Stroke Etiology Research Articles

Lack of impact of HIV status on carotid intima media thickness in a cohort of stroke patients in South Africa

IntroductionPeople living with HIV (PLWH) are at increased risk for cardiovascular disease. Carotid intima media thickness (cIMT) is a validated surrogate marker of atherosclerosis, and an accurate predictor of future cardiovascular events. It is uncertain whether HIV potentiates stroke risk through atherosclerosis in Sub-Saharan Africa and what effect HIV status has on cIMT. We sought to investigate the relationship between HIV status and cIMT in stroke patients in a region that is burdened with dual epidemics of HIV and stroke in the young. MethodsConsecutive patients with new onset ischaemic stroke were recruited from a quaternary-level hospital in Johannesburg, South Africa, from August 2014 to November 2017. Patients were assessed for the presence of traditional cardiovascular risk factors and HIV infection, and investigated for stroke aetiology. cIMT was measured using high resolution B-mode ultrasound following standardized techniques. Results168 patients were included in the study, of which 62 (36.9%) were PLWH. Mean cIMT was higher in HIV-uninfected patients when compared to PLWH (0.79 ± 0.19 mm vs 0.69 ± 0.18 mm, p = 0.0021). However after adjusting for age, sex, hypertension, diabetes mellitus, smoking, total cholesterol, body mass index and stroke aetiology, there was no difference in mean cIMT between the groups (0.76 ± 0.16 mm vs 0.73 ± 0.17 mm, p = 0.29). Regression models revealed the determinants of cIMT to be age (p < 0.0001), hypertension (p = 0.0098) and total cholesterol (p = 0.005), while the determinants of increased cIMT (≥0.70 mm) were only age (p < 0.0001) and hypertension (p = 0.0002). ConclusionHIV status had no effect on cIMT in our cohort of stroke patients. The main determinants of cIMT were age and hypertension.

Classification of childhood arterial ischemic stroke

The etiology of childhood arterial ischemic stroke is complex, and identifying the underlying cause is crucial for optimizing treatment and preventing recurrence. Currently, the classification methods for childhood arterial ischemic stroke are largely based on data from international studies, but a unified consensus have not yet been reached. This paper reviews the existing classification methods and their subtype definitions, and points out some doubts and ambiguities. On this basisi, combined with the data collected by Beijing Children's Hospital on Chinese children with arterial ischemic stroke, a new classification method (COIST) was proposed according to the etiology and pathogenesis, namely: inflammation (I), abnormal vascular structure (S), thrombophilia (T), heart disease (C), other identifiable causes (O), and uncertain causes; and various subtypes are listed. It is hoped that this new classification method can attract the attention and discussion of domestic colleagues, with the aim of further refinement, in order to help clinicians better understand and quickly identify the etiologies of childhood ischemic stroke.

Natriuretic Peptides to Classify Risk of Atrial Fibrillation Detection After Stroke: Analysis of the BIOSIGNAL and PRECISE Cohort Studies.

