Transient Ischemic Attack Patients Research Articles

ABCD2-I Score Predicts Unplanned Emergency Department Revisits within 72 Hours Due to Recurrent Acute Ischemic Stroke

Background: the ABCD2 score is valuable for predicting early stroke recurrence after a transient ischemic attack (TIA), and Doppler ultrasound can aid in expediting stroke triage. The study aimed to investigate whether combining the ABCD2 score with carotid duplex results can enhance the identification of early acute ischemic stroke after TIA. Methods: we employed a retrospective cohort design for this study, enrolling patients diagnosed with TIA who were discharged from the emergency department (ED). The modified ABCD2-I (c50) score, which incorporates a Doppler ultrasound assessment of internal carotid artery stenosis > 50%, was used to evaluate the risk of acute ischemic stroke within 72 h. Patients were categorized into three risk groups: low risk (with ABCD2 and ABCD2-I scores = 0–4), moderate risk (ABCD2 score = 4–5 and ABCD2-I score = 5–7), and high risk (ABCD2 score = 6–7 and ABCD2-I score = 8–9). Results: between 1 January 2014, and 31 December 2019, 1124 patients with new neurological deficits were screened, with 151 TIA patients discharged from the ED and included in the analysis. Cox proportional hazards analysis showed that patients in the high-risk group, as per the ABCD2-I (c50) score, were significantly associated with revisiting the ED within 72 h due to acute ischemic stroke (HR: 3.12, 95% CI: 1.31–7.41, p = 0.0102), while the ABCD2 alone did not show significant association (HR: 1.12, 95% CI: 0.57–2.22, p = 0.7427). Conclusion: ABCD2-I (c50) scores effectively predict early acute ischemic stroke presentations to the ED within 72 h after TIA.

European Stroke Organisation (ESO) Guidelines on the diagnosis and management of patent foramen ovale (PFO) after stroke.

Patent foramen ovale (PFO) is frequently identified in young patients with cryptogenic ischaemic stroke. Potential stroke mechanisms include paradoxical embolism from a venous clot which traverses the PFO, in situ clot formation within the PFO, and atrial arrhythmias due to electrical signalling disruption. The purpose of this guideline is to provide recommendations for diagnosing, treating, and long-term managing patients with ischaemic stroke and PFO. Conversely, Transient Ischaemic Attack (TIA) was not considered an index event in this context because only one RCT involved TIA patients. However, this subgroup analysis showed no significant differences between TIA and stroke outcomes. The working group identified questions and outcomes, graded evidence, and developed recommendations following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach and the European Stroke Organisation (ESO) standard operating procedure for guideline development. This document underwent peer-review by independent experts and members of the ESO Guideline Board and Executive Committee. The working group acknowledges the current evidentiary gap in delineating an unequivocal diagnostic algorithm for the detection of PFO. Although transoesophageal echocardiography is conventionally held as the most accurate diagnostic tool for PFO identification, its status as the 'gold standard' remains unsubstantiated by rigorously validated evidence. We found high-quality evidence to recommend PFO closure plus antiplatelet therapy in selected patients aged 18-60 years in whom no other evident cause of stroke is found but a PFO (i.e. PFO-associated stroke). The PASCAL classification system can be used to select such candidates for PFO closure. Patients with both a large right-to-left shunt and an atrial septal aneurysm benefit most from PFO closure. There is insufficient evidence to make an evidence-based recommendation on PFO closure in patients older than 60 and younger than 18 years. We found low quality evidence to suggest against PFO closure in patients with unlikely PFO-related stroke according to the PASCAL classification, except in specific scenarios (Expert Consensus). We suggest against long-term anticoagulation in patients with PFO-associated stroke unless anticoagulation is indicated for other medical reasons. Regarding the long-term AF monitoring after PFO closure, the working group concluded that there remains significant uncertainty regarding the risks and benefits associated with the use of long-term cardiac monitoring, such as implantable loop recorders. This document provides additional guidance, in the form of evidence-based recommendations or expert consensus statements, on diagnostic methods for PFO detection, and medical management after PFO closure.

Anticoagulants versus Antiplatelet Treatment in the Medical Management of Carotid Floating Thrombus

