3) drug actions, (4) follow-up duration, and (5) dose reduction criteria. Similarities in the clinical background shared by the 4 different PMSSs' participants and knowledge from previous studies did not support a dominant contribution of any of those former 4 factors to the increased major bleeding incidence in STANDARD. A possibility of the 5th factor was then examined. An estimated calculation we created showed that apixaban's dose reduction criteria was strict enough to considerably reduce the opportunity for participants to take its reduced rather than standard dose. We then successfully simulated how the "strict" dose reduction criteria would have increased the bleeding event rates under DOAC therapy. The discussion in this review may therefore raise a question about the validity of the current dose reduction criteria of apixaban for Japanese AF patients.

Secondary Ischemic Stroke Prevention.

The health burden of ischemic stroke is high and will continue to increase with an aging population. Recurrent ischemic stroke is increasingly recognized as a major public health concern with potentially debilitating sequelae. Thus, it is imperative to develop and implement effective strategies for stroke prevention. When considering secondary ischemic stroke prevention, it is important to consider the mechanism of the first stroke and the related vascular risk factors. Secondary ischemic stroke prevention typically includes multiple medical and, potentially, surgical treatments, but with the shared goal of reducing the risk of recurrent ischemic stroke. Providers, health care systems, and insurers also need to consider the availability of treatments, their cost and patient burden, methods for improving adherence, and interventions that target lifestyle risk factors such as diet or activity. In this article, we discuss aspects from the 2021 AHA Guideline on Secondary Stroke Prevention as well as highlight additional information relevant to best practices for reducing recurrent stroke risk.

Interventional strategies for ischemic stroke based on the modulation of the gut microbiota.

The microbiota-gut-brain axis connects the brain and the gut in a bidirectional manner. The organism's homeostasis is disrupted during an ischemic stroke (IS). Cerebral ischemia affects the intestinal flora and microbiota metabolites. Microbiome dysbiosis, on the other hand, exacerbates the severity of IS outcomes by inducing systemic inflammation. Some studies have recently provided novel insights into the pathogenesis, efficacy, prognosis, and treatment-related adverse events of the gut microbiome in IS. In this review, we discussed the view that the gut microbiome is of clinical value in personalized therapeutic regimens for IS. Based on recent non-clinical and clinical studies on stroke, we discussed new therapeutic strategies that might be developed by modulating gut bacterial flora. These strategies include dietary intervention, fecal microbiota transplantation, probiotics, antibiotics, traditional Chinese medication, and gut-derived stem cell transplantation. Although the gut microbiota-targeted intervention is optimistic, some issues need to be addressed before clinical translation. These issues include a deeper understanding of the potential underlying mechanisms, conducting larger longitudinal cohort studies on the gut microbiome and host responses with multiple layers of data, developing standardized protocols for conducting and reporting clinical analyses, and performing a clinical assessment of multiple large-scale IS cohorts. In this review, we presented certain opportunities and challenges that might be considered for developing effective strategies by manipulating the gut microbiome to improve the treatment and prevention of ischemic stroke.

Terapia farmacológica en la prevención secundaria del ictus isquémico en los muy ancianos: ¿ha mejorado en las últimas décadas?