Prolonged cardiac monitoring (PCM) increases atrial fibrillation (AF) detection after ischemic stroke, but access is limited, and it is burdensome for patients. Our objective was to assess whether midregional proatrial natriuretic peptide (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) could classify people who are unlikely to have AF after ischemic stroke and allow better targeting of PCM. We analyzed people from the Biomarker Signature of Stroke Aetiology (BIOSIGNAL) study with ischemic stroke, no known AF, and ≥3 days cardiac monitoring. External validation was performed in the Preventing Recurrent Cardioembolic Stroke: Right Approach, Right Patient (PRECISE) study of 28 days of cardiac monitoring in people with ischemic stroke or transient ischemic attack and no known AF. The main outcome is no AF detection. We assessed the discriminatory value of MR-proANP and NT-proBNP combined with clinical variables to identify people with no AF. A decision curve analysis was performed with combined data to determine the net reduction in people who would undergo PCM using the models based on a 15% threshold probability for AF detection. We included 621 people from the BIOSIGNAL study. The clinical multivariable prediction model included age, NIH Stroke Scale score, lipid-lowering therapy, creatinine, and smoking status. The area under the receiver-operating characteristic curve (AUROC) for clinical variables was 0.68 (95% CI 0.62-0.74), which improved with the addition of log10MR-proANP (0.72, 0.66-0.78; p = 0.001) or log10NT-proBNP (0.71, 0.65-0.77; p = 0.009). Performance was similar for the models with log10MR-proANP vs log10NT-proBNP (p = 0.28). In 239 people from the PRECISE study, the AUROC for clinical variables was 0.68 (0.59-0.76), which improved with the addition of log10NT-proBNP (0.73, 0.65-0.82; p < 0.001) or log10MR-proANP (0.79, 0.72-0.86; p < 0.001). Performance was better for the model with log10MR-proANP vs log10NT-proBNP (p = 0.03). The models could reduce the number of people who would undergo PCM by 30% (clinical and log10MR-proANP), 27% (clinical and log10NT-proBNP), or 20% (clinical only). MR-proANP and NT-proBNP help classify people who are unlikely to have AF after ischemic stroke. Measuring MR-proANP or NT-proBNP could reduce the number of people who need PCM by 30%, without reducing the amount of AF detected. NCT02274727; clinicaltrials.gov/study/NCT02274727.

Causal Relationship between Chronic Hepatitis B and Stroke in East Asians: A Mendelian Randomization Study.

Both chronic hepatitis B (CHB) and stroke contribute to a high burden of disease in the majority of low- and middle-income countries. Epidemiological studies yield conflicting results on the association between CHB and stroke, and the causal relationship remains inconclusive. This study aimed to assess the causal effects of CHB on stroke and its subtypes in East Asians by Mendelian randomization (MR) analysis. Variants associated with CHB were obtained from a genome-wide association study (GWAS) of Chinese samples as instrumental variables. The summary statistics for stroke in East Asians were derived from the largest published GWAS to date. Two-sample MR analyses were implemented to evaluate the causal effects of CHB on stroke and its subtypes by using the canonical inverse variance weighting method and other supplementary approaches. We observed an association between genetic predisposition to CHB and a decreased risk of large-artery atherosclerotic stroke (odds ratio = 0.872, 95% confidence interval = 0.786-0.967, p = 0.010). The causal effects of CHB on other stroke outcomes were not statistically significant. Evidence for heterogeneity and horizontal pleiotropy were not found in our analyses. This study provides genetic evidence for a negative association between CHB and stroke in East Asians, which helps improve our understanding of the etiology of stroke.

Association of baseline blood pressure and outcomes in etiology subtypes of large vessel occlusion stroke: Data from ANGEL-ACT registry

BackgroundBlood pressure (BP) management at the initial stage of stroke caused by large-vessel occlusion (LVO) remains challenging. We assessed the association between baseline BP and clinical and safety outcomes of endovascular treatment (EVT) in different stroke etiologies. MethodsPatients with acute ischemic stroke and anterior circulation LVO were screened from a prospective, multicenter registry of EVT from November 2017 to March 2019. The primary outcome was poor 90-day outcome (modified Rankin Scale score 3–6). The safety outcome was 24 h post-procedure parenchymal hematoma (PH). The Trial of Org 101072 in Acute Stroke Treatment criteria were used for etiologic stroke classification. Restricted cubic spline and binary logistic regression analysis were performed to examine the association between study outcomes and natural log-transformed BP. ResultsIn subgroup analyses, a U-shaped correlation existed between baseline mean arterial pressure (MAP) and poor outcome in large-artery atherosclerosis stroke only. Higher MAP was an independent risk factor compared with a central reference value (≥ 133 mm Hg vs 96–115 mm Hg; adjusted OR [aOR], 2.50; 95 % CI, 1.09 to 5.71, P = 0.030). Whereas elevated MAP was associated with PH (aOR, 1.58; 95 % CI 1.04 to 2.39, P = 0.030 for a ln10-unit increase in natural log-transformed MAP) in the range <110 mm Hg exclusively for cardioembolic stroke. ConclusionWhether it is cause or epiphenomenon, baseline BP was associated with 90-day outcome in large-artery atherosclerosis stroke, whereas in cardioembolic stroke baseline BP was correlated with post-procedure PH within a certain range. Identifying these features based on etiological subtypes may offer a reference for BP management in acute LVO stroke.