Carotid free-floating thrombus (CFT) is a rare cause of stroke describing an intraluminal thrombus that is loosely associated with the arterial wall and manifesting as a filling defect fully surrounded by flow on vascular imaging. Unfortunately, there is no clear consensus among experts on the ideal treatment for this pathology. Retrospective analysis of acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients diagnosed with CFT on computed tomography angiogram (CTA) between January 2015-March 2023. We aimed to compare two treatment regimens: anticoagulation (ACT) and antiplatelet (APT) in the treatment of CFT. APT regimens included the use of dual or single antiplatelets (DAPT or SAPT; aspirin, clopidogrel and ticagrelor) and ACT regimens included the use of direct oral anticoagulants, warfarin, heparin or low molecular weight heparin +/- ASA. Patients that underwent mechanical thrombectomy were excluded. During study time there were 8252 acute ischemic stroke hospitalizations, of which 135 (1.63%) patients were diagnosed with CFT. Sixty-six patients were included in our analysis. Patients assigned to APT were older (60.41years ± 12.82;p<0.01). Other demographic variables were similar between ACT and APT groups. Complete CFT resolution on repeat vascular imaging was numerically higher at 30 days (58.8 vs 31.6%, respectively; p=0.1) and at latest follow-up (70.8 vs 50%; p=0.1) on ACT vs APT, respectively without reaching statistical significance. Similarly, there was numerically higher rates of any ICH with ACT compared to APT but it did not achieve statistical significance (27.6% vs 13.5%; p=0.5). There were similar rates of PH1/2 hemorrhagic transformation, independence at discharge and similar hospital length of stay between ACT and APT groups. Patients assigned to APT were more likely to be discharged on their assigned treatment compared to those assigned to ACT (86.5 vs 55.2%; p<0.001). The rate of 30-day recurrent stroke was comparable among ACT and APT at 30 days (3.4 vs 0%; p=0.1, respectively). Sensitivity analysis comparing exclusive ACT vs Dual APT lead to similar results. Our study showed comparable efficacy and safety outcomes in CFT patients who were exclusively managed medically with ACT vs APT. Larger prospective studies are needed.

Diagnostic value of cervical vascular ultrasound in large arterial lesions of the neck in patients with transient ischemic attack

Objective To assess the diagnostic value of cervical vascular ultrasound in identifying large arterial lesions in patients with transient ischemic attack (TIA). Methods The current study matched 84 TIA patients (disease group) with 66 healthy controls (control group). The baseline patient profiles and biochemical indices of the patients were analyzed. All patients received color Doppler ultrasonography, and outcome measures of its diagnostic efficiency included plaque status, plaque properties, and the degree of carotid stenosis. The patients in the disease group were assigned to group A (TIA of the internal carotid artery system, n = 40) and group B (TIA of the vertebrobasilar artery system, n = 44), and the plaque distribution of the patients was analyzed. Results TIA patients had higher rates of diabetes, hypertension, hyperlipidemia, obesity, and smoking compared to controls (p < 0.05). Their serum TC, LDL-C, and FBG levels were significantly elevated, while HDL-C levels were decreased (p < 0.05). TIA patients had more plaques, especially soft plaques, than controls (p < 0.05). They also showed higher rates of moderate to severe carotid stenosis (p < 0.05). TIA involving the internal carotid artery system was associated with a higher risk of plaques at the entrance of the subclavian artery compared to TIA involving the vertebrobasilar artery system (p < 0.05). Conclusion The diagnostic value of cervical vascular ultrasound in patients with TIA is remarkable, and it provides a reliable monitoring approach as well as an essential screening modality for TIA. The rational use of this technique will markedly benefit the diagnosis, treatment, and prevention of TIA.

Large variations in atrial fibrillation screening practice after ischemic stroke and transient ischemic attack in Sweden: a survey study

BackgroundAtrial fibrillation (AF) screening after ischemic stroke or transient ischemic attack (TIA) is given high priority in clinical guidelines. However, patient selection, electrocardiogram (ECG) modality and screening duration remains undecided and current recommendations vary.MethodsThe aim of this study was to investigate the clinical practice of AF screening after ischemic stroke or TIA at Swedish stroke units. In collaboration with the stakeholders of the Swedish Stroke Register (Riksstroke) a digital survey was drafted, then tested and revised by three stroke consultants. The survey consisted of 17 multiple choice/ free text questions and was sent by e-mail to the medical directors at all stroke units in Sweden.ResultsAll 72 stroke units in Sweden responded to the survey. Most stroke units reported that ≥ 75% of ischemic stroke (69/72 stroke units) or TIA patients (67/72 stroke units), without previously known AF, were screened for AF. Inpatient telemetry ECG was the method of first-choice in 81% of the units, but 7% reported lack of access. A variety of standard monitoring durations were used for inpatient telemetry ECG. The second most common choice was Holter ECG (17%), also with considerable variations in monitoring duration. Other AF screening modalities were used as a first-choice method (handheld and patch ECG) but less frequently.ConclusionsClinical practice for AF screening after ischemic stroke or TIA differed between Swedish stroke units, both in choice of AF screening methods as well as in monitoring durations. There is an urgent need for evidence and evidence-based recommendations in this field.Trial registrationNot applicable.