IntroductionPopulation aging has led to an increase in strokes in older patients (OP) aged ≥80 years. This work assesses how secondary prevention of ischemic stroke in OP has changed in recent decades. MethodThis work is a retrospective study of discharges due to ischemic stroke in the Virgen Macarena, Virgen del Rocío, and Virgen de Valme hospitals in Seville (Spain) during the periods of 1999-2001, 2014-2016, and 2019-2020. ResultOf the 1,806 patients studied, 349 (19.3%) were OPs. Over the 3time periods, the percentage of OPs doubled (13.5% vs. 25.9% vs. 28%; p=0.0001) and their age increased (83.3±3 vs. 84.1±3 vs. 85.2±4; p=0.001). Comparing the periods, OPs had more hypertension (69.9% vs. 84.8% vs. 84.6%; p=0.0001) and dyslipidemia (12% vs. 41.7% vs. 52.3%; p=0.0001) and a greater percentage had prescriptions for antihypertensives (69.1% vs. 86.7% vs. 92.3%; p=0.0001), statins (5.3% vs. 78% vs. 81.5%; p=0.0001), and anticoagulants (16.5% vs. 19.4% vs. 53.1%; p=0.001). OPs also received more antihypertensives (1±0.9 vs. 1.6±0.9 vs. 1.9±0.8 drugs; p=0.0001) and high-intensity statins (2.3% vs. 42.7% vs. 69.2%; p=0.0001). Comparing OPs to younger patients, there were no differences in antihypertensive treatment in any period, though there were differences in antithrombotic treatment in the first period. In regard to statins, the differences were maintained until the end. ConclusionsThe number of OPs has doubled in the last 20 years and they now represent over one-quarter of discharges. Although progress has been made in secondary stroke prevention in OP, there is room for improvement.

Abstract Number ‐ 267: The Role of Non‐stenosing Carotid Artery Plaques in ESUS, is it a Silent Offender?

Introduction The secondary prevention of Acute ischemic stroke (AIS)varies based on the root cause of the initial event; thus, determining the cause of an individual AIS is critical for implementing effective care. The well‐described TOAST classification is used to classify stroke etiology, and according to this paradigm, the presence of large vessel disease is considered a high risk for subsequent stroke only if >50% carotid artery stenosis is present. Cryptogenic strokes represent around 30% of all AIS and Embolic stroke of unknown source (ESUS) is a subcategory of the cryptogenic strokes and is characterized as a non‐lacunar ischemic stroke presumed to be of an embolic origin with no evidence of an obvious source of emboli. Here we discuss the most important and latest evidence on the relationship between ESUS and high‐risk plaque features not causing significant stenosis per NASCET criteria. Methods N/A Results The Relationship Between ESUS and Non‐stenosing Carotid Artery Plaques is mainly illustrated in the following points: Plaque vulnerability Researchers have described the following high‐risk features of plaques that may lead to stroke (Table). Plaque vulnerability is a plaque’s susceptibility to rupture and is a proposed determinant of high risk for superimposed thrombosis. According to a meta‐analysis conducted by Kamtchum‐Tatuene et al, high‐risk plaque features were three times more prevalent in patients with symptomatic versus asymptomatic carotid stenosis.3 Laterality of cartid plaques and stroke A meta‐analysis of 8 studies that assessed 323 patients with ESUS showed that mild carotid stenosis with high‐risk plaque features was more commonly located ipsilateral to the stroke side (32.5%) versus being contralaterally located (4.6%).4 Knight‐Greenfield et al evaluated plaque features by CTA in patients with AIS who did not have hemodynamic stenosis. It was also found that ESUS patients had a higher total plaque thickness ipsilateral to the stroke side when compared to the contralateral stroke‐free hemisphere.5 Clot composition and stroke etiology Fibrin/platelet component was dominant in cardioembolic thrombi and cryptogenic stroke, while red blood cells were seen more frequently in non‐cardioembolic thrombi. This supports the hypothesis that plaque histological features play a major role in causing large vessel occlusion despite the absence of significant stenosis.8 Conclusions Despite the evidence that high‐risk plaque features can predict a recurrent stroke, adoption of this principle and its integration into the medical guidelines have not yet been established. This reflects a lack of clinical trials that have utilized detailed plaque characterization for assessing risk of stroke.