A case report about anorexia nervosa and ischemic stroke: what can we learn?

IntroductionAnorexia Nervosa (AN) is a complex psychiatric illness, characterized by a high risk of developing cardiovascular complications. Given the high risk of vascular diseases in patients with AN, we can assume that patients with severe AN have a high risk of developing ischemic stroke. However, to the best of our knowledge, no reports of patients with AN presenting with ischemic stroke have been published, other than a report of the development of IS during refeeding therapy in patients with severe AN.Case presentationThe present case report is aimed at describing the characteristics of an ischemic stroke occurring in a 19-year-old university student who had a 6-month history of AN. She was a non-smoker, had no relevant medical history and no family history of stroke. Upon hospital admission due to symptoms of stroke (aphasia and facial droop), she exhibited severe malnutrition with a BMI of 12.8 kg/m2. Computerized tomography imaging revealed occlusion of the left M2 branch and a congruous extensive area of hypoperfusion. Further investigations ruled out all common causes of stroke: she had no vascular stenosis, no heart diseases or arrhythmias, and no shunts, and gave negative results in autoimmune, toxicological and thrombophilia screenings.ConclusionClinicians should suspect development of severe complications, including ischemic stroke, in patients with severe AN. Further extensive group studies or group-based studies are needed to elucidate the etiology of ischemic stroke in patients with severe AN. This will enable us to develop more precise and effective interventions.Graphical

Small vessel disease burden and prognosis of recent subcortical ischaemic stroke differ by parent artery atherosclerosis.

Parent artery atherosclerosis is an important aetiology of recent subcortical ischaemic stroke (RSIS). However, comparisons of RSIS with different degrees of parent artery atherosclerosis are lacking. Prospectively collected data from our multicentre cohort (all were tertiary centres) of the Stroke Imaging Package Study between 2015 and 2017 were retrospectively reviewed. The patients with RSIS defined as a single clinically relevant diffusion-weighted imaging positive lesion in the territory of lenticulostriate arteries were categorized into three subgroups: (1) normal middle cerebral artery (MCA) on magnetic resonance angiography and high-resolution magnetic resonance imaging (HR-MRI); (2) low-grade MCA atherosclerosis (normal or <50% stenosis on magnetic resonance angiography and with MCA plaques on HR-MRI); (3) steno-occlusive MCA atherosclerosis (stenosis ≥50% or occlusion). The primary outcome was 90-day functional dependence (modified Rankin Scale score >2). The clinical and imaging findings were compared between subgroups. A total of 239 patients (median age 60.0 [52.0-67.0] years, 72% male) were enrolled, including 140 with normal MCA, 64 with low-grade MCA atherosclerosis and 35 with steno-occlusive MCA atherosclerosis. Patients with steno-occlusive MCA atherosclerosis had the largest infarct volume. Low-grade MCA atherosclerosis was independently associated with cerebral microbleeding, more severe perivascular spaces in basal ganglia and higher total cerebral small vessel disease burden. Low-grade MCA atherosclerosis was an independent determinant of 90-day functional dependence (odds ratio 3.897; 95% confidence interval 1.309-11.604). Our study suggested RSIS with varying severity of parent artery atherosclerosis exhibits distinctive clinical and neuroimaging characteristics, with low-grade MCA atherosclerosis associating with higher cerebral small vessel disease burden and worse prognosis.