Impact of early MRI in ischemic strokes beyond hyper-acute stage to improve patient outcomes, enable early discharge, and realize cost savings

BackgroundEarly in-patient MR Imaging may assist in identifying stroke etiology, facilitating prompt secondary prevention for ischemic strokes (IS), and potentially enhancing patient outcomes. This study explores the impact of early in patient MRI on IS patient outcomes and healthcare resource use beyond the hyper-acute stage. MethodsIn this retrospective registry-based study, 771 admitted transient ischemic attack (TIA) and IS patients at Halifax's QEII Health Centre from 2015 to 2019 underwent in-patient MRI. Cohort was categorized into two groups based on MRI timing: early (within 48 h) and late. Logistic regression and Poisson log-linear models, adjusted for age, sex, stroke severity, acute stroke protocol (ASP) activation, thrombolytic, and thrombectomy, were employed to examine in-hospital, discharge, post-discharge, and healthcare resource utilization outcomes. ResultsAmong the cohort, 39.6 % received early in-patient MRI. ASP activation and TIA were associated with a higher likelihood of receiving early MRI. Early MRI was independently associated with a lower rate of symptomatic changes in neurological status during hospitalization (adjusted odds ratio [OR], 0.42; 95 % confidence interval [CI], 0.20–0.88), higher odds of good functional outcomes at discharge (1.55; 1.11–2.16), lower rate of non-home discharge (0.65; 0.46–0.91), shorter length of stay (regression coefficient, 0.93; 95 % CI, 0.89–0.97), and reduced direct cost of hospitalization (0.77; 0.75–0.79). ConclusionEarly in-patient MRI utilization in IS patients post-hyper-acute stage was independently associated with improved patient outcomes and decreased healthcare resource utilization, underscoring the potential benefits of early MRI during in-patient management of IS. Further research, including randomized controlled trials, is warranted to validate these findings.

Abstract 70: Rich-Club Behaviour and Analyses in the Human Brain Connectome as Novel Early Biomarkers of Cognitive Decline

Introduction: Transient ischemic attack (TIA) patients have an increased risk of early dementia, but the mechanism is unclear. One potential mechanism is the damaging effects of microvascular disease on brain networks. Rich club is a phenomenon where highly connected nodes form a “rich club” amongst themselves, thus playing an important role in global brain network communication. In this study we aim to determine 1) whether the prominence of the rich club effect declines greater in TIA patients than controls over time, and 2) the relationship of rich club prominence with cognition. Methods: TIA patients (n=47) and controls (n=43) underwent DTI imaging and cognitive assessment at baseline, 1-year, 3-year, and 5-year. Whole-brain tractography utilizing constrained spherical deconvolution was performed to construct whole-brain connectomes for both groups at all available timepoints. The maximum normalized rich club coefficient (Φ max ) was used as an indicator of the prominence of the rich club effect. Independent-sample T-tests were used to compare Φ max cross-sectionally, while a linear mixed effect (LME) model was used to examine the longitudinal change in Φ max in TIA patients vs. controls, while controlling for covariates including age, sex, WMH volume, whole-brain volume, and peak width of skeletonized mean diffusivity. Results: TIA patients had a mean age of 63.94 ( SD =8.62) and 20 females. Controls had a mean age of 60.73 (8.16) and 29 females. The prominence of the rich club was not significantly different between TIA patients and controls at baseline or 1-year ( p &gt;0.05). However, TIA patients showed a significantly less prominent rich club at 3-year and 5-year compared to controls ( p =0.047 and 0.018, respectively). TIA patients exhibited a significantly greater decrease in rich club prominence over time, relative to controls ( p =0.023), after accounting for covariates. Longitudinal LME models showed no association between changes in rich club prominence and changes in cognition ( p &gt;0.05 for all cognitive domains). Conclusion: In this study, we show a decrease in rich club prominence in TIA patients compared to controls which might identify their increased risk of cognitive impairment, and the potential benefits of aggressive vascular risk reduction.

Abstract 91: Patients With Intracranial Hemorrhage Have Greater Post-Stroke Mood Disturbance Than Those With Ischemic Stroke