IS SCREENING FOR EXTRACRANIAL CAROTID STENOSIS EFFECTIVE IN PREVENTING ISCHEMIC STROKE? LITERATURE REVIEW

This literature review shows the essence of the problem of extracranial carotid artery stenosis, since this disease is a treatable cause of ischemic stroke and can be reliably detected and assessed by using vascular ultrasound. In Kazakhstan, due to acute disorders of cerebral circulation, 11.1 thousand patients die every year. The reliability of the information in the article was obtained by using the literature data of the last 10 years. The reflection of the criteria for diagnosing stenosis of the extracranial carotid artery, the use of which, in conjunction with standard tests and other sensitive methods, makes it possible to determine the lesion of the extracranial carotid artery at an early stage, as well as a detailed description of diagnostic methods of this complication and evaluation of their effectiveness. Screening for carotid stenosis is important, and whether routine carotid ultrasound is recommended in general population for the prevention of ischemic stroke remains controversial. Screening for carotid stenosis by ultrasound is crucial not only for the daily clinical setting, but also for the management of patients with acute ischemic stroke.

Pharmacological therapy in the secondary prevention of ischemic stroke in the oldest-old patients: has it improved in recent decades?

IntroductionPopulation aging has caused an increase in strokes in very elderly patients (VEP). We assess how secondary prevention of ischemic stroke has changed in VEP in recent decades. MethodRetrospective study of discharges due to ischemic stroke in the Virgen Macarena, Virgen del Rocio and Valme hospitals in Seville (Spain), during the periods 1999–2001, 2014−16 and 2019−2020. VEP were considered those with ≥80 years. ResultWe studied 1806 patients, 349 (19.3%) were VEP. Over the years, VEPs have doubled (13.5% vs. 25.9% and 28% p = 0.0001) and age has increased (83.3 ± 3 vs. 84.1 ± 3 vs. 85.2 ± 4 p = 0.001). Comparing the periods, the VEPs have more hypertension (69.9% vs. 84.8% vs. 84.6%; p = 0.0001) and dyslipidemia (12% vs. 41.7% vs. 52.3%; p = 0.0001) and have prescribed more antihypertensives (69.1% vs. 86.7% vs. 92.3%; p = 0.0001), statins (5.3% vs. 78% vs. 81.5%; p = 0.0001) and anticoagulants (16.5% vs. 19.4% vs. 53.1%; p = 0.001), increasing the number of antihypertensives (1 ± 0.9 vs. 1.6 ± 0, 9 vs. 1.9 ± 0.8 drugs p = 0.0001), and high-intensity statins (2.3% vs. 42.7 vs. 69.2% p = 0.0001). Comparing the VEPs with the younger ones, there were no differences in antihypertensive treatment in any period, there were differences in antithrombotic treatment in the first period, and with statins the differences were maintained until the end. ConclusionsIn the last 20 years the number of VEPs has doubled, exceeding a quarter of the discharges. Although there is improvement in secondary stroke prevention in VEPs, there is room for improvement.

Dual antiplatelet therapy in acute ischaemic stroke with or without cerebral microbleeds.

Antiplatelet therapy (APT) plays an important role in the prevention of ischaemic stroke (IS). Our aim was to assess the influence of short-term single APT (SAPT) and dual APT (DAPT) on the prognosis of patients with acute IS with and without cerebral microbleeds (CMBs). We conducted a single-centre, retrospective, observational cohort study of patients with acute IS who underwent susceptibility-weighted imaging (SWI) to determine the presence of CMBs between January 2015 and December 2020. The patients were treated with either DAPT or SAPT and followed up for at least 2 years. The primary endpoint was a composite of recurrent IS and intracerebral haemorrhage (ICH), while either recurrent IS or ICH was considered as other endpoints. We computed weighted Kaplan-Meier curves and identified risk factors using the Cox proportional hazards model. Among the 581 enrolled patients, those with CMBs (n = 225; P = 0.004) had a higher risk of the primary endpoint than those without CMBs (n = 356), especially higher risk of recurrent IS (P = 0.029). In the SAPT group, the presence of CMBs increased the risk of the primary endpoint (P = 0.013), especially that of recurrent IS (P = 0.019). In the DAPT group, the occurrence of ICH was higher in patients with CMBs (P = 0.031). The CMB distribution did not influence the risk of recurrent IS or ICH. In patients with acute IS and CMBs, DAPT may offset the risk of recurrent IS due to CMBs but increase the risk of ICH.