Cardioembolic stroke in an HIV endemic region: underdiagnosed and severe

Background and objectivesCardioembolic stroke (CES) appears to be a rare cause of stroke (4%–9%) in people living with HIV (PLWH) in sub-Saharan Africa (SSA). However, due to limited access to...

Effect of Stroke Etiology on Endovascular Treatment for Acute Basilar-Artery Occlusion: A Post Hoc Analysis of the ATTENTION Randomized Trial.

Stroke etiology could influence the outcomes in patients with basilar-artery occlusion (BAO). This study aimed to evaluate the differences in efficacy and safety of best medical treatment (BMT) plus endovascular treatment (EVT) versus BMT alone in acute BAO across different stroke etiologies. The study was a post hoc analysis of the ATTENTION trial (Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion), which was a multicenter, randomized trial at 36 centers in China from February 2021 to September 2022. Patients with acute BAO were classified into 3 groups according to stroke etiology (large-artery atherosclerosis [LAA], cardioembolism, and undetermined cause/other determined cause [UC/ODC]). The primary outcome was a favorable outcome (modified Rankin Scale score of 0-3) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 90-day mortality. A total of 340 patients with BAO were included, 150 (44.1%) had LAA, 72 (21.2%) had cardioembolism, and 118 (34.7%) had UC/ODC. For patients treated with BMT plus EVT and BMT alone, respectively, the rate of favorable outcome at 90 days was 49.1% and 23.8% in the LAA group (odds ratio, 3.08 [95% CI, 1.38-6.89]); 52.2% and 30.8% in the cardioembolism group (odds ratio, 2.45 [95% CI, 0.89-6.77]); and 37.5% and 17.4% in the UC/ODC group (odds ratio, 2.85 [95% CI, 1.16-7.01]), with P=0.89 for the stroke etiology×treatment interaction. The rate of symptomatic intracranial hemorrhage in EVT-treated patients with LAA, cardioembolism, and UC/ODC was 8.3%, 2.2%, and 3.2%, respectively, and none of the BMT-treated patients. Lower 90-day mortality was observed in patients with EVT compared with BMT alone across 3 etiology groups. Among patients with acute BAO, EVT compared with BMT alone might be associated with favorable outcomes and lower 90-day mortality, regardless of cardioembolism, LAA, or UC/ODC etiologies. The influence of stroke etiology on the benefit of EVT should be explored by further trials. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04751708.

Endovascular thrombectomy versus medical management for moderate-to-severe anterior cerebral artery occlusion stroke.

There are no established patient selection criteria for endovascular thrombectomy (EVT) for anterior cerebral artery (ACA) stroke. This was a retrospective cohort study of the 2016-2020 National Inpatient Sample in the United States. Isolated ACA-occlusion stroke patients with moderate-to-severe stroke symptoms (NIH stroke scale [NIHSS] ≥ 6) were included. Primary outcome was hospital discharge to home with self-care. Secondary outcomes include in-hospital mortality and intracranial hemorrhage (ICH). Confounders were accounted for by multivariable logistic regression. 6685 patients were included; 335 received EVT. Compared to medical management (MM), EVT patients were younger (mean 67.2 versus 72.2years; p = 0.014) and had higher NIHSS (mean 16.0 versus 12.5; p < 0.001). EVT was numerically but not statistically significantly associated with higher odds of home discharge compared to MM (aOR 2.26 [95%CI 0.99-5.17], p = 0.053). EVT was significantly associated with higher odds of home discharge among patients with NIHSS 10 or greater (aOR 3.35 [95%CI 1.06-10.58], p = 0.039), those who did not receive prior thrombolysis (aOR 3.96 [95%CI 1.53-10.23], p = 0.005), and those with embolic stroke etiology (aOR 4.03 [95%CI 1.21-13.47], p = 0.024). EVT was not significantly associated with higher rates of mortality (aOR 1.93 [95%CI 0.80-4.63], p = 0.14); however, it was significantly associated with higher rates of ICH (22.4% vs. 8.5%, p < 0.001). EVT was associated with higher odds of favorable short-term outcomes for moderate-to-severe ACA-occlusion stroke in select patients. Future studies are needed to confirm the efficacy of EVT in terms of longer term neurological outcomes.