Background: Patients with stroke frequently suffer from post-stroke mood disturbances (PSMD) which decrease their quality of life. It remains unclear whether the prevalence of PSMD differs according to stroke subtype. The aim of our study was to investigate PSMD incidence among stroke subtypes in the large, prospective Field Administration of Stroke Therapy - Magnesium (FAST-MAG) Trial. Methods: In the publicly-available FAST-MAG database, we identified all patients with imaging-confirmed diagnoses of ischemic stroke (IS), transient ischemic attack (TIA), and intracerebral hemorrhage (ICH). Data on age, sex, NIHSS at presentation, stroke subtypes, and Stroke Impact Scale (SIS) 64 v3.0 at 90 days were collected. Differences in SIS Emotion Domain scores between IS, TIA, and ICH were assessed using the Mann-Witney U Test. Results: SIS Emotion Domain scores were available in 1239/1370 (90.4%) of patients. Mean age was 68.7 years (SD 13.4), and 41% were female. Median NIHSS was 7.0 (IQR 3-14). 65.3% had IS, 14.3% TIA, and 20.3% ICH. The preponderance of SIS-64 scores were patient-reported (86%) with the remainder completed by a patient proxy (14%). Emotion domain scores at 3 months were: lowest (most abnormal) in ICH patients (median 77.8, IQR 58.3-88.9); intermediate in IS patients (median 83.3, IQR 66.7-94.4); and highest in TIA patients (median 88.9, IQR 72.2-97.2), p&lt;.01) (Figure). Neither age nor sex were strongly associated, but more abnormal mood scores were associated with greater presenting deficit severity (NIHSS 0-4: median SIS-64 mood score 88.9; NIHSS 5-14: 81.3; NIHSS ≥15: 75.0; Spearman’s rho: -0.30, p&lt;.01). Conclusions: In this prospective study of a large population with broad enrollment criteria, mood disturbances at 90 days were most common among ICH patients and least common among TIA patients. Further work should investigate the driving factors of greater PSMD in patients with ICH compared to other patients with acute cerebrovascular disease.

Abstract 110: Pre-Operative Risks of Major Adverse Cerebrovascular Events in Pediatric Moyamoya Disease

Objective: This study aims to evaluate the risk of cerebrovascular events in pediatric MMD during the preoperative waiting period, and explore the related risk factors and appropriate operation opportunities. Methods: This study is an observational cohort study, including 736 children with MMD from their initial visit until the completion of surgery. The patients were divided into three subgroups according to their initial symptoms: no cerebrovascular event group, cerebral infarction (CI) group, and transient ischemic attack (TIA) group. Results: A total of 736 children with MMD were included, and the median time from diagnosis to surgery was 13 months (IQR: 4-33). During the waiting period, 166 patients (26.6%) experienced CI, and 17 patients (2.3%) had cerebral hemorrhage. The incidence rates of CI and cerebral hemorrhage were 10.49 and 1.08 per 1000 person-months, respectively. Cox regression analysis revealed that male (HR: 1.586; p=0.004), CI at onset (HR: 2.889; p&lt;0.001) or TIA at onset (HR: 1.943; p=0.006), age≤3 years at onset (HR: 2.208; p&lt;0.001), and involvement of the posterior cerebral arteries (HR: 1.670; p=0.001) were risk factors for CI during the waiting period. No specific risk factors for cerebral hemorrhage during the waiting period were identified. For patients with CI at onset, the risk of CI during the waiting period significantly increased when the waiting time exceeded 2.5 months (AUC=0.722, specificity=0.561, sensitivity=0.882; OR: 8.253; p&lt;0.001). In pediatric MMD patients without cerebrovascular events at onset, the risk of preoperative cerebral hemorrhage significantly increased when the waiting time exceeded 5 years (AUC=0.761, specificity=0.856, sensitivity=0.571; OR: 6.667; p=0.018). No significant correlation was found between waiting time and preoperative CI in TIA patients. Conclusions: For children MMD with CI or TIA at onset, early surgery is recommended, especially for younger patients and those with involvement of the posterior circulation. For patients with CI at onset, surgery should be performed within 2.5 months of waiting, while patients without cerebrovascular events should undergo surgery within 5 years.

Abstract WP261: Healthcare Utilization Patterns and Disparities in High Intensity Statin Use in Stroke Patients

Objective: Physician adherence to evidence-based clinical guidelines improves outcomes in acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients. We investigated compliance with the AHA 2008 high intensity statin recommendation for secondary prevention of AIS/TIA, and factors associated with adherence. Methods: In this population-based, cohort study of incident AIS/TIA patients, we included a random sample of U.S. Medicare beneficiaries age≥67 with Part A/B/D coverage, ≥1 ICD code for AIS/TIA in 2015-2018, and no prior AIS/TIA or high intensity statin use (N=76,707). We followed the cohort forward until end of 2019 for high intensity statin use (atorvastatin ≥40mg or rosuvastatin ≥20mg). We used logistic regression to examine factors associated with high intensity statin use within 3 months: demographics, urban residence, Area Deprivation Index (ADI), and provider specialty (neurologist vs. other). Results: Overall, during follow up, only 62.5% of beneficiaries with incident AIS/TIA received neurologist care. In this period only 19.4% incident AIS/TIA patients received a high intensity statin and 27.8% did not receive any statin. Female patients (OR 0.88, 95%CI 0.84-0.92), older beneficiaries (OR 0.984, 95%CI 0.981-0.987 per year), and urban residents (OR 0.84, 95%CI 0.80-0.88) were less likely to receive a high intensity statin within 3 months of their stroke. Race/ethnicity but not ADI was associated with high intensity statin use. Neurologist-treated patients were markedly more likely to receive a high intensity statin than other AIS/TIA patients (OR 3.42, 95%CI 3.22-3.63), even after adjusting for all sociodemographic variables. Conclusions: AIS/TIA patients treated by neurologists received care consistent with the clinical guidelines more often than those not treated by a neurologist. Female, older, and urban beneficiaries were less likely to receive care consistent with the guidelines.