Is improved access to magnetic resonance imaging imperative for optimal ischemic stroke care?

Neuroimaging, including CT and MRI, is integral to ischemic stroke (IS) treatment, management, and prevention. However, the use of MRI for IS patients is limited despite its potential to provide high-quality images that yield definitive information related to the management of IS. MRI is beneficial when the information provided by CT is insufficient for decisions related to the diagnosis, etiology, or treatment of IS. In the emergency setting, MRI can improve the diagnostic accuracy of CT-negative acute ischemic strokes (AIS) and ensure a better selection of patients for reperfusion therapies with thrombolysis and/or thrombectomy. Moreover, MR imaging may help avoid hospital admissions for patients with stroke mimics, facilitate earlier discharge, and reduce overall hospital costs. MRI in the in-patient setting can help determine stroke etiology to aid in stroke prevention management upon discharge. Furthermore, early access to MRI in IS out-patients can aid in diagnosing, risk stratifying, and determining optimal management strategies for patients with a TIA or a minor stroke. Recent technological advances, particularly low-to-mid-field MR scanners, can improve access to MRI. These MR scanners provide faster protocols, cost-effectiveness, smaller footprints, safety, and lower power requirements. In conclusion, MRI use for IS treatment, management, and prevention is imperative and justifiable, and the latest technological advancements in MR scanners hold the potential to enhance access.

Small-vessel disease in the brain

Cerebral small-vessels are generally located in the brain at branch points from major cerebral blood vessels and perfuse subcortical structures such as the white matter tracts, basal ganglia, thalamus, and pons. Cerebral small-vessel disease (CSVD) can lead to several different clinical manifestations including ischemic lacunar stroke, intracerebral hemorrhage, and vascular dementia. Risk factors for CSVD overlap with conventional vascular risk factors including hypertension, diabetes mellitus, and hypercholesterolemia, as well as genetic causes. As in cardiovascular disease, treatment of CSVD involves both primary and secondary prevention. Aspirin has not been established as a primary prevention strategy for CSVD among the general population; however, long-term antiplatelet therapy with aspirin alone continues to be the mainstay of secondary stroke prevention for non-cardioembolic ischemic stroke and high-risk TIA.

Gut Microbiome and Risk of Ischemic Stroke: A Comprehensive Mendelian Randomization Study.

Increasing evidence implicates the microbiome as a susceptibility factor for ischemic stroke (IS). Interpretation of this evidence is difficult for the composition of the microbiome is influenced by various factors and might affect differently in IS subtypes. We aim to determine if the specific gut microbiome is causally associated with IS subtypes and suggest potential approaches for stroke prevention. We conducted a two-sample Mendelian Randomization analysis to test the causal relationship between gut microbiome and IS subtypes. For exposure data, we extracted genetic variants associated with 194 bacterial traits from MiBioGen consortium (N = 18,340). For outcomes, we selected three IS subtypes including cardioembolic stroke (CES, N = 410,484), small vessel stroke (SVS, N = 198,048), and large artery stroke (LAS, N = 198,048). Additionally, we performed a sequence of sensitivity analyses to validate preliminary MR results. There were four, three, and four bacteria showing an increased risk for LAS, SVS, and CES, respectively, and there were five, six, and five bacteria leading a decreasing risk for LAS, SVS, and CES, respectively. Among these, the genus_Intestinimonas showed negative associations with LAS [odds ratio (OR) = 0.77, 95% confidence interval (CI) (0.61-0.98)] and SVS (0.85, 0.73-0.98). The genus_LachnospiraceaeNK4A136group was genetically associated with decreased risk of both SVS (0.81, 0.66-0.99) and CES (0.75, 0.60-0.94). The study revealed the causal effect of the abundance of specific bacterial features on the risk of IS subtypes. Notably, genus_Intestinimonas and genus_LachnospiraceaeNK4A136group displayed significant protection against more than one IS subtype, further suggesting potential applications of targeted probiotics in IS prevention.