Relationship between carotid web morphology on CT angiography and stroke: A pooled multicenter analysis.

The Carotid web (CaW) is a cause of stroke, particularly in younger individuals. However, the frequency and the radiological features of the web's morphology associated with stroke risk are uncertain. We determined the CaW radiological features on computed tomography (CT) angiography associated with ipsilateral stroke. Data from six studies of patients with acute ischemic stroke were pooled. Identification and measurement of CaWs were performed by experienced readers using baseline neck CT angiography. We assessed six 2D CaW radiological features on sagittal oblique images, namely, main axis length, thickness, height, base width, distance to wall, and angle between the web main axis and carotid wall, and CaW volume on 3D images. CaWs were divided into symptomatic if acute ischemic stroke was in the ipsilateral internal carotid artery territory and its etiology was undetermined and asymptomatic if one condition was unmet. Univariable and multivariable analyses were conducted to assess the association between each radiological CaW feature and symptomatic CaW. Of the 3442 patients in the pooled data with assessable CTAs, 60 (1.7%) had CaW. In patients with CaW, median age was 59 (interquartile range [IQR]: 50-68) years, 60% were women, and 3 patients had bilateral CaWs. There were 39 (62%) symptomatic and 24 (38%) asymptomatic CaWs. Patients with symptomatic CaW were younger (55 (IQR: 49-61) years versus 69 (IQR: 52-75) years), had lower rates of hypertension (9 (25.0%) versus 12 (57.1%)) and more intracranial large vessel occlusions compared to patients with asymptomatic CaWs. After adjusting for age, hypertension, and occlusion location, CaW length (adjusted odds ratio (aOR) 1.84 (95% confidence interval [CI]: 1.03-3.28)), thickness (aOR: 2.31 (95% CI 1.08-4.97)), volume (aOR: 1.07 per 1 mm3 increment (95% CI: 1.01-1.12)), and angle relative to the carotid wall (aOR: 0.95 (95% CI: 0.91-0.99)) were associated with symptomatic CaW. Radiological assessment of CaW morphology may determine its potential causal role in ischemic stroke etiology. Symptomatic CaWs tend to be longer, larger, and oriented at more acute angles relative to the carotid wall as compared to asymptomatic CaWs.

Association between ischaemic stroke aetiology and leptomeningeal collateral status: a retrospective cohort study.

There is limited understanding of the pathomechanistic relationship between leptomeningeal collateral formation and ischaemic stroke aetiology. We aimed to assess the association of leptomeningeal collateral status and ischaemic stroke aetiology, using the widely recognised "Trial of Org 10172 in Acute Stroke Treatment" (TOAST) classification categorising strokes into five distinct aetiologies. Retrospective study of consecutively admitted adult ischaemic stroke patients at a Swiss stroke centre. Leptomeningeal collateral status was assessed on admission with single-phase CT-angiographies using a validated 4-point score. Patients were categorised into large-artery atherosclerosis (LAA), cardioembolic (CE), small-vessel disease (SVD) and cryptogenic (CG) according to the TOAST classification. We performed ordinal and binary (poor [collaterals filling ≤50% of the occluded territory] vs good [collaterals filling >50% of the occluded territory] collateralisation) logistic regression to evaluate the impact of TOAST aetiology on collateral status. Among 191 patients, LAA patients had better collateral status compared to non-LAA aetiology (LAA: 2 vs CE: 2 vs SVD: 3 vs CG: 2, pLAAvsnon-LAA= 0.04). In weighted multivariate logistic regression, LAA and SVD independently predicted better collateral status (binary models [adjusted odds ratio; aOR]: LAA: 3.72 [1.21-11.44] and SVD: 4.19 [1.21-14.52]; ordinal models [adjusted common odds ratio; acOR]: LAA: 2.26 [95% CI: 1.23-4.15] and SVD: 1.94 [1.03-3.66]), while CE predicted worse collateral status (binary models [aOR]: CE: 0.17 [0.07-0.41]; ordinal models [acOR]: CE: 0.24 [0.11-0.51]). The aetiology of ischaemic stroke is associated with leptomeningeal collateral status on single-phase CT-angiography, with LAA and SVD predicting better and CE predicting worse collateral status.