Measurement of optic nerve sheath diameter on computed tomography for the differentiation of transient ischemic attacks.

The objective of this study was to investigate whether the measurement of mean optic nerve sheath diameter in patients with transient ischemic attack could be used to distinguish between control groups, the acute ischemic stroke group, and subgroups within the acute ischemic stroke category. Retrospectively, the mean optic nerve sheath diameters of patients aged 18 years and older belonging to control, transient ischemic attack, acute ischemic stroke, and subgroups within the acute ischemic stroke category were measured with initial computed tomography conducted in the emergency department. Out of the 773 patients included in the study, 318 (41.1%) were in the control group, 77 (10%) had transient ischemic attack, and 378 (49%) were categorized as stroke patients. The average mean optic nerve sheath diameter was significantly higher in both the stroke and transient ischemic attack groups compared with the control group (p<0.001 for both comparisons). Furthermore, the mean optic nerve sheath diameter in the stroke subgroups was significantly higher than in both the transient ischemic attack and control groups (p<0.001 for all comparisons). In transient ischemic attack patients, the mean optic nerve sheath diameter showed a significant ability to predict transient ischemic attack (AUC=0.913, p<0.001), with a calculated optimal cutoff value of 4.72, sensitivity of 94.8%, and specificity of 73.9%. The mean optic nerve sheath diameter of patients in the transient ischemic attack group was lower compared with those in the stroke subgroups but higher compared with the control group.

Evaluation of the Correlation Between Distribution Location and Vulnerability of Carotid Plaque in Patients with Transient Ischemic Attack.

To analyze the relationship among distribution location, characteristics, and vulnerability of carotid plaque using CTA and provide more information on the risk factors of carotid atherosclerotic plaque. We retrospectively analyzed the CTA images of the head and neck of 93 patients with carotid atherosclerosis. Atherosclerosis was developed in 148 carotid arteries. The plaques were divided into a high-risk plaque group and a low-risk plaque group according to whether the plaques had high-risk characteristics. The maximum cross-sectional area of carotid artery bifurcation plaque on the axial image was selected, and the cross-sectional lumen was equally divided into four 90-degree sectors, ventral side wall, dorsal side wall, inner side wall, and outer side wall. The differences in the characteristics and distribution locations of the plaques in the two groups were analyzed. The characteristic parameters of the cross-sectional plaques at the bifurcation of the carotid artery. The logistic regression analysis was used to further analyze the risk factors associated with plaque vulnerability. Among 148 carotid arteries,80 were classified as high-risk and 68 as low-risk groups. There were significant differences between the two groups concerning the thickness, length, maximum cross-sectional area, burden, and cross-sectional distribution of the plaques (P < 0.05). The plaque distribution on the dorsal side wall of the carotid bifurcation was higher in the high-risk group than that in the low-risk group (P < 0.05), dorsal side wall plaque-independent risk factors for the development of vulnerability of plaques in transient ischemic attack (TIA) patients (95% CI:1.522~6.991, P<0.05). High-risk plaques tend to occur on the dorsal side wall of the carotid bifurcation, whereas low-risk plaques tend to occur on the outer side wall of the carotid bifurcation.

Antiplatelet Therapy for Secondary Prevention in Patients with Ischaemic Stroke and Transient Ischaemic Attack: A Retrospective Cohort Study in Malaysia

In this study, we evaluated clinical outcomes of antiplatelet therapy for secondary prevention in ischaemic stroke and transient ischaemic attack (TIA) patients. This was a retrospective cohort study that included patients with newly diagnosed ischaemic stroke or TIA between 2014 and 2017 using data from routine practice in Malaysia. Patients were grouped into single antiplatelet therapy (SAPT) and dual antiplatelet therapy (DAPT) users. Primary outcome was composite of stroke, myocardial infarction, and all-cause death in 90 days and 1 year. Safety outcome was major bleeding events. Among 3344 stroke patients, 8.1% received DAPT and 91.2% received SAPT. The 1-year cumulative incidence of composite events was 16.0 and 7.2 per 100 person-years for SAPT and DAPT, respectively. Propensity score-matched analysis of Cox hazard model showed DAPT reduced the risk of composite event (hazard ratio (HR) 0.48; 95% CI 0.25-0.91) and recurrent stroke (HR 0.38; 95% CI 0.16-0.92) in 1-year follow-up. Results were not significant for myocardial infarction, all-cause death, and 90-day outcomes. The risks of bleeding were not significantly different between SAPT and DAPT. Treatment with DAPT after an ischaemic stroke/TIA was associated with reduced risk of the composite events (stroke, myocardial infarction, or death) and recurrent stroke at 1 year.