48 hours Holter monitoring in detecting occult atrial fibrillation in young patients with possible cardioembolic stroke

Background and objective: 
 Atrial fibrillation (AF) is a common cause of ischemic stroke. AF is usually paroxysmal and could escape detection via single lead electrocardiogram ECG recorder. Holter monitoring is useful in this scenario. The objective of this study was to assess the role of 48 hours Holter monitoring in identifying clinically inapparent AF in young patients with ischemic stroke
 Methods: 
 A retrospective cross-sectional study was conducted with patient data from November 2019 to February 2021. It was conducted in Neurology department of Pakistan Institute of Medical Sciences, Islamabad, Pakistan. Study contained medical records of 60 patients which were admitted in this time period. Forty-eight hours Holter monitoring was carried out for all the patients. Patient medical records were examined according to predetermined risk factors and criteria. Statistical analysis was done on SPSS version 25.0.
 Results: 
 Ten out of 60 cases had positive results for AF during Holter’s monitoring. Fifty cases had negative results for AF during Holter monitoring. While the p value of the data obtained remained non-significant, results depict efficacy of Holter’s monitoring in detection of AF to some extent.
 Conclusion:
 Holter monitoring can identify AF, providing aid in prevention of secondary ischemic stroke. However, instead of 48 hours monitoring, a through 72 hours or extended monitoring will increase the effectiveness of this monitoring. In future, a study could be conducted where a large number of cases should be included so that statistical significance of data could be increased.

Aneurysmal Subarachnoid Hemorrhage in Hospitalized Patients on Anticoagulants—A Two Center Matched Case-Control Study

Objective-Direct oral anticoagulants (DOAC) are replacing vitamin K antagonists (VKA) for the prevention of ischemic stroke and venous thromboembolism. We set out to assess the effect of prior treatment with DOAC and VKA in patients with aneurysmal subarachnoid hemorrhage (SAH). Methods-Consecutive SAH patients treated at two (Aachen, Germany and Helsinki, Finland) university hospitals were considered for inclusion. To assess the association between anticoagulant treatments on SAH severity measure by modified Fisher grading (mFisher) and outcome as measured by the Glasgow outcome scale (GOS, 6 months), DOAC- and VKA-treated patients were compared against age- and sex-matched SAH controls without anticoagulants. Results-During the inclusion timeframes, 964 SAH patients were treated in both centers. At the time point of aneurysm rupture, nine patients (0.93%) were on DOAC treatment, and 15 (1.6%) patients were on VKA. These were matched to 34 and 55 SAH age- and sex-matched controls, re-spectively. Overall, 55.6% of DOAC-treated patients suffered poor-grade (WFNS4-5) SAH compared to 38.2% among their respective controls (p = 0.35); 53.3% of patients on VKA suffered poor-grade SAH compared to 36.4% in their respective controls (p = 0.23). Neither treatment with DOAC (aOR 2.70, 95%CI 0.30 to 24.23; p = 0.38), nor VKA (aOR 2.78, 95%CI 0.63 to 12.23; p = 0.18) were inde-pendently associated with unfavorable outcome (GOS1-3) after 12 months. Conclusions-Iatrogenic coagulopathy caused by DOAC or VKA was not associated with more severe radiological or clinical subarachnoid hemorrhage or worse clinical outcome in hospitalized SAH patients.