Mineralizing angiopathy as a rare cause of pediatric stroke: review and report of two cases.

In the Indian subcontinent, traumatic brain injury stands as the leading cause of pediatric stroke, whereas in Europe, it is considered a rare or potentially underdiagnosed factor. The etiology of post-traumatic stroke is unknown, although it has been associated with the presence of calcification in the lenticulostriate arteries, a condition known as "mineralizing angiopathy." The theory suggests that calcified lenticulostriate vessels in a brain with inadequate myelination could have an increased vulnerability to mechanical injuries, which may result in their obstruction. This ischemic stroke associated with mineralizing angiopathy usually occurs after mild traumatic brain injury, with an asymptomatic interval following the trauma. The typical age of presentation is between 6 and 24months. Children with mineralizing lenticulostriate vasculopathy generally experience a favorable outcome after stroke, with the majority achieving complete or nearly complete recovery of their motor functions. Despite aspirin treatment, a small proportion of children may still face stroke recurrence following repeat head trauma. We present the cases of two male patients with clinical features compatible with childhood stroke after a mild traumatic brain injury.

Chronic mitral regurgitation predicts acute heart failure and worse outcomes after endovascular treatment for large vessel occlusion stroke

BackgroundValvular diseases are widely recognized as important etiologies for large vessel occlusion stroke (LVO) but their impact on outcomes among patients with LVO receiving endovascular treatment (EVT) are less well...

Family History of Stroke Is Associated with Large- and Small-Vessel Etiology: A Systematic Review and Meta-Analysis.

Several studies have investigated the association between family history of stroke (FHS) and stroke etiology, recurrence, or mortality; however, the results have been discrepant. We conducted a systematic review with meta-analysis to further evaluate the associations. We searched Scopus database using the term "family history" AND "stroke" up to December 2023 to identify observational studies and systematic reviews reporting both the prevalence of FHS and the rates of stroke etiology or recurrence or mortality. Case reports, series, and narrative reviews were excluded. We used odds ratio (OR) as a common measure of association and I2 to determine heterogeneity of effects across studies. We have identified 22 articles (130,999 patients, 53% female), which met the prespecified inclusion criteria. After pooling the results, FHS was associated with large-vessel (OR, 1.24, 95% CI [1.07-1.44]), as well as small-vessel (OR, 1.17, 95% CI [1.05-1.31]), but not cardioembolic stroke etiology (OR, 0.74, 95% CI [0.60-0.90]). There was no relationship between FHS and stroke recurrence (OR, 1.16, 96% CI [0.84-1.61]), nor mortality (0.94, 95% CI [0.63-1.41]). FHS is associated with large- and small-vessel stroke etiology, but not stroke recurrence or mortality. These findings might be useful to physicians caring for stroke patients in their everyday practice.