Blood Pressure Fluctuation Pattern Associated with 90-Day Ischemic Stroke and Transient Ischemic Attack After Total Knee Arthroplasty-A Retrospective Study.

Blood pressure (BP) fluctuation has been demonstrated to be closely associated with stroke. However, at present, no attention is paid to the BP fluctuation following total knee arthroplasty (TKA). The aim of this study is to investigate what is BP fluctuation patterns in stroke and transient ischemic attack (TIA) patients after primary TKA, compare clinical characteristics among different BP fluctuation patterns and determine whether it could predict the occurrence of a 90-day stroke. A retrospective study was conducted from February 1, 2011 to February 15, 2021. Stroke or TIA patients within 90 days after TKA were included. Data from a hospitalization management system were analyzed, including demographics, smoking status, comorbidities, medications, surgical variables, and 90-day stroke, mortality, and readmission rates. BP fluctuation patterns were defined based on the average BP in the first 3 days after TKA. A logistic regression analysis model was used to identify risk factors for 90-day stroke or TIA following TKA. Of the 1687 patients who underwent primary TKA, 4.0% (68/1687) experienced a 90-day stroke or TIA. A total of 63 patients met the inclusion criteria, with an average age of 67.5 years and 55.6% (35/63) female. The number of stroke or TIA patients in each BP fluctuation pattern (T1-T5) was 6 (9.5%), 5 (7.9%), 4 (6.3%), 13 (20.6%), and 35 (55.6%) respectively. Patients with a T5 pattern tended to be older and had a greater reduction in average systolic blood pressure (SBP) 3 days after surgery compared to other patterns. The T5 pattern was associated with a higher occurrence of stroke and a lower occurrence of TIA. Patients with a T5 pattern also had a longer length of stay within 90 days following TKA. After adjusting for confounding factors, average SBP fluctuation ≥40 mmHg and the T5 pattern of BP fluctuation remained risk factors for 90-day stroke or TIA after TKA. BP fluctuation patterns in the early postoperative period are associated with 90-day stroke and TIA following primary TKA.

Urine-based point-of-care testing for factor-Xa-inhibitors in acute ischemic stroke patients: a feasibility study.

Direct oral anticoagulants (DOACs) have become widely used in clinical practice for preventing thromboembolic events. Point-of-care testing methods, particularly those based on urine samples, offer a promising approach for rapid and accurate assessment of DOAC presence. This pilot study aims to evaluate the utility of a urine-based DOAC dipstick test as a point-of-care tool for identifying DOAB presence in acute ischemic stroke (AIS) or transient ischemic attack (TIA) patients. This prospective pilot study included patients with AIS/TIA eligible for DOAC-measurement. After exclusion of 3 patients, 23 patients with DOAC-intake (DOAC group; factor-Xa-inhibitors; n = 23) and 21 patients without DOAC-intake (control-group) remained for analyses. The urine-based DOAC dipstick test and parallel blood-based specific DOAC-level assessment were performed in all patients. Time-intervals of sampling urine/blood sampling and result of DOAC-test were recorded to analyze a potential time benefit based on dipstick evaluation. The urine-based DOAC dipstick test demonstrated high sensitivity (100%) and specificity (100%), correctly identifying all patients with anticoagulatory activity due to DOAC intake (i.e., anti-Xalevel ≥30 ng/mL). Moreover, the visual readout of the test provided semiquantitative information on drug-specific anti-Xa levels, showing a sensitivity of 83% and specificity of 93% to detect anti-Xa levels ≥120 ng/mL. The dipstick test exhibited a median time-benefit of 2:25 h compared to standard blood-based DOAC-level testing. The results of this pilot study underline the efficacy of urine-based point-of-care testing as a rapid and reliable method for assessing DOAC presence in patients with acute ischemic stroke. The value of this tool for clinical decision-making in stroke management needs to be established in future trials.Clinical Trial Registration: Clinicaltrails.org identifier [NCT06037200].

Impact of CYP2C19 Genotype on Efficacy and Safety of Clopidogrel-based Antiplatelet Therapy in Stroke or Transient Ischemic Attack Patients: An Updated Systematic Review and Meta-analysis of Non-East Asian Studies.