Abstract WP241: Phenylalanine, Apob/apoa-1 Ratio, Ketone Bodies, Fatty Acids, And Microrna 9-3p Patterns Are Altered In Acute Ischemic Stroke

Background: Stroke is a significant health issue in the United States and identifying biomarkers for prevention and functional recovery of acute ischemic stroke (AIS) remains the highest priority. This study aims to identify metabolite and microRNA (miRNA) signatures that may be associated with AIS pathophysiology by performing longitudinal and case-control studies. Methods: We evaluated 260 patients during acute (<72 hours, T1), and chronic (3-5 months, T2) phases of stroke with 160 controls by performing global metabolomics using high-throughput nuclear magnetic resonance spectroscopy. In a subset, we also examined differential expression patterns of blood and serum exosome miRNAs between the T1 and T2 using RNA sequencing. Results: Our study identified 19 metabolites to be significantly perturbed during the T1 using the orthogonal partial least square discrimination analysis and multivariate mixed regression. Phenylalanine showed a 15.9-fold increase in T1 and remained high at the T2 stage. The Apolipoprotein B/Apolipoprotein A-1 ratio and ketone bodies were markedly increased while several essential fatty acids and amino acids were decreased in the T1. Our data also identified 3 exosomal miRNAs upregulated in the T1 stage. The miR-9-3p showed a 14.7-fold increase in T1 (Bonferroni p= 9.44x10 -6 ) which is strongly supported by the literature to trigger brain injury and cell death via the caspase pathway. Increased expression of miR-4508 correlated positively with phenylalanine both in T1 (r = 0.88, p = 0.001) and T2 (r = 0.71, p = 0.02). Conclusion: This study elucidates significant alterations in amino acids, fatty acids, and apolipoprotein patterns between the acute and chronic stages of stroke compared to controls. Our results on exosomal miRNAs and pathway analysis using metabolites identified four major pathways; apoptosis, excitotoxicity, oxidative stress, and stroke-mediated inflammation to play a critical role in the AIS leading to neuronal cell death. Further validation in independent datasets is warranted, and if confirmed some of these may become clinically meaningful biomarkers to predict AIS in humans.

Abstract TP162: Age, Weight, And Prior Stroke Predicts Ischemic Stroke Despite Direct Acting Oral Anticoagulant Use In Patients With Atrial Fibrillation

Introduction: Direct-acting oral anticoagulants (DOACs) and warfarin are standard of care for secondary prevention of ischemic stroke (IS) in persons with atrial fibrillation (AF). However, despite adequate anticoagulation (AC), patients may still experience recurrent IS. We aimed to study the characteristics of patients who developed IS despite therapeutic AC, specifically with DOACs. Methods: Between 2012 and 2021, patients admitted at our hospital with IS despite adequate AC for AF were enrolled. Clinical variables collected included National Institute of Health Stroke Scale (NIHSS), CHA 2 DS 2 -VASc and modified Rankin Score (mRS) at admission. Baseline characteristics were compared between patients taking DOACs and warfarin. Logistic regression analyses were performed to identify predictors of IS in patients using DOACs. Results: A total of 595 patients were included. Of these, 291 patients (48.9%) were on DOACs with a mean age of 75.21 and 43.9% were female. The median CHA 2 DS 2 -VASc and NIHSS score in the DOAC group was 4 and 6, respectively. Compared to those on Warfarin, patients on DOACs were younger (75.21 vs. 78.99 p < 0.001), more likely to be men (55.3% vs. 45.2% p = 0.01) and had higher rates of prior TIA/IS (37.5% vs. 29.3% p = 0.04). Both groups had similar rates of hemorrhagic transformation, but more patients in the DOAC group were on antiplatelet agents concomitantly (21% vs. 6.9% p < 0.001). The most prescribed DOAC was apixaban (66.3%) and cardioembolism was the most common stroke etiology (63.6%), followed by cryptogenic, which was significantly higher in the DOAC group (18.2% vs. 8.3% p = 0.02). Notably, DOAC failure in preventing IS was associated with younger age, overweight/obesity, and prior TIA/IS (Table) . Conclusions: IS despite the use of DOACs is more likely to occur in younger people with prior TIA/IS and obesity. Focusing on preventative strategies and risk factor control for competing mechanisms in this subgroup may help prevent IS recurrence.