Safety and efficacy of tirofiban combined with intravenous thrombolysis and endovascular treatment in acute large vessel occlusion stroke

ObjectiveThis study assesses the safety and efficacy of tirofiban for patients with large vessel occlusion stroke after intravenous thrombolysis. MethodsThis study data was from SUSTAIN, DEVT, and RESCUE BT trials. According to whether the use of tirofiban who underwent endovascular treatment and preceding intravenous thrombolysis was divided into the tirofiban group and the no-tirofiban group. The safety outcomes were symptomatic intracranial hemorrhage, any intracranial hemorrhage within 48 h, and 3-month mortality. The efficacy outcome was defined as a score of 0–2 on the modified Rankin Scale scores at 3 months. ResultsA total of 372 patients with intravenous thrombolysis were included in these SUSTAIN, DEVT, and RESCUE BT trials. Adjusted multivariate analysis showed that tirofiban with intravenous thrombolysis was not associated with symptomatic intracranial hemorrhage (aOR, 0.87; 95 % CI, 0.49–1.57; P=0.65), any intracranial hemorrhage within 48 h (aOR, 1.00; 95 % CI, 0.60–1.66; P=1.00), 3-month mortality (aOR, 1.10; 95 % CI, 0.56–2.19; P=0.78) and 3-month modified Rankin Scale scores 0–2 (aOR, 0.72; 95 % CI, 0.42–1.25; P=0.25) in patients with acute large vessel occlusion. In the subgroup analysis, we found that tirofiban was not recommended for females (aOR, 0.34; 95 % CI, 0.12–0.93), baseline Alberta Stroke Program Early CT Score≤9 (aOR, 0.37; 95 % CI, 0.18–0.76), and cardiogenic embolism (aOR, 0.36; 95 % CI, 0.14–0.97). ConclusionTirofiban combined with intravenous thrombolysis in patients with acute large vessel occlusion may be safe. Further studies need to confirm the effectiveness of tirofiban after intravenous thrombolysis in different stroke etiology.

Circulating levels of neurofilament light chain as a biomarker of infarct and white matter hyperintensity volumes after ischemic stroke

Serum neurofilament light chain protein (sNfL) shows promise as a biomarker for infarct size in acute ischemic stroke and for monitoring cerebral small vessel disease (cSVD). However, distinguishing the cSVD contribution after stroke may not be possible due to post-stroke sNfL increase. Additionally, it remains unclear if etiologic subtype differences exist. We measured infarct and white matter hyperintensity (WMH) volumes using MRI at the index stroke in ischemic stroke patients (n = 316, mean age 53 years, 65% males) and at 7-year follow-up (n = 187). Serum NfL concentration was measured in the acute phase (n = 235), at 3-months (n = 288), and 7-years (n = 190) post stroke. In multivariable regression, acute and 3-month sNfL concentrations were associated with infarct volume and time since stroke, but not with stroke etiology or infarct location. Seven years post-stroke, sNfL was associated with WMHs and age, but not with stroke etiology. Nonlinear regression estimated that sNfL peaks around 1 month, and declines by 50% at 3 months, and 99% at 9 months. We conclude that sNfL can indicate infarct volume and time since brain injury in the acute and subacute phases after stroke. Due to the significant post-stroke sNfL increase, several months are needed for reliable assessment of cSVD activity.

Symptomatic carotid webs and patent foramen ovale: RoPE score in competing stroke etiologies

BackgroundPatent foramen ovale (PFO)-associated stroke is diagnosed more frequently in young patients with infrequent vascular risk factors and embolic appearing infarcts. The risk of paradoxical embolism (RoPE) score is used to identify PFO-associated stroke. Patients with symptomatic carotid artery web (CaW) share a very similar risk profile and these lesions are frequently overlooked. In this study, we evaluate the RoPE score profile in patients with suspected symptomatic CaW. MethodsRetrospective analysis of prospectively collected data of patients with symptomatic CaW as the presumed cause of stroke presenting to 2 comprehensive stroke centers from 2014 to 2021. CaW was diagnosed using computed tomography angiography (CTA) of the neck & head. Shunt study was done using a transthoracic, transesophageal, and/or transcranial-Doppler with bubbles. RoPE score ≥7 was considered high. ResultsSeventy-five patients had stroke from a symptomatic ipsilateral CaW. Mean age was 49.7±11.2 years and 74.7 % were females. Median RoPE score was 7 [5–8], and 52.0 % had a high RoPE score. PFO was detected in 13.3 % of the patients and 20.5 % within the high RoPE score group. Ten percent of the cases would have been misclassified as PFO-associated strokes based on RoPE score. ConclusionHigh RoPE scores were observed in the majority of patients with CaW-attributed stroke, and it should not be used to differentiate CaW- versus PFO-associated stroke. Careful extracranial internal carotid artery evaluation for CaW is warranted in cryptogenic strokes, including in PFO positive patients before defining stroke etiology.