Inconclusive and limited results have been reported on the clinical utility of CYP2C19 genotyping in stroke/TIA patients of non-East Asian ancestries. We herein performed an updated systematic review and meta-analysis to quantitatively estimate the association of CYP2C19 loss-of function (LOF) status with efficacy and safety of clopidogrel-based antiplatelet therapy in non-East Asian patients affected by stroke or TIA. A comprehensive search was performed up to July 2023 using PubMed, Web of Knowledge, and Cochrane Library databases. The clinical outcomes investigated were stroke, composite vascular events and bleeding. Pooled estimates were calculated as risk ratios (RR) with 95% CI using the Mantel- Haenszel random-effects model. The quality of evidence was assessed using the GRADEpro tool. A total number of 1673 stroke/TIA patients from 8 non-East Asian studies, published between 2014 and 2022, were included in the systematic review. Clopidogrel-treated carriers of CYP2C19 LOF alleles were found at increased risk of stroke compared to non-carriers (RR: 1.68, 95%CI: 1.04-2.71, P = 0.03). However, no significant association was observed with the risk of composite vascular events (RR: 1.15, 95%CI: 0.58-2.28, P = 0.69) or bleeding (RR: 0.84, 95%CI: 0.38-1.86, P = 0.67). Similarly, European ancestry patients carrying CYP2C19 LOF alleles displayed a higher risk of stroke (RR: 2.69 (1.11-6.51, P = 0.03), but not of composite vascular events or bleeding. The present updated meta-analysis provides moderate quality evidence of association between CYP2C19 LOF alleles and an increased risk of stroke in non-East Asian patients with stroke/TIA after receiving clopidogrel therapy. Further large pharmacogenetic studies are still warranted to corroborate these findings.

Proposed general diagnostic criteria for secondary headaches.

The distinction between a pre-existing primary headache and a secondary headache at the onset of a disorder is important and has not been taken into account in the International Classification of Headache Disorders-3. This study aimed to improve the general diagnostic criteria for secondary headaches using results of our previous studies. We analyzed characteristics of headaches including their changes in intensity, duration, frequency, localization and side, development of new accompanying symptoms, and therapeutic response at the onset of transient ischemic attacks (TIA) (n = 120, mean age 56.1, 55% females) and ischemic stroke (n = 550, mean age 63.1, 56% females) compared to the control group (n = 192, mean age 58.7, 64% females). Headache of a new type occurred in 8.4% of ischemic stroke patients and 5% of TIA patients on the day of admission but did not occur at all in the control group. Pre-existing headache with a change of at least one characteristic occurred significantly more often in stroke (5.4%) and TIA (7.5%) than in the control group (1%) (p = 0.01 and p = 0.003 respectively). The presence of a new type of headache and a pre-existing headache with altered characteristics in close temporal relation to a disorder indicates causality. Based on these data we propose revised general diagnostic criteria for secondary headaches.

Complement Activation Is Increased in Antiphospholipid Syndrome-Related Ischemic Stroke with Higher Risk Features

Introduction: Antiphospholipid syndrome (APS) patients with arterial thrombosis, mostly ischemic stroke, have concerningly high rates of recurrent thrombosis despite antithrombotic treatment, with over 20% thrombosis recurrence within two years. Complement activation is increased in thrombotic APS patients, although its role has not been fully investigated in APS-related stroke. This study aimed to evaluate the degree of complement activation in APS-related ischemic stroke, transient ischemic attack (TIA) or other ischemic brain injury patients and whether complement activation correlated with APS severity and platelet hyperreactivity as a potential mechanism for increased thrombotic risk. Method: Patients with confirmed APS by Sydney Criteria and imaging-proven ischemic stroke, TIA or other ischemic brain injury were recruited, subcategorized as high-risk APS (HR-APS, n=30) and lower-risk APS (LR-APS, n=41). HR-APS included triple antiphospholipid antibody (aPL) positive, anticoagulant refractory or both arterial and venous thromboembolism patients. LR-APS included patients with a single thrombotic event who were single or double aPL positive. Ischemic stroke patients without aPL (n=40) and healthy donors (n=40) were utilized as controls. Patients with active cancer, inflammation, infection or use of hydroxychloroquine, immunosuppression and heparins were excluded. Complement activation markers were measured as Bb fragment (Bb), C3a-desArg (C3a), C5a-des-Arg (C5a), and SC5b-9 using ELISA (MicroVue kits, Quidel Corp, Pathway Diagnostics Ltd). Complement-mediated cell killing was measured by the modified Ham (mHam) test, which determines the degree of cell lysis after adding patient serum to a paroxysmal nocturnal hemoglobinuria cell line (PIGA-null TF-1 cells) lacking cell surface complement regulators. A positive result was considered 20% or greater cell killing. Flow cytometry was used to evaluate whether complement activation correlated with platelet hyperreactivity. For this, plasma from mHam positive patients was added to healthy donor whole blood and procoagulant platelet response was measured as the absolute change in proportion of platelet events that were positive for annexin V and P-selectin following stimulation with thrombin 2U/mL. Results: There was no significant difference in median age between the patient cohorts, ranging from 49 to 56 years, although the healthy controls were younger, with median age 36 (range 25-73, p&amp;lt;0.001). Circulating complement activation markers were all significantly increased in the APS cohorts compared to healthy controls (p&amp;lt;0.01). The most prominent increase was observed in C3a levels: HR-APS median (interquartile range - IQR) 215 ng/mL (137.1-297.4), LR-APS 290.8 ng/mL (120.3-450.3) and healthy controls 62 ng/mL (27.9-121.1)(p=0.004 and p&amp;lt;0.0001 compared to healthy controls, respectively); and Bb fragment levels: HR-APS 1.2 µg/mL (IQR 1.0-1.4), LR-APS 1.3 µg/mL (IQR 1.0-1.5) and healthy controls 0.8 µg/mL (IQR 0.7-0.9)(both p&amp;lt;0.0001 compared to healthy controls). However, only C3a, SC5b-9 and Bb fragment levels in LR-APS remained significantly elevated when compared to stroke controls (p=0.0009, p=0.01 and p=0.03, respectively). There were no differences between HR-APS and LR-APS, nor between stroke controls and healthy controls. Complement-mediated cell killing was also significantly higher in APS patients overall, median (IQR) proportion of non-viable cells 18% (IQR 12-33), compared to stroke controls: 10% (IQR 8-15, p&amp;lt;0.0001) and healthy controls: 12.5% (IQR 6.3-17, p=0.0009). Notably, HR-APS had significantly higher proportion of positive mHam tests (60%), compared to LR-APS: 36.6%, stroke controls: 12.5%, and healthy controls: 17.5% (p&amp;lt;0.0001, Figure 1A). Importantly, HR-APS patients with positive mHam results (n=5) induced a substantially higher increase in procoagulant platelets, median 17.2% (IQR 11.2-28.6), whereas healthy controls (n=4) only resulted in median change of -0.7% (IQR -7.0-1.4, p=0.02) (Figure 1B). Conclusion: Preliminary data suggest that APS-related ischemic stroke, TIA or ischemic brain injury are associated with increased, functionally important, complement activation, more prominent in higher risk disease. Complement-mediated platelet hyperreactivity may have a contributory role that remains to be established.