Prolonged and repeated microemboli detection in acute ischemic stroke – The Norwegian Microemboli in Acute Stroke Study (NOR-MASS)

ObjectivesCerebral microemboli can be detected by transcranial Doppler monitoring (TCDM) and may elucidate stroke etiology, the effect of preventive therapy, and the risk of stroke recurrence. Microemboli detection is usually performed for up to 60 minutes, but due to temporal variability, microembolization may be missed if the monitoring time is too short. We aimed to assess the time course of microembolization in acute ischemic stroke and explore the utility of prolonged and repeated microemboli detection. Materials and MethodsPatients with suspected ischemic stroke and symptom onset within 24 hours were examined with bilateral, stationary TCDM for one hour followed by unilateral, ambulatory TCDM for two hours. Unilateral TCDM was repeated for the following two days and after three months. ResultsWe included 47 patients, of which 41 had ischemic stroke, five had transient ischemic attack, and one had amaurosis fugax. Microemboli were detected in 60 % of patients. The occurrence was highest within 24 hours after onset and significantly lower at three months. Prolonged and repeated microemboli detection yielded only one additional microemboli-positive patient. Hence, patients who initially were microemboli negative tended to remain negative. We could not demonstrate an association between microemboli occurrence and clinical outcome or stroke recurrence. ConclusionsMicroembolic signals are frequent within 24 hours after ischemic stroke onset, but prolonged and repeated microemboli detection did not increase the yield of MES positive patients. Clinical Trial Registration-URLhttp://www.clinicaltrials.gov. Unique identifier: NCT03543319.

Increased plasma levels of N-terminal pro-B-type natriuretic peptide as biomarker for the diagnosis of cardioembolic ischaemic stroke

BackgroundDespite comprehensive study, the aetiology of stroke is not identified in 35% of cases. AimsWe conducted a study to assess the diagnostic capacity of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the identification of ischaemic stroke of cardioembolic origin. The secondary purpose of the study was to evaluate the prognostic value of NT-proBNP for predicting 90-day all-cause mortality. MethodsWe designed a prospective observational study including patients hospitalised due to stroke between March 2019 and March 2020. Blood samples were collected on admission to the emergency department and serum NT-proBNP levels were determined. Statistical analysis was performed using a bivariate logistic regression model and receiver operating characteristic (ROC) and Kaplan–Meier curves. Statistical significance was established at p<.05. ResultsThe study included 207 patients with first ischaemic stroke. Plasma NT-proBNP levels were significantly higher (p<.001) in the cardioembolic stroke group (2069pg/mL±488.5). ROC curves showed that NT-proBNP>499pg/mL was the optimum value for diagnosing cardioembolic ischaemic stroke (sensitivity, 82%; specificity, 80%). Moreover, plasma NT-proBNP levels>499pg/mL were independently associated with cardioembolic stroke (OR: 9.881; p=.001). Finally, NT-proBNP>1500pg/mL was useful for predicting 90-day mortality (sensitivity, 70%; specificity, 93%). ConclusionsNT-proBNP was independently associated with cardioembolic stroke and should be quantified in blood tests within 24h of stroke onset. High plasma levels (>499pg/mL) may indicate an underlying cardioembolic cause, which should be further studied, while NT-proBNP >1500pg/mL was associated with increased 90-day mortality.