Quantitative patient graph analysis for transient ischemic attack risk factor distribution based on electronic medical records

A transient ischemic attack (TIA) affects millions of people worldwide. Although TIA risk factors have been identified individually, a systemic quantitative analysis of all health factors relevant to TIA using electronic medical records (EMR) remains lacking. This study employed a data-driven approach, leveraging hospital EMR data to create a TIA patient health factor graph. This graph consisted of 737 TIA and 737 control patient nodes, 740 health factor nodes, and over 33,000 relations between patients and factors. For all health factors in the graph, the connection delta ratios (CDRs) were determined and ranked, generating a quantitative distribution of TIA health factors. A literature review confirmed 56 risk factors in the distribution and unveiled a potential new risk factor “rhinosinusitis” for future validation. Moreover, the patient graph was visualized together with the TIA knowledge graph in the Unified Medical Language System. This integration enables clinicians to access and visualize patient data and international standard knowledge within a unified graph. In conclusion, graph CDR analysis can effectively quantify the distribution of TIA risk factors. The resulting TIA risk factor distribution might be instrumental in developing new risk prediction machine learning models for screening and early detection of TIA.

Cost-effectiveness analysis of CYP2C19 genotype-guided antiplatelet therapy for patients with acute minor ischemic stroke and high-risk transient ischemic attack in China.

The study aimed to estimate the cost-effectiveness of CYP2C19 genotype-guided antiplatelet therapy using cilostazol and ticagrelor as an alternative to clopidogrel, compared to conventional antiplatelet therapy with clopidogrel and aspirin. A 90-day decision tree and 30-year Markov model were employed to assess the costs and quality-adjusted life years (QALYs) of personalized antiplatelet therapy for patients with minor ischemic stroke and high-risk transient ischemic attack, compared to conventional antiplatelet therapy in the Chinese healthcare system. The primary outcome was the incremental cost-effectiveness ratio (ICER). The data sources included clinical trials, published literature, official documents and local prices. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to confirm the robustness of the findings. The base-case analysis indicated that the CYP2C19 genotype-guided antiplatelet strategy was cost-effective, and cilostazol group and ticagrelor group yielded an ICER of 3327.40 US dollars (USD)/QALY and 3426.92 USD/QALY, respectively, which were less than threshold. The one-way sensitivity analysis showed the results were robust, where the most sensitive parameter was the disability distribution in the modified Rankin scale 3-5. The probabilistic analysis showed that the CYP2C19 genotype-guided antiplatelet therapy with either cilostazol or ticagrelor was 100% cost-effective under the willingness-to-pay threshold. CYP2C19 genotype-guided antiplatelet therapy usingcilostazol and ticagrelor as an alternative to clopidogrel appeared to be more cost-effective than conventional antiplatelet therapy for acute minor ischemic stroke and high-risk transient ischemic attack patients over 30 years in